US (United States) Code. Title 21. Chapter 9: Federal Food, Drug and Cosmetic Act

Codificación normativa de EEUU (Estados Unidos) Legislación Federal estadounidense # Food and drugs

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AMENDMENTS

2002 - Subsec. (i)(1)(D). Pub. L. 107-109 added subpar. (D).

1999 - Subsec. (m). Pub. L. 106-113 substituted ''United States

Patent and Trademark Office'' for ''Patent and Trademark Office of

the Department of Commerce''.

1997 - Subsec. (b)(1). Pub. L. 105-115, Sec. 115(b), inserted at

end ''The Secretary shall, in consultation with the Director of the

National Institutes of Health and with representatives of the drug

manufacturing industry, review and develop guidance, as

appropriate, on the inclusion of women and minorities in clinical

trials required by clause (A).''

Subsec. (b)(4). Pub. L. 105-115, Sec. 119(a), added par. (4).

Subsec. (c)(4). Pub. L. 105-115, Sec. 124(a), added par. (4).

Subsec. (d). Pub. L. 105-115, Sec. 115(a), inserted at end ''If

the Secretary determines, based on relevant science, that data from

one adequate and well-controlled clinical investigation and

confirmatory evidence (obtained prior to or after such

investigation) are sufficient to establish effectiveness, the

Secretary may consider such data and evidence to constitute

substantial evidence for purposes of the preceding sentence.''

Subsec. (i). Pub. L. 105-115, Sec. 117, inserted ''(1)'' after

''(i)'', redesignated former pars. (1) to (3) as subpars. (A) to

(C), respectively, of par. (1), added pars. (2) to (4), and struck

out closing provisions which read as follows: ''Such regulations

shall provide that such exemption shall be conditioned upon the

manufacturer, or the sponsor of the investigation, requiring that

experts using such drugs for investigational purposes certify to

such manufacturer or sponsor that they will inform any human beings

to whom such drugs, or any controls used in connection therewith,

are being administered, or their representatives, that such drugs

are being used for investigational purposes and will obtain the

consent of such human beings or their representatives, except where

they deem it not feasible or, in their professional judgment,

contrary to the best interests of such human beings. Nothing in

this subsection shall be construed to require any clinical

investigator to submit directly to the Secretary reports on the

investigational use of drugs.''

Subsec. (j)(2)(A)(i). Pub. L. 105-115, Sec. 119(b)(2)(A),

substituted ''paragraph (7)'' for ''paragraph (6)''.

Subsec. (j)(3). Pub. L. 105-115, Sec. 119(b)(1)(B), added par.

(3). Former par. (3) redesignated (4).

Subsec. (j)(4). Pub. L. 105-115, Sec. 119(b)(1)(A), (2)(B),

redesignated par. (3) as (4) and in introductory provisions

substituted ''paragraph (5)'' for ''paragraph (4)''. Former par.

(4) redesignated (5).

Subsec. (j)(4)(I). Pub. L. 105-115, Sec. 119(b)(2)(C),

substituted ''paragraph (6)'' for ''paragraph (5)''.

Subsec. (j)(5), (6). Pub. L. 105-115, Sec. 119(b)(1)(A),

redesignated pars. (4) and (5) as (5) and (6), respectively.

Former par. (6) redesignated (7).

Subsec. (j)(7). Pub. L. 105-115, Sec. 119(b)(1)(A), (2)(D),

redesignated par. (6) as (7) and in subpar. (C) substituted

''paragraph (6)'' for ''paragraph (5)'' in two places. Former par.

(7) redesignated (8).

Subsec. (j)(8), (9). Pub. L. 105-115, Sec. 119(b)(1)(A),

redesignated pars. (7) and (8) as (8) and (9), respectively.

Subsec. (n). Pub. L. 105-115, Sec. 120, added subsec. (n).

1993 - Subsec. (j)(6)(A)(ii). Pub. L. 103-80, Sec. 3(n)(1)(A),

substituted ''Secretary'' for ''Secretry''.

Subsec. (j)(6)(A)(iii). Pub. L. 103-80, Sec. 3(n)(1)(B), inserted

comma after ''published by the Secretary''.

Subsec. (k)(1). Pub. L. 103-80, Sec. 3(n)(2), substituted

''section. Regulations'' for ''section: Provided, however, That

regulations''.

1992 - Subsec. (j)(8). Pub. L. 102-282 added par. (8).

1984 - Subsec. (a). Pub. L. 98-417, Sec. 102(b)(1), inserted ''or

(j)'' after ''subsection (b)''.

Subsec. (b). Pub. L. 98-417, Sec. 102(a)(1), 103(a), designated

existing provisions of subsec. (b) as par. (1) thereof and

redesignated existing cls. (1) through (6) of such par. (1) as cls.

(A) through (F) thereof, respectively, inserted requirement that

the applicant file with the application the patent number and the

expiration date of any patent which claims the drug for which the

applicant submitted the application or which claims a method of

using such drug and with respect to which a claim of patent

infringement could reasonably by asserted if a person not licensed

by the owner engaged in the manufacture, use, or sale of the drug,

that the applicant amend the application to include such

information if an application is filed under this subsection for a

drug and a patent which claims such drug or a method of using such

drug is issued after the filing date but before approval of the

application, and that upon approval of the application, the

Secretary publish the information submitted, and added pars. (2)

and (3).

Subsec. (c). Pub. L. 98-417, Sec. 102(a)(2), (b)(2), 103(b),

designated existing provisions of subsec. (c) as par. (1) thereof

and in par. (1) as so designated substituted ''subsection (b) of

this section'' for ''this subsection'' and redesignated former

pars. (1) and (2) as subpars. (A) and (B), respectively, and added

pars. (2) and (3).

Subsec. (d)(6), (7). Pub. L. 98-417, Sec. 102(a)(3)(A), added cl.

(6) relating to the failure of the application to contain the

patent information prescribed by subsec. (b) of this section, and

redesignated former cl. (6) as (7).

Subsec. (e). Pub. L. 98-417, Sec. 102(a)(3)(B), in first

sentence, added a new cl. (4) relating to the failure to file the

patent information prescribed by subsec. (c) of this section within

30 days after the receipt of written notice from the Secretary

specifying the failure to file such information, and redesignated

former cl. (4) as (5).

Pub. L. 98-417, Sec. 102(b)(3), (4), in second sentence, inserted

in provisions preceding cl. (1) ''submitted under subsection (b) or

(j) of this section'' and in cl. (1) substituted ''under subsection

(k) of this section or to comply with the notice requirements of

section 360(k)(2) of this title'' for ''under subsection (j) of

this section or to comply with the notice requirements of section

360(j)(2) of this title''.

Subsecs. (j), (k). Pub. L. 98-417, Sec. 101, added subsec. (j)

and redesignated former subsec. (j) as (k).

Subsec. (k)(1). Pub. L. 98-417, Sec. 102(b)(5), substituted

''under subsection (b) or (j) of this section'' for ''pursuant to

this section''.

Subsecs. (l), (m). Pub. L. 98-417, Sec. 104, added subsecs. (l)

and (m).

1972 - Subsec. (e). Pub. L. 92-387 inserted ''or to comply with

the notice requirements of section 360(j)(2) of this title'' in cl.

(1) of second sentence relating to the maintenance of records.

1962 - Subsec. (a). Pub. L. 87-781, Sec. 104(a), inserted ''an

approval of'' before ''an application''.

Subsec. (b). Pub. L. 87-781, Sec. 102(b), inserted ''and whether

such drug is effective in use'' after ''is safe for use''.

Subsec. (c). Pub. L. 87-781, Sec. 104(b), substituted provisions

requiring the Secretary, within 180 days after filing an

application, or such additional period as the Secretary and the

applicant agree upon, to either approve the application, if meeting

the requirements of subsec. (d) of this section, or give notice of

opportunity for hearing on question of whether such application is

approvable, and providing that if applicant requests hearing in

writing within 30 days, the hearing shall begin within 90 days

after expiration of said 30 days, unless the Secretary and

applicant agree otherwise, that such hearing shall be expedited,

and that the Secretary's order shall be issued within 90 days after

date for filing final briefs, for provisions which had an

application become effective on the sixtieth day after filing

thereof unless prior thereto the Secretary postponed the date by

written notice to such time, but not more than 180 days after

filing, as the Secretary deemed necessary to study and investigate

the application.

Subsec. (d). Pub. L. 87-781, Sec. 102(c), inserted references to

subsec. (c), added cls. (5) and (6), provided that if after notice

and opportunity for hearing, the Secretary finds that cls. (1) to

(6) do not apply, he shall approve the application, and defined

''substantial evidence'' as used in this subsection and subsec. (e)

of this section.

Subsec. (e). Pub. L. 87-781, Sec. 102(d), amended subsec. (e)

generally, and among other changes, directed the Secretary to

withdraw approval of an application if by tests, other scientific

data or experience, or new evidence of clinical experience not

contained in the application or available at the time of its

approval, the drug is shown to be unsafe, or on the basis of new

information, there is shown a lack of substantial evidence that the

drug has the effect it is represented to have, and provided that if

the Secretary, or acting Secretary, finds there is an imminent

hazard to the public health, he may suspend approval immediately,

notify the applicant, and give him opportunity for an expedited

hearing, that the Secretary may withdraw approval if the applicant

fails to establish a system for maintaining required records, or

has repeatedly or deliberately failed to maintain records and make

reports, or has refused access to, or copying or verification of

such records, or if the Secretary finds on new evidence that the

methods, facilities and controls in the manufacturing, processing,

and packing are inadequate to assure and preserve the drugs'

identity, strength, quality and purity, and were not made adequate

within a reasonable time after receipt of written notice thereof,

or finds on new evidence, that the labeling is false or misleading

and was not corrected within a reasonable time after receipt of

written notice thereof.

Subsec. (f). Pub. L. 87-781, Sec. 104(c), substituted provisions

requiring the Secretary to revoke any previous order under subsecs.

(d) or (e) of this section refusing, withdrawing, or suspending

approval of an application and to approve such application or

reinstate such approval, for provisions which required him to

revoke an order refusing effectiveness to an application.

Subsec. (h). Pub. L. 87-781, Sec. 104(d)(1), (2), inserted ''as

provided in section 2112 of title 28'', and ''except that until the

filing of the record the Secretary may modify or set aside his

order'', substituted ''or withdrawing approval of an application

under this section'' for ''to permit the application to become

effective, or suspending the effectiveness of the application'',

''United States court of appeals for the circuit'' for ''district

court of the United States within any district'', ''Court of

Appeals for the District of Columbia Circuit'' for ''District Court

for the District of Columbia'', ''transmitted by the clerk of the

court to'' for ''served upon'', and ''by the Supreme Court of the

United States upon certiorari or certification as provided in

section 1254 of title 28'' for ''as provided in sections 225, 346,

and 347 of title 28, as amended, and in section 7, as amended, of

the Act entitled 'An Act to establish a Court of Appeals for the

District of Columbia', approved February 9, 1893'', and eliminated

''upon'' before ''any officer designated'', ''a transcript of''

before ''the record'' and ''and decree'' before ''of the court

affirming''.

Subsec. (i). Pub. L. 87-781, Sec. 103(b), inserted ''the

foregoing subsections of'' after ''operation of'', and ''and

effectiveness'' after ''safety'', and provided that the regulations

may condition exemptions upon the submission of reports of

preclinical tests to justify the proposed clinical testing, upon

the obtaining by the manufacturer or sponsor of the investigation

of a new drug of a signed agreement from each of the investigators

that patients to whom the drug is administered will be under his

supervision or under investigators responsible to him, and that he

will not supply such drug to any other investigator, or to clinics,

for administration to human beings, or upon the establishment and

maintenance of records and reports of data obtained by the

investigational use of such drug, as the Secretary finds will

enable him to evaluate the safety and effectiveness of such drug,

and provided that the regulations shall condition an exemption upon

the manufacturer or sponsor of the investigation requiring that

experts using such drugs certify that they will inform humans to

whom such drugs or any controls connected therewith are

administered, or their representatives, and will obtain the consent

of such people where feasible and not contrary to the best

interests of such people, and that reports on the investigational

use of drugs are not required to be submitted directly to the

Secretary.

Subsec. (j). Pub. L. 87-781, Sec. 103(a), added subsec. (j).

1960 - Subsec. (g). Pub. L. 86-507 inserted ''or by certified

mail'' after ''registered mail''.

EFFECTIVE DATE OF 1999 AMENDMENT

Amendment by Pub. L. 106-113 effective 4 months after Nov. 29,

1999, see section 1000(a)(9) (title IV, Sec. 4731) of Pub. L.

106-113, set out as a note under section 1 of Title 35, Patents.

EFFECTIVE DATE OF 1997 AMENDMENT

Amendment by Pub. L. 105-115 effective 90 days after Nov. 21,

1997, except as otherwise provided, see section 501 of Pub. L.

105-115, set out as a note under section 321 of this title.

EFFECTIVE DATE OF 1984 AMENDMENT

Section 105 of Pub. L. 98-417 provided that:

''(a) The Secretary of Health and Human Services shall

promulgate, in accordance with the notice and comment requirements

of section 553 of title 5, United States Code, such regulations as

may be necessary for the administration of section 505 of the

Federal Food, Drug, and Cosmetic Act (this section), as amended by

sections 101, 102, and 103 of this Act, within one year of the date

of enactment of this Act (Sept. 24, 1984).

''(b) During the period beginning sixty days after the date of

the enactment of this Act (Sept. 24, 1984), and ending on the date

regulations promulgated under subsection (a) take effect,

abbreviated new drug applications may be submitted in accordance

with the provisions of section 314.2 of title 21 of the Code of

Federal Regulations and shall be considered as suitable for any

drug which has been approved for safety and effectiveness under

section 505(c) of the Federal Food, Drug, and Cosmetic Act (subsec.

(c) of this section) before the date of the enactment of this Act.

If any such provision is inconsistent with the requirements of

section 505(j) of the Federal Food, Drug, and Cosmetic Act, the

Secretary shall consider the application under the applicable

requirements of such section. The Secretary of Health and Human

Services may not approve such an abbreviated new drug application

which is filed for a drug which is described in sections

505(c)(3)(D) and 505(j)(4)(D) of the Federal Food, Drug, and

Cosmetic Act, except in accordance with such section.''

EFFECTIVE DATE OF 1972 AMENDMENT

Amendment by Pub. L. 92-387 effective on first day of sixth month

beginning after Aug. 16, 1972, see section 5 of Pub. L. 92-387, set

out as a note under section 360 of this title.

EFFECTIVE DATE OF 1962 AMENDMENT

Amendment by Pub. L. 87-781 effective on first day of seventh

calendar month following October 1962, see section 107 of Pub. L.

87-781, set out as a note under section 321 of this title.

CONSTRUCTION OF AMENDMENTS BY PUB. L. 102-282

Amendment by Pub. L. 102-282 not to preclude any other civil,

criminal, or administrative remedy provided under Federal or State

law, including any private right of action against any person for

the same action subject to any action or civil penalty under an

amendment made by Pub. L. 102-282, see section 7 of Pub. L.

102-282, set out as a note under section 335a of this title.

-TRANS-

TRANSFER OF FUNCTIONS

For transfer of functions of Federal Security Administrator to

Secretary of Health, Education, and Welfare (now Health and Human

Services), and of Food and Drug Administration in the Department of

Agriculture to Federal Security Agency, see note set out under

section 41 of this title.

-MISC5-

REPORT ON PATIENT ACCESS TO NEW THERAPEUTIC AGENTS FOR PEDIATRIC

CANCER

Pub. L. 107-109, Sec. 15(d), Jan. 4, 2002, 115 Stat. 1421,

provided that: ''Not later than January 31, 2003, the Secretary of

Health and Human Services, acting through the Commissioner of Food

and Drugs and in consultation with the Director of the National

Institutes of Health, shall submit to the Committee on Health,

Education, Labor, and Pensions of the Senate and the Committee on

Energy and Commerce of the House of Representatives a report on

patient access to new therapeutic agents for pediatric cancer,

including access to single patient use of new therapeutic agents.''

DATA REQUIREMENTS FOR DRUGS AND BIOLOGICS

Section 118 of Pub. L. 105-115 provided that: ''Within 12 months

after the date of enactment of this Act (Nov. 21, 1997), the

Secretary of Health and Human Services, acting through the

Commissioner of Food and Drugs, shall issue guidance that describes

when abbreviated study reports may be submitted, in lieu of full

reports, with a new drug application under section 505(b) of the

Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(b)) and with a

biologics license application under section 351 of the Public

Health Service Act (42 U.S.C. 262) for certain types of studies.

Such guidance shall describe the kinds of studies for which

abbreviated reports are appropriate and the appropriate abbreviated

report formats.''

REQUIREMENTS FOR REVIEW OF APPROVAL PROCEDURES AND CURRENT GOOD

MANUFACTURING PRACTICES FOR POSITRON EMISSION TECHNOLOGY

Section 121(c) of Pub. L. 105-115 provided that:

''(1) Procedures and requirements. -

''(A) In general. - In order to take account of the special

characteristics of positron emission tomography drugs and the

special techniques and processes required to produce these drugs,

not later than 2 years after the date of enactment of this Act

(Nov. 21, 1997), the Secretary of Health and Human Services shall

establish -

''(i) appropriate procedures for the approval of positron

emission tomography drugs pursuant to section 505 of the

Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355); and

''(ii) appropriate current good manufacturing practice

requirements for such drugs.

''(B) Considerations and consultation. - In establishing the

procedures and requirements required by subparagraph (A), the

Secretary of Health and Human Services shall take due account of

any relevant differences between not-for-profit institutions that

compound the drugs for their patients and commercial

manufacturers of the drugs. Prior to establishing the procedures

and requirements, the Secretary of Health and Human Services

shall consult with patient advocacy groups, professional

associations, manufacturers, and physicians and scientists

licensed to make or use positron emission tomography drugs.

''(2) Submission of new drug applications and abbreviated new

drug applications. -

''(A) In general. - Except as provided in subparagraph (B), the

Secretary of Health and Human Services shall not require the

submission of new drug applications or abbreviated new drug

applications under subsection (b) or (j) of section 505 (21

U.S.C. 355), for compounded positron emission tomography drugs

that are not adulterated drugs described in section 501(a)(2)(C)

of the Federal Food, Drug, and Cosmetic Act (21 U.S.C.

351(a)(2)(C)) (as amended by subsection (b)), for a period of 4

years after the date of enactment of this Act (Nov. 21, 1997), or

for 2 years after the date on which the Secretary establishes

procedures and requirements under paragraph (1), whichever is

longer.

''(B) Exception. - Nothing in this Act (see Short Title of 1997

Amendment note set out under section 301 of this title) shall

prohibit the voluntary submission of such applications or the

review of such applications by the Secretary of Health and Human

Services. Nothing in this Act shall constitute an exemption for a

positron emission tomography drug from the requirements of

regulations issued under section 505(i) of the Federal Food,

Drug, and Cosmetic Act (21 U.S.C. 355(i)).''

''COMPOUNDED POSITRON EMISSION TOPOGRAPHY DRUG'' DEFINED

Section 121(e) of Pub. L. 105-115 provided that: ''As used in

this section (amending sections 321 and 351 of this title and

enacting provisions set out as notes under this section and section

351 of this title), the term 'compounded positron emission

tomography drug' has the meaning given the term in section 201 of

the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321).''

REQUIREMENTS FOR RADIOPHARMACEUTICALS

Section 122 of Pub. L. 105-115 provided that:

''(a) Requirements. -

''(1) Regulations. -

''(A) Proposed regulations. - Not later than 180 days after

the date of enactment of this Act (Nov. 21, 1997), the

Secretary of Health and Human Services, after consultation with

patient advocacy groups, associations, physicians licensed to

use radiopharmaceuticals, and the regulated industry, shall

issue proposed regulations governing the approval of

radiopharmaceuticals. The regulations shall provide that the

determination of the safety and effectiveness of such a

radiopharmaceutical under section 505 of the Federal Food,

Drug, and Cosmetic Act (21 U.S.C. 355) or section 351 of the

Public Health Service Act (42 U.S.C. 262) shall include

consideration of the proposed use of the radiopharmaceutical in

the practice of medicine, the pharmacological and toxicological

activity of the radiopharmaceutical (including any carrier or

ligand component of the radiopharmaceutical), and the estimated

absorbed radiation dose of the radiopharmaceutical.

''(B) Final regulations. - Not later than 18 months after the

date of enactment of this Act, the Secretary shall promulgate

final regulations governing the approval of the

radiopharmaceuticals.

''(2) Special rule. - In the case of a radiopharmaceutical, the

indications for which such radiopharmaceutical is approved for

marketing may, in appropriate cases, refer to manifestations of

disease (such as biochemical, physiological, anatomic, or

pathological processes) common to, or present in, one or more

disease states.

''(b) Definition. - In this section, the term

'radiopharmaceutical' means -

''(1) an article -

''(A) that is intended for use in the diagnosis or monitoring

of a disease or a manifestation of a disease in humans; and

''(B) that exhibits spontaneous disintegration of unstable

nuclei with the emission of nuclear particles or photons; or

''(2) any nonradioactive reagent kit or nuclide generator that

is intended to be used in the preparation of any such article.''

SPECIAL RULE

Section 123(f) of Pub. L. 105-115 provided that: ''The Secretary

of Health and Human Services shall take measures to minimize

differences in the review and approval of products required to have

approved biologics license applications under section 351 of the

Public Health Service Act (42 U.S.C. 262) and products required to

have approved new drug applications under section 505(b)(1) of the

Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(b)(1)).''

TRANSITION

Section 125(d) of Pub. L. 105-115 provided that:

''(1) In general. - An application that was approved by the

Secretary of Health and Human Services before the date of the

enactment of this Act (Nov. 21, 1997) for the marketing of an

antibiotic drug under section 507 of the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 357), as in effect on the day before the

date of the enactment of this Act, shall, on and after such date of

enactment, be considered to be an application that was submitted

and filed under section 505(b) of such Act (21 U.S.C. 355(b)) and

approved for safety and effectiveness under section 505(c) of such

Act (21 U.S.C. 355(c)), except that if such application for

marketing was in the form of an abbreviated application, the

application shall be considered to have been filed and approved

under section 505(j) of such Act (21 U.S.C. 355(j)).

''(2) Exception. - The following subsections of section 505 (21

U.S.C. 355) shall not apply to any application for marketing in

which the drug that is the subject of the application contains an

antibiotic drug and the antibiotic drug was the subject of any

application for marketing received by the Secretary of Health and

Human Services under section 507 of such Act (21 U.S.C. 357) before

the date of the enactment of this Act (Nov. 21, 1997):

''(A)(i) Subsections (c)(2), (d)(6), (e)(4), (j)(2)(A)(vii),

(j)(2)(A)(viii), (j)(2)(B), (j)(4)(B), and (j)(4)(D); and

''(ii) The third and fourth sentences of subsection (b)(1)

(regarding the filing and publication of patent information); and

''(B) Subsections (b)(2)(A), (b)(2)(B), (b)(3), and (c)(3) if

the investigations relied upon by the applicant for approval of

the application were not conducted by or for the applicant and

for which the applicant has not obtained a right of reference or

use from the person by or for whom the investigations were

conducted.

''(3) Publication. - For purposes of this section, the Secretary

is authorized to make available to the public the established name

of each antibiotic drug that was the subject of any application for

marketing received by the Secretary for Health and Human Services

under section 507 of the Federal Food, Drug, and Cosmetic Act (21

U.S.C. 357) before the date of enactment of this Act (Nov. 21,

1997).''

TERMINATION OF ADVISORY PANELS

Advisory panels established after Jan. 5, 1973, to terminate not

later than the expiration of the 2-year period beginning on the

date of their establishment, unless, in the case of a panel

established by the President or an officer of the Federal

Government, such panel is renewed by appropriate action prior to

the expiration of such 2-year period, or in the case of a panel

established by Congress, its duration is otherwise provided for by

law. See sections 3(2) and 14 of Pub. L. 92-463, Oct. 6, 1972, 86

Stat. 770, 776, set out in the Appendix to Title 5, Government

Organization and Employees.

APPEALS TAKEN PRIOR TO OCTOBER 10, 1962

Section 104(d)(3) of Pub. L. 87-781 made amendments to subsec.

(h) of this section inapplicable to any appeal taken prior to Oct.

10, 1962.

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in sections 321, 331, 333, 334, 335a,

352, 353, 353a, 355a, 355b, 356, 356-1, 356a, 356c, 360, 360b,

360j, 360aa to 360ee, 360aaa, 360bbb, 360bbb-1, 374, 379g, 379h,

379i, 379r, 381, 382, 384, 802, 811, 827 of this title; title 10

section 1107; title 26 section 45C; title 28 section 2201; title 35

sections 155A, 156, 271; title 42 sections 236, 262, 282, 284m,

300cc-12, 300cc-13, 300cc-17, 1395y, 1396r-8.

-CITE-

21 USC Sec. 355a 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 355a. Pediatric studies of drugs

-STATUTE-

(a) Definitions

As used in this section, the term ''pediatric studies'' or

''studies'' means at least one clinical investigation (that, at the

Secretary's discretion, may include pharmacokinetic studies) in

pediatric age groups (including neonates in appropriate cases) in

which a drug is anticipated to be used.

(b) Market exclusivity for new drugs

If, prior to approval of an application that is submitted under

section 355(b)(1) of this title, the Secretary determines that

information relating to the use of a new drug in the pediatric

population may produce health benefits in that population, the

Secretary makes a written request for pediatric studies (which

shall include a timeframe for completing such studies), and such

studies are completed within any such timeframe and the reports

thereof submitted in accordance with subsection (d)(2) of this

section or accepted in accordance with subsection (d)(3) of this

section -

(1)(A)(i) the period referred to in subsection (c)(3)(D)(ii) of

section 355 of this title, and in subsection (j)(5)(D)(ii) of

such section, is deemed to be five years and six months rather

than five years, and the references in subsections (c)(3)(D)(ii)

and (j)(5)(D)(ii) of such section to four years, to forty-eight

months, and to seven and one-half years are deemed to be four and

one-half years, fifty-four months, and eight years, respectively;

or

(ii) the period referred to in clauses (iii) and (iv) of

subsection (c)(3)(D) of such section, and in clauses (iii) and

(iv) of subsection (j)(5)(D) of such section, is deemed to be

three years and six months rather than three years; and

(B) if the drug is designated under section 360bb of this title

for a rare disease or condition, the period referred to in

section 360cc(a) of this title is deemed to be seven years and

six months rather than seven years; and

(2)(A) if the drug is the subject of -

(i) a listed patent for which a certification has been

submitted under subsection (b)(2)(A)(ii) or (j)(2)(A)(vii)(II)

of section 355 of this title and for which pediatric studies

were submitted prior to the expiration of the patent (including

any patent extensions); or

(ii) a listed patent for which a certification has been

submitted under subsections (b)(2)(A)(iii) or

(j)(2)(A)(vii)(III) of section 355 of this title,

the period during which an application may not be approved under

section 355(c)(3) of this title or section 355(j)(4)(B) of this

title shall be extended by a period of six months after the date

the patent expires (including any patent extensions); or

(B) if the drug is the subject of a listed patent for which a

certification has been submitted under subsection (b)(2)(A)(iv)

or (j)(2)(A)(vii)(IV) of section 355 of this title, and in the

patent infringement litigation resulting from the certification

the court determines that the patent is valid and would be

infringed, the period during which an application may not be

approved under section 355(c)(3) of this title or section

355(j)(4)(B) of this title shall be extended by a period of six

months after the date the patent expires (including any patent

extensions).

(c) Market exclusivity for already-marketed drugs

If the Secretary determines that information relating to the use

of an approved drug in the pediatric population may produce health

benefits in that population and makes a written request to the

holder of an approved application under section 355(b)(1) of this

title for pediatric studies (which shall include a timeframe for

completing such studies), the holder agrees to the request, the

studies are completed within any such timeframe, and the reports

thereof are submitted in accordance with subsection (d)(2) of this

section or accepted in accordance with subsection (d)(3) of this

section -

(1)(A)(i) the period referred to in subsection (c)(3)(D)(ii) of

section 355 of this title, and in subsection (j)(5)(D)(ii) of

such section, is deemed to be five years and six months rather

than five years, and the references in subsections (c)(3)(D)(ii)

and (j)(5)(D)(ii) of such section to four years, to forty-eight

months, and to seven and one-half years are deemed to be four and

one-half years, fifty-four months, and eight years, respectively;

or

(ii) the period referred to in clauses (iii) and (iv) of

subsection (c)(3)(D) of such section, and in clauses (iii) and

(iv) of subsection (j)(5)(D) of such section, is deemed to be

three years and six months rather than three years; and

(B) if the drug is designated under section 360bb of this title

for a rare disease or condition, the period referred to in

section 360cc(a) of this title is deemed to be seven years and

six months rather than seven years; and

(2)(A) if the drug is the subject of -

(i) a listed patent for which a certification has been

submitted under subsection (b)(2)(A)(ii) or (j)(2)(A)(vii)(II)

of section 355 of this title and for which pediatric studies

were submitted prior to the expiration of the patent (including

any patent extensions); or

(ii) a listed patent for which a certification has been

submitted under subsection (b)(2)(A)(iii) or

(j)(2)(A)(vii)(III) of section 355 of this title,

the period during which an application may not be approved under

section 355(c)(3) of this title or section 355(j)(4)(B) of this

title shall be extended by a period of six months after the date

the patent expires (including any patent extensions); or

(B) if the drug is the subject of a listed patent for which a

certification has been submitted under subsection (b)(2)(A)(iv)

or (j)(2)(A)(vii)(IV) of section 355 of this title, and in the

patent infringement litigation resulting from the certification

the court determines that the patent is valid and would be

infringed, the period during which an application may not be

approved under section 355(c)(3) of this title or section

355(j)(4)(B) of this title shall be extended by a period of six

months after the date the patent expires (including any patent

extensions).

(d) Conduct of pediatric studies

(1) Agreement for studies

The Secretary may, pursuant to a written request from the

Secretary under subsection (b) or (c) of this section, after

consultation with -

(A) the sponsor of an application for an investigational new

drug under section 355(i) of this title;

(B) the sponsor of an application for a new drug under

section 355(b)(1) of this title; or

(C) the holder of an approved application for a drug under

section 355(b)(1) of this title,

agree with the sponsor or holder for the conduct of pediatric

studies for such drug. Such agreement shall be in writing and

shall include a timeframe for such studies.

(2) Written protocols to meet the studies requirement

If the sponsor or holder and the Secretary agree upon written

protocols for the studies, the studies requirement of subsection

(b) or (c) of this section is satisfied upon the completion of

the studies and submission of the reports thereof in accordance

with the original written request and the written agreement

referred to in paragraph (1). In reaching an agreement regarding

written protocols, the Secretary shall take into account adequate

representation of children of ethnic and racial minorities. Not

later than 60 days after the submission of the report of the

studies, the Secretary shall determine if such studies were or

were not conducted in accordance with the original written

request and the written agreement and reported in accordance with

the requirements of the Secretary for filing and so notify the

sponsor or holder.

(3) Other methods to meet the studies requirement

If the sponsor or holder and the Secretary have not agreed in

writing on the protocols for the studies, the studies requirement

of subsection (b) or (c) of this section is satisfied when such

studies have been completed and the reports accepted by the

Secretary. Not later than 90 days after the submission of the

reports of the studies, the Secretary shall accept or reject such

reports and so notify the sponsor or holder. The Secretary's

only responsibility in accepting or rejecting the reports shall

be to determine, within the 90 days, whether the studies fairly

respond to the written request, have been conducted in accordance

with commonly accepted scientific principles and protocols, and

have been reported in accordance with the requirements of the

Secretary for filing.

(4) Written request to holders of approved applications for drugs

that have market exclusivity

(A) Request and response

If the Secretary makes a written request for pediatric

studies (including neonates, as appropriate) under subsection

(c) of this section to the holder of an application approved

under section 355(b)(1) of this title, the holder, not later

than 180 days after receiving the written request, shall

respond to the Secretary as to the intention of the holder to

act on the request by -

(i) indicating when the pediatric studies will be

initiated, if the holder agrees to the request; or

(ii) indicating that the holder does not agree to the

request.

(B) No agreement to request

(i) Referral

If the holder does not agree to a written request within

the time period specified in subparagraph (A), and if the

Secretary determines that there is a continuing need for

information relating to the use of the drug in the pediatric

population (including neonates, as appropriate), the

Secretary shall refer the drug to the Foundation for the

National Institutes of Health established under section 290b

of title 42 (referred to in this paragraph as the

''Foundation'') for the conduct of the pediatric studies

described in the written request.

(ii) Public notice

The Secretary shall give public notice of the name of the

drug, the name of the manufacturer, and the indications to be

studied made in a referral under clause (i).

(C) Lack of funds

On referral of a drug under subparagraph (B)(i), the

Foundation shall issue a proposal to award a grant to conduct

the requested studies unless the Foundation certifies to the

Secretary, within a timeframe that the Secretary determines is

appropriate through guidance, that the Foundation does not have

funds available under section 290b(j)(9)(B)(i) (FOOTNOTE 1) of

title 42 to conduct the requested studies. If the Foundation

so certifies, the Secretary shall refer the drug for inclusion

on the list established under section 284m of title 42 for the

conduct of the studies.

(FOOTNOTE 1) See References in Text note below.

(D) Effect of subsection

Nothing in this subsection (including with respect to

referrals from the Secretary to the Foundation) alters or

amends section 331(j) of this title or section 552 of title 5

or section 1905 of title 18.

(E) No requirement to refer

Nothing in this subsection shall be construed to require that

every declined written request shall be referred to the

Foundation.

(F) Written requests under subsection (b)

For drugs under subsection (b) of this section for which

written requests have not been accepted, if the Secretary

determines that there is a continuing need for information

relating to the use of the drug in the pediatric population

(including neonates, as appropriate), the Secretary shall issue

a written request under subsection (c) of this section after

the date of approval of the drug.

(e) Delay of effective date for certain application

If the Secretary determines that the acceptance or approval of an

application under section 355(b)(2) or 355(j) of this title for a

new drug may occur after submission of reports of pediatric studies

under this section, which were submitted prior to the expiration of

the patent (including any patent extension) or the applicable

period under clauses (ii) through (iv) of section 355(c)(3)(D) of

this title or clauses (ii) through (iv) of section 355(j)(5)(D) of

this title, but before the Secretary has determined whether the

requirements of subsection (d) of this section have been satisfied,

the Secretary shall delay the acceptance or approval under section

355(b)(2) or 355(j) of this title until the determination under

subsection (d) of this section is made, but any such delay shall

not exceed 90 days. In the event that requirements of this section

are satisfied, the applicable six-month period under subsection (b)

or (c) of this section shall be deemed to have been running during

the period of delay.

(f) Notice of determinations on studies requirement

The Secretary shall publish a notice of any determination that

the requirements of subsection (d) of this section have been met

and that submissions and approvals under subsection (b)(2) or (j)

of section 355 of this title for a drug will be subject to the

provisions of this section.

(g) Limitations

A drug to which the six-month period under subsection (b) or (c)

of this section has already been applied -

(1) may receive an additional six-month period under subsection

(c)(1)(A)(ii) of this section for a supplemental application if

all other requirements under this section are satisfied, except

that such a drug may not receive any additional such period under

subsection (c)(2) of this section; and

(2) may not receive any additional such period under subsection

(c)(1)(B) of this section.

(h) Relationship to regulations

Notwithstanding any other provision of law, if any pediatric

study is required pursuant to regulations promulgated by the

Secretary and such study meets the completeness, timeliness, and

other requirements of this section, such study shall be deemed to

satisfy the requirement for market exclusivity pursuant to this

section.

(i) Labeling supplements

(1) Priority status for pediatric supplements

Any supplement to an application under section 355 of this

title proposing a labeling change pursuant to a report on a

pediatric study under this section -

(A) shall be considered to be a priority supplement; and

(B) shall be subject to the performance goals established by

the Commissioner for priority drugs.

(2) Dispute resolution

(A) Request for labeling change and failure to agree

If the Commissioner determines that an application with

respect to which a pediatric study is conducted under this

section is approvable and that the only open issue for final

action on the application is the reaching of an agreement

between the sponsor of the application and the Commissioner on

appropriate changes to the labeling for the drug that is the

subject of the application, not later than 180 days after the

date of submission of the application -

(i) the Commissioner shall request that the sponsor of the

application make any labeling change that the Commissioner

determines to be appropriate; and

(ii) if the sponsor of the application does not agree to

make a labeling change requested by the Commissioner, the

Commissioner shall refer the matter to the Pediatric Advisory

Subcommittee of the Anti-Infective Drugs Advisory Committee.

(B) Action by the Pediatric Advisory Subcommittee of the

Anti-Infective Drugs Advisory Committee

Not later than 90 days after receiving a referral under

subparagraph (A)(ii), the Pediatric Advisory Subcommittee of

the Anti-Infective Drugs Advisory Committee shall -

(i) review the pediatric study reports; and

(ii) make a recommendation to the Commissioner concerning

appropriate labeling changes, if any.

(C) Consideration of recommendations

The Commissioner shall consider the recommendations of the

Pediatric Advisory Subcommittee of the Anti-Infective Drugs

Advisory Committee and, if appropriate, not later than 30 days

after receiving the recommendation, make a request to the

sponsor of the application to make any labeling change that the

Commissioner determines to be appropriate.

(D) Misbranding

If the sponsor of the application, within 30 days after

receiving a request under subparagraph (C), does not agree to

make a labeling change requested by the Commissioner, the

Commissioner may deem the drug that is the subject of the

application to be misbranded.

(E) No effect on authority

Nothing in this subsection limits the authority of the United

States to bring an enforcement action under this chapter when a

drug lacks appropriate pediatric labeling. Neither course of

action (the Pediatric Advisory Subcommittee of the

Anti-Infective Drugs Advisory Committee process or an

enforcement action referred to in the preceding sentence) shall

preclude, delay, or serve as the basis to stay the other course

of action.

(j) Dissemination of pediatric information

(1) In general

Not later than 180 days after the date of submission of a

report on a pediatric study under this section, the Commissioner

shall make available to the public a summary of the medical and

clinical pharmacology reviews of pediatric studies conducted for

the supplement, including by publication in the Federal Register.

(2) Effect of subsection

Nothing in this subsection alters or amends section 331(j) of

this title or section 552 of title 5 or section 1905 of title 18.

(k) Clarification of interaction of market exclusivity under this

section and market exclusivity awarded to an applicant for

approval of a drug under section 355(j) of this title

If a 180-day period under section 355(j)(5)(B)(iv) of this title

overlaps with a 6-month exclusivity period under this section, so

that the applicant for approval of a drug under section 355(j) of

this title entitled to the 180-day period under that section loses

a portion of the 180-day period to which the applicant is entitled

for the drug, the 180-day period shall be extended from -

(1) the date on which the 180-day period would have expired by

the number of days of the overlap, if the 180-day period would,

but for the application of this subsection, expire after the

6-month exclusivity period; or

(2) the date on which the 6-month exclusivity period expires,

by the number of days of the overlap if the 180-day period would,

but for the application of this subsection, expire during the

six-month exclusivity period.

(l) Prompt approval of drugs under section 355(j) of this title

when pediatric information is added to labeling

(1) General rule

A drug for which an application has been submitted or approved

under section 355(j) of this title shall not be considered

ineligible for approval under that section or misbranded under

section 352 of this title on the basis that the labeling of the

drug omits a pediatric indication or any other aspect of labeling

pertaining to pediatric use when the omitted indication or other

aspect is protected by patent or by exclusivity under clause

(iii) or (iv) of section 355(j)(5)(D) of this title.

(2) Labeling

Notwithstanding clauses (iii) and (iv) of section 355(j)(5)(D)

of this title, the Secretary may require that the labeling of a

drug approved under section 355(j) of this title that omits a

pediatric indication or other aspect of labeling as described in

paragraph (1) include -

(A) a statement that, because of marketing exclusivity for a

manufacturer -

(i) the drug is not labeled for pediatric use; or

(ii) in the case of a drug for which there is an additional

pediatric use not referred to in paragraph (1), the drug is

not labeled for the pediatric use under paragraph (1); and

(B) a statement of any appropriate pediatric

contraindications, warnings, or precautions that the Secretary

considers necessary.

(3) Preservation of pediatric exclusivity and other provisions

This subsection does not affect -

(A) the availability or scope of exclusivity under this

section;

(B) the availability or scope of exclusivity under section

355 of this title for pediatric formulations;

(C) the question of the eligibility for approval of any

application under section 355(j) of this title that omits any

other conditions of approval entitled to exclusivity under

clause (iii) or (iv) of section 355(j)(5)(D) of this title; or

(D) except as expressly provided in paragraphs (1) and (2),

the operation of section 355 of this title.

(m) Report

The Secretary shall conduct a study and report to Congress not

later than January 1, 2001, based on the experience under the

program established under this section. The study and report shall

examine all relevant issues, including -

(1) the effectiveness of the program in improving information

about important pediatric uses for approved drugs;

(2) the adequacy of the incentive provided under this section;

(3) the economic impact of the program on taxpayers and

consumers, including the impact of the lack of lower cost generic

drugs on patients, including on lower income patients; and

(4) any suggestions for modification that the Secretary

determines to be appropriate.

(n) Sunset

A drug may not receive any 6-month period under subsection (b) or

(c) of this section unless -

(1) on or before October 1, 2007, the Secretary makes a written

request for pediatric studies of the drug;

(2) on or before October 1, 2007, an application for the drug

is accepted for filing under section 355(b) of this title; and

(3) all requirements of this section are met.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 505A, as added Pub. L. 105-115, title

I, Sec. 111, Nov. 21, 1997, 111 Stat. 2305; amended Pub. L.

107-109, Sec. 2, 4, 5(b)(2), 7-11(a), 18(a), 19, Jan. 4, 2002, 115

Stat. 1408, 1411, 1413-1415, 1423, 1424.)

-REFTEXT-

REFERENCES IN TEXT

Section 290b(j)(9)(B)(i) of title 42, referred to in subsec.

(d)(4)(C), was in the original ''section 499(j)(9)(B)(i)'' and was

translated as meaning section 499(j)(9)(B)(i) of the Public Health

Service Act to reflect the probable intent of Congress because

there is no section 499 of the Federal Food, Drug, and Cosmetic Act

and section 499 of the Public Health Service Act relates to the

establishment and duties of the National Foundation for Biomedical

Research.

-MISC2-

AMENDMENTS

2002 - Subsec. (a). Pub. L. 107-109, Sec. 19(2), (3),

redesignated subsec. (g) as (a). Former subsec. (a) redesignated

(b).

Subsec. (a)(1)(A). Pub. L. 107-109, Sec. 19(1)(A), (B),

substituted ''(j)(5)(D)(ii)'' for ''(j)(4)(D)(ii)'' in two places

in cl. (i) and ''(j)(5)(D)'' for ''(j)(4)(D)'' in cl. (ii).

Subsec. (b). Pub. L. 107-109, Sec. 19(2), (3), redesignated

subsec. (a) as (b).

Pub. L. 107-109, Sec. 2(1), struck out heading and text of

subsec. (b). Text read as follows: ''Not later than 180 days after

November 21, 1997, the Secretary, after consultation with experts

in pediatric research shall develop, prioritize, and publish an

initial list of approved drugs for which additional pediatric

information may produce health benefits in the pediatric

population. The Secretary shall annually update the list.''

Subsec. (c). Pub. L. 107-109, Sec. 2(2), in introductory

provisions, inserted ''determines that information relating to the

use of an approved drug in the pediatric population may produce

health benefits in that population and'' after ''the Secretary''

and struck out ''concerning a drug identified in the list described

in subsection (b) of this section'' after ''such studies)''.

Subsec. (c)(1)(A). Pub. L. 107-109, Sec. 19(1)(A), (B),

substituted ''(j)(5)(D)(ii)'' for ''(j)(4)(D)(ii)'' in two places

in cl. (i) and ''(j)(5)(D)'' for ''(j)(4)(D)'' in cl. (ii).

Subsec. (d)(1). Pub. L. 107-109, Sec. 19(4), substituted

''subsection (b) or (c)'' for ''subsection (a) or (c)'' in

introductory provisions.

Subsec. (d)(2). Pub. L. 107-109, Sec. 18(a), 19(4), substituted

''subsection (b) or (c)'' for ''subsection (a) or (c)'' and

inserted ''In reaching an agreement regarding written protocols,

the Secretary shall take into account adequate representation of

children of ethnic and racial minorities.'' after first sentence.

Subsec. (d)(3). Pub. L. 107-109, Sec. 19(4), substituted

''subsection (b) or (c)'' for ''subsection (a) or (c)''.

Subsec. (d)(4). Pub. L. 107-109, Sec. 4, added par. (4).

Subsec. (e). Pub. L. 107-109, Sec. 19(1)(C), (4), substituted

''section 355(j)(5)(D)'' for ''section 355(j)(4)(D)'' and

''subsection (b) or (c)'' for ''subsection (a) or (c)''.

Subsec. (g). Pub. L. 107-109, Sec. 19(2), (3), (5), redesignated

subsec. (h) as (g) and substituted ''subsection (b) or (c)'' for

''subsection (a) or (b)'' in introductory provisions. Former

subsec. (g) redesignated (a).

Pub. L. 107-109, Sec. 7, inserted ''(including neonates in

appropriate cases)'' after ''pediatric age groups''.

Subsec. (h). Pub. L. 107-109, Sec. 19(2), (3), redesignated

subsec. (i) as (h). Former subsec. (h) redesignated (g).

Subsec. (i). Pub. L. 107-109, Sec. 19(2), (3), redesignated

subsec. (l) as (i). Former subsec. (i) redesignated (h).

Subsec. (j). Pub. L. 107-109, Sec. 19(2), (3), redesignated

subsec. (m) as (j). Former subsec. (j) redesignated (n).

Pub. L. 107-109, Sec. 8, added subsec. (j) and struck out heading

and text of former subsec. (j). Text read as follows: ''A drug may

not receive any six-month period under subsection (a) or (c) of

this section unless the application for the drug under section

355(b)(1) of this title is submitted on or before January 1, 2002.

After January 1, 2002, a drug shall receive a six-month period

under subsection (c) of this section if -

''(1) the drug was in commercial distribution as of November

21, 1997;

''(2) the drug was included by the Secretary on the list under

subsection (b) of this section as of January 1, 2002;

''(3) the Secretary determines that there is a continuing need

for information relating to the use of the drug in the pediatric

population and that the drug may provide health benefits in that

population; and

''(4) all requirements of this section are met.''

Subsec. (k). Pub. L. 107-109, Sec. 19(2), (3), redesignated

subsec. (n) as (k). Former subsec. (k) redesignated (m).

Subsec. (l). Pub. L. 107-109, Sec. 19(2), (3), redesignated

subsec. (o) as (l). Former subsec. (l) redesignated (i).

Pub. L. 107-109, Sec. 5(b)(2), added subsec. (l).

Subsec. (m). Pub. L. 107-109, Sec. 19(2), (3), redesignated

subsec. (k) as (m). Former subsec. (m) redesignated (j).

Pub. L. 107-109, Sec. 9, added subsec. (m).

Subsec. (n). Pub. L. 107-109, Sec. 19(4), which directed

substitution of ''subsection (b) or (c)'' for ''subsection (a) or

(c)'' in subsec. (m), was executed by making the substitution in

introductory provisions of subsec. (n), to reflect the probable

intent of Congress.

Pub. L. 107-109, Sec. 19(2), (3), redesignated subsec. (j) as

(n). Former subsec. (n) redesignated (k).

Pub. L. 107-109, Sec. 10, added subsec. (n).

Subsec. (o). Pub. L. 107-109, Sec. 19(2), (3), redesignated

subsec. (o) as (l).

Pub. L. 107-109, Sec. 11(a), added subsec. (o).

EFFECTIVE DATE OF 2002 AMENDMENT

Pub. L. 107-109, Sec. 11(b), Jan. 4, 2002, 115 Stat. 1416,

provided that: ''The amendment made by subsection (a) (amending

this section) takes effect on the date of enactment of this Act

(Jan. 4, 2002), including with respect to applications under

section 505(j) of the Federal Food, Drug, and Cosmetic Act (21

U.S.C. 355(j)) that are approved or pending on that date.''

REPORT ON PEDIATRIC EXCLUSIVITY PROGRAM

Pub. L. 107-109, Sec. 16, Jan. 4, 2002, 115 Stat. 1421, provided

that: ''Not later than October 1, 2006, the Comptroller General of

the United States, in consultation with the Secretary of Health and

Human Services, shall submit to Congress a report that addresses

the following issues, using publicly available data or data

otherwise available to the Government that may be used and

disclosed under applicable law:

''(1) The effectiveness of section 505A of the Federal Food,

Drug, and Cosmetic Act (21 U.S.C. 355a) and section 409I of the

Public Health Service Act (42 U.S.C. 284m) (as added by this Act)

in ensuring that medicines used by children are tested and

properly labeled, including -

''(A) the number and importance of drugs for children that

are being tested as a result of this legislation and the

importance for children, health care providers, parents, and

others of labeling changes made as a result of such testing;

''(B) the number and importance of drugs for children that

are not being tested for their use notwithstanding the

provisions of this legislation, and possible reasons for the

lack of testing; and

''(C) the number of drugs for which testing is being done,

exclusivity granted, and labeling changes required, including

the date pediatric exclusivity is granted and the date labeling

changes are made and which labeling changes required the use of

the dispute resolution process established pursuant to the

amendments made by this Act (see Short Title of 2002 Amendment

note set out under section 301 of this title), together with a

description of the outcomes of such process, including a

description of the disputes and the recommendations of the

Pediatric Advisory Subcommittee of the Anti-Infective Drugs

Advisory Committee.

''(2) The economic impact of section 505A of the Federal Food,

Drug, and Cosmetic Act and section 409I of the Public Health

Service Act (as added by this Act), including an estimate of -

''(A) the costs to taxpayers in the form of higher

expenditures by medicaid and other Government programs;

''(B) sales for each drug during the 6-month period for which

exclusivity is granted, as attributable to such exclusivity;

''(C) costs to consumers and private insurers as a result of

any delay in the availability of lower cost generic equivalents

of drugs tested and granted exclusivity under the Federal Food,

Drug, and Cosmetic Act (21 U.S.C. 301 et seq.), and loss of

revenue by the generic drug industry and retail pharmacies as a

result of any such delay; and

''(D) the benefits to the government, to private insurers,

and to consumers resulting from decreased health care costs,

including -

''(i) decreased hospitalizations and fewer medical errors,

due to more appropriate and more effective use of medications

in children as a result of testing and re-labeling because of

the amendments made by this Act;

''(ii) direct and indirect benefits associated with fewer

physician visits not related to hospitalization;

''(iii) benefits to children from missing less time at

school and being less affected by chronic illnesses, thereby

allowing a better quality of life;

''(iv) benefits to consumers from lower health insurance

premiums due to lower treatment costs and hospitalization

rates; and

''(v) benefits to employers from reduced need for employees

to care for family members.

''(3) The nature and type of studies in children for each drug

granted exclusivity under the Federal Food, Drug, and Cosmetic

Act (21 U.S.C. 301 et seq.), including -

''(A) a description of the complexity of the studies;

''(B) the number of study sites necessary to obtain

appropriate data;

''(C) the number of children involved in any clinical

studies; and

''(D) the estimated cost of each of the studies.

''(4) Any recommendations for modifications to the programs

established under section 505A of the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 355a) and section 409I of the Public

Health Service Act (42 U.S.C. 284m) (as added by section 3) that

the Secretary determines to be appropriate, including a detailed

rationale for each recommendation.

''(5) The increased private and Government-funded pediatric

research capability associated with this Act and the amendments

made by this Act.

''(6) The number of written requests and additional letters of

recommendation that the Secretary issues.

''(7) The prioritized list of off-patent drugs for which the

Secretary issues written requests.

''(8)(A) The efforts made by the Secretary to increase the

number of studies conducted in the neonate population; and

''(B) the results of those efforts, including efforts made to

encourage the conduct of appropriate studies in neonates by

companies with products that have sufficient safety and other

information to make the conduct of studies ethical and safe.''

STUDY BY GENERAL ACCOUNTING OFFICE

Pub. L. 107-109, Sec. 18(b), Jan. 4, 2002, 115 Stat. 1423,

provided that:

''(1) In general. - The Comptroller General of the United States

shall conduct a study for the purpose of determining the following:

''(A) The extent to which children of ethnic and racial

minorities are adequately represented in studies under section

505A of the Federal Food, Drug, and Cosmetic Act (21 U.S.C.

355a); and to the extent ethnic and racial minorities are not

adequately represented, the reasons for such under representation

and recommendations to increase such representation.

''(B) Whether the Food and Drug Administration has appropriate

management systems to monitor the representation of the children

of ethnic and racial minorities in such studies.

''(C) Whether drugs used to address diseases that

disproportionately affect racial and ethnic minorities are being

studied for their safety and effectiveness under section 505A of

the Federal Food, Drug, and Cosmetic Act.

''(2) Date certain for completing study. - Not later than January

10, 2003, the Comptroller General shall complete the study required

in paragraph (1) and submit to the Congress a report describing the

findings of the study.''

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in section 355b of this title; title

42 sections 284m, 290b.

-CITE-

21 USC Sec. 355b 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 355b. Adverse-event reporting

-STATUTE-

(a) Toll-free number in labeling

Not later than one year after January 4, 2002, the Secretary of

Health and Human Services shall promulgate a final rule requiring

that the labeling of each drug for which an application is approved

under section 505 of the Federal Food, Drug, and Cosmetic Act (21

U.S.C. 355) (regardless of the date on which approved) include the

toll-free number maintained by the Secretary for the purpose of

receiving reports of adverse events regarding drugs and a statement

that such number is to be used for reporting purposes only, not to

receive medical advice. With respect to the final rule:

(1) The rule shall provide for the implementation of such

labeling requirement in a manner that the Secretary considers to

be most likely to reach the broadest consumer audience.

(2) In promulgating the rule, the Secretary shall seek to

minimize the cost of the rule on the pharmacy profession.

(3) The rule shall take effect not later than 60 days after the

date on which the rule is promulgated.

(b) Drugs with pediatric market exclusivity

(1) In general

During the one year beginning on the date on which a drug

receives a period of market exclusivity under 505A (FOOTNOTE 1)

of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a), any

report of an adverse event regarding the drug that the Secretary

of Health and Human Services receives shall be referred to the

Office of Pediatric Therapeutics established under section 393a

of this title. In considering the report, the Director of such

Office shall provide for the review of the report by the

Pediatric Advisory Subcommittee of the Anti-Infective Drugs

Advisory Committee, including obtaining any recommendations of

such subcommittee regarding whether the Secretary should take

action under the Federal Food, Drug, and Cosmetic Act (21 U.S.C.

301 et seq.) in response to the report.

(FOOTNOTE 1) So in original. Probably should be preceded by

''section''.

(2) Rule of construction

Paragraph (1) may not be construed as restricting the authority

of the Secretary of Health and Human Services to continue

carrying out the activities described in such paragraph regarding

a drug after the one-year period described in such paragraph

regarding the drug has expired.

-SOURCE-

(Pub. L. 107-109, Sec. 17, Jan. 4, 2002, 115 Stat. 1422.)

-REFTEXT-

REFERENCES IN TEXT

The Federal Food, Drug, and Cosmetic Act, referred to in subsec.

(b)(1), is act June 25, 1938, ch. 675, 52 Stat. 1040, as amended,

which is classified generally to this chapter. For complete

classification of this Act to the Code, see section 301 of this

title and Tables.

-COD-

CODIFICATION

Section was enacted as part of the Best Pharmaceuticals for

Children Act, and not as part of the Federal Food, Drug, and

Cosmetic Act which comprises this chapter.

-CITE-

21 USC Sec. 356 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 356. Fast track products

-STATUTE-

(a) Designation of drug as fast track product

(1) In general

The Secretary shall, at the request of the sponsor of a new

drug, facilitate the development and expedite the review of such

drug if it is intended for the treatment of a serious or

life-threatening condition and it demonstrates the potential to

address unmet medical needs for such a condition. (In this

section, such a drug is referred to as a ''fast track product''.)

(2) Request for designation

The sponsor of a new drug may request the Secretary to

designate the drug as a fast track product. A request for the

designation may be made concurrently with, or at any time after,

submission of an application for the investigation of the drug

under section 355(i) of this title or section 262(a)(3) of title

42.

(3) Designation

Within 60 calendar days after the receipt of a request under

paragraph (2), the Secretary shall determine whether the drug

that is the subject of the request meets the criteria described

in paragraph (1). If the Secretary finds that the drug meets the

criteria, the Secretary shall designate the drug as a fast track

product and shall take such actions as are appropriate to

expedite the development and review of the application for

approval of such product.

(b) Approval of application for fast track product

(1) In general

The Secretary may approve an application for approval of a fast

track product under section 355(c) of this title or section 262

of title 42 upon a determination that the product has an effect

on a clinical endpoint or on a surrogate endpoint that is

reasonably likely to predict clinical benefit.

(2) Limitation

Approval of a fast track product under this subsection may be

subject to the requirements -

(A) that the sponsor conduct appropriate post-approval

studies to validate the surrogate endpoint or otherwise confirm

the effect on the clinical endpoint; and

(B) that the sponsor submit copies of all promotional

materials related to the fast track product during the

preapproval review period and, following approval and for such

period thereafter as the Secretary determines to be

appropriate, at least 30 days prior to dissemination of the

materials.

(3) Expedited withdrawal of approval

The Secretary may withdraw approval of a fast track product

using expedited procedures (as prescribed by the Secretary in

regulations which shall include an opportunity for an informal

hearing) if -

(A) the sponsor fails to conduct any required post-approval

study of the fast track drug with due diligence;

(B) a post-approval study of the fast track product fails to

verify clinical benefit of the product;

(C) other evidence demonstrates that the fast track product

is not safe or effective under the conditions of use; or

(D) the sponsor disseminates false or misleading promotional

materials with respect to the product.

(c) Review of incomplete applications for approval of fast track

product

(1) In general

If the Secretary determines, after preliminary evaluation of

clinical data submitted by the sponsor, that a fast track product

may be effective, the Secretary shall evaluate for filing, and

may commence review of portions of, an application for the

approval of the product before the sponsor submits a complete

application. The Secretary shall commence such review only if

the applicant -

(A) provides a schedule for submission of information

necessary to make the application complete; and

(B) pays any fee that may be required under section 379h of

this title.

(2) Exception

Any time period for review of human drug applications that has

been agreed to by the Secretary and that has been set forth in

goals identified in letters of the Secretary (relating to the use

of fees collected under section 379h of this title to expedite

the drug development process and the review of human drug

applications) shall not apply to an application submitted under

paragraph (1) until the date on which the application is

complete.

(d) Awareness efforts

The Secretary shall -

(1) develop and disseminate to physicians, patient

organizations, pharmaceutical and biotechnology companies, and

other appropriate persons a description of the provisions of this

section applicable to fast track products; and

(2) establish a program to encourage the development of

surrogate endpoints that are reasonably likely to predict

clinical benefit for serious or life-threatening conditions for

which there exist significant unmet medical needs.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 506, as added Pub. L. 105-115, title

I, Sec. 112(a), Nov. 21, 1997, 111 Stat. 2309.)

-MISC1-

PRIOR PROVISIONS

A prior section 356, act June 25, 1938, ch. 675, Sec. 506, as

added Dec. 22, 1941, ch. 613, Sec. 3, 55 Stat. 851; amended Pub. L.

102-300, Sec. 6(b)(2), June 16, 1992, 106 Stat. 240; Pub. L.

103-80, Sec. 3(o), Aug. 13, 1993, 107 Stat. 777, related to

certification of drugs containing insulin, prior to repeal by Pub.

L. 105-115, title I, Sec. 125(a)(1), Nov. 21, 1997, 111 Stat. 2325.

EFFECTIVE DATE

Section effective 90 days after Nov. 21, 1997, except as

otherwise provided, see section 501 of Pub. L. 105-115, set out as

an Effective Date of 1997 Amendment note under section 321 of this

title.

GUIDANCE

Section 112(b) of Pub. L. 105-115 provided that: ''Within 1 year

after the date of enactment of this Act (Nov. 21, 1997), the

Secretary of Health and Human Services shall issue guidance for

fast track products (as defined in section 506(a)(1) of the Federal

Food, Drug, and Cosmetic Act (21 U.S.C. 356(a)(1))) that describes

the policies and procedures that pertain to section 506 of such

Act.''

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in sections 356-1, 356b of this

title; title 15 section 1459; title 42 section 1396r-8.

-CITE-

21 USC Sec. 356-1 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 356-1. Accelerated approval of priority countermeasures

-STATUTE-

(a) In general

The Secretary of Health and Human Services may designate a

priority countermeasure as a fast-track product pursuant to section

356 of this title or as a device granted review priority pursuant

to section 360e(d)(5) of this title. Such a designation may be

made prior to the submission of -

(1) a request for designation by the sponsor or applicant; or

(2) an application for the investigation of the drug under

section 355(i) of this title or section 262(a)(3) of title 42.

Nothing in this subsection shall be construed to prohibit a sponsor

or applicant from declining such a designation.

(b) Use of animal trials

A drug for which approval is sought under section 355(b) of this

title or section 262 of title 42 on the basis of evidence of

effectiveness that is derived from animal studies pursuant to

section 123 (FOOTNOTE 1) may be designated as a fast track product

for purposes of this section.

(FOOTNOTE 1) See References in Text note below.

(c) Priority review of drugs and biological products

A priority countermeasure that is a drug or biological product

shall be considered a priority drug or biological product for

purposes of performance goals for priority drugs or biological

products agreed to by the Commissioner of Food and Drugs.

(d) Definitions

For purposes of this title: (FOOTNOTE 1)

(1) The term ''priority countermeasure'' has the meaning given

such term in section 247d-6(h)(4) of title 42.

(2) The term ''priority drugs or biological products'' means a

drug or biological product that is the subject of a drug or

biologics application referred to in section 101(4) of the Food

and Drug Administration Modernization Act of 1997.

-SOURCE-

(Pub. L. 107-188, title I, Sec. 122, June 12, 2002, 116 Stat. 613.)

-REFTEXT-

REFERENCES IN TEXT

Section 123, referred to in subsec. (b), is section 123 of Pub.

L. 107-188, title I, June 12, 2002, 116 Stat. 613, which is not

classified to the Code.

This title, referred to in subsec. (d), is title I of Pub. L.

107-188, June 12, 2002, 116 Stat. 596, which enacted this section,

section 669a of Title 29, Labor, and sections 244, 245, 247d-3a,

247d-3b, 247d-7a to 247d-7d, 300hh, 300hh-11 to 300hh-13, 1320b-5,

and 7257d of Title 42, The Public Health and Welfare, amended

sections 247d to 247d-6, 264, 266, 290hh-1, and 5196b of Title 42,

and enacted provisions set out as notes preceding section 8101 of

Title 38, Veterans' Benefits, and under sections 201, 244, 247d,

247d-6, 300hh, 300hh-12, and 1320b-5 of Title 42. For complete

classification of this title to the Code, see Tables.

Section 101(4) of the Food and Drug Administration Modernization

Act of 1997, referred to in subsec. (d)(2), is section 101(4) of

Pub. L. 105-115, which is set out as a note under section 379g of

this title.

-COD-

CODIFICATION

Section was enacted as part of the Public Health Security and

Bioterrorism Preparedness and Response Act of 2002, and not as part

of the Federal Food, Drug, and Cosmetic Act which comprises this

chapter.

-CITE-

21 USC Sec. 356a 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 356a. Manufacturing changes

-STATUTE-

(a) In general

With respect to a drug for which there is in effect an approved

application under section 355 or 360b of this title or a license

under section 262 of title 42, a change from the manufacturing

process approved pursuant to such application or license may be

made, and the drug as made with the change may be distributed, if -

(1) the holder of the approved application or license (referred

to in this section as a ''holder'') has validated the effects of

the change in accordance with subsection (b) of this section; and

(2)(A) in the case of a major manufacturing change, the holder

has complied with the requirements of subsection (c) of this

section; or

(B) in the case of a change that is not a major manufacturing

change, the holder complies with the applicable requirements of

subsection (d) of this section.

(b) Validation of effects of changes

For purposes of subsection (a)(1) of this section, a drug made

with a manufacturing change (whether a major manufacturing change

or otherwise) may be distributed only if, before distribution of

the drug as so made, the holder involved validates the effects of

the change on the identity, strength, quality, purity, and potency

of the drug as the identity, strength, quality, purity, and potency

may relate to the safety or effectiveness of the drug.

(c) Major manufacturing changes

(1) Requirement of supplemental application

For purposes of subsection (a)(2)(A) of this section, a drug

made with a major manufacturing change may be distributed only

if, before the distribution of the drug as so made, the holder

involved submits to the Secretary a supplemental application for

such change and the Secretary approves the application. The

application shall contain such information as the Secretary

determines to be appropriate, and shall include the information

developed under subsection (b) of this section by the holder in

validating the effects of the change.

(2) Changes qualifying as major changes

For purposes of subsection (a)(2)(A) of this section, a major

manufacturing change is a manufacturing change that is determined

by the Secretary to have substantial potential to adversely

affect the identity, strength, quality, purity, or potency of the

drug as they may relate to the safety or effectiveness of a

drug. Such a change includes a change that -

(A) is made in the qualitative or quantitative formulation of

the drug involved or in the specifications in the approved

application or license referred to in subsection (a) of this

section for the drug (unless exempted by the Secretary by

regulation or guidance from the requirements of this

subsection);

(B) is determined by the Secretary by regulation or guidance

to require completion of an appropriate clinical study

demonstrating equivalence of the drug to the drug as

manufactured without the change; or

(C) is another type of change determined by the Secretary by

regulation or guidance to have a substantial potential to

adversely affect the safety or effectiveness of the drug.

(d) Other manufacturing changes

(1) In general

For purposes of subsection (a)(2)(B) of this section, the

Secretary may regulate drugs made with manufacturing changes that

are not major manufacturing changes as follows:

(A) The Secretary may in accordance with paragraph (2)

authorize holders to distribute such drugs without submitting a

supplemental application for such changes.

(B) The Secretary may in accordance with paragraph (3)

require that, prior to the distribution of such drugs, holders

submit to the Secretary supplemental applications for such

changes.

(C) The Secretary may establish categories of such changes

and designate categories to which subparagraph (A) applies and

categories to which subparagraph (B) applies.

(2) Changes not requiring supplemental application

(A) Submission of report

A holder making a manufacturing change to which paragraph

(1)(A) applies shall submit to the Secretary a report on the

change, which shall contain such information as the Secretary

determines to be appropriate, and which shall include the

information developed under subsection (b) of this section by

the holder in validating the effects of the change. The report

shall be submitted by such date as the Secretary may specify.

(B) Authority regarding annual reports

In the case of a holder that during a single year makes more

than one manufacturing change to which paragraph (1)(A)

applies, the Secretary may in carrying out subparagraph (A)

authorize the holder to comply with such subparagraph by

submitting a single report for the year that provides the

information required in such subparagraph for all the changes

made by the holder during the year.

(3) Changes requiring supplemental application

(A) Submission of supplemental application

The supplemental application required under paragraph (1)(B)

for a manufacturing change shall contain such information as

the Secretary determines to be appropriate, which shall include

the information developed under subsection (b) of this section

by the holder in validating the effects of the change.

(B) Authority for distribution

In the case of a manufacturing change to which paragraph

(1)(B) applies:

(i) The holder involved may commence distribution of the

drug involved 30 days after the Secretary receives the

supplemental application under such paragraph, unless the

Secretary notifies the holder within such 30-day period that

prior approval of the application is required before

distribution may be commenced.

(ii) The Secretary may designate a category of such changes

for the purpose of providing that, in the case of a change

that is in such category, the holder involved may commence

distribution of the drug involved upon the receipt by the

Secretary of a supplemental application for the change.

(iii) If the Secretary disapproves the supplemental

application, the Secretary may order the manufacturer to

cease the distribution of the drugs that have been made with

the manufacturing change.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 506A, as added Pub. L. 105-115, title

I, Sec. 116(a), Nov. 21, 1997, 111 Stat. 2313.)

-MISC1-

EFFECTIVE DATE

Section 116(b) of Pub. L. 105-115 provided that: ''The amendment

made by subsection (a) (enacting this section) takes effect upon

the effective date of regulations promulgated by the Secretary of

Health and Human Services to implement such amendment, or upon the

expiration of the 24-month period beginning on the date of the

enactment of this Act (Nov. 21, 1997), whichever occurs first.''

-CITE-

21 USC Sec. 356b 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 356b. Reports of postmarketing studies

-STATUTE-

(a) Submission

(1) In general

A sponsor of a drug that has entered into an agreement with the

Secretary to conduct a postmarketing study of a drug shall submit

to the Secretary, within 1 year after the approval of such drug

and annually thereafter until the study is completed or

terminated, a report of the progress of the study or the reasons

for the failure of the sponsor to conduct the study. The report

shall be submitted in such form as is prescribed by the Secretary

in regulations issued by the Secretary.

(2) Agreements prior to effective date

Any agreement entered into between the Secretary and a sponsor

of a drug, prior to November 21, 1997, to conduct a postmarketing

study of a drug shall be subject to the requirements of paragraph

(1). An initial report for such an agreement shall be submitted

within 6 months after the date of the issuance of the regulations

under paragraph (1).

(b) Consideration of information as public information

Any information pertaining to a report described in subsection

(a) of this section shall be considered to be public information to

the extent that the information is necessary -

(1) to identify the sponsor; and

(2) to establish the status of a study described in subsection

(a) of this section and the reasons, if any, for any failure to

carry out the study.

(c) Status of studies and reports

The Secretary shall annually develop and publish in the Federal

Register a report that provides information on the status of the

postmarketing studies -

(1) that sponsors have entered into agreements to conduct; and

(2) for which reports have been submitted under subsection

(a)(1) of this section.

(d) Disclosure

If a sponsor fails to complete an agreed upon study required by

this section by its original or otherwise negotiated deadline, the

Secretary shall publish a statement on the Internet site of the

Food and Drug Administration stating that the study was not

completed and, if the reasons for such failure to complete the

study were not satisfactory to the Secretary, a statement that such

reasons were not satisfactory to the Secretary.

(e) Notification

With respect to studies of the type required under section

356(b)(2)(A) of this title or under section 314.510 or 601.41 of

title 21, Code of Federal Regulations, as each of such sections was

in effect on the day before the effective date of this subsection,

the Secretary may require that a sponsor who, for reasons not

satisfactory to the Secretary, fails to complete by its deadline a

study under any of such sections of such type for a drug or

biological product (including such a study conducted after such

effective date) notify practitioners who prescribe such drug or

biological product of the failure to complete such study and the

questions of clinical benefit, and, where appropriate, questions of

safety, that remain unanswered as a result of the failure to

complete such study. Nothing in this subsection shall be construed

as altering the requirements of the types of studies required under

section 356(b)(2)(A) of this title or under section 314.510 or

601.41 of title 21, Code of Federal Regulations, as so in effect,

or as prohibiting the Secretary from modifying such sections of

title 21 of such Code to provide for studies in addition to those

of such type.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 506B, as added Pub. L. 105-115, title

I, Sec. 130(a), Nov. 21, 1997, 111 Stat. 2331; amended Pub. L.

107-188, title V, Sec. 506, June 12, 2002, 116 Stat. 693.)

-REFTEXT-

REFERENCES IN TEXT

The effective date of this subsection, referred to in subsec.

(e), is Oct. 1, 2002, see Effective Date of 2002 Amendment note set

out below.

-MISC2-

AMENDMENTS

2002 - Subsecs. (d), (e). Pub. L. 107-188 added subsecs. (d) and

(e).

EFFECTIVE DATE OF 2002 AMENDMENT

Pub. L. 107-188, title V, Sec. 508, June 12, 2002, 116 Stat. 694,

provided that: ''The amendments made by this subtitle (subtitle A

(Sec. 501-509) of title V of Pub. L. 107-188, amending this section

and sections 379g and 379h of this title) shall take effect October

1, 2002.''

EFFECTIVE DATE

Section effective 90 days after Nov. 21, 1997, except as

otherwise provided, see section 501 of Pub. L. 105-115, set out as

an Effective Date of 1997 Amendment note under section 321 of this

title.

REPORT TO CONGRESSIONAL COMMITTEES

Section 130(b) of Pub. L. 105-115 provided that: ''Not later than

October 1, 2001, the Secretary shall prepare and submit to the

Committee on Labor and Human Resources of the Senate and the

Committee on Commerce (now Committee on Energy and Commerce) of the

House of Representatives a report containing -

''(1) a summary of the reports submitted under section 506B of

the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 356b);

''(2) an evaluation of -

''(A) the performance of the sponsors referred to in such

section in fulfilling the agreements with respect to the

conduct of postmarketing studies described in such section of

such Act; and

''(B) the timeliness of the Secretary's review of the

postmarketing studies; and

''(3) any legislative recommendations respecting the

postmarketing studies.''

-CITE-

21 USC Sec. 356c 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 356c. Discontinuance of life saving product

-STATUTE-

(a) In general

A manufacturer that is the sole manufacturer of a drug -

(1) that is -

(A) life-supporting;

(B) life-sustaining; or

(C) intended for use in the prevention of a debilitating

disease or condition;

(2) for which an application has been approved under section

355(b) or 355(j) of this title; and

(3) that is not a product that was originally derived from

human tissue and was replaced by a recombinant product,

shall notify the Secretary of a discontinuance of the manufacture

of the drug at least 6 months prior to the date of the

discontinuance.

(b) Reduction in notification period

The notification period required under subsection (a) of this

section for a manufacturer may be reduced if the manufacturer

certifies to the Secretary that good cause exists for the

reduction, such as a situation in which -

(1) a public health problem may result from continuation of the

manufacturing for the 6-month period;

(2) a biomaterials shortage prevents the continuation of the

manufacturing for the 6-month period;

(3) a liability problem may exist for the manufacturer if the

manufacturing is continued for the 6-month period;

(4) continuation of the manufacturing for the 6-month period

may cause substantial economic hardship for the manufacturer;

(5) the manufacturer has filed for bankruptcy under chapter 7

or 11 of title 11; or

(6) the manufacturer can continue the distribution of the drug

involved for 6 months.

(c) Distribution

To the maximum extent practicable, the Secretary shall distribute

information on the discontinuation of the drugs described in

subsection (a) of this section to appropriate physician and patient

organizations.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 506C, as added Pub. L. 105-115, title

I, Sec. 131(a), Nov. 21, 1997, 111 Stat. 2332.)

-MISC1-

EFFECTIVE DATE

Section effective 90 days after Nov. 21, 1997, except as

otherwise provided, see section 501 of Pub. L. 105-115, set out as

an Effective Date of 1997 Amendment note under section 321 of this

title.

-CITE-

21 USC Sec. 357 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 357. Repealed. Pub. L. 105-115, title I, Sec. 125(b)(1), Nov.

21, 1997, 111 Stat. 2325

-MISC1-

Section, act June 25, 1938, ch. 675, Sec. 507, as added July 6,

1945, ch. 281, Sec. 3, 59 Stat. 463; amended Mar. 10, 1947, ch. 16,

Sec. 3, 61 Stat. 12; July 13, 1949, ch. 305, Sec. 2, 63 Stat. 409;

Aug. 5, 1953, ch. 334, Sec. 2, 67 Stat. 389; Pub. L. 87-781, title

I, Sec. 105(a), (b), (d)-(f), 106(a), (b), Oct. 10, 1962, 76 Stat.

785, 786, 787; Pub. L. 90-399, Sec. 105(b), July 13, 1968, 82 Stat.

352; Pub. L. 102-300, Sec. 6(b)(2), June 16, 1992, 106 Stat. 240;

Pub. L. 103-80, Sec. 3(p), Aug. 13, 1993, 107 Stat. 777, related to

certification of drugs containing penicillin, streptomycin,

chlortetracycline, chloramphenicol, bacitracin, or any other

antibiotic drug.

-CITE-

21 USC Sec. 358 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 358. Authority to designate official names

-STATUTE-

(a) Necessity or desirability; use in official compendiums;

infringement of trademarks

The Secretary may designate an official name for any drug or

device if he determines that such action is necessary or desirable

in the interest of usefulness and simplicity. Any official name

designated under this section for any drug or device shall be the

only official name of that drug or device used in any official

compendium published after such name has been prescribed or for any

other purpose of this chapter. In no event, however, shall the

Secretary establish an official name so as to infringe a valid

trademark.

(b) Review of names in official compendiums

Within a reasonable time after October 10, 1962, and at such

other times as he may deem necessary, the Secretary shall cause a

review to be made of the official names by which drugs are

identified in the official United States Pharmacopoeia, the

official Homoeopathic Pharmacopoeia of the United States, and the

official National Formulary, and all supplements thereto, and at

such times as he may deem necessary shall cause a review to be made

of the official names by which devices are identified in any

official compendium (and all supplements thereto) to determine

whether revision of any of those names is necessary or desirable in

the interest of usefulness and simplicity.

(c) Determinations of complexity, usefulness, multiplicity, or lack

of name; designation by Secretary

Whenever he determines after any such review that (1) any such

official name is unduly complex or is not useful for any other

reason, (2) two or more official names have been applied to a

single drug or device, or to two or more drugs which are identical

in chemical structure and pharmacological action and which are

substantially identical in strength, quality, and purity, or to two

or more devices which are substantially equivalent in design and

purpose or (3) no official name has been applied to a medically

useful drug or device, he shall transmit in writing to the compiler

of each official compendium in which that drug or drugs or device

are identified and recognized his request for the recommendation of

a single official name for such drug or drugs or device which will

have usefulness and simplicity. Whenever such a single official

name has not been recommended within one hundred and eighty days

after such request, or the Secretary determines that any name so

recommended is not useful for any reason, he shall designate a

single official name for such drug or drugs or device. Whenever he

determines that the name so recommended is useful, he shall

designate that name as the official name of such drug or drugs or

device. Such designation shall be made as a regulation upon public

notice and in accordance with the procedure set forth in section

553 of title 5.

(d) Revised official names; compilation, publication, and public

distribution of listings

After each such review, and at such other times as the Secretary

may determine to be necessary or desirable, the Secretary shall

cause to be compiled, published, and publicly distributed a list

which shall list all revised official names of drugs or devices

designated under this section and shall contain such descriptive

and explanatory matter as the Secretary may determine to be

required for the effective use of those names.

(e) Request by compiler of official compendium for designation of

name

Upon a request in writing by any compiler of an official

compendium that the Secretary exercise the authority granted to him

under subsection (a) of this section, he shall upon public notice

and in accordance with the procedure set forth in section 553 of

title 5 designate the official name of the drug or device for which

the request is made.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 508, as added Pub. L. 87-781, title

I, Sec. 111(a), Oct. 10, 1962, 76 Stat. 789; amended Pub. L.

94-295, Sec. 5(b), May 28, 1976, 90 Stat. 581; Pub. L. 103-80, Sec.

3(q), Aug. 13, 1993, 107 Stat. 777.)

-MISC1-

AMENDMENTS

1993 - Subsecs. (c), (e). Pub. L. 103-80 substituted reference to

section 553 of title 5 for ''section 4 of the Administrative

Procedure Act (5 U.S.C. 1003)''.

1976 - Subsec. (a). Pub. L. 94-295 substituted ''drug or device''

for ''drug'' wherever appearing.

Subsec. (b). Pub. L. 94-295 substituted ''National Formulary, and

all supplements thereto, and at such times as he may deem necessary

shall cause a review to be made of the official names by which

devices are identified in any official compendium (and all

supplements thereto)'' for ''National Formulary, and all

supplements thereto,''.

Subsec. (c)(2). Pub. L. 94-295 inserted ''or device'' after

''single drug'', and ''or to two or more devices which are

substantially equivalent in design and purpose'' after ''purity,''.

Subsec. (c)(3). Pub. L. 94-295 inserted ''or device'' after

''useful drug'' and after ''drug or drugs'' wherever appearing.

Subsec. (d). Pub. L. 94-295 inserted ''or devices'' after

''drugs''.

Subsec. (e). Pub. L. 94-295 substituted ''drug or device'' for

''drug''.

EFFECTIVE DATE

Section 111(b) of Pub. L. 87-781 provided that: ''This section

(enacting this section) shall take effect on the date of its

enactment (Oct. 10, 1962).''

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in section 352 of this title.

-CITE-

21 USC Sec. 359 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 359. Nonapplicability of subchapter to cosmetics

-STATUTE-

This subchapter, as amended by the Drug Amendments of 1962, shall

not apply to any cosmetic unless such cosmetic is also a drug or

device or component thereof.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 509, as added Pub. L. 87-781, title

I, Sec. 113, Oct. 10, 1962, 76 Stat. 791.)

-REFTEXT-

REFERENCES IN TEXT

This subchapter, as amended by the Drug Amendments of 1962,

referred to in text, means the amendment of this subchapter by Pub.

L. 87-781 which enacted sections 358 to 360 of this title, amended

sections 351 to 353, 355, and 357 of this title, and enacted

provisions set out as notes under sections 352, 355, 358, and 360

of this title.

The Drug Amendments of 1962, referred to in text, is Pub. L.

87-781, Oct. 10, 1962, 76 Stat. 780, as amended. For complete

classification of this Act to the Code, see Short Title of 1962

Amendment note set out under section 301 of this title and Tables.

-CITE-

21 USC Sec. 360 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 360. Registration of producers of drugs or devices

-STATUTE-

(a) Definitions

As used in this section -

(1) the term ''manufacture, preparation, propagation,

compounding, or processing'' shall include repackaging or

otherwise changing the container, wrapper, or labeling of any

drug package or device package in furtherance of the distribution

of the drug or device from the original place of manufacture to

the person who makes final delivery or sale to the ultimate

consumer or user; and

(2) the term ''name'' shall include in the case of a

partnership the name of each partner and, in the case of a

corporation, the name of each corporate officer and director, and

the State of incorporation.

(b) Annual registration

On or before December 31 of each year every person who owns or

operates any establishment in any State engaged in the manufacture,

preparation, propagation, compounding, or processing of a drug or

drugs or a device or devices shall register with the Secretary his

name, places of business, and all such establishments.

(c) New producers

Every person upon first engaging in the manufacture, preparation,

propagation, compounding, or processing of a drug or drugs or a

device or devices in any establishment which he owns or operates in

any State shall immediately register with the Secretary his name,

place of business, and such establishment.

(d) Additional establishments

Every person duly registered in accordance with the foregoing

subsections of this section shall immediately register with the

Secretary any additional establishment which he owns or operates in

any State and in which he begins the manufacture, preparation,

propagation, compounding, or processing of a drug or drugs or a

device or devices.

(e) Registration number; uniform system for identification of

devices intended for human use

The Secretary may assign a registration number to any person or

any establishment registered in accordance with this section. The

Secretary may also assign a listing number to each drug or class of

drugs listed under subsection (j) of this section. Any number

assigned pursuant to the preceding sentence shall be the same as

that assigned pursuant to the National Drug Code. The Secretary may

by regulation prescribe a uniform system for the identification of

devices intended for human use and may require that persons who are

required to list such devices pursuant to subsection (j) of this

section shall list such devices in accordance with such system.

(f) Availability of registrations for inspection

The Secretary shall make available for inspection, to any person

so requesting, any registration filed pursuant to this section;

except that any list submitted pursuant to paragraph (3) of

subsection (j) of this section and the information accompanying any

list or notice filed under paragraph (1) or (2) of that subsection

shall be exempt from such inspection unless the Secretary finds

that such an exemption would be inconsistent with protection of the

public health.

(g) Exclusions from application of section

The foregoing subsections of this section shall not apply to -

(1) pharmacies which maintain establishments in conformance

with any applicable local laws regulating the practice of

pharmacy and medicine and which are regularly engaged in

dispensing prescription drugs or devices, upon prescriptions of

practitioners licensed to administer such drugs or devices to

patients under the care of such practitioners in the course of

their professional practice, and which do not manufacture,

prepare, propagate, compound, or process drugs or devices for

sale other than in the regular course of their business of

dispensing or selling drugs or devices at retail;

(2) practitioners licensed by law to prescribe or administer

drugs or devices and who manufacture, prepare, propagate,

compound, or process drugs or devices solely for use in the

course of their professional practice;

(3) persons who manufacture, prepare, propagate, compound, or

process drugs or devices solely for use in research, teaching, or

chemical analysis and not for sale;

(4) any distributor who acts as a wholesale distributor of

devices, and who does not manufacture, repackage, process, or

relabel a device; or

(5) such other classes of persons as the Secretary may by

regulation exempt from the application of this section upon a

finding that registration by such classes of persons in

accordance with this section is not necessary for the protection

of the public health.

In this subsection, the term ''wholesale distributor'' means any

person (other than the manufacturer or the initial importer) who

distributes a device from the original place of manufacture to the

person who makes the final delivery or sale of the device to the

ultimate consumer or user.

(h) Inspection of premises

Every establishment in any State registered with the Secretary

pursuant to this section shall be subject to inspection pursuant to

section 374 of this title and every such establishment engaged in

the manufacture, propagation, compounding, or processing of a drug

or drugs or of a device or devices classified in class II or III

shall be so inspected by one or more officers or employees duly

designated by the Secretary, or by persons accredited to conduct

inspections under section 374(g) of this title, at least once in

the two-year period beginning with the date of registration of such

establishment pursuant to this section and at least once in every

successive two-year period thereafter.

(i) Registration of foreign establishments

(1) On or before December 31 of each year, any establishment

within any foreign country engaged in the manufacture, preparation,

propagation, compounding, or processing of a drug or a device that

is imported or offered for import into the United States shall,

through electronic means in accordance with the criteria of the

Secretary, register with the Secretary the name and place of

business of the establishment, the name of the United States agent

for the establishment, the name of each importer of such drug or

device in the United States that is known to the establishment, and

the name of each person who imports or offers for import such drug

or device to the United States for purposes of importation.

(2) The establishment shall also provide the information required

by subsection (j) of this section.

(3) The Secretary is authorized to enter into cooperative

arrangements with officials of foreign countries to ensure that

adequate and effective means are available for purposes of

determining, from time to time, whether drugs or devices

manufactured, prepared, propagated, compounded, or processed by an

establishment described in paragraph (1), if imported or offered

for import into the United States, shall be refused admission on

any of the grounds set forth in section 381(a) of this title.

(j) Filing of lists of drugs and devices manufactured, prepared,

propagated and compounded by registrants; statements;

accompanying disclosures

(1) Every person who registers with the Secretary under

subsection (b), (c), (d), or (i) of this section shall, at the time

of registration under any such subsection, file with the Secretary

a list of all drugs and a list of all devices and a brief statement

of the basis for believing that each device included in the list is

a device rather than a drug (with each drug and device in each list

listed by its established name (as defined in section 352(e) of

this title) and by any proprietary name) which are being

manufactured, prepared, propagated, compounded, or processed by him

for commercial distribution and which he has not included in any

list of drugs or devices filed by him with the Secretary under this

paragraph or paragraph (2) before such time of registration. Such

list shall be prepared in such form and manner as the Secretary may

prescribe and shall be accompanied by -

(A) in the case of a drug contained in the applicable list and

subject to section 355 or 360b of this title, or a device

intended for human use contained in the applicable list with

respect to which a performance standard has been established

under section 360d of this title or which is subject to section

360e of this title, a reference to the authority for the

marketing of such drug or device and a copy of all labeling for

such drug or device;

(B) in the case of any other drug or device contained in an

applicable list -

(i) which drug is subject to section 353(b)(1) of this title,

or which device is a restricted device, a copy of all labeling

for such drug or device, a representative sampling of

advertisements for such drug or device, and, upon request made

by the Secretary for good cause, a copy of all advertisements

for a particular drug product or device, or

(ii) which drug is not subject to section 353(b)(1) of this

title or which device is not a restricted device, the label and

package insert for such drug or device and a representative

sampling of any other labeling for such drug or device;

(C) in the case of any drug contained in an applicable list

which is described in subparagraph (B), a quantitative listing of

its active ingredient or ingredients, except that with respect to

a particular drug product the Secretary may require the

submission of a quantitative listing of all ingredients if he

finds that such submission is necessary to carry out the purposes

of this chapter; and

(D) if the registrant filing a list has determined that a

particular drug product or device contained in such list is not

subject to section 355 or 360b of this title, or the particular

device contained in such list is not subject to a performance

standard established under section 360d of this title or to

section 360e of this title or is not a restricted device a brief

statement of the basis upon which the registrant made such

determination if the Secretary requests such a statement with

respect to that particular drug product or device.

(2) Each person who registers with the Secretary under this

section shall report to the Secretary once during the month of June

of each year and once during the month of December of each year the

following information:

(A) A list of each drug or device introduced by the registrant

for commercial distribution which has not been included in any

list previously filed by him with the Secretary under this

subparagraph or paragraph (1) of this subsection. A list under

this subparagraph shall list a drug or device by its established

name (as defined in section 352(e) of this title), and by any

proprietary name it may have and shall be accompanied by the

other information required by paragraph (1).

(B) If since the date the registrant last made a report under

this paragraph (or if he has not made a report under this

paragraph, since February 1, 1973) he has discontinued the

manufacture, preparation, propagation, compounding, or processing

for commercial distribution of a drug or device included in a

list filed by him under subparagraph (A) or paragraph (1); notice

of such discontinuance, the date of such discontinuance, and the

identity (by established name (as defined in section 352(e) of

this title) and by any proprietary name) of such drug or device.

(C) If since the date the registrant reported pursuant to

subparagraph (B) a notice of discontinuance he has resumed the

manufacture, preparation, propagation, compounding, or processing

for commercial distribution of the drug or device with respect to

which such notice of discontinuance was reported; notice of such

resumption, the date of such resumption, the identity of such

drug or device (each by established name (as defined in section

352(e) of this title) and by any proprietary name), and the other

information required by paragraph (1), unless the registrant has

previously reported such resumption to the Secretary pursuant to

this subparagraph.

(D) Any material change in any information previously submitted

pursuant to this paragraph or paragraph (1).

(3) The Secretary may also require each registrant under this

section to submit a list of each drug product which (A) the

registrant is manufacturing, preparing, propagating, compounding,

or processing for commercial distribution, and (B) contains a

particular ingredient. The Secretary may not require the

submission of such a list unless he has made a finding that the

submission of such a list is necessary to carry out the purposes of

this chapter.

(k) Report preceding introduction of devices into interstate

commerce

Each person who is required to register under this section and

who proposes to begin the introduction or delivery for introduction

into interstate commerce for commercial distribution of a device

intended for human use shall, at least ninety days before making

such introduction or delivery, report to the Secretary or person

who is accredited under section 360m(a) of this title (in such form

and manner as the Secretary shall by regulation prescribe) -

(1) the class in which the device is classified under section

360c of this title or if such person determines that the device

is not classified under such section, a statement of that

determination and the basis for such person's determination that

the device is or is not so classified, and

(2) action taken by such person to comply with requirements

under section 360d or 360e of this title which are applicable to

the device.

(l) Exemption from reporting requirements

A report under subsection (k) of this section is not required for

a device intended for human use that is exempted from the

requirements of this subsection under subsection (m) of this

section or is within a type that has been classified into class I

under section 360c of this title. The exception established in the

preceding sentence does not apply to any class I device that is

intended for a use which is of substantial importance in preventing

impairment of human health, or to any class I device that presents

a potential unreasonable risk of illness or injury.

(m) List of exempt class II devices; determination by Secretary;

publication in Federal Register

(1) Not later than 60 days after November 21, 1997, the Secretary

shall publish in the Federal Register a list of each type of class

II device that does not require a report under subsection (k) of

this section to provide reasonable assurance of safety and

effectiveness. Each type of class II device identified by the

Secretary as not requiring the report shall be exempt from the

requirement to provide a report under subsection (k) of this

section as of the date of the publication of the list in the

Federal Register. The Secretary shall publish such list on the

Internet site of the Food and Drug Administration. The list so

published shall be updated not later than 30 days after each

revision of the list by the Secretary.

(2) Beginning on the date that is 1 day after the date of the

publication of a list under this subsection, the Secretary may

exempt a class II device from the requirement to submit a report

under subsection (k) of this section, upon the Secretary's own

initiative or a petition of an interested person, if the Secretary

determines that such report is not necessary to assure the safety

and effectiveness of the device. The Secretary shall publish in

the Federal Register notice of the intent of the Secretary to

exempt the device, or of the petition, and provide a 30-day period

for public comment. Within 120 days after the issuance of the

notice in the Federal Register, the Secretary shall publish an

order in the Federal Register that sets forth the final

determination of the Secretary regarding the exemption of the

device that was the subject of the notice. If the Secretary fails

to respond to a petition within 180 days of receiving it, the

petition shall be deemed to be granted.

(n) Review of report; time for determination by Secretary

The Secretary shall review the report required in subsection (k)

of this section and make a determination under section 360c(f)(1)

of this title not later than 90 days after receiving the report.

(o) Reprocessed single-use devices

(1) With respect to reprocessed single-use devices for which

reports are required under subsection (k) of this section:

(A) The Secretary shall identify such devices or types of

devices for which reports under such subsection must, in order to

ensure that the device is substantially equivalent to a predicate

device, include validation data, the types of which shall be

specified by the Secretary, regarding cleaning and sterilization,

and functional performance demonstrating that the single-use

device will remain substantially equivalent to its predicate

device after the maximum number of times the device is

reprocessed as intended by the person submitting the premarket

notification. Within six months after October 26, 2002, the

Secretary shall publish in the Federal Register a list of the

types so identified, and shall revise the list as appropriate.

Reports under subsection (k) of this section for devices or types

of devices within a type included on the list are, upon

publication of the list, required to include such validation

data.

(B) In the case of each report under subsection (k) of this

section that was submitted to the Secretary before the

publication of the initial list under subparagraph (A), or any

revision thereof, and was for a device or type of device included

on such list, the person who submitted the report under

subsection (k) of this section shall submit validation data as

described in subparagraph (A) to the Secretary not later than

nine months after the publication of the list. During such

nine-month period, the Secretary may not take any action under

this chapter against such device solely on the basis that the

validation data for the device have not been submitted to the

Secretary. After the submission of the validation data to the

Secretary, the Secretary may not determine that the device is

misbranded under section 352(o) of this title, adulterated under

section 351(f)(1)(B) of this title, or take action against the

device under section 331(p) of this title for failure to provide

any information required by subsection (k) of this section until

(i) the review is terminated by withdrawal of the submission of

the report under subsection (k) of this section; (ii) the

Secretary finds the data to be acceptable and issues a letter; or

(iii) the Secretary determines that the device is not

substantially equivalent to a predicate device. Upon a

determination that a device is not substantially equivalent to a

predicate device, or if such submission is withdrawn, the device

can no longer be legally marketed.

(C) In the case of a report under subsection (k) of this

section for a device identified under subparagraph (A) that is of

a type for which the Secretary has not previously received a

report under such subsection, the Secretary may, in advance of

revising the list under subparagraph (A) to include such type,

require that the report include the validation data specified in

subparagraph (A).

(D) Section 352(o) of this title applies with respect to the

failure of a report under subsection (k) of this section to

include validation data required under subparagraph (A).

(2) With respect to critical or semi-critical reprocessed

single-use devices that, under subsection (l) or (m) of this

section, are exempt from the requirement of submitting reports

under subsection (k) of this section:

(A) The Secretary shall identify such devices or types of

devices for which such exemptions should be terminated in order

to provide a reasonable assurance of the safety and effectiveness

of the devices. The Secretary shall publish in the Federal

Register a list of the devices or types of devices so identified,

and shall revise the list as appropriate. The exemption for each

device or type included on the list is terminated upon the

publication of the list. For each report under subsection (k) of

this section submitted pursuant to this subparagraph the

Secretary shall require the validation data described in

paragraph (1)(A).

(B) For each device or type of device included on the list

under subparagraph (A), a report under subsection (k) of this

section shall be submitted to the Secretary not later than 15

months after the publication of the initial list, or a revision

of the list, whichever terminates the exemption for the device.

During such 15-month period, the Secretary may not take any

action under this chapter against such device solely on the basis

that such report has not been submitted to the Secretary. After

the submission of the report to the Secretary the Secretary may

not determine that the device is misbranded under section 352(o)

of this title, adulterated under section 351(f)(1)(B) of this

title, or take action against the device under section 331(p) of

this title for failure to provide any information required by

subsection (k) of this section until (i) the review is terminated

by withdrawal of the submission; (ii) the Secretary determines by

order that the device is substantially equivalent to a predicate

device; or (iii) the Secretary determines by order that the

device is not substantially equivalent to a predicate device.

Upon a determination that a device is not substantially

equivalent to a predicate device, the device can no longer be

legally marketed.

(C) In the case of semi-critical devices, the initial list

under subparagraph (A) shall be published not later than 18

months after the effective date of this subsection. In the case

of critical devices, the initial list under such subparagraph

shall be published not later than six months after such effective

date.

(D) Section 352(o) of this title applies with respect to the

failure to submit a report under subsection (k) of this section

that is required pursuant to subparagraph (A), including a

failure of the report to include validation data required in such

subparagraph.

(E) The termination under subparagraph (A) of an exemption

under subsection (l) or (m) of this section for a critical or

semicritical reprocessed single-use device does not terminate the

exemption under subsection (l) or (m) of this section for the

original device.

(p) Electronic registration

Registrations under subsections (b), (c), (d), and (i) of this

section (including the submission of updated information) shall be

submitted to the Secretary by electronic means, upon a finding by

the Secretary that the electronic receipt of such registrations is

feasible, unless the Secretary grants a request for waiver of such

requirement because use of electronic means is not reasonable for

the person requesting such waiver.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 510, as added Pub. L. 87-781, title

III, Sec. 302, Oct. 10, 1962, 76 Stat. 794; amended Pub. L. 89-74,

Sec. 4, July 15, 1965, 79 Stat. 231; Pub. L. 91-513, title II, Sec.

701(e), Oct. 27, 1970, 84 Stat. 1282; Pub. L. 92-387, Sec. 3,

4(a)-(c), Aug. 16, 1972, 86 Stat. 560-562; Pub. L. 94-295, Sec.

4(a), May 28, 1976, 90 Stat. 579; Pub. L. 105-115, title I, Sec.

125(a)(2)(C), title II, Sec. 206(a), 209(a), 213(b), title IV, Sec.

417, Nov. 21, 1997, 111 Stat. 2325, 2338, 2341, 2347, 2379; Pub. L.

107-188, title III, Sec. 321(a), June 12, 2002, 116 Stat. 675; Pub.

L. 107-250, title II, Sec. 201(e), 207, 211, title III, Sec.

302(b), Oct. 26, 2002, 116 Stat. 1609, 1613, 1614, 1616.)

-REFTEXT-

REFERENCES IN TEXT

The effective date of this subsection, referred to in subsec.

(o)(2)(C), probably means the date of the enactment of Pub. L.

107-250, which enacted subsec. (o) of this section and was approved

Oct. 26, 2002.

-MISC2-

AMENDMENTS

2002 - Subsec. (h). Pub. L. 107-250, Sec. 201(e), inserted '', or

by persons accredited to conduct inspections under section 374(g)

of this title,'' after ''duly designated by the Secretary''.

Subsec. (i)(1). Pub. L. 107-188, Sec. 321(a)(1), substituted ''On

or before December 31 of each year, any establishment'' for ''Any

establishment'' and ''shall, through electronic means in accordance

with the criteria of the Secretary, register with the Secretary the

name and place of business of the establishment, the name of the

United States agent for the establishment, the name of each

importer of such drug or device in the United States that is known

to the establishment, and the name of each person who imports or

offers for import such drug or device to the United States for

purposes of importation'' for ''shall register with the Secretary

the name and place of business of the establishment and the name of

the United States agent for the establishment''.

Subsec. (j)(1). Pub. L. 107-188, Sec. 321(a)(2), substituted

''subsection (b), (c), (d), or (i)'' for ''subsection (b), (c), or

(d)'' in first sentence.

Subsec. (m)(1). Pub. L. 107-250, Sec. 211, inserted at end ''The

Secretary shall publish such list on the Internet site of the Food

and Drug Administration. The list so published shall be updated not

later than 30 days after each revision of the list by the

Secretary.''

Subsec. (o). Pub. L. 107-250, Sec. 302(b), added subsec. (o).

Subsec. (p). Pub. L. 107-250, Sec. 207, added subsec. (p).

1997 - Subsec. (g). Pub. L. 105-115, Sec. 213(b)(3), inserted at

end ''In this subsection, the term 'wholesale distributor' means

any person (other than the manufacturer or the initial importer)

who distributes a device from the original place of manufacture to

the person who makes the final delivery or sale of the device to

the ultimate consumer or user.''

Subsec. (g)(4), (5). Pub. L. 105-115, Sec. 213(b)(1), (2), added

par. (4) and redesignated former par. (4) as (5).

Subsec. (i). Pub. L. 105-115, Sec. 417, amended subsec. (i)

generally. Prior to amendment, subsec. (i) read as follows: ''Any

establishment within any foreign country engaged in the

manufacture, preparation, propagation, compounding, or processing

of a drug or drugs, or a device or devices, shall be permitted to

register under this section pursuant to regulations promulgated by

the Secretary. Such regulations shall require such establishment to

provide the information required by subsection (j) of this section

and shall require such establishment to provide the information

required by subsection (j) of this section in the case of a device

or devices and shall include provisions for registration of any

such establishment upon condition that adequate and effective means

are available, by arrangement with the government of such foreign

country or otherwise, to enable the Secretary to determine from

time to time whether drugs or devices manufactured, prepared,

propagated, compounded, or processed in such establishment, if

imported or offered for import into the United States, shall be

refused admission on any of the grounds set forth in section 381(a)

of this title.''

Subsec. (j)(1)(A), (D). Pub. L. 105-115, Sec. 125(a)(2)(C),

struck out '', 356, 357,'' before ''or 360b of this title''.

Subsec. (k). Pub. L. 105-115, Sec. 206(a)(1), inserted ''or

person who is accredited under section 360m(a) of this title''

after ''report to the Secretary''.

Subsecs. (l), (m). Pub. L. 105-115, Sec. 206(a)(2), added

subsecs. (l) and (m).

Subsec. (n). Pub. L. 105-115, Sec. 209(a), added subsec. (n).

1976 - Subsec. (a)(1). Pub. L. 94-295, Sec. 4(a)(2), substituted

''drug package or device package'' for ''drug package'',

''distribution of the drug or device'' for ''distribution of the

drug'', and ''ultimate consumer or user'' for ''ultimate

consumer''.

Subsecs. (b) to (d). Pub. L. 94-295, Sec. 4(a)(3), inserted ''or

a device or devices'' after ''drug or drugs''.

Subsec. (e). Pub. L. 94-295, Sec. 4(a)(4), authorized the

Secretary to prescribe by regulation a uniform system for the

identification of devices intended for human use and authorized

him, in addition, to require that persons who are required to list

devices pursuant to subsec. (j) also list such devices in

accordance with the system.

Subsec. (g)(1) to (3). Pub. L. 94-295, Sec. 4(a)(5), substituted

''drugs or devices'' for ''drugs''.

Subsec. (h). Pub. L. 94-295, Sec. 4(a)(6), inserted reference to

establishments engaged in the manufacture, propagation,

compounding, or processing of a drug or drugs or of a device or

devices classified in class II or III.

Subsec. (i). Pub. L. 94-295, Sec. 4(a)(7), inserted reference to

devices and inserted requirement that regulations require

establishments to provide the information required by subsection

(j) of this section in the case of a device or devices.

Subsec. (j)(1). Pub. L. 94-295, Sec. 4(a)(8)(A), in introductory

provisions substituted ''a list of all drugs and a list of all

devices and a brief statement of the basis for believing that each

device included in the list is a device rather than a drug (with

each drug and device in each list listed by its established name''

for ''a list of all drugs (by established name'' and ''drugs or

devices filed'' for ''drugs filed''.

Subsec. (j)(1)(A). Pub. L. 94-295, Sec. 4(a)(8)(B), substituted

''the applicable list'' for ''such list'', inserted ''or a device

intended for human use contained in the applicable list with

respect to which a performance standard has been established under

section 360d of this title or which is subject to section 360e of

this title,'' after ''360b of this title,'', and substituted ''such

drug or device'' for ''such drug'' wherever appearing.

Subsec. (j)(1)(B). Pub. L. 94-295, Sec. 4(a)(8)(C), in

introductory provisions substituted ''drug or device contained in

an applicable list'' for ''drug contained in such list''.

Subsec. (j)(1)(B)(i). Pub. L. 94-295, Sec. 4(a)(8)(D),

substituted ''which drug is subject to section 353(b)(1) of this

title, or which device is a restricted device, a copy of all

labeling for such drug or device, a representative sampling of

advertisements for such drug or device, and, upon request made by

the Secretary for good cause, a copy of all advertisements for a

particular drug product or device, or'' for ''which is subject to

section 353(b)(1) of this title, a copy of all labeling for such

drug, a representative sampling of advertisements for such drug,

and, upon request made by the Secretary for good cause, a copy of

all advertisements for a particular drug product, or''.

Subsec. (j)(1)(B)(ii). Pub. L. 94-295, Sec. 4(a)(8)(E),

substituted ''which drug is not subject to section 353(b)(1) of

this title or which device is not a restricted device, the label

and package insert for such drug or device and a representative

sampling of any other labeling for such drug or device'' for

''which is not subject to section 353(b)(1) of this title, the

label and package insert for such drug and a representative

sampling of any other labeling for such drug''.

Subsec. (j)(1)(C). Pub. L. 94-295, Sec. 4(a)(8)(F), substituted

''an applicable list'' for ''such list''.

Subsec. (j)(1)(D). Pub. L. 94-295, Sec. 4(a)(8)(G), substituted

''a list'' for ''the list'', inserted ''or the particular device

contained in such list is not subject to a performance standard

established under section 360d of this title or to section 360e of

this title or is not a restricted device'' after ''or 360b of this

title,'', and substituted ''particular drug product or device'' for

''particular drug product'' wherever appearing.

Subsec. (j)(2). Pub. L. 94-295, Sec. 4(a)(8)(H), substituted

''drug or ''device'' for ''drug'' in subpars. (A), (B), and (C),

and substituted ''(each by established name'' for ''(by established

name'' in subpar. (C).

Subsec. (k). Pub. L. 94-295, Sec. 4(a)(9), added subsec. (k).

1972 - Subsec. (e). Pub. L. 92-387, Sec. 4(a), inserted provision

that the Secretary may assign a listing number to each drug or

class of drugs listed under subsec. (j).

Subsec. (f). Pub. L. 92-387, Sec. 4(b), inserted exception that

the list submitted under subsec. (j)(3) and information submitted

under subsec. (j)(1), (2) shall be exempt from inspection unless

the Secretary determines otherwise.

Subsec. (i). Pub. L. 92-387, Sec. 4(c), inserted provision that

the regulations shall require such establishment to provide the

information required by subsec. (j).

Subsec. (j). Pub. L. 92-387, Sec. 3, added subsec. (j).

1970 - Subsec. (a). Pub. L. 91-513 struck out provisions defining

the wholesaling, jobbing, or distributing of depressant or

stimulant drugs.

Subsec. (b). Pub. L. 91-513 struck out provisions covering

establishments engaged in the wholesaling, jobbing, or distributing

of depressant or stimulant drugs and the inclusion of the fact of

such activity in the annual registration.

Subsec. (c). Pub. L. 91-513 struck out provisions covering new

registrations of persons first engaging in the wholesaling,

jobbing, or distributing of depressant or stimulant drugs and the

inclusion of the fact of such activity in the registration.

Subsec. (d). Pub. L. 91-513 struck out number designation ''(1)''

preceding first sentence, struck out portion of such redesignated

provisions covering the wholesaling, jobbing, or distributing of

depressant or stimulant drugs, and struck out par. (2) covering the

filing of supplemental registration whenever a person not

previously engaged or involved with depressant or stimulant drugs

goes into the manufacturing, preparation, or processing thereof.

1965 - Pub. L. 89-74, Sec. 4(e), included certain wholesalers in

section catchline.

Subsec. (a)(2), (3). Pub. L. 89-74, Sec. 4(a), added par. (2) and

redesignated former par. (2) as (3).

Subsecs. (b), (c). Pub. L. 89-74, Sec. 4(b), (c), inserted ''or

in the wholesaling, jobbing, or distributing of any depressant or

stimulant drug'' after ''drug or drugs'' and inserted requirement

that establishment indicate activity in depressant or stimulant

drugs at time of registration.

Subsec. (d). Pub. L. 89-74 Sec. 4(d), designated existing

provisions as par. (1), inserted ''or the wholesaling, jobbing, or

distributing of any depressant or stimulant drug'' and the

requirement that the additional establishment indicate activity in

depressant or stimulant drugs at time of registration, and added

par. (2).

EFFECTIVE DATE OF 2002 AMENDMENT

Amendment by Pub. L. 107-188 effective upon the expiration of the

180-day period beginning June 12, 2002, see section 321(c) of Pub.

L. 107-188, set out as a note under section 331 of this title.

EFFECTIVE DATE OF 1997 AMENDMENT

Amendment by sections 206(a), 209(a), 213(b), and 417 of Pub. L.

105-115 effective 90 days after Nov. 21, 1997, except as otherwise

provided, see section 501 of Pub. L. 105-115, set out as a note

under section 321 of this title.

EFFECTIVE DATE OF 1972 AMENDMENT

Section 5 of Pub. L. 92-387 provided that: ''The amendments made

by this Act (amending this section and sections 331 and 335 of this

title and enacting provisions set out below) shall take effect on

the first day of the sixth month beginning after the date of

enactment of this Act (Aug. 16, 1972).''

EFFECTIVE DATE OF 1970 AMENDMENT

Amendment by Pub. L. 91-513 effective on first day of seventh

calendar month that begins after Oct. 26, 1970, see section 704 of

Pub. L. 91-513, set out as an Effective Date note under section 801

of this title.

EFFECTIVE DATE OF 1965 AMENDMENT

Amendment by Pub. L. 89-74 effective Feb. 1, 1966, subject to

registration with Secretary of names, places of business,

establishments, and other prescribed information prior to Feb. 1,

1966, see section 11 of Pub. L. 89-74, set out as a note under

section 321 of this title.

SAVINGS PROVISION

Amendment by Pub. L. 91-513 not to affect or abate any

prosecutions for any violation of law or any civil seizures or

forfeitures and injunctive proceedings commenced prior to the

effective date of such amendment, and all administrative

proceedings pending before the Bureau of Narcotics and Dangerous

Drugs (now the Drug Enforcement Administration) on Oct. 27, 1970,

to be continued and brought to final determination in accord with

laws and regulations in effect prior to Oct. 27, 1970, see section

702 of Pub. L. 91-513, set out as a note under section 321 of this

title.

CONGRESSIONAL DECLARATION OF NEED FOR REGISTRATION AND INSPECTION

OF DRUG ESTABLISHMENTS

Section 301 of Pub. L. 87-781 provided that: ''The Congress

hereby finds and declares that in order to make regulation of

interstate commerce in drugs effective, it is necessary to provide

for registration and inspection of all establishments in which

drugs are manufactured, prepared, propagated, compounded, or

processed; that the products of all such establishments are likely

to enter the channels of interstate commerce and directly affect

such commerce; and that the regulation of interstate commerce in

drugs without provision for registration and inspection of

establishments that may be engaged only in intrastate commerce in

such drugs would discriminate against and depress interstate

commerce in such drugs, and adversely burden, obstruct, and affect

such interstate commerce.''

DECLARATION OF POLICY OF DRUG LISTING ACT OF 1972

Section 2 of Pub. L. 92-387 provided that: ''The Federal

Government which is responsible for regulating drugs has no ready

means of determining what drugs are actually being manufactured or

packed by establishments registered under the Federal Food, Drug,

and Cosmetic Act (this chapter) except by periodic inspection of

such registered establishments. Knowledge of which particular

drugs are being manufactured or packed by each registered

establishment would substantially assist in the enforcement of

Federal laws requiring that such drugs be pure, safe, effective,

and properly labeled. Information on the discontinuance of a

particular drug could serve to alleviate the burden of reviewing

and implementing enforcement actions against drugs which, although

commercially discontinued, remain active for regulatory purposes.

Information on the type and number of different drugs being

manufactured or packed by drug establishments could permit more

effective and timely regulation by the agencies of the Federal

Government responsible for regulating drugs, including

identification of which drugs in interstate commerce are subject to

section 505 or 507 (section 355 or 357 of this title), or to other

provisions of the Federal Food, Drug, and Cosmetic Act.''

REGISTRATION OF CERTAIN PERSONS OWNING OR OPERATING DRUG

ESTABLISHMENTS PRIOR TO OCT. 10, 1962

Section 303 of Pub. L. 87-781 provided that any person who, on

the day immediately preceding Oct. 10, 1962, owned or operated an

establishment which manufactured or processed drugs, registered

before the first day of the seventh month following October, 1962,

would be deemed to be registered in accordance with subsec. (b) of

this section for the calendar year 1962 and if registered within

this period and effected in 1963, be deemed in compliance for that

calendar year.

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in sections 331, 352, 353a, 355,

360c, 360e, 360i, 360j, 360m, 374, 379h, 379i, 381, 1602, 1604,

1605 of this title; title 42 section 1395l.

-CITE-

21 USC Sec. 360a 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 360a. Repealed. Pub. L. 91-513, title II, Sec. 701(a), Oct.

27, 1970, 84 Stat. 1281

-MISC1-

Section, act June 25, 1938, ch. 675, Sec. 511, as added July 15,

1965, Pub. L. 89-74, Sec. 3(b), 79 Stat. 227; amended Oct. 24,

1968, Pub. L. 90-639, Sec. 2(a), 82 Stat. 1361, regulated the

manufacture, compounding, and processing of depressant and

stimulant drugs and their sale, delivery, disposal, possession, and

recordkeeping activities connected therewith. See section 801 et

seq. of this title.

EFFECTIVE DATE OF REPEAL

Repeal by Pub. L. 91-513 effective on first day of seventh

calendar month that begins after Oct. 26, 1970, see section 704 of

Pub. L. 91-513, set out as an Effective Date note under section 801

of this title.

SAVINGS PROVISION

Repeal not to affect or abate any prosecutions for violation of

law or any civil seizures or forfeitures and injunctive proceedings

commenced prior to the effective date of such repeal, and all

administrative proceedings pending before the Bureau of Narcotics

and Dangerous Drugs (now Drug Enforcement Administration) on Oct.

27, 1970, to be continued and brought to final determination in

accord with laws and regulations in effect prior to Oct. 27, 1970,

see section 702 of Pub. L. 91-513, set out as a note under section

321 of this title.

-CITE-

21 USC Sec. 360b 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 360b. New animal drugs

-STATUTE-

(a) Unsafe new animal drugs and animal feed containing such drugs;

conditions of safety; exemption of drugs for research; import

tolerances

(1) A new animal drug shall, with respect to any particular use

or intended use of such drug, be deemed unsafe for the purposes of

section 351(a)(5) of this title and section 342(a)(2)(D) (FOOTNOTE

1) of this title unless -

(FOOTNOTE 1) See References in Text note below.

(A) there is in effect an approval of an application filed

pursuant to subsection (b) of this section with respect to such

use or intended use of such drug, and

(B) such drug, its labeling, and such use conform to such

approved application.

A new animal drug shall also be deemed unsafe for such purposes in

the event of removal from the establishment of a manufacturer,

packer, or distributor of such drug for use in the manufacture of

animal feed in any State unless at the time of such removal such

manufacturer, packer, or distributor has an unrevoked written

statement from the consignee of such drug, or notice from the

Secretary, to the effect that, with respect to the use of such drug

in animal feed, such consignee (i) holds a license issued under

subsection (m) of this section and has in its possession current

approved labeling for such drug in animal feed; or (ii) will, if

the consignee is not a user of the drug, ship such drug only to a

holder of a license issued under subsection (m) of this section.

(2) An animal feed bearing or containing a new animal drug shall,

with respect to any particular use or intended use of such animal

feed be deemed unsafe for the purposes of section 351(a)(6) of this

title unless -

(A) there is in effect an approval of an application filed

pursuant to subsection (b) of this section with respect to such

drug, as used in such animal feed,

(B) such animal feed is manufactured at a site for which there

is in effect a license issued pursuant to subsection (m)(1) of

this section to manufacture such animal feed, and

(C) such animal feed and its labeling, distribution, holding,

and use conform to the conditions and indications of use

published pursuant to subsection (i) of this section.

(3) A new animal drug or an animal feed bearing or containing a

new animal drug shall not be deemed unsafe for the purposes of

section 351(a)(5) or (6) of this title if such article is for

investigational use and conforms to the terms of an exemption in

effect with respect thereto under subsection (j) of this section.

(4)(A) Except as provided in subparagraph (B), if an approval of

an application filed under subsection (b) of this section is in

effect with respect to a particular use or intended use of a new

animal drug, the drug shall not be deemed unsafe for the purposes

of paragraph (1) and shall be exempt from the requirements of

section 352(f) of this title with respect to a different use or

intended use of the drug, other than a use in or on animal feed, if

such use or intended use -

(i) is by or on the lawful written or oral order of a licensed

veterinarian within the context of a veterinarian-client-patient

relationship, as defined by the Secretary; and

(ii) is in compliance with regulations promulgated by the

Secretary that establish the conditions for such different use or

intended use.

The regulations promulgated by the Secretary under clause (ii) may

prohibit particular uses of an animal drug and shall not permit

such different use of an animal drug if the labeling of another

animal drug that contains the same active ingredient and which is

in the same dosage form and concentration provides for such

different use.

(B) If the Secretary finds that there is a reasonable probability

that a use of an animal drug authorized under subparagraph (A) may

present a risk to the public health, the Secretary may -

(i) establish a safe level for a residue of an animal drug when

it is used for such different use authorized by subparagraph (A);

and

(ii) require the development of a practical, analytical method

for the detection of residues of such drug above the safe level

established under clause (i).

The use of an animal drug that results in residues exceeding a safe

level established under clause (i) shall be considered an unsafe

use of such drug under paragraph (1). Safe levels may be

established under clause (i) either by regulation or order.

(C) The Secretary may by general regulation provide access to the

records of veterinarians to ascertain any use or intended use

authorized under subparagraph (A) that the Secretary has determined

may present a risk to the public health.

(D) If the Secretary finds, after affording an opportunity for

public comment, that a use of an animal drug authorized under

subparagraph (A) presents a risk to the public health or that an

analytical method required under subparagraph (B) has not been

developed and submitted to the Secretary, the Secretary may, by

order, prohibit any such use.

(5) If the approval of an application filed under section 355 of

this title is in effect, the drug under such application shall not

be deemed unsafe for purposes of paragraph (1) and shall be exempt

from the requirements of section 352(f) of this title with respect

to a use or intended use of the drug in animals if such use or

intended use -

(A) is by or on the lawful written or oral order of a licensed

veterinarian within the context of a veterinarian-client-patient

relationship, as defined by the Secretary; and

(B) is in compliance with regulations promulgated by the

Secretary that establish the conditions for the use or intended

use of the drug in animals.

(6) For purposes of section 342(a)(2)(D) (FOOTNOTE 1) of this

title, a use or intended use of a new animal drug shall not be

deemed unsafe under this section if the Secretary establishes a

tolerance for such drug and any edible portion of any animal

imported into the United States does not contain residues exceeding

such tolerance. In establishing such tolerance, the Secretary

shall rely on data sufficient to demonstrate that a proposed

tolerance is safe based on similar food safety criteria used by the

Secretary to establish tolerances for applications for new animal

drugs filed under subsection (b)(1) of this section. The Secretary

may consider and rely on data submitted by the drug manufacturer,

including data submitted to appropriate regulatory authorities in

any country where the new animal drug is lawfully used or data

available from a relevant international organization, to the extent

such data are not inconsistent with the criteria used by the

Secretary to establish a tolerance for applications for new animal

drugs filed under subsection (b)(1) of this section. For purposes

of this paragraph, ''relevant international organization'' means

the Codex Alimenterius Commission or other international

organization deemed appropriate by the Secretary. The Secretary

may, under procedures specified by regulation, revoke a tolerance

established under this paragraph if information demonstrates that

the use of the new animal drug under actual use conditions results

in food being imported into the United States with residues

exceeding the tolerance or if scientific evidence shows the

tolerance to be unsafe.

(b) Filing application for uses of new animal drug; contents;

patent information; abbreviated application; presubmission

conference

(1) Any person may file with the Secretary an application with

respect to any intended use or uses of a new animal drug. Such

person shall submit to the Secretary as a part of the application

(A) full reports of investigations which have been made to show

whether or not such drug is safe and effective for use; (B) a full

list of the articles used as components of such drug; (C) a full

statement of the composition of such drug; (D) a full description

of the methods used in, and the facilities and controls used for,

the manufacture, processing, and packing of such drug; (E) such

samples of such drug and of the articles used as components

thereof, of any animal feed for use in or on which such drug is

intended, and of the edible portions or products (before or after

slaughter) of animals to which such drug (directly or in or on

animal feed) is intended to be administered, as the Secretary may

require; (F) specimens of the labeling proposed to be used for such

drug, or in case such drug is intended for use in animal feed,

proposed labeling appropriate for such use, and specimens of the

labeling for the drug to be manufactured, packed, or distributed by

the applicant; (G) a description of practicable methods for

determining the quantity, if any, of such drug in or on food, and

any substance formed in or on food, because of its use; and (H) the

proposed tolerance or withdrawal period or other use restrictions

for such drug if any tolerance or withdrawal period or other use

restrictions are required in order to assure that the proposed use

of such drug will be safe. The applicant shall file with the

application the patent number and the expiration date of any patent

which claims the new animal drug for which the applicant filed the

application or which claims a method of using such drug and with

respect to which a claim of patent infringement could reasonably be

asserted if a person not licensed by the owner engaged in the

manufacture, use, or sale of the drug. If an application is filed

under this subsection for a drug and a patent which claims such

drug or a method of using such drug is issued after the filing date

but before approval of the application, the applicant shall amend

the application to include the information required by the

preceding sentence. Upon approval of the application, the

Secretary shall publish information submitted under the two

preceding sentences.

(2) Any person may file with the Secretary an abbreviated

application for the approval of a new animal drug. An abbreviated

application shall contain the information required by subsection

(n) of this section.

(3) Any person intending to file an application under paragraph

(1) or a request for an investigational exemption under subsection

(j) of this section shall be entitled to one or more conferences

prior to such submission to reach an agreement acceptable to the

Secretary establishing a submission or an investigational

requirement, which may include a requirement for a field

investigation. A decision establishing a submission or an

investigational requirement shall bind the Secretary and the

applicant or requestor unless (A) the Secretary and the applicant

or requestor mutually agree to modify the requirement, or (B) the

Secretary by written order determines that a substantiated

scientific requirement essential to the determination of safety or

effectiveness of the animal drug involved has appeared after the

conference. No later than 25 calendar days after each such

conference, the Secretary shall provide a written order setting

forth a scientific justification specific to the animal drug and

intended uses under consideration if the agreement referred to in

the first sentence requires more than one field investigation as

being essential to provide substantial evidence of effectiveness

for the intended uses of the drug. Nothing in this paragraph shall

be construed as compelling the Secretary to require a field

investigation.

(c) Period for submission and approval of application; period for

notice and expedition of hearing; period for issuance of order;

abbreviated applications; withdrawal periods; effective date of

approval; relationship to other applications; withdrawal or

suspension of approval; bioequivalence; filing of additional

patent information

(1) Within one hundred and eighty days after the filing of an

application pursuant to subsection (b) of this section, or such

additional period as may be agreed upon by the Secretary and the

applicant, the Secretary shall either (A) issue an order approving

the application if he then finds that none of the grounds for

denying approval specified in subsection (d) of this section

applies, or (B) give the applicant notice of an opportunity for a

hearing before the Secretary under subsection (d) of this section

on the question whether such application is approvable. If the

applicant elects to accept the opportunity for a hearing by written

request within thirty days after such notice, such hearing shall

commence not more than ninety days after the expiration of such

thirty days unless the Secretary and the applicant otherwise

agree. Any such hearing shall thereafter be conducted on an

expedited basis and the Secretary's order thereon shall be issued

within ninety days after the date fixed by the Secretary for filing

final briefs.

(2)(A) Subject to subparagraph (C), the Secretary shall approve

an abbreviated application for a drug unless the Secretary finds -

(i) the methods used in, or the facilities and controls used

for, the manufacture, processing, and packing of the drug are

inadequate to assure and preserve its identity, strength,

quality, and purity;

(ii) the conditions of use prescribed, recommended, or

suggested in the proposed labeling are not reasonably certain to

be followed in practice or, except as provided in subparagraph

(B), information submitted with the application is insufficient

to show that each of the proposed conditions of use or similar

limitations (whether in the labeling or published pursuant to

subsection (i) of this section) have been previously approved for

the approved new animal drug referred to in the application;

(iii) information submitted with the application is

insufficient to show that the active ingredients are the same as

those of the approved new animal drug referred to in the

application;

(iv)(I) if the application is for a drug whose active

ingredients, route of administration, dosage form, strength, or

use with other animal drugs in animal feed is the same as the

active ingredients, route of administration, dosage form,

strength, or use with other animal drugs in animal feed of the

approved new animal drug referred to in the application,

information submitted in the application is insufficient to show

that the active ingredients, route of administration, dosage

form, strength, or use with other animal drugs in animal feed is

the same as that of the approved new animal drug, or

(II) if the application is for a drug whose active ingredients,

route of administration, dosage form, strength, or use with other

animal drugs in animal feed is different from that of the

approved new animal drug referred to in the application, no

petition to file an application for the drug with the different

active ingredients, route of administration, dosage form,

strength, or use with other animal drugs in animal feed was

approved under subsection (n)(3) of this section;

(v) if the application was filed pursuant to the approval of a

petition under subsection (n)(3) of this section, the application

did not contain the information required by the Secretary

respecting the active ingredients, route of administration,

dosage form, strength, or use with other animal drugs in animal

feed which is not the same;

(vi) information submitted in the application is insufficient

to show that the drug is bioequivalent to the approved new animal

drug referred to in the application, or if the application is

filed under a petition approved pursuant to subsection (n)(3) of

this section, information submitted in the application is

insufficient to show that the active ingredients of the new

animal drug are of the same pharmacological or therapeutic class

as the pharmacological or therapeutic class of the approved new

animal drug and that the new animal drug can be expected to have

the same therapeutic effect as the approved new animal drug when

used in accordance with the labeling;

(vii) information submitted in the application is insufficient

to show that the labeling proposed for the drug is the same as

the labeling approved for the approved new animal drug referred

to in the application except for changes required because of

differences approved under a petition filed under subsection

(n)(3) of this section, because of a different withdrawal period,

or because the drug and the approved new animal drug are produced

or distributed by different manufacturers;

(viii) information submitted in the application or any other

information available to the Secretary shows that (I) the

inactive ingredients of the drug are unsafe for use under the

conditions prescribed, recommended, or suggested in the labeling

proposed for the drug, (II) the composition of the drug is unsafe

under such conditions because of the type or quantity of inactive

ingredients included or the manner in which the inactive

ingredients are included, or (III) in the case of a drug for food

producing animals, the inactive ingredients of the drug or its

composition may be unsafe with respect to human food safety;

(ix) the approval under subsection (b)(1) of this section of

the approved new animal drug referred to in the application filed

under subsection (b)(2) of this section has been withdrawn or

suspended for grounds described in paragraph (1) of subsection

(e) of this section, the Secretary has published a notice of a

hearing to withdraw approval of the approved new animal drug for

such grounds, the approval under this paragraph of the new animal

drug for which the application under subsection (b)(2) of this

section was filed has been withdrawn or suspended under

subparagraph (G) for such grounds, or the Secretary has

determined that the approved new animal drug has been withdrawn

from sale for safety or effectiveness reasons;

(x) the application does not meet any other requirement of

subsection (n) of this section; or

(xi) the application contains an untrue statement of material

fact.

(B) If the Secretary finds that a new animal drug for which an

application is submitted under subsection (b)(2) of this section is

bioequivalent to the approved new animal drug referred to in such

application and that residues of the new animal drug are consistent

with the tolerances established for such approved new animal drug

but at a withdrawal period which is different than the withdrawal

period approved for such approved new animal drug, the Secretary

may establish, on the basis of information submitted, such

different withdrawal period as the withdrawal period for the new

animal drug for purposes of the approval of such application for

such drug.

(C) Within 180 days of the initial receipt of an application

under subsection (b)(2) of this section or within such additional

period as may be agreed upon by the Secretary and the applicant,

the Secretary shall approve or disapprove the application.

(D) The approval of an application filed under subsection (b)(2)

of this section shall be made effective on the last applicable date

determined under the following:

(i) If the applicant only made a certification described in

clause (i) or (ii) of subsection (n)(1)(G) of this section or in

both such clauses, the approval may be made effective

immediately.

(ii) If the applicant made a certification described in clause

(iii) of subsection (n)(1)(G) of this section, the approval may

be made effective on the date certified under clause (iii).

(iii) If the applicant made a certification described in clause

(iv) of subsection (n)(1)(G) of this section, the approval shall

be made effective immediately unless an action is brought for

infringement of a patent which is the subject of the

certification before the expiration of 45 days from the date the

notice provided under subsection (n)(2)(B)(i) of this section is

received. If such an action is brought before the expiration of

such days, the approval shall be made effective upon the

expiration of the 30 month period beginning on the date of the

receipt of the notice provided under subsection (n)(2)(B) of this

section or such shorter or longer period as the court may order

because either party to the action failed to reasonably cooperate

in expediting the action, except that if before the expiration of

such period -

(I) the court decides that such patent is invalid or not

infringed, the approval shall be made effective on the date of

the court decision,

(II) the court decides that such patent has been infringed,

the approval shall be made effective on such date as the court

orders under section 271(e)(4)(A) of title 35, or

(III) the court grants a preliminary injunction prohibiting

the applicant from engaging in the commercial manufacture or

sale of the drug until the court decides the issues of patent

validity and infringement and if the court decides that such

patent is invalid or not infringed, the approval shall be made

effective on the date of such court decision.

In such an action, each of the parties shall reasonably cooperate

in expediting the action. Until the expiration of 45 days from

the date the notice made under subsection (n)(2)(B) of this

section is received, no action may be brought under section 2201

of title 28 for a declaratory judgment with respect to the

patent. Any action brought under section 2201 of title 28 shall

be brought in the judicial district where the defendant has its

principal place of business or a regular and established place of

business.

(iv) If the application contains a certification described in

clause (iv) of subsection (n)(1)(G) of this section and is for a

drug for which a previous application has been filed under this

subsection containing such a certification, the application shall

be made effective not earlier than 180 days after -

(I) the date the Secretary receives notice from the applicant

under the previous application of the first commercial

marketing of the drug under the previous application, or

(II) the date of a decision of a court in an action described

in subclause (III) (FOOTNOTE 2) holding the patent which is the

subject of the certification to be invalid or not infringed,

(FOOTNOTE 2) So in original. Probably should be ''clause

(iii)(III)''.

whichever is earlier.

(E) If the Secretary decides to disapprove an application, the

Secretary shall give the applicant notice of an opportunity for a

hearing before the Secretary on the question of whether such

application is approvable. If the applicant elects to accept the

opportunity for hearing by written request within 30 days after

such notice, such hearing shall commence not more than 90 days

after the expiration of such 30 days unless the Secretary and the

applicant otherwise agree. Any such hearing shall thereafter be

conducted on an expedited basis and the Secretary's order thereon

shall be issued within 90 days after the date fixed by the

Secretary for filing final briefs.

(F)(i) If an application submitted under subsection (b)(1) of

this section for a drug, no active ingredient (including any ester

or salt of the active ingredient) of which has been approved in any

other application under subsection (b)(1) of this section, is

approved after November 16, 1988, no application may be submitted

under subsection (b)(2) of this section which refers to the drug

for which the subsection (b)(1) application was submitted before

the expiration of 5 years from the date of the approval of the

application under subsection (b)(1) of this section, except that

such an application may be submitted under subsection (b)(2) of

this section after the expiration of 4 years from the date of the

approval of the subsection (b)(1) application if it contains a

certification of patent invalidity or noninfringement described in

clause (iv) of subsection (n)(1)(G) of this section. The approval

of such an application shall be made effective in accordance with

subparagraph (B) except that, if an action for patent infringement

is commenced during the one-year period beginning 48 months after

the date of the approval of the subsection (b) application, the 30

month period referred to in subparagraph (D)(iii) shall be extended

by such amount of time (if any) which is required for seven and

one-half years to have elapsed from the date of approval of the

subsection (b) application.

(ii) If an application submitted under subsection (b)(1) of this

section for a drug, which includes an active ingredient (including

any ester or salt of the active ingredient) that has been approved

in another application approved under such subsection, is approved

after November 16, 1988, and if such application contains

substantial evidence of the effectiveness of the drug involved, any

studies of animal safety, or, in the case of food producing

animals, human food safety studies (other than bioequivalence or

residue studies) required for the approval of the application and

conducted or sponsored by the applicant, the Secretary may not make

the approval of an application submitted under subsection (b)(2) of

this section for the conditions of approval of such drug in the

subsection (b)(1) application effective before the expiration of 3

years from the date of the approval of the application under

subsection (b)(1) of this section for such drug.

(iii) If a supplement to an application approved under subsection

(b)(1) of this section is approved after November 16, 1988, and the

supplement contains substantial evidence of the effectiveness of

the drug involved, any studies of animal safety, or, in the case of

food producing animals, human food safety studies (other than

bioequivalence or residue studies) required for the approval of the

supplement and conducted or sponsored by the person submitting the

supplement, the Secretary may not make the approval of an

application submitted under subsection (b)(2) of this section for a

change approved in the supplement effective before the expiration

of 3 years from the date of the approval of the supplement.

(iv) An applicant under subsection (b)(1) of this section who

comes within the provisions of clause (i) of this subparagraph as a

result of an application which seeks approval for a use solely in

non-food producing animals, may elect, within 10 days of receiving

such approval, to waive clause (i) of this subparagraph, in which

event the limitation on approval of applications submitted under

subsection (b)(2) of this section set forth in clause (ii) of this

subparagraph shall be applicable to the subsection (b)(1)

application.

(v) If an application (including any supplement to a new animal

drug application) submitted under subsection (b)(1) of this section

for a new animal drug for a food-producing animal use, which

includes an active ingredient (including any ester or salt of the

active ingredient) which has been the subject of a waiver under

clause (iv) is approved after November 16, 1988, and if the

application contains substantial evidence of the effectiveness of

the drug involved, any studies of animal safety, or human food

safety studies (other than bioequivalence or residue studies)

required for the new approval of the application and conducted or

sponsored by the applicant, the Secretary may not make the approval

of an application (including any supplement to such application)

submitted under subsection (b)(2) of this section for the new

conditions of approval of such drug in the subsection (b)(1)

application effective before the expiration of five years from the

date of approval of the application under subsection (b)(1) of this

section for such drug. The provisions of this paragraph shall

apply only to the first approval for a food-producing animal use

for the same applicant after the waiver under clause (iv).

(G) If an approved application submitted under subsection (b)(2)

of this section for a new animal drug refers to a drug the approval

of which was withdrawn or suspended for grounds described in

paragraph (1) or (2) of subsection (e) of this section or was

withdrawn or suspended under this subparagraph or which, as

determined by the Secretary, has been withdrawn from sale for

safety or effectiveness reasons, the approval of the drug under

this paragraph shall be withdrawn or suspended -

(i) for the same period as the withdrawal or suspension under

subsection (e) of this section or this subparagraph, or

(ii) if the approved new animal drug has been withdrawn from

sale, for the period of withdrawal from sale or, if earlier, the

period ending on the date the Secretary determines that the

withdrawal from sale is not for safety or effectiveness reasons.

(H) For purposes of this paragraph:

(i) The term ''bioequivalence'' means the rate and extent to

which the active ingredient or therapeutic ingredient is absorbed

from a new animal drug and becomes available at the site of drug

action.

(ii) A new animal drug shall be considered to be bioequivalent

to the approved new animal drug referred to in its application

under subsection (n) of this section if -

(I) the rate and extent of absorption of the drug do not show

a significant difference from the rate and extent of absorption

of the approved new animal drug referred to in the application

when administered at the same dose of the active ingredient

under similar experimental conditions in either a single dose

or multiple doses;

(II) the extent of absorption of the drug does not show a

significant difference from the extent of absorption of the

approved new animal drug referred to in the application when

administered at the same dose of the active ingredient under

similar experimental conditions in either a single dose or

multiple doses and the difference from the approved new animal

drug in the rate of absorption of the drug is intentional, is

reflected in its proposed labeling, is not essential to the

attainment of effective drug concentrations in use, and is

considered scientifically insignificant for the drug in

attaining the intended purposes of its use and preserving human

food safety; or

(III) in any case in which the Secretary determines that the

measurement of the rate and extent of absorption or excretion

of the new animal drug in biological fluids is inappropriate or

impractical, an appropriate acute pharmacological effects test

or other test of the new animal drug and, when deemed

scientifically necessary, of the approved new animal drug

referred to in the application in the species to be tested or

in an appropriate animal model does not show a significant

difference between the new animal drug and such approved new

animal drug when administered at the same dose under similar

experimental conditions.

If the approved new animal drug referred to in the application

for a new animal drug under subsection (n) of this section is

approved for use in more than one animal species, the

bioequivalency information described in subclauses (I), (II), and

(III) shall be obtained for one species, or if the Secretary

deems appropriate based on scientific principles, shall be

obtained for more than one species. The Secretary may prescribe

the dose to be used in determining bioequivalency under subclause

(I), (II), or (III). To assure that the residues of the new

animal drug will be consistent with the established tolerances

for the approved new animal drug referred to in the application

under subsection (b)(2) of this section upon the expiration of

the withdrawal period contained in the application for the new

animal drug, the Secretary shall require bioequivalency data or

residue depletion studies of the new animal drug or such other

data or studies as the Secretary considers appropriate based on

scientific principles. If the Secretary requires one or more

residue studies under the preceding sentence, the Secretary may

not require that the assay methodology used to determine the

withdrawal period of the new animal drug be more rigorous than

the methodology used to determine the withdrawal period for the

approved new animal drug referred to in the application. If such

studies are required and if the approved new animal drug,

referred to in the application for the new animal drug for which

such studies are required, is approved for use in more than one

animal species, such studies shall be conducted for one species,

or if the Secretary deems appropriate based on scientific

principles, shall be conducted for more than one species.

(3) If the patent information described in subsection (b)(1) of

this section could not be filed with the submission of an

application under subsection (b)(1) of this section because the

application was filed before the patent information was required

under subsection (b)(1) of this section or a patent was issued

after the application was approved under such subsection, the

holder of an approved application shall file with the Secretary the

patent number and the expiration date of any patent which claims

the new animal drug for which the application was filed or which

claims a method of using such drug and with respect to which a

claim of patent infringement could reasonably be asserted if a

person not licensed by the owner engaged in the manufacture, use,

or sale of the drug. If the holder of an approved application

could not file patent information under subsection (b)(1) of this

section because it was not required at the time the application was

approved, the holder shall file such information under this

subsection not later than 30 days after November 16, 1988, and if

the holder of an approved application could not file patent

information under subsection (b)(1) of this section because no

patent had been issued when an application was filed or approved,

the holder shall file such information under this subsection not

later than 30 days after the date the patent involved is issued.

Upon the submission of patent information under this subsection,

the Secretary shall publish it.

(4) A drug manufactured in a pilot or other small facility may be

used to demonstrate the safety and effectiveness of the drug and to

obtain approval for the drug prior to manufacture of the drug in a

larger facility, unless the Secretary makes a determination that a

full scale production facility is necessary to ensure the safety or

effectiveness of the drug.

(d) Grounds for refusing application; approval of application;

factors; ''substantial evidence'' defined; combination drugs

(1) If the Secretary finds, after due notice to the applicant in

accordance with subsection (c) of this section and giving him an

opportunity for a hearing, in accordance with said subsection, that

-

(A) the investigations, reports of which are required to be

submitted to the Secretary pursuant to subsection (b) of this

section, do not include adequate tests by all methods reasonably

applicable to show whether or not such drug is safe for use under

the conditions prescribed, recommended, or suggested in the

proposed labeling thereof;

(B) the results of such tests show that such drug is unsafe for

use under such conditions or do not show that such drug is safe

for use under such conditions;

(C) the methods used in, and the facilities and controls used

for, the manufacture, processing, and packing of such drug are

inadequate to preserve its identity, strength, quality, and

purity;

(D) upon the basis of the information submitted to him as part

of the application, or upon the basis of any other information

before him with respect to such drug, he has insufficient

information to determine whether such drug is safe for use under

such conditions;

(E) evaluated on the basis of the information submitted to him

as part of the application and any other information before him

with respect to such drug, there is a lack of substantial

evidence that the drug will have the effect it purports or is

represented to have under the conditions of use prescribed,

recommended, or suggested in the proposed labeling thereof;

(F) upon the basis of information submitted to the Secretary as

part of the application or any other information before the

Secretary with respect to such drug, any use prescribed,

recommended, or suggested in labeling proposed for such drug will

result in a residue of such drug in excess of a tolerance found

by the Secretary to be safe for such drug;

(G) the application failed to contain the patent information

prescribed by subsection (b)(1) of this section;

(H) based on a fair evaluation of all material facts, such

labeling is false or misleading in any particular; or

(I) such drug induces cancer when ingested by man or animal or,

after tests which are appropriate for the evaluation of the

safety of such drug, induces cancer in man or animal, except that

the foregoing provisions of this subparagraph shall not apply

with respect to such drug if the Secretary finds that, under the

conditions of use specified in proposed labeling and reasonably

certain to be followed in practice (i) such drug will not

adversely affect the animals for which it is intended, and (ii)

no residue of such drug will be found (by methods of examination

prescribed or approved by the Secretary by regulations, which

regulations shall not be subject to subsections (c), (d), and (h)

of this section), in any edible portion of such animals after

slaughter or in any food yielded by or derived from the living

animals;

he shall issue an order refusing to approve the application. If,

after such notice and opportunity for hearings, the Secretary finds

that subparagraphs (A) through (I) do not apply, he shall issue an

order approving the application.

(2) In determining whether such drug is safe for use under the

conditions prescribed, recommended, or suggested in the proposed

labeling thereof, the Secretary shall consider, among other

relevant factors, (A) the probable consumption of such drug and of

any substance formed in or on food because of the use of such drug,

(B) the cumulative effect on man or animal of such drug, taking

into account any chemically or pharmacologically related substance,

(C) safety factors which in the opinion of experts, qualified by

scientific training and experience to evaluate the safety of such

drugs, are appropriate for the use of animal experimentation data,

and (D) whether the conditions of use prescribed, recommended, or

suggested in the proposed labeling are reasonably certain to be

followed in practice. Any order issued under this subsection

refusing to approve an application shall state the findings upon

which it is based.

(3) As used in this section, the term ''substantial evidence''

means evidence consisting of one or more adequate and well

controlled investigations, such as -

(A) a study in a target species;

(B) a study in laboratory animals;

(C) any field investigation that may be required under this

section and that meets the requirements of subsection (b)(3) of

this section if a presubmission conference is requested by the

applicant;

(D) a bioequivalence study; or

(E) an in vitro study;

by experts qualified by scientific training and experience to

evaluate the effectiveness of the drug involved, on the basis of

which it could fairly and reasonably be concluded by such experts

that the drug will have the effect it purports or is represented to

have under the conditions of use prescribed, recommended, or

suggested in the labeling or proposed labeling thereof.

(4) In a case in which an animal drug contains more than one

active ingredient, or the labeling of the drug prescribes,

recommends, or suggests use of the drug in combination with one or

more other animal drugs, and the active ingredients or drugs

intended for use in the combination have previously been separately

approved for particular uses and conditions of use for which they

are intended for use in the combination -

(A) the Secretary shall not issue an order under paragraph

(1)(A), (1)(B), or (1)(D) refusing to approve the application for

such combination on human food safety grounds unless the

Secretary finds that the application fails to establish that -

(i) none of the active ingredients or drugs intended for use

in the combination, respectively, at the longest withdrawal

time of any of the active ingredients or drugs in the

combination, respectively, exceeds its established tolerance;

or

(ii) none of the active ingredients or drugs in the

combination interferes with the methods of analysis for another

of the active ingredients or drugs in the combination,

respectively;

(B) the Secretary shall not issue an order under paragraph

(1)(A), (1)(B), or (1)(D) refusing to approve the application for

such combination on target animal safety grounds unless the

Secretary finds that -

(i)(I) there is a substantiated scientific issue, specific to

one or more of the active ingredients or animal drugs in the

combination, that cannot adequately be evaluated based on

information contained in the application for the combination

(including any investigations, studies, or tests for which the

applicant has a right of reference or use from the person by or

for whom the investigations, studies, or tests were conducted);

or

(II) there is a scientific issue raised by target animal

observations contained in studies submitted to the Secretary as

part of the application; and

(ii) based on the Secretary's evaluation of the information

contained in the application with respect to the issues

identified in clauses (i)(I) and (II), paragraph (1)(A), (B),

or (D) apply;

(C) except in the case of a combination that contains a

nontopical antibacterial ingredient or animal drug, the Secretary

shall not issue an order under paragraph (1)(E) refusing to

approve an application for a combination animal drug intended for

use other than in animal feed or drinking water unless the

Secretary finds that the application fails to demonstrate that -

(i) there is substantial evidence that any active ingredient

or animal drug intended only for the same use as another active

ingredient or animal drug in the combination makes a

contribution to labeled effectiveness;

(ii) each active ingredient or animal drug intended for at

least one use that is different from all other active

ingredients or animal drugs used in the combination provides

appropriate concurrent use for the intended target population;

or

(iii) where based on scientific information the Secretary has

reason to believe the active ingredients or animal drugs may be

physically incompatible or have disparate dosing regimens, such

active ingredients or animal drugs are physically compatible or

do not have disparate dosing regimens; and

(D) the Secretary shall not issue an order under paragraph

(1)(E) refusing to approve an application for a combination

animal drug intended for use in animal feed or drinking water

unless the Secretary finds that the application fails to

demonstrate that -

(i) there is substantial evidence that any active ingredient

or animal drug intended only for the same use as another active

ingredient or animal drug in the combination makes a

contribution to the labeled effectiveness;

(ii) each of the active ingredients or animal drugs intended

for at least one use that is different from all other active

ingredients or animal drugs used in the combination provides

appropriate concurrent use for the intended target population;

(iii) where a combination contains more than one nontopical

antibacterial ingredient or animal drug, there is substantial

evidence that each of the nontopical antibacterial ingredients

or animal drugs makes a contribution to the labeled

effectiveness, except that for purposes of this clause,

antibacterial ingredient or animal drug does not include the

ionophore or arsenical classes of animal drugs; or

(iv) where based on scientific information the Secretary has

reason to believe the active ingredients or animal drugs

intended for use in drinking water may be physically

incompatible, such active ingredients or animal drugs intended

for use in drinking water are physically compatible.

(e) Withdrawal of approval; grounds; immediate suspension upon

finding imminent hazard to health of man or animals

(1) The Secretary shall, after due notice and opportunity for

hearing to the applicant, issue an order withdrawing approval of an

application filed pursuant to subsection (b) of this section with

respect to any new animal drug if the Secretary finds -

(A) that experience or scientific data show that such drug is

unsafe for use under the conditions of use upon the basis of

which the application was approved or the condition of use

authorized under subsection (a)(4)(A) of this section;

(B) that new evidence not contained in such application or not

available to the Secretary until after such application was

approved, or tests by new methods, or tests by methods not deemed

reasonably applicable when such application was approved,

evaluated together with the evidence available to the Secretary

when the application was approved, shows that such drug is not

shown to be safe for use under the conditions of use upon the

basis of which the application was approved or that subparagraph

(I) of paragraph (1) of subsection (d) of this section applies to

such drug;

(C) on the basis of new information before him with respect to

such drug, evaluated together with the evidence available to him

when the application was approved, that there is a lack of

substantial evidence that such drug will have the effect it

purports or is represented to have under the conditions of use

prescribed, recommended, or suggested in the labeling thereof;

(D) the patent information prescribed by subsection (c)(3) of

this section was not filed within 30 days after the receipt of

written notice from the Secretary specifying the failure to file

such information;

(E) that the application contains any untrue statement of a

material fact; or

(F) that the applicant has made any changes from the standpoint

of safety or effectiveness beyond the variations provided for in

the application unless he has supplemented the application by

filing with the Secretary adequate information respecting all

such changes and unless there is in effect an approval of the

supplemental application. The supplemental application shall be

treated in the same manner as the original application.

If the Secretary (or in his absence the officer acting as

Secretary) finds that there is an imminent hazard to the health of

man or of the animals for which such drug is intended, he may

suspend the approval of such application immediately, and give the

applicant prompt notice of his action and afford the applicant the

opportunity for an expedited hearing under this subsection; but the

authority conferred by this sentence to suspend the approval of an

application shall not be delegated.

(2) The Secretary may also, after due notice and opportunity for

hearing to the applicant, issue an order withdrawing the approval

of an application with respect to any new animal drug under this

section if the Secretary finds -

(A) that the applicant has failed to establish a system for

maintaining required records, or has repeatedly or deliberately

failed to maintain such records or to make required reports in

accordance with a regulation or order under subsection (1) of

this section, or the applicant has refused to permit access to,

or copying or verification of, such records as required by

paragraph (2) of such subsection;

(B) that on the basis of new information before him, evaluated

together with the evidence before him when the application was

approved, the methods used in, or the facilities and controls

used for, the manufacture, processing, and packing of such drug

are inadequate to assure and preserve its identity, strength,

quality, and purity and were not made adequate within a

reasonable time after receipt of written notice from the

Secretary specifying the matter complained of; or

(C) that on the basis of new information before him, evaluated

together with the evidence before him when the application was

approved, the labeling of such drug, based on a fair evaluation

of all material facts, is false or misleading in any particular

and was not corrected within a reasonable time after receipt of

written notice from the Secretary specifying the matter

complained of.

(3) Any order under this subsection shall state the findings upon

which it is based.

(f) Revocation of order refusing, withdrawing or suspending

approval of application

Whenever the Secretary finds that the facts so require, he shall

revoke any previous order under subsection (d), (e), or (m) of this

section refusing, withdrawing, or suspending approval of an

application and shall approve such application or reinstate such

approval, as may be appropriate.

(g) Service of orders

Orders of the Secretary issued under this section (other than

orders issuing, amending, or repealing regulations) shall be served

(1) in person by any officer or employee of the department

designated by the Secretary or (2) by mailing the order by

registered mail or by certified mail addressed to the applicant or

respondent at his last known address in the records of the

Secretary.

(h) Appeal from order

An appeal may be taken by the applicant from an order of the

Secretary refusing or withdrawing approval of an application filed

under subsection (b) or (m) of this section. The provisions of

subsection (h) of section 355 of this title shall govern any such

appeal.

(i) Publication in Federal Register; effective date and revocation

or suspension of regulation

When a new animal drug application filed pursuant to subsection

(b) of this section is approved, the Secretary shall by notice,

which upon publication shall be effective as a regulation, publish

in the Federal Register the name and address of the applicant and

the conditions and indications of use of the new animal drug

covered by such application, including any tolerance and withdrawal

period or other use restrictions and, if such new animal drug is

intended for use in animal feed, appropriate purposes and

conditions of use (including special labeling requirements and any

requirement that an animal feed bearing or containing the new

animal drug be limited to use under the professional supervision of

a licensed veterinarian) applicable to any animal feed for use in

which such drug is approved, and such other information, upon the

basis of which such application was approved, as the Secretary

deems necessary to assure the safe and effective use of such drug.

Upon withdrawal of approval of such new animal drug application or

upon its suspension, the Secretary shall forthwith revoke or

suspend, as the case may be, the regulation published pursuant to

this subsection (i) insofar as it is based on the approval of such

application.

(j) Exemption of drugs for research; discretionary and mandatory

conditions

To the extent consistent with the public health, the Secretary

shall promulgate regulations for exempting from the operation of

this section new animal drugs, and animal feeds bearing or

containing new animal drugs, intended solely for investigational

use by experts qualified by scientific training and experience to

investigate the safety and effectiveness of animal drugs. Such

regulations may, in the discretion of the Secretary, among other

conditions relating to the protection of the public health, provide

for conditioning such exemption upon the establishment and

maintenance of such records, and the making of such reports to the

Secretary, by the manufacturer or the sponsor of the investigation

of such article, of data (including but not limited to analytical

reports by investigators) obtained as a result of such

investigational use of such article, as the Secretary finds will

enable him to evaluate the safety and effectiveness of such article

in the event of the filing of an application pursuant to this

section. Such regulations, among other things, shall set forth the

conditions (if any) upon which animals treated with such articles,

and any products of such animals (before or after slaughter), may

be marketed for food use.

(k) Food containing new animal drug considered unadulterated while

approval of application for such drug is effective

While approval of an application for a new animal drug is

effective, a food shall not, by reason of bearing or containing

such drug or any substance formed in or on the food because of its

use in accordance with such application (including the conditions

and indications of use prescribed pursuant to subsection (i) of

this section), be considered adulterated within the meaning of

clause (1) of section 342(a) of this title.

(l) Records and reports; required information; regulations and

orders; examination of data; access to records

(1) In the case of any new animal drug for which an approval of

an application filed pursuant to subsection (b) of this section is

in effect, the applicant shall establish and maintain such records,

and make such reports to the Secretary, of data relating to

experience, including experience with uses authorized under

subsection (a)(4)(A) of this section, and other data or

information, received or otherwise obtained by such applicant with

respect to such drug, or with respect to animal feeds bearing or

containing such drug, as the Secretary may by general regulation,

or by order with respect to such application, prescribe on the

basis of a finding that such records and reports are necessary in

order to enable the Secretary to determine, or facilitate a

determination, whether there is or may be ground for invoking

subsection (e) or subsection (m)(4) of this section. Such

regulation or order shall provide, where the Secretary deems it to

be appropriate, for the examination, upon request, by the persons

to whom such regulation or order is applicable, of similar

information received or otherwise obtained by the Secretary.

(2) Every person required under this subsection to maintain

records, and every person in charge or custody thereof, shall, upon

request of an officer or employee designated by the Secretary,

permit such officer or employee at all reasonable times to have

access to and copy and verify such records.

(m) Feed mill licenses

(1) Any person may file with the Secretary an application for a

license to manufacture animal feeds bearing or containing new

animal drugs. Such person shall submit to the Secretary as part of

the application (A) a full statement of the business name and

address of the specific facility at which the manufacturing is to

take place and the facility's registration number, (B) the name and

signature of the responsible individual or individuals for that

facility, (C) a certification that the animal feeds bearing or

containing new animal drugs are manufactured and labeled in

accordance with the applicable regulations published pursuant to

subsection (i) of this section, and (D) a certification that the

methods used in, and the facilities and controls used for,

manufacturing, processing, packaging, and holding such animal feeds

are in conformity with current good manufacturing practice as

described in section 351(a)(2)(B) of this title.

(2) Within 90 days after the filing of an application pursuant to

paragraph (1), or such additional period as may be agreed upon by

the Secretary and the applicant, the Secretary shall (A) issue an

order approving the application if the Secretary then finds that

none of the grounds for denying approval specified in paragraph (3)

applies, or (B) give the applicant notice of an opportunity for a

hearing before the Secretary under paragraph (3) on the question

whether such application is approvable. The procedure governing

such a hearing shall be the procedure set forth in the last two

sentences of subsection (c)(1) of this section.

(3) If the Secretary, after due notice to the applicant in

accordance with paragraph (2) and giving the applicant an

opportunity for a hearing in accordance with such paragraph, finds,

on the basis of information submitted to the Secretary as part of

the application, on the basis of a preapproval inspection, or on

the basis of any other information before the Secretary -

(A) that the application is incomplete, false, or misleading in

any particular;

(B) that the methods used in, and the facilities and controls

used for, the manufacture, processing, and packing of such animal

feed are inadequate to preserve the identity, strength, quality,

and purity of the new animal drug therein; or

(C) that the facility manufactures animal feeds bearing or

containing new animal drugs in a manner that does not accord with

the specifications for manufacture or labels animal feeds bearing

or containing new animal drugs in a manner that does not accord

with the conditions or indications of use that are published

pursuant to subsection (i) of this section,

the Secretary shall issue an order refusing to approve the

application. If, after such notice and opportunity for hearing,

the Secretary finds that subparagraphs (A) through (C) do not

apply, the Secretary shall issue an order approving the

application. An order under this subsection approving an

application for a license to manufacture animal feeds bearing or

containing new animal drugs shall permit a facility to manufacture

only those animal feeds bearing or containing new animal drugs for

which there are in effect regulations pursuant to subsection (i) of

this section relating to the use of such drugs in or on such animal

feed.

(4)(A) The Secretary shall, after due notice and opportunity for

hearing to the applicant, revoke a license to manufacture animal

feeds bearing or containing new animal drugs under this subsection

if the Secretary finds -

(i) that the application for such license contains any untrue

statement of a material fact; or

(ii) that the applicant has made changes that would cause the

application to contain any untrue statements of material fact or

that would affect the safety or effectiveness of the animal feeds

manufactured at the facility unless the applicant has

supplemented the application by filing with the Secretary

adequate information respecting all such changes and unless there

is in effect an approval of the supplemental application.

If the Secretary (or in the Secretary's absence the officer acting

as the Secretary) finds that there is an imminent hazard to the

health of humans or of the animals for which such animal feed is

intended, the Secretary may suspend the license immediately, and

give the applicant prompt notice of the action and afford the

applicant the opportunity for an expedited hearing under this

subsection; but the authority conferred by this sentence shall not

be delegated.

(B) The Secretary may also, after due notice and opportunity for

hearing to the applicant, revoke a license to manufacture animal

feed under this subsection if the Secretary finds -

(i) that the applicant has failed to establish a system for

maintaining required records, or has repeatedly or deliberately

failed to maintain such records or to make required reports in

accordance with a regulation or order under paragraph (5)(A) of

this subsection or section 354(a)(3)(A) of this title, or the

applicant has refused to permit access to, or copying or

verification of, such records as required by subparagraph (B) of

such paragraph or section 354(a)(3)(B) of this title;

(ii) that on the basis of new information before the Secretary,

evaluated together with the evidence before the Secretary when

such license was issued, the methods used in, or the facilities

and controls used for, the manufacture, processing, packing, and

holding of such animal feed are inadequate to assure and preserve

the identity, strength, quality, and purity of the new animal

drug therein, and were not made adequate within a reasonable time

after receipt of written notice from the Secretary, specifying

the matter complained of;

(iii) that on the basis of new information before the

Secretary, evaluated together with the evidence before the

Secretary when such license was issued, the labeling of any

animal feeds, based on a fair evaluation of all material facts,

is false or misleading in any particular and was not corrected

within a reasonable time after receipt of written notice from the

Secretary specifying the matter complained of; or

(iv) that on the basis of new information before the Secretary,

evaluated together with the evidence before the Secretary when

such license was issued, the facility has manufactured,

processed, packed, or held animal feed bearing or containing a

new animal drug adulterated under section 351(a)(6) of this title

and the facility did not discontinue the manufacture, processing,

packing, or holding of such animal feed within a reasonable time

after receipt of written notice from the Secretary specifying the

matter complained of.

(C) The Secretary may also revoke a license to manufacture animal

feeds under this subsection if an applicant gives notice to the

Secretary of intention to discontinue the manufacture of all animal

feed covered under this subsection and waives an opportunity for a

hearing on the matter.

(D) Any order under this paragraph shall state the findings upon

which it is based.

(5) When a license to manufacture animal feeds bearing or

containing new animal drugs has been issued -

(A) the applicant shall establish and maintain such records,

and make such reports to the Secretary, or (at the option of the

Secretary) to the appropriate person or persons holding an

approved application filed under subsection (b) of this section,

as the Secretary may by general regulation, or by order with

respect to such application, prescribe on the basis of a finding

that such records and reports are necessary in order to enable

the Secretary to determine, or facilitate a determination,

whether there is or may be ground for invoking subsection (e) of

this section or paragraph (4); and

(B) every person required under this subsection to maintain

records, and every person in charge or custody thereof, shall,

upon request of an officer or employee designated by the

Secretary, permit such officer or employee at all reasonable

times to have access to and copy and verify such records.

(6) To the extent consistent with the public health, the

Secretary may promulgate regulations for exempting from the

operation of this subsection facilities that manufacture, process,

pack, or hold animal feeds bearing or containing new animal drugs.

(n) Abbreviated applications for new animal drugs; contents,

filing, etc.; lists of approved drugs

(1) An abbreviated application for a new animal drug shall

contain -

(A)(i) except as provided in clause (ii), information to show

that the conditions of use or similar limitations (whether in the

labeling or published pursuant to subsection (i) of this section)

prescribed, recommended, or suggested in the labeling proposed

for the new animal drug have been previously approved for a new

animal drug listed under paragraph (4) (hereinafter in this

subsection referred to as an ''approved new animal drug''), and

(ii) information to show that the withdrawal period at which

residues of the new animal drug will be consistent with the

tolerances established for the approved new animal drug is the

same as the withdrawal period previously established for the

approved new animal drug or, if the withdrawal period is proposed

to be different, information showing that the residues of the new

animal drug at the proposed different withdrawal period will be

consistent with the tolerances established for the approved new

animal drug;

(B)(i) information to show that the active ingredients of the

new animal drug are the same as those of the approved new animal

drug, and

(ii) if the approved new animal drug has more than one active

ingredient, and if one of the active ingredients of the new

animal drug is different from one of the active ingredients of

the approved new animal drug and the application is filed

pursuant to the approval of a petition filed under paragraph (3)

-

(I) information to show that the other active ingredients of

the new animal drug are the same as the active ingredients of

the approved new animal drug,

(II) information to show either that the different active

ingredient is an active ingredient of another approved new

animal drug or of an animal drug which does not meet the

requirements of section 321(v) of this title, and

(III) such other information respecting the different active

ingredients as the Secretary may require;

(C)(i) if the approved new animal drug is permitted to be used

with one or more animal drugs in animal feed, information to show

that the proposed uses of the new animal drug with other animal

drugs in animal feed are the same as the uses of the approved new

animal drug, and

(ii) if the approved new animal drug is permitted to be used

with one or more other animal drugs in animal feed, and one of

the other animal drugs proposed for use with the new animal drug

in animal feed is different from one of the other animal drugs

permitted to be used in animal feed with the approved new animal

drug, and the application is filed pursuant to the approval of a

petition filed under paragraph (3) -

(I) information to show either that the different animal drug

proposed for use with the approved new animal drug in animal

feed is an approved new animal drug permitted to be used in

animal feed or does not meet the requirements of section 321(v)

of this title when used with another animal drug in animal

feed,

(II) information to show that other animal drugs proposed for

use with the new animal drug in animal feed are the same as the

other animal drugs permitted to be used with the approved new

animal drug, and

(III) such other information respecting the different animal

drug or combination with respect to which the petition was

filed as the Secretary may require,

(D) information to show that the route of administration, the

dosage form, and the strength of the new animal drug are the same

as those of the approved new animal drug or, if the route of

administration, the dosage form, or the strength of the new

animal drug is different and the application is filed pursuant to

the approval of a petition filed under paragraph (3), such

information respecting the route of administration, dosage form,

or strength with respect to which the petition was filed as the

Secretary may require;

(E) information to show that the new animal drug is

bioequivalent to the approved new animal drug, except that if the

application is filed pursuant to the approval of a petition filed

under paragraph (3) for the purposes described in subparagraph

(B) or (C), information to show that the active ingredients of

the new animal drug are of the same pharmacological or

therapeutic class as the pharmacological or therapeutic class of

the approved new animal drug and that the new animal drug can be

expected to have the same therapeutic effect as the approved new

animal drug when used in accordance with the labeling;

(F) information to show that the labeling proposed for the new

animal drug is the same as the labeling approved for the approved

new animal drug except for changes required because of

differences approved under a petition filed under paragraph (3),

because of a different withdrawal period, or because the new

animal drug and the approved new animal drug are produced or

distributed by different manufacturers;

(G) the items specified in clauses (B) through (F) of

subsection (b)(1) of this section;

(H) a certification, in the opinion of the applicant and to the

best of his knowledge, with respect to each patent which claims

the approved new animal drug or which claims a use for such

approved new animal drug for which the applicant is seeking

approval under this subsection and for which information is

required to be filed under subsection (b)(1) or (c)(3) of this

section -

(i) that such patent information has not been filed,

(ii) that such patent has expired,

(iii) of the date on which such patent will expire, or

(iv) that such patent is invalid or will not be infringed by

the manufacture, use, or sale of the new animal drug for which

the application is filed; and

(I) if with respect to the approved new animal drug information

was filed under subsection (b)(1) or (c)(3) of this section for a

method of use patent which does not claim a use for which the

applicant is seeking approval of an application under subsection

(c)(2) of this section, a statement that the method of use patent

does not claim such a use.

The Secretary may not require that an abbreviated application

contain information in addition to that required by subparagraphs

(A) through (I).

(2)(A) An applicant who makes a certification described in

paragraph (1)(G)(iv) shall include in the application a statement

that the applicant will give the notice required by subparagraph

(B) to -

(i) each owner of the patent which is the subject of the

certification or the representative of such owner designated to

receive such notice, and

(ii) the holder of the approved application under subsection

(c)(1) of this section for the drug which is claimed by the

patent or a use of which is claimed by the patent or the

representative of such holder designated to receive such notice.

(B) The notice referred to in subparagraph (A) shall state that

an application, which contains data from bioequivalence studies,

has been filed under this subsection for the drug with respect to

which the certification is made to obtain approval to engage in the

commercial manufacture, use, or sale of such drug before the

expiration of the patent referred to in the certification. Such

notice shall include a detailed statement of the factual and legal

basis of the applicant's opinion that the patent is not valid or

will not be infringed.

(C) If an application is amended to include a certification

described in paragraph (1)(G)(iv), the notice required by

subparagraph (B) shall be given when the amended application is

filed.

(3) If a person wants to submit an abbreviated application for a

new animal drug -

(A) whose active ingredients, route of administration, dosage

form, or strength differ from that of an approved new animal

drug, or

(B) whose use with other animal drugs in animal feed differs

from that of an approved new animal drug,

such person shall submit a petition to the Secretary seeking

permission to file such an application. The Secretary shall

approve a petition for a new animal drug unless the Secretary finds

that -

(C) investigations must be conducted to show the safety and

effectiveness, in animals to be treated with the drug, of the

active ingredients, route of administration, dosage form,

strength, or use with other animal drugs in animal feed which

differ from the approved new animal drug, or

(D) investigations must be conducted to show the safety for

human consumption of any residues in food resulting from the

proposed active ingredients, route of administration, dosage

form, strength, or use with other animal drugs in animal feed for

the new animal drug which is different from the active

ingredients, route of administration, dosage form, strength, or

use with other animal drugs in animal feed of the approved new

animal drug.

The Secretary shall approve or disapprove a petition submitted

under this paragraph within 90 days of the date the petition is

submitted.

(4)(A)(i) Within 60 days of November 16, 1988, the Secretary

shall publish and make available to the public a list in

alphabetical order of the official and proprietary name of each new

animal drug which has been approved for safety and effectiveness

before November 16, 1988.

(ii) Every 30 days after the publication of the first list under

clause (i) the Secretary shall revise the list to include each new

animal drug which has been approved for safety and effectiveness

under subsection (c) of this section during the 30 day period.

(iii) When patent information submitted under subsection (b)(1)

or (c)(3) of this section respecting a new animal drug included on

the list is to be published by the Secretary, the Secretary shall,

in revisions made under clause (ii), include such information for

such drug.

(B) A new animal drug approved for safety and effectiveness

before November 16, 1988, or approved for safety and effectiveness

under subsection (c) of this section shall, for purposes of this

subsection, be considered to have been published under subparagraph

(A) on the date of its approval or November 16, 1988, whichever is

later.

(C) If the approval of a new animal drug was withdrawn or

suspended under subsection (c)(2)(G) of this section or for grounds

described in subsection (e) of this section or if the Secretary

determines that a drug has been withdrawn from sale for safety or

effectiveness reasons, it may not be published in the list under

subparagraph (A) or, if the withdrawal or suspension occurred after

its publication in such list, it shall be immediately removed from

such list -

(i) for the same period as the withdrawal or suspension under

subsection (c)(2)(G) or (e) of this section, or

(ii) if the listed drug has been withdrawn from sale, for the

period of withdrawal from sale or, if earlier, the period ending

on the date the Secretary determines that the withdrawal from

sale is not for safety or effectiveness reasons.

A notice of the removal shall be published in the Federal Register.

(5) If an application contains the information required by

clauses (A), (G), and (H) of subsection (b)(1) of this section and

such information -

(A) is relied on by the applicant for the approval of the

application, and

(B) is not information derived either from investigations,

studies, or tests conducted by or for the applicant or for which

the applicant had obtained a right of reference or use from the

person by or for whom the investigations, studies, or tests were

conducted,

such application shall be considered to be an application filed

under subsection (b)(2) of this section.

(o) ''Patent'' defined

For purposes of this section, the term ''patent'' means a patent

issued by the United States Patent and Trademark Office.

(p) Safety and effectiveness data

(1) Safety and effectiveness data and information which has been

submitted in an application filed under subsection (b)(1) of this

section for a drug and which has not previously been disclosed to

the public shall be made available to the public, upon request,

unless extraordinary circumstances are shown -

(A) if no work is being or will be undertaken to have the

application approved,

(B) if the Secretary has determined that the application is not

approvable and all legal appeals have been exhausted,

(C) if approval of the application under subsection (c) of this

section is withdrawn and all legal appeals have been exhausted,

(D) if the Secretary has determined that such drug is not a new

drug, or

(E) upon the effective date of the approval of the first

application filed under subsection (b)(2) of this section which

refers to such drug or upon the date upon which the approval of

an application filed under subsection (b)(2) of this section

which refers to such drug could be made effective if such an

application had been filed.

(2) Any request for data and information pursuant to paragraph

(1) shall include a verified statement by the person making the

request that any data or information received under such paragraph

shall not be disclosed by such person to any other person -

(A) for the purpose of, or as part of a plan, scheme, or device

for, obtaining the right to make, use, or market, or making,

using, or marketing, outside the United States, the drug

identified in the application filed under subsection (b)(1) of

this section, and

(B) without obtaining from any person to whom the data and

information are disclosed an identical verified statement, a copy

of which is to be provided by such person to the Secretary, which

meets the requirements of this paragraph.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 512, as added Pub. L. 90-399, Sec.

101(b), July 13, 1968, 82 Stat. 343; amended Pub. L. 100-670, title

I, Sec. 101, 102, 104, 107(a)(2), Nov. 16, 1988, 102 Stat. 3971,

3981, 3982, 3984; Pub. L. 102-108, Sec. 2(e), Aug. 17, 1991, 105

Stat. 550; Pub. L. 103-80, Sec. 3(r), Aug. 13, 1993, 107 Stat. 777;

Pub. L. 103-396, Sec. 2(a), (b)(2), (3), Oct. 22, 1994, 108 Stat.

4153, 4154; Pub. L. 104-250, Sec. 2(a)-(d), 3-5(c), 6(a), (b), Oct.

9, 1996, 110 Stat. 3151-3153, 3155-3157; Pub. L. 105-115, title I,

Sec. 124(b), Nov. 21, 1997, 111 Stat. 2325; Pub. L. 105-277, div.

A, Sec. 101(a) (title VII, Sec. 737), Oct. 21, 1998, 112 Stat.

2681, 2681-30; Pub. L. 106-113, div. B, Sec. 1000(a)(9) (title IV,

Sec. 4732(b)(11)), Nov. 29, 1999, 113 Stat. 1536, 1501A-584.)

-REFTEXT-

REFERENCES IN TEXT

Section 342(a)(2) of this title, referred to in subsec. (a)(1),

(6), was amended by Pub. L. 104-170, title IV, Sec. 404, Aug. 3,

1996, 110 Stat. 1514, and, as so amended, no longer contains a

subcl. (D). See section 342(a)(2)(C)(ii) of this title.

-MISC2-

AMENDMENTS

1999 - Subsec. (o). Pub. L. 106-113 substituted ''United States

Patent and Trademark Office'' for ''Patent and Trademark Office of

the Department of Commerce''.

1998 - Subsec. (d)(4)(D)(iii). Pub. L. 105-277 inserted before

semicolon '', except that for purposes of this clause,

antibacterial ingredient or animal drug does not include the

ionophore or arsenical classes of animal drugs''.

1997 - Subsec. (c)(4). Pub. L. 105-115 added par. (4).

1996 - Subsec. (a)(1). Pub. L. 104-250, Sec. 6(a), amended par.

(1) generally. Prior to amendment, par. (1) read as follows: ''A

new animal drug shall, with respect to any particular use or

intended use of such drug, be deemed unsafe for the purposes of

section 351(a)(5) and section 342(a)(2)(D) of this title unless -

''(A) there is in effect an approval of an application filed

pursuant to subsection (b) of this section with respect to such

use or intended use of such drug, and

''(B) such drug, its labeling, and such use conform to such

approved application.

A new animal drug shall also be deemed unsafe for such purposes in

the event of removal from the establishment of a manufacturer,

packer, or distributor of such drug for use in the manufacture of

animal feed in any State unless at the time of such removal such

manufacturer, packer, or distributor has an unrevoked written

statement from the consignee of such drug, or notice from the

Secretary, to the effect that, with respect to the use of such drug

in animal feed, such consignee -

''(i) is the holder of an approved application under subsection

(m) of this section; or

''(ii) will, if the consignee is not a user of the drug, ship

such drug only to a holder of an approved application under

subsection (m) of this section.''

Subsec. (a)(2). Pub. L. 104-250, Sec. 6(a), amended par. (2)

generally. Prior to amendment, par. (2) read as follows: ''An

animal feed bearing or containing a new animal drug shall, with

respect to any particular use or intended use of such animal feed,

be deemed unsafe for the purposes of section 351(a)(6) of this

title unless -

''(A) there is in effect an approval of an application filed

pursuant to subsection (b) of this section with respect to such

drugs, as used in such animal feed,

''(B) there is in effect an approval of an application pursuant

to subsection (m)(1) of this section with respect to such animal

feed, and

''(C) such animal feed, its labeling, and such use conform to

the conditions and indications of use published pursuant to

subsection (i) of this section and to the application with

respect thereto approved under subsection (m) of this section.''

Subsec. (a)(6). Pub. L. 104-250, Sec. 4, added par. (6).

Subsec. (b)(3). Pub. L. 104-250, Sec. 2(d), added par. (3).

Subsec. (c)(2)(F)(ii), (iii). Pub. L. 104-250, Sec. 2(b)(1),

substituted ''substantial evidence of the effectiveness of the drug

involved, any studies of animal safety, or,'' for ''reports of new

clinical or field investigations (other than bioequivalence or

residue studies) and,'' and ''required for the approval'' for

''essential to the approval''.

Subsec. (c)(2)(F)(v). Pub. L. 104-250, Sec. 2(b)(2), substituted

''clause (iv)'' for ''subparagraph (B)(iv)'' in two places,

''substantial evidence of the effectiveness of the drug involved,

any studies of animal safety,'' for ''reports of clinical or field

investigations'' and ''required for the new approval'' for

''essential to the new approval''.

Subsec. (d)(1)(F). Pub. L. 104-250, Sec. 3, amended subpar. (F)

generally. Prior to amendment, subpar. (F) read as follows: ''upon

the basis of the information submitted to him as part of the

application or any other information before him with respect to

such drug, the tolerance limitation proposed, if any, exceeds that

reasonably required to accomplish the physical or other technical

effect for which the drug is intended;''.

Subsec. (d)(3). Pub. L. 104-250, Sec. 2(a), amended par. (3)

generally. Prior to amendment, par. (3) read as follows: ''As used

in this subsection and subsection (e) of this section, the term

'substantial evidence' means evidence consisting of adequate and

well-controlled investigations, including field investigation, by

experts qualified by scientific training and experience to evaluate

the effectiveness of the drug involved, on the basis of which it

could fairly and reasonably be concluded by such experts that the

drug will have the effect it purports or is represented to have

under the conditions of use prescribed, recommended, or suggested

in the labeling or proposed labeling thereof.''

Subsec. (d)(4). Pub. L. 104-250, Sec. 2(c), added par. (4).

Subsec. (i). Pub. L. 104-250, Sec. 5(c), inserted ''and any

requirement that an animal feed bearing or containing the new

animal drug be limited to use under the professional supervision of

a licensed veterinarian'' after ''(including special labeling

requirements''.

Subsec. (m). Pub. L. 104-250, Sec. 6(b), amended subsec. (m)

generally, substituting provisions relating to application for feed

mill licenses, including approval, refusal, revocation, and

suspension of such licenses, and provisions for record and

reporting requirements for, as well as exemption from, such

licenses, for provisions relating to application for uses of animal

feed containing new animal drug, including required contents,

approval, refusal, and withdrawal of approval or suspension of such

usage applications, and provisions for record and reporting

requirements of such usage applications.

1994 - Subsec. (a)(4), (5). Pub. L. 103-396, Sec. 2(a), added

pars. (4) and (5).

Subsec. (e)(1)(A). Pub. L. 103-396, Sec. 2(b)(2), inserted before

semicolon at end ''or the condition of use authorized under

subsection (a)(4)(A) of this section''.

Subsec. (l)(1). Pub. L. 103-396, Sec. 2(b)(3), substituted

''relating to experience, including experience with uses authorized

under subsection (a)(4)(A) of this section,'' for ''relating to

experience''.

1993 - Subsec. (c)(2)(A)(ii). Pub. L. 103-80, Sec. 3(r)(1),

inserted ''in'' after ''except as provided''.

Subsec. (c)(2)(F)(i). Pub. L. 103-80, Sec. 3(r)(2), substituted

''subparagraph (D)(iii)'' for ''subparagraph (C)(iii)''.

Subsec. (c)(2)(H)(ii). Pub. L. 103-80, Sec. 3(r)(3), substituted

''subclauses'' for ''subclause'' after ''bioequivalency information

described in'' in concluding provisions.

Subsec. (d)(1). Pub. L. 103-80, Sec. 3(r)(4), substituted

''subparagraphs (A) through (I)'' for ''subparagraphs (A) through

(G)'' in concluding provisions.

Subsec. (n)(1). Pub. L. 103-80, Sec. 3(r)(5), substituted

''section 321(v) of this title'' for ''section 321(w) of this

title'' in subpars. (B)(ii)(II) and (C)(ii)(I) and substituted

''through (I)'' for ''through (H)'' in concluding provisions.

1991 - Subsec. (e)(1)(B). Pub. L. 102-108 substituted ''(I)'' for

''(H)''.

1988 - Subsec. (a)(1)(C). Pub. L. 100-670, Sec. 107(a)(2), struck

out subpar. (C) which read as follows: ''in the case of a new

animal drug subject to subsection (n) of this section and not

exempted therefrom by regulations it is from a batch with respect

to which a certificate or release issued pursuant to subsection (n)

of this section is in effect with respect to such drug.''

Subsec. (b). Pub. L. 100-670, Sec. 101(a), 102(a), designated

existing provisions as par. (1), redesignated cls. (1) to (8) as

cls. (A) to (H), respectively, added par. (2), and inserted

provisions at end of par. (1) which require applicant to file with

application, patent number and expiration date of any patent which

claims new animal drug, to amend application to include such

information if patent which claims such drug or method of using

such drug is issued after filing date but before approval of

application, and to publish such information upon approval.

Subsec. (c). Pub. L. 100-670, Sec. 101(c), 102(b)(1), designated

existing provisions as par. (1), redesignated cls. (1) and (2) as

cls. (A) and (B), respectively, and added pars. (2) and (3).

Subsec. (d)(1). Pub. L. 100-670, Sec. 102(b)(3), substituted

''(G)'' for ''(H)'' in last sentence.

Subsec. (d)(1)(G) to (I). Pub. L. 100-670, Sec. 102(b)(2), added

subpar. (G) and redesignated former subpars. (G) and (H) as (H) and

(I), respectively.

Subsec. (e)(1)(D) to (F). Pub. L. 100-670, Sec. 102(b)(4), added

subpar. (D) and redesignated former subpars. (D) and (E) as (E) and

(F), respectively.

Subsecs. (n) to (p). Pub. L. 100-670, Sec. 101(b), added subsecs.

(n) to (p) and struck out former subsec. (n) which related to

certification of new drugs containing penicillin, streptomycin,

chlortetracycline, chloramphenicol, or bacitracin, and release

prior to certification.

EFFECTIVE DATE OF 1999 AMENDMENT

Amendment by Pub. L. 106-113 effective 4 months after Nov. 29,

1999, see section 1000(a)(9) (title IV, Sec. 4731) of Pub. L.

106-113, set out as a note under section 1 of Title 35, Patents.

EFFECTIVE DATE OF 1997 AMENDMENT

Amendment by Pub. L. 105-115 effective 90 days after Nov. 21,

1997, except as otherwise provided, see section 501 of Pub. L.

105-115, set out as a note under section 321 of this title.

EFFECTIVE DATE OF 1994 AMENDMENT

Section 2(d) of Pub. L. 103-396 provided that: ''The amendments

made by this section (amending this section and section 331 of this

title) shall take effect upon the adoption of the final regulations

under subsection (c) (set out below).'' (Final regulations were

dated Oct. 22, 1996, filed Nov. 6, 1996, published Nov. 7, 1996, 61

F.R. 57732, and effective Dec. 9, 1996.)

EFFECTIVE DATE OF 1988 AMENDMENT

Section 108 of Pub. L. 100-670 provided that: ''The Secretary of

Health and Human Services may not make an approval of an

application submitted under section 512(b)(2) of the Federal Food,

Drug, and Cosmetic Act (21 U.S.C. 360b(b)(2)) effective before

January 1, 1991.''

EFFECTIVE DATE AND TRANSITIONAL PROVISIONS

Section 108 of Pub. L. 90-399 provided that:

''(a) Except as otherwise provided in this section, the

amendments made by the foregoing sections (see Short Title of 1968

Amendment note set out under section 301 of this title) shall take

effect on the first day of the thirteenth calendar month which

begins after the date of enactment of this Act (July 13, 1968).

''(b)(1) As used in this subsection, the term 'effective date'

means the effective date specified in subsection (a) of this

section; the term 'basic Act' means the Federal Food, Drug, and

Cosmetic Act (this chapter); and other terms used both in this

section and the basic Act shall have the same meaning as they have,

or had, at the time referred to in the context, under the basic

Act.

''(2) Any approval, prior to the effective date, of a new animal

drug or of an animal feed bearing or containing a new animal drug,

whether granted by approval of a new-drug application, master file,

antibiotic regulation, or food additive regulations, shall continue

in effect, and shall be subject to change in accordance with the

provisions of the basic Act as amended by this Act (see Short Title

of 1968 Amendment note set out under section 301 of this title).

''(3) In the case of any drug (other than a drug subject to

section 512(n) of the basic Act as amended by this Act) (subsection

(n) of this section) intended for use in animals other than man

which, on October 9, 1962, (A) was commercially used or sold in the

United States, (B) was not a new drug as defined by section 201(p)

of the basic Act (section 321(p) of this title) as then in force,

and (C) was not covered by an effective application under section

505 of that Act (section 355 of this title), the words

'effectiveness' and 'effective' contained in section 201(w) as

added by this Act to the basic Act (section 321(w) of this title)

shall not apply to such drug when intended solely for use under

conditions prescribed, recommended, or suggested in labeling with

respect to such drug on that day.

''(4) Regulations providing for fees (and advance deposits to

cover fees) which on the day preceding the effective date

applicable under subsection (a) of this section were in effect

pursuant to section 507 of the basic Act (section 357 of this

title) shall, except as the Secretary may otherwise prescribe, be

deemed to apply also under section 512(n) of the basic Act

(subsection (n) of this section), and appropriations of fees (and

of advance deposits to cover fees) available for the purposes

specified in such section 507 (section 357 of this title) as in

effect prior to the effective date shall also be available for the

purposes specified in section 512(n) (subsection (n) of this

section), including preparatory work or proceedings prior to that

date.''

REGULATIONS

Section 2(e) of Pub. L. 104-250 provided that:

''(1) In general. - Not later than 6 months after the date of

enactment of this Act (Oct. 9, 1996), the Secretary of Health and

Human Services shall issue proposed regulations implementing the

amendments made by this Act as described in paragraph (2)(A) of

this subsection, and not later than 18 months after the date of

enactment of this Act, the Secretary shall issue final regulations

implementing such amendments. Not later than 12 months after the

date of enactment of this Act, the Secretary shall issue proposed

regulations implementing the other amendments made by this Act as

described in paragraphs (2)(B) and (2)(C) of this subsection, and

not later than 24 months after the date of enactment of this Act,

the Secretary shall issue final regulations implementing such

amendments.

''(2) Contents. - In issuing regulations implementing the

amendments made by this Act (see Short Title of 1996 Amendments

note set out under section 301 of this title), and in taking an

action to review an application for approval of a new animal drug

under section 512 of the Federal Food, Drug, and Cosmetic Act (21

U.S.C. 360b), or a request for an investigational exemption for a

new animal drug under subsection (j) of such section, that is

pending or has been submitted prior to the effective date of the

regulations, the Secretary shall -

''(A) further define the term 'adequate and well controlled',

as used in subsection (d)(3) of section 512 of such Act, to

require that field investigations be designed and conducted in a

scientifically sound manner, taking into account practical

conditions in the field and differences between field conditions

and laboratory conditions;

''(B) further define the term 'substantial evidence', as

defined in subsection (d)(3) of such section, in a manner that

encourages the submission of applications and supplemental

applications; and

''(C) take into account the proposals contained in the citizen

petition (FDA Docket No. 91P-0434/CP) jointly submitted by the

American Veterinary Medical Association and the Animal Health

Institute, dated October 21, 1991.

Until the regulations required by subparagraph (A) are issued,

nothing in the regulations published at 21 C.F.R. 514.111(a)(5)

(April 1, 1996) shall be construed to compel the Secretary of

Health and Human Services to require a field investigation under

section 512(d)(1)(E) of the Federal Food, Drug, and Cosmetic Act

(21 U.S.C. 360b(d)(1)(E)) or to apply any of its provisions in a

manner inconsistent with the considerations for scientifically

sound field investigations set forth in subparagraph (A).''

Section 2(c) of Pub. L. 103-396 provided that: ''Not later than 2

years after the date of the enactment of this Act (Oct. 22, 1994),

the Secretary of Health and Human Services shall promulgate

regulations to implement paragraphs (4)(A) and (5) of section

512(a) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C.

360b(a)(4)(A), (5)) (as amended by subsection (a)).''

Section 103 of Pub. L. 100-670 provided that:

''(a) General Rule. - The Secretary of Health and Human Services

shall promulgate, in accordance with the notice and comment

requirements of section 553 of title 5, United States Code, such

regulations as may be necessary for the administration of section

512 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360b),

as amended by sections 101 through 103 of this title, within one

year of the date of enactment of this Act (Nov. 16, 1988).

''(b) Transition. - During the period beginning 60 days after the

date of enactment of this Act (Nov. 16, 1988) and ending on the

date regulations promulgated under subsection (a) take effect,

abbreviated new animal drug applications may be submitted in

accordance with the provisions of section 314.55 and part 320 of

title 21 of the Code of Federal Regulations and shall be considered

as suitable for any drug which has been approved for safety and

effectiveness under section 512(c) of the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 360b(c)) before the date of enactment of

this Act. If any such provision of section 314.55 or part 320 is

inconsistent with the requirements of section 512 of the Federal

Food, Drug, and Cosmetic Act (as amended by this title), the

Secretary shall consider the application under the applicable

requirements of section 512 (as so amended).''

DRUGS INTENDED FOR MINOR SPECIES AND MINOR USES

Section 2(f) of Pub. L. 104-250 provided that: ''The Secretary of

Health and Human Services shall consider legislative and regulatory

options for facilitating the approval under section 512 of the

Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360b) of animal

drugs intended for minor species and for minor uses and, within 18

months after the date of enactment of this Act (Oct. 9, 1996),

announce proposals for legislative or regulatory change to the

approval process under such section for animal drugs intended for

use in minor species or for minor uses.''

TRANSITIONAL PROVISION REGARDING IMPLEMENTATION OF PUB. L. 104-250;

APPROVED MEDICATED FEED APPLICATION DEEMED LICENSE

Section 6(c) of Pub. L. 104-250 provided that: ''A person engaged

in the manufacture of animal feeds bearing or containing new animal

drugs who holds at least one approved medicated feed application

for an animal feed bearing or containing new animal drugs, the

manufacture of which was not otherwise exempt from the requirement

for an approved medicated feed application on the date of the

enactment of this Act (Oct. 9, 1996), shall be deemed to hold a

license for the manufacturing site identified in the approved

medicated feed application. The revocation of license provisions

of section 512(m)(4) of the Federal Food, Drug, and Cosmetic Act

(21 U.S.C. 360b(m)(4)), as amended by this Act, shall apply to such

licenses. Such license shall expire within 18 months from the date

of enactment of this Act unless the person submits to the Secretary

a completed license application for the manufacturing site

accompanied by a copy of an approved medicated feed application for

such site, which license application shall be deemed to be approved

upon receipt by the Secretary.''

DRUGS PRIMARILY MANUFACTURED USING BIOTECHNOLOGY

Section 106 of Pub. L. 100-670 provided that: ''Notwithstanding

section 512(b)(2) of the Federal Food, Drug, and Cosmetic Act (21

U.S.C. 360b(b)(2)), the Secretary of Health and Human Services may

not approve an abbreviated application submitted under such section

for a new animal drug which is primarily manufactured using

recombinant DNA, recombinant RNA, hybridoma technology, or other

processes involving site specific genetic manipulation

techniques.''

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in sections 321, 331, 342, 351, 353,

354, 356a, 360, 381, 827 of this title; title 7 section 7642; title

28 section 2201; title 35 sections 156, 271.

-CITE-

21 USC Sec. 360c 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 360c. Classification of devices intended for human use

-STATUTE-

(a) Classes of devices

(1) There are established the following classes of devices

intended for human use:

(A) Class I, General Controls. -

(i) A device for which the controls authorized by or under

section 351, 352, 360, 360f, 360h, 360i, or 360j of this title

or any combination of such sections are sufficient to provide

reasonable assurance of the safety and effectiveness of the

device.

(ii) A device for which insufficient information exists to

determine that the controls referred to in clause (i) are

sufficient to provide reasonable assurance of the safety and

effectiveness of the device or to establish special controls to

provide such assurance, but because it -

(I) is not purported or represented to be for a use in

supporting or sustaining human life or for a use which is of

substantial importance in preventing impairment of human

health, and

(II) does not present a potential unreasonable risk of

illness or injury,

is to be regulated by the controls referred to in clause (i).

(B) Class II, Special Controls. - A device which cannot be

classified as a class I device because the general controls by

themselves are insufficient to provide reasonable assurance of

the safety and effectiveness of the device, and for which there

is sufficient information to establish special controls to

provide such assurance, including the promulgation of performance

standards, postmarket surveillance, patient registries,

development and dissemination of guidelines (including guidelines

for the submission of clinical data in premarket notification

submissions in accordance with section 360(k) of this title),

recommendations, and other appropriate actions as the Secretary

deems necessary to provide such assurance. For a device that is

purported or represented to be for a use in supporting or

sustaining human life, the Secretary shall examine and identify

the special controls, if any, that are necessary to provide

adequate assurance of safety and effectiveness and describe how

such controls provide such assurance.

(C) Class III, Premarket Approval. - A device which because -

(i) it (I) cannot be classified as a class I device because

insufficient information exists to determine that the

application of general controls are sufficient to provide

reasonable assurance of the safety and effectiveness of the

device, and (II) cannot be classified as a class II device

because insufficient information exists to determine that the

special controls described in subparagraph (B) would provide

reasonable assurance of its safety and effectiveness, and

(ii)(I) is purported or represented to be for a use in

supporting or sustaining human life or for a use which is of

substantial importance in preventing impairment of human

health, or

(II) presents a potential unreasonable risk of illness or

injury,

is to be subject, in accordance with section 360e of this title,

to premarket approval to provide reasonable assurance of its

safety and effectiveness.

If there is not sufficient information to establish a performance

standard for a device to provide reasonable assurance of its safety

and effectiveness, the Secretary may conduct such activities as may

be necessary to develop or obtain such information.

(2) For purposes of this section and sections 360d and 360e of

this title, the safety and effectiveness of a device are to be

determined -

(A) with respect to the persons for whose use the device is

represented or intended,

(B) with respect to the conditions of use prescribed,

recommended, or suggested in the labeling of the device, and

(C) weighing any probable benefit to health from the use of the

device against any probable risk of injury or illness from such

use.

(3)(A) Except as authorized by subparagraph (B), the

effectiveness of a device is, for purposes of this section and

sections 360d and 360e of this title, to be determined, in

accordance with regulations promulgated by the Secretary, on the

basis of well-controlled investigations, including 1 or more

clinical investigations where appropriate, by experts qualified by

training and experience to evaluate the effectiveness of the

device, from which investigations it can fairly and responsibly be

concluded by qualified experts that the device will have the effect

it purports or is represented to have under the conditions of use

prescribed, recommended, or suggested in the labeling of the

device.

(B) If the Secretary determines that there exists valid

scientific evidence (other than evidence derived from

investigations described in subparagraph (A)) -

(i) which is sufficient to determine the effectiveness of a

device, and

(ii) from which it can fairly and responsibly be concluded by

qualified experts that the device will have the effect it

purports or is represented to have under the conditions of use

prescribed, recommended, or suggested in the labeling of the

device,

then, for purposes of this section and sections 360d and 360e of

this title, the Secretary may authorize the effectiveness of the

device to be determined on the basis of such evidence.

(C) In making a determination of a reasonable assurance of the

effectiveness of a device for which an application under section

360e of this title has been submitted, the Secretary shall consider

whether the extent of data that otherwise would be required for

approval of the application with respect to effectiveness can be

reduced through reliance on postmarket controls.

(D)(i) The Secretary, upon the written request of any person

intending to submit an application under section 360e of this

title, shall meet with such person to determine the type of valid

scientific evidence (within the meaning of subparagraphs (A) and

(B)) that will be necessary to demonstrate for purposes of approval

of an application the effectiveness of a device for the conditions

of use proposed by such person. The written request shall include

a detailed description of the device, a detailed description of the

proposed conditions of use of the device, a proposed plan for

determining whether there is a reasonable assurance of

effectiveness, and, if available, information regarding the

expected performance from the device. Within 30 days after such

meeting, the Secretary shall specify in writing the type of valid

scientific evidence that will provide a reasonable assurance that a

device is effective under the conditions of use proposed by such

person.

(ii) Any clinical data, including one or more well-controlled

investigations, specified in writing by the Secretary for

demonstrating a reasonable assurance of device effectiveness shall

be specified as result of a determination by the Secretary that

such data are necessary to establish device effectiveness. The

Secretary shall consider, in consultation with the applicant, the

least burdensome appropriate means of evaluating device

effectiveness that would have a reasonable likelihood of resulting

in approval.

(iii) The determination of the Secretary with respect to the

specification of valid scientific evidence under clauses (i) and

(ii) shall be binding upon the Secretary, unless such determination

by the Secretary could be contrary to the public health.

(b) Classification panels

(1) For purposes of -

(A) determining which devices intended for human use should be

subject to the requirements of general controls, performance

standards, or premarket approval, and

(B) providing notice to the manufacturers and importers of such

devices to enable them to prepare for the application of such

requirements to devices manufactured or imported by them,

the Secretary shall classify all such devices (other than devices

classified by subsection (f) of this section) into the classes

established by subsection (a) of this section. For the purpose of

securing recommendations with respect to the classification of

devices, the Secretary shall establish panels of experts or use

panels of experts established before May 28, 1976, or both.

Section 14 of the Federal Advisory Committee Act shall not apply to

the duration of a panel established under this paragraph.

(2) The Secretary shall appoint to each panel established under

paragraph (1) persons who are qualified by training and experience

to evaluate the safety and effectiveness of the devices to be

referred to the panel and who, to the extent feasible, possess

skill in the use of, or experience in the development, manufacture,

or utilization of, such devices. The Secretary shall make

appointments to each panel so that each panel shall consist of

members with adequately diversified expertise in such fields as

clinical and administrative medicine, engineering, biological and

physical sciences, and other related professions. In addition,

each panel shall include as nonvoting members a representative of

consumer interests and a representative of interests of the device

manufacturing industry. Scientific, trade, and consumer

organizations shall be afforded an opportunity to nominate

individuals for appointment to the panels. No individual who is in

the regular full-time employ of the United States and engaged in

the administration of this chapter may be a member of any panel.

The Secretary shall designate one of the members of each panel to

serve as chairman thereof.

(3) Panel members (other than officers or employees of the United

States), while attending meetings or conferences of a panel or

otherwise engaged in its business, shall be entitled to receive

compensation at rates to be fixed by the Secretary, but not at

rates exceeding the daily equivalent of the rate in effect for

grade GS-18 of the General Schedule, for each day so engaged,

including traveltime; and while so serving away from their homes or

regular places of business each member may be allowed travel

expenses (including per diem in lieu of subsistence) as authorized

by section 5703 of title 5, for persons in the Government service

employed intermittently.

(4) The Secretary shall furnish each panel with adequate clerical

and other necessary assistance.

(5) Classification panels covering each type of device shall be

scheduled to meet at such times as may be appropriate for the

Secretary to meet applicable statutory deadlines.

(6)(A) Any person whose device is specifically the subject of

review by a classification panel shall have -

(i) the same access to data and information submitted to a

classification panel (except for data and information that are

not available for public disclosure under section 552 of title 5)

as the Secretary;

(ii) the opportunity to submit, for review by a classification

panel, information that is based on the data or information

provided in the application submitted under section 360e of this

title by the person, which information shall be submitted to the

Secretary for prompt transmittal to the classification panel; and

(iii) the same opportunity as the Secretary to participate in

meetings of the panel.

(B) Any meetings of a classification panel shall provide adequate

time for initial presentations and for response to any differing

views by persons whose devices are specifically the subject of a

classification panel review, and shall encourage free and open

participation by all interested persons.

(7) After receiving from a classification panel the conclusions

and recommendations of the panel on a matter that the panel has

reviewed, the Secretary shall review the conclusions and

recommendations, shall make a final decision on the matter in

accordance with section 360e(d)(2) of this title, and shall notify

the affected persons of the decision in writing and, if the

decision differs from the conclusions and recommendations of the

panel, shall include the reasons for the difference.

(8) A classification panel under this subsection shall not be

subject to the annual chartering and annual report requirements of

the Federal Advisory Committee Act.

(c) Classification panel organization and operation

(1) The Secretary shall organize the panels according to the

various fields of clinical medicine and fundamental sciences in

which devices intended for human use are used. The Secretary shall

refer a device to be classified under this section to an

appropriate panel established or authorized to be used under

subsection (b) of this section for its review and for its

recommendation respecting the classification of the device. The

Secretary shall by regulation prescribe the procedure to be

followed by the panels in making their reviews and

recommendations. In making their reviews of devices, the panels,

to the maximum extent practicable, shall provide an opportunity for

interested persons to submit data and views on the classification

of the devices.

(2)(A) Upon completion of a panel's review of a device referred

to it under paragraph (1), the panel shall, subject to

subparagraphs (B) and (C), submit to the Secretary its

recommendation for the classification of the device. Any such

recommendation shall (i) contain (I) a summary of the reasons for

the recommendation, (II) a summary of the data upon which the

recommendation is based, and (III) an identification of the risks

to health (if any) presented by the device with respect to which

the recommendation is made, and (ii) to the extent practicable,

include a recommendation for the assignment of a priority for the

application of the requirements of section 360d or 360e of this

title to a device recommended to be classified in class II or class

III.

(B) A recommendation of a panel for the classification of a

device in class I shall include a recommendation as to whether the

device should be exempted from the requirements of section 360,

360i, or 360j(f) of this title.

(C) In the case of a device which has been referred under

paragraph (1) to a panel, and which -

(i) is intended to be implanted in the human body or is

purported or represented to be for a use in supporting or

sustaining human life, and

(ii)(I) has been introduced or delivered for introduction into

interstate commerce for commercial distribution before May 28,

1976, or

(II) is within a type of device which was so introduced or

delivered before such date and is substantially equivalent to

another device within that type,

such panel shall recommend to the Secretary that the device be

classified in class III unless the panel determines that

classification of the device in such class is not necessary to

provide reasonable assurance of its safety and effectiveness. If a

panel does not recommend that such a device be classified in class

III, it shall in its recommendation to the Secretary for the

classification of the device set forth the reasons for not

recommending classification of the device in such class.

(3) The panels shall submit to the Secretary within one year of

the date funds are first appropriated for the implementation of

this section their recommendations respecting all devices of a type

introduced or delivered for introduction into interstate commerce

for commercial distribution before May 28, 1976.

(d) Panel recommendation; publication; priorities

(1) Upon receipt of a recommendation from a panel respecting a

device, the Secretary shall publish in the Federal Register the

panel's recommendation and a proposed regulation classifying such

device and shall provide interested persons an opportunity to

submit comments on such recommendation and the proposed

regulation. After reviewing such comments, the Secretary shall,

subject to paragraph (2), by regulation classify such device.

(2)(A) A regulation under paragraph (1) classifying a device in

class I shall prescribe which, if any, of the requirements of

section 360, 360i, or 360j(f) of this title shall not apply to the

device. A regulation which makes a requirement of section 360,

360i, or 360j(f) of this title inapplicable to a device shall be

accompanied by a statement of the reasons of the Secretary for

making such requirement inapplicable.

(B) A device described in subsection (c)(2)(C) of this section

shall be classified in class III unless the Secretary determines

that classification of the device in such class is not necessary to

provide reasonable assurance of its safety and effectiveness. A

proposed regulation under paragraph (1) classifying such a device

in a class other than class III shall be accompanied by a full

statement of the reasons of the Secretary (and supporting

documentation and data) for not classifying such device in such

class and an identification of the risks to health (if any)

presented by such device.

(3) In the case of devices classified in class II and devices

classified under this subsection in class III and described in

section 360e(b)(1) of this title the Secretary may establish

priorities which, in his discretion, shall be used in applying

sections 360d and 360e of this title, as appropriate, to such

devices.

(e) Classification changes

(1) Based on new information respecting a device, the Secretary

may, upon his own initiative or upon petition of an interested

person, by regulation (A) change such device's classification, and

(B) revoke, because of the change in classification, any regulation

or requirement in effect under section 360d or 360e of this title

with respect to such device. In the promulgation of such a

regulation respecting a device's classification, the Secretary may

secure from the panel to which the device was last referred

pursuant to subsection (c) of this section a recommendation

respecting the proposed change in the device's classification and

shall publish in the Federal Register any recommendation submitted

to the Secretary by the panel respecting such change. A regulation

under this subsection changing the classification of a device from

class III to class II may provide that such classification shall

not take effect until the effective date of a performance standard

established under section 360d of this title for such device.

(2) By regulation promulgated under paragraph (1), the Secretary

may change the classification of a device from class III -

(A) to class II if the Secretary determines that special

controls would provide reasonable assurance of the safety and

effectiveness of the device and that general controls would not

provide reasonable assurance of the safety and effectiveness of

the device, or

(B) to class I if the Secretary determines that general

controls would provide reasonable assurance of the safety and

effectiveness of the device.

(f) Initial classification and reclassification of certain devices

(1) Any device intended for human use which was not introduced or

delivered for introduction into interstate commerce for commercial

distribution before May 28, 1976, is classified in class III unless

-

(A) the device -

(i) is within a type of device (I) which was introduced or

delivered for introduction into interstate commerce for

commercial distribution before such date and which is to be

classified pursuant to subsection (b) of this section, or (II)

which was not so introduced or delivered before such date and

has been classified in class I or II, and

(ii) is substantially equivalent to another device within

such type, or

(B) the Secretary in response to a petition submitted under

paragraph (3) has classified such device in class I or II.

A device classified in class III under this paragraph shall be

classified in that class until the effective date of an order of

the Secretary under paragraph (2) or (3) classifying the device in

class I or II.

(2)(A) Any person who submits a report under section 360(k) of

this title for a type of device that has not been previously

classified under this chapter, and that is classified into class

III under paragraph (1), may request, within 30 days after

receiving written notice of such a classification, the Secretary to

classify the device under the criteria set forth in subparagraphs

(A) through (C) of subsection (a)(1) of this section. The person

may, in the request, recommend to the Secretary a classification

for the device. Any such request shall describe the device and

provide detailed information and reasons for the recommended

classification.

(B)(i) Not later than 60 days after the date of the submission of

the request under subparagraph (A), the Secretary shall by written

order classify the device involved. Such classification shall be

the initial classification of the device for purposes of paragraph

(1) and any device classified under this paragraph shall be a

predicate device for determining substantial equivalence under

paragraph (1).

(ii) A device that remains in class III under this subparagraph

shall be deemed to be adulterated within the meaning of section

351(f)(1)(B) of this title until approved under section 360e of

this title or exempted from such approval under section 360j(g) of

this title.

(C) Within 30 days after the issuance of an order classifying a

device under this paragraph, the Secretary shall publish a notice

in the Federal Register announcing such classification.

(3)(A) The Secretary may initiate the reclassification of a

device classified into class III under paragraph (1) of this

subsection or the manufacturer or importer of a device classified

under paragraph (1) may petition the Secretary (in such form and

manner as he shall prescribe) for the issuance of an order

classifying the device in class I or class II. Within thirty days

of the filing of such a petition, the Secretary shall notify the

petitioner of any deficiencies in the petition which prevent the

Secretary from making a decision on the petition.

(B)(i) Upon determining that a petition does not contain any

deficiency which prevents the Secretary from making a decision on

the petition, the Secretary may for good cause shown refer the

petition to an appropriate panel established or authorized to be

used under subsection (b) of this section. A panel to which such a

petition has been referred shall not later than ninety days after

the referral of the petition make a recommendation to the Secretary

respecting approval or denial of the petition. Any such

recommendation shall contain (I) a summary of the reasons for the

recommendation, (II) a summary of the data upon which the

recommendation is based, and (III) an identification of the risks

to health (if any) presented by the device with respect to which

the petition was filed. In the case of a petition for a device

which is intended to be implanted in the human body or which is

purported or represented to be for a use in supporting or

sustaining human life, the panel shall recommend that the petition

be denied unless the panel determines that the classification in

class III of the device is not necessary to provide reasonable

assurance of its safety and effectiveness. If the panel recommends

that such petition be approved, it shall in its recommendation to

the Secretary set forth its reasons for such recommendation.

(ii) The requirements of paragraphs (1) and (2) of subsection (c)

of this section (relating to opportunities for submission of data

and views and recommendations respecting priorities and exemptions

from sections 360, 360i, and 360j(f) of this title) shall apply

with respect to consideration by panels of petitions submitted

under subparagraph (A).

(C)(i) Within ninety days from the date the Secretary receives

the recommendation of a panel respecting a petition (but not later

than 210 days after the filing of such petition) the Secretary

shall by order deny or approve the petition. If the Secretary

approves the petition, the Secretary shall order the classification

of the device into class I or class II in accordance with the

criteria prescribed by subsection (a)(1)(A) or (a)(1)(B) of this

section. In the case of a petition for a device which is intended

to be implanted in the human body or which is purported or

represented to be for a use in supporting or sustaining human life,

the Secretary shall deny the petition unless the Secretary

determines that the classification in class III of the device is

not necessary to provide reasonable assurance of its safety and

effectiveness. An order approving such petition shall be

accompanied by a full statement of the reasons of the Secretary

(and supporting documentation and data) for approving the petition

and an identification of the risks to health (if any) presented by

the device to which such order applies.

(ii) The requirements of paragraphs (1) and (2)(A) of subsection

(d) of this section (relating to publication of recommendations,

opportunity for submission of comments, and exemption from sections

360, 360i, and 360j(f) of this title) shall apply with respect to

action by the Secretary on petitions submitted under subparagraph

(A).

(4) If a manufacturer reports to the Secretary under section

360(k) of this title that a device is substantially equivalent to

another device -

(A) which the Secretary has classified as a class III device

under subsection (b) of this section,

(B) which was introduced or delivered for introduction into

interstate commerce for commercial distribution before December

1, 1990, and

(C) for which no final regulation requiring premarket approval

has been promulgated under section 360e(b) of this title,

the manufacturer shall certify to the Secretary that the

manufacturer has conducted a reasonable search of all information

known or otherwise available to the manufacturer respecting such

other device and has included in the report under section 360(k) of

this title a summary of and a citation to all adverse safety and

effectiveness data respecting such other device and respecting the

device for which the section 360(k) report is being made and which

has not been submitted to the Secretary under section 360i of this

title. The Secretary may require the manufacturer to submit the

adverse safety and effectiveness data described in the report.

(5) The Secretary may not withhold a determination of the initial

classification of a device under paragraph (1) because of a failure

to comply with any provision of this chapter unrelated to a

substantial equivalence decision, including a finding that the

facility in which the device is manufactured is not in compliance

with good manufacturing requirements as set forth in regulations of

the Secretary under section 360j(f) of this title (other than a

finding that there is a substantial likelihood that the failure to

comply with such regulations will potentially present a serious

risk to human health).

(g) Information

Within sixty days of the receipt of a written request of any

person for information respecting the class in which a device has

been classified or the requirements applicable to a device under

this chapter, the Secretary shall provide such person a written

statement of the classification (if any) of such device and the

requirements of this chapter applicable to the device.

(h) Definitions

For purposes of this section and sections 351, 360, 360d, 360e,

360f, 360i, and 360j of this title

(1) a reference to ''general controls'' is a reference to the

controls authorized by or under sections 351, 352, 360, 360f,

360h, 360i, and 360j of this title,

(2) a reference to ''class I'', ''class II'', or ''class III''

is a reference to a class of medical devices described in

subparagraph (A), (B), or (C) of subsection (a)(1) of this

section, and

(3) a reference to a ''panel under section 360c of this title''

is a reference to a panel established or authorized to be used

under this section.

(i) Substantial equivalence

(1)(A) For purposes of determinations of substantial equivalence

under subsection (f) of this section and section 360j(l) of this

title, the term ''substantially equivalent'' or ''substantial

equivalence'' means, with respect to a device being compared to a

predicate device, that the device has the same intended use as the

predicate device and that the Secretary by order has found that the

device -

(i) has the same technological characteristics as the predicate

device, or

(ii)(I) has different technological characteristics and the

information submitted that the device is substantially equivalent

to the predicate device contains information, including

appropriate clinical or scientific data if deemed necessary by

the Secretary or a person accredited under section 360m of this

title, that demonstrates that the device is as safe and effective

as a legally marketed device, and (II) does not raise different

questions of safety and effectiveness than the predicate device.

(B) For purposes of subparagraph (A), the term ''different

technological characteristics'' means, with respect to a device

being compared to a predicate device, that there is a significant

change in the materials, design, energy source, or other features

of the device from those of the predicate device.

(C) To facilitate reviews of reports submitted to the Secretary

under section 360(k) of this title, the Secretary shall consider

the extent to which reliance on postmarket controls may expedite

the classification of devices under subsection (f)(1) of this

section.

(D) Whenever the Secretary requests information to demonstrate

that devices with differing technological characteristics are

substantially equivalent, the Secretary shall only request

information that is necessary to making substantial equivalence

determinations. In making such request, the Secretary shall

consider the least burdensome means of demonstrating substantial

equivalence and request information accordingly.

(E)(i) Any determination by the Secretary of the intended use of

a device shall be based upon the proposed labeling submitted in a

report for the device under section 360(k) of this title. However,

when determining that a device can be found substantially

equivalent to a legally marketed device, the director of the

organizational unit responsible for regulating devices (in this

subparagraph referred to as the ''Director'') may require a

statement in labeling that provides appropriate information

regarding a use of the device not identified in the proposed

labeling if, after providing an opportunity for consultation with

the person who submitted such report, the Director determines and

states in writing -

(I) that there is a reasonable likelihood that the device will

be used for an intended use not identified in the proposed

labeling for the device; and

(II) that such use could cause harm.

(ii) Such determination shall -

(I) be provided to the person who submitted the report within

10 days from the date of the notification of the Director's

concerns regarding the proposed labeling;

(II) specify the limitations on the use of the device not

included in the proposed labeling; and

(III) find the device substantially equivalent if the

requirements of subparagraph (A) are met and if the labeling for

such device conforms to the limitations specified in subclause

(II).

(iii) The responsibilities of the Director under this

subparagraph may not be delegated.

(F) Not later than 270 days after November 21, 1997, the

Secretary shall issue guidance specifying the general principles

that the Secretary will consider in determining when a specific

intended use of a device is not reasonably included within a

general use of such device for purposes of a determination of

substantial equivalence under subsection (f) of this section or

section 360j(l) of this title.

(2) A device may not be found to be substantially equivalent to a

predicate device that has been removed from the market at the

initiative of the Secretary or that has been determined to be

misbranded or adulterated by a judicial order.

(3)(A) As part of a submission under section 360(k) of this title

respecting a device, the person required to file a premarket

notification under such section shall provide an adequate summary

of any information respecting safety and effectiveness or state

that such information will be made available upon request by any

person.

(B) Any summary under subparagraph (A) respecting a device shall

contain detailed information regarding data concerning adverse

health effects and shall be made available to the public by the

Secretary within 30 days of the issuance of a determination that

such device is substantially equivalent to another device.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 513, as added Pub. L. 94-295, Sec. 2,

May 28, 1976, 90 Stat. 540; amended Pub. L. 101-629, Sec. 4(a),

5(a)-(c)(1), (3), 12(a), 18(a), Nov. 28, 1990, 104 Stat. 4515,

4517, 4518, 4523, 4528; Pub. L. 102-300, Sec. 6(e), June 16, 1992,

106 Stat. 240; Pub. L. 103-80, Sec. 3(s), Aug. 13, 1993, 107 Stat.

778; Pub. L. 105-115, title II, Sec. 205(a), (b), 206(b), (c), 207,

208, 217, Nov. 21, 1997, 111 Stat. 2336, 2337, 2339, 2340, 2350;

Pub. L. 107-250, title II, Sec. 208, Oct. 26, 2002, 116 Stat.

1613.)

-REFTEXT-

REFERENCES IN TEXT

The Federal Advisory Committee Act, referred to in subsec.

(b)(1), (8), is Pub. L. 92-463, Oct. 6, 1972, 86 Stat. 770, as

amended, which is set out in the Appendix to Title 5, Government

Organization and Employees.

-MISC2-

AMENDMENTS

2002 - Subsec. (i)(1)(E)(iv). Pub. L. 107-250 struck out cl. (iv)

which read as follows: ''This subparagraph has no legal effect

after the expiration of the five-year period beginning on November

21, 1997.''

1997 - Subsec. (a)(3)(A). Pub. L. 105-115, Sec. 217, substituted

''1 or more clinical investigations'' for ''clinical

investigations''.

Subsec. (a)(3)(C), (D). Pub. L. 105-115, Sec. 205(a), added

subpars. (C) and (D).

Subsec. (b)(5) to (8). Pub. L. 105-115, Sec. 208, added pars. (5)

to (8).

Subsec. (f)(1). Pub. L. 105-115, Sec. 207(1)(B), substituted

''paragraph (2) or (3)'' for ''paragraph (2)'' in closing

provisions.

Subsec. (f)(1)(B). Pub. L. 105-115, Sec. 207(1)(A), substituted

''paragraph (3)'' for ''paragraph (2)''.

Subsec. (f)(2) to (4). Pub. L. 105-115, Sec. 207(2), (3), added

par. (2) and redesignated former pars. (2) and (3) as (3) and (4),

respectively.

Subsec. (f)(5). Pub. L. 105-115, Sec. 206(b), added par. (5).

Subsec. (i)(1)(A)(ii). Pub. L. 105-115, Sec. 206(c)(1),

substituted ''appropriate clinical or scientific data'' for

''clinical data'', inserted ''or a person accredited under section

360m of this title'' after ''Secretary'', and substituted

''effectiveness'' for ''efficacy''.

Subsec. (i)(1)(C) to (E). Pub. L. 105-115, Sec. 205(b), added

subpars. (C) to (E).

Subsec. (i)(1)(F). Pub. L. 105-115, Sec. 206(c)(2), added subpar.

(F).

1993 - Subsec. (b)(3). Pub. L. 103-80 substituted ''5703'' for

''5703(b)''.

1992 - Subsec. (f)(3). Pub. L. 102-300 redesignated clauses (i)

to (iii) as subpars. (A) to (C), respectively, and substituted

''the section 360(k) report'' for ''the 360(k) report'' in closing

provisions.

1990 - Subsec. (a)(1)(A)(ii). Pub. L. 101-629, Sec. 5(a)(1),

substituted ''or to establish special controls'' for ''or to

establish a performance standard''.

Subsec. (a)(1)(B). Pub. L. 101-629, Sec. 5(a)(2), amended subpar.

(B) generally. Prior to amendment, subpar. (B) read as follows:

''Class II, Performance Standards. - A device which cannot be

classified as a class I device because the controls authorized by

or under sections 351, 352, 360, 360f, 360h, 360i, and 360j of this

title by themselves are insufficient to provide reasonable

assurance of the safety and effectiveness of the device, for which

there is sufficient information to establish a performance standard

to provide such assurance, and for which it is therefore necessary

to establish for the device a performance standard under section

360d of this title to provide reasonable assurance of its safety

and effectiveness.''

Subsec. (a)(1)(C)(i). Pub. L. 101-629, Sec. 5(a)(3), amended cl.

(i) generally. Prior to amendment, cl. (i) read as follows: ''it

(I) cannot be classified as a class I device because insufficient

information exists to determine that the controls authorized by or

under sections 351, 352, 360, 360f, 360h, 360i, and 360j of this

title are sufficient to provide reasonable assurance of the safety

and effectiveness of the device and (II) cannot be classified as a

class II device because insufficient information exists for the

establishment of a performance standard to provide reasonable

assurance of its safety and effectiveness, and''.

Subsec. (e). Pub. L. 101-629, Sec. 5(b), designated existing

provisions as par. (1), redesignated cls. (1) and (2) as (A) and

(B), respectively, and added par. (2).

Subsec. (f). Pub. L. 101-629, Sec. 5(c)(3), inserted ''and

reclassification'' before ''of'' in heading.

Subsec. (f)(2)(A). Pub. L. 101-629, Sec. 5(c)(1), substituted

''The Secretary may initiate the reclassification of a device

classified into class III under paragraph (1) of this subsection or

the manufacturer'' for ''The manufacturer''.

Subsec. (f)(2)(B)(i). Pub. L. 101-629, Sec. 18(a), substituted

''the Secretary may for good cause shown'' for ''the Secretary

shall''.

Subsec. (f)(3). Pub. L. 101-629, Sec. 4(a), added par. (3).

Subsec. (i). Pub. L. 101-629, Sec. 12(a), added subsec. (i).

EFFECTIVE DATE OF 1997 AMENDMENT

Amendment by Pub. L. 105-115 effective 90 days after Nov. 21,

1997, except as otherwise provided, see section 501 of Pub. L.

105-115, set out as a note under section 321 of this title.

SHORT TITLE OF 1976 AMENDMENT

Pub. L. 94-295, Sec. 1(a), May 28, 1976, 90 Stat. 539, provided

that: ''This Act (enacting sections 360c to 360k, 379, and 379a of

this title and section 3512 of Title 42, The Public Health and

Welfare, and amending sections 321, 331, 334, 351, 352, 358, 360,

374, 379e, and 381 of this title and section 55 of Title 15,

Commerce and Trade) may be cited as the 'Medical Device Amendments

of 1976'.''

REGULATIONS

Section 12(b) of Pub. L. 101-629 provided that: ''Within 12

months of the date of the enactment of this Act (Nov. 28, 1990),

the Secretary of Health and Human Services shall issue regulations

establishing the requirements of the summaries under section

513(i)(3) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C.

360c(i)(3)), as added by the amendment made by subsection (a).''

DAILY WEAR SOFT OR DAILY WEAR NONHYDROPHILIC PLASTIC CONTACT LENSES

Section 4(b)(3) of Pub. L. 101-629 provided that:

''(A) Notwithstanding section 520(l)(5) of the Federal Food,

Drug, and Cosmetic Act (21 U.S.C. 360j(l)(5)), the Secretary of

Health and Human Services shall not retain any daily wear soft or

daily wear nonhydrophilic plastic contact lens in class III under

such Act (this chapter) unless the Secretary finds that it meets

the criteria set forth in section 513(a)(1)(C) of such Act (21

U.S.C. 360c(a)(1)(C)). The finding and the grounds for the finding

shall be published in the Federal Register. For any such lens, the

Secretary shall make the determination respecting reclassification

required in section 520(l)(5)(B) of such Act within 24 months of

the date of the enactment of this paragraph (Nov. 28, 1990).

''(B) The Secretary of Health and Human Services may by notice

published in the Federal Register extend the two-year period

prescribed by subparagraph (A) for a lens for an additional period

not to exceed one year.

''(C)(i) Before classifying a lens in class II pursuant to

subparagraph (A), the Secretary of Health and Human Services shall

pursuant to section 513(a)(1)(B) of such Act assure that

appropriate regulatory safeguards are in effect which provide

reasonable assurance of the safety and effectiveness of such lens,

including clinical and preclinical data if deemed necessary by the

Secretary.

''(ii) Prior to classifying a lens in class I pursuant to

subparagraph (A), the Secretary shall assure that appropriate

regulatory safeguards are in effect which provide reasonable

assurance of the safety and effectiveness of such lens, including

clinical and preclinical data if deemed necessary by the Secretary.

''(D) Notwithstanding section 520(l)(5) of such Act, if the

Secretary of Health and Human Services has not made the finding and

published the finding required by subparagraph (A) within 36 months

of the date of the enactment of this subparagraph (Nov. 28, 1990),

the Secretary shall issue an order placing the lens in class II.

''(E) Any person adversely affected by a final regulation under

this paragraph revising the classification of a lens may challenge

the revision of the classification of such lens only by filing a

petition under section 513(e) for a classification change.''

REFERENCES IN OTHER LAWS TO GS-16, 17, OR 18 PAY RATES

References in laws to the rates of pay for GS-16, 17, or 18, or

to maximum rates of pay under the General Schedule, to be

considered references to rates payable under specified sections of

Title 5, Government Organization and Employees, see section 529

(title I, Sec. 101(c)(1)) of Pub. L. 101-509, set out in a note

under section 5376 of Title 5.

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in sections 331, 351, 360, 360d,

360e, 360g, 360j, 360m, 360aaa, 379i, 1604 of this title.

-CITE-

21 USC Sec. 360d 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 360d. Performance standards

-STATUTE-

(a) Reasonable assurance of safe and effective performance;

periodic evaluation

(1) The special controls required by section 360c(a)(1)(B) of

this title shall include performance standards for a class II

device if the Secretary determines that a performance standard is

necessary to provide reasonable assurance of the safety and

effectiveness of the device. A class III device may also be

considered a class II device for purposes of establishing a

standard for the device under subsection (b) of this section if the

device has been reclassified as a class II device under a

regulation under section 360c(e) of this title but such regulation

provides that the reclassification is not to take effect until the

effective date of such a standard for the device.

(2) A performance standard established under subsection (b) of

this section for a device -

(A) shall include provisions to provide reasonable assurance of

its safe and effective performance;

(B) shall, where necessary to provide reasonable assurance of

its safe and effective performance, include -

(i) provisions respecting the construction, components,

ingredients, and properties of the device and its compatibility

with power systems and connections to such systems,

(ii) provisions for the testing (on a sample basis or, if

necessary, on an individual basis) of the device or, if it is

determined that no other more practicable means are available

to the Secretary to assure the conformity of the device to the

standard, provisions for the testing (on a sample basis or, if

necessary, on an individual basis) by the Secretary or by

another person at the direction of the Secretary,

(iii) provisions for the measurement of the performance

characteristics of the device,

(iv) provisions requiring that the results of each or of

certain of the tests of the device required to be made under

clause (ii) show that the device is in conformity with the

portions of the standard for which the test or tests were

required, and

(v) a provision requiring that the sale and distribution of

the device be restricted but only to the extent that the sale

and distribution of a device may be restricted under a

regulation under section 360j(e) of this title; and

(C) shall, where appropriate, require the use and prescribe the

form and content of labeling for the proper installation,

maintenance, operation, and use of the device.

(3) The Secretary shall provide for periodic evaluation of

performance standards established under subsection (b) of this

section to determine if such standards should be changed to reflect

new medical, scientific, or other technological data.

(4) In carrying out his duties under this subsection and

subsection (b) of this section, the Secretary shall, to the maximum

extent practicable -

(A) use personnel, facilities, and other technical support

available in other Federal agencies,

(B) consult with other Federal agencies concerned with

standard-setting and other nationally or internationally

recognized standard-setting entities, and

(C) invite appropriate participation, through joint or other

conferences, workshops, or other means, by informed persons

representative of scientific, professional, industry, or consumer

organizations who in his judgment can make a significant

contribution.

(b) Establishment of a standard

(1)(A) The Secretary shall publish in the Federal Register a

notice of proposed rulemaking for the establishment, amendment, or

revocation of any performance standard for a device.

(B) A notice of proposed rulemaking for the establishment or

amendment of a performance standard for a device shall -

(i) set forth a finding with supporting justification that the

performance standard is appropriate and necessary to provide

reasonable assurance of the safety and effectiveness of the

device,

(ii) set forth proposed findings with respect to the risk of

illness or injury that the performance standard is intended to

reduce or eliminate,

(iii) invite interested persons to submit to the Secretary,

within 30 days of the publication of the notice, requests for

changes in the classification of the device pursuant to section

360c(e) of this title based on new information relevant to the

classification, and

(iv) invite interested persons to submit an existing

performance standard for the device, including a draft or

proposed performance standard, for consideration by the

Secretary.

(C) A notice of proposed rulemaking for the revocation of a

performance standard shall set forth a finding with supporting

justification that the performance standard is no longer necessary

to provide reasonable assurance of the safety and effectiveness of

a device.

(D) The Secretary shall provide for a comment period of not less

than 60 days.

(2) If, after publication of a notice in accordance with

paragraph (1), the Secretary receives a request for a change in the

classification of the device, the Secretary shall, within 60 days

of the publication of the notice, after consultation with the

appropriate panel under section 360c of this title, either deny the

request or give notice of an intent to initiate such change under

section 360c(e) of this title.

(3)(A) After the expiration of the period for comment on a notice

of proposed rulemaking published under paragraph (1) respecting a

performance standard and after consideration of such comments and

any report from an advisory committee under paragraph (5), the

Secretary shall (i) promulgate a regulation establishing a

performance standard and publish in the Federal Register findings

on the matters referred to in paragraph (1), or (ii) publish a

notice terminating the proceeding for the development of the

standard together with the reasons for such termination. If a

notice of termination is published, the Secretary shall (unless

such notice is issued because the device is a banned device under

section 360f of this title) initiate a proceeding under section

360c(e) of this title to reclassify the device subject to the

proceeding terminated by such notice.

(B) A regulation establishing a performance standard shall set

forth the date or dates upon which the standard shall take effect,

but no such regulation may take effect before one year after the

date of its publication unless (i) the Secretary determines that an

earlier effective date is necessary for the protection of the

public health and safety, or (ii) such standard has been

established for a device which, effective upon the effective date

of the standard, has been reclassified from class III to class II.

Such date or dates shall be established so as to minimize,

consistent with the public health and safety, economic loss to, and

disruption or dislocation of, domestic and international trade.

(4)(A) The Secretary, upon his own initiative or upon petition of

an interested person may by regulation, promulgated in accordance

with the requirements of paragraphs (1), (2), and (3)(B) of this

subsection, amend or revoke a performance standard.

(B) The Secretary may declare a proposed amendment of a

performance standard to be effective on and after its publication

in the Federal Register and until the effective date of any final

action taken on such amendment if he determines that making it so

effective is in the public interest. A proposed amendment of a

performance standard made so effective under the preceding sentence

may not prohibit, during the period in which it is so effective,

the introduction or delivery for introduction into interstate

commerce of a device which conforms to such standard without the

change or changes provided by such proposed amendment.

(5)(A) The Secretary -

(i) may on his own initiative refer a proposed regulation for

the establishment, amendment, or revocation of a performance

standard, or

(ii) shall, upon the request of an interested person which

demonstrates good cause for referral and which is made before the

expiration of the period for submission of comments on such

proposed regulation refer such proposed regulation,

to an advisory committee of experts, established pursuant to

subparagraph (B), for a report and recommendation with respect to

any matter involved in the proposed regulation which requires the

exercise of scientific judgment. If a proposed regulation is

referred under this subparagraph to an advisory committee, the

Secretary shall provide the advisory committee with the data and

information on which such proposed regulation is based. The

advisory committee shall, within sixty days of the referral of a

proposed regulation and after independent study of the data and

information furnished to it by the Secretary and other data and

information before it, submit to the Secretary a report and

recommendation respecting such regulation, together with all

underlying data and information and a statement of the reason or

basis for the recommendation. A copy of such report and

recommendation shall be made public by the Secretary.

(B) The Secretary shall establish advisory committees (which may

not be panels under section 360c of this title) to receive

referrals under subparagraph (A). The Secretary shall appoint as

members of any such advisory committee persons qualified in the

subject matter to be referred to the committee and of appropriately

diversified professional background, except that the Secretary may

not appoint to such a committee any individual who is in the

regular full-time employ of the United States and engaged in the

administration of this chapter. Each such committee shall include

as nonvoting members a representative of consumer interests and a

representative of interests of the device manufacturing industry.

Members of an advisory committee who are not officers or employees

of the United States, while attending conferences or meetings of

their committee or otherwise serving at the request of the

Secretary, shall be entitled to receive compensation at rates to be

fixed by the Secretary, which rates may not exceed the daily

equivalent of the rate in effect for grade GS-18 of the General

Schedule, for each day (including traveltime) they are so engaged;

and while so serving away from their homes or regular places of

business each member may be allowed travel expenses, including per

diem in lieu of subsistence, as authorized by section 5703 of title

5 for persons in the Government service employed intermittently.

The Secretary shall designate one of the members of each advisory

committee to serve as chairman thereof. The Secretary shall

furnish each advisory committee with clerical and other assistance,

and shall by regulation prescribe the procedures to be followed by

each such committee in acting on referrals made under subparagraph

(A).

(c) Recognition of standard

(1)(A) In addition to establishing a performance standard under

this section, the Secretary shall, by publication in the Federal

Register, recognize all or part of an appropriate standard

established by a nationally or internationally recognized standard

development organization for which a person may submit a

declaration of conformity in order to meet a premarket submission

requirement or other requirement under this chapter to which such

standard is applicable.

(B) If a person elects to use a standard recognized by the

Secretary under subparagraph (A) to meet the requirements described

in such subparagraph, the person shall provide a declaration of

conformity to the Secretary that certifies that the device is in

conformity with such standard. A person may elect to use data, or

information, other than data required by a standard recognized

under subparagraph (A) to meet any requirement regarding devices

under this chapter.

(2) The Secretary may withdraw such recognition of a standard

through publication of a notice in the Federal Register if the

Secretary determines that the standard is no longer appropriate for

meeting a requirement regarding devices under this chapter.

(3)(A) Subject to subparagraph (B), the Secretary shall accept a

declaration of conformity that a device is in conformity with a

standard recognized under paragraph (1) unless the Secretary finds

-

(i) that the data or information submitted to support such

declaration does not demonstrate that the device is in conformity

with the standard identified in the declaration of conformity; or

(ii) that the standard identified in the declaration of

conformity is not applicable to the particular device under

review.

(B) The Secretary may request, at any time, the data or

information relied on by the person to make a declaration of

conformity with respect to a standard recognized under paragraph

(1).

(C) A person making a declaration of conformity with respect to a

standard recognized under paragraph (1) shall maintain the data and

information demonstrating conformity of the device to the standard

for a period of two years after the date of the classification or

approval of the device by the Secretary or a period equal to the

expected design life of the device, whichever is longer.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 514, as added Pub. L. 94-295, Sec. 2,

May 28, 1976, 90 Stat. 546; amended Pub. L. 94-460, title III, Sec.

304, Oct. 8, 1976, 90 Stat. 1960; Pub. L. 101-629, Sec. 6(a),

(b)(1), 18(b), Nov. 28, 1990, 104 Stat. 4519, 4528; Pub. L.

102-300, Sec. 6(g), June 16, 1992, 106 Stat. 241; Pub. L. 103-80,

Sec. 4(a)(1), Aug. 13, 1993, 107 Stat. 779; Pub. L. 105-115, title

II, Sec. 204(a), (d), Nov. 21, 1997, 111 Stat. 2335, 2336.)

-MISC1-

AMENDMENTS

1997 - Subsec. (a)(1). Pub. L. 105-115, Sec. 204(d)(1),

substituted ''under subsection (b) of this section'' for ''under

this section''.

Subsec. (a)(2). Pub. L. 105-115, Sec. 204(d)(2), substituted

''under subsection (b) of this section'' for ''under this section''

in introductory provisions.

Subsec. (a)(3). Pub. L. 105-115, Sec. 204(d)(3), substituted

''under subsection (b) of this section'' for ''under this

section''.

Subsec. (a)(4). Pub. L. 105-115, Sec. 204(d)(4), substituted

''this subsection and subsection (b) of this section'' for ''this

section'' in introductory provisions.

Subsec. (c). Pub. L. 105-115, Sec. 204(a), added subsec. (c).

1993 - Subsec. (b)(4)(B), (5)(A)(ii). Pub. L. 103-80 amended

directory language of Pub. L. 101-619, Sec. 18(b), identical to

amendment by Pub. L. 102-300, Sec. 6(g)(1). See 1992 and 1990

Amendment notes below.

1992 - Subsec. (b)(4)(B), (5)(A)(ii). Pub. L. 102-300 made

technical corrections to directory language of Pub. L. 101-629,

Sec. 18(b)(1), (2). See 1990 Amendment note below.

1990 - Subsec. (a)(1). Pub. L. 101-629, Sec. 6(a)(1), substituted

''The special controls required by section 360c(a)(1)(B) of this

title shall include performance standards for a class II device if

the Secretary determines that a performance standard is necessary

to provide reasonable assurance of the safety and effectiveness of

the device.'' for ''The Secretary may by regulation, promulgated in

accordance with this section, establish a performance standard for

a class II device.''

Subsec. (b). Pub. L. 101-629, Sec. 6(a)(2), (3), redesignated

subsec. (g) as (b) and struck out former subsec. (b) which read as

follows:

''(1) A proceeding for the development of a performance standard

for a device shall be initiated by the Secretary by the publication

in the Federal Register of notice of the opportunity to submit to

the Secretary a request (within fifteen days of the date of the

publication of the notice) for a change in the classification of

the device based on new information relevant to its classification.

''(2) If, after publication of a notice pursuant to paragraph (1)

the Secretary receives a request for a change in the device's

classification, he shall, within sixty days of the publication of

such notice and after consultation with the appropriate panel under

section 360c of this title, by order published in the Federal

Register, either deny the request for change in classification or

give notice of his intent to initiate such a change under section

360c(e) of this title.''

Subsec. (b)(1), (2). Pub. L. 101-629, Sec. 6(a)(4), amended pars.

(1) and (2) generally. Prior to amendment, pars. (1) and (2) read

as follows:

''(1)(A) After publication pursuant to subsection (c) of this

section of a notice respecting a performance standard for a device,

the Secretary shall either -

''(i) publish, in the Federal Register in a notice of proposed

rulemaking, a proposed performance standard for the device (I)

developed by an offeror under such notice and accepted by the

Secretary, (II) developed under subsection (c)(4) of this

section, (III) accepted by the Secretary under subsection (d) of

this section, or (IV) developed by him under subsection (f) of

this section, or

''(ii) issue a notice in the Federal Register that the

proceeding is terminated together with the reasons for such

termination.

''(B) If the Secretary issues under subparagraph (A)(ii) a notice

of termination of a proceeding to establish a performance standard

for a device, he shall (unless such notice is issued because the

device is a banned device under section 360f of this title)

initiate a proceeding under section 360c(e) of this title to

reclassify the device subject to the proceeding terminated by such

notice.

''(2) A notice of proposed rulemaking for the establishment of a

performance standard for a device published under paragraph

(1)(A)(i) shall set forth proposed findings with respect to the

degree of the risk of illness or injury designed to be eliminated

or reduced by the proposed standard and the benefit to the public

from the device.''

Subsec. (b)(3)(A)(i). Pub. L. 101-629, Sec. 6(b)(1)(A),

substituted ''paragraph (1)'' for ''paragraph (2)''.

Subsec. (b)(4)(A). Pub. L. 101-629, Sec. 6(b)(1)(B), substituted

''paragraphs (1), (2), and (3)(B)'' for ''paragraphs (2) and

(3)(B)''.

Subsec. (b)(4)(B). Pub. L. 101-629, Sec. 18(b)(1), as amended by

Pub. L. 102-300, Sec. 6(g)(1), (2), and Pub. L. 103-80, Sec.

4(a)(1), struck out '', after affording all interested persons an

opportunity for an informal hearing,'' after ''if he determines''.

Subsec. (b)(5)(A)(ii). Pub. L. 101-629, Sec. 18(b)(2), as amended

by Pub. L. 102-300, Sec. 6(g)(1), (3), and Pub. L. 103-80, Sec.

4(a)(1), substituted ''which demonstrates good cause for referral

and which is made before the expiration of the period for

submission of comments on such proposed regulation refer such

proposed regulation,'' for ''unless the Secretary finds the request

to be without good cause or the request is made after the

expiration of the period for submission of comments on such

proposed regulation refer such proposed regulation,''.

Subsecs. (c) to (f). Pub. L. 101-629, Sec. 6(a)(2), struck out

subsec. (c) relating to invitations for standards, subsec. (d)

relating to acceptance of certain existing standards, subsec. (e)

relating to acceptance of offers to develop standards, and subsec.

(f) relating to development of standards by the Secretary after

publication of notice inviting submissions or offers of standards.

Subsec. (g). Pub. L. 101-629, Sec. 6(a)(3), redesignated subsec.

(g) as (b).

1976 - Subsec. (a). Pub. L. 94-460 redesignated pars. (4) and (5)

as (3) and (4), respectively. Section as originally enacted

contained no par. (3).

EFFECTIVE DATE OF 1997 AMENDMENT

Amendment by Pub. L. 105-115 effective 90 days after Nov. 21,

1997, except as otherwise provided, see section 501 of Pub. L.

105-115, set out as a note under section 321 of this title.

REFERENCES IN OTHER LAWS TO GS-16, 17, OR 18 PAY RATES

References in laws to the rates of pay for GS-16, 17, or 18, or

to maximum rates of pay under the General Schedule, to be

considered references to rates payable under specified sections of

Title 5, Government Organization and Employees, see section 529

(title I, Sec. 101(c)(1)) of Pub. L. 101-509, set out in a note

under section 5376 of Title 5.

TERMINATION OF ADVISORY COMMITTEES

Advisory committees in existence on Jan. 5, 1973, to terminate

not later than the expiration of the 2-year period following Jan.

5, 1973, and advisory committees established after Jan. 5, 1973, to

terminate not later than the expiration of the 2-year period

beginning on the date of their establishment, unless in the case of

a committee established by the President or an officer of the

Federal Government, such committee is renewed by appropriate action

prior to the expiration of such 2-year period, or in the case of a

committee established by Congress, its duration is otherwise

provided by law. See section 14 of Pub. L. 92-463, Oct. 6, 1972,

86 Stat. 776, set out in the Appendix to Title 5, Government

Organization and Employees.

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in sections 331, 351, 352, 360, 360c,

360e, 360g, 360j, 379i, 381, 382 of this title.

-CITE-

21 USC Sec. 360e 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 360e. Premarket approval

-STATUTE-

(a) General requirement

A class III device -

(1) which is subject to a regulation promulgated under

subsection (b) of this section; or

(2) which is a class III device because of section 360c(f) of

this title,

is required to have, unless exempt under section 360j(g) of this

title, an approval under this section of an application for

premarket approval or, as applicable, an approval under subsection

(c)(2) of this section of a report seeking premarket approval.

(b) Regulation to require premarket approval

(1) In the case of a class III device which -

(A) was introduced or delivered for introduction into

interstate commerce for commercial distribution before May 28,

1976; or

(B) is (i) of a type so introduced or delivered, and (ii) is

substantially equivalent to another device within that type,

the Secretary shall by regulation, promulgated in accordance with

this subsection, require that such device have an approval under

this section of an application for premarket approval.

(2)(A) A proceeding for the promulgation of a regulation under

paragraph (1) respecting a device shall be initiated by the

publication in the Federal Register of a notice of proposed

rulemaking. Such notice shall contain -

(i) the proposed regulation;

(ii) proposed findings with respect to the degree of risk of

illness or injury designed to be eliminated or reduced by

requiring the device to have an approved application for

premarket approval and the benefit to the public from use of the

device;

(iii) opportunity for the submission of comments on the

proposed regulation and the proposed findings; and

(iv) opportunity to request a change in the classification of

the device based on new information relevant to the

classification of the device.

(B) If, within fifteen days after publication of a notice under

subparagraph (A), the Secretary receives a request for a change in

the classification of a device, he shall, within sixty days of the

publication of such notice and after consultation with the

appropriate panel under section 360c of this title, by order

published in the Federal Register, either deny the request for

change in classification or give notice of his intent to initiate

such a change under section 360c(e) of this title.

(3) After the expiration of the period for comment on a proposed

regulation and proposed findings published under paragraph (2) and

after consideration of comments submitted on such proposed

regulation and findings, the Secretary shall (A) promulgate such

regulation and publish in the Federal Register findings on the

matters referred to in paragraph (2)(A)(ii), or (B) publish a

notice terminating the proceeding for the promulgation of the

regulation together with the reasons for such termination. If a

notice of termination is published, the Secretary shall (unless

such notice is issued because the device is a banned device under

section 360f of this title) initiate a proceeding under section

360c(e) of this title to reclassify the device subject to the

proceeding terminated by such notice.

(4) The Secretary, upon his own initiative or upon petition of an

interested person, may by regulation amend or revoke any regulation

promulgated under this subsection. A regulation to amend or revoke

a regulation under this subsection shall be promulgated in

accordance with the requirements prescribed by this subsection for

the promulgation of the regulation to be amended or revoked.

(c) Application for premarket approval

(1) Any person may file with the Secretary an application for

premarket approval for a class III device. Such an application for

a device shall contain -

(A) full reports of all information, published or known to or

which should reasonably be known to the applicant, concerning

investigations which have been made to show whether or not such

device is safe and effective;

(B) a full statement of the components, ingredients, and

properties and of the principle or principles of operation, of

such device;

(C) a full description of the methods used in, and the

facilities and controls used for, the manufacture, processing,

and, when relevant, packing and installation of, such device;

(D) an identifying reference to any performance standard under

section 360d of this title which would be applicable to any

aspect of such device if it were a class II device, and either

adequate information to show that such aspect of such device

fully meets such performance standard or adequate information to

justify any deviation from such standard;

(E) such samples of such device and of components thereof as

the Secretary may reasonably require, except that where the

submission of such samples is impracticable or unduly burdensome,

the requirement of this subparagraph may be met by the submission

of complete information concerning the location of one or more

such devices readily available for examination and testing;

(F) specimens of the labeling proposed to be used for such

device; and

(G) such other information relevant to the subject matter of

the application as the Secretary, with the concurrence of the

appropriate panel under section 360c of this title, may require.

(2)(A) Any person may file with the Secretary a report seeking

premarket approval for a class III device referred to in subsection

(a) of this section that is a reprocessed single-use device. Such

a report shall contain the following:

(i) The device name, including both the trade or proprietary

name and the common or usual name.

(ii) The establishment registration number of the owner or

operator submitting the report.

(iii) Actions taken to comply with performance standards under

section 360d of this title.

(iv) Proposed labels, labeling, and advertising sufficient to

describe the device, its intended use, and directions for use.

(v) Full reports of all information, published or known to or

which should be reasonably known to the applicant, concerning

investigations which have been made to show whether or not the

device is safe or effective.

(vi) A description of the device's components, ingredients, and

properties.

(vii) A full description of the methods used in, and the

facilities and controls used for, the reprocessing and packing of

the device.

(viii) Such samples of the device that the Secretary may

reasonably require.

(ix) A financial certification or disclosure statement or both,

as required by part 54 of title 21, Code of Federal Regulations.

(x) A statement that the applicant believes to the best of the

applicant's knowledge that all data and information submitted to

the Secretary are truthful and accurate and that no material fact

has been omitted in the report.

(xi) Any additional data and information, including information

of the type required in paragraph (1) for an application under

such paragraph, that the Secretary determines is necessary to

determine whether there is reasonable assurance of safety and

effectiveness for the reprocessed device.

(xii) Validation data described in section 360(o)(1)(A) of this

title that demonstrates that the reasonable assurance of the

safety or effectiveness of the device will remain after the

maximum number of times the device is reprocessed as intended by

the person submitting such report.

(B) In the case of a class III device referred to in subsection

(a) of this section that is a reprocessed single-use device:

(i) Subparagraph (A) of this paragraph applies in lieu of

paragraph (1).

(ii) Subject to clause (i), the provisions of this section

apply to a report under subparagraph (A) to the same extent and

in the same manner as such provisions apply to an application

under paragraph (1).

(iii) Each reference in other sections of this chapter to an

application under this section, other than such a reference in

section 379i or 379j of this title, shall be considered to be a

reference to a report under subparagraph (A).

(iv) Each reference in other sections of this chapter to a

device for which an application under this section has been

approved, or has been denied, suspended, or withdrawn, other than

such a reference in section 379i or 379j of this title, shall be

considered to be a reference to a device for which a report under

subparagraph (A) has been approved, or has been denied,

suspended, or withdrawn, respectively.

(3) (FOOTNOTE 1) Upon receipt of an application meeting the

requirements set forth in paragraph (1), the Secretary -

(FOOTNOTE 1) So in original. Two pars. (3) have been enacted.

(A) may on the Secretary's own initiative, or

(B) shall, upon the request of an applicant unless the

Secretary finds that the information in the application which

would be reviewed by a panel substantially duplicates information

which has previously been reviewed by a panel appointed under

section 360c of this title,

refer such application to the appropriate panel under section 360c

of this title for study and for submission (within such period as

he may establish) of a report and recommendation respecting

approval of the application, together with all underlying data and

the reasons or basis for the recommendation. Where appropriate,

the Secretary shall ensure that such panel includes, or consults

with, one or more pediatric experts.

(3)(A) (FOOTNOTE 1) Prior to the submission of an application

under this subsection, the Secretary shall accept and review any

portion of the application that the applicant and the Secretary

agree is complete, ready, and appropriate for review, except that

such requirement does not apply, and the Secretary has discretion

whether to accept and review such portion, during any period in

which, under section 379j(g) of this title, the Secretary does not

have the authority to collect fees under section 379j(a) of this

title.

(B) Each portion of a submission reviewed under subparagraph (A)

and found acceptable by the Secretary shall not be further reviewed

after receipt of an application that satisfies the requirements of

paragraph (1), unless an issue of safety or effectiveness provides

the Secretary reason to review such accepted portion.

(C) Whenever the Secretary determines that a portion of a

submission under subparagraph (A) is unacceptable, the Secretary

shall, in writing, provide to the applicant a description of any

deficiencies in such portion and identify the information that is

required to correct these deficiencies, unless the applicant is no

longer pursuing the application.

(d) Action on application for premarket approval

(1)(A) As promptly as possible, but in no event later than one

hundred and eighty days after the receipt of an application under

subsection (c) of this section (except as provided in section

360j(l)(3)(D)(ii) of this title or unless, in accordance with

subparagraph (B)(i), an additional period as agreed upon by the

Secretary and the applicant), the Secretary, after considering the

report and recommendation submitted under paragraph (2) of such

subsection, shall -

(i) issue an order approving the application if he finds that

none of the grounds for denying approval specified in paragraph

(2) of this subsection applies; or

(ii) deny approval of the application if he finds (and sets

forth the basis for such finding as part of or accompanying such

denial) that one or more grounds for denial specified in

paragraph (2) of this subsection apply.

In making the determination whether to approve or deny the

application, the Secretary shall rely on the conditions of use

included in the proposed labeling as the basis for determining

whether or not there is a reasonable assurance of safety and

effectiveness, if the proposed labeling is neither false nor

misleading. In determining whether or not such labeling is false

or misleading, the Secretary shall fairly evaluate all material

facts pertinent to the proposed labeling.

(B)(i) The Secretary may not enter into an agreement to extend

the period in which to take action with respect to an application

submitted for a device subject to a regulation promulgated under

subsection (b) of this section unless he finds that the continued

availability of the device is necessary for the public health.

(ii) An order approving an application for a device may require

as a condition to such approval that the sale and distribution of

the device be restricted but only to the extent that the sale and

distribution of a device may be restricted under a regulation under

section 360j(e) of this title.

(iii) The Secretary shall accept and review statistically valid

and reliable data and any other information from investigations

conducted under the authority of regulations required by section

360j(g) of this title to make a determination of whether there is a

reasonable assurance of safety and effectiveness of a device

subject to a pending application under this section if -

(I) the data or information is derived from investigations of

an earlier version of the device, the device has been modified

during or after the investigations (but prior to submission of an

application under subsection (c) of this section) and such a

modification of the device does not constitute a significant

change in the design or in the basic principles of operation of

the device that would invalidate the data or information; or

(II) the data or information relates to a device approved under

this section, is available for use under this chapter, and is

relevant to the design and intended use of the device for which

the application is pending.

(2) The Secretary shall deny approval of an application for a

device if, upon the basis of the information submitted to the

Secretary as part of the application and any other information

before him with respect to such device, the Secretary finds that -

(A) there is a lack of a showing of reasonable assurance that

such device is safe under the conditions of use prescribed,

recommended, or suggested in the proposed labeling thereof;

(B) there is a lack of a showing of reasonable assurance that

the device is effective under the conditions of use prescribed,

recommended, or suggested in the proposed labeling thereof;

(C) the methods used in, or the facilities or controls used

for, the manufacture, processing, packing, or installation of

such device do not conform to the requirements of section 360j(f)

of this title;

(D) based on a fair evaluation of all material facts, the

proposed labeling is false or misleading in any particular; or

(E) such device is not shown to conform in all respects to a

performance standard in effect under section 360d of this title

compliance with which is a condition to approval of the

application and there is a lack of adequate information to

justify the deviation from such standard.

Any denial of an application shall, insofar as the Secretary

determines to be practicable, be accompanied by a statement

informing the applicant of the measures required to place such

application in approvable form (which measures may include further

research by the applicant in accordance with one or more protocols

prescribed by the Secretary).

(3)(A)(i) The Secretary shall, upon the written request of an

applicant, meet with the applicant, not later than 100 days after

the receipt of an application that has been filed as complete under

subsection (c) of this section, to discuss the review status of the

application.

(ii) The Secretary shall, in writing and prior to the meeting,

provide to the applicant a description of any deficiencies in the

application that, at that point, have been identified by the

Secretary based on an interim review of the entire application and

identify the information that is required to correct those

deficiencies.

(iii) The Secretary shall notify the applicant promptly of -

(I) any additional deficiency identified in the application, or

(II) any additional information required to achieve completion

of the review and final action on the application,

that was not described as a deficiency in the written description

provided by the Secretary under clause (ii).

(B) The Secretary and the applicant may, by mutual consent,

establish a different schedule for a meeting required under this

paragraph.

(4) An applicant whose application has been denied approval may,

by petition filed on or before the thirtieth day after the date

upon which he receives notice of such denial, obtain review thereof

in accordance with either paragraph (1) or (2) of subsection (g) of

this section, and any interested person may obtain review, in

accordance with paragraph (1) or (2) of subsection (g) of this

section, of an order of the Secretary approving an application.

(5) In order to provide for more effective treatment or diagnosis

of life-threatening or irreversibly debilitating human diseases or

conditions, the Secretary shall provide review priority for devices

-

(A) representing breakthrough technologies,

(B) for which no approved alternatives exist,

(C) which offer significant advantages over existing approved

alternatives, or

(D) the availability of which is in the best interest of the

patients.

(6)(A)(i) A supplemental application shall be required for any

change to a device subject to an approved application under this

subsection that affects safety or effectiveness, unless such change

is a modification in a manufacturing procedure or method of

manufacturing and the holder of the approved application submits a

written notice to the Secretary that describes in detail the

change, summarizes the data or information supporting the change,

and informs the Secretary that the change has been made under the

requirements of section 360j(f) of this title.

(ii) The holder of an approved application who submits a notice

under clause (i) with respect to a manufacturing change of a device

may distribute the device 30 days after the date on which the

Secretary receives the notice, unless the Secretary within such

30-day period notifies the holder that the notice is not adequate

and describes such further information or action that is required

for acceptance of such change. If the Secretary notifies the

holder that a supplemental application is required, the Secretary

shall review the supplement within 135 days after the receipt of

the supplement. The time used by the Secretary to review the

notice of the manufacturing change shall be deducted from the

135-day review period if the notice meets appropriate content

requirements for premarket approval supplements.

(B)(i) Subject to clause (ii), in reviewing a supplement to an

approved application, for an incremental change to the design of a

device that affects safety or effectiveness, the Secretary shall

approve such supplement if -

(I) nonclinical data demonstrate that the design modification

creates the intended additional capacity, function, or

performance of the device; and

(II) clinical data from the approved application and any

supplement to the approved application provide a reasonable

assurance of safety and effectiveness for the changed device.

(ii) The Secretary may require, when necessary, additional

clinical data to evaluate the design modification of the device to

provide a reasonable assurance of safety and effectiveness.

(e) Withdrawal and temporary suspension of approval of application

(1) The Secretary shall, upon obtaining, where appropriate,

advice on scientific matters from a panel or panels under section

360c of this title, and after due notice and opportunity for

informal hearing to the holder of an approved application for a

device, issue an order withdrawing approval of the application if

the Secretary finds -

(A) that such device is unsafe or ineffective under the

conditions of use prescribed, recommended, or suggested in the

labeling thereof;

(B) on the basis of new information before him with respect to

such device, evaluated together with the evidence available to

him when the application was approved, that there is a lack of a

showing of reasonable assurance that the device is safe or

effective under the conditions of use prescribed, recommended, or

suggested in the labeling thereof;

(C) that the application contained or was accompanied by an

untrue statement of a material fact;

(D) that the applicant (i) has failed to establish a system for

maintaining records, or has repeatedly or deliberately failed to

maintain records or to make reports, required by an applicable

regulation under section 360i(a) of this title, (ii) has refused

to permit access to, or copying or verification of, such records

as required by section 374 of this title, or (iii) has not

complied with the requirements of section 360 of this title;

(E) on the basis of new information before him with respect to

such device, evaluated together with the evidence before him when

the application was approved, that the methods used in, or the

facilities and controls used for, the manufacture, processing,

packing, or installation of such device do not conform with the

requirements of section 360j(f) of this title and were not

brought into conformity with such requirements within a

reasonable time after receipt of written notice from the

Secretary of nonconformity;

(F) on the basis of new information before him, evaluated

together with the evidence before him when the application was

approved, that the labeling of such device, based on a fair

evaluation of all material facts, is false or misleading in any

particular and was not corrected within a reasonable time after

receipt of written notice from the Secretary of such fact; or

(G) on the basis of new information before him, evaluated

together with the evidence before him when the application was

approved, that such device is not shown to conform in all

respects to a performance standard which is in effect under

section 360d of this title compliance with which was a condition

to approval of the application and that there is a lack of

adequate information to justify the deviation from such standard.

(2) The holder of an application subject to an order issued under

paragraph (1) withdrawing approval of the application may, by

petition filed on or before the thirtieth day after the date upon

which he receives notice of such withdrawal, obtain review thereof

in accordance with either paragraph (1) or (2) of subsection (g) of

this section.

(3) If, after providing an opportunity for an informal hearing,

the Secretary determines there is reasonable probability that the

continuation of distribution of a device under an approved

application would cause serious, adverse health consequences or

death, the Secretary shall by order temporarily suspend the

approval of the application approved under this section. If the

Secretary issues such an order, the Secretary shall proceed

expeditiously under paragraph (1) to withdraw such application.

(f) Product development protocol

(1) In the case of a class III device which is required to have

an approval of an application submitted under subsection (c) of

this section, such device shall be considered as having such an

approval if a notice of completion of testing conducted in

accordance with a product development protocol approved under

paragraph (4) has been declared completed under paragraph (6).

(2) Any person may submit to the Secretary a proposed product

development protocol with respect to a device. Such a protocol

shall be accompanied by data supporting it. If, within thirty days

of the receipt of such a protocol, the Secretary determines that it

appears to be appropriate to apply the requirements of this

subsection to the device with respect to which the protocol is

submitted, the Secretary -

(A) may, at the initiative of the Secretary, refer the proposed

protocol to the appropriate panel under section 360c of this

title for its recommendation respecting approval of the protocol;

or

(B) shall so refer such protocol upon the request of the

submitter, unless the Secretary finds that the proposed protocol

and accompanying data which would be reviewed by such panel

substantially duplicate a product development protocol and

accompanying data which have previously been reviewed by such a

panel.

(3) A proposed product development protocol for a device may be

approved only if -

(A) the Secretary determines that it is appropriate to apply

the requirements of this subsection to the device in lieu of the

requirement of approval of an application submitted under

subsection (c) of this section; and

(B) the Secretary determines that the proposed protocol

provides -

(i) a description of the device and the changes which may be

made in the device,

(ii) a description of the preclinical trials (if any) of the

device and a specification of (I) the results from such trials

to be required before the commencement of clinical trials of

the device, and (II) any permissible variations in preclinical

trials and the results therefrom,

(iii) a description of the clinical trials (if any) of the

device and a specification of (I) the results from such trials

to be required before the filing of a notice of completion of

the requirements of the protocol, and (II) any permissible

variations in such trials and the results therefrom,

(iv) a description of the methods to be used in, and the

facilities and controls to be used for, the manufacture,

processing, and, when relevant, packing and installation of the

device,

(v) an identifying reference to any performance standard

under section 360d of this title to be applicable to any aspect

of such device,

(vi) if appropriate, specimens of the labeling proposed to be

used for such device,

(vii) such other information relevant to the subject matter

of the protocol as the Secretary, with the concurrence of the

appropriate panel or panels under section 360c of this title,

may require, and

(viii) a requirement for submission of progress reports and,

when completed, records of the trials conducted under the

protocol which records are adequate to show compliance with the

protocol.

(4) The Secretary shall approve or disapprove a proposed product

development protocol submitted under paragraph (2) within one

hundred and twenty days of its receipt unless an additional period

is agreed upon by the Secretary and the person who submitted the

protocol. Approval of a protocol or denial of approval of a

protocol is final agency action subject to judicial review under

chapter 7 of title 5.

(5) At any time after a product development protocol for a device

has been approved pursuant to paragraph (4), the person for whom

the protocol was approved may submit a notice of completion -

(A) stating (i) his determination that the requirements of the

protocol have been fulfilled and that, to the best of his

knowledge, there is no reason bearing on safety or effectiveness

why the notice of completion should not become effective, and

(ii) the data and other information upon which such determination

was made, and

(B) setting forth the results of the trials required by the

protocol and all the information required by subsection (c)(1) of

this section.

(6)(A) The Secretary may, after providing the person who has an

approved protocol and opportunity for an informal hearing and at

any time prior to receipt of notice of completion of such protocol,

issue a final order to revoke such protocol if he finds that -

(i) such person has failed substantially to comply with the

requirements of the protocol,

(ii) the results of the trials obtained under the protocol

differ so substantially from the results required by the protocol

that further trials cannot be justified, or

(iii) the results of the trials conducted under the protocol or

available new information do not demonstrate that the device

tested under the protocol does not present an unreasonable risk

to health and safety.

(B) After the receipt of a notice of completion of an approved

protocol the Secretary shall, within the ninety-day period

beginning on the date such notice is received, by order either

declare the protocol completed or declare it not completed. An

order declaring a protocol not completed may take effect only after

the Secretary has provided the person who has the protocol

opportunity for an informal hearing on the order. Such an order

may be issued only if the Secretary finds -

(i) such person has failed substantially to comply with the

requirements of the protocol,

(ii) the results of the trials obtained under the protocol

differ substantially from the results required by the protocol,

or

(iii) there is a lack of a showing of reasonable assurance of

the safety and effectiveness of the device under the conditions

of use prescribed, recommended, or suggested in the proposed

labeling thereof.

(C) A final order issued under subparagraph (A) or (B) shall be

in writing and shall contain the reasons to support the conclusions

thereof.

(7) At any time after a notice of completion has become

effective, the Secretary may issue an order (after due notice and

opportunity for an informal hearing to the person for whom the

notice is effective) revoking the approval of a device provided by

a notice of completion which has become effective as provided in

subparagraph (B) if he finds that any of the grounds listed in

subparagraphs (A) through (G) of subsection (e)(1) of this section

apply. Each reference in such subparagraphs to an application

shall be considered for purposes of this paragraph as a reference

to a protocol and the notice of completion of such protocol, and

each reference to the time when an application was approved shall

be considered for purposes of this paragraph as a reference to the

time when a notice of completion took effect.

(8) A person who has an approved protocol subject to an order

issued under paragraph (6)(A) revoking such protocol, a person who

has an approved protocol with respect to which an order under

paragraph (6)(B) was issued declaring that the protocol had not

been completed, or a person subject to an order issued under

paragraph (7) revoking the approval of a device may, by petition

filed on or before the thirtieth day after the date upon which he

receives notice of such order, obtain review thereof in accordance

with either paragraph (1) or (2) of subsection (g) of this section.

(g) Review

(1) Upon petition for review of -

(A) an order under subsection (d) of this section approving or

denying approval of an application or an order under subsection

(e) of this section withdrawing approval of an application, or

(B) an order under subsection (f)(6)(A) of this section

revoking an approved protocol, under subsection (f)(6)(B) of this

section declaring that an approved protocol has not been

completed, or under subsection (f)(7) of this section revoking

the approval of a device,

the Secretary shall, unless he finds the petition to be without

good cause or unless a petition for review of such order has been

submitted under paragraph (2), hold a hearing, in accordance with

section 554 of title 5, on the order. The panel or panels which

considered the application, protocol, or device subject to such

order shall designate a member to appear and testify at any such

hearing upon request of the Secretary, the petitioner, or the

officer conducting the hearing, but this requirement does not

preclude any other member of the panel or panels from appearing and

testifying at any such hearing. Upon completion of such hearing

and after considering the record established in such hearing, the

Secretary shall issue an order either affirming the order subject

to the hearing or reversing such order and, as appropriate,

approving or denying approval of the application, reinstating the

application's approval, approving the protocol, or placing in

effect a notice of completion.

(2)(A) Upon petition for review of -

(i) an order under subsection (d) of this section approving or

denying approval of an application or an order under subsection

(e) of this section withdrawing approval of an application, or

(ii) an order under subsection (f)(6)(A) of this section

revoking an approved protocol, under subsection (f)(6)(B) of this

section declaring that an approved protocol has not been

completed, or under subsection (f)(7) of this section revoking

the approval of a device,

the Secretary shall refer the application or protocol subject to

the order and the basis for the order to an advisory committee of

experts established pursuant to subparagraph (B) for a report and

recommendation with respect to the order. The advisory committee

shall, after independent study of the data and information

furnished to it by the Secretary and other data and information

before it, submit to the Secretary a report and recommendation,

together with all underlying data and information and a statement

of the reasons or basis for the recommendation. A copy of such

report shall be promptly supplied by the Secretary to any person

who petitioned for such referral to the advisory committee.

(B) The Secretary shall establish advisory committees (which may

not be panels under section 360c of this title) to receive

referrals under subparagraph (A). The Secretary shall appoint as

members of any such advisory committee persons qualified in the

subject matter to be referred to the committee and of appropriately

diversified professional backgrounds, except that the Secretary may

not appoint to such a committee any individual who is in the

regular full-time employ of the United States and engaged in the

administration of this chapter. Members of an advisory committee

(other than officers or employees of the United States), while

attending conferences or meetings of their committee or otherwise

serving at the request of the Secretary, shall be entitled to

receive compensation at rates to be fixed by the Secretary, which

rates may not exceed the daily equivalent for grade GS-18 of the

General Schedule for each day (including traveltime) they are so

engaged; and while so serving away from their homes or regular

places of business each member may be allowed travel expenses,

including per diem in lieu of subsistence, as authorized by section

5703 of title 5 for persons in the Government service employed

intermittently. The Secretary shall designate the chairman of an

advisory committee from its members. The Secretary shall furnish

each advisory committee with clerical and other assistance, and

shall by regulation prescribe the procedures to be followed by each

such committee in acting on referrals made under subparagraph (A).

(C) The Secretary shall make public the report and recommendation

made by an advisory committee with respect to an application and

shall by order, stating the reasons therefor, either affirm the

order referred to the advisory committee or reverse such order and,

if appropriate, approve or deny approval of the application,

reinstate the application's approval, approve the protocol, or

place in effect a notice of completion.

(h) Service of orders

Orders of the Secretary under this section shall be served (1) in

person by any officer or employee of the department designated by

the Secretary, or (2) by mailing the order by registered mail or

certified mail addressed to the applicant at his last known address

in the records of the Secretary.

(i) Revision

(1) Before December 1, 1995, the Secretary shall by order require

manufacturers of devices, which were introduced or delivered for

introduction into interstate commerce for commercial distribution

before May 28, 1976, and which are subject to revision of

classification under paragraph (2), to submit to the Secretary a

summary of and citation to any information known or otherwise

available to the manufacturer respecting such devices, including

adverse safety or effectiveness information which has not been

submitted under section 360i of this title. The Secretary may

require the manufacturer to submit the adverse safety or

effectiveness data for which a summary and citation were submitted,

if such data are available to the manufacturer.

(2) After the issuance of an order under paragraph (1) but before

December 1, 1995, the Secretary shall publish a regulation in the

Federal Register for each device -

(A) which the Secretary has classified as a class III device,

and

(B) for which no final regulation has been promulgated under

subsection (b) of this section,

revising the classification of the device so that the device is

classified into class I or class II, unless the regulation requires

the device to remain in class III. In determining whether to revise

the classification of a device or to require a device to remain in

class III, the Secretary shall apply the criteria set forth in

section 360c(a) of this title. Before the publication of a

regulation requiring a device to remain in class III or revising

its classification, the Secretary shall publish a proposed

regulation respecting the classification of a device under this

paragraph and provide reasonable opportunity for the submission of

comments on any such regulation. No regulation requiring a device

to remain in class III or revising its classification may take

effect before the expiration of 90 days from the date of its

publication in the Federal Register as a proposed regulation.

(3) The Secretary shall, as promptly as is reasonably achievable,

but not later than 12 months after the effective date of the

regulation requiring a device to remain in class III, establish a

schedule for the promulgation of a subsection (b) of this section

regulation for each device which is subject to the regulation

requiring the device to remain in class III.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 515, as added Pub. L. 94-295, Sec. 2,

May 28, 1976, 90 Stat. 552; amended Pub. L. 101-629, Sec. 4(b)(1),

9(a), 18(c), Nov. 28, 1990, 104 Stat. 4515, 4521, 4528; Pub. L.

103-80, Sec. 3(t), Aug. 13, 1993, 107 Stat. 778; Pub. L. 105-115,

title II, Sec. 201(b), 202, 205(c), 209(b), 216(b), Nov. 21, 1997,

111 Stat. 2334, 2338, 2341, 2349; Pub. L. 107-250, title II, Sec.

209, 210, title III, Sec. 302(c), Oct. 26, 2002, 116 Stat. 1613,

1614, 1618.)

-MISC1-

AMENDMENTS

2002 - Subsec. (a). Pub. L. 107-250, Sec. 302(c)(1), inserted

''or, as applicable, an approval under subsection (c)(2) of this

section of a report seeking premarket approval'' before period in

concluding provisions.

Subsec. (c)(2). Pub. L. 107-250, Sec. 302(c)(2)(B), added par.

(2). Former par. (2) redesignated (3).

Subsec. (c)(3). Pub. L. 107-250, Sec. 302(c)(2)(A), redesignated

par. (2) relating to Secretary's referral of application to

appropriate panel as (3).

Pub. L. 107-250, Sec. 210, which directed amendment of subsec.

(c), as amended by section 302(c)(2)(A) of Pub. L. 107-250, by

adding at the end of par. (3) ''Where appropriate, the Secretary

shall ensure that such panel includes, or consults with, one or

more pediatric experts.'', was executed by inserting the language

at the end of the concluding provisions of par. (3) relating to

Secretary's referral of application to appropriate panel, to

reflect the probable intent of Congress.

Pub. L. 107-250, Sec. 209, added par. (3) relating to acceptance

and review of any portion of the application prior to submission.

1997 - Subsec. (d)(1)(A). Pub. L. 105-115, Sec. 205(c)(1),

inserted at end ''In making the determination whether to approve or

deny the application, the Secretary shall rely on the conditions of

use included in the proposed labeling as the basis for determining

whether or not there is a reasonable assurance of safety and

effectiveness, if the proposed labeling is neither false nor

misleading. In determining whether or not such labeling is false

or misleading, the Secretary shall fairly evaluate all material

facts pertinent to the proposed labeling.''

Subsec. (d)(1)(B)(iii). Pub. L. 105-115, Sec. 201(b), added cl.

(iii).

Subsec. (d)(3), (4). Pub. L. 105-115, Sec. 202(1), 209(b), added

par. (3) and redesignated former par. (3) as (4).

Subsec. (d)(5). Pub. L. 105-115, Sec. 202(2), added par. (5).

Subsec. (d)(6). Pub. L. 105-115, Sec. 205(c)(2), added par. (6).

Subsec. (f)(2). Pub. L. 105-115, Sec. 216(b), substituted ''the

Secretary - '' and subpars. (A) and (B) for ''he shall refer the

proposed protocol to the appropriate panel under section 360c of

this title for its recommendation respecting approval of the

protocol.''

1993 - Subsec. (c)(2)(A). Pub. L. 103-80 struck out ''refer such

application'' after ''own initiative''.

1990 - Subsec. (c)(2). Pub. L. 101-629, Sec. 18(c), substituted

''the Secretary - '' for ''the Secretary shall'' and added subpars.

(A) and (B).

Subsec. (e). Pub. L. 101-629, Sec. 9(a)(2), inserted ''and

temporary suspension'' after ''Withdrawal'' in heading.

Subsec. (e)(3). Pub. L. 101-629, Sec. 9(a)(1), added par. (3).

Subsec. (i). Pub. L. 101-629, Sec. 4(b)(1), added subsec. (i).

EFFECTIVE DATE OF 1997 AMENDMENT

Amendment by Pub. L. 105-115 effective 90 days after Nov. 21,

1997, except as otherwise provided, see section 501 of Pub. L.

105-115, set out as a note under section 321 of this title.

TERMINATION OF ADVISORY COMMITTEES

Advisory committees in existence on Jan. 5, 1973, to terminate

not later than the expiration of the 2-year period following Jan.

5, 1973, and advisory committees established after Jan. 5, 1973, to

terminate not later than the expiration of the 2-year period

beginning on the date of their establishment, unless in the case of

a committee established by the President or an officer of the

Federal Government, such committee is renewed by appropriate action

prior to the expiration of such 2-year period, or in the case of a

committee established by Congress, its duration is otherwise

provided by law. See section 14 of Pub. L. 92-463, Oct. 6, 1972,

86 Stat. 776, set out in the Appendix to Title 5, Government

Organization and Employees.

REPORT ON CERTAIN DEVICES

Pub. L. 107-250, title II, Sec. 205, Oct. 26, 2002, 116 Stat.

1612, provided that: ''Not later than one year after the date of

enactment of this Act (Oct. 26, 2002), the Secretary of Health and

Human Services shall report to the appropriate committees of

Congress on the timeliness and effectiveness of device premarket

reviews by centers other than the Center for Devices and

Radiological Health. Such report shall include information on the

times required to log in and review original submissions and

supplements, times required to review manufacturers' replies to

submissions, and times to approve or clear such devices. Such

report shall contain the Secretary's recommendations on any

measures needed to improve performance including, but not limited

to, the allocation of additional resources. Such report also shall

include the Secretary's specific recommendation on whether

responsibility for regulating such devices should be reassigned to

those persons within the Food and Drug Administration who are

primarily charged with regulating other types of devices, and

whether such a transfer could have a deleterious impact on the

public health and on the safety of such devices.''

REFERENCES IN OTHER LAWS TO GS-16, 17, OR 18 PAY RATES

References in laws to the rates of pay for GS-16, 17, or 18, or

to maximum rates of pay under the General Schedule, to be

considered references to rates payable under specified sections of

Title 5, Government Organization and Employees, see section 529

(title I, Sec. 101(c)(1)) of Pub. L. 101-509, set out in a note

under section 5376 of Title 5.

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in sections 331, 351, 353, 356-1,

360, 360c, 360g, 360j, 360aaa, 360bbb-1, 374, 379i, 379j, 381, 382,

1604 of this title; title 35 section 156; title 42 section 1395l.

-CITE-

21 USC Sec. 360f 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 360f. Banned devices

-STATUTE-

(a) General rule

Whenever the Secretary finds, on the basis of all available data

and information, that -

(1) a device intended for human use presents substantial

deception or an unreasonable and substantial risk of illness or

injury; and

(2) in the case of substantial deception or an unreasonable and

substantial risk of illness or injury which the Secretary

determined could be corrected or eliminated by labeling or change

in labeling and with respect to which the Secretary provided

written notice to the manufacturer specifying the deception or

risk of illness or injury, the labeling or change in labeling to

correct the deception or eliminate or reduce such risk, and the

period within which such labeling or change in labeling was to be

done, such labeling or change in labeling was not done within

such period;

he may initiate a proceeding to promulgate a regulation to make

such device a banned device.

(b) Special effective date

The Secretary may declare a proposed regulation under subsection

(a) of this section to be effective upon its publication in the

Federal Register and until the effective date of any final action

taken respecting such regulation if (1) he determines, on the basis

of all available data and information, that the deception or risk

of illness or injury associated with the use of the device which is

subject to the regulation presents an unreasonable, direct, and

substantial danger to the health of individuals, and (2) before the

date of the publication of such regulation, the Secretary notifies

the manufacturer of such device that such regulation is to be made

so effective. If the Secretary makes a proposed regulation so

effective, he shall, as expeditiously as possible, give interested

persons prompt notice of his action under this subsection, provide

reasonable opportunity for an informal hearing on the proposed

regulation, and either affirm, modify, or revoke such proposed

regulation.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 516, as added Pub. L. 94-295, Sec. 2,

May 28, 1976, 90 Stat. 560; amended Pub. L. 101-629, Sec. 18(d),

Nov. 28, 1990, 104 Stat. 4529.)

-MISC1-

AMENDMENTS

1990 - Subsec. (a). Pub. L. 101-629 struck out ''and after

consultation with the appropriate panel or panels under section

360c of this title'' after ''data and information'' in introductory

provisions and struck out at end ''The Secretary shall afford all

interested persons opportunity for an informal hearing on a

regulation proposed under this subsection.''

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in sections 331, 360c, 360e, 360g,

360j, 381, 382 of this title.

-CITE-

21 USC Sec. 360g 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 360g. Judicial review

-STATUTE-

(a) Petition; record

Not later than thirty days after -

(1) the promulgation of a regulation under section 360c of this

title classifying a device in class I or changing the

classification of a device to class I or an order under

subsection (f)(2) of such section reclassifying a device or

denying a petition for reclassification of a device,

(2) the promulgation of a regulation under section 360d of this

title establishing, amending, or revoking a performance standard

for a device,

(3) the issuance of an order under section 360d(b)(2) or

360e(b)(2)(B) of this title denying a request for

reclassification of a device,

(4) the promulgation of a regulation under paragraph (3) of

section 360e(b) of this title requiring a device to have an

approval of a premarket application, a regulation under paragraph

(4) of that section amending or revoking a regulation under

paragraph (3), or an order pursuant to section 360e(g)(1) or

360e(g)(2)(C) of this title,

(5) the promulgation of a regulation under section 360f of this

title (other than a proposed regulation made effective under

subsection (b) of such section upon the regulation's publication)

making a device a banned device,

(6) the issuance of an order under section 360j(f)(2) of this

title,

(7) an order under section 360j(g)(4) of this title

disapproving an application for an exemption of a device for

investigational use or an order under section 360j(g)(5) of this

title withdrawing such an exemption for a device,

(8) an order pursuant to section 360c(i) of this title, or

(9) a regulation under section 360e(i)(2) or 360j(l)(5)(B) of

this title,

any person adversely affected by such regulation or order may file

a petition with the United States Court of Appeals for the District

of Columbia or for the circuit wherein such person resides or has

his principal place of business for judicial review of such

regulation or order. A copy of the petition shall be transmitted

by the clerk of the court to the Secretary or other officer

designated by him for that purpose. The Secretary shall file in

the court the record of the proceedings on which the Secretary

based his regulation or order as provided in section 2112 of title

28. For purposes of this section, the term ''record'' means all

notices and other matter published in the Federal Register with

respect to the regulation or order reviewed, all information

submitted to the Secretary with respect to such regulation or

order, proceedings of any panel or advisory committee with respect

to such regulation or order, any hearing held with respect to such

regulation or order, and any other information identified by the

Secretary, in the administrative proceeding held with respect to

such regulation or order, as being relevant to such regulation or

order.

(b) Additional data, views, and arguments

If the petitioner applies to the court for leave to adduce

additional data, views, or arguments respecting the regulation or

order being reviewed and shows to the satisfaction of the court

that such additional data, views, or arguments are material and

that there were reasonable grounds for the petitioner's failure to

adduce such data, views, or arguments in the proceedings before the

Secretary, the court may order the Secretary to provide additional

opportunity for the oral presentation of data, views, or arguments

and for written submissions. The Secretary may modify his

findings, or make new findings by reason of the additional data,

views, or arguments so taken and shall file with the court such

modified or new findings, and his recommendation, if any, for the

modification or setting aside of the regulation or order being

reviewed, with the return of such additional data, views, or

arguments.

(c) Standard for review

Upon the filing of the petition under subsection (a) of this

section for judicial review of a regulation or order, the court

shall have jurisdiction to review the regulation or order in

accordance with chapter 7 of title 5 and to grant appropriate

relief, including interim relief, as provided in such chapter. A

regulation described in paragraph (2) or (5) of subsection (a) of

this section and an order issued after the review provided by

section 360e(g) of this title shall not be affirmed if it is found

to be unsupported by substantial evidence on the record taken as a

whole.

(d) Finality of judgments

The judgment of the court affirming or setting aside, in whole or

in part, any regulation or order shall be final, subject to review

by the Supreme Court of the United States upon certiorari or

certification, as provided in section 1254 of title 28.

(e) Remedies

The remedies provided for in this section shall be in addition to

and not in lieu of any other remedies provided by law.

(f) Statement of reasons

To facilitate judicial review under this section or under any

other provision of law of a regulation or order issued under

section 360c, 360d, 360e, 360f, 360h, 360i, 360j, or 360k of this

title each such regulation or order shall contain a statement of

the reasons for its issuance and the basis, in the record of the

proceedings held in connection with its issuance, for its issuance.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 517, as added Pub. L. 94-295, Sec. 2,

May 28, 1976, 90 Stat. 560; amended Pub. L. 101-629, Sec. 13, Nov.

28, 1990, 104 Stat. 4524; Pub. L. 102-300, Sec. 6(f), June 16,

1992, 106 Stat. 240; Pub. L. 105-115, title II, Sec. 216(a)(2),

Nov. 21, 1997, 111 Stat. 2349.)

-MISC1-

AMENDMENTS

1997 - Subsec. (a)(8). Pub. L. 105-115, Sec. 216(a)(2)(A),

inserted ''or'' at end.

Subsec. (a)(9). Pub. L. 105-115, Sec. 216(a)(2)(B), substituted

comma for '', or'' at end.

Subsec. (a)(10). Pub. L. 105-115, Sec. 216(a)(2)(C), struck out

par. (10) which read as follows: ''an order under section

360j(h)(4)(B) of this title,''.

1992 - Subsec. (a)(10). Pub. L. 102-300 substituted

''360j(h)(4)(B)'' for ''360j(c)(4)(B)''.

1990 - Subsec. (a)(8) to (10). Pub. L. 101-629 added pars. (8) to

(10).

EFFECTIVE DATE OF 1997 AMENDMENT

Amendment by Pub. L. 105-115 effective 90 days after Nov. 21,

1997, except as otherwise provided, see section 501 of Pub. L.

105-115, set out as a note under section 321 of this title.

-CITE-

21 USC Sec. 360h 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 360h. Notification and other remedies

-STATUTE-

(a) Notification

If the Secretary determines that -

(1) a device intended for human use which is introduced or

delivered for introduction into interstate commerce for

commercial distribution presents an unreasonable risk of

substantial harm to the public health, and

(2) notification under this subsection is necessary to

eliminate the unreasonable risk of such harm and no more

practicable means is available under the provisions of this

chapter (other than this section) to eliminate such risk,

the Secretary may issue such order as may be necessary to assure

that adequate notification is provided in an appropriate form, by

the persons and means best suited under the circumstances involved,

to all health professionals who prescribe or use the device and to

any other person (including manufacturers, importers, distributors,

retailers, and device users) who should properly receive such

notification in order to eliminate such risk. An order under this

subsection shall require that the individuals subject to the risk

with respect to which the order is to be issued be included in the

persons to be notified of the risk unless the Secretary determines

that notice to such individuals would present a greater danger to

the health of such individuals than no such notification. If the

Secretary makes such a determination with respect to such

individuals, the order shall require that the health professionals

who prescribe or use the device provide for the notification of the

individuals whom the health professionals treated with the device

of the risk presented by the device and of any action which may be

taken by or on behalf of such individuals to eliminate or reduce

such risk. Before issuing an order under this subsection, the

Secretary shall consult with the persons who are to give notice

under the order.

(b) Repair, replacement, or refund

(1)(A) If, after affording opportunity for an informal hearing,

the Secretary determines that -

(i) a device intended for human use which is introduced or

delivered for introduction into interstate commerce for

commercial distribution presents an unreasonable risk of

substantial harm to the public health,

(ii) there are reasonable grounds to believe that the device

was not properly designed or manufactured with reference to the

state of the art as it existed at the time of its design or

manufacture,

(iii) there are reasonable grounds to believe that the

unreasonable risk was not caused by failure of a person other

than a manufacturer, importer, distributor, or retailer of the

device to exercise due care in the installation, maintenance,

repair, or use of the device, and

(iv) the notification authorized by subsection (a) of this

section would not by itself be sufficient to eliminate the

unreasonable risk and action described in paragraph (2) of this

subsection is necessary to eliminate such risk,

the Secretary may order the manufacturer, importer, or any

distributor of such device, or any combination of such persons, to

submit to him within a reasonable time a plan for taking one or

more of the actions described in paragraph (2). An order issued

under the preceding sentence which is directed to more than one

person shall specify which person may decide which action shall be

taken under such plan and the person specified shall be the person

who the Secretary determines bears the principal, ultimate

financial responsibility for action taken under the plan unless the

Secretary cannot determine who bears such responsibility or the

Secretary determines that the protection of the public health

requires that such decision be made by a person (including a device

user or health professional) other than the person he determines

bears such responsibility.

(B) The Secretary shall approve a plan submitted pursuant to an

order issued under subparagraph (A) unless he determines (after

affording opportunity for an informal hearing) that the action or

actions to be taken under the plan or the manner in which such

action or actions are to be taken under the plan will not assure

that the unreasonable risk with respect to which such order was

issued will be eliminated. If the Secretary disapproves a plan, he

shall order a revised plan to be submitted to him within a

reasonable time. If the Secretary determines (after affording

opportunity for an informal hearing) that the revised plan is

unsatisfactory or if no revised plan or no initial plan has been

submitted to the Secretary within the prescribed time, the

Secretary shall (i) prescribe a plan to be carried out by the

person or persons to whom the order issued under subparagraph (A)

was directed, or (ii) after affording an opportunity for an

informal hearing, by order prescribe a plan to be carried out by a

person who is a manufacturer, importer, distributor, or retailer of

the device with respect to which the order was issued but to whom

the order under subparagraph (A) was not directed.

(2) The actions which may be taken under a plan submitted under

an order issued under paragraph (1) are as follows:

(A) To repair the device so that it does not present the

unreasonable risk of substantial harm with respect to which the

order under paragraph (1) was issued.

(B) To replace the device with a like or equivalent device

which is in conformity with all applicable requirements of this

chapter.

(C) To refund the purchase price of the device (less a

reasonable allowance for use if such device has been in the

possession of the device user for one year or more -

(i) at the time of notification ordered under subsection (a)

of this section, or

(ii) at the time the device user receives actual notice of

the unreasonable risk with respect to which the order was

issued under paragraph (1),

whichever first occurs).

(3) No charge shall be made to any person (other than a

manufacturer, importer, distributor or retailer) for availing

himself of any remedy, described in paragraph (2) and provided

under an order issued under paragraph (1), and the person subject

to the order shall reimburse each person (other than a

manufacturer, importer, distributor, or retailer) who is entitled

to such a remedy for any reasonable and foreseeable expenses

actually incurred by such person in availing himself of such

remedy.

(c) Reimbursement

An order issued under subsection (b) of this section with respect

to a device may require any person who is a manufacturer, importer,

distributor, or retailer of the device to reimburse any other

person who is a manufacturer, importer, distributor, or retailer of

such device for such other person's expenses actually incurred in

connection with carrying out the order if the Secretary determines

such reimbursement is required for the protection of the public

health. Any such requirement shall not affect any rights or

obligations under any contract to which the person receiving

reimbursement or the person making such reimbursement is a party.

(d) Effect on other liability

Compliance with an order issued under this section shall not

relieve any person from liability under Federal or State law. In

awarding damages for economic loss in an action brought for the

enforcement of any such liability, the value to the plaintiff in

such action of any remedy provided him under such order shall be

taken into account.

(e) Recall authority

(1) If the Secretary finds that there is a reasonable probability

that a device intended for human use would cause serious, adverse

health consequences or death, the Secretary shall issue an order

requiring the appropriate person (including the manufacturers,

importers, distributors, or retailers of the device) -

(A) to immediately cease distribution of such device, and

(B) to immediately notify health professionals and device user

facilities of the order and to instruct such professionals and

facilities to cease use of such device.

The order shall provide the person subject to the order with an

opportunity for an informal hearing, to be held not later than 10

days after the date of the issuance of the order, on the actions

required by the order and on whether the order should be amended to

require a recall of such device. If, after providing an

opportunity for such a hearing, the Secretary determines that

inadequate grounds exist to support the actions required by the

order, the Secretary shall vacate the order.

(2)(A) If, after providing an opportunity for an informal hearing

under paragraph (1), the Secretary determines that the order should

be amended to include a recall of the device with respect to which

the order was issued, the Secretary shall, except as provided in

subparagraphs (B) and (C), amend the order to require a recall.

The Secretary shall specify a timetable in which the device recall

will occur and shall require periodic reports to the Secretary

describing the progress of the recall.

(B) An amended order under subparagraph (A) -

(i) shall -

(I) not include recall of a device from individuals, and

(II) not include recall of a device from device user

facilities if the Secretary determines that the risk of

recalling such device from the facilities presents a greater

health risk than the health risk of not recalling the device

from use, and

(ii) shall provide for notice to individuals subject to the

risks associated with the use of such device.

In providing the notice required by clause (ii), the Secretary may

use the assistance of health professionals who prescribed or used

such a device for individuals. If a significant number of such

individuals cannot be identified, the Secretary shall notify such

individuals pursuant to section 375(b) of this title.

(3) The remedy provided by this subsection shall be in addition

to remedies provided by subsections (a), (b), and (c) of this

section.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 518, as added Pub. L. 94-295, Sec. 2,

May 28, 1976, 90 Stat. 562; amended Pub. L. 101-629, Sec. 8, Nov.

28, 1990, 104 Stat. 4520; Pub. L. 102-300, Sec. 4, June 16, 1992,

106 Stat. 239.)

-MISC1-

AMENDMENTS

1992 - Subsec. (b)(1)(A)(ii). Pub. L. 102-300 substituted ''or''

for ''and'' after ''properly designed'' and ''time of its design''.

1990 - Subsec. (e). Pub. L. 101-629 added subsec. (e).

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in sections 331, 352, 360c, 360g,

360j of this title.

-CITE-

21 USC Sec. 360i 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 360i. Records and reports on devices

-STATUTE-

(a) General rule

Every person who is a manufacturer or importer of a device

intended for human use shall establish and maintain such records,

make such reports, and provide such information, as the Secretary

may by regulation reasonably require to assure that such device is

not adulterated or misbranded and to otherwise assure its safety

and effectiveness. Regulations prescribed under the preceding

sentence -

(1) shall require a device manufacturer or importer to report

to the Secretary whenever the manufacturer or importer receives

or otherwise becomes aware of information that reasonably

suggests that one of its marketed devices -

(A) may have caused or contributed to a death or serious

injury, or

(B) has malfunctioned and that such device or a similar

device marketed by the manufacturer or importer would be likely

to cause or contribute to a death or serious injury if the

malfunction were to recur;

(2) shall define the term ''serious injury'' to mean an injury

that -

(A) is life threatening,

(B) results in permanent impairment of a body function or

permanent damage to a body structure, or

(C) necessitates medical or surgical intervention to preclude

permanent impairment of a body function or permanent damage to

a body structure;

(3) shall require reporting of other significant adverse device

experiences as determined by the Secretary to be necessary to be

reported;

(4) shall not impose requirements unduly burdensome to a device

manufacturer or importer taking into account his cost of

complying with such requirements and the need for the protection

of the public health and the implementation of this chapter;

(5) which prescribe the procedure for making requests for

reports or information shall require that each request made under

such regulations for submission of a report or information to the

Secretary state the reason or purpose for such request and

identify to the fullest extent practicable such report or

information;

(6) which require submission of a report or information to the

Secretary shall state the reason or purpose for the submission of

such report or information and identify to the fullest extent

practicable such report or information;

(7) may not require that the identity of any patient be

disclosed in records, reports, or information required under this

subsection unless required for the medical welfare of an

individual, to determine the safety or effectiveness of a device,

or to verify a record, report, or information submitted under

this chapter; and

(8) may not require a manufacturer or importer of a class I

device to -

(A) maintain for such a device records respecting information

not in the possession of the manufacturer or importer, or

(B) to submit for such a device to the Secretary any report

or information -

(i) not in the possession of the manufacturer or importer,

or

(ii) on a periodic basis,

unless such report or information is necessary to determine if

the device should be reclassified or if the device is

adulterated or misbranded. and (FOOTNOTE 1)

(FOOTNOTE 1) So in original. The word ''and'' probably should

not appear.

In prescribing such regulations, the Secretary shall have due

regard for the professional ethics of the medical profession and

the interests of patients. The prohibitions of paragraph (7) of

this subsection continue to apply to records, reports, and

information concerning any individual who has been a patient,

irrespective of whether or when he ceases to be a patient. The

Secretary shall by regulation require distributors to keep records

and make such records available to the Secretary upon request.

Paragraphs (4) and (8) apply to distributors to the same extent and

in the same manner as such paragraphs apply to manufacturers and

importers.

(b) User reports

(1)(A) Whenever a device user facility receives or otherwise

becomes aware of information that reasonably suggests that a device

has or may have caused or contributed to the death of a patient of

the facility, the facility shall, as soon as practicable but not

later than 10 working days after becoming aware of the information,

report the information to the Secretary and, if the identity of the

manufacturer is known, to the manufacturer of the device. In the

case of deaths, the Secretary may by regulation prescribe a shorter

period for the reporting of such information.

(B) Whenever a device user facility receives or otherwise becomes

aware of -

(i) information that reasonably suggests that a device has or

may have caused or contributed to the serious illness of, or

serious injury to, a patient of the facility, or

(ii) other significant adverse device experiences as determined

by the Secretary by regulation to be necessary to be reported,

the facility shall, as soon as practicable but not later than 10

working days after becoming aware of the information, report the

information to the manufacturer of the device or to the Secretary

if the identity of the manufacturer is not known.

(C) Each device user facility shall submit to the Secretary on an

annual basis a summary of the reports made under subparagraphs (A)

and (B). Such summary shall be submitted on January 1 of each

year. The summary shall be in such form and contain such

information from such reports as the Secretary may require and

shall include -

(i) sufficient information to identify the facility which made

the reports for which the summary is submitted,

(ii) in the case of any product which was the subject of a

report, the product name, serial number, and model number,

(iii) the name and the address of the manufacturer of such

device, and

(iv) a brief description of the event reported to the

manufacturer.

(D) For purposes of subparagraphs (A), (B), and (C), a device

user facility shall be treated as having received or otherwise

become aware of information with respect to a device of that

facility when medical personnel who are employed by or otherwise

formally affiliated with the facility receive or otherwise become

aware of information with respect to that device in the course of

their duties.

(2) The Secretary may not disclose the identity of a device user

facility which makes a report under paragraph (1) except in

connection with -

(A) an action brought to enforce section 331(q) of this title,

or

(B) a communication to a manufacturer of a device which is the

subject of a report under paragraph (1).

This paragraph does not prohibit the Secretary from disclosing the

identity of a device user facility making a report under paragraph

(1) or any information in such a report to employees of the

Department of Health and Human Services, to the Department of

Justice, or to the duly authorized committees and subcommittees of

the Congress.

(3) No report made under paragraph (1) by -

(A) a device user facility,

(B) an individual who is employed by or otherwise formally

affiliated with such a facility, or

(C) a physician who is not required to make such a report,

shall be admissible into evidence or otherwise used in any civil

action involving private parties unless the facility, individual,

or physician who made the report had knowledge of the falsity of

the information contained in the report.

(4) A report made under paragraph (1) does not affect any

obligation of a manufacturer who receives the report to file a

report as required under subsection (a) of this section.

(5) With respect to device user facilities:

(A) The Secretary shall by regulation plan and implement a

program under which the Secretary limits user reporting under

paragraphs (1) through (4) to a subset of user facilities that

constitutes a representative profile of user reports for device

deaths and serious illnesses or serious injuries.

(B) During the period of planning the program under

subparagraph (A), paragraphs (1) through (4) continue to apply.

(C) During the period in which the Secretary is providing for a

transition to the full implementation of the program, paragraphs

(1) through (4) apply except to the extent that the Secretary

determines otherwise.

(D) On and after the date on which the program is fully

implemented, paragraphs (1) through (4) do not apply to a user

facility unless the facility is included in the subset referred

to in subparagraph (A).

(E) Not later than 2 years after November 21, 1997, the

Secretary shall submit to the Committee on Commerce of the House

of Representatives, and to the Committee on Labor and Human

Resources of the Senate, a report describing the plan developed

by the Secretary under subparagraph (A) and the progress that has

been made toward the implementation of the plan.

(6) For purposes of this subsection:

(A) The term ''device user facility'' means a hospital,

ambulatory surgical facility, nursing home, or outpatient

treatment facility which is not a physician's office. The

Secretary may by regulation include an outpatient diagnostic

facility which is not a physician's office in such term.

(B) The terms ''serious illness'' and ''serious injury'' mean

illness or injury, respectively, that -

(i) is life threatening,

(ii) results in permanent impairment of a body function or

permanent damage to a body structure, or

(iii) necessitates medical or surgical intervention to

preclude permanent impairment of a body function or permanent

damage to a body structure.

(c) Persons exempt

Subsection (a) of this section shall not apply to -

(1) any practitioner who is licensed by law to prescribe or

administer devices intended for use in humans and who

manufactures or imports devices solely for use in the course of

his professional practice;

(2) any person who manufactures or imports devices intended for

use in humans solely for such person's use in research or

teaching and not for sale (including any person who uses a device

under an exemption granted under section 360j(g) of this title);

and

(3) any other class of persons as the Secretary may by

regulation exempt from subsection (a) of this section upon a

finding that compliance with the requirements of such subsection

by such class with respect to a device is not necessary to (A)

assure that a device is not adulterated or misbranded or (B)

otherwise to assure its safety and effectiveness.

(d) Repealed. Pub. L. 105-115, title II, Sec. 213(a)(2), Nov. 21,

1997, 111 Stat. 2347

(e) Device tracking

(1) The Secretary may by order require a manufacturer to adopt a

method of tracking a class II or class III device -

(A) the failure of which would be reasonably likely to have

serious adverse health consequences; or

(B) which is -

(i) intended to be implanted in the human body for more than

one year, or

(ii) a life sustaining or life supporting device used outside

a device user facility.

(2) Any patient receiving a device subject to tracking under

paragraph (1) may refuse to release, or refuse permission to

release, the patient's name, address, social security number, or

other identifying information for the purpose of tracking.

(f) Reports of removals and corrections

(1) Except as provided in paragraph (2), the Secretary shall by

regulation require a manufacturer or importer of a device to report

promptly to the Secretary any correction or removal of a device

undertaken by such manufacturer or importer if the removal or

correction was undertaken -

(A) to reduce a risk to health posed by the device, or

(B) to remedy a violation of this chapter caused by the device

which may present a risk to health.

A manufacturer or importer of a device who undertakes a correction

or removal of a device which is not required to be reported under

this paragraph shall keep a record of such correction or removal.

(2) No report of the corrective action or removal of a device may

be required under paragraph (1) if a report of the corrective

action or removal is required and has been submitted under

subsection (a) of this section.

(3) For purposes of paragraphs (1) and (2), the terms

''correction'' and ''removal'' do not include routine servicing.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 519, as added Pub. L. 94-295, Sec. 2,

May 28, 1976, 90 Stat. 564; amended Pub. L. 101-629, Sec. 2(a),

3(a)(1), (b)(1), 7, Nov. 28, 1990, 104 Stat. 4511, 4513, 4514,

4520; Pub. L. 102-300, Sec. 5(a), June 16, 1992, 106 Stat. 239;

Pub. L. 103-80, Sec. 3(u), Aug. 13, 1993, 107 Stat. 778; Pub. L.

105-115, title II, Sec. 211, 213(a), (c), Nov. 21, 1997, 111 Stat.

2345-2347.)

-MISC1-

AMENDMENTS

1997 - Subsec. (a). Pub. L. 105-115, Sec. 213(a)(1)(A), (F), in

introductory provisions, substituted ''manufacturer or importer''

for ''manufacturer, importer, or distributor'' and, in closing

provisions, inserted at end ''The Secretary shall by regulation

require distributors to keep records and make such records

available to the Secretary upon request. Paragraphs (4) and (8)

apply to distributors to the same extent and in the same manner as

such paragraphs apply to manufacturers and importers.''

Subsec. (a)(4). Pub. L. 105-115, Sec. 213(a)(1)(B), substituted

''manufacturer or importer'' for ''manufacturer, importer, or

distributor''.

Subsec. (a)(7). Pub. L. 105-115, Sec. 213(a)(1)(C), inserted

''and'' after semicolon at end.

Subsec. (a)(8). Pub. L. 105-115, Sec. 213(a)(1)(D), substituted

''manufacturer or importer'' for ''manufacturer, importer, or

distributor'' wherever appearing and substituted period for

semicolon after ''misbranded''.

Subsec. (a)(9). Pub. L. 105-115, Sec. 213(a)(1)(E), struck out

par. (9) which read as follows: ''shall require distributors who

submit such reports to submit copies of the reports to the

manufacturer of the device for which the report was made.''

Subsec. (b)(1)(C). Pub. L. 105-115, Sec. 213(c)(1)(A), in

introductory provisions, substituted ''on an annual basis'' for

''on a semi-annual basis'' and struck out ''and July 1'' after

''January 1'' and struck out closing provisions which read as

follows: ''The Secretary may by regulation alter the frequency and

timing of reports required by this subparagraph.''

Subsec. (b)(2)(A). Pub. L. 105-115, Sec. 213(c)(1)(B)(i),

inserted ''or'' after comma at end.

Subsec. (b)(2)(B). Pub. L. 105-115, Sec. 213(c)(1)(B)(ii),

substituted period for '', or'' at end.

Subsec. (b)(2)(C). Pub. L. 105-115, Sec. 213(c)(1)(B)(iii),

struck out subpar. (C) which read as follows: ''a disclosure

required under subsection (a) of this section.''

Subsec. (b)(5), (6). Pub. L. 105-115, Sec. 213(c)(2), added par.

(5) and redesignated former par. (5) as (6).

Subsec. (d). Pub. L. 105-115, Sec. 213(a)(2), struck out heading

and text of subsec. (d). Text read as follows: ''Each manufacturer,

importer, and distributor required to make reports under subsection

(a) of this section shall submit to the Secretary annually a

statement certifying that -

''(1) the manufacturer, importer, or distributor did file a

certain number of such reports, or

''(2) the manufacturer, importer, or distributor did not file

any report under subsection (a) of this section.''

Subsec. (e). Pub. L. 105-115, Sec. 211, amended heading and text

of subsec. (e) generally. Prior to amendment, text read as

follows: ''Every person who registers under section 360 of this

title and is engaged in the manufacture of -

''(1) a device the failure of which would be reasonably likely

to have serious adverse health consequences and which is (A) a

permanently implantable device, or (B) a life sustaining or life

supporting device used outside a device user facility, or

''(2) any other device which the Secretary may designate,

shall adopt a method of device tracking.''

Subsec. (f)(1). Pub. L. 105-115, Sec. 213(a)(3), substituted ''or

importer'' for '', importer, or distributor'' wherever appearing.

1993 - Subsec. (a). Pub. L. 103-80 substituted ''paragraph (7)''

for ''paragraph (4)'' in last sentence.

1992 - Subsec. (a). Pub. L. 102-300, Sec. 5(a)(1), added pars.

(1) to (3) and redesignated former pars. (1) to (6) as (4) to (9),

respectively.

Subsec. (b)(1)(A). Pub. L. 102-300, Sec. 5(a)(2)(A), substituted

''a device has or may have'' for ''there is a probability that a

device has''.

Subsec. (b)(1)(B). Pub. L. 102-300, Sec. 5(a)(2)(A), (B),

substituted ''a device has or may have'' for ''there is a

probability that a device has'', designated existing provisions as

cl. (i), and added cl. (ii).

Subsec. (b)(5)(B)(iii). Pub. L. 102-300, Sec. 5(a)(2)(C), struck

out ''immediate'' before ''medical''.

1990 - Subsec. (a)(6). Pub. L. 101-629, Sec. 3(a)(1), added par.

(6).

Subsecs. (b), (c). Pub. L. 101-629, Sec. 2(a), added subsec. (b)

and redesignated former subsec. (b) as (c).

Subsecs. (d), (e). Pub. L. 101-629, Sec. 3(b)(1), added subsecs.

(d) and (e).

Subsec. (f). Pub. L. 101-629, Sec. 7, added subsec. (f).

EFFECTIVE DATE OF 1997 AMENDMENT

Section 211 of Pub. L. 105-115 provided in part that the

amendment made by that section is effective 90 days after Nov. 21,

1997.

Amendment by section 213(a), (c) of Pub. L. 105-115 effective 90

days after Nov. 21, 1997, except as otherwise provided, see section

501 of Pub. L. 105-115, set out as a note under section 321 of this

title.

EFFECTIVE DATE OF 1992 AMENDMENT

Section 2(b) of Pub. L. 102-300 provided that: ''The amendments

made by subsection (a) (amending sections 3(b)(3) and 3(c) of Pub.

L. 101-629, set out as notes below) shall take effect as of May 27,

1992 and any rule to implement section 519(e) of the Federal Food,

Drug, and Cosmetic Act (21 U.S.C. 360i(e)) proposed under section

3(c)(2) of the Safe Medical Devices Act of 1990 (Pub. L. 101-629,

set out as a note below) shall revert to its proposed status as of

such date.''

Section 5(b) of Pub. L. 102-300 provided that: ''The amendments

made by subsection (a) (amending this section) shall take effect -

''(1) 1 year after the date of the enactment of this Act (June

16, 1992); or

''(2) on the effective date of regulations of the Secretary to

implement such amendments,

whichever occurs first.''

EFFECTIVE DATE OF 1990 AMENDMENT

Section 2(c) of Pub. L. 101-629 provided that: ''Section 519(b)

of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360i(b)), as

added by the amendment made by subsection (a), shall take effect -

''(1) upon the effective date of regulations promulgated under

subsection (b) (set out below), or

''(2) upon the expiration of 12 months from the date of the

enactment of this Act (Nov. 28, 1990),

whichever occurs first.''

Section 3(a)(2) of Pub. L. 101-629 provided that: ''Section

519(a)(6) (21 U.S.C. 360i(a)(6)), as added by the amendment made by

paragraph (1), shall take effect upon the effective date of final

regulations under subsection (c) (set out below).''

Section 3(b)(3) of Pub. L. 101-629, as amended by Pub. L.

102-300, Sec. 2(a)(1), June 16, 1992, 106 Stat. 238, provided that:

''Section 519(e) (21 U.S.C. 360i(e)), as added by the amendment

made by paragraph (1), shall take effect upon the expiration of 9

months after the issuance of final regulations under subsection (c)

(set out below).''

(For effective date of amendment by Pub. L. 102-300, see section

2(b) of Pub. L. 102-300, set out above as an Effective Date of 1992

Amendment note.)

REGULATIONS

Section 2(b) of Pub. L. 101-629 provided that: ''The Secretary of

Health and Human Services shall promulgate regulations to implement

section 519(b) of the Federal Food, Drug, and Cosmetic Act (21

U.S.C. 360i(b)), as added by the amendment made by subsection (a)

(including a definition of the summary required by paragraph (1)(C)

of such section) not later than 12 months after the date of

enactment of this Act (Nov. 28, 1990). In promulgating the

regulations, the Secretary shall minimize the administrative

burdens on device user facilities consistent with the need to

assure adequate information.''

Section 3(c) of Pub. L. 101-629, as amended by Pub. L. 102-300,

Sec. 2(a)(2), (3), June 16, 1992, 106 Stat. 238, provided that:

''(1)(A) Not later than 9 months after the date of the enactment

of this Act (Nov. 28, 1990), the Secretary of Health and Human

Services shall issue proposed regulations -

''(i) to require distributors of devices to establish and

maintain records and to make reports (including reports required

by part 803 of title 21 of the Code of Federal Regulations) under

section 519(a)(6) of the Federal Food, Drug, and Cosmetic Act (21

U.S.C. 360i(a)(6)), and

''(ii) to implement section 519(e) of such Act.

The Secretary may exempt from regulations described in clause (i)

classes of distributors of class I and class II devices from whom

reports are not necessary for the protection of the public health.

''(B) Regulations under subparagraph (A) shall -

''(i) require appropriate methods for maintenance of records to

ensure that patients who receive devices can be provided the

notification required by such Act (this chapter),

''(ii) require that manufacturers adopt effective methods of

tracking devices,

''(iii) take into account the position of distributors in the

device distribution process, and

''(iv) include such other requirements as the Secretary deems

necessary for the adoption of an effective user tracking program

under section 519(e) of such Act.

''(2) Not later than 18 months after the date of the enactment of

this Act, the Secretary shall issue final regulations to implement

sections (sic) 519(a)(6) of the Federal Food, Drug, and Cosmetic

Act. If the Secretary does not promulgate such final regulations

upon the expiration of such 18 months, the Congress finds that

there is good cause for the proposed regulations to be considered

as the final regulations without response to comment because the

implementation of sections (sic) 519(a)(6) of such Act is essential

to protect the health of patients who use such devices.

Consequently, in such event, the proposed regulations issued under

paragraph (1) shall become final regulations as of the expiration

of such 18 months. There shall be promptly published in the

Federal Register notice of the new status of the proposed

regulations.

''(3) Not later than November 28, 1992, the Secretary shall issue

final regulations to implement section 519(e) of the Federal Food,

Drug, and Cosmetic Act. If the Secretary does not promulgate such

final regulations by November 28, 1992, the Congress finds that

there is good cause for the proposed regulations to be considered

as the final regulations without response to comment because the

implementation of section 519(e) of such Act is essential to

protect the health of patients who use devices. In such event, the

proposed regulations issued under paragraph (1) shall become the

issued final regulations on November 29, 1992. There shall be

promptly published in the Federal Register notice of the new status

of the proposed regulations.''

(For effective date of amendment by Pub. L. 102-300, see section

2(b) of Pub. L. 102-300, set out above as an Effective Date of 1992

Amendment note.)

INFORMATION CONCERNING REPORTING REQUIREMENTS FOR DEVICE USER

FACILITIES

Section 2(d) of Pub. L. 101-629 directed Secretary of Health and

Human Services, during the 18-month period beginning on Nov. 28,

1990, to inform device user facilities (as defined in 21 U.S.C.

360i(b)(5)(A)) and manufacturers and distributors of devices

respecting the requirements of 21 U.S.C. 360i(b), and, to the

extent practicable, provide persons subject to such requirements

assistance in the form of publications regarding such requirements.

STUDY OF REPORTING REQUIREMENTS; COMPLIANCE BY DEVICE USER

FACILITIES; ACTIONS BY MANUFACTURERS; COST EFFECTIVENESS;

RECOMMENDATIONS

Section 2(e) of Pub. L. 101-629 directed Comptroller General of

the United States, not more than 36 months after Nov. 28, 1990, to

conduct a study of compliance by device user facilities with the

requirements of 21 U.S.C. 360i(b), actions taken by manufacturers

of devices in response to reports made to them, cost effectiveness

of such requirements and their implementation, and any

recommendations for improvements to such requirements, with

Comptroller General to complete the study and submit a report on

the study not later than 45 months from Nov. 28, 1990, to

appropriate committees of Congress.

REPORT TO CONGRESS ON REPORTING REQUIREMENTS FOR DEVICE USER

FACILITIES

Section 2(f) of Pub. L. 101-629 directed Secretary of Health and

Human Services, not later than 36 months after Nov. 28, 1990, to

prepare and submit to appropriate committees of Congress a report

containing an evaluation of the requirements of 21 U.S.C. 360i(b),

consisting of an evaluation of the safety benefits of the

requirements, the burdens placed on the Food and Drug

Administration and on device user facilities by the requirements,

and the cost-effectiveness of the requirements and recommendations

for legislative reform.

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in sections 331, 333, 352, 360c,

360e, 360g, 360j, 374 of this title.

-CITE-

21 USC Sec. 360j 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 360j. General provisions respecting control of devices

intended for human use

-STATUTE-

(a) General rule

Any requirement authorized by or under section 351, 352, 360, or

360i of this title applicable to a device intended for human use

shall apply to such device until the applicability of the

requirement to the device has been changed by action taken under

section 360c, 360d, or 360e of this title or under subsection (g)

of this section, and any requirement established by or under

section 351, 352, 360, or 360i of this title which is inconsistent

with a requirement imposed on such device under section 360d or

360e of this title or under subsection (g) of this section shall

not apply to such device.

(b) Custom devices

Sections 360d and 360e of this title do not apply to any device

which, in order to comply with the order of an individual physician

or dentist (or any other specially qualified person designated

under regulations promulgated by the Secretary after an opportunity

for an oral hearing) necessarily deviates from an otherwise

applicable performance standard or requirement prescribed by or

under section 360e of this title if (1) the device is not generally

available in finished form for purchase or for dispensing upon

prescription and is not offered through labeling or advertising by

the manufacturer, importer, or distributor thereof for commercial

distribution, and (2) such device -

(A)(i) is intended for use by an individual patient named in

such order of such physician or dentist (or other specially

qualified person so designated) and is to be made in a specific

form for such patient, or

(ii) is intended to meet the special needs of such physician or

dentist (or other specially qualified person so designated) in

the course of the professional practice of such physician or

dentist (or other specially qualified person so designated), and

(B) is not generally available to or generally used by other

physicians or dentists (or other specially qualified persons so

designated).

(c) Trade secrets

Any information reported to or otherwise obtained by the

Secretary or his representative under section 360c, 360d, 360e,

360f, 360h, 360i, or 374 of this title or under subsection (f) or

(g) of this section which is exempt from disclosure pursuant to

subsection (a) of section 552 of title 5 by reason of subsection

(b)(4) of such section shall be considered confidential and shall

not be disclosed and may not be used by the Secretary as the basis

for the reclassification of a device from class III to class II or

class I or as the basis for the establishment or amendment of a

performance standard under section 360d of this title for a device

reclassified from class III to class II, except (1) in accordance

with subsection (h) of this section, and (2) that such information

may be disclosed to other officers or employees concerned with

carrying out this chapter or when relevant in any proceeding under

this chapter (other than section 360c or 360d of this title).

(d) Notices and findings

Each notice of proposed rulemaking under section 360c, 360d,

360e, 360f, 360h, or 360i of this title, or under this section, any

other notice which is published in the Federal Register with

respect to any other action taken under any such section and which

states the reasons for such action, and each publication of

findings required to be made in connection with rulemaking under

any such section shall set forth -

(1) the manner in which interested persons may examine data and

other information on which the notice or findings is based, and

(2) the period within which interested persons may present

their comments on the notice or findings (including the need

therefor) orally or in writing, which period shall be at least

sixty days but may not exceed ninety days unless the time is

extended by the Secretary by a notice published in the Federal

Register stating good cause therefor.

(e) Restricted devices

(1) The Secretary may by regulation require that a device be

restricted to sale, distribution, or use -

(A) only upon the written or oral authorization of a

practitioner licensed by law to administer or use such device, or

(B) upon such other conditions as the Secretary may prescribe

in such regulation,

if, because of its potentiality for harmful effect or the

collateral measures necessary to its use, the Secretary determines

that there cannot otherwise be reasonable assurance of its safety

and effectiveness. No condition prescribed under subparagraph (B)

may restrict the use of a device to persons with specific training

or experience in its use or to persons for use in certain

facilities unless the Secretary determines that such a restriction

is required for the safe and effective use of the device. No such

condition may exclude a person from using a device solely because

the person does not have the training or experience to make him

eligible for certification by a certifying board recognized by the

American Board of Medical Specialties or has not been certified by

such a Board. A device subject to a regulation under this

subsection is a restricted device.

(2) The label of a restricted device shall bear such appropriate

statements of the restrictions required by a regulation under

paragraph (1) as the Secretary may in such regulation prescribe.

(f) Good manufacturing practice requirements

(1)(A) The Secretary may, in accordance with subparagraph (B),

prescribe regulations requiring that the methods used in, and the

facilities and controls used for, the manufacture, pre-production

design validation (including a process to assess the performance of

a device but not including an evaluation of the safety or

effectiveness of a device), packing, storage, and installation of a

device conform to current good manufacturing practice, as

prescribed in such regulations, to assure that the device will be

safe and effective and otherwise in compliance with this chapter.

(B) Before the Secretary may promulgate any regulation under

subparagraph (A) he shall -

(i) afford the advisory committee established under paragraph

(3) an opportunity to submit recommendations to him with respect

to the regulation proposed to be promulgated;

(ii) afford opportunity for an oral hearing; and

(iii) ensure that such regulation conforms, to the extent

practicable, with internationally recognized standards defining

quality systems, or parts of the standards, for medical devices.

The Secretary shall provide the advisory committee a reasonable

time to make its recommendation with respect to proposed

regulations under subparagraph (A).

(2)(A) Any person subject to any requirement prescribed by

regulations under paragraph (1) may petition the Secretary for an

exemption or variance from such requirement. Such a petition shall

be submitted to the Secretary in such form and manner as he shall

prescribe and shall -

(i) in the case of a petition for an exemption from a

requirement, set forth the basis for the petitioner's

determination that compliance with the requirement is not

required to assure that the device will be safe and effective and

otherwise in compliance with this chapter,

(ii) in the case of a petition for a variance from a

requirement, set forth the methods proposed to be used in, and

the facilities and controls proposed to be used for, the

manufacture, packing, storage, and installation of the device in

lieu of the methods, facilities, and controls prescribed by the

requirement, and

(iii) contain such other information as the Secretary shall

prescribe.

(B) The Secretary may refer to the advisory committee established

under paragraph (3) any petition submitted under subparagraph (A).

The advisory committee shall report its recommendations to the

Secretary with respect to a petition referred to it within sixty

days of the date of the petition's referral. Within sixty days

after -

(i) the date the petition was submitted to the Secretary under

subparagraph (A), or

(ii) if the petition was referred to an advisory committee, the

expiration of the sixty-day period beginning on the date the

petition was referred to the advisory committee,

whichever occurs later, the Secretary shall by order either deny

the petition or approve it.

(C) The Secretary may approve -

(i) a petition for an exemption for a device from a requirement

if he determines that compliance with such requirement is not

required to assure that the device will be safe and effective and

otherwise in compliance with this chapter, and

(ii) a petition for a variance for a device from a requirement

if he determines that the methods to be used in, and the

facilities and controls to be used for, the manufacture, packing,

storage, and installation of the device in lieu of the methods,

controls, and facilities prescribed by the requirement are

sufficient to assure that the device will be safe and effective

and otherwise in compliance with this chapter.

An order of the Secretary approving a petition for a variance shall

prescribe such conditions respecting the methods used in, and the

facilities and controls used for, the manufacture, packing,

storage, and installation of the device to be granted the variance

under the petition as may be necessary to assure that the device

will be safe and effective and otherwise in compliance with this

chapter.

(D) After the issuance of an order under subparagraph (B)

respecting a petition, the petitioner shall have an opportunity for

an informal hearing on such order.

(3) The Secretary shall establish an advisory committee for the

purpose of advising and making recommendations to him with respect

to regulations proposed to be promulgated under paragraph (1)(A)

and the approval or disapproval of petitions submitted under

paragraph (2). The advisory committee shall be composed of nine

members as follows:

(A) Three of the members shall be appointed from persons who

are officers or employees of any State or local government or of

the Federal Government.

(B) Two of the members shall be appointed from persons who are

representative of interests of the device manufacturing industry;

two of the members shall be appointed from persons who are

representative of the interests of physicians and other health

professionals; and two of the members shall be representative of

the interests of the general public.

Members of the advisory committee who are not officers or employees

of the United States, while attending conferences or meetings of

the committee or otherwise engaged in its business, shall be

entitled to receive compensation at rates to be fixed by the

Secretary, which rates may not exceed the daily equivalent of the

rate in effect for grade GS-18 of the General Schedule, for each

day (including traveltime) they are so engaged; and while so

serving away from their homes or regular places of business each

member may be allowed travel expenses, including per diem in lieu

of subsistence, as authorized by section 5703 of title 5 for

persons in the Government service employed intermittently. The

Secretary shall designate one of the members of the advisory

committee to serve as its chairman. The Secretary shall furnish

the advisory committee with clerical and other assistance. Section

14 of the Federal Advisory Committee Act shall not apply with

respect to the duration of the advisory committee established under

this paragraph.

(g) Exemption for devices for investigational use

(1) It is the purpose of this subsection to encourage, to the

extent consistent with the protection of the public health and

safety and with ethical standards, the discovery and development of

useful devices intended for human use and to that end to maintain

optimum freedom for scientific investigators in their pursuit of

that purpose.

(2)(A) The Secretary shall, within the one hundred and twenty-day

period beginning on May 28, 1976, by regulation prescribe

procedures and conditions under which devices intended for human

use may upon application be granted an exemption from the

requirements of section 352, 360, 360d, 360e, 360f, 360i, or 379e

of this title or subsection (e) or (f) of this section or from any

combination of such requirements to permit the investigational use

of such devices by experts qualified by scientific training and

experience to investigate the safety and effectiveness of such

devices.

(B) The conditions prescribed pursuant to subparagraph (A) shall

include the following:

(i) A requirement that an application be submitted to the

Secretary before an exemption may be granted and that the

application be submitted in such form and manner as the Secretary

shall specify.

(ii) A requirement that the person applying for an exemption

for a device assure the establishment and maintenance of such

records, and the making of such reports to the Secretary of data

obtained as a result of the investigational use of the device

during the exemption, as the Secretary determines will enable him

to assure compliance with such conditions, review the progress of

the investigation, and evaluate the safety and effectiveness of

the device.

(iii) Such other requirements as the Secretary may determine to

be necessary for the protection of the public health and safety.

(C) Procedures and conditions prescribed pursuant to subparagraph

(A) for an exemption may appropriately vary depending on (i) the

scope and duration of clinical testing to be conducted under such

exemption, (ii) the number of human subjects that are to be

involved in such testing, (iii) the need to permit changes to be

made in the device subject to the exemption during testing

conducted in accordance with a clinical testing plan required under

paragraph (3)(A), and (iv) whether the clinical testing of such

device is for the purpose of developing data to obtain approval for

the commercial distribution of such device.

(3) Procedures and conditions prescribed pursuant to paragraph

(2)(A) shall require, as a condition to the exemption of any device

to be the subject of testing involving human subjects, that the

person applying for the exemption -

(A) submit a plan for any proposed clinical testing of the

device and a report of prior investigations of the device

(including, where appropriate, tests on animals) adequate to

justify the proposed clinical testing -

(i) to the local institutional review committee which has

been established in accordance with regulations of the

Secretary to supervise clinical testing of devices in the

facilities where the proposed clinical testing is to be

conducted, or

(ii) to the Secretary, if -

(I) no such committee exists, or

(II) the Secretary finds that the process of review by such

committee is inadequate (whether or not the plan for such

testing has been approved by such committee),

for review for adequacy to justify the commencement of such

testing; and, unless the plan and report are submitted to the

Secretary, submit to the Secretary a summary of the plan and a

report of prior investigations of the device (including, where

appropriate, tests on animals);

(B) promptly notify the Secretary (under such circumstances and

in such manner as the Secretary prescribes) of approval by a

local institutional review committee of any clinical testing plan

submitted to it in accordance with subparagraph (A);

(C) in the case of a device to be distributed to investigators

for testing, obtain signed agreements from each of such

investigators that any testing of the device involving human

subjects will be under such investigator's supervision and in

accordance with subparagraph (D) and submit such agreements to

the Secretary; and

(D) assure that informed consent will be obtained from each

human subject (or his representative) of proposed clinical

testing involving such device, except where subject to such

conditions as the Secretary may prescribe, the investigator

conducting or supervising the proposed clinical testing of the

device determines in writing that there exists a life threatening

situation involving the human subject of such testing which

necessitates the use of such device and it is not feasible to

obtain informed consent from the subject and there is not

sufficient time to obtain such consent from his representative.

The determination required by subparagraph (D) shall be concurred

in by a licensed physician who is not involved in the testing of

the human subject with respect to which such determination is made

unless immediate use of the device is required to save the life of

the human subject of such testing and there is not sufficient time

to obtain such concurrence.

(4)(A) An application, submitted in accordance with the

procedures prescribed by regulations under paragraph (2), for an

exemption for a device (other than an exemption from section 360f

of this title) shall be deemed approved on the thirtieth day after

the submission of the application to the Secretary unless on or

before such day the Secretary by order disapproves the application

and notifies the applicant of the disapproval of the application.

(B) The Secretary may disapprove an application only if he finds

that the investigation with respect to which the application is

submitted does not conform to procedures and conditions prescribed

under regulations under paragraph (2). Such a notification shall

contain the order of disapproval and a complete statement of the

reasons for the Secretary's disapproval of the application and

afford the applicant opportunity for an informal hearing on the

disapproval order.

(5) The Secretary may by order withdraw an exemption granted

under this subsection for a device if the Secretary determines that

the conditions applicable to the device under this subsection for

such exemption are not met. Such an order may be issued only after

opportunity for an informal hearing, except that such an order may

be issued before the provision of an opportunity for an informal

hearing if the Secretary determines that the continuation of

testing under the exemption with respect to which the order is to

be issued will result in an unreasonable risk to the public health.

(6)(A) Not later than 1 year after November 21, 1997, the

Secretary shall by regulation establish, with respect to a device

for which an exemption under this subsection is in effect,

procedures and conditions that, without requiring an additional

approval of an application for an exemption or the approval of a

supplement to such an application, permit -

(i) developmental changes in the device (including

manufacturing changes) that do not constitute a significant

change in design or in basic principles of operation and that are

made in response to information gathered during the course of an

investigation; and

(ii) changes or modifications to clinical protocols that do not

affect -

(I) the validity of data or information resulting from the

completion of an approved protocol, or the relationship of

likely patient risk to benefit relied upon to approve a

protocol;

(II) the scientific soundness of an investigational plan

submitted under paragraph (3)(A); or

(III) the rights, safety, or welfare of the human subjects

involved in the investigation.

(B) Regulations under subparagraph (A) shall provide that a

change or modification described in such subparagraph may be made

if -

(i) the sponsor of the investigation determines, on the basis

of credible information (as defined by the Secretary) that the

applicable conditions under subparagraph (A) are met; and

(ii) the sponsor submits to the Secretary, not later than 5

days after making the change or modification, a notice of the

change or modification.

(7)(A) In the case of a person intending to investigate the

safety or effectiveness of a class III device or any implantable

device, the Secretary shall ensure that the person has an

opportunity, prior to submitting an application to the Secretary or

to an institutional review committee, to submit to the Secretary,

for review, an investigational plan (including a clinical

protocol). If the applicant submits a written request for a

meeting with the Secretary regarding such review, the Secretary

shall, not later than 30 days after receiving the request, meet

with the applicant for the purpose of reaching agreement regarding

the investigational plan (including a clinical protocol). The

written request shall include a detailed description of the device,

a detailed description of the proposed conditions of use of the

device, a proposed plan (including a clinical protocol) for

determining whether there is a reasonable assurance of

effectiveness, and, if available, information regarding the

expected performance from the device.

(B) Any agreement regarding the parameters of an investigational

plan (including a clinical protocol) that is reached between the

Secretary and a sponsor or applicant shall be reduced to writing

and made part of the administrative record by the Secretary. Any

such agreement shall not be changed, except -

(i) with the written agreement of the sponsor or applicant; or

(ii) pursuant to a decision, made in accordance with

subparagraph (C) by the director of the office in which the

device involved is reviewed, that a substantial scientific issue

essential to determining the safety or effectiveness of the

device involved has been identified.

(C) A decision under subparagraph (B)(ii) by the director shall

be in writing, and may be made only after the Secretary has

provided to the sponsor or applicant an opportunity for a meeting

at which the director and the sponsor or applicant are present and

at which the director documents the scientific issue involved.

(h) Release of information respecting safety and effectiveness

(1) The Secretary shall promulgate regulations under which a

detailed summary of information respecting the safety and

effectiveness of a device which information was submitted to the

Secretary and which was the basis for -

(A) an order under section 360e(d)(1)(A) of this title

approving an application for premarket approval for the device or

denying approval of such an application or an order under section

360e(e) of this title withdrawing approval of such an application

for the device,

(B) an order under section 360e(f)(6)(A) of this title revoking

an approved protocol for the device, an order under section

360e(f)(6)(B) of this title declaring a protocol for the device

completed or not completed, or an order under section 360e(f)(7)

of this title revoking the approval of the device, or

(C) an order approving an application under subsection (g) of

this section for an exemption for the device from section 360f of

this title or an order disapproving, or withdrawing approval of,

an application for an exemption under such subsection for the

device,

shall be made available to the public upon issuance of the order.

Summaries of information made available pursuant to this paragraph

respecting a device shall include information respecting any

adverse effects on health of the device.

(2) The Secretary shall promulgate regulations under which each

advisory committee established under section 360e(g)(2)(B) of this

title shall make available to the public a detailed summary of

information respecting the safety and effectiveness of a device

which information was submitted to the advisory committee and which

was the basis for its recommendation to the Secretary made pursuant

to section 360e(g)(2)(A) of this title. A summary of information

upon which such a recommendation is based shall be made available

pursuant to this paragraph only after the issuance of the order

with respect to which the recommendation was made and each summary

shall include information respecting any adverse effect on health

of the device subject to such order.

(3) Except as provided in paragraph (4), any information

respecting a device which is made available pursuant to paragraph

(1) or (2) of this subsection (A) may not be used to establish the

safety or effectiveness of another device for purposes of this

chapter by any person other than the person who submitted the

information so made available, and (B) shall be made available

subject to subsection (c) of this section.

(4)(A) Any information contained in an application for premarket

approval filed with the Secretary pursuant to section 360e(c) of

this title (including information from clinical and preclinical

tests or studies that demonstrate the safety and effectiveness of a

device, but excluding descriptions of methods of manufacture and

product composition and other trade secrets) shall be available, 6

years after the application has been approved by the Secretary, for

use by the Secretary in -

(i) approving another device;

(ii) determining whether a product development protocol has

been completed, under section 360e of this title for another

device;

(iii) establishing a performance standard or special control

under this chapter; or

(iv) classifying or reclassifying another device under section

360c of this title and subsection (l)(2) of this section.

(B) The publicly available detailed summaries of information

respecting the safety and effectiveness of devices required by

paragraph (1)(A) shall be available for use by the Secretary as the

evidentiary basis for the agency actions described in subparagraph

(A).

(i) Proceedings of advisory panels and committees

Each panel under section 360c of this title and each advisory

committee established under section 360d(b)(5)(B) or 360e(g) of

this title or under subsection (f) of this section shall make and

maintain a transcript of any proceeding of the panel or committee.

Each such panel and committee shall delete from any transcript made

pursuant to this subsection information which under subsection (c)

of this section is to be considered confidential.

(j) Traceability

Except as provided in section 360i(e) of this title, no

regulation under this chapter may impose on a type or class of

device requirements for the traceability of such type or class of

device unless such requirements are necessary to assure the

protection of the public health.

(k) Research and development

The Secretary may enter into contracts for research, testing, and

demonstrations respecting devices and may obtain devices for

research, testing, and demonstration purposes without regard to

section 3324(a) and (b) of title 31 and section 5 of title 41.

(l) Transitional provisions for devices considered as new drugs

(1) Any device intended for human use -

(A) for which on May 28, 1976 (hereinafter in this subsection

referred to as the ''enactment date'') an approval of an

application submitted under section 355(b) of this title was in

effect;

(B) for which such an application was filed on or before the

enactment date and with respect to which application no order of

approval or refusing to approve had been issued on such date

under subsection (c) or (d) of such section;

(C) for which on the enactment date an exemption under

subsection (i) of such section was in effect;

(D) which is within a type of device described in subparagraph

(A), (B), or (C) and is substantially equivalent to another

device within that type;

(E) which the Secretary in a notice published in the Federal

Register before the enactment date has declared to be a new drug

subject to section 355 of this title; or

(F) with respect to which on the enactment date an action is

pending in a United States court under section 332, 333, or 334

of this title for an alleged violation of a provision of section

331 of this title which enforces a requirement of section 355 of

this title or for an alleged violation of section 355(a) of this

title,

is classified in class III unless the Secretary in response to a

petition submitted under paragraph (2) has classified such device

in class I or II.

(2) The Secretary may initiate the reclassification of a device

classified into class III under paragraph (1) of this subsection or

the manufacturer or importer of a device classified under paragraph

(1) may petition the Secretary (in such form and manner as he shall

prescribe) for the issuance of an order classifying the device in

class I or class II. Within thirty days of the filing of such a

petition, the Secretary shall notify the petitioner of any

deficiencies in the petition which prevent the Secretary from

making a decision on the petition. Except as provided in paragraph

(3)(D)(ii), within one hundred and eighty days after the filing of

a petition under this paragraph, the Secretary shall, after

consultation with the appropriate panel under section 360c of this

title, by order either deny the petition or order the

classification, in accordance with the criteria prescribed by

section 360c(a)(1)(A) of this title or 360c(a)(1)(B) of this title,

of the device in class I or class II.

(3)(A) In the case of a device which is described in paragraph

(1)(A) and which is in class III -

(i) such device shall on the enactment date be considered a

device with an approved application under section 360e of this

title, and

(ii) the requirements applicable to such device before the

enactment date under section 355 of this title shall continue to

apply to such device until changed by the Secretary as authorized

by this chapter.

(B) In the case of a device which is described in paragraph

(1)(B) and which is in class III, an application for such device

shall be considered as having been filed under section 360e of this

title on the enactment date. The period in which the Secretary

shall act on such application in accordance with section 360e(d)(1)

of this title shall be one hundred and eighty days from the

enactment date (or such greater period as the Secretary and the

applicant may agree upon after the Secretary has made the finding

required by section 360e(d)(1)(B)(i) of this title) less the number

of days in the period beginning on the date an application for such

device was filed under section 355 of this title and ending on the

enactment date. After the expiration of such period such device is

required, unless exempt under subsection (g) of this section, to

have in effect an approved application under section 360e of this

title.

(C) A device which is described in paragraph (1)(C) and which is

in class III shall be considered a new drug until the expiration of

the ninety-day period beginning on the date of the promulgation of

regulations under subsection (g) of this section. After the

expiration of such period such device is required, unless exempt

under subsection (g) of this section, to have in effect an approved

application under section 360e of this title.

(D)(i) Except as provided in clauses (ii) and (iii), a device

which is described in subparagraph (D), (E), or (F) of paragraph

(1) and which is in class III is required, unless exempt under

subsection (g) of this section, to have on and after sixty days

after the enactment date in effect an approved application under

section 360e of this title.

(ii) If -

(I) a petition is filed under paragraph (2) for a device

described in subparagraph (D), (E), or (F) of paragraph (1), or

(II) an application for premarket approval is filed under

section 360e of this title for such a device,

within the sixty-day period beginning on the enactment date (or

within such greater period as the Secretary, after making the

finding required under section 360e(d)(1)(B) of this title, and the

petitioner or applicant may agree upon), the Secretary shall act on

such petition or application in accordance with paragraph (2) or

section 360e of this title except that the period within which the

Secretary must act on the petition or application shall be within

the one hundred and twenty-day period beginning on the date the

petition or application is filed. If such a petition or

application is filed within such sixty-day (or greater) period,

clause (i) of this subparagraph shall not apply to such device

before the expiration of such one hundred and twenty-day period, or

if such petition is denied or such application is denied approval,

before the date of such denial, whichever occurs first.

(iii) In the case of a device which is described in subparagraph

(E) of paragraph (1), which the Secretary in a notice published in

the Federal Register after March 31, 1976, declared to be a new

drug subject to section 355 of this title, and which is in class

III -

(I) the device shall, after eighteen months after the enactment

date, have in effect an approved application under section 360e

of this title unless exempt under subsection (g) of this section,

and

(II) the Secretary may, during the period beginning one hundred

and eighty days after the enactment date and ending eighteen

months after such date, restrict the use of the device to

investigational use by experts qualified by scientific training

and experience to investigate the safety and effectiveness of

such device, and to investigational use in accordance with the

requirements applicable under regulations under subsection (g) of

this section to investigational use of devices granted an

exemption under such subsection.

If the requirements under subsection (g) of this section are made

applicable to the investigational use of such a device, they shall

be made applicable in such a manner that the device shall be made

reasonably available to physicians meeting appropriate

qualifications prescribed by the Secretary.

(4) Repealed. Pub. L. 105-115, title I, Sec. 125(b)(2)(E), Nov.

21, 1997, 111 Stat. 2325.

(5)(A) Before December 1, 1991, the Secretary shall by order

require manufacturers of devices described in paragraph (1), which

are subject to revision of classification under subparagraph (B),

to submit to the Secretary a summary of and citation to any

information known or otherwise available to the manufacturers

respecting the devices, including adverse safety or effectiveness

information which has not been submitted under section 360i of this

title. The Secretary may require a manufacturer to submit the

adverse safety or effectiveness data for which a summary and

citation were submitted, if such data are available to the

manufacturer.

(B) Except as provided in subparagraph (C), after the issuance of

an order under subparagraph (A) but before December 1, 1992, the

Secretary shall publish a regulation in the Federal Register for

each device which is classified in class III under paragraph (1)

revising the classification of the device so that the device is

classified into class I or class II, unless the regulation requires

the device to remain in class III. In determining whether to revise

the classification of a device or to require a device to remain in

class III, the Secretary shall apply the criteria set forth in

section 360c(a) of this title. Before the publication of a

regulation requiring a device to remain in class III or revising

its classification, the Secretary shall publish a proposed

regulation respecting the classification of a device under this

subparagraph and provide an opportunity for the submission of

comments on any such regulation. No regulation under this

subparagraph requiring a device to remain in class III or revising

its classification may take effect before the expiration of 90 days

from the date of the publication in the Federal Register of the

proposed regulation.

(C) The Secretary may by notice published in the Federal Register

extend the period prescribed by subparagraph (B) for a device for

an additional period not to exceed 1 year.

(m) Humanitarian device exemption

(1) To the extent consistent with the protection of the public

health and safety and with ethical standards, it is the purpose of

this subsection to encourage the discovery and use of devices

intended to benefit patients in the treatment and diagnosis of

diseases or conditions that affect fewer than 4,000 individuals in

the United States.

(2) The Secretary may grant a request for an exemption from the

effectiveness requirements of sections 360d and 360e of this title

for a device for which the Secretary finds that -

(A) the device is designed to treat or diagnose a disease or

condition that affects fewer than 4,000 individuals in the United

States,

(B) the device would not be available to a person with a

disease or condition referred to in subparagraph (A) unless the

Secretary grants such an exemption and there is no comparable

device, other than under this exemption, available to treat or

diagnose such disease or condition, and

(C) the device will not expose patients to an unreasonable or

significant risk of illness or injury and the probable benefit to

health from the use of the device outweighs the risk of injury or

illness from its use, taking into account the probable risks and

benefits of currently available devices or alternative forms of

treatment.

The request shall be in the form of an application submitted to the

Secretary. Not later than 75 days after the date of the receipt of

the application, the Secretary shall issue an order approving or

denying the application.

(3) No person granted an exemption under paragraph (2) with

respect to a device may sell the device for an amount that exceeds

the costs of research and development, fabrication, and

distribution of the device.

(4) Devices granted an exemption under paragraph (2) may only be

used -

(A) in facilities that have established, in accordance with

regulations of the Secretary, a local institutional review

committee to supervise clinical testing of devices in the

facilities, and

(B) if, before the use of a device, an institutional review

committee approves the use in the treatment or diagnosis of a

disease or condition referred to in paragraph (2)(A), unless a

physician determines in an emergency situation that approval from

a local institutional review committee can not be obtained in

time to prevent serious harm or death to a patient.

In a case described in subparagraph (B) in which a physician uses a

device without an approval from an institutional review committee,

the physician shall, after the use of the device, notify the

chairperson of the local institutional review committee of such

use. Such notification shall include the identification of the

patient involved, the date on which the device was used, and the

reason for the use.

(5) The Secretary may require a person granted an exemption under

paragraph (2) to demonstrate continued compliance with the

requirements of this subsection if the Secretary believes such

demonstration to be necessary to protect the public health or if

the Secretary has reason to believe that the criteria for the

exemption are no longer met.

(6) The Secretary may suspend or withdraw an exemption from the

effectiveness requirements of sections 360d and 360e of this title

for a humanitarian device only after providing notice and an

opportunity for an informal hearing.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 520, as added Pub. L. 94-295, Sec. 2,

May 28, 1976, 90 Stat. 565; amended Pub. L. 101-629, Sec. 3(b)(2),

4(b)(2), 5(c)(2), 6(b)(2), 11, 14(a), 18(e), (f), Nov. 28, 1990,

104 Stat. 4514, 4516, 4518, 4519, 4522, 4524, 4529; Pub. L.

102-571, title I, Sec. 107(10), Oct. 29, 1992, 106 Stat. 4499; Pub.

L. 105-115, title I, Sec. 125(b)(2)(E), title II, Sec. 201(a), 203,

216(a)(1), title IV, Sec. 410(a), Nov. 21, 1997, 111 Stat. 2325,

2332, 2334, 2349, 2372.)

-REFTEXT-

REFERENCES IN TEXT

Section 14 of the Federal Advisory Committee Act, referred to in

subsec. (f)(3), is section 14 of Pub. L. 92-463, which is set out

in the Appendix to Title 5, Government Organization and Employees.

-COD-

CODIFICATION

In subsec. (k), ''section 3324(a) and (b) of title 31''

substituted for reference to section 3648 of the Revised Statutes

(31 U.S.C. 529) on authority of Pub. L. 97-258, Sec. 4(b), Sept.

13, 1982, 96 Stat. 1067, the first section of which enacted Title

31, Money and Finance.

-MISC3-

AMENDMENTS

1997 - Subsec. (f)(1)(B)(iii). Pub. L. 105-115, Sec. 410(a),

added cl. (iii).

Subsec. (g)(6), (7). Pub. L. 105-115, Sec. 201(a), added pars.

(6) and (7).

Subsec. (h)(4). Pub. L. 105-115, Sec. 216(a)(1), amended par. (4)

generally. Prior to amendment, par. (4) related to premarket

approval of devices.

Subsec. (l). Pub. L. 105-115, Sec. 125(b)(2)(E), struck out ''or

antibiotic drugs'' after ''new drugs'' in heading.

Subsec. (l)(4). Pub. L. 105-115, Sec. 125(b)(2)(E), struck out

par. (4) which read as follows: ''Any device intended for human use

which on the enactment date was subject to the requirements of

section 357 of this title shall be subject to such requirements as

follows:

''(A) In the case of such a device which is classified into

class I, such requirements shall apply to such device until the

effective date of the regulation classifying the device into such

class.

''(B) In the case of such a device which is classified into

class II, such requirements shall apply to such device until the

effective date of a performance standard applicable to the device

under section 360d of this title.

''(C) In the case of such a device which is classified into

class III, such requirements shall apply to such device until the

date on which the device is required to have in effect an

approved application under section 360e of this title.''

Subsec. (m)(2). Pub. L. 105-115, Sec. 203(1), inserted at end

''The request shall be in the form of an application submitted to

the Secretary. Not later than 75 days after the date of the receipt

of the application, the Secretary shall issue an order approving or

denying the application.''

Subsec. (m)(4). Pub. L. 105-115, Sec. 203(2)(B), inserted at end

''In a case described in subparagraph (B) in which a physician uses

a device without an approval from an institutional review

committee, the physician shall, after the use of the device, notify

the chairperson of the local institutional review committee of such

use. Such notification shall include the identification of the

patient involved, the date on which the device was used, and the

reason for the use.''

Subsec. (m)(4)(B). Pub. L. 105-115, Sec. 203(2)(A), inserted

before period at end '', unless a physician determines in an

emergency situation that approval from a local institutional review

committee can not be obtained in time to prevent serious harm or

death to a patient''.

Subsec. (m)(5). Pub. L. 105-115, Sec. 203(3), amended par. (5)

generally. Prior to amendment, par. (5) read as follows: ''An

exemption under paragraph (2) shall be for a term of 18 months and

may only be initially granted in the 5-year period beginning on the

date regulations under paragraph (6) take effect. The Secretary

may extend such an exemption for a period of 18 months if the

Secretary is able to make the findings set forth in paragraph (2)

and if the applicant supplies information demonstrating compliance

with paragraph (3). An exemption may be extended more than once and

may be extended after the expiration of such 5-year period.''

Subsec. (m)(6). Pub. L. 105-115, Sec. 203(4), amended par. (6)

generally. Prior to amendment, par. (6) read as follows: ''Within

one year of November 28, 1990, the Secretary shall issue

regulations to implement this subsection.''

1992 - Subsec. (g)(2)(A). Pub. L. 102-571 substituted ''379e''

for ''376''.

1990 - Subsec. (c). Pub. L. 101-629, Sec. 11(1), substituted

''from class III to class II or class I'' for ''under section 360c

of this title from class III to class II'' and inserted ''(1) in

accordance with subsection (h) of this section, and (2)'' after

''except''.

Subsec. (f)(1)(A). Pub. L. 101-629, Sec. 18(e), inserted

''pre-production design validation (including a process to assess

the performance of a device but not including an evaluation of the

safety or effectiveness of a device),'' after ''manufacture,''.

Subsec. (h)(3). Pub. L. 101-629, Sec. 11(2)(A), substituted

''Except as provided in paragraph (4), any'' for ''Any''.

Subsec. (h)(4). Pub. L. 101-629, Sec. 11(2)(B), added par. (4).

Subsec. (i). Pub. L. 101-629, Sec. 6(b)(2), substituted ''section

360d(b)(5)(B)'' for ''section 360d(g)(5)(B)''.

Subsec. (j). Pub. L. 101-629, Sec. 3(b)(2), substituted ''Except

as provided in section 360i(e) of this title, no'' for ''No''.

Subsec. (l)(2). Pub. L. 101-629, Sec. 18(f), struck out ''and

after affording the petitioner an opportunity for an informal

hearing'' after ''under this paragraph''.

Pub. L. 101-629, Sec. 5(c)(2), substituted ''The Secretary may

initiate the reclassification of a device classified into class III

under paragraph (1) of this subsection or the manufacturer'' for

''The manufacturer''.

Subsec. (l)(5). Pub. L. 101-629, Sec. 4(b)(2), added par. (5).

Subsec. (m). Pub. L. 101-629, Sec. 14(a), added subsec. (m).

EFFECTIVE DATE OF 1997 AMENDMENT

Amendment by sections 201(a), 203, 216(a)(1), and 410(a) of Pub.

L. 105-115 effective 90 days after Nov. 21, 1997, except as

otherwise provided, see section 501 of Pub. L. 105-115, set out as

a note under section 321 of this title.

EFFECTIVE DATE OF 1990 AMENDMENT

Section 14(b) of Pub. L. 101-629 provided that: ''Subsection (m)

of section 520 of the Federal Food, Drug, and Cosmetic Act (21

U.S.C. 360j(m)), as added by the amendment made by subsection (a),

shall take effect on the effective date of the regulations issued

by the Secretary under paragraph (6) of such subsection.''

GUIDANCE REGARDING PEDIATRIC DEVICES

Pub. L. 107-250, title II, Sec. 213, Oct. 26, 2002, 116 Stat.

1614, provided that: ''Not later than 270 days after the date of

the enactment of this Act (Oct. 26, 2002), the Secretary of Health

and Human Services shall issue guidance on the following:

''(1) The type of information necessary to provide reasonable

assurance of the safety and effectiveness of medical devices

intended for use in pediatric populations.

''(2) Protections for pediatric subjects in clinical

investigations of the safety or effectiveness of such devices.''

REPORT ON HUMANITARIAN DEVICE EXEMPTIONS

Section 14(c) of Pub. L. 101-629 directed Secretary of Health and

Human Services, within 4 years after issuance of regulations under

21 U.S.C. 360j(m)(6), to report to Congress on types of devices

exempted, an evaluation of effects of such section, and a

recommendation on extension of the section.

REFERENCES IN OTHER LAWS TO GS-16, 17, OR 18 PAY RATES

References in laws to the rates of pay for GS-16, 17, or 18, or

to maximum rates of pay under the General Schedule, to be

considered references to rates payable under specified sections of

Title 5, Government Organization and Employees, see section 529

(title I, Sec. 101(c)(1)) of Pub. L. 101-509, set out in a note

under section 5376 of Title 5.

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in sections 331, 333, 351, 352, 353,

360c, 360d, 360e, 360g, 360i, 360bbb, 374, 379i, 379j, 381, 382,

383, 1604 of this title; title 42 section 1395l.

-CITE-

21 USC Sec. 360k 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 360k. State and local requirements respecting devices

-STATUTE-

(a) General rule

Except as provided in subsection (b) of this section, no State or

political subdivision of a State may establish or continue in

effect with respect to a device intended for human use any

requirement -

(1) which is different from, or in addition to, any requirement

applicable under this chapter to the device, and

(2) which relates to the safety or effectiveness of the device

or to any other matter included in a requirement applicable to

the device under this chapter.

(b) Exempt requirements

Upon application of a State or a political subdivision thereof,

the Secretary may, by regulation promulgated after notice and

opportunity for an oral hearing, exempt from subsection (a) of this

section, under such conditions as may be prescribed in such

regulation, a requirement of such State or political subdivision

applicable to a device intended for human use if -

(1) the requirement is more stringent than a requirement under

this chapter which would be applicable to the device if an

exemption were not in effect under this subsection; or

(2) the requirement -

(A) is required by compelling local conditions, and

(B) compliance with the requirement would not cause the

device to be in violation of any applicable requirement under

this chapter.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 521, as added Pub. L. 94-295, Sec. 2,

May 28, 1976, 90 Stat. 574.)

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in section 360g of this title.

-CITE-

21 USC Sec. 360l 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 360l. Postmarket surveillance

-STATUTE-

(a) In general

The Secretary may by order require a manufacturer to conduct

postmarket surveillance for any device of the manufacturer which is

a class II or class III device the failure of which would be

reasonably likely to have serious adverse health consequences or

which is intended to be -

(1) implanted in the human body for more than one year, or

(2) a life sustaining or life supporting device used outside a

device user facility.

(b) Surveillance approval

Each manufacturer required to conduct a surveillance of a device

shall, within 30 days of receiving an order from the Secretary

prescribing that the manufacturer is required under this section to

conduct such surveillance, submit, for the approval of the

Secretary, a plan for the required surveillance. The Secretary,

within 60 days of the receipt of such plan, shall determine if the

person designated to conduct the surveillance has appropriate

qualifications and experience to undertake such surveillance and if

the plan will result in the collection of useful data that can

reveal unforeseen adverse events or other information necessary to

protect the public health. The Secretary, in consultation with the

manufacturer, may by order require a prospective surveillance

period of up to 36 months. Any determination by the Secretary that

a longer period is necessary shall be made by mutual agreement

between the Secretary and the manufacturer or, if no agreement can

be reached, after the completion of a dispute resolution process as

described in section 360bbb-1 of this title.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 522, as added Pub. L. 101-629, Sec.

10, Nov. 28, 1990, 104 Stat. 4521; amended Pub. L. 102-300, Sec.

3(b), June 16, 1992, 106 Stat. 239; Pub. L. 105-115, title II, Sec.

212, Nov. 21, 1997, 111 Stat. 2346.)

-MISC1-

AMENDMENTS

1997 - Pub. L. 105-115 amended section generally, substituting

present provisions for former provisions which related to required

surveillance, discretionary surveillance, and surveillance

approval.

1992 - Subsec. (b). Pub. L. 102-300 substituted ''(a)(1)'' for

''(a)'', inserted comma after ''commerce'', and inserted after

first sentence ''Each manufacturer required to conduct a

surveillance of a device under subsection (a)(2) of this section

shall, within 30 days after receiving notice that the manufacturer

is required to conduct such surveillance, submit, for the approval

of the Secretary, a protocol for the required surveillance.''

EFFECTIVE DATE OF 1997 AMENDMENT

Section 212 of Pub. L. 105-115 provided in part that the

amendment made by that section is effective 90 days after Nov. 21,

1997.

STUDY BY INSTITUTE OF MEDICINE OF POSTMARKET SURVEILLANCE REGARDING

PEDIATRIC POPULATIONS

Pub. L. 107-250, title II, Sec. 212, Oct. 26, 2002, 116 Stat.

1614, provided that:

''(a) In General. - The Secretary of Health and Human Services

(referred to in this section as the 'Secretary') shall request the

Institute of Medicine to enter into an agreement with the Secretary

under which such Institute conducts a study for the purpose of

determining whether the system under the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 301 et seq.) for the postmarket

surveillance of medical devices provides adequate safeguards

regarding the use of devices in pediatric populations.

''(b) Certain Matters. - The Secretary shall ensure that

determinations made in the study under subsection (a) include

determinations of -

''(1) whether postmarket surveillance studies of implanted

medical devices are of long enough duration to evaluate the

impact of growth and development for the number of years that the

child will have the implant, and whether the studies are adequate

to evaluate how children's active lifestyles may affect the

failure rate and longevity of the implant; and

''(2) whether the postmarket surveillance by the Food and Drug

Administration of medical devices used in pediatric populations

is sufficient to provide adequate safeguards for such

populations, taking into account the Secretary's monitoring of

commitments made at the time of approval of medical devices, such

as phase IV trials, and the Secretary's monitoring and use of

adverse reaction reports, registries, and other postmarket

surveillance activities.

''(c) Report to Congress. - The Secretary shall ensure that, not

later than four years after the date of the enactment of this Act

(Oct. 26, 2002), a report describing the findings of the study

under subsection (a) is submitted to the Congress. The report shall

include any recommendations of the Secretary for administrative or

legislative changes to the system of postmarket surveillance

referred to in such subsection.''

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in sections 331, 352 of this title.

-CITE-

21 USC Sec. 360m 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part A - Drugs and Devices

-HEAD-

Sec. 360m. Accredited persons

-STATUTE-

(a) In general

(1) Review and classification of devices

Not later than 1 year after November 21, 1997, the Secretary

shall, subject to paragraph (3), accredit persons for the purpose

of reviewing reports submitted under section 360(k) of this title

and making recommendations to the Secretary regarding the initial

classification of devices under section 360c(f)(1) of this title.

(2) Requirements regarding review

(A) In general

In making a recommendation to the Secretary under paragraph

(1), an accredited person shall notify the Secretary in writing

of the reasons for the recommendation.

(B) Time period for review

Not later than 30 days after the date on which the Secretary

is notified under subparagraph (A) by an accredited person with

respect to a recommendation of an initial classification of a

device, the Secretary shall make a determination with respect

to the initial classification.

(C) Special rule

The Secretary may change the initial classification under

section 360c(f)(1) of this title that is recommended under

paragraph (1) by an accredited person, and in such case shall

provide to such person, and the person who submitted the report

under section 360(k) of this title for the device, a statement

explaining in detail the reasons for the change.

(3) Certain devices

(A) In general

An accredited person may not be used to perform a review of -

(i) a class III device;

(ii) a class II device which is intended to be permanently

implantable or life sustaining or life supporting; or

(iii) a class II device which requires clinical data in the

report submitted under section 360(k) of this title for the

device, except that the number of class II devices to which

the Secretary applies this clause for a year, less the number

of such reports to which clauses (i) and (ii) apply, may not

exceed 6 percent of the number that is equal to the total

number of reports submitted to the Secretary under such

section for such year less the number of such reports to

which such clauses apply for such year.

(B) Adjustment

In determining for a year the ratio described in subparagraph

(A)(iii), the Secretary shall not include in the numerator

class III devices that the Secretary reclassified into class

II, and the Secretary shall include in the denominator class II

devices for which reports under section 360(k) of this title

were not required to be submitted by reason of the operation of

section 360(m) of this title.

(b) Accreditation

(1) Programs

The Secretary shall provide for such accreditation through

programs administered by the Food and Drug Administration, other

government agencies, or by other qualified nongovernment

organizations.

(2) Accreditation

(A) In general

Not later than 180 days after November 21, 1997, the

Secretary shall establish and publish in the Federal Register

criteria to accredit or deny accreditation to persons who

request to perform the duties specified in subsection (a) of

this section. The Secretary shall respond to a request for

accreditation within 60 days of the receipt of the request.

The accreditation of such person shall specify the particular

activities under subsection (a) of this section for which such

person is accredited.

(B) Withdrawal of accreditation

The Secretary may suspend or withdraw accreditation of any

person accredited under this paragraph, after providing notice

and an opportunity for an informal hearing, when such person is

substantially not in compliance with the requirements of this

section or poses a threat to public health or fails to act in a

manner that is consistent with the purposes of this section.

(C) Performance auditing

To ensure that persons accredited under this section will

continue to meet the standards of accreditation, the Secretary

shall -

(i) make onsite visits on a periodic basis to each

accredited person to audit the performance of such person;

and

(ii) take such additional measures as the Secretary

determines to be appropriate.

(D) Annual report

The Secretary shall include in the annual report required

under section 393(g) of this title the names of all accredited

persons and the particular activities under subsection (a) of

this section for which each such person is accredited and the

name of each accredited person whose accreditation has been

withdrawn during the year.

(3) Qualifications

An accredited person shall, at a minimum, meet the following

requirements:

(A) Such person may not be an employee of the Federal

Government.

(B) Such person shall be an independent organization which is

not owned or controlled by a manufacturer, supplier, or vendor

of devices and which has no organizational, material, or

financial affiliation with such a manufacturer, supplier, or

vendor.

(C) Such person shall be a legally constituted entity

permitted to conduct the activities for which it seeks

accreditation.

(D) Such person shall not engage in the design, manufacture,

promotion, or sale of devices.

(E) The operations of such person shall be in accordance with

generally accepted professional and ethical business practices

and shall agree in writing that as a minimum it will -

(i) certify that reported information accurately reflects

data reviewed;

(ii) limit work to that for which competence and capacity

are available;

(iii) treat information received, records, reports, and

recommendations as proprietary information;

(iv) promptly respond and attempt to resolve complaints

regarding its activities for which it is accredited; and

(v) protect against the use, in carrying out subsection (a)

of this section with respect to a device, of any officer or

employee of the person who has a financial conflict of

interest regarding the device, and annually make available to

the public disclosures of the extent to which the person, and

the officers and employees of the person, have maintained

compliance with requirements under this clause relating to

financial conflicts of interest.

(4) Selection of accredited persons

The Secretary shall provide each person who chooses to use an

accredited person to receive a section 360(k) of this title

report a panel of at least two or more accredited persons from

which the regulated person may select one for a specific

regulatory function.

(5) Compensation of accredited persons

Compensation for an accredited person shall be determined by

agreement between the accredited person and the person who

engages the services of the accredited person, and shall be paid

by the person who engages such services.

(c) Duration

The authority provided by this section terminates October 1,

2007.

(d) Report

Not later than January 10, 2007, the Secretary shall conduct a

study based on the experience under the program under this section

and submit to the Committee on Energy and Commerce of the House of

Representatives, and the Committee on Health, Education, Labor, and

Pensions of the Senate, a report describing the findings of the

study. The objectives of the study shall include determining -

(1) the number of devices reviewed under this section;

(2) the number of devices reviewed under this section that were

ultimately cleared by the Secretary;

(3) the number of devices reviewed under this section that were

ultimately not cleared by the Secretary;

(4) the average time period for a review under this section

(including the time it takes for the Secretary to review a

recommendation of an accredited person under subsection (a) of

this section and determine the initial device classification);

(5) the average time period identified in paragraph (4)

compared to the average time period for review of devices solely

by the Secretary pursuant to section 360(k) of this title;

(6) if there is a difference in the average time period under

paragraph (4) and the average time period under paragraph (5),

the reasons for such difference;

(7) whether the quality of reviews under this section for

devices for which no guidance has been issued is qualitatively

inferior to reviews by the Secretary for devices for which no

guidance has been issued;

(8) whether the quality of reviews under this section of

devices for which no guidance has been issued is qualitatively

inferior to reviews under this section of devices for which

guidance has been issued;

(9) whether this section has in any way jeopardized or improved

the public health;

(10) any impact of this section on resources available to the

Secretary to review reports under section 360(k) of this title;

and

(11) any suggestions for continuation, modification (including

contraction or expansion of device eligibility), or termination

of this section that the Secretary determines to be appropriate.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 523, as added Pub. L. 105-115, title

II, Sec. 210(a), Nov. 21, 1997, 111 Stat. 2342; amended Pub. L.

107-250, title II, Sec. 202, Oct. 26, 2002, 116 Stat. 1609.)

-MISC1-

AMENDMENTS

2002 - Subsec. (c). Pub. L. 107-250, Sec. 202(1), substituted

''The authority provided by this section terminates October 1,

2007.'' for ''The authority provided by this section terminates -

''(1) 5 years after the date on which the Secretary notifies

Congress that at least 2 persons accredited under subsection (b)

of this section are available to review at least 60 percent of

the submissions under section 360(k) of this title, or

''(2) 4 years after the date on which the Secretary notifies

Congress that the Secretary has made a determination described in

paragraph (2)(B) of subsection (a) of this section for at least

35 percent of the devices that are subject to review under

paragraph (1) of such subsection,

whichever occurs first.''

Subsec. (d). Pub. L. 107-250, Sec. 202(2), added subsec. (d).

EFFECTIVE DATE

Section effective 90 days after Nov. 21, 1997, except as

otherwise provided, see section 501 of Pub. L. 105-115, set out as

a note under section 321 of this title.

REPORTS ON PROGRAM OF ACCREDITATION

Section 210(d) of Pub. L. 105-115 provided that:

''(1) Comptroller general. -

''(A) Implementation of program. - Not later than 5 years after

the date of the enactment of this Act (Nov. 21, 1997), the

Comptroller General of the United States shall submit to the

Committee on Commerce (now Committee on Energy and Commerce) of

the House of Representatives and the Committee on Labor and Human

Resources of the Senate a report describing the extent to which

the program of accreditation required by the amendment made by

subsection (a) (enacting this section) has been implemented.

''(B) Evaluation of program. - Not later than 6 months prior to

the date on which, pursuant to subsection (c) of section 523 of

the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360m(c)) (as

added by subsection (a)), the authority provided under subsection

(a) of such section will terminate, the Comptroller General shall

submit to the Committee on Commerce (now Committee on Energy and

Commerce) of the House of Representatives and the Committee on

Labor and Human Resources of the Senate a report describing the

use of accredited persons under such section 523, including an

evaluation of the extent to which such use assisted the Secretary

in carrying out the duties of the Secretary under such Act (21

U.S.C. 301 et seq.) with respect to devices, and the extent to

which such use promoted actions which are contrary to the

purposes of such Act.

''(2) Inclusion of certain devices within program. - Not later

than 3 years after the date of the enactment of this Act (Nov. 21,

1997), the Secretary of Health and Human Services shall submit to

the Committee on Commerce of the House of Representatives and the

Committee on Labor and Human Resources of the Senate a report

providing a determination by the Secretary of whether, in the

program of accreditation established pursuant to the amendment made

by subsection (a), the limitation established in clause (iii) of

section 523(a)(3)(A) of the Federal Food, Drug, and Cosmetic Act

(21 U.S.C. 360m(a)(3)(A)) (relating to class II devices for which

clinical data are required in reports under section 510(k) (21

U.S.C. 360(k))) should be removed.''

-SECREF-

SECTION REFERRED TO IN OTHER SECTIONS

This section is referred to in sections 331, 335a, 360, 360c,

374, 379j of this title.

-CITE-

21 USC Part B - Drugs for Rare Diseases or Conditions 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part B - Drugs for Rare Diseases or Conditions

.

-HEAD-

Part B - Drugs for Rare Diseases or Conditions

-SECREF-

PART REFERRED TO IN OTHER SECTIONS

This part is referred to in title 42 sections 236, 1395l.

-CITE-

21 USC Sec. 360aa 01/06/03

-EXPCITE-

TITLE 21 - FOOD AND DRUGS

CHAPTER 9 - FEDERAL FOOD, DRUG, AND COSMETIC ACT

SUBCHAPTER V - DRUGS AND DEVICES

Part B - Drugs for Rare Diseases or Conditions

-HEAD-

Sec. 360aa. Recommendations for investigations of drugs for rare

diseases or conditions

-STATUTE-

(a) Request by sponsor; response by Secretary

The sponsor of a drug for a disease or condition which is rare in

the States may request the Secretary to provide written

recommendations for the non-clinical and clinical investigations

which must be conducted with the drug before -

(1) it may be approved for such disease or condition under

section 355 of this title, or

(2) if the drug is a biological product, it may be licensed for

such disease or condition under section 262 of title 42.

If the Secretary has reason to believe that a drug for which a

request is made under this section is a drug for a disease or

condition which is rare in the States, the Secretary shall provide

the person making the request written recommendations for the

non-clinical and clinical investigations which the Secretary

believes, on the basis of information available to the Secretary at

the time of the request under this section, would be necessary for

approval of such drug for such disease or condition under section

355 of this title or licensing of such drug for such disease or

condition under section 262 of title 42.

(b) Regulations

The Secretary shall by regulation promulgate procedures for the

implementation of subsection (a) of this section.

-SOURCE-

(June 25, 1938, ch. 675, Sec. 525, as added Pub. L. 97-414, Sec.

2(a), Jan. 4, 1983, 96 Stat. 2049; amended Pub. L. 99-91, Sec.

3(a)(1), Aug. 15, 1985, 99 Stat. 387; Pub. L. 105-115, title I,

Sec. 125(b)(2)(F), (G), Nov. 21, 1997, 111 Stat. 2325, 2326.)

-MISC1-

AMENDMENTS

1997 - Subsec. (a). Pub. L. 105-115, Sec. 125(b)(2)(G), struck

out '', certification of such drug for such disease or condition

under section 357 of this title,'' before ''or licensing of such

drug'' in closing provisions.

Subsec. (a)(1) to (3). Pub. L. 105-115, Sec. 125(b)(2)(F),

inserted ''or'' at end of par. (1), redesignated par. (3) as (2),

and struck out former par. (2), which read as follows: ''if the

drug is an antibiotic, it may be certified for such disease or

condition under section 357 of this title, or''.

1985 - Subsec. (a). Pub. L. 99-91 struck out ''or'' at end of

par. (1), inserted par. (2), redesignated former par. (2) as (3)

and struck out ''before'' after ''product,'', and in last sentence

inserted provisions relating to certification of such drug for

disease or condition under section 357 of this title and

substituted ''licensing of such drug for such disease or condition

under section 262 of title 42'' for ''licensing under section 262

of title 42 for such disease or condition''.

EFFECTIVE DATE OF 1985 AMENDMENT

Section 8 of Pub. L. 99-91 provided that:

''(a) General Rule. - Except as provided in subsection (b), this

Act and the amendments made by this Act (amending this section,

sections 360bb, 360cc, and 360ee of this title, and sections 295g-1

and 6022 of Title 42, The Public Health and Welfare, and enacting

provisions set out as notes under section 301 of this title and

section 236 of Title 42) shall take effect October 1, 1985.

''(b) Exception. - The amendments made by sections 2, 3, and 6(a)

(amending this section and sections 360bb and 360cc of this title)

shall take effect on the date of the enactment of this Act (Aug.

15, 1985). The amendment made by section 6(b) (amending section

6022 of Title 42) shall take effect October 19, 1984. The

amendments made by section 7 (amending section 295g-1 of Title 42)

shall take effect October 1, 1984 and shall cease to be in effect

after September 30, 1985.''

STUDY

Pub. L. 100-290, Sec. 3(d), Apr. 18, 1988, 102 Stat. 91, directed

Secretary of Health and Human Services to conduct a study to

determine whether the application of subchapter B of chapter V of

the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 360aa et seq.

(relating to drugs for rare diseases and conditions), and 26 U.S.C.

28 (relating to tax credit) to medical devices or medical foods for

rare diseases or conditions or to both was needed to encourage

development of such devices and foods and report results of the

study to Congress not later than one year after Apr. 18, 1988.

CONGRESSIONAL FINDINGS

Section 1(b) of Pub. L. 97-414 provided that: ''The Congress

finds that -

''(1) there are many diseases and conditions, such as

Huntington's disease, myoclonus, ALS (Lou Gehrig's disease),

Tourette syndrome, and muscular dystrophy which affect such small

numbers of individuals residing in the United States that the

diseases and conditions are considered rare in the United States;

''(2) adequate drugs for many of such diseases and conditions

have not been developed;

''(3) drugs for these diseases and conditions are commonly

referred to as 'orphan drugs';

''(4) because so few individuals are affected by any one rare

disease or condition, a pharmaceutical company which develops an

orphan drug may reasonably expect the drug to generate relatively

small sales in comparison to the cost of developing the drug and

consequently to incur a financial loss;

''(5) there is reason to believe that some promising orphan

drugs will not be developed unless changes are made in the

applicable Federal laws to reduce the costs of developing such

drugs and to provide financial incentives to develop such drugs;

and

''(6) it is in the public interest to provide such changes and

incentives for the development of orphan drugs.''

-CITE-

21 USC Sec. 360bb 01/06/03