PUBLIC LAW 107–109—JAN. 4, 2002

BEST PHARMACEUTICALS FOR CHILDREN

ACT

115 STAT. 1408 PUBLIC LAW 107–109—JAN. 4, 2002

Public Law 107–109

107th Congress

An Act

To amend the Federal Food, Drug, and Cosmetic Act to improve the safety and

efficacy of pharmaceuticals for children.

Be it enacted by the Senate and House of Representatives of

the United States of America in Congress assembled,

SECTION 1. SHORT TITLE.

This Act may be cited as the ‘‘Best Pharmaceuticals for Children

Act’’.

SEC. 2. PEDIATRIC STUDIES OF ALREADY-MARKETED DRUGS.

Section 505A of the Federal Food, Drug, and Cosmetic Act

(21 U.S.C. 355a) is amended— (1) by striking subsection (b); and

(2) in subsection (c)— (A) by inserting after ‘‘the Secretary’’ the following:

‘‘determines that information relating to the use of an

approved drug in the pediatric population may produce

health benefits in that population and’’; and

(B) by striking ‘‘concerning a drug identified in the

list described in subsection (b)’’.

SEC. 3. RESEARCH FUND FOR THE STUDY OF DRUGS.

Part B of title IV of the Public Health Service Act (42 U.S.C.

284 et seq.) is amended— (1) by redesignating the second section 409C, relating to

clinical research (42 U.S.C. 284k), as section 409G;

(2) by redesignating the second section 409D, relating to

enhancement awards (42 U.S.C. 284l), as section 409H; and

(3) by adding at the end the following:

‘‘SEC. 409I. PROGRAM FOR PEDIATRIC STUDIES OF DRUGS.

‘‘(a) LIST OF DRUGS FOR WHICH PEDIATRIC STUDIES ARE

NEEDED.—

‘‘(1) IN GENERAL.—Not later than one year after the date

of enactment of this section, the Secretary, acting through

the Director of the National Institutes of Health and in consultation with the Commissioner of Food and Drugs and experts

in pediatric research, shall develop, prioritize, and publish an

annual list of approved drugs for which—

‘‘(A)(i) there is an approved application under section

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

U.S.C. 355(j));

‘‘(ii) there is a submitted application that could be

approved under the criteria of section 505(j) of the Federal

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

42 USC 284m.

21 USC 301 note.

Best

Pharmaceuticals

for Children Act.

Jan. 4, 2002

[S. 1789]

PUBLIC LAW 107–109—JAN. 4, 2002 115 STAT. 1409

‘‘(iii) there is no patent protection or market exclusivity

protection under the Federal Food, Drug, and Cosmetic

Act (21 U.S.C. 301 et seq.); or ‘‘(iv) there is a referral for inclusion on the list under

section 505A(d)(4)(C) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a(d)(4)(C)); and

‘‘(B) in the case of a drug referred to in clause (i),

(ii), or (iii) of subparagraph (A), additional studies are

needed to assess the safety and effectiveness of the use

of the drug in the pediatric population.

‘‘(2) CONSIDERATION OF AVAILABLE INFORMATION.—In developing and prioritizing the list under paragraph (1), the Secretary shall consider, for each drug on the list— ‘‘(A) the availability of information concerning the safe

and effective use of the drug in the pediatric population; ‘‘(B) whether additional information is needed;

‘‘(C) whether new pediatric studies concerning the drug

may produce health benefits in the pediatric population;

and ‘‘(D) whether reformulation of the drug is necessary. ‘‘(b) CONTRACTS FOR PEDIATRIC STUDIES.—The Secretary shall

award contracts to entities that have the expertise to conduct pediatric clinical trials (including qualified universities, hospitals, laboratories, contract research organizations, federally funded programs such as pediatric pharmacology research units, other public

or private institutions, or individuals) to enable the entities to

conduct pediatric studies concerning one or more drugs identified

in the list described in subsection (a).

‘‘(c) PROCESS FOR CONTRACTS AND LABELING CHANGES.—

‘‘(1) WRITTEN REQUEST TO HOLDERS OF APPROVED APPLICATIONS FOR DRUGS LACKING EXCLUSIVITY.—The Commissioner

of Food and Drugs, in consultation with the Director of the

National Institutes of Health, may issue a written request

(which shall include a timeframe for negotiations for an agreement) for pediatric studies concerning a drug identified in the

list described in subsection (a)(1)(A) (except clause (iv)) to all

holders of an approved application for the drug under section

505 of the Federal Food, Drug, and Cosmetic Act. Such a

written request shall be made in a manner equivalent to the

manner in which a written request is made under subsection

(a) or (b) of section 505A of the Federal Food, Drug, and

Cosmetic Act, including with respect to information provided

on the pediatric studies to be conducted pursuant to the request.

‘‘(2) REQUESTS FOR CONTRACT PROPOSALS.—If the Commissioner of Food and Drugs does not receive a response to a

written request issued under paragraph (1) within 30 days

of the date on which a request was issued, or if a referral

described in subsection (a)(1)(A)(iv) is made, the Secretary,

acting through the Director of the National Institutes of Health

and in consultation with the Commissioner of Food and Drugs,

shall publish a request for contract proposals to conduct the

pediatric studies described in the written request.

‘‘(3) DISQUALIFICATION.—A holder that receives a first right

of refusal shall not be entitled to respond to a request for

contract proposals under paragraph (2).

‘‘(4) GUIDANCE.—Not later than 270 days after the date

of enactment of this section, the Commissioner of Food and

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115 STAT. 1410 PUBLIC LAW 107–109—JAN. 4, 2002

Drugs shall promulgate guidance to establish the process for

the submission of responses to written requests under paragraph (1).

‘‘(5) CONTRACTS.—A contract under this section may be

awarded only if a proposal for the contract is submitted to

the Secretary in such form and manner, and containing such

agreements, assurances, and information as the Secretary

determines to be necessary to carry out this section.

‘‘(6) REPORTING OF STUDIES.—

‘‘(A) IN GENERAL.—On completion of a pediatric study

in accordance with a contract awarded under this section,

a report concerning the study shall be submitted to the

Director of the National Institutes of Health and the

Commissioner of Food and Drugs. The report shall include

all data generated in connection with the study.

‘‘(B) AVAILABILITY OF REPORTS.—Each report submitted

under subparagraph (A) shall be considered to be in the

public domain (subject to section 505A(d)(4)(D) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a(d)(4)(D))

and shall be assigned a docket number by the Commissioner of Food and Drugs. An interested person may submit

written comments concerning such pediatric studies to the

Commissioner of Food and Drugs, and the written comments shall become part of the docket file with respect

to each of the drugs.

‘‘(C) ACTION BY COMMISSIONER.—The Commissioner of

Food and Drugs shall take appropriate action in response

to the reports submitted under subparagraph (A) in accordance with paragraph (7).

‘‘(7) REQUESTS FOR LABELING CHANGE.—During the 180-

day period after the date on which a report is submitted under

paragraph (6)(A), the Commissioner of Food and Drugs shall—

‘‘(A) review the report and such other data as are

available concerning the safe and effective use in the pediatric population of the drug studied;

‘‘(B) negotiate with the holders of approved applications

for the drug studied for any labeling changes that the

Commissioner of Food and Drugs determines to be appropriate and requests the holders to make; and

‘‘(C)(i) place in the public docket file a copy of the

report and of any requested labeling changes; and

‘‘(ii) publish in the Federal Register a summary of

the report and a copy of any requested labeling changes.

‘‘(8) DISPUTE RESOLUTION.—

‘‘(A) REFERRAL TO PEDIATRIC ADVISORY SUBCOMMITTEE

OF THE ANTI-INFECTIVE DRUGS ADVISORY COMMITTEE.—If,

not later than the end of the 180-day period specified

in paragraph (7), the holder of an approved application

for the drug involved does not agree to any labeling change

requested by the Commissioner of Food and Drugs under

that paragraph, the Commissioner of Food and Drugs shall

refer the request 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 COM- Deadline. MITTEE.—Not later than 90 days after receiving a referral

PUBLIC LAW 107–109—JAN. 4, 2002 115 STAT. 1411

under subparagraph (A), the Pediatric Advisory Subcommittee of the Anti-Infective Drugs Advisory Committee

shall—

‘‘(i) review the available information on the safe

and effective use of the drug in the pediatric population, including study reports submitted under this

section; and

‘‘(ii) make a recommendation to the Commissioner

of Food and Drugs as to appropriate labeling changes,

if any.

‘‘(9) FDA DETERMINATION.—Not later than 30 days after

receiving a recommendation from the Pediatric Advisory Subcommittee of the Anti-Infective Drugs Advisory Committee

under paragraph (8)(B)(ii) with respect to a drug, the Commissioner of Food and Drugs shall consider the recommendation

and, if appropriate, make a request to the holders of approved

applications for the drug to make any labeling change that

the Commissioner of Food and Drugs determines to be appropriate.

‘‘(10) FAILURE TO AGREE.—If a holder of an approved

application for a drug, within 30 days after receiving a request

to make a labeling change under paragraph (9), does not agree

to make a requested labeling change, the Commissioner may

deem the drug to be misbranded under the Federal Food,

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

‘‘(11) NO EFFECT ON AUTHORITY.—Nothing in this subsection limits the authority of the United States to bring an

enforcement action under the Federal Food, Drug, and Cosmetic

Act 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.

‘‘(12) RECOMMENDATION FOR FORMULATION CHANGES.—If a

pediatric study completed under public contract indicates that

a formulation change is necessary and the Secretary agrees,

the Secretary shall send a nonbinding letter of recommendation

regarding that change to each holder of an approved application.

‘‘(d) AUTHORIZATION OF APPROPRIATIONS.—

‘‘(1) IN GENERAL.—There are authorized to be appropriated

to carry out this section—

‘‘(A) $200,000,000 for fiscal year 2002; and

‘‘(B) such sums as are necessary for each of the five

succeeding fiscal years.

‘‘(2) AVAILABILITY.—Any amount appropriated under paragraph (1) shall remain available to carry out this section until

expended.’’.

SEC. 4. WRITTEN REQUEST TO HOLDERS OF APPROVED APPLICATIONS FOR DRUGS THAT HAVE MARKET EXCLUSIVITY.

Section 505A(d) of the Federal Food, Drug, and Cosmetic Act

(21 U.S.C. 355a(d)) is amended by adding at the end the following:

‘‘(4) WRITTEN REQUEST TO HOLDERS OF APPROVED APPLICATIONS FOR DRUGS THAT HAVE MARKET EXCLUSIVITY.—

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115 STAT. 1412 PUBLIC LAW 107–109—JAN. 4, 2002

‘‘(A) REQUEST AND RESPONSE.—If the Secretary makes

a written request for pediatric studies (including neonates,

as appropriate) under subsection (c) to the holder of an

application approved under section 505(b)(1), 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 499 of

the Public Health Service Act (42 U.S.C. 290b) (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 499(j)(9)(B)(i) to conduct the requested

studies. If the Foundation so certifies, the Secretary shall

refer the drug for inclusion on the list established under

section 409I of the Public Health Service Act for the conduct

of the studies.

‘‘(D) EFFECT OF SUBSECTION.—Nothing in this subsection (including with respect to referrals from the Secretary to the Foundation) alters or amends section 301(j)

of this Act or section 552 of title 5 or section 1905 of

title 18, United States Code.

‘‘(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) 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) after the date of approval of the drug.’’.

Deadline.

PUBLIC LAW 107–109—JAN. 4, 2002 115 STAT. 1413

SEC. 5. TIMELY LABELING CHANGES FOR DRUGS GRANTED EXCLUSIVITY; DRUG FEES.

(a) ELIMINATION OF USER FEE WAIVER FOR PEDIATRIC SUPPLE- MENTS.—Section 736(a)(1) of the Federal Food, Drug, and Cosmetic

Act (21 U.S.C. 379h(a)(1)) is amended— (1) by striking subparagraph (F); and

(2) by redesignating subparagraph (G) as subparagraph

(F).

(b) LABELING CHANGES.— (1) DEFINITION OF PRIORITY SUPPLEMENT.—Section 201 of

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

is amended by adding at the end the following: ‘‘(kk) PRIORITY SUPPLEMENT.—The term ‘priority supplement’ means a drug application referred to in section 101(4)

of the Food and Drug Administration Modernization Act of

1997 (111 Stat. 2298).’’. (2) TREATMENT AS PRIORITY SUPPLEMENTS.—Section 505A

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

is amended by adding at the end the following:

‘‘(l) LABELING SUPPLEMENTS.— ‘‘(1) PRIORITY STATUS FOR PEDIATRIC SUPPLEMENTS.—Any

supplement to an application under section 505 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 COM- MITTEE.—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.

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115 STAT. 1414 PUBLIC LAW 107–109—JAN. 4, 2002

‘‘(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 Act 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.’’.

SEC. 6. OFFICE OF PEDIATRIC THERAPEUTICS.

(a) ESTABLISHMENT.—The Secretary of Health and Human

Services shall establish an Office of Pediatric Therapeutics within

the Food and Drug Administration.

(b) DUTIES.—The Office of Pediatric Therapeutics shall be

responsible for coordination and facilitation of all activities of the

Food and Drug Administration that may have any effect on a

pediatric population or the practice of pediatrics or may in any

other way involve pediatric issues.

(c) STAFF.—The staff of the Office of Pediatric Therapeutics

shall coordinate with employees of the Department of Health and

Human Services who exercise responsibilities relating to pediatric

therapeutics and shall include—

(1) one or more additional individuals with expertise concerning ethical issues presented by the conduct of clinical

research in the pediatric population; and

(2) one or more additional individuals with expertise in

pediatrics as may be necessary to perform the activities

described in subsection (b).

SEC. 7. NEONATES.

Section 505A(g) of the Federal Food, Drug, and Cosmetic Act

(21 U.S.C. 355a(g)) is amended by inserting ‘‘(including neonates

in appropriate cases)’’ after ‘‘pediatric age groups’’.

SEC. 8. SUNSET.

Section 505A of the Federal Food, Drug, and Cosmetic Act

(21 U.S.C. 355a) is amended by striking subsection (j) and inserting

the following:

‘‘(j) SUNSET.—A drug may not receive any 6-month period under

subsection (a) or (c) unless—

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

a written request for pediatric studies of the drug;

21 USC 393a.

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PUBLIC LAW 107–109—JAN. 4, 2002 115 STAT. 1415

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

drug is accepted for filing under section 505(b); and ‘‘(3) all requirements of this section are met.’’.

SEC. 9. DISSEMINATION OF PEDIATRIC INFORMATION.

Section 505A of the Federal Food, Drug, and Cosmetic Act

(21 U.S.C. 355a) (as amended by section 5(b)(2)) is amended by

adding at the end the following: ‘‘(m) 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 301(j) of this Act or section 552 of

title 5 or section 1905 of title 18, United States Code.’’.

SEC. 10. CLARIFICATION OF INTERACTION OF PEDIATRIC EXCLUSIVITY UNDER SECTION 505A OF THE FEDERAL FOOD,

DRUG, AND COSMETIC ACT AND 180-DAY EXCLUSIVITY

AWARDED TO AN APPLICANT FOR APPROVAL OF A DRUG

UNDER SECTION 505(j) OF THAT ACT.

Section 505A of the Federal Food, Drug, and Cosmetic Act

(21 U.S.C. 355a) (as amended by section 9) is amended by adding

at the end the following:

‘‘(n) CLARIFICATION OF INTERACTION OF MARKET EXCLUSIVITY

UNDER THIS SECTION AND MARKET EXCLUSIVITY AWARDED TO AN

APPLICANT FOR APPROVAL OF A DRUG UNDER SECTION 505(j).—

If a 180-day period under section 505(j)(5)(B)(iv) overlaps with

a 6-month exclusivity period under this section, so that the

applicant for approval of a drug under section 505(j) 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.’’.

SEC. 11. PROMPT APPROVAL OF DRUGS UNDER SECTION 505(j) WHEN

PEDIATRIC INFORMATION IS ADDED TO LABELING.

(a) IN GENERAL.—Section 505A of the Federal Food, Drug,

and Cosmetic Act (21 U.S.C. 355a) (as amended by section 10)

is amended by adding at the end the following:

‘‘(o) PROMPT APPROVAL OF DRUGS UNDER SECTION 505(j) WHEN

PEDIATRIC INFORMATION IS ADDED TO LABELING.— ‘‘(1) GENERAL RULE.—A drug for which an application has

been submitted or approved under section 505(j) shall not be

considered ineligible for approval under that section or misbranded under section 502 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

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115 STAT. 1416 PUBLIC LAW 107–109—JAN. 4, 2002

or other aspect is protected by patent or by exclusivity under

clause (iii) or (iv) of section 505(j)(5)(D). ‘‘(2) LABELING.—Notwithstanding clauses (iii) and (iv) of

section 505(j)(5)(D), the Secretary may require that the labeling

of a drug approved under section 505(j) 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 505 for pediatric formulations;

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

application under section 505(j) that omits any other conditions of approval entitled to exclusivity under clause (iii)

or (iv) of section 505(j)(5)(D); or

‘‘(D) except as expressly provided in paragraphs (1)

and (2), the operation of section 505.’’.

(b) EFFECTIVE DATE.—The amendment made by subsection (a)

takes effect on the date of enactment of this Act, 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.

SEC. 12. STUDY CONCERNING RESEARCH INVOLVING CHILDREN.

(a) CONTRACT WITH INSTITUTE OF MEDICINE.—The Secretary

of Health and Human Services shall enter into a contract with

the Institute of Medicine for—

(1) the conduct, in accordance with subsection (b), of a

review of—

(A) Federal regulations in effect on the date of the

enactment of this Act relating to research involving children;

(B) federally prepared or supported reports relating

to research involving children; and

(C) federally supported evidence-based research

involving children; and

(2) the submission to the Committee on Health, Education,

Labor, and Pensions of the Senate and the Committee on

Energy and Commerce of the House of Representatives, not

later than two years after the date of enactment of this Act,

of a report concerning the review conducted under paragraph

(1) that includes recommendations on best practices relating

to research involving children.

(b) AREAS OF REVIEW.—In conducting the review under subsection (a)(1), the Institute of Medicine shall consider the following:

42 USC 289 note.

21 USC 355a

note.

PUBLIC LAW 107–109—JAN. 4, 2002 115 STAT. 1417

(1) The written and oral process of obtaining and defining ‘‘assent’’, ‘‘permission’’ and ‘‘informed consent’’ with respect to

child clinical research participants and the parents, guardians,

and the individuals who may serve as the legally authorized

representatives of such children (as defined in subpart A of

part 46 of title 45, Code of Federal Regulations).

(2) The expectations and comprehension of child research

participants and the parents, guardians, or legally authorized

representatives of such children, for the direct benefits and

risks of the child’s research involvement, particularly in terms

of research versus therapeutic treatment.

(3) The definition of ‘‘minimal risk’’ with respect to a

healthy child or a child with an illness.

(4) The appropriateness of the regulations applicable to

children of differing ages and maturity levels, including regulations relating to legal status.

(5) Whether payment (financial or otherwise) may be provided to a child or his or her parent, guardian, or legally

authorized representative for the participation of the child in

research, and if so, the amount and type of payment that

may be made.

(6) Compliance with the regulations referred to in subsection (a)(1)(A), the monitoring of such compliance (including

the role of institutional review boards), and the enforcement

actions taken for violations of such regulations.

(7) The unique roles and responsibilities of institutional

review boards in reviewing research involving children,

including composition of membership on institutional review

boards.

(c) REQUIREMENTS OF EXPERTISE.—The Institute of Medicine

shall conduct the review under subsection (a)(1) and make recommendations under subsection (a)(2) in conjunction with experts

in pediatric medicine, pediatric research, and the ethical conduct

of research involving children.

SEC. 13. FOUNDATION FOR THE NATIONAL INSTITUTES OF HEALTH.

Section 499 of the Public Health Service Act (42 U.S.C. 290b)

is amended—

(1) in subsection (b), by inserting ‘‘(including collection

of funds for pediatric pharmacologic research)’’ after ‘‘mission’’;

(2) in subsection (c)(1)—

(A) by redesignating subparagraph (C) as subparagraph (D); and

(B) by inserting after subparagraph (B) the following:

‘‘(C) A program to collect funds for pediatric pharmacologic research and studies listed by the Secretary pursuant

to section 409I(a)(1)(A) of this Act and referred under section 505A(d)(4)(C) of the Federal Food, Drug, and Cosmetic

Act (21 U.S.C. 355a(d)(4)(C)).’’;

(3) in subsection (d)—

(A) in paragraph (1)—

(i) in subparagraph (B)—

(I) in clause (ii), by striking ‘‘and’’ at the end;

(II) in clause (iii), by striking the period and

inserting ‘‘; and’’; and

(III) by adding at the end the following:

‘‘(iv) the Commissioner of Food and Drugs.’’; and

115 STAT. 1418 PUBLIC LAW 107–109—JAN. 4, 2002

(ii) by striking subparagraph (C) and inserting

the following:

‘‘(C) The ex officio members of the Board under

subparagraph (B) shall appoint to the Board individuals

from among a list of candidates to be provided by the

National Academy of Science. Such appointed members

shall include—

‘‘(i) representatives of the general biomedical field;

‘‘(ii) representatives of experts in pediatric medicine and research;

‘‘(iii) representatives of the general biobehavioral

field, which may include experts in biomedical ethics;

and

‘‘(iv) representatives of the general public, which

may include representatives of affected industries.’’;

and

(B) in paragraph (2), by realigning the margin of

subparagraph (B) to align with subparagraph (A);

(4) in subsection (k)(9)—

(A) by striking ‘‘The Foundation’’ and inserting the

following:

‘‘(A) IN GENERAL.—The Foundation’’; and

(B) by adding at the end the following:

‘‘(B) GIFTS, GRANTS, AND OTHER DONATIONS.—

‘‘(i) IN GENERAL.—Gifts, grants, and other donations to the Foundation may be designated for pediatric

research and studies on drugs, and funds so designated

shall be used solely for grants for research and studies

under subsection (c)(1)(C).

‘‘(ii) OTHER GIFTS.—Other gifts, grants, or donations received by the Foundation and not described

in clause (i) may also be used to support such pediatric

research and studies.

‘‘(iii) REPORT.—The recipient of a grant for

research and studies shall agree to provide the Director

of the National Institutes of Health and the Commissioner of Food and Drugs, at the conclusion of the

research and studies—

‘‘(I) a report describing the results of the

research and studies; and

‘‘(II) all data generated in connection with the

research and studies.

‘‘(iv) ACTION BY THE COMMISSIONER OF FOOD AND

DRUGS.—The Commissioner of Food and Drugs shall

take appropriate action in response to a report received

under clause (iii) in accordance with paragraphs (7)

through (12) of section 409I(c), including negotiating

with the holders of approved applications for the drugs

studied for any labeling changes that the Commissioner determines to be appropriate and requests the

holders to make.

‘‘(C) APPLICABILITY.—Subparagraph (A) does not apply

to the program described in subsection (c)(1)(C).’’;

(5) by redesignating subsections (f) through (m) as subsections (e) through (l), respectively;

(6) in subsection (h)(11) (as so redesignated), by striking

‘‘solicit’’ and inserting ‘‘solicit,’’; and

PUBLIC LAW 107–109—JAN. 4, 2002 115 STAT. 1419

(7) in paragraphs (1) and (2) of subsection (j) (as so redesignated), by striking ‘‘(including those developed under subsection

(d)(2)(B)(i)(II))’’ each place it appears.

SEC. 14. PEDIATRIC PHARMACOLOGY ADVISORY COMMITTEE.

(a) IN GENERAL.—The Secretary of Health and Human Services

shall, under section 222 of the Public Health Service Act (42 U.S.C.

217a), convene and consult an advisory committee on pediatric

pharmacology (referred to in this section as the ‘‘advisory committee’’).

(b) PURPOSE.— (1) IN GENERAL.—The advisory committee shall advise and

make recommendations to the Secretary, through the Commissioner of Food and Drugs and in consultation with the Director

of the National Institutes of Health, on matters relating to

pediatric pharmacology.

(2) MATTERS INCLUDED.—The matters referred to in paragraph (1) include—

(A) pediatric research conducted under sections 351,

409I, and 499 of the Public Health Service Act and sections

501, 502, 505, and 505A of the Federal Food, Drug, and

Cosmetic Act;

(B) identification of research priorities related to pediatric pharmacology and the need for additional treatments

of specific pediatric diseases or conditions; and

(C) the ethics, design, and analysis of clinical trials

related to pediatric pharmacology.

(c) COMPOSITION.—The advisory committee shall include representatives of pediatric health organizations, pediatric researchers,

relevant patient and patient-family organizations, and other experts

selected by the Secretary.

SEC. 15. PEDIATRIC SUBCOMMITTEE OF THE ONCOLOGIC DRUGS

ADVISORY COMMITTEE.

(a) CLARIFICATION OF AUTHORITIES.—

(1) IN GENERAL.—The Pediatric Subcommittee of the Oncologic Drugs Advisory Committee (referred to in this section

as the ‘‘Subcommittee’’), in carrying out the mission of reviewing

and evaluating the data concerning the safety and effectiveness

of marketed and investigational human drug products for use

in the treatment of pediatric cancers, shall—

(A) evaluate and, to the extent practicable, prioritize

new and emerging therapeutic alternatives available to

treat pediatric cancer;

(B) provide recommendations and guidance to help

ensure that children with cancer have timely access to

the most promising new cancer therapies; and

(C) advise on ways to improve consistency in the availability of new therapeutic agents.

(2) MEMBERSHIP.—

(A) IN GENERAL.—The Secretary shall appoint not more

than 11 voting members to the Pediatric Subcommittee

from the membership of the Pediatric Pharmacology

Advisory Committee and the Oncologic Drugs Advisory

Committee.

(B) REQUEST FOR PARTICIPATION.—The Subcommittee

shall request participation of the following members in

42 USC 284m

note.

115 STAT. 1420 PUBLIC LAW 107–109—JAN. 4, 2002

the scientific and ethical consideration of topics of pediatric

cancer, as necessary:

(i) At least two pediatric oncology specialists from

the National Cancer Institute.

(ii) At least four pediatric oncology specialists

from—

(I) the Children’s Oncology Group;

(II) other pediatric experts with an established

history of conducting clinical trials in children;

or

(III) consortia sponsored by the National

Cancer Institute, such as the Pediatric Brain

Tumor Consortium, the New Approaches to Neuroblastoma Therapy or other pediatric oncology consortia.

(iii) At least two representatives of the pediatric

cancer patient and patient-family community.

(iv) One representative of the nursing community.

(v) At least one statistician.

(vi) At least one representative of the pharmaceutical industry.

(b) PRE-CLINICAL MODELS TO EVALUATE PROMISING PEDIATRIC

CANCER THERAPIES.—Section 413 of the Public Health Service Act

(42 U.S.C. 285a–2) is amended by adding at the end the following:

‘‘(c) PRE-CLINICAL MODELS TO EVALUATE PROMISING PEDIATRIC

CANCER THERAPIES.—

‘‘(1) EXPANSION AND COORDINATION OF ACTIVITIES.—The

Director of the National Cancer Institute shall expand, intensify, and coordinate the activities of the Institute with respect

to research on the development of preclinical models to evaluate

which therapies are likely to be effective for treating pediatric

cancer.

‘‘(2) COORDINATION WITH OTHER INSTITUTES.—The Director

of the Institute shall coordinate the activities under paragraph

(1) with similar activities conducted by other national research

institutes and agencies of the National Institutes of Health

to the extent that those Institutes and agencies have responsibilities that are related to pediatric cancer.’’.

(c) CLARIFICATION OF AVAILABILITY OF INVESTIGATIONAL NEW

DRUGS FOR PEDIATRIC STUDY AND USE.—

(1) AMENDMENT OF THE FEDERAL FOOD, DRUG, AND COSMETIC ACT.—Section 505(i)(1) of the Federal Food, Drug, and

Cosmetic Act (21 U.S.C. 355(i)(1)) is amended—

(A) in subparagraph (B), by striking ‘‘and’’ at the end;

(B) in subparagraph (C), by striking the period at

the end and inserting ‘‘; and’’; and

(C) by adding at the end the following:

‘‘(D) the submission to the Secretary by the manufacturer or the sponsor of the investigation of a new drug

of a statement of intent regarding whether the manufacturer or sponsor has plans for assessing pediatric safety

and efficacy.’’.

(2) AMENDMENT OF THE PUBLIC HEALTH SERVICE ACT.—

Section 402(j)(3)(A) of the Public Health Service Act (42 U.S.C.

282(j)(3)(A)) is amended in the first sentence—

(A) by striking ‘‘trial sites, and’’ and inserting ‘‘trial

sites,’’; and

PUBLIC LAW 107–109—JAN. 4, 2002 115 STAT. 1421

(B) by striking ‘‘in the trial,’’ and inserting ‘‘in the

trial, and a description of whether, and through what procedure, the manufacturer or sponsor of the investigation of

a new drug will respond to requests for protocol exception,

with appropriate safeguards, for single-patient and

expanded protocol use of the new drug, particularly in

children,’’.

(d) REPORT.—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.

SEC. 16. REPORT ON PEDIATRIC EXCLUSIVITY PROGRAM.

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 and section 409I of the Public Health

Service Act (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,

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;

Deadline.

21 USC 355a

note.

Deadline.

21 USC 355 note.

115 STAT. 1422 PUBLIC LAW 107–109—JAN. 4, 2002

(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 (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.

SEC. 17. ADVERSE-EVENT REPORTING.

(a) TOLL-FREE NUMBER IN LABELING.—Not later than one year

after the date of the enactment of this Act, the Secretary of Health

and Human Services shall promulgate a final rule requiring that

Deadline.

Regulations.

21 USC 355b.

PUBLIC LAW 107–109—JAN. 4, 2002 115 STAT. 1423

the labeling of each drug for which an application is approved

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

(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 of the Federal Food, Drug, and Cosmetic Act,

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 6 of this Act. In considering the report, the

Director of such Office shall provide for the review of the

report by the Pediatric Advisory Subcommittee of the AntiInfective 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 in response to the report.

(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 oneyear period described in such paragraph regarding the drug

has expired.

SEC. 18. MINORITY CHILDREN AND PEDIATRIC-EXCLUSIVITY PROGRAM.

(a) PROTOCOLS FOR PEDIATRIC STUDIES.—Section 505A of the

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

in subsection (d)(2) by inserting after the first sentence the following: ‘‘In reaching an agreement regarding written protocols,

the Secretary shall take into account adequate representation of

children of ethnic and racial minorities.’’.

(b) STUDY BY GENERAL ACCOUNTING OFFICE.—

(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;

and to the extent ethnic and racial minorities are not

adequately represented, the reasons for such under representation and recommendations to increase such representation.

21 USC 355a

note.

115 STAT. 1424 PUBLIC LAW 107–109—JAN. 4, 2002

LEGISLATIVE HISTORY—S. 1789 (H.R. 2887):

HOUSE REPORTS: No. 107–277 accompanying H.R. 2887 (Comm. on Energy and

Commerce).

CONGRESSIONAL RECORD, Vol. 147 (2001):

Dec. 12, considered and passed Senate.

Dec. 18, considered and passed House.

Æ

(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.

SEC. 19. TECHNICAL AND CONFORMING AMENDMENTS.

Section 505A of the Federal Food, Drug, and Cosmetic Act

(21 U.S.C. 355a) (as amended by sections 2(1), 5(b)(2), 9, 10, 11,

and 17) is amended— (1)(A) by striking ‘‘(j)(4)(D)(ii)’’ each place it appears and

inserting ‘‘(j)(5)(D)(ii)’’;

(B) by striking ‘‘(j)(4)(D)’’ each place it appears and

inserting ‘‘(j)(5)(D)’’; and

(C) by striking ‘‘505(j)(4)(D)’’ each place it appears and

inserting ‘‘505(j)(5)(D)’’;

(2) by redesignating subsections (a), (g), (h), (i), (j), (k),

(l), (m), (n), and (o) as subsections (b), (a), (g), (h), (n), (m),

(i), (j), (k), and (l) respectively;

(3) by moving the subsections so as to appear in alphabetical order;

(4) in paragraphs (1), (2), and (3) of subsection (d), subsection (e), and subsection (m) (as redesignated by paragraph

(2)), by striking ‘‘subsection (a) or (c)’’ and inserting ‘‘subsection

(b) or (c)’’; and

(5) in subsection (g) (as redesignated by paragraph (2)),

by striking ‘‘subsection (a) or (b)’’ and inserting ‘‘subsection

(b) or (c)’’.

Approved January 4, 2002.

Deadline.