S. 650 Text
12-3-03
Became Public Law No: 108-155
One Hundred Eighth Congress
of the
United States of America
AT THE FIRST SESSION
Begun and held at the City of Washington on Tuesday,
the seventh day of January, two thousand and three
An Act
To amend the Federal Food, Drug, and Cosmetic Act to authorize the
Food and Drug Administration to require certain research into drugs used in
pediatric patients.
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 `Pediatric Research Equity Act of 2003'.
SEC. 2. RESEARCH INTO PEDIATRIC USES FOR DRUGS AND BIOLOGICAL PRODUCTS.
(a) IN GENERAL- Subchapter A of chapter V of the Federal Food, Drug, and Cosmetic
Act (21 U.S.C. 351 et seq.) is amended by inserting after section 505A the
following:
`SEC. 505B. RESEARCH INTO PEDIATRIC USES FOR DRUGS AND BIOLOGICAL PRODUCTS.
`(a) NEW DRUGS AND BIOLOGICAL PRODUCTS-
`(1) IN GENERAL- A person that submits an application (or supplement to
an application)--
`(A) under section 505 for a new active ingredient, new indication, new
dosage form, new dosing regimen, or new route of administration; or
`(B) under section 351 of the Public Health Service Act (42 U.S.C. 262)
for a new active ingredient, new indication, new dosage form, new dosing
regimen, or new route of administration;
shall submit with the application the assessments described in paragraph
(2).
`(A) IN GENERAL- The assessments referred to in paragraph (1) shall contain
data, gathered using appropriate formulations for each age group for which
the assessment is required, that are adequate--
`(i) to assess the safety and effectiveness of the drug or the biological
product for the claimed indications in all relevant pediatric subpopulations;
and
`(ii) to support dosing and administration for each pediatric subpopulation
for which the drug or the biological product is safe and effective.
`(B) SIMILAR COURSE OF DISEASE OR SIMILAR EFFECT OF DRUG OR BIOLOGICAL
PRODUCT-
`(i) IN GENERAL- If the course of the disease and the effects of the
drug are sufficiently similar in adults and pediatric patients, the
Secretary may conclude that pediatric effectiveness can be extrapolated
from adequate and well-controlled studies in adults, usually supplemented
with other information obtained in pediatric patients, such as pharmacokinetic
studies.
`(ii) EXTRAPOLATION BETWEEN AGE GROUPS- A study may not be needed in
each pediatric age group if data from one age group can be extrapolated
to another age group.
`(3) DEFERRAL- On the initiative of the Secretary or at the request of the
applicant, the Secretary may defer submission of some or all assessments
required under paragraph (1) until a specified date after approval of the
drug or issuance of the license for a biological product if--
`(A) the Secretary finds that--
`(i) the drug or biological product is ready for approval for use in
adults before pediatric studies are complete;
`(ii) pediatric studies should be delayed until additional safety or
effectiveness data have been collected; or
`(iii) there is another appropriate reason for deferral; and
`(B) the applicant submits to the Secretary--
`(i) certification of the grounds for deferring the assessments;
`(ii) a description of the planned or ongoing studies; and
`(iii) evidence that the studies are being conducted or will be conducted
with due diligence and at the earliest possible time.
`(A) FULL WAIVER- On the initiative of the Secretary or at the request
of an applicant, the Secretary shall grant a full waiver, as appropriate,
of the requirement to submit assessments for a drug or biological product
under this subsection if the applicant certifies and the Secretary finds
that--
`(i) necessary studies are impossible or highly impracticable (because,
for example, the number of patients is so small or the patients are
geographically dispersed);
`(ii) there is evidence strongly suggesting that the drug or biological
product would be ineffective or unsafe in all pediatric age groups;
or
`(iii) the drug or biological product--
`(I) does not represent a meaningful therapeutic benefit over existing
therapies for pediatric patients; and
`(II) is not likely to be used in a substantial number of pediatric
patients.
`(B) PARTIAL WAIVER- On the initiative of the Secretary or at the request
of an applicant, the Secretary shall grant a partial waiver, as appropriate,
of the requirement to submit assessments for a drug or biological product
under this subsection with respect to a specific pediatric age group if
the applicant certifies and the Secretary finds that--
`(i) necessary studies are impossible or highly impracticable (because,
for example, the number of patients in that age group is so small or
patients in that age group are geographically dispersed);
`(ii) there is evidence strongly suggesting that the drug or biological
product would be ineffective or unsafe in that age group;
`(iii) the drug or biological product--
`(I) does not represent a meaningful therapeutic benefit over existing
therapies for pediatric patients in that age group; and
`(II) is not likely to be used by a substantial number of pediatric
patients in that age group; or
`(iv) the applicant can demonstrate that reasonable attempts to produce
a pediatric formulation necessary for that age group have failed.
`(C) PEDIATRIC FORMULATION NOT POSSIBLE- If a waiver is granted on the
ground that it is not possible to develop a pediatric formulation, the
waiver shall cover only the pediatric groups requiring that formulation.
`(D) LABELING REQUIREMENT- If the Secretary grants a full or partial waiver
because there is evidence that a drug or biological product would be ineffective
or unsafe in pediatric populations, the information shall be included
in the labeling for the drug or biological product.
`(b) MARKETED DRUGS AND BIOLOGICAL PRODUCTS-
`(1) IN GENERAL- After providing notice in the form of a letter and an opportunity
for written response and a meeting, which may include an advisory committee
meeting, the Secretary may (by order in the form of a letter) require the
holder of an approved application for a drug under section 505 or the holder
of a license for a biological product under section 351 of the Public Health
Service Act (42 U.S.C. 262) to submit by a specified date the assessments
described in subsection (a)(2) if the Secretary finds that--
`(A)(i) the drug or biological product is used for a substantial number
of pediatric patients for the labeled indications; and
`(ii) the absence of adequate labeling could pose significant risks to
pediatric patients; or
`(B)(i) there is reason to believe that the drug or biological product
would represent a meaningful therapeutic benefit over existing therapies
for pediatric patients for one or more of the claimed indications; and
`(ii) the absence of adequate labeling could pose significant risks to
pediatric patients.
`(A) FULL WAIVER- At the request of an applicant, the Secretary shall
grant a full waiver, as appropriate, of the requirement to submit assessments
under this subsection if the applicant certifies and the Secretary finds
that--
`(i) necessary studies are impossible or highly impracticable (because,
for example, the number of patients in that age group is so small or
patients in that age group are geographically dispersed); or
`(ii) there is evidence strongly suggesting that the drug or biological
product would be ineffective or unsafe in all pediatric age groups.
`(B) PARTIAL WAIVER- At the request of an applicant, the Secretary shall
grant a partial waiver, as appropriate, of the requirement to submit assessments
under this subsection with respect to a specific pediatric age group if
the applicant certifies and the Secretary finds that--
`(i) necessary studies are impossible or highly impracticable (because,
for example, the number of patients in that age group is so small or
patients in that age group are geographically dispersed);
`(ii) there is evidence strongly suggesting that the drug or biological
product would be ineffective or unsafe in that age group;
`(iii)(I) the drug or biological product--
`(aa) does not represent a meaningful therapeutic benefit over existing
therapies for pediatric patients in that age group; and
`(bb) is not likely to be used in a substantial number of pediatric
patients in that age group; and
`(II) the absence of adequate labeling could not pose significant risks
to pediatric patients; or
`(iv) the applicant can demonstrate that reasonable attempts to produce
a pediatric formulation necessary for that age group have failed.
`(C) PEDIATRIC FORMULATION NOT POSSIBLE- If a waiver is granted on the
ground that it is not possible to develop a pediatric formulation, the
waiver shall cover only the pediatric groups requiring that formulation.
`(D) LABELING REQUIREMENT- If the Secretary grants a full or partial waiver
because there is evidence that a drug or biological product would be ineffective
or unsafe in pediatric populations, the information shall be included
in the labeling for the drug or biological product.
`(3) RELATIONSHIP TO OTHER PEDIATRIC PROVISIONS-
`(A) NO ASSESSMENT WITHOUT WRITTEN REQUEST- No assessment may be required
under paragraph (1) for a drug subject to an approved application under
section 505 unless--
`(i) the Secretary has issued a written request for a related pediatric
study under section 505A(c) of this Act or section 409I of the Public
Health Service Act (42 U.S.C. 284m);
`(ii)(I) if the request was made under section 505A(c)--
`(aa) the recipient of the written request does not agree to the request;
or
`(bb) the Secretary does not receive a response as specified under
section 505A(d)(4)(A); or
`(II) if the request was made under section 409I of the Public Health
Service Act (42 U.S.C. 284m)--
`(aa) the recipient of the written request does not agree to the request;
or
`(bb) the Secretary does not receive a response as specified under
section 409I(c)(2) of that Act; and
`(iii)(I) the Secretary certifies under subparagraph (B) that there
are insufficient funds under sections 409I and 499 of the Public Health
Service Act (42 U.S.C. 284m, 290b) to conduct the study; or
`(II) the Secretary publishes in the Federal Register a certification
that certifies that--
`(aa) no contract or grant has been awarded under section 409I or
499 of the Public Health Service Act (42 U.S.C. 284m, 290b); and
`(bb) not less than 270 days have passed since the date of a certification
under subparagraph (B) that there are sufficient funds to conduct
the study.
`(B) NO AGREEMENT TO REQUEST- Not later than 60 days after determining
that no holder will agree to the written request (including a determination
that the Secretary has not received a response specified under section
505A(d) of this Act or section 409I of the Public Health Service Act (42
U.S.C. 284m), the Secretary shall certify whether the Secretary has sufficient
funds to conduct the study under section 409I or 499 of the Public Health
Service Act (42 U.S.C. 284m, 290b), taking into account the prioritization
under section 409I.
`(c) MEANINGFUL THERAPEUTIC BENEFIT- For the purposes of paragraph (4)(A)(iii)(I)
and (4)(B)(iii)(I) of subsection (a) and paragraphs (1)(B)(i) and (2)(B)(iii)(I)(aa)
of subsection (b), a drug or biological product shall be considered to represent
a meaningful therapeutic benefit over existing therapies if the Secretary
estimates that--
`(1) if approved, the drug or biological product would represent a significant
improvement in the treatment, diagnosis, or prevention of a disease, compared
with marketed products adequately labeled for that use in the relevant pediatric
population; or
`(2) the drug or biological product is in a class of products or for an
indication for which there is a need for additional options.
`(d) SUBMISSION OF ASSESSMENTS- If a person fails to submit an assessment
described in subsection (a)(2), or a request for approval of a pediatric formulation
described in subsection (a) or (b), in accordance with applicable provisions
of subsections (a) and (b)--
`(1) the drug or biological product that is the subject of the assessment
or request may be considered misbranded solely because of that failure and
subject to relevant enforcement action (except that the drug or biological
product shall not be subject to action under section 303); but
`(2) the failure to submit the assessment or request shall not be the basis
for a proceeding--
`(A) to withdraw approval for a drug under section 505(e); or
`(B) to revoke the license for a biological product under section 351
of the Public Health Service Act (42 U.S.C. 262).
`(e) MEETINGS- Before and during the investigational process for a new drug
or biological product, the Secretary shall meet at appropriate times with
the sponsor of the new drug or biological product to discuss--
`(1) information that the sponsor submits on plans and timelines for pediatric
studies; or
`(2) any planned request by the sponsor for waiver or deferral of pediatric
studies.
`(f) SCOPE OF AUTHORITY- Nothing in this section provides to the Secretary
any authority to require a pediatric assessment of any drug or biological
product, or any assessment regarding other populations or uses of a drug or
biological product, other than the pediatric assessments described in this
section.
`(g) ORPHAN DRUGS- Unless the Secretary requires otherwise by regulation,
this section does not apply to any drug for an indication for which orphan
designation has been granted under section 526.
`(h) INTEGRATION WITH OTHER PEDIATRIC STUDIES- The authority under this section
shall remain in effect so long as an application subject to this section may
be accepted for filing by the Secretary on or before the date specified in
section 505A(n).'.
(b) CONFORMING AMENDMENTS- (1) Section 505(b)(1) of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 355(b)(1)) is amended in the second sentence--
(A) by striking `and (F)' and inserting `(F)'; and
(B) by striking the period at the end and inserting `, and (G) any assessments
required under section 505B.'.
(2) Section 505A(h) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C.
355a(h)) is amended--
(A) in the subsection heading, by striking `REGULATIONS' and inserting `PEDIATRIC
RESEARCH REQUIREMENTS'; and
(B) by striking `pursuant to regulations promulgated by the Secretary' and
inserting `by a provision of law (including a regulation) other than this
section'.
(3) Section 351(a)(2) of the Public Health Service Act (42 U.S.C. 262(a)(2))
is amended--
(A) by redesignating subparagraph (B) as subparagraph (C); and
(B) by inserting after subparagraph (A) the following:
`(B) PEDIATRIC STUDIES- A person that submits an application for a license
under this paragraph shall submit to the Secretary as part of the application
any assessments required under section 505B of the Federal Food, Drug,
and Cosmetic Act.'.
SEC. 3. TECHNICAL AND CONFORMING AMENDMENTS.
(a) ABBREVIATED NEW DRUG APPLICATION- Section 505A of the Federal Food, Drug,
and Cosmetic Act (21 U.S.C. 355a) is amended in subparagraphs (A) and (B)
of subsection (b)(2) and subparagraphs (A) and (B) of subsection (c)(2) by
striking `505(j)(4)(B)' and inserting `505(j)(5)(B)'.
(b) PEDIATRIC ADVISORY COMMITTEE- (1) Section 505A(i)(2) of the Federal Food,
Drug, and Cosmetic Act (21 U.S.C. 355a(i)(2)) is amended by striking `Advisory
Subcommittee of the Anti-Infective Drugs' each place it appears.
(2) Section 14 of the Best Pharmaceuticals for Children Act (42 U.S.C. 284m
note; Public Law 107-109) is amended--
(A) in the section heading, by striking `pharmacology';
(B) in subsection (a), by striking `(42 U.S.C. 217a),' and inserting (42
U.S.C. 217a) or other appropriate authority,';
(i) in paragraph (1), by striking `and in consultation with the Director
of the National Institutes of Health'; and
(ii) in paragraph (2), by striking `and 505A' and inserting `505A, and
505B'; and
(D) by striking `pharmacology' each place it appears and inserting `therapeutics'.
(3) Section 15(a)(2)(A) of the Best Pharmaceuticals for Children Act (115
Stat. 1419) is amended by striking `Pharmacology'.
(4) Section 16(1)(C) of the Best Pharmaceuticals for Children Act (21 U.S.C.
355a note; Public Law 107-109) is amended by striking `Advisory Subcommittee
of the Anti-Infective Drugs'.
(5) Section 17(b)(1) of the Best Pharmaceuticals for Children Act (21 U.S.C.
355b(b)(1)) is amended in the second sentence by striking `Advisory Subcommittee
of the Anti-Infective Drugs'.
(6) Paragraphs (8), (9), and (11) of section 409I(c) of the Public Health
Service Act (42 U.S.C. 284m(c)) are amended by striking `Advisory Subcommittee
of the Anti-Infective Drugs' each place it appears.
SEC. 4. EFFECTIVE DATE.
(a) IN GENERAL- Subject to subsection (b), this Act and the amendments made
by this Act take effect on the date of enactment of this Act.
(b) APPLICABILITY TO NEW DRUGS AND BIOLOGICAL PRODUCTS-
(1) IN GENERAL- Subsection (a) of section 505B of the Federal Food, Drug,
and Cosmetic Act (as added by section 2) shall apply to an application described
in paragraph (1) of that subsection submitted to the Secretary of Health
and Human Services on or after April 1, 1999.
(2) WAIVERS AND DEFERRALS-
(A) WAIVER OR DEFERRAL GRANTED- If, with respect to an application submitted
to the Secretary of Health and Human Services between April 1, 1999, and
the date of enactment of this Act, a waiver or deferral of pediatric assessments
was granted under regulations of the Secretary then in effect, the waiver
or deferral shall be a waiver or deferral under subsection (a) of section
505B of the Federal Food, Drug, and Cosmetic Act, except that any date
specified in such a deferral shall be extended by the number of days that
is equal to the number of days between October 17, 2002, and the date
of enactment of this Act.
(B) WAIVER AND DEFERRAL NOT GRANTED- If, with respect to an application
submitted to the Secretary of Health and Human Services between April
1, 1999, and the date of enactment of this Act, neither a waiver nor deferral
of pediatric assessments was granted under regulations of the Secretary
then in effect, the person that submitted the application shall be required
to submit assessments under subsection (a)(2) of section 505B of the Federal
Food, Drug, and Cosmetic Act on the date that is the later of--
(i) the date that is 1 year after the date of enactment of this Act;
or
(ii) such date as the Secretary may specify under subsection (a)(3)
of that section;
unless the Secretary grants a waiver under subsection (a)(4) of that section.
(c) NO LIMITATION OF AUTHORITY- Neither the lack of guidance or regulations
to implement this Act or the amendments made by this Act nor the pendency
of the process for issuing guidance or regulations shall limit the authority
of the Secretary of Health and Human Services under, or defer any requirement
under, this Act or those amendments.
Speaker of the House of Representatives.
Vice President of the United States and
President of the Senate.
END
