[Congressional Bills 108th Congress]
[From the U.S. Government Publishing Office]
[S. 650 Enrolled Bill (ENR)]
S.650
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).
``(2) Assessments.--
``(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.
``(4) Waivers.--
``(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.
``(2) Waivers.--
``(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,'';
(C) in subsection (b)--
(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.