[United States Statutes at Large, Volume 117, 108th Congress, 1st Session]
[From the U.S. Government Printing Office, www.gpo.gov]

117 STAT. 1936

Public Law 108-155
108th Congress

An Act


 
To amend the Federal Food, Drug, and Cosmetic [NOTE: Dec. 3,
2003 -  [S. 650]] 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 [NOTE: Pediatric Research
Equity Act of 2003.] Representatives of the United States of America in
Congress assembled,

SECTION 1. [NOTE: 21 USC 301 note.] 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 [NOTE: 21 USC 355c.] 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

[[Page 1937]]
117 STAT. 1937

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

[[Page 1938]]
117 STAT. 1938

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

[[Page 1939]]
117 STAT. 1939

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

[[Page 1940]]
117 STAT. 1940

``(bb) the Secretary does not
receive a response as specified under
section 409I(c)(2) of that Act; and
``(iii)(I) [NOTE: Certification.] 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 [NOTE: Deadline. Certification.] 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).

[[Page 1941]]
117 STAT. 1941

``(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--

[[Page 1942]]
117 STAT. 1942

(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. [NOTE: 21 USC 355c note.] 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--

[[Page 1943]]
117 STAT. 1943

(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.

Approved December 3, 2003.

LEGISLATIVE HISTORY--S. 650:
---------------------------------------------------------------------------

SENATE REPORTS: No. 108-84 (Comm. on Health, Education, Labor, and
Pensions).
CONGRESSIONAL RECORD, Vol. 149 (2003):
July 21, considered and passed Senate.
Nov. 19, considered and passed House.