    [United States Statutes at Large, Volume 117, 108th Congress, 1st Session]
    [From the U.S. Government Publishing 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.