[Congressional Bills 108th Congress]
[From the U.S. Government Publishing Office]
[S. 650 Engrossed in Senate (ES)]

  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
108th CONGRESS
  1st Session
                                 S. 650

_______________________________________________________________________

                                 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 1 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 1 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.

            Passed the Senate July 23 (legislative day, July 21), 2003.

            Attest:

                                                             Secretary.
108th CONGRESS

  1st Session

                                 S. 650

_______________________________________________________________________

                                 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.