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<PRE>[DOCID: f:s1789pcs.txt]





                                                       Calendar No. 271
107th CONGRESS
  1st Session
                                S. 1789

To amend the Federal Food, Drug, and Cosmetic Act to improve the safety 
             and efficacy of pharmaceuticals for children.


_______________________________________________________________________


                   IN THE SENATE OF THE UNITED STATES

             December 8 (legislative day, December 7), 2001

 Mr. Dodd (for himself and Mr. DeWine) introduced the following bill; 
                     which was read the first time

                           December 10, 2001

            Read the second time and placed on the calendar

_______________________________________________________________________

                                 A BILL


 
To amend the Federal Food, Drug, and Cosmetic Act to improve the safety 
             and efficacy of pharmaceuticals for children.

    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 ``Best Pharmaceuticals for Children 
Act''.

SEC. 2. PEDIATRIC STUDIES OF ALREADY-MARKETED DRUGS.

    Section 505A of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 
355a) is amended--
            (1) by striking subsection (b); and
            (2) in subsection (c)--
                    (A) by inserting after ``the Secretary'' the 
                following: ``determines that information relating to 
                the use of an approved drug in the pediatric population 
                may produce health benefits in that population and''; 
                and
                    (B) by striking ``concerning a drug identified in 
                the list described in subsection (b)''.

SEC. 3. RESEARCH FUND FOR THE STUDY OF DRUGS.

    Part B of title IV of the Public Health Service Act (42 U.S.C. 284 
et seq.) is amended--
            (1) by redesignating the second section 409C, relating to 
        clinical research (42 U.S.C. 284k), as section 409G;
            (2) by redesignating the second section 409D, relating to 
        enhancement awards (42 U.S.C. 284l), as section 409H; and
            (3) by adding at the end the following:

``SEC. 409I. PROGRAM FOR PEDIATRIC STUDIES OF DRUGS.

    ``(a) List of Drugs for Which Pediatric Studies Are Needed.--
            ``(1) In general.--Not later than 1 year after the date of 
        enactment of this section, the Secretary, acting through the 
        Director of the National Institutes of Health and in 
        consultation with the Commissioner of Food and Drugs and 
        experts in pediatric research, shall develop, prioritize, and 
        publish an annual list of approved drugs for which--
                    ``(A)(i) there is an approved application under 
                section 505(j) of the Federal Food, Drug, and Cosmetic 
                Act (21 U.S.C. 355(j));
                    ``(ii) there is a submitted application that could 
                be approved under the criteria of section 505(j) of the 
                Federal Food, Drug, and Cosmetic Act (21 U.S.C. 
                355(j));
                    ``(iii) there is no patent protection or market 
                exclusivity protection under the Federal Food, Drug, 
                and Cosmetic Act (21 U.S.C. 301 et seq.); or
                    ``(iv) there is a referral for inclusion on the 
                list under section 505A(d)(4)(C) of the Federal Food, 
                Drug, and Cosmetic Act (21 U.S.C. 355a(d)(4)(C)); and
                    ``(B) in the case of a drug referred to in clause 
                (i), (ii), or (iii) of subparagraph (A), additional 
                studies are needed to assess the safety and 
                effectiveness of the use of the drug in the pediatric 
                population.
            ``(2) Consideration of available information.--In 
        developing and prioritizing the list under paragraph (1), the 
        Secretary shall consider, for each drug on the list--
                    ``(A) the availability of information concerning 
                the safe and effective use of the drug in the pediatric 
                population;
                    ``(B) whether additional information is needed;
                    ``(C) whether new pediatric studies concerning the 
                drug may produce health benefits in the pediatric 
                population; and
                    ``(D) whether reformulation of the drug is 
                necessary.
    ``(b) Contracts for Pediatric Studies.--The Secretary shall award 
contracts to entities that have the expertise to conduct pediatric 
clinical trials (including qualified universities, hospitals, 
laboratories, contract research organizations, federally funded 
programs such as pediatric pharmacology research units, other public or 
private institutions, or individuals) to enable the entities to conduct 
pediatric studies concerning one or more drugs identified in the list 
described in subsection (a).
    ``(c) Process for Contracts and Labeling Changes.--
            ``(1) Written request to holders of approved applications 
        for drugs lacking exclusivity.--The Commissioner of Food and 
        Drugs, in consultation with the Director of the National 
        Institutes of Health, may issue a written request (which shall 
        include a timeframe for negotiations for an agreement) for 
        pediatric studies concerning a drug identified in the list 
        described in subsection (a)(1)(A) (except clause (iv)) to all 
        holders of an approved application for the drug under section 
        505 of the Federal Food, Drug, and Cosmetic Act. Such a written 
        request shall be made in a manner equivalent to the manner in 
        which a written request is made under subsection (a) or (b) of 
        section 505A of the Federal Food, Drug, and Cosmetic Act, 
        including with respect to information provided on the pediatric 
        studies to be conducted pursuant to the request.
            ``(2) Requests for contract proposals.--If the Commissioner 
        of Food and Drugs does not receive a response to a written 
        request issued under paragraph (1) within 30 days of the date 
        on which a request was issued, or if a referral described in 
        subsection (a)(1)(A)(iv) is made, the Secretary, acting through 
        the Director of the National Institutes of Health and in 
        consultation with the Commissioner of Food and Drugs, shall 
        publish a request for contract proposals to conduct the 
        pediatric studies described in the written request.
            ``(3) Disqualification.--A holder that receives a first 
        right of refusal shall not be entitled to respond to a request 
        for contract proposals under paragraph (2).
            ``(4) Guidance.--Not later than 270 days after the date of 
        enactment of this section, the Commissioner of Food and Drugs 
        shall promulgate guidance to establish the process for the 
        submission of responses to written requests under paragraph 
        (1).
            ``(5) Contracts.--A contract under this section may be 
        awarded only if a proposal for the contract is submitted to the 
        Secretary in such form and manner, and containing such 
        agreements, assurances, and information as the Secretary 
        determines to be necessary to carry out this section.
            ``(6) Reporting of studies.--
                    ``(A) In general.--On completion of a pediatric 
                study in accordance with a contract awarded under this 
                section, a report concerning the study shall be 
                submitted to the Director of the National Institutes of 
                Health and the Commissioner of Food and Drugs. The 
                report shall include all data generated in connection 
with the study.
                    ``(B) Availability of reports.--Each report 
           
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     submitted under subparagraph (A) shall be considered to 
                be in the public domain (subject to section 
                505A(d)(4)(D) of the Federal Food, Drug, and Cosmetic 
                Act (21 U.S.C. 355a(d)(4)(D)) and shall be assigned a 
                docket number by the Commissioner of Food and Drugs. An 
                interested person may submit written comments 
                concerning such pediatric studies to the Commissioner 
                of Food and Drugs, and the written comments shall 
                become part of the docket file with respect to each of 
                the drugs.
                    ``(C) Action by commissioner.--The Commissioner of 
                Food and Drugs shall take appropriate action in 
                response to the reports submitted under subparagraph 
                (A) in accordance with paragraph (7).
            ``(7) Requests for labeling change.--During the 180-day 
        period after the date on which a report is submitted under 
        paragraph (6)(A), the Commissioner of Food and Drugs shall--
                    ``(A) review the report and such other data as are 
                available concerning the safe and effective use in the 
                pediatric population of the drug studied;
                    ``(B) negotiate with the holders of approved 
                applications for the drug studied for any labeling 
                changes that the Commissioner of Food and Drugs 
                determines to be appropriate and requests the holders 
                to make; and
                    ``(C)(i) place in the public docket file a copy of 
                the report and of any requested labeling changes; and
                    ``(ii) publish in the Federal Register a summary of 
                the report and a copy of any requested labeling 
                changes.
            ``(8) Dispute resolution.--
                    ``(A) Referral to pediatric advisory subcommittee 
                of the anti-infective drugs advisory committee.--If, 
                not later than the end of the 180-day period specified 
                in paragraph (7), the holder of an approved application 
                for the drug involved does not agree to any labeling 
                change requested by the Commissioner of Food and Drugs 
                under that paragraph, the Commissioner of Food and 
                Drugs shall refer the request to the Pediatric Advisory 
                Subcommittee of the Anti-Infective Drugs Advisory 
                Committee.
                    ``(B) Action by the pediatric advisory subcommittee 
                of the anti-infective drugs advisory committee.--Not 
                later than 90 days after receiving a referral under 
                subparagraph (A), the Pediatric Advisory Subcommittee 
                of the Anti-Infective Drugs Advisory Committee shall--
                            ``(i) review the available information on 
                        the safe and effective use of the drug in the 
                        pediatric population, including study reports 
                        submitted under this section; and
                            ``(ii) make a recommendation to the 
                        Commissioner of Food and Drugs as to 
                        appropriate labeling changes, if any.
            ``(9) FDA determination.--Not later than 30 days after 
        receiving a recommendation from the Pediatric Advisory 
        Subcommittee of the Anti-Infective Drugs Advisory Committee 
        under paragraph (8)(B)(ii) with respect to a drug, the 
        Commissioner of Food and Drugs shall consider the 
        recommendation and, if appropriate, make a request to the 
        holders of approved applications for the drug to make any 
        labeling change that the Commissioner of Food and Drugs 
        determines to be appropriate.
            ``(10) Failure to agree.--If a holder of an approved 
        application for a drug, within 30 days after receiving a 
        request to make a labeling change under paragraph (9), does not 
        agree to make a requested labeling change, the Commissioner may 
        deem the drug to be misbranded under the Federal Food, Drug, 
        and Cosmetic Act (21 U.S.C. 301 et seq.).
            ``(11) No effect on authority.--Nothing in this subsection 
        limits the authority of the United States to bring an 
        enforcement action under the Federal Food, Drug, and Cosmetic 
        Act when a drug lacks appropriate pediatric labeling. Neither 
        course of action (the Pediatric Advisory Subcommittee of the 
        Anti-Infective Drugs Advisory Committee process or an 
        enforcement action referred to in the preceding sentence) shall 
        preclude, delay, or serve as the basis to stay the other course 
        of action.
            ``(12) Recommendation for formulation changes.--If a 
        pediatric study completed under public contract indicates that 
        a formulation change is necessary and the Secretary agrees, the 
        Secretary shall send a nonbinding letter of recommendation 
        regarding that change to each holder of an approved 
        application.
    ``(d) Authorization of Appropriations.--
            ``(1) In general.--There are authorized to be appropriated 
        to carry out this section--
                    ``(A) $200,000,000 for fiscal year 2002; and
                    ``(B) such sums as are necessary for each of the 5 
                succeeding fiscal years.
            ``(2) Availability.--Any amount appropriated under 
        paragraph (1) shall remain available to carry out this section 
        until expended.''.

SEC. 4. WRITTEN REQUEST TO HOLDERS OF APPROVED APPLICATIONS FOR DRUGS 
              THAT HAVE MARKET EXCLUSIVITY.

    Section 505A(d) of the Federal Food, Drug, and Cosmetic Act (21 
U.S.C. 355a(d)) is amended by adding at the end the following:
            ``(4) Written request to holders of approved applications 
        for drugs that have market exclusivity.--
                    ``(A) Request and response.--If the Secretary makes 
                a written request for pediatric studies (including 
                neonates, as appropriate) under subsection (c) to the 
                holder of an application approved under section 
                505(b)(1), the holder, not later than 180 days after 
                receiving the written request, shall respond to the 
                Secretary as to the intention of the holder to act on 
                the request by--
                            ``(i) indicating when the pediatric studies 
                        will be initiated, if the holder agrees to the 
                        request; or
                            ``(ii) indicating that the holder does not 
                        agree to the request.
                    ``(B) No agreement to request.--
                            ``(i) Referral.--If the holder does not 
                        agree to a written request within the time 
                        period specified in subparagraph (A), and if 
                        the Secretary determines that there is a 
                        continuing need for information relating to the 
                        use of the drug in the pediatric population 
                        (including neonates, as appropriate), the 
                        Secretary shall refer the drug to the 
                        Foundation for the National Institutes of 
                        Health established under section 499 of the 
                        Public Health Service Act (42 U.S.C. 290b) 
                        (referred to in this paragraph as the 
                        `Foundation') for the conduct of the pediatric 
studies described in the written request.
                            ``(ii) Public notice.--The Secretary shall 
                        give public notice of the name of the drug, the 
                        name of the manufacturer, and the indi
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cations 
                        to be studied made in a referral under clause 
                        (i).
                    ``(C) Lack of funds.--On referral of a drug under 
                subparagraph (B)(i), the Foundation shall issue a 
                proposal to award a grant to conduct the requested 
                studies unless the Foundation certifies to the 
                Secretary, within a timeframe that the Secretary 
                determines is appropriate through guidance, that the 
                Foundation does not have funds available under section 
                499(j)(9)(B)(i) to conduct the requested studies. If 
                the Foundation so certifies, the Secretary shall refer 
                the drug for inclusion on the list established under 
                section 409I of the Public Health Service Act for the 
                conduct of the studies.
                    ``(D) Effect of subsection.--Nothing in this 
                subsection (including with respect to referrals from 
                the Secretary to the Foundation) alters or amends 
                section 301(j) of this Act or section 552 of title 5 or 
                section 1905 of title 18, United States Code.
                    ``(E) No requirement to refer.--Nothing in this 
                subsection shall be construed to require that every 
                declined written request shall be referred to the 
                Foundation.
                    ``(F) Written requests under subsection (b).--For 
                drugs under subsection (b) for which written requests 
                have not been accepted, if the Secretary determines 
                that there is a continuing need for information 
                relating to the use of the drug in the pediatric 
                population (including neonates, as appropriate), the 
                Secretary shall issue a written request under 
                subsection (c) after the date of approval of the 
                drug.''.

SEC. 5. TIMELY LABELING CHANGES FOR DRUGS GRANTED EXCLUSIVITY; DRUG 
              FEES.

    (a) Elimination of User Fee Waiver for Pediatric Supplements.--
Section 736(a)(1) of the Federal Food, Drug, and Cosmetic Act (21 
U.S.C. 379h(a)(1)) is amended--
            (1) by striking subparagraph (F); and
            (2) by redesignating subparagraph (G) as subparagraph (F).
    (b) Labeling Changes.--
            (1) Definition of priority supplement.--Section 201 of the 
        Federal Food Drug, and Cosmetic Act (21 U.S.C. 321) is amended 
        by adding at the end the following:
            ``(kk) Priority supplement.--The term `priority supplement' 
        means a drug application referred to in section 101(4) of the 
        Food and Drug Administration Modernization Act of 1997 (111 
        Stat. 2298).''.
            (2) Treatment as priority supplements.--Section 505A of the 
        Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a) is 
        amended by adding at the end the following:
    ``(l) Labeling Supplements.--
            ``(1) Priority status for pediatric supplements.--Any 
        supplement to an application under section 505 proposing a 
        labeling change pursuant to a report on a pediatric study under 
        this section--
                    ``(A) shall be considered to be a priority 
                supplement; and
                    ``(B) shall be subject to the performance goals 
                established by the Commissioner for priority drugs.
            ``(2) Dispute resolution.--
                    ``(A) Request for labeling change and failure to 
                agree.--If the Commissioner determines that an 
                application with respect to which a pediatric study is 
                conducted under this section is approvable and that the 
                only open issue for final action on the application is 
                the reaching of an agreement between the sponsor of the 
                application and the Commissioner on appropriate changes 
                to the labeling for the drug that is the subject of the 
                application, not later than 180 days after the date of 
                submission of the application--
                            ``(i) the Commissioner shall request that 
                        the sponsor of the application make any 
                        labeling change that the Commissioner 
                        determines to be appropriate; and
                            ``(ii) if the sponsor of the application 
                        does not agree to make a labeling change 
                        requested by the Commissioner, the Commissioner 
                        shall refer the matter to the Pediatric 
                        Advisory Subcommittee of the Anti-Infective 
                        Drugs Advisory Committee.
                    ``(B) Action by the pediatric advisory subcommittee 
                of the anti-infective drugs advisory committee.--Not 
                later than 90 days after receiving a referral under 
                subparagraph (A)(ii), the Pediatric Advisory 
                Subcommittee of the Anti-Infective Drugs Advisory 
                Committee shall--
                            ``(i) review the pediatric study reports; 
                        and
                            ``(ii) make a recommendation to the 
                        Commissioner concerning appropriate labeling 
                        changes, if any.
                    ``(C) Consideration of recommendations.--The 
                Commissioner shall consider the recommendations of the 
                Pediatric Advisory Subcommittee of the Anti-Infective 
                Drugs Advisory Committee and, if appropriate, not later 
                than 30 days after receiving the recommendation, make a 
                request to the sponsor of the application to make any 
                labeling change that the Commissioner determines to be 
                appropriate.
                    ``(D) Misbranding.--If the sponsor of the 
                application, within 30 days after receiving a request 
                under subparagraph (C), does not agree to make a 
                labeling change requested by the Commissioner, the 
                Commissioner may deem the drug that is the subject of 
                the application to be misbranded.
                    ``(E) No effect on authority.--Nothing in this 
                subsection limits the authority of the United States to 
                bring an enforcement action under this Act when a drug 
                lacks appropriate pediatric labeling. Neither course of 
                action (the Pediatric Advisory Subcommittee of the 
                Anti-Infective Drugs Advisory Committee process or an 
                enforcement action referred to in the preceding 
                sentence) shall preclude, delay, or serve as the basis 
                to stay the other course of action.''.

SEC. 6. OFFICE OF PEDIATRIC THERAPEUTICS.

    (a) Establishment.--The Secretary of Health and Human Services 
shall establish an Office of Pediatric Therapeutics within the Food and 
Drug Administration.
    (b) Duties.--The Office of Pediatric Therapeutics shall be 
responsible for coordination and facilitation of all activities of the 
Food and Drug Administration that may have any effect on a pediatric 
population or the practice of pediatrics or may in any other way 
involve pediatric issues.
    (c) Staff.--The staff of the Office of Pediatric Therapeutics shall 
coordinate with employees of the Department of Health and Human 
Services who exercise re- sponsibilities relating to pediatric 
therapeutics and shall include--
            (1) 1 or more additional individuals with expertise 
        concerning ethical issues presented by the conduct of clinical 
        research in the pediatric population; and
            (2) 1 or more additional individuals with expertise in 
        pediatrics as may be necessary to perform the activities 
 
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       described in subsection (b).

SEC. 7. NEONATES.

    Section 505A(g) of the Federal Food, Drug, and Cosmetic Act (21 
U.S.C. 355a(g)) is amended by inserting ``(including neonates in 
appropriate cases)'' after ``pediatric age groups''.

SEC. 8. SUNSET.

    Section 505A of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 
355a) is amended by striking subsection (j) and inserting the 
following:
    ``(j) Sunset.--A drug may not receive any 6-month period under 
subsection (a) or (c) unless--
            ``(1) on or before October 1, 2007, the Secretary makes a 
        written request for pediatric studies of the drug;
            ``(2) on or before October 1, 2007, an application for the 
        drug is accepted for filing under section 505(b); and
            ``(3) all requirements of this section are met.''.

SEC. 9. DISSEMINATION OF PEDIATRIC INFORMATION.

    Section 505A of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 
355a) (as amended by section 5(b)(2)) is amended by adding at the end 
the following:
    ``(m) Dissemination of Pediatric Information.--
            ``(1) In general.--Not later than 180 days after the date 
        of submission of a report on a pediatric study under this 
        section, the Commissioner shall make available to the public a 
        summary of the medical and clinical pharmacology reviews of 
        pediatric studies conducted for the supplement, including by 
        publication in the Federal Register.
            ``(2) Effect of subsection.--Nothing in this subsection 
        alters or amends section 301(j) of this Act or section 552 of 
        title 5 or section 1905 of title 18, United States Code.''.

SEC. 10. CLARIFICATION OF INTERACTION OF PEDIATRIC EXCLUSIVITY UNDER 
              SECTION 505A OF THE FEDERAL FOOD, DRUG, AND COSMETIC ACT 
              AND 180-DAY EXCLUSIVITY AWARDED TO AN APPLICANT FOR 
              APPROVAL OF A DRUG UNDER SECTION 505(J) OF THAT ACT.

    Section 505A of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 
355a) (as amended by section 9) is amended by adding at the end the 
following:
    ``(n) Clarification of Interaction of Market Exclusivity Under This 
Section and Market Exclusivity Awarded to an Applicant for Approval of 
a Drug Under Section 505(j).--If a 180-day period under section 
505(j)(5)(B)(iv) overlaps with a 6-month exclusivity period under this 
section, so that the applicant for approval of a drug under section 
505(j) entitled to the 180-day period under that section loses a 
portion of the 180-day period to which the applicant is entitled for 
the drug, the 180-day period shall be extended from--
            ``(1) the date on which the 180-day period would have 
        expired by the number of days of the overlap, if the 180-day 
        period would, but for the application of this subsection, 
        expire after the 6-month exclusivity period; or
            ``(2) the date on which the 6-month exclusivity period 
        expires, by the number of days of the overlap if the 180-day 
        period would, but for the application of this subsection, 
        expire during the 6 month exclusivity period.''.

SEC. 11. PROMPT APPROVAL OF DRUGS UNDER SECTION 505(J) WHEN PEDIATRIC 
              INFORMATION IS ADDED TO LABELING.

    (a) In General.--Section 505A of the Federal Food, Drug, and 
Cosmetics Act (21 U.S.C. 355a) (as amended by section 10) is amended by 
adding at the end the following:
    ``(o) Prompt Approval of Drugs Under Section 505(j) When Pediatric 
Information Is Added to Labeling.--
            ``(1) General rule.--A drug for which an application has 
        been submitted or approved under section 505(j) shall not be 
        considered ineligible for approval under that section or 
        misbranded under section 502 on the basis that the labeling of 
        the drug omits a pediatric indication or any other aspect of 
        labeling pertaining to pediatric use when the omitted 
        indication or other aspect is protected by patent or by 
        exclusivity under clause (iii) or (iv) of section 505(j)(5)(D).
            ``(2) Labeling.--Notwithstanding clauses (iii) and (iv) of 
        section 505(j)(5)(D), the Secretary may require that the 
        labeling of a drug approved under section 505(j) that omits a 
        pediatric indication or other aspect of labeling as described 
        in paragraph (1) include--
                    ``(A) a statement that, because of marketing 
                exclusivity for a manufacturer--
                            ``(i) the drug is not labeled for pediatric 
                        use; or
                            ``(ii) in the case of a drug for which 
                        there is an additional pediatric use not 
                        referred to in paragraph (1), the drug is not 
                        labeled for the pediatric use under paragraph 
                        (1); and
                    ``(B) a statement of any appropriate pediatric 
                contraindications, warnings, or precautions that the 
                Secretary considers necessary.
            ``(3) Preservation of pediatric exclusivity and other 
        provisions.--This subsection does not affect--
                    ``(A) the availability or scope of exclusivity 
                under this section;
                    ``(B) the availability or scope of exclusivity 
                under section 505 for pediatric formulations;
                    ``(C) the question of the eligibility for approval 
                of any application under section 505(j) that omits any 
                other conditions of approval entitled to exclusivity 
                under clause (iii) or (iv) of section 505(j)(5)(D); or
                    ``(D) except as expressly provided in paragraphs 
                (1) and (2), the operation of section 505.''.
    (b) Effective Date.--The amendment made by subsection (a) takes 
effect on the date of enactment of this Act, including with respect to 
applications under section 505(j) of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 355(j)) that are approved or pending on that 
date.

SEC. 12. STUDY CONCERNING RESEARCH INVOLVING CHILDREN.

    (a) Contract With Institute of Medicine.--The Secretary of Health 
and Human Services shall enter into a contract with the Institute of 
Medicine for--
            (1) the conduct, in accordance with subsection (b), of a 
        review of--
                    (A) Federal regulations in effect on the date of 
                the enactment of this Act relating to research 
                involving children;
                    (B) federally prepared or supported reports 
                relating to research involving children; and
                    (C) federally supported evidence-based research 
                involving children; and
            (2) the submission to the Committee on Health, Education, 
        Labor, and Pensions of the Senate and the Committee on Energy 
        and Commerce of the House of Representatives, not later than 2 
        years after the date of enactment of this Act, of a report 
        concerning the review conducted under paragraph (1) that 
        includes recommendations on best practices relating to research 
        involving children.
    (b) Areas of Review.--In conducting the review under subsection 
(a)(1), the Institute of Medicine shall consider the following:
            (1) The written and oral process of obtaining and defining 
        ``assent'', ``permission'' and ``informed consent'' with 
        respect to child clinical research participants and the 
        parents, guardians, and the individuals who may serve as the 
        legally authorized representatives of such children (as defined 
        in subpart A of part 46 of title 45, Code of Federal 
        Regulations).
            (2) The expectations and comprehension of child research 
        participants and the parents, guardians, or legally authorized 
        representatives of such children, for the direct benefits and 
        risks of the child's rese
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arch involvement, particularly in 
        terms of research versus therapeutic treatment.
            (3) The definition of ``minimal risk'' with respect to a 
        healthy child or a child with an illness.
            (4) The appropriateness of the regulations applicable to 
        children of differing ages and maturity levels, including 
        regulations relating to legal status.
            (5) Whether payment (financial or otherwise) may be 
        provided to a child or his or her parent, guardian, or legally 
        authorized representative for the participation of the child in 
        research, and if so, the amount and type of payment that may be 
        made.
            (6) Compliance with the regulations referred to in 
        subsection (a)(1)(A), the monitoring of such compliance 
        (including the role of institutional review boards), and the 
        enforcement actions taken for violations of such regulations.
            (7) The unique roles and responsibilities of institutional 
        review boards in reviewing research involving children, 
        including composition of membership on institutional review 
        boards.
    (c) Requirements of Expertise.--The Institute of Medicine shall 
conduct the review under subsection (a)(1) and make recommendations 
under subsection (a)(2) in conjunction with experts in pediatric 
medicine, pediatric research, and the ethical conduct of research 
involving children.

SEC. 13. FOUNDATION FOR THE NATIONAL INSTITUTES OF HEALTH.

    Section 499 of the Public Health Service Act (42 U.S.C. 290b) is 
amended--
            (1) in subsection (b), by inserting ``(including collection 
        of funds for pediatric pharmacologic research)'' after 
        ``mission'';
            (2) in subsection (c)(1)--
                    (A) by redesignating subparagraph (C) as 
                subparagraph (D); and
                    (B) by inserting after subparagraph (B) the 
                following:
                    ``(C) A program to collect funds for pediatric 
                pharmacologic research and studies listed by the 
                Secretary pursuant to section 409I(a)(1)(A) of this Act 
                and referred under section 505A(d)(4)(C) of the Federal 
                Food, Drug, and Cosmetic Act (21 U.S.C. 
                355a(d)(4)(C)).'';
            (3) in subsection (d)--
                    (A) in paragraph (1)--
                            (i) in subparagraph (B)--
                                    (I) in clause (ii), by striking 
                                ``and'' at the end;
                                    (II) in clause (iii), by striking 
                                the period and inserting ``; and''; and
                                    (III) by adding at the end the 
                                following:
                            ``(iv) the Commissioner of Food and 
                        Drugs.''; and
                            (ii) by striking subparagraph (C) and 
                        inserting the following:
                    ``(C) The ex officio members of the Board under 
                subparagraph (B) shall appoint to the Board individuals 
                from among a list of candidates to be provided by the 
                National Academy of Science. Such appointed members 
                shall include--
                            ``(i) representatives of the general 
                        biomedical field;
                            ``(ii) representatives of experts in 
                        pediatric medicine and research;
                            ``(iii) representatives of the general 
                        biobehavioral field, which may include experts 
                        in biomedical ethics; and
                            ``(iv) representatives of the general 
                        public, which may include representatives of 
                        affected industries.''; and
                    (B) in paragraph (2), by realigning the margin of 
                subparagraph (B) to align with subparagraph (A);
            (4) in subsection (k)(9)--
                    (A) by striking ``The Foundation'' and inserting 
                the following:
                    ``(A) In general.--The Foundation''; and
                    (B) by adding at the end the following:
                    ``(B) Gifts, grants, and other donations.--
                            ``(i) In general.--Gifts, grants, and other 
                        donations to the Foundation may be designated 
                        for pediatric research and studies on drugs, 
                        and funds so designated shall be used solely 
                        for grants for research and studies under 
                        subsection (c)(1)(C).
                            ``(ii) Other gifts.--Other gifts, grants, 
                        or donations received by the Foundation and not 
                        described in clause (i) may also be used to 
                        support such pediatric research and studies.
                            ``(iii) Report.--The recipient of a grant 
                        for research and studies shall agree to provide 
                        the Director of the National Institutes of 
                        Health and the Commissioner of Food and Drugs, 
                        at the conclusion of the research and studies--
                                    ``(I) a report describing the 
                                results of the research and studies; 
                                and
                                    ``(II) all data generated in 
                                connection with the research and 
                                studies.
                            ``(iv) Action by the commissioner of food 
                        and drugs.--The Commissioner of Food and Drugs 
                        shall take appropriate action in response to a 
                        report received under clause (iii) in 
                        accordance with paragraphs (7) through (12) of 
                        section 409I(c), including negotiating with the 
                        holders of approved applications for the drugs 
                        studied for any labeling changes that the 
                        Commissioner determines to be appropriate and 
                        requests the holders to make.
                    ``(C) Applicability.--Subparagraph (A) does not 
                apply to the program described in subsection 
                (c)(1)(C).'';
            (5) by redesignating subsections (f) through (m) as 
        subsections (e) through (l), respectively;
            (6) in subsection (h)(11) (as so redesignated), by striking 
        ``solicit'' and inserting ``solicit,''; and
            (7) in paragraphs (1) and (2) of subsection (j) (as so 
        redesignated), by striking ``(including those developed under 
        subsection (d)(2)(B)(i)(II))'' each place it appears.

SEC. 14. PEDIATRIC PHARMACOLOGY ADVISORY COMMITTEE.

    (a) In General.--The Secretary of Health and Human Services shall, 
under section 222 of the Public Health Service Act (42 U.S.C. 217a), 
convene and consult an advisory committee on pediatric pharmacology 
(referred to in this section as the ``advisory committee'').
    (b) Purpose.--
            (1) In general.--The advisory committee shall advise and 
        make recommendations to the Secretary, through the Commissioner 
        of Food and Drugs and in consultation with the Director of the 
        National Institutes of Health, on matters relating to pediatric 
        pharmacology.
            (2) Matters included.--The matters referred to in paragraph 
        (1) include--
                    (A) pediatric research conducted under sections 
                351, 409I, and 499 of the Public Health Service Act and 
                sections 501, 502, 505, and 505A of the Federal Food, 
                Drug, and Cosmetic Act;
                    (B) identif
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ication of research priorities related 
                to pediatric pharmacology and the need for additional 
                treatments of specific pediatric diseases or 
                conditions; and
                    (C) the ethics, design, and analysis of clinical 
                trials related to pediatric pharmacology.
    (c) Composition.--The advisory committee shall include 
representatives of pediatric health organizations, pediatric 
researchers, relevant patient and patient-family organizations, and 
other experts selected by the Secretary.

SEC. 15. PEDIATRIC SUBCOMMITTEE OF THE ONCOLOGIC DRUGS ADVISORY 
              COMMITTEE.

    (a) Clarification of Authorities.--
            (1) In general.--The Pediatric Subcommittee of the 
        Oncologic Drugs Advisory Committee (referred to in this section 
        as the ``Subcommittee''), in carrying out the mission of 
        reviewing and evaluating the data concerning the safety and 
        effectiveness of marketed and investigational human drug 
        products for use in the treatment of pediatric cancers, shall--
                    (A) evaluate and, to the extent practicable, 
                prioritize new and emerging therapeutic alternatives 
                available to treat pediatric cancer;
                    (B) provide recommendations and guidance to help 
                ensure that children with cancer have timely access to 
                the most promising new cancer therapies; and
                    (C) advise on ways to improve consistency in the 
                availability of new therapeutic agents.
            (2) Membership.--
                    (A) In general.--The Secretary shall appoint not 
                more than 11 voting members to the Pediatric 
                Subcommittee from the membership of the Pediatric 
                Pharmacology Advisory Committee and the Oncologic Drugs 
                Advisory Committee.
                    (B) Request for participation.--The Subcommittee 
                shall request participation of the following members in 
                the scientific and ethical consideration of topics of 
                pediatric cancer, as necessary:
                            (i) At least 2 pediatric oncology 
                        specialists from the National Cancer Institute.
                            (ii) At least 4 pediatric oncology 
                        specialists from--
                                    (I) the Children's Oncology Group;
                                    (II) other pediatric experts with 
                                an established history of conducting 
                                clinical trials in children; or
                                    (III) consortia sponsored by the 
                                National Cancer Institute, such as the 
                                Pediatric Brain Tumor Consortium, the 
                                New Approaches to Neuroblastoma Therapy 
                                or other pediatric oncology consortia.
                            (iii) At least 2 representatives of the 
                        pediatric cancer patient and patient-family 
                        community.
                            (iv) 1 representative of the nursing 
                        community.
                            (v) At least 1 statistician.
                            (vi) At least 1 representative of the 
                        pharmaceutical industry.
    (b) Pre-Clinical Models To Evaluate Promising Pediatric Cancer 
Therapies.--Section 413 of the Public Health Service Act (42 U.S.C. 
285a-2) is amended by adding at the end the following:
    ``(c) Pre-Clinical Models To Evaluate Promising Pediatric Cancer 
Therapies.--
            ``(1) Expansion and coordination of activities.--The 
        Director of the National Cancer Institute shall expand, 
        intensify, and coordinate the activities of the Institute with 
        respect to research on the development of preclinical models to 
        evaluate which therapies are likely to be effective for 
        treating pediatric cancer.
            ``(2) Coordination with other institutes.--The Director of 
        the Institute shall coordinate the activities under paragraph 
        (1) with similar activities conducted by other national 
        research institutes and agencies of the National Institutes of 
        Health to the extent that those Institutes and agencies have 
        responsibilities that are related to pediatric cancer.''.
    (c) Clarification of Availability of Investigational New Drugs for 
Pediatric Study and Use.--
            (1) Amendment of the federal food, drug, and cosmetic 
        act.--Section 505(i)(1) of the Federal Food, Drug, and Cosmetic 
        Act (21 U.S.C. 355(i)(1)) is amended--
                    (A) in subparagraph (B), by striking ``and'' at the 
                end;
                    (B) in subparagraph (C), by striking the period at 
                the end and inserting ``; and''; and
                    (C) by adding at the end the following:
                    ``(D) the submission to the Secretary by the 
                manufacturer or the sponsor of the investigation of a 
                new drug of a statement of intent regarding whether the 
                manufacturer or sponsor has plans for assessing 
                pediatric safety and efficacy.''.
            (2) Amendment of the public health service act.--Section 
        402(j)(3)(A) of the Public Health Service Act (42 U.S.C. 
        282(j)(3)(A)) is amended in the first sentence--
                    (A) by striking ``trial sites, and'' and inserting 
                ``trial sites,''; and
                    (B) by striking ``in the trial,'' and inserting 
                ``in the trial, and a description of whether, and 
                through what procedure, the manufacturer or sponsor of 
                the investigation of a new drug will respond to 
                requests for protocol exception, with appropriate 
                safeguards, for single-patient and expanded protocol 
                use of the new drug, particularly in children,''.
    (d) Report.--Not later than January 31, 2003, the Secretary of 
Health and Human Services, acting through the Commissioner of Food and 
Drugs and in consultation with the Director of the National Institutes 
of Health, shall submit to the Committee on Health, Education, Labor, 
and Pensions of the Senate and the Committee on Energy and Commerce of 
the House of Representatives a report on patient access to new 
therapeutic agents for pediatric cancer, including access to single 
patient use of new therapeutic agents.

SEC. 16. REPORT ON PEDIATRIC EXCLUSIVITY PROGRAM.

    Not later than October 1, 2006, the Comptroller General of the 
United States, in consultation with the Secretary of Health and Human 
Services, shall submit to Congress a report that addresses the 
following issues, using publicly available data or data otherwise 
available to the Government that may be used and disclosed under 
applicable law:
            (1) The effectiveness of section 505A of the Federal Food, 
        Drug, and Cosmetic Act and section 409I of the Public Health 
        Service Act (as added by this Act) in ensuring that medicines 
        used by children are tested and properly labeled, including--
                    (A) the number and importance of drugs for children 
                that are being tested as a result of this legislation 
                and the importance for children, health care providers, 
                parents, and others of labeling changes made as a 
                result of such testing;
                    (B) the number and importance of drugs for children 
                that are not being tested for their use notwithstanding 
                the provisions of this legislation, and possible 
                reasons for the lack of testing; and
                    (C) the number of drugs for which testing is being 
                done, exclusivity 
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granted, and labeling changes 
                required, including the date pediatric exclusivity is 
                granted and the date labeling changes are made and 
                which labeling changes required the use of the dispute 
                resolution process established pursuant to the 
                amendments made by this Act, together with a 
                description of the outcomes of such process, including 
                a description of the disputes and the recommendations 
                of the Pediatric Advisory Subcommittee of the Anti-
                Infective Drugs Advisory Committee.
            (2) The economic impact of section 505A of the Federal 
        Food, Drug, and Cosmetic Act and section 409I of the Public 
        Health Service Act (as added by this Act), including an 
        estimate of--
                    (A) the costs to taxpayers in the form of higher 
                expenditures by medicaid and other Government programs;
                    (B) sales for each drug during the 6-month period 
                for which exclusivity is granted, as attributable to 
                such exclusivity;
                    (C) costs to consumers and private insurers as a 
                result of any delay in the availability of lower cost 
                generic equivalents of drugs tested and granted 
                exclusivity under the Federal Food, Drug, and Cosmetic 
                Act (21 U.S.C. 301 et seq.), and loss of revenue by the 
                generic drug industry and retail pharmacies as a result 
                of any such delay; and
                    (D) the benefits to the government, to private 
                insurers, and to consumers resulting from decreased 
                health care costs, including--
                            (i) decreased hospitalizations and fewer 
                        medical errors, due to more appropriate and 
                        more effective use of medications in children 
                        as a result of testing and re-labeling because 
                        of the amendments made by this Act;
                            (ii) direct and indirect benefits 
                        associated with fewer physician visits not 
                        related to hospitalization;
                            (iii) benefits to children from missing 
                        less time at school and being less affected by 
                        chronic illnesses, thereby allowing a better 
                        quality of life;
                            (iv) benefits to consumers from lower 
                        health insurance premiums due to lower 
                        treatment costs and hospitalization rates; and
                            (v) benefits to employers from reduced need 
                        for employees to care for family members.
            (3) The nature and type of studies in children for each 
        drug granted exclusivity under the Federal Food, Drug, and 
        Cosmetic Act (21 U.S.C. 301 et seq.), including--
                    (A) a description of the complexity of the studies;
                    (B) the number of study sites necessary to obtain 
                appropriate data;
                    (C) the numbers of children involved in any 
                clinical studies; and
                    (D) the estimated cost of each of the studies.
            (4) Any recommendations for modifications to the programs 
        established under section 505A of the Federal Food, Drug, and 
        Cosmetic Act (21 U.S.C. 355a) and section 409I of the Public 
        Health Service Act (as added by section 3) that the Secretary 
        determines to be appropriate, including a detailed rationale 
        for each recommendation.
            (5) The increased private and Government-funded pediatric 
        research capability associated with this Act and the amendments 
        made by this Act.
            (6) The number of written requests and additional letters 
        of recommendation that the Secretary issues.
            (7) The prioritized list of off-patent drugs for which the 
        Secretary issues written requests.
            (8)(A) The efforts made by Secretary to increase the number 
        of studies conducted in the neonate population; and
            (B) the results of those efforts, including efforts made to 
        encourage the conduct of appropriate studies in neonates by 
        companies with products that have sufficient safety and other 
        information to make the conduct of studies ethical and safe.

SEC. 17. ADVERSE-EVENT REPORTING.

    (a) Toll-Free Number in Labeling.--Not later than one year after 
the date of the enactment of this Act, the Secretary of Health and 
Human Services shall promulgate a final rule requiring that the 
labeling of each drug for which an application is approved under 
section 505 of the Federal Food, Drug, and Cosmetic Act (regardless of 
the date on which approved) include the toll-free number maintained by 
the Secretary for the purpose of receiving reports of adverse events 
regarding drugs and a statement that such number is to be used for 
reporting purposes only, not to receive medical advice. With respect to 
the final rule:
            (1) The rule shall provide for the implementation of such 
        labeling requirement in a manner that the Secretary considers 
        to be most likely to reach the broadest consumer audience.
            (2) In promulgating the rule, the Secretary shall seek to 
        minimize the cost of the rule on the pharmacy profession.
            (3) The rule shall take effect not later than 60 days after 
        the date on which the rule is promulgated.
    (b) Drugs With Pediatric Market Exclusivity.--
            (1) In general.--During the one-year beginning on the date 
        on which a drug receives a period of market exclusivity under 
        505A of the Federal Food, Drug, and Cosmetic Act, any report of 
        an adverse event regarding the drug that the Secretary of 
        Health and Human Services receives shall be referred to the 
        Office of Pediatric Therapeutics established under section 6 of 
        this Act. In considering the report, the Director of such 
        Office shall provide for the review of the report by the 
        Pediatric Advisory Subcommittee of the Anti-Infective Drugs 
        Advisory Committee, including obtaining any recommendations of 
        such Subcommittee regarding whether the Secretary should take 
        action under the Federal Food, Drug, and Cosmetic Act in 
        response to the report.
            (2) Rule of construction.--Paragraph (1) may not be 
        construed as restricting the authority of the Secretary of 
        Health and Human Services to continue carrying out the 
        activities described in such paragraph regarding a drug after 
        the one-year period described in such paragraph regarding the 
        drug has expired.

SEC. 18. MINORITY CHILDREN AND PEDIATRIC-EXCLUSIVITY PROGRAM.

    (a) Protocols for Pediatric Studies.--Section 505A of the Federal 
Food, Drug, and Cosmetic Act (21 U.S.C. 355a) is amended in subsection 
(d)(2) by inserting after the first sentence the following: ``In 
reaching an agreement regarding written protocols, the Secretary shall 
take into account adequate representation of children of ethnic and 
racial minorities.''.
    (b) Study by General Accounting Office.--
            (1) In general.--The Comptroller General of the United 
        States shall conduct a study for the purpose of determining the 
        following:
                    (A) The extent to which children of ethnic and 
                racial minorities are adequately represented in studies 
                under section 505A of the Federal Food, Drug, and 
                Cosmetic Act; and to the extent ethnic and racial 
                minorities are not adequately represented, the reasons 
                for such under representation and recommendations to 
              
a5b
  increase such representation.
                    (B) Whether the Food and Drug Administration has 
                appropriate management systems to monitor the 
                representation of the children of ethnic and racial 
                minorities in such studies.
                    (C) Whether drugs used to address diseases that 
                disproportionately affect racial and ethnic minorities 
                are being studied for their safety and effectiveness 
                under section 505A of the Federal Food, Drug, and 
                Cosmetic Act.
            (2) Date certain for completing study.--Not later than 
        January 10, 2003, the Comptroller General shall complete the 
        study required in paragraph (1) and submit to the Congress a 
        report describing the findings of the study.

SEC. 19. TECHNICAL AND CONFORMING AMENDMENTS.

    Section 505A of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 
355a) (as amended by sections 2(1), 5(b)(2), 9, 10, 11, and 17) is 
amended--
            (1)(A) by striking ``(j)(4)(D)(ii)'' each place it appears 
        and inserting ``(j)(5)(D)(ii)'';
            (B) by striking ``(j)(4)(D)'' each place it appears and 
        inserting ``(j)(5)(D)''; and
            (C) by striking ``505(j)(4)(D)'' each place it appears and 
        inserting ``505(j)(5)(D)'';
            (2) by redesignating subsections (a), (g), (h), (i), (j), 
        (k), (l), (m), (n), and (o) as subsections (b), (a), (g), (h), 
        (n), (m), (i), (j), (k), and (l) respectively;
            (3) by moving the subsections so as to appear in 
        alphabetical order;
            (4) in paragraphs (1), (2), and (3) of subsection (d), 
        subsection (e), and subsection (m) (as redesignated by 
        paragraph (2)), by striking ``subsection (a) or (c)'' and 
        inserting ``subsection (b) or (c)''; and
            (5) in subsection (g) (as redesignated by paragraph (2)), 
        by striking ``subsection (a) or (b)'' and inserting 
        ``subsection (b) or (c)''.




                                                       Calendar No. 271

107th CONGRESS

  1st Session

                                S. 1789

_______________________________________________________________________

                                 A BILL

To amend the Federal Food, Drug, and Cosmetic Act to improve the safety 
             and efficacy of pharmaceuticals for children.

_______________________________________________________________________

                           December 10, 2001

            Read the second time and placed on the calendar

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