[Congressional Bills 110th Congress]
[From the U.S. Government Publishing Office]
[S. 993 Introduced in Senate (IS)]







110th CONGRESS
  1st Session
                                 S. 993

                     To improve pediatric research.


_______________________________________________________________________


                   IN THE SENATE OF THE UNITED STATES

                             March 27, 2007

Mrs. Clinton (for herself and Mr. Dodd) introduced the following bill; 
     which was read twice and referred to the Committee on Health, 
                     Education, Labor, and Pensions

_______________________________________________________________________

                                 A BILL


 
                     To improve pediatric research.

    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 Improvement 
Act''.

SEC. 2. PEDIATRIC FORMULATIONS, EXTRAPOLATIONS, AND DEFERRALS.

    Section 505B(a) of the Federal Food, Drug, and Cosmetic Act (21 
U.S.C. 355c(a)) is amended--
            (1) in paragraph (4)(C), by adding at the end the 
        following: ``An applicant seeking either a partial or full 
        waiver shall submit to the Secretary documentation detailing 
        why a pediatric formulation cannot be developed, and, if the 
        waiver is granted, the applicant's submission shall promptly be 
        made available to the public in an easily accessible manner, 
        including through posting on the website of the Food and Drug 
        Administration'';
            (2) in paragraph (2)(B), by adding at the end the 
        following:
                            ``(iii) Information on extrapolation.--A 
                        brief documentation of the scientific data 
                        supporting the conclusion under clauses (i) and 
                        (ii) shall be included in the medical review 
                        that is collected as part of the application 
                        under section 505 or section 351 of the Public 
                        Health Service Act.''; and
            (3) by striking paragraph (3) and inserting the following:
            ``(3) Deferral.--
                    ``(A) In general.--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--
                            ``(i) 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
                            ``(ii) the applicant submits to the 
                        Secretary--
                                    ``(I) certification of the grounds 
                                for deferring the assessments;
                                    ``(II) a description of the planned 
                                or ongoing studies;
                                    ``(III) evidence that the studies 
                                are being conducted or will be 
                                conducted with due diligence and at the 
                                earliest possible time; and
                                    ``(IV) a timeline for the 
                                completion of such studies.
                    ``(B) Annual review.--
                            ``(i) In general.--On an annual basis 
                        following the approval of a deferral under 
                        subparagraph (A), the applicant shall submit to 
                        the Secretary the following information:
                                    ``(I) Information detailing the 
                                progress made in conducting pediatric 
                                studies.
                                    ``(II) If no progress has been made 
                                in conducting such studies, evidence 
                                and documentation that such studies 
                                will be conducted with due diligence 
                                and at the earliest possible time.
                            ``(ii) Public availability.--The 
                        information submitted through the annual review 
                        under clause (i) shall promptly be made 
                        available to the public in an easily accessible 
                        manner, including through the website of the 
                        Food and Drug Administration.''.

SEC. 3. IMPROVING AVAILABILITY OF PEDIATRIC DATA FOR ALREADY MARKETED 
              PRODUCTS.

    Section 505B(b) of the Federal Food, Drug, and Cosmetic Act (21 
U.S.C. 355c(b)) is amended--
            (1) by striking paragraph (1) and inserting the following:
            ``(1) In general.--After providing notice in the form of a 
        letter, or a written request under section 505A that was 
        declined by the sponsor or holder, 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 sponsor or 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) 
        and the written request, as appropriate, 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) adequate pediatric labeling could confer a 
                benefit on pediatric patients;
                    ``(B) 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; or
                    ``(C) the absence of adequate pediatric labeling 
                could pose a risk to pediatric patients.'';
            (2) in paragraph (2)(C), by adding at the end the 
        following: ``An applicant seeking either a partial or full 
        waiver shall submit to the Secretary documentation detailing 
        why a pediatric formulation cannot be developed, and, if the 
        waiver is granted, the applicant's submission shall promptly be 
        made available to the public in an easily accessible manner, 
        including through posting on the website of the Food and Drug 
        Administration.''; and
            (3) by striking paragraph (3).

SEC. 4. REVIEW OF PEDIATRIC ASSESSMENTS; ADVERSE EVENT REPORTING; 
              STRIKE OF SUNSET; LABELING CHANGES; AND PEDIATRIC 
              ASSESSMENTS.

    Section 505B of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 
355c) is amended--
            (1) by striking subsection (h);
            (2) by redesignating subsection (f) as subsection (k);
            (3) by redesignating subsection (g) as subsection (l); and
            (4) by inserting after subsection (e) the following:
    ``(f) Review of Pediatric Assessment Requests, Pediatric 
Assessments, Deferrals, and Waivers.--
            ``(1) Review.--The Secretary shall create an internal 
        committee to review all pediatric assessment requests issued 
        under this section, all pediatric assessments conducted under 
        this section, and all deferral and waiver requests made 
        pursuant to this section. Such internal committee shall include 
        individuals with the following expertise:
                    ``(A) Pediatrics.
                    ``(B) Biopharmacology.
                    ``(C) Statistics.
                    ``(D) Drugs and drug formulations.
                    ``(E) Pediatric ethics.
                    ``(F) Legal issues.
                    ``(G) Appropriate expertise pertaining to the 
                pediatric product under review.
                    ``(H) 1 or more experts from the Office of 
                Pediatric Therapeutics.
                    ``(I) Other individuals as designated by the 
                Secretary.
            ``(2) Review of requests for pediatric assessments, 
        deferrals, and waivers.--All written requests for a pediatric 
        assessment issued pursuant to this section and all requests for 
        deferrals and waivers from the requirement to conduct a 
        pediatric assessment under this section shall be reviewed and 
        approved by the committee established under paragraph (1).
            ``(3) Review of assessments.--The committee established 
        under paragraph (1) shall review all assessments conducted 
        under this section to determine whether such assessments meet 
        the requirements of this section.
            ``(4) Tracking of assessments and labeling changes.--The 
        committee established under paragraph (1) is responsible for 
        tracking and making public in an easily accessible manner, 
        including through posting on the website of the Food and Drug 
        Administration--
                    ``(A) the number of assessments conducted under 
                this section;
                    ``(B) the specific drugs and drug uses assessed 
                under this section;
                    ``(C) the types of assessments conducted under this 
                section, including trial design, the number of 
                pediatric patients studied, and the number of centers 
                and countries involved;
                    ``(D) the total number of deferrals requested and 
                granted under this section, and, if granted, the 
                reasons for such deferrals, the timeline for 
                completion, and the number completed and pending by the 
                specified date, as outlined in subsection (a)(3);
                    ``(E) the number of waivers requested and granted 
                under this section, and, if granted, the reasons for 
                the waivers;
                    ``(F) the number of pediatric formulations 
                developed and the number of pediatric formulations not 
                developed and the reasons any such formulations were 
                not developed;
                    ``(G) the labeling changes made as a result of 
                assessments conducted under this section;
                    ``(H) an annual summary of labeling changes made as 
                a result of assessments conducted under this section 
                for distribution pursuant to subsection (i)(2); and
                    ``(I) an annual summary of the information 
                submitted pursuant to subsection (a)(3)(B).
    ``(g) Labeling Changes.--
            ``(1) Priority status for pediatric supplement.--Any 
        supplement to an application under section 505 and section 351 
        of the Public Health Service Act proposing a labeling change as 
        a result of any pediatric assessments conducted pursuant to 
        this section--
                    ``(A) shall be considered 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 a sponsor 
                and the Commissioner have been unable to reach 
                agreement on appropriate changes to the labeling for 
                the drug that is the subject of the application or 
                supplement, not later than 180 days after the date of 
                the submission of the application or supplement--
                            ``(i) the Commissioner shall request that 
                        the sponsor make any labeling change that the 
                        Commissioner determines to be appropriate; and
                            ``(ii) if the sponsor does not agree to 
                        make a labeling change requested by the 
                        Commissioner, the Commissioner shall refer the 
                        matter to the Pediatric Advisory Committee.
                    ``(B) Action by the pediatric advisory committee.--
                Not later than 90 days after receiving a referral under 
                subparagraph (A)(ii), the Pediatric 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 Committee and, if appropriate, not 
                later than 30 days after receiving the recommendation, 
                make a request to the sponsor of the application or 
                supplement to make any labeling changes that the 
                Commissioner determines to be appropriate.
                    ``(D) Misbranding.--If the sponsor, 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 or supplement 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 Committee process of an 
                enforcement action referred to in the preceding 
                sentence) shall preclude, delay, or serve as the basis 
                to stay the other course of action.
            ``(3) Other labeling changes.--If the Secretary makes a 
        determination that a pediatric assessment conducted under this 
        section does not demonstrate that the drug that is the subject 
        of such assessment is safe and effective, the Secretary shall 
        order the label of such product to include information about 
        the results of the assessment and a statement of the 
        Secretary's determination.
    ``(h) Dissemination of Pediatric Information.--
            ``(1) In general.--Not later than 180 days after the date 
        of submission of a pediatric assessment under this section, the 
        Commissioner shall make available to the public in an easily 
        accessible manner the medical, statistical, and clinical 
        pharmacology reviews of such pediatric assessments and shall 
        post such assessments on the website of the Food and Drug 
        Administration.
            ``(2) Dissemination of information regarding labeling 
        changes.--The Secretary shall require that the sponsors of the 
        assessments that result in labeling changes that are reflected 
        in the annual summary developed pursuant to subsection 
        (f)(4)(H) distribute such information to physicians and other 
        health care providers.
            ``(3) Effect of subsection.--Nothing in this subsection 
        shall alter or amend section 301(j) of this Act or section 552 
        of title 5, United States Code, or section 1905 of title 18, 
        United States Code.
    ``(i) Adverse Event Reporting.--
            ``(1) Reporting in year 1.--During the 1-year period 
        beginning on the date a labeling change is made pursuant to 
        subsection (g), the Secretary shall ensure that all adverse 
        event reports that have been received for such drug (regardless 
        of when such report was received) are referred to the Office of 
        Pediatric Therapeutics. In considering the report, the Director 
        of such Office shall provide for the review of the report by 
        the Pediatric Advisory Committee, including obtaining any 
        recommendations of such committee regarding whether the 
        Secretary should take action under this Act in response to such 
        report.
            ``(2) Reporting in subsequent years.--Following the 1-year 
        period described in paragraph (1), the Secretary shall, as 
        appropriate, provide the Office of Pediatric Therapeutics with 
        a report regarding pediatric adverse events for a drug for 
        which a pediatric study was conducted under this section. In 
        considering the report, the Director of such Office may provide 
        for the review of the report by the Pediatric Advisory 
        Committee, including obtaining any recommendation of such 
        Committee regarding whether the Secretary should take action in 
        response to such report.''.

SEC. 5. MEANINGFUL THERAPEUTIC BENEFIT.

    Section 505B(c) of the Federal Food, Drug, and Cosmetic Act (21 
U.S.C. 355c) is amended--
            (1) by striking ``estimates'' and inserting ``determines''; 
        and
            (2) by striking ``would'' and inserting ``could''.

SEC. 6. REPORTS.

    (a) IOM Study.--Section 505B of the Federal Food, Drug, and 
Cosmetic Act (21 U.S.C. 355c), as amended by section 4, is further 
amended by adding after subsection (l), the following:
    ``(m) Institute of Medicine Study.--
            ``(1) In general.--Not later than 3 years after the date of 
        enactment of the Pediatric Research Improvement Act, the 
        Secretary shall contract with the Institute of Medicine to 
        conduct a study and report to Congress regarding the pediatric 
        studies conducted pursuant to this section since 1997.
            ``(2) Content of study.--The study under paragraph (1) 
        shall review and assess--
                    ``(A) pediatric studies conducted pursuant to this 
                section since 1997 and labeling changes made as a 
                result of such studies; and
                    ``(B) the use of extrapolation for pediatric 
                subpopulations, the use of alternative endpoints for 
                pediatric populations, neonatal assessment tools, 
                number and type of pediatric adverse events, and 
                ethical issues in pediatric clinical trials.
            ``(3) Representative sample.--The Institute of Medicine may 
        devise an appropriate mechanism to review a representative 
        sample of studies conducted pursuant to this section from each 
        review division within the Center for Drug Evaluation and 
        Research and the Center for Biologics Evaluation and Research 
        in order to make the required assessment.''.
    (b) PREA Report.--The Pediatric Research Equity Act of 2003 (Public 
Law 108-155) is amended by adding at the end the following:

``SEC. 5. REPORT.

    ``Not later than September 1, 2010, 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 
effectiveness of section 505B of the Federal Food, Drug, and Cosmetic 
Act (21 U.S.C. 355a) in ensuring that medicines used by children are 
tested and properly labeled, including--
            ``(1) the number and importance of drugs for children that 
        are being tested as a result of this provision and the 
        importance for children, health care providers, parents, and 
        others of labeling changes made as a result of such testing;
            ``(2) the number and importance of drugs for children that 
        are not being tested for their use notwithstanding the 
        provisions of this Act, and possible reasons for the lack of 
        testing; and
            ``(3) the number of drugs for which testing is being done 
        and labeling changes required, including 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 
        Committee.''.

SEC. 7. TECHNICAL CORRECTIONS.

    Section 505B(a)(2)(B)(ii) of the Federal Food, Drug, and Cosmetic 
Act (21 U.S.C. 355c(a)(2)(B)(ii)) is amended by striking ``one'' and 
inserting ``1''.
                                 <all>