REAUTHORIZATION OF BEST PHARMACEUTICALS FOR CHILDREN ACT.

SEC. 502. REAUTHORIZATION OF BEST PHARMACEUTICALS FOR CHILDREN ACT.(a) Pediatric Studies of Drugs.—(1) In general.—Section 505A of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a) is amended to read as follows:“SEC. 505A. PEDIATRIC STUDIES OF DRUGS.“(a) Definitions.—As used in this section, the term ‘pediatric studies’ or ‘studies’ means at least one clinical investigation (that, at the Secretary’s discretion, may include pharmacokinetic studies) in pediatric age groups (including neonates in appropriate cases) in which a drug is anticipated to be used, and, at the discretion of the Secretary, may include preclinical studies.“(b) Market Exclusivity for New Drugs.—“(1) In general.—Except as provided in paragraph (2), if, prior to approval of an application that is submitted under section 505(b)(1), the Secretary determines that information relating to the use of a new drug in the pediatric population may produce health benefits in that population, the Secretary makes a written request for pediatric studies (which shall 121 STAT. 877 include a timeframe for completing such studies), the applicant agrees to the request, such studies are completed using appropriate formulations for each age group for which the study is requested within any such timeframe, and the reports thereof are submitted and accepted in accordance with subsection (d)(3)—“(A)(i)(I) the period referred to in subsection (c)(3)(E)(ii) of section 505, and in subsection (j)(5)(F)(ii) of such section, is deemed to be five years and six months rather than five years, and the references in subsections (c)(3)(E)(ii) and (j)(5)(F)(ii) of such section to four years, to forty-eight months, and to seven and one-half years are deemed to be four and one-half years, fifty-four months, and eight years, respectively; or“(II) the period referred to in clauses (iii) and (iv) of subsection (c)(3)(E) of such section, and in clauses (iii) and (iv) of subsection (j)(5)(F) of such section, is deemed to be three years and six months rather than three years; and“(ii) if the drug is designated under section 526 for a rare disease or condition, the period referred to in section 527(a) is deemed to be seven years and six months rather than seven years; and“(B)(i) if the drug is the subject of—“(I) a listed patent for which a certification has been submitted under subsection (b)(2)(A)(ii) or (j)(2)(A)(vii)(II) of section 505 and for which pediatric studies were submitted prior to the expiration of the patent (including any patent extensions); or“(II) a listed patent for which a certification has been submitted under subsections (b)(2)(A)(iii) or (j)(2)(A)(vii)(III) of section 505,the period during which an application may not be approved under section 505(c)(3) or section 505(j)(5)(B) shall be extended by a period of six months after the date the patent expires (including any patent extensions); or“(ii) if the drug is the subject of a listed patent for which a certification has been submitted under subsection (b)(2)(A)(iv) or (j)(2)(A)(vii)(IV) of section 505, and in the patent infringement litigation resulting from the certification the court determines that the patent is valid and would be infringed, the period during which an application may not be approved under section 505(c)(3) or section 505(j)(5)(B) shall be extended by a period of six months after the date the patent expires (including any patent extensions).“(2) Exception.—The Secretary shall not extend the period referred to in paragraph (1)(A) or (1)(B) if the determination made under subsection (d)(3) is made later than 9 months prior to the expiration of such period.“(c) Market Exclusivity for Already-Marketed Drugs.—“(1) In general.—Except as provided in paragraph (2), if the Secretary determines that information relating to the use of an approved drug in the pediatric population may produce health benefits in that population and makes a written request to the holder of an approved application under section 121 STAT. 878 505(b)(1) for pediatric studies (which shall include a timeframe for completing such studies), the holder agrees to the request, such studies are completed using appropriate formulations for each age group for which the study is requested within any such timeframe, and the reports thereof are submitted and accepted in accordance with subsection (d)(3)—“(A)(i)(I) the period referred to in subsection (c)(3)(E)(ii) of section 505, and in subsection (j)(5)(F)(ii) of such section, is deemed to be five years and six months rather than five years, and the references in subsections (c)(3)(E)(ii) and (j)(5)(F)(ii) of such section to four years, to forty-eight months, and to seven and one-half years are deemed to be four and one-half years, fifty-four months, and eight years, respectively; or“(II) the period referred to in clauses (iii) and (iv) of subsection (c)(3)(D) of such section, and in clauses (iii) and (iv) of subsection (j)(5)(F) of such section, is deemed to be three years and six months rather than three years; and“(ii) if the drug is designated under section 526 for a rare disease or condition, the period referred to in section 527(a) is deemed to be seven years and six months rather than seven years; and“(B)(i) if the drug is the subject of—“(I) a listed patent for which a certification has been submitted under subsection (b)(2)(A)(ii) or (j)(2)(A)(vii)(II) of section 505 and for which pediatric studies were submitted prior to the expiration of the patent (including any patent extensions); or“(II) a listed patent for which a certification has been submitted under subsection (b)(2)(A)(iii) or (j)(2)(A)(vii)(III) of section 505,the period during which an application may not be approved under section 505(c)(3) or section 505(j)(5)(B)(ii) shall be extended by a period of six months after the date the patent expires (including any patent extensions); or“(ii) if the drug is the subject of a listed patent for which a certification has been submitted under subsection (b)(2)(A)(iv) or (j)(2)(A)(vii)(IV) of section 505, and in the patent infringement litigation resulting from the certification the court determines that the patent is valid and would be infringed, the period during which an application may not be approved under section 505(c)(3) or section 505(j)(5)(B) shall be extended by a period of six months after the date the patent expires (including any patent extensions).“(2) Exception.—The Secretary shall not extend the period referred to in paragraph (1)(A) or (1)(B) if the determination made under subsection (d)(3) is made later than 9 months prior to the expiration of such period.“(d) Conduct of Pediatric Studies.—“(1) Request for studies.—“(A) In general.—The Secretary may, after consultation with the sponsor of an application for an investigational new drug under section 505(i), the sponsor of an application for a new drug under section 505(b)(1), or the 121 STAT. 879 holder of an approved application for a drug under section 505(b)(1), issue to the sponsor or holder a written request for the conduct of pediatric studies for such drug. In issuing such request, the Secretary shall take into account adequate representation of children of ethnic and racial minorities. Such request to conduct pediatric studies shall be in writing and shall include a timeframe for such studies and a request to the sponsor or holder to propose pediatric labeling resulting from such studies.“(B) Single written request.—A single written request—“(i) may relate to more than one use of a drug; and“(ii) may include uses that are both approved and unapproved.“(2) Written request for pediatric studies.—“(A) Request and response.—“(i) In general.—If the Secretary makes a written request for pediatric studies (including neonates, as appropriate) under subsection (b) or (c), the applicant or holder, not later than 180 days after receiving the written request, shall respond to the Secretary as to the intention of the applicant or holder to act on the request by—“(I) indicating when the pediatric studies will be initiated, if the applicant or holder agrees to the request; or“(II) indicating that the applicant or holder does not agree to the request and stating the reasons for declining the request.“(ii) Disagree with request.—If, on or after the date of the enactment of the Best Pharmaceuticals for Children Act of 2007, the applicant or holder does not agree to the request on the grounds that it is not possible to develop the appropriate pediatric formulation, the applicant or holder shall submit to the Secretary the reasons such pediatric formulation cannot be developed.“(B) Adverse event reports.—An applicant or holder that, on or after the date of the enactment of the Best Pharmaceuticals for Children Act of 2007, agrees to the request for such studies shall provide the Secretary, at the same time as the submission of the reports of such studies, with all postmarket adverse event reports regarding the drug that is the subject of such studies and are available prior to submission of such reports.“(3) Meeting the studies requirement.—Not later than 180 days after the submission of the reports of the studies, the Secretary shall accept or reject such reports and so notify the sponsor or holder. The Secretary’s only responsibility in accepting or rejecting the reports shall be to determine, within the 180-day period, whether the studies fairly respond to the written request, have been conducted in accordance with commonly accepted scientific principles and protocols, and have been reported in accordance with the requirements of the Secretary for filing.121 STAT. 880“(4) 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.“(e) Notice of Determinations on Studies Requirement.—“(1) In general.—The Secretary shall publish a notice of any determination, made on or after the date of the enactment of the Best Pharmaceuticals for Children Act of 2007, that the requirements of subsection (d) have been met and that submissions and approvals under subsection (b)(2) or (j) of section 505 for a drug will be subject to the provisions of this section. Such notice shall be published not later than 30 days after the date of the Secretary’s determination regarding market exclusivity and shall include a copy of the written request made under subsection (b) or (c).“(2) Identification of certain drugs.—The Secretary shall publish a notice identifying any drug for which, on or after the date of the enactment of the Best Pharmaceuticals for Children Act of 2007, a pediatric formulation was developed, studied, and found to be safe and effective in the pediatric population (or specified subpopulation) if the pediatric formulation for such drug is not introduced onto the market within one year after the date that the Secretary publishes the notice described in paragraph (1). Such notice identifying such drug shall be published not later than 30 days after the date of the expiration of such one year period.“(f) Internal Review of Written Requests and Pediatric Studies.—“(1) Internal review.—The Secretary shall utilize the internal review committee established under section 505C to review all written requests issued on or after the date of the enactment of the Best Pharmaceuticals for Children Act of 2007, in accordance with paragraph (2).“(2) Review of written requests.—The committee referred to in paragraph (1) shall review all written requests issued pursuant to this section prior to being issued.“(3) Review of pediatric studies.—The committee referred to in paragraph (1) may review studies conducted pursuant to this section to make a recommendation to the Secretary whether to accept or reject such reports under subsection (d)(3).“(4) Activity by committee.—The committee referred to in paragraph (1) may operate using appropriate members of such committee and need not convene all members of the committee.“(5) Documentation of committee action.—For each drug, the committee referred to in paragraph (1) shall document, for each activity described in paragraph (2) or (3), which members of the committee participated in such activity.“(6) Tracking pediatric studies and labeling changes.—The Secretary, in consultation with the committee referred to in paragraph (1), shall track and make available to the public, in an easily accessible manner, including through posting on the Web site of the Food and Drug Administration—“(A) the number of studies conducted under this section and under section 409I of the Public Health Service Act;“(B) the specific drugs and drug uses, including labeled and off-labeled indications, studied under such sections;121 STAT. 881“(C) the types of studies conducted under such sections, including trial design, the number of pediatric patients studied, and the number of centers and countries involved;“(D) the number of pediatric formulations developed and the number of pediatric formulations not developed and the reasons such formulations were not developed;“(E) the labeling changes made as a result of studies conducted under such sections;“(F) an annual summary of labeling changes made as a result of studies conducted under such sections for distribution pursuant to subsection (k)(2); and“(G) information regarding reports submitted on or after the date of the enactment of the Best Pharmaceuticals for Children Act of 2007.“(g) Limitations.—Notwithstanding subsection (c)(2), a drug to which the six-month period under subsection (b) or (c) has already been applied—“(1) may receive an additional six-month period under subsection (c)(1)(A)(i)(II) for a supplemental application if all other requirements under this section are satisfied, except that such drug may not receive any additional such period under subsection (c)(1)(B); and“(2) may not receive any additional such period under subsection (c)(1)(A)(ii).“(h) Relationship to Pediatric Research Requirements.—Notwithstanding any other provision of law, if any pediatric study is required by a provision of law (including a regulation) other than this section and such study meets the completeness, timeliness, and other requirements of this section, such study shall be deemed to satisfy the requirement for market exclusivity pursuant to this section.“(i) Labeling Changes.—“(1) Priority status for pediatric applications and supplements.—Any application or supplement to an application under section 505 proposing a labeling change as a result of any pediatric study conducted pursuant to this section—“(A) shall be considered to be a priority application or 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, on or after the date of the enactment of the Best Pharmaceuticals for Children Act of 2007, the Commissioner determines that the 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, 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 within 30 days after the Commissioner’s request to 121 STAT. 882 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 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 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.“(j) Other Labeling Changes.—If, on or after the date of the enactment of the Best Pharmaceuticals for Children Act of 2007, the Secretary determines that a pediatric study conducted under this section does or does not demonstrate that the drug that is the subject of the study is safe and effective, including whether such study results are inconclusive, in pediatric populations or subpopulations, the Secretary shall order the labeling of such product to include information about the results of the study and a statement of the Secretary’s determination.“(k) Dissemination of Pediatric Information.—“(1) In general.—Not later than 210 days after the date of submission of a report on a pediatric study under this section, the Secretary shall make available to the public the medical, statistical, and clinical pharmacology reviews of pediatric studies conducted under subsection (b) or (c).“(2) Dissemination of information regarding labeling changes.—Beginning on the date of the enactment of the Best Pharmaceuticals for Children Act of 2007, the Secretary shall include as a requirement of a written request that the sponsors of the studies that result in labeling changes that are reflected in the annual summary developed pursuant to subsection (f)(3)(F) distribute, at least annually (or more frequently if the Secretary determines that it would be beneficial to the public health), such information to physicians and other health care providers.121 STAT. 883“(3) 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.“(l) Adverse Event Reporting.—“(1) Reporting in year one.—Beginning on the date of the enactment of the Best Pharmaceuticals for Children Act of 2007, during the one-year period beginning on the date a labeling change is approved pursuant to subsection (i), 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 established under section 6 of the Best Pharmaceuticals for Children Act (Public Law 107–109). In considering the reports, the Director of such Office shall provide for the review of the reports 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 reports.“(2) Reporting in subsequent years.—Following the one-year period described in paragraph (1), the Secretary shall, as appropriate, refer to the Office of Pediatric Therapeutics all pediatric adverse event reports for a drug for which a pediatric study was conducted under this section. In considering such reports, the Director of such Office may provide for the review of such reports by the Pediatric Advisory Committee, including obtaining any recommendation of such Committee regarding whether the Secretary should take action in response to such reports.“(3) Effect.—The requirements of this subsection shall supplement, not supplant, other review of such adverse event reports by the Secretary.“(m) 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 six-month exclusivity period.“(n) Referral if Pediatric Studies Not Completed.—“(1) In general.—Beginning on the date of the enactment of the Best Pharmaceuticals for Children Act of 2007, if pediatric studies of a drug have not been completed under subsection (d) and if the Secretary, through the committee established under section 505C, 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 carry out the following:121 STAT. 884 “(A) For a drug for which a listed patent has not expired, make a determination regarding whether an assessment shall be required to be submitted under section 505B(b). Prior to making such a determination, the Secretary may not take more than 30 days to certify whether the Foundation for the National Institutes of Health has sufficient funding at the time of such certification to initiate and fund all of the studies in the written request in their entirety within the timeframes specified within the written request. Only if the Secretary makes such certification in the affirmative, the Secretary shall refer all pediatric studies in the written request to the Foundation for the National Institutes of Health for the conduct of such studies, and such Foundation shall fund such studies. If no certification has been made at the end of the 30-day period, or if the Secretary certifies that funds are not sufficient to initiate and fund all the studies in their entirety, the Secretary shall consider whether assessments shall be required under section 505B(b) for such drug.“(B) For a drug that has no listed patents or has 1 or more listed patents that have expired, 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 studies.“(2) Public notice.—The Secretary shall give the public notice of a decision under paragraph (1)(A) not to require an assessment under section 505B and the basis for such decision.“(3) 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.“(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)(F).“(2) Labeling.—Notwithstanding clauses (iii) and (iv) of section 505(j)(5)(F), 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—121 STAT. 885“(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)(F); or“(D) except as expressly provided in paragraphs (1) and (2), the operation of section 505.“(p) Institute of Medicine Study.—Not later than 3 years after the date of the enactment of the Best Pharmaceuticals for Children Act of 2007, the Secretary shall enter into a contract with the Institute of Medicine to conduct a study and report to Congress regarding the written requests made and the studies conducted pursuant to this section. The Institute of Medicine may devise an appropriate mechanism to review a representative sample of requests made and studies conducted pursuant to this section in order to conduct such study. Such study shall—“(1) review such representative written requests issued by the Secretary since 1997 under subsections (b) and (c);“(2) review and assess such representative pediatric studies conducted under subsections (b) and (c) since 1997 and labeling changes made as a result of such studies;“(3) review the use of extrapolation for pediatric subpopulations, the use of alternative endpoints for pediatric populations, neonatal assessment tools, and ethical issues in pediatric clinical trials;“(4) review and assess the pediatric studies of biological products as required under subsections (a) and (b) of section 505B; and“(5) make recommendations regarding appropriate incentives for encouraging pediatric studies of biologics.“(q) Sunset.—A drug may not receive any 6-month period under subsection (b) or (c) unless—“(1) on or before October 1, 2012, the Secretary makes a written request for pediatric studies of the drug;“(2) on or before October 1, 2012, an application for the drug is accepted for filing under section 505(b); and“(3) all requirements of this section are met.” .(2) Applicability.—(A) In general.—The amendment made by this subsection shall apply to written requests under section 505A of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a) issued on or after the date of the enactment of this Act.(B) Certain written requests.—A written request issued under section 505A of the Federal Food, Drug, and Cosmetic Act, as in effect on the day before the date of the enactment of this Act, which has been accepted and for which no determination under subsection (d)(2) of such section has been made before such date of enactment, shall be subject to such section 505A, except that such written requests shall be subject to subsections (d)(2)(A)(ii), (e)(1) and (2), (f), (i)(2)(A), (j), (k)(1), (l)(1), and (n) of section 505A of the Federal Food, Drug, and Cosmetic Act, as 121 STAT. 886 in effect on or after the date of the enactment of this Act.(b) Program for Pediatric Studies of Drugs.—Section 409I of the Public Health Service Act (42 U.S.C. 284m) is amended to read as follows:“SEC. 409I. PROGRAM FOR PEDIATRIC STUDIES OF DRUGS.“(a) List of Priority Issues in Pediatric Therapeutics.—“(1) In general.—Not later than one year after the date of the enactment of the Best Pharmaceuticals for Children Act of 2007, 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 and publish a priority list of needs in pediatric therapeutics, including drugs or indications that require study. The list shall be revised every three years.“(2) Consideration of available information.—In developing and prioritizing the list under paragraph (1), the Secretary shall consider—“(A) therapeutic gaps in pediatrics that may include developmental pharmacology, pharmacogenetic determinants of drug response, metabolism of drugs and biologics in children, and pediatric clinical trials;“(B) particular pediatric diseases, disorders or conditions where more complete knowledge and testing of therapeutics, including drugs and biologics, may be beneficial in pediatric populations; and“(C) the adequacy of necessary infrastructure to conduct pediatric pharmacological research, including research networks and trained pediatric investigators.“(b) Pediatric Studies and Research.—The Secretary, acting through the National Institutes of Health, shall award funds to entities that have the expertise to conduct pediatric clinical trials or other research (including qualified universities, hospitals, laboratories, contract research organizations, practice groups, federally funded programs such as pediatric pharmacology research units, other public or private institutions, or individuals) to enable the entities to conduct the drug studies or other research on the issues described in subsection (a). The Secretary may use contracts, grants, or other appropriate funding mechanisms to award funds under this subsection.“(c) Process for Proposed Pediatric Study Requests and Labeling Changes.—“(1) Submission of proposed pediatric study request.—The Director of the National Institutes of Health shall, as appropriate, submit proposed pediatric study requests for consideration by the Commissioner of Food and Drugs for pediatric studies of a specific pediatric indication identified under subsection (a). Such a proposed pediatric study request shall be made in a manner equivalent to a written request made under subsection (b) or (c) of section 505A of the Federal Food, Drug, and Cosmetic Act, including with respect to the information provided on the pediatric studies to be conducted pursuant to the request. The Director of the National Institutes of Health may submit a proposed pediatric study request for a drug for which—121 STAT. 887“(A)(i) there is an approved application under section 505(j) of the Federal Food, Drug, and Cosmetic Act; or“(ii) there is a submitted application that could be approved under the criteria of such section; and“(B) there is no patent protection or market exclusivity protection for at least one form of the drug under the Federal Food, Drug, and Cosmetic Act; and“(C) additional studies are needed to assess the safety and effectiveness of the use of the drug in the pediatric population.“(2) 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 based on the proposed pediatric study request for the indication or indications submitted pursuant to paragraph (1) (which shall include a timeframe for negotiations for an agreement) for pediatric studies concerning a drug identified under subsection (a) 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 (b) or (c) of section 505A of such Act, including with respect to information provided on the pediatric studies to be conducted pursuant to the request and using appropriate formulations for each age group for which the study is requested.“(3) Requests for proposals.—If the Commissioner of Food and Drugs does not receive a response to a written request issued under paragraph (2) not later than 30 days after the date on which a request was issued, 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 proposals to conduct the pediatric studies described in the written request in accordance with subsection (b).“(4) Disqualification.—A holder that receives a first right of refusal shall not be entitled to respond to a request for proposals under paragraph (3).“(5) Contracts, grants, or other funding mechanisms.—A contract, grant, or other funding may be awarded under this section only if a proposal 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 an award 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, including a written request if issued.“(B) Availability of reports.—Each report submitted under subparagraph (A) shall be considered to be in the public domain (subject to section 505A(d)(4) of the Federal Food, Drug, and Cosmetic Act) and shall be assigned a 121 STAT. 888 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 and through a posting on the Web site of the Food and Drug Administration a summary of the report and a copy of any requested labeling changes.“(8) Dispute resolution.—“(A) Referral to pediatric 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 Committee.“(B) Action by the pediatric advisory committee.—Not later than 90 days after receiving a referral under subparagraph (A), the Pediatric 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 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 of 121 STAT. 889 Food and Drugs may deem the drug to be misbranded under the Federal Food, Drug, and Cosmetic Act.“(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 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.“(d) Dissemination of Pediatric Information.—Not later than one year after the date of the enactment of the Best Pharmaceuticals for Children Act of 2007, the Secretary, acting through the Director of the National Institutes of Health, shall study the feasibility of establishing a compilation of information on pediatric drug use and report the findings to Congress.“(e) Authorization of Appropriations.—“(1) In general.—There are authorized to be appropriated to carry out this section—“(A) $200,000,000 for fiscal year 2008; and“(B) such sums as are necessary for each of the four succeeding fiscal years.“(2) Availability.—Any amount appropriated under paragraph (1) shall remain available to carry out this section until expended.” .(c) Foundation for the National Institutes of Health.—Section 499(c)(1)(C) of the Public Health Service Act (42 U.S.C. 290b(c)(1)(C)) is amended by striking “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. 355(a)(d)(4)(C)’ ” and inserting “and studies for which the Secretary issues a certification in the affirmative under section 505A(n)(1)(A) of the Federal Food, Drug, and Cosmetic Act”.(d) Continuation of Operation of Committee.—Section 14 of the Best Pharmaceuticals for Children Act (42 U.S.C. 284m note) is amended by adding at the end the following new subsection:“(d) Continuation of Operation of Committee.—Notwithstanding section 14 of the Federal Advisory Committee Act, the advisory committee shall continue to operate during the five-year period beginning on the date of the enactment of the Best Pharmaceuticals for Children Act of 2007.”.(e) Pediatric Subcommittee of the Oncologic Drugs Advisory Committee.—Section 15 of the Best Pharmaceuticals for Children Act (42 U.S.C. 284m note) is amended—(1) in subsection (a)—(A) in paragraph (1)—(i) in subparagraph (B), by striking “and” after the semicolon;(ii) in subparagraph (C), by striking the period at the end and inserting “; and”; and(iii) by adding at the end the following new subparagraph:“(D) provide recommendations to the internal review committee created under section 505B(f) of the Federal Food, Drug, and Cosmetic Act regarding the implementation of amendments to sections 505A and 505B of the 121 STAT. 890 Federal Food, Drug, and Cosmetic Act with respect to the treatment of pediatric cancers.”; and(B) by adding at the end the following new paragraph:“(3) Continuation of operation of subcommittee.—Notwithstanding section 14 of the Federal Advisory Committee Act, the Subcommittee shall continue to operate during the five-year period beginning on the date of the enactment of the Best Pharmaceuticals for Children Act of 2007.”; and(2) in subsection (d), by striking “2003” and inserting “2009”.(f) Effective Date and Limitation for Rule Relating to Toll-Free Number for Adverse Events on Labeling for Human Drug Products.—(1) In general.—Notwithstanding subchapter II of chapter 5, and chapter 7, of title 5, United States Code (commonly known as the “Administrative Procedure Act”) and any other provision of law, the proposed rule issued by the Commissioner of Food and Drugs entitled “Toll-Free Number for Reporting Adverse Events on Labeling for Human Drug Products,” 69 Fed. Reg. 21778, (April 22, 2004) shall take effect on January 1, 2008, unless such Commissioner issues the final rule before such date.(2) Limitation.—The proposed rule that takes effect under subsection (a), or the final rule described under subsection (a), shall, notwithstanding section 17(a) of the Best Pharmaceuticals for Children Act (21 U.S.C. 355b(a)), not apply to a drug—(A) for which an application is approved under section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355);(B) that is not described under section 503(b)(1) of such Act (21 U.S.C. 353(b)(1)); and(C) the packaging of which includes a toll-free number through which consumers can report complaints to the manufacturer or distributor of the drug.