Short title; table of contents

(a)

Short title

This Act may be cited as the

Improving Pharmaceuticals for Children Act of 2007

. (b)

Table of contents

The table of contents for this Act is as follows:

Sec. 1. Short title; table of contents.

Sec. 2. Reauthorization of Best Pharmaceuticals for Children Act.

Sec. 3. Reauthorization of Pediatric Research Equity Act.

Sec. 4. Government Accountability Office report.

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:

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 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), and if the Secretary determines that labeling changes are appropriate, such changes are made within the timeframe requested by the Secretary— (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 is made later than one year 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 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), and if the Secretary determines that labeling changes are appropriate and such changes are made within the timeframe requested by the Secretary— (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

Exception

The Secretary shall not extend the period referred to in paragraph (1)(A) or (1)(B) if the determination is made later than one year 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 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 related 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 Improving 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 Improving 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. (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 Improving 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 Improving 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

(A)

In general

The Secretary shall establish an internal review committee to review all written requests issued on or after the date of the enactment of the Improving Pharmaceuticals for Children Act of 2007, in accordance with paragraph (2). (B)

Members

The committee established under subparagraph (A) shall include individuals with expertise in pediatrics, biopharmacology, statistics, drugs and drug formulations, legal issues, pediatric ethics, the appropriate expertise, such as expertise in child and adolescent psychiatry, pertaining to the pediatric product under review, one or more experts from the Office of Pediatric Therapeutics, and other individuals designated by the Secretary. (2)

Review of written requests

The committee established under paragraph (1) shall review all written requests issued pursuant to this section prior to being issued. (3)

Tracking pediatric studies and labeling changes

The Secretary shall track and make available to the public, in an easily accessible manner, including through posting on the website 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 (42 U.S.C. 284m); (B)the specific drugs and biological products and their uses, including labeled and off-labeled indications, studied under such sections; (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 Improving Pharmaceuticals for Children Act of 2007. (4)

Committee

The Committee established under paragraph (1) is the committee established in section 505B(f)(1).” (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; 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 Improving 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 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 Improving 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 in pediatric populations or subpopulations, including whether such study results are inconclusive, 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 180 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 Improving Pharmaceuticals for Children Act of 2007, the Secretary shall require 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. (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 Improving Pharmaceuticals for Children Act of 2007, during the one-year period beginning on the date a labeling change is made 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 Improving Pharmaceuticals for Children Act of 2007, if pediatric studies have not been completed under subsection (d) and if the Secretary, through the committee established under subsection (f), 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— (A)for a drug for which listed patents have not expired, make a determination regarding whether an assessment shall be required to be submitted under section 505B; or (B)for a drug that has no listed patents or has 1 or more listed patents that have expired, determine whether there are funds available under section 736 to award a grant to conduct the requested studies pursuant to paragraph (2). (2)

Funding of studies

If, pursuant to paragraph (1), the Secretary determines that there are funds available under section 736 to award a grant to conduct the requested pediatric studies, then the Secretary shall issue a proposal to award a grant to conduct the requested studies. If the Secretary determines that funds are not available under section 736, the Secretary shall refer the drug for inclusion on the list established under section 409I of the Public Health Services Act or the conduct of studies. (3)

Public notice

The Secretary shall give the public notice of— (A)a decision under paragraph (1)(A) not to require an assessment under section 505B and the basis for such decision; (B)the name of any drug, its manufacturer, and the indications to be studied pursuant to a grant made under paragraph (2); and (C)any decision under paragraph (2) to include a drug on the list established under section 409I of the Public Health Services Act. (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 (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— (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 Improving 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; and (4)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)

Effective date

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) made 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:

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 Improving 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 the 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 (21 U.S.C. 355a), 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— (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)); 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 the 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 (21 U.S.C. 355). 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 such Act (21 U.S.C. 355a), 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 the 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 the 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)(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 and through a posting on the website 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 Food and Drugs 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 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 Improving 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)

Fees relating to drugs

Section 735(6) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 379(6)) is amended by adding at the end the following new subparagraph:

(G)Activities relating to the support of studies of drugs on pediatric populations under section 505A(n)(1).

(d)

Training of pediatric pharmacologists

(1)

Investment in tomorrow’s pediatric researchers

Section 452G(2) of the Public Health Service Act (42 U.S.C. 285g–10(2)) is amended by inserting before the period at the end the following: “, including pediatric pharmacological research”. (2)

Pediatric research loan repayment program

Section 487F(a)(1) of the Public Health Service Act (42 U.S.C. 288–6(a)(1)) is amended by inserting “including pediatric pharmacological research,” after “pediatric research,”. (e)

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))”. (f)

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 (5 U.S.C. App.), the advisory committee shall continue to operate during the five-year period beginning on the date of the enactment of the Improving Pharmaceuticals for Children Act of 2007.

(g)

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 505A(f) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a(f)) regarding the implementation of amendments to sections 505A and 505B of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a and 355c) 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 (5 U.S.C. App.), the Subcommittee shall continue to operate during the five-year period beginning on the date of the enactment of the Improving Pharmaceuticals for Children Act of 2007.

; and

(2)in subsection (d), by striking “2003” and inserting “2009”. (h)

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.

Reauthorization of Pediatric Research Equity Act

Section 505B of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355c) is amended to read as follows:

505B.

Research into pediatric uses for drugs and biological products

(a)

New drugs and biological products

(1)

In general

A person that submits an application (or supplement to an application)— (A)under section 505 for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration; or (B)under section 351 of the Public Health Service Act (42 U.S.C. 262) for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration; shall submit with the application the assessments described in paragraph (2). (2)

Assessments

(A)

In general

The assessments referred to in paragraph (1) shall contain data, gathered using appropriate formulations for each age group for which the assessment is required, that are adequate— (i)to assess the safety and effectiveness of the drug or the biological product for the claimed indications in all relevant pediatric subpopulations; and (ii)to support dosing and administration for each pediatric subpopulation for which the drug or the biological product is safe and effective. (B)

Similar course of disease or similar effect of drug or biological product

(i)

In general

If the course of the disease and the effects of the drug are sufficiently similar in adults and pediatric patients, the Secretary may conclude that pediatric effectiveness can be extrapolated from adequate and well-controlled studies in adults, usually supplemented with other information obtained in pediatric patients, such as pharmacokinetic studies. (ii)

Extrapolation between age groups

A study may not be needed in each pediatric age group if data from one age group can be extrapolated to another age group. (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 of this Act or section 351 of the Public Health Service Act (42 U.S.C. 262). (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. (4)

Waivers

(A)

Full waiver

On the initiative of the Secretary or at the request of an applicant, the Secretary shall grant a full waiver, as appropriate, of the requirement to submit assessments for a drug or biological product under this subsection if the applicant certifies and the Secretary finds that— (i)necessary studies are impossible or highly impracticable (because, for example, the number of patients is so small or the patients are geographically dispersed); (ii)there is evidence strongly suggesting that the drug or biological product would be ineffective or unsafe in all pediatric age groups; or (iii)The drug or biological product— (I)does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients; and (II)is not likely to be used in a substantial number of pediatric patients. (B)

Partial waiver

On the initiative of the Secretary or at the request of an applicant, the Secretary shall grant a partial waiver, as appropriate, of the requirement to submit assessments for a drug or biological product under this subsection with respect to a specific pediatric age group if the applicant certifies and the secretary finds that— (i)necessary studies are impossible or highly impracticable (because, for example, the number of patients in that age group is so small or patients in that age group are geographically dispersed); (ii)there is evidence strongly suggesting that the drug or biological product would be ineffective or unsafe in that age group; (iii)the drug or biological product— (I)does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients in that age group; and (II)is not likely to be used by a substantial number of pediatric patients in that age group; or (iv)the applicant can demonstrate that reasonable attempts to produce a pediatric formulation necessary for that age group have failed. (C)

Pediatric formulation not possible

If a waiver is granted on the ground that it is not possible to develop a pediatric formulation, the waiver shall cover only the pediatric groups requiring that formulation. An applicant seeking either a full or partial 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. (D)

Labeling requirement

If the Secretary grants a full or partial waiver because there is evidence that a drug or biological product would be ineffective or unsafe in pediatric populations, the information shall be included in the labeling for the drug or biological product. (b)

Marketed drugs and biological products

(1)

In general

After providing notice in the form of a letter and an opportunity for written response and a meeting, which may include an advisory committee meeting, the Secretary may (by order in the form of a letter) require the 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)

Waivers

(A)

Full waiver

At the request of an applicant, the Secretary shall grant a full waiver, as appropriate, of the requirement to submit assessments under this subsection if the applicant certifies and the Secretary finds that— (i)necessary studies are impossible or highly impracticable (because, for example, the number of patients in that age group is so small or patients in that age group are geographically dispersed); or (ii)there is evidence strongly suggesting that the drug or biological product would be ineffective or unsafe in all pediatric age groups. (B)

Partial waiver

At the request of an applicant, the Secretary shall grant a partial waiver, as appropriate, of the requirement to submit assessments under this subsection with respect to a specific pediatric age group if the applicant certifies and the Secretary finds that— (i)necessary studies are impossible or highly impracticable (because, for example, the number of patients in that age group is so small or patients in that age group are geographically dispersed); (ii)there is evidence strongly suggesting that the drug or biological product would be ineffective or unsafe in that age group; (iii)(I)the drug or biological product— (aa)does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients in that age group; and (bb)is not likely to be used in a substantial number of pediatric patients in that age group; and (II)the absence of adequate labeling could not pose significant risks to pediatric patients; or (iv)the applicant can demonstrate that reasonable attempts to produce a pediatric formulation necessary for that age group have failed. (C)

Pediatric formulation not possible

Labeling requirement

Meaningful therapeutic benefit

For the purposes of paragraph (4)(A)(iii)(I) and (4)(B)(iii)(I) of subsection (a) and paragraphs (1)(B)(I) and (2)(B)(iii)(I)(aa) of subsection (b), a drug or biological product shall be considered to represent a meaningful therapeutic benefit over existing therapies if the Secretary determines that— (1)if approved, the drug or biological product could represent an improvement in the treatment, diagnosis, or prevention of a disease, compared with marketed products adequately labeled for that use in the relevant pediatric population; or (2)the drug or biological product is in a class of products or for an indication for which there is a need for additional options. (d)

Submission of assessments

If a person fails to submit an assessment described in subsection (a)(2), or a request for approval of a pediatric formulation described in subsection (a) or (b), in accordance with applicable provisions of subsections (a) and (b)— (1)the drug or biological product that is the subject of the assessment or request may be considered misbranded solely because of that failure and subject to relevant enforcement action (except that the drug or biological product shall not be subject to action under section 303); but (2)the failure to submit the assessment or request shall not be the basis for a proceeding— (A)to withdraw approval for a drug under section 505(e); or (B)to revoke the license for a biological product under section 351 of the Public Health Service Act (42 U.S.C. 262). (e)

Meetings

Before and during the investigational process for a new drug or biological product, the Secretary shall meet at appropriate times with the sponsor of the new drug or biological product to discuss— (1)information that the sponsor submits on plans and timelines for pediatric studies; or (2)any planned request by the sponsor for waiver or deferral of pediatric studies. (f)

Review of pediatric assessments, deferrals, and waivers

(1)

Review

The Secretary shall create an internal committee to review all pediatric assessments issued under this section and all deferral and waiver requests made pursuant to this section. Such internal committee shall include individuals, each of whom is an employee of the Food and Drug Administration, with expertise in pediatrics, biopharmacology, statistics, drugs and drug formulations, legal issues, pediatric ethics, the appropriate expertise, such as expertise in child and adolescent psychiatry, pertaining to the pediatric product under review, one or more experts from the Office of Pediatric Therapeutics, and other individuals designated by the Secretary. (2)

Action by Committee

The committee established under paragraph (1) may perform a function under this section using appropriate members of the committee described in paragraph (1) and need not convene all members of the committee described in paragraph (1) in order to perform a function under this section. (3)

Documentation of Committee Action

For each drug or biological product, the committee established under this paragraph shall document for each function described in paragraph (4) which members of the committee participated in such function. (4)

Review of requests for pediatric assessments, deferrals and waivers

All 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 by the committee established under paragraph (1). (5)

Tracking of assessments and labeling changes

The Secretary shall track and make available to the public in an easily accessible manner, including through post on the website of the Food and Drug Administration— (A)the number of assessments conducted under this section; (B)the specific drugs and biological products and their 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 formulation 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 (h)(2); and (I)an annual summary of information submitted pursuant to subsection (a)(3)(B). (6)

Committee

The committee established under paragraph (1) is the committee established under section 505A(f)(1). (g)

Labeling changes

(1)

Priority status for pediatric applications

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 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 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 of the application make any labeling change that the Commissioner determines to be appropriate; and (ii)if the sponsor does not agree within 30 days after the Commissioner’s request 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

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 changes that the Commissioner determines to be appropriate. (D)

Misbranding

No effect on authority

Other labeling changes

If the Secretary makes a determination that a pediatric assessment conducted under this section does or does not demonstrate that the drug that is the subject of such assessment is safe and effective in pediatric populations or subpopulations, including whether such assessment results are inconclusive, 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 Secretary 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)(5)(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 or section 1905 of title 18, United States Code. (i)

Adverse event reporting

(1)

Reporting in year one

During the one-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 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 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. (3)

Effect

The requirements of this subsection shall supplement, not supplant, other review of such adverse event reports by the Secretary. (j)

Scope of authority

Nothing in this section provides to the Secretary any authority to require a pediatric assessment of any drug or biological product, or any assessment regarding other populations or uses of a drug or biological product, other than the pediatric assessments described in this section. (k)

Orphan drugs

Unless the Secretary requires otherwise by regulation, this section does not apply to any drug for an indication for which orphan designation has been granted under section 526. (l)

Institute of Medicine study

(1)

In general

Not later than three years after the date of the enactment of the Improving Pharmaceuticals for Children Act of 2007, 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, the 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 in order to make the requested assessment.

Government Accountability Office report

Not later than September 1, 2011, 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 sections 505A and 505B of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a) and section 409I of the Public Health Service Act (42 U.S.C. 284m) in ensuring that medicines used by children are tested and properly labeled. Such report shall include— (1)the number and importance of drugs and biological products for children that are being tested as a result of the amendments made by this Act 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 and biological products for children that are not being tested for their use notwithstanding the provisions of this Act and possible reasons for the lack of testing, including whether the number of written requests declined by sponsors or holders of drugs subject to section 505A(g)(2) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a(g)(2)) has increased or decreased as a result of the amendments made by this Act; (3)the number of drugs and biological products 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; (4)any recommendations for modifications to the programs established under sections 505A and 505B of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a) and section 409I of the Public Health Service Act (42 U.S.C. 284m) that the Secretary determines to be appropriate, including a detailed rationale for each recommendation; and (5)(A)the efforts made by the 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 the studies ethical and safe.