A person that submits, on or after September 27, 2007, an application (or supplement to an application)—
(A) under section 355 of this title for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration, or
(B) under section 262 of title 42 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).
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.
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.
A study may not be needed in each pediatric age group if data from one age group can be extrapolated to another age group.
A brief documentation of the scientific data supporting the conclusion under clauses (i) and (ii) shall be included in any pertinent reviews for the application under section 355 of this title or section 262 of title 42.
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.
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.
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 Web site of the Food and Drug Administration.
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.
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.
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 Web site of the Food and Drug Administration.
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.
After providing notice in the form of a letter (that, for a drug approved under section 355 of this title, references a declined written request under section 355a of this title for a labeled indication which written request is not referred under section 355a(n)(1)(A) of this title to the Foundation of the National Institutes of Health for the pediatric studies), 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 355 of this title or the holder of a license for a biological product under section 262 of title 42 to submit by a specified date the assessments described in subsection (a)(2), if the Secretary finds that—
(A)(i) the drug or biological product is used for a substantial number of pediatric patients for the labeled indications; and
(ii) 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.
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.
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.
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 Web site of the Food and Drug Administration.
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.
Nothing in this subsection alters or amends section 331(j) of this title or section 552 of title 5 or section 1905 of title 18.
For the purposes of paragraph (4)(A)(iii)(I) and (4)(B)(iii)(I) of subsection (a) and paragraphs (1)(B) 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.
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 333 of this title); 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 355(e) of this title; or
(B) to revoke the license for a biological product under section 262 of title 42.
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.
Beginning not later than 30 days after September 27, 2007, the Secretary shall utilize the internal committee established under section 355d of this title to provide consultation to reviewing divisions on all pediatric plans and assessments prior to approval of an application or supplement for which a pediatric assessment is required under this section and all deferral and waiver requests granted pursuant to this section.
The committee referred to in paragraph (1) may operate using appropriate members of such committee and need not convene all members of the committee.
For each drug or biological product, the committee referred to in paragraph (1) shall document, for each activity described in paragraph (4) or (5), which members of the committee participated in such activity.
Consultation on pediatric plans and assessments by the committee referred to in paragraph (1) pursuant to this section shall occur prior to approval of an application or supplement for which a pediatric assessment is required under this section. The committee shall review all requests for deferrals and waivers from the requirement to submit a pediatric assessment granted under this section and shall provide recommendations as needed to reviewing divisions, including with respect to whether such a supplement, when submitted, shall be considered for priority review.
Not later than 1 year after September 27, 2007, the committee referred to in paragraph (1) shall conduct a retrospective review and analysis of a representative sample of assessments submitted and deferrals and waivers approved under this section since December 3, 2003. Such review shall include an analysis of the quality and consistency of pediatric information in pediatric assessments and the appropriateness of waivers and deferrals granted. Based on such review, the Secretary shall issue recommendations to the review divisions for improvements and initiate guidance to industry related to the scope of pediatric studies required under this section.
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 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 was 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);
(I) an annual summary of information submitted pursuant to subsection (a)(3)(B); and
(J) the number of times the committee referred to in paragraph (1) made a recommendation to the Secretary under paragraph (4) regarding priority review, the number of times the Secretary followed or did not follow such a recommendation, and, if not followed, the reasons why such a recommendation was not followed.
If, on or after September 27, 2007, 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.
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.
The Commissioner shall consider the recommendations of the Pediatric Advisory Committee and, if appropriate, not later than 30 days after receiving the recommendation, make a request to the sponsor of the application or supplement to make any labeling changes that the Commissioner determines to be appropriate.
If the sponsor of the application or supplement, within 30 days after receiving a request under subparagraph (C), does not agree to make a labeling change requested by the Commissioner, the Commissioner may deem the drug that is the subject of the application or supplement to be misbranded.
Nothing in this subsection limits the authority of the United States to bring an enforcement action under this chapter 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.
If, on or after September 27, 2007, 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.
Not later than 210 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 Web site of the Food and Drug Administration.
Beginning on September 27, 2007, 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)(6)(H) distribute such information to physicians and other health care providers.
Nothing in this subsection shall alter or amend section 331(j) of this title or section 552 of title 5 or section 1905 of title 18.
Beginning on September 27, 2007, 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 such reports, the Director of such Office shall provide for the review of such reports by the Pediatric Advisory Committee, including obtaining any recommendations of such committee regarding whether the Secretary should take action under this chapter in response to such reports.
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.
The requirements of this subsection shall supplement, not supplant, other review of such adverse event reports by the Secretary.
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.
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 360bb of this title.
Not later than three years after September 27, 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 or precursor regulations since 1997 and labeling changes made as a result of such studies.
The study under paragraph (1) shall review and assess 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.
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.
The authority under this section shall remain in effect so long as an application subject to this section may be accepted for filing by the Secretary on or before the date specified in section 355a(q) of this title.
A biological product that is biosimilar to a reference product under section 262 of title 42, and that the Secretary has not determined to meet the standards described in subsection (k)(4) of such section for interchangeability with the reference product, shall be considered to have a new active ingredient under this section.
A biological product that is interchangeable with a reference product under section 262 of title 42 shall not be considered to have a new active ingredient under this section.
(June 25, 1938, ch. 675, §505B, as added Pub. L. 108–155, §2(a), Dec. 3, 2003, 117 Stat. 1936; amended Pub. L. 110–85, title IV, §402(a), Sept. 27, 2007, 121 Stat. 866; Pub. L. 111–148, title VII, §7002(d)(2), Mar. 23, 2010, 124 Stat. 816.)
2010—Subsec. (n). Pub. L. 111–148 added subsec. (n).
2007—Pub. L. 110–85 amended section generally. Prior to amendment, section related to required submission of assessments with an application for a new drug or new biological product and by order of the Secretary for certain marketed drugs and biological products used for pediatric patients, a definition of meaningful therapeutic benefit, consequences of failure to submit required assessments, meetings of the Secretary and the sponsor of a new drug or biological product, a limitation of the scope of the Secretary's authority, application to orphan drugs, and integration with other pediatric studies.
Pub. L. 110–85, title IV, §402(b), Sept. 27, 2007, 121 Stat. 875, provided that:
“(1)
“(2)
Pub. L. 108–155, §4, Dec. 3, 2003, 117 Stat. 1942, provided that:
“(a)
“(b)
“(1)
“(2)
“(A)
“(B)
“(i) the date that is 1 year after the date of enactment of this Act; or
“(ii) such date as the Secretary may specify under subsection (a)(3) of that section;
unless the Secretary grants a waiver under subsection (a)(4) of that section.
“(c)