---
kind: "section"
citation: "21 U.S.C. § 355c"
title: "21"
title_heading: "Food and Drugs"
number: "355c"
heading: "Research into pediatric uses for drugs and biological products"
release: "119-102"
date: "2026-07-12"
url: "https://uscodex.org/usc/21/355c"
units:
  - "Chapter 9 — Federal Food, Drug, and Cosmetic Act"
  - "Subchapter V — Drugs and Devices"
  - "Part A — Drugs and Devices"
---

# §355c. Research into pediatric uses for drugs and biological products

- (a) **New drugs and biological products—**
  - (1) **In general—**
    - (A) **General requirements—** Except with respect to an application for which [subparagraph (B)](#a-1-B) applies, a [person](/usc/21/321.md?p=e) that submits, on or after September 27, 2007, an application (or supplement to an application) for a [drug](/usc/21/321.md?p=g-1)—
      - (i) under [section 355 of this title](/usc/21/355.md) for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration; or
      - (ii) under [section 262 of title 42](/usc/42/262.md) 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)](#a-2).

    - (B) **Certain molecularly targeted cancer indications—** A [person](/usc/21/321.md?p=e) that submits, on or after the date that is 3 years after August 18, 2017, an original application for a new active ingredient under [section 355 of this title](/usc/21/355.md) or [section 262 of title 42](/usc/42/262.md), shall submit with the application reports on the investigation described in [paragraph (3)](#a-3) if the [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) that is the subject of the application is—
      - (i) intended for the treatment of an adult cancer; and
      - (ii) directed at a molecular target that the [Secretary](/usc/21/321.md?p=d) determines to be substantially relevant to the growth or progression of a pediatric cancer.
    - (C) **1 Rule of construction—** No application that is subject to the requirements of [subparagraph (B)](#a-1-B) shall be subject to the requirements of [subparagraph (A)](#a-1-A), and no application (or supplement to an application) that is subject to the requirements of [subparagraph (A)](#a-1-A) shall be subject to the requirements of [subparagraph (B)](#a-1-B).
  - (2) **Assessments—**
    - (A) **In general—** The assessments referred to in [paragraph (1)(A)](#a-1-A) 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](/usc/21/321.md?p=g-1) or the biological [product](/usc/21/360eee.md?p=13) for the claimed indications in all relevant pediatric subpopulations; and
      - (ii) to support dosing and administration for each pediatric subpopulation for which the [drug](/usc/21/321.md?p=g-1) or the biological [product](/usc/21/360eee.md?p=13) is [safe](/usc/21/321.md?p=u) 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](/usc/21/321.md?p=g-1) are sufficiently similar in adults and pediatric patients, the [Secretary](/usc/21/321.md?p=d) 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)](#a-2-B-i) and [(ii)](#a-2-B-ii) shall be included in any pertinent reviews for the application under [section 355 of this title](/usc/21/355.md) or [section 262 of title 42](/usc/42/262.md).
  - (3) **1 Molecularly targeted pediatric cancer investigation—**
    - (A) **In general—** For purposes of [paragraph (1)(B)](#a-1-B), the investigation described in this paragraph is a molecularly targeted pediatric cancer investigation of—
      - (i) the [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) for which the application referred to in such paragraph is submitted; or
      - (ii) such [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) used in combination with—
        - (I) an active ingredient of a [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13)—
          - (aa) for which an approved application under [section 355(j)](/usc/21/355.md?p=j) under[^2] this title or under [section 262(k) of title 42](/usc/42/262.md?p=k) is in effect; and
          - (bb) that is determined by the [Secretary](/usc/21/321.md?p=d), after consultation with the applicant, to be part of the standard of care for treating a pediatric cancer; or
        - (II) an active ingredient of a [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13)—
          - (aa) for which an approved application under [section 355(b) of this title](/usc/21/355.md?p=b) or [section 262(a) of title 42](/usc/42/262.md?p=a) to treat an adult cancer is in effect and is held by the same [person](/usc/21/321.md?p=e) submitting the application under [paragraph (1)(B)](#a-1-B); and
          - (bb) that is directed at a molecular target that the [Secretary](/usc/21/321.md?p=d) determines to be substantially relevant to the growth or progression of a pediatric cancer.
    - (B) **Additional requirements—**
      - (i) **Design of investigation—** A molecularly targeted pediatric cancer investigation referred to in [subparagraph (A)](#a-3-A) shall be designed to yield clinically meaningful pediatric study data that is gathered using appropriate formulations for each age group for which the study is required, regarding dosing, safety, and preliminary efficacy to inform potential pediatric [labeling](/usc/21/321.md?p=m).
      - (ii) **Limitation—** An investigation described in [subparagraph (A)(ii)](#a-3-A-ii) may be required only if the [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) for which the application referred to in [paragraph (1)(B)](#a-1-B) contains either—
        - (I) a single new active ingredient; or
        - (II) more than one active ingredient, if an application for the combination of active ingredients has not previously been approved but each active ingredient is in a [drug product](/usc/21/321.md?p=dd) that has been previously approved to treat an adult cancer.
      - (iii) **Results of already-completed preclinical studies of application drug—** With respect to an investigation required pursuant to [paragraph (1)(B)](#a-1-B), the [Secretary](/usc/21/321.md?p=d) may require the results of any completed preclinical studies relevant to the initial pediatric study plan be submitted to the [Secretary](/usc/21/321.md?p=d) at the same time that the initial pediatric study plan required under [subsection (e)(1)](#e-1) is submitted.
      - (iv) **Rule of construction regarding inactive ingredients—** With respect to a combination of active ingredients referred to in [subparagraph (A)(ii)](#a-3-A-ii), such subparagraph shall not be construed as addressing the use of inactive ingredients with such combination.
    - (C) **Extrapolation of data—** [Paragraph (2)(B)](#a-2-B) shall apply to investigations referred to in [subparagraph (A)](#a-3-A) to the same extent and in the same manner as [paragraph (2)(B)](#a-2-B) applies with respect to the assessments required under [paragraph (1)(A)](#a-1-A).
    - (D) **Deferrals and waivers—** Deferrals and waivers under paragraphs [(4)](#a-4) and [(5)](#a-5) shall apply to investigations described in this paragraph to the same extent and in the same manner as such deferrals and waivers apply with respect to the assessments required under [paragraph (1)(A)](#a-1-A).
  - (4) **Deferral—**
    - (A) **In general—** On the initiative of the [Secretary](/usc/21/321.md?p=d) or at the request of the applicant, the [Secretary](/usc/21/321.md?p=d) may defer submission of some or all assessments required under [paragraph (1)(A)](#a-1-A) or reports on the investigation required under [paragraph (1)(B)](#a-1-B) until a specified date after approval of the [drug](/usc/21/321.md?p=g-1) or issuance of the license for a biological [product](/usc/21/360eee.md?p=13) if—
      - (i) the [Secretary](/usc/21/321.md?p=d) finds that—
        - (I) the [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) 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](/usc/21/321.md?p=d)—
        - (I) certification of the grounds for deferring the assessments or reports on the investigation;
        - (II) a pediatric study plan as described in [subsection (e)](#e);
        - (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) **Deferral extension—**
      - (i) **In general—** On the initiative of the [Secretary](/usc/21/321.md?p=d) or at the request of the applicant, the [Secretary](/usc/21/321.md?p=d) may grant an extension of a deferral approved under [subparagraph (A)](#a-4-A) for submission of some or all assessments required under [paragraph (1)(A)](#a-1-A) or reports on the investigation required under [paragraph (1)(B)](#a-1-B) if—
        - (I) the [Secretary](/usc/21/321.md?p=d) determines that the conditions described in subclause [(II)](#a-4-A-i-II) or [(III)](#a-4-A-i-III) of subparagraph (A)(i) continue to be met; and
        - (II) the applicant submits a new timeline under [subparagraph (A)(ii)(IV)](#a-4-A-ii-IV) and any significant updates to the information required under [subparagraph (A)(ii)](#a-4-A-ii).
      - (ii) **Timing and information—** If the deferral extension under this subparagraph is requested by the applicant, the applicant shall submit the deferral extension request containing the information described in this subparagraph not less than 90 days prior to the date that the deferral would expire. The [Secretary](/usc/21/321.md?p=d) shall respond to such request not later than 45 days after the receipt of such letter. If the [Secretary](/usc/21/321.md?p=d) grants such an extension, the specified date shall be the extended date. The [sponsor](/usc/21/360fff.md?p=8) of the required assessment under [paragraph (1)(A)](#a-1-A) or reports on the investigation under [paragraph (1)(B)](#a-1-B) shall not be issued a letter described in [subsection (d)](#d) unless the specified or extended date of submission for such required studies has passed or if the request for an extension is pending. For a deferral that has expired prior to July 9, 2012, or that will expire prior to 270 days after July 9, 2012, a deferral extension shall be requested by an applicant not later than 180 days after July 9, 2012. The [Secretary](/usc/21/321.md?p=d) shall respond to any such request as soon as practicable, but not later than 1 year after July 9, 2012. Nothing in this clause shall prevent the [Secretary](/usc/21/321.md?p=d) from updating the status of a study or studies publicly if components of such study or studies are late or delayed.
    - (C) **Annual review—**
      - (i) **In general—** On an annual basis following the approval of a deferral under [subparagraph (A)](#a-4-A), the applicant shall submit to the [Secretary](/usc/21/321.md?p=d) 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.
        - (III) Projected completion date for pediatric studies.
        - (IV) The reason or reasons why a deferral or deferral extension continues to be necessary.
      - (ii) **Public availability—** Not later than 90 days after the submission to the [Secretary](/usc/21/321.md?p=d) of the information submitted through the annual review under [clause (i)](#a-4-C-i), the [Secretary](/usc/21/321.md?p=d) shall make available to the public in an easily accessible manner, including through the Internet Web site of the [Food](/usc/21/321.md?p=f) and [Drug](/usc/21/321.md?p=g-1) Administration—
        - (I) such information;
        - (II) the name of the applicant for the [product](/usc/21/360eee.md?p=13) subject to the assessment or investigation;
        - (III) the date on which the [product](/usc/21/360eee.md?p=13) was approved; and
        - (IV) the date of each deferral or deferral extension under this paragraph for the [product](/usc/21/360eee.md?p=13).
  - (5) **Waivers—**
    - (A) **Full waiver—** On the initiative of the [Secretary](/usc/21/321.md?p=d) or at the request of an applicant, the [Secretary](/usc/21/321.md?p=d) shall grant a full waiver, as appropriate, of the requirement to submit assessments or reports on the investigation for a [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) under this subsection if the applicant certifies and the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) would be ineffective or unsafe in all pediatric age groups; or
      - (iii) the [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13)—
        - (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](/usc/21/321.md?p=d) or at the request of an applicant, the [Secretary](/usc/21/321.md?p=d) shall grant a partial waiver, as appropriate, of the requirement to submit assessments or reports on the investigation for a [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) under this subsection with respect to a specific pediatric age group if the applicant certifies and the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) would be ineffective or unsafe in that age group;
      - (iii) the [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13)—
        - (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 partial 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 such a partial waiver shall submit to the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=f) and [Drug](/usc/21/321.md?p=g-1) Administration.
    - (D) **Labeling requirement—** If the [Secretary](/usc/21/321.md?p=d) grants a full or partial waiver because there is evidence that a [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) would be ineffective or unsafe in pediatric populations, the information shall be included in the [labeling](/usc/21/321.md?p=m) for the [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13).
- (b) **Marketed drugs and biological products—**
  - (1) **In general—** The [Secretary](/usc/21/321.md?p=d) may (by order in the form of a letter) require the [sponsor](/usc/21/360fff.md?p=8) or holder of an approved application for a [drug](/usc/21/321.md?p=g-1) under [section 355 of this title](/usc/21/355.md) or the holder of a license for a biological [product](/usc/21/360eee.md?p=13) under [section 262 of title 42](/usc/42/262.md) to submit by a specified date the assessments described in [subsection (a)(2)](#a-2), if the [Secretary](/usc/21/321.md?p=d) finds that—
    - (A)
      - (i) the [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) is used for a substantial number of pediatric patients for the labeled indications; and
      - (ii) adequate pediatric [labeling](/usc/21/321.md?p=m) could confer a benefit on pediatric patients;
    - (B) there is reason to believe that the [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) 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](/usc/21/321.md?p=m) could pose a risk to pediatric patients.
  - (2) **Waivers—**
    - (A) **Full waiver—** At the request of an applicant, the [Secretary](/usc/21/321.md?p=d) shall grant a full waiver, as appropriate, of the requirement to submit assessments under this subsection if the applicant certifies and the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) would be ineffective or unsafe in all pediatric age groups.
    - (B) **Partial waiver—** At the request of an applicant, the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) would be ineffective or unsafe in that age group;
      - (iii)
        - (I) the [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13)—
          - (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](/usc/21/321.md?p=m) 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—** 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](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=f) and [Drug](/usc/21/321.md?p=g-1) Administration.
    - (D) **Labeling requirement—** If the [Secretary](/usc/21/321.md?p=d) grants a full or partial waiver because there is evidence that a [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) would be ineffective or unsafe in pediatric populations, the information shall be included in the [labeling](/usc/21/321.md?p=m) for the [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13).
  - (3) **Effect of subsection—** Nothing in this subsection alters or amends [section 331(j) of this title](/usc/21/331.md?p=j) or [section 552 of title 5](/usc/5/552.md) or [section 1905 of title 18](/usc/18/1905.md).
- (c) **Meaningful therapeutic benefit—** For the purposes of paragraph (4)(A)(iii)(I) and (4)(B)(iii)(I) of subsection (a) and paragraphs [(1)(B)](#b-1-B) and [(2)(B)(iii)(I)(aa)](#b-2-B-iii-I-aa) of subsection (b), a [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) shall be considered to represent a meaningful therapeutic benefit over existing therapies if the [Secretary](/usc/21/321.md?p=d) determines that—
  - (1) if approved, the [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) could represent an improvement in the treatment, diagnosis, or prevention of a disease, compared with marketed [products](/usc/21/360eee.md?p=13) adequately labeled for that use in the relevant pediatric population; or
  - (2) the [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) is in a class of [products](/usc/21/360eee.md?p=13) or for an indication for which there is a need for additional options.
- (d) **Submission of assessments and reports on the investigation—** If a [person](/usc/21/321.md?p=e) fails to submit a required assessment described in [subsection (a)(2)](#a-2) or the investigation described in [subsection (a)(3)](#a-3), fails to meet the applicable requirements in [subsection (a)(4)](#a-4), or fails to submit a request for approval of a pediatric formulation described in subsection [(a)](#a) or [(b)](#b), in accordance with applicable provisions of subsections [(a)](#a) and [(b)](#b), the following shall apply:
  - (1) **Noncompliance letter—** Beginning 270 days after July 9, 2012, the [Secretary](/usc/21/321.md?p=d) shall issue a non-compliance letter to such [person](/usc/21/321.md?p=e) informing them of such failure to submit or meet the requirements of the applicable subsection. Such letter shall require the [person](/usc/21/321.md?p=e) to respond in writing within 45 calendar days of issuance of such letter. Such response may include the [person](/usc/21/321.md?p=e)’s request for a deferral extension if applicable. Such letter and the [person](/usc/21/321.md?p=e)’s written response to such letter shall be made publicly available on the Internet Web site of the [Food](/usc/21/321.md?p=f) and [Drug](/usc/21/321.md?p=g-1) Administration 60 calendar days after issuance, with redactions for any trade secrets and confidential commercial information. If the [Secretary](/usc/21/321.md?p=d) determines that the letter was issued in error, the requirements of this paragraph shall not apply. The [Secretary](/usc/21/321.md?p=d) shall inform the Pediatric [Advisory Committee](/usc/21/360fff.md?p=1) of letters issued under this paragraph and responses to such letters.
  - (2) **Effect of noncompliance—** The [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) that is the subject of an assessment described in [subsection (a)(2)](#a-2) or the investigation described in [subsection (a)(3)](#a-3), applicable requirements in [subsection (a)(4)](#a-4), or request for approval of a pediatric formulation, may be considered misbranded solely because of that failure and subject to relevant enforcement action (except that the [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) shall be subject to action under [section 333 of this title](/usc/21/333.md) only if such [person](/usc/21/321.md?p=e) demonstrated a lack of due diligence in satisfying the applicable requirement), but such failure shall not be the basis for a proceeding—
    - (A) to withdraw approval for a [drug](/usc/21/321.md?p=g-1) under [section 355(e) of this title](/usc/21/355.md?p=e); or
    - (B) to revoke the license for a biological [product](/usc/21/360eee.md?p=13) under [section 262 of title 42](/usc/42/262.md).
  - (3) **Limitation—** The [Secretary](/usc/21/321.md?p=d) shall not issue enforcement actions under [section 333 of this title](/usc/21/333.md) for failures under this subsection in the case of a [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) that is no longer marketed.
  - (4) **Due diligence—** Before the [Secretary](/usc/21/321.md?p=d) may conclude that a [person](/usc/21/321.md?p=e) failed to submit or otherwise meet a requirement as described in the matter preceding [paragraph (1)](#d-1), the [Secretary](/usc/21/321.md?p=d) shall—
    - (A) issue a noncompliance letter pursuant to [paragraph (1)](#d-1);
    - (B) provide such [person](/usc/21/321.md?p=e) with a 45-day period beginning on the date of receipt of such noncompliance letter to respond in writing as set forth in such paragraph; and
    - (C) after reviewing such written response, determine whether the [person](/usc/21/321.md?p=e) demonstrated a lack of due diligence in satisfying such requirement.
- (e) **Pediatric study plans—**
  - (1) **In general—** An applicant subject to [subsection (a)](#a) shall submit to the [Secretary](/usc/21/321.md?p=d) an initial pediatric study plan prior to the submission of the assessments described under [subsection (a)(2)](#a-2) or the investigation described in [subsection (a)(3)](#a-3). The [Secretary](/usc/21/321.md?p=d) shall determine whether subparagraph [(A)](#a-1-A) or [(B)](#a-1-B) of subsection (a)(1) applies with respect to an application before the date on which the applicant is required to submit the initial pediatric study plan under [paragraph (2)(A)](#e-2-A).[^1]
  - (2) **Timing; content; meetings—**
    - (A) **Timing—** An applicant shall submit the initial pediatric study plan under [paragraph (1)](#e-1)—
      - (i) before the date on which the applicant submits the assessments under [subsection (a)(2)](#a-2) or the investigation described in [subsection (a)(3)](#a-3); and
      - (ii) not later than—
        - (I) 60 calendar days after the date of the end-of-Phase 2 meeting (as such term is used in section 312.47 of title 21, Code of Federal Regulations, or successor regulations); or
        - (II) such other time as may be agreed upon between the [Secretary](/usc/21/321.md?p=d) and the applicant.

      Nothing in this section shall preclude the [Secretary](/usc/21/321.md?p=d) from accepting the submission of an initial pediatric study plan earlier than the date otherwise applicable under this subparagraph.

    - (B) **Content of initial pediatric study plan—** The initial pediatric study plan shall include—
      - (i) an outline of the pediatric study or studies that the applicant plans to conduct (including, to the extent practicable study objectives and design, age groups, relevant endpoints, and statistical approach);
      - (ii) any request for a deferral, partial waiver, or waiver under this section, if applicable, along with any supporting information; and
      - (iii) other information specified in the regulations promulgated under [paragraph (7)](#e-7).
    - (C) **Meetings—** The [Secretary](/usc/21/321.md?p=d)—
      - (i) shall meet with the applicant—
        - (I) if requested by the applicant with respect to a [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) that is intended to treat a serious or life-threatening disease or condition, to discuss preparation of the initial pediatric study plan, not later than the end-of-Phase 1 meeting (as such term is used in section 312.82(b) of title 21, Code of Federal Regulations, or successor regulations) or within 30 calendar days of receipt of such request, whichever is later;
        - (II) to discuss the initial pediatric study plan as soon as practicable, but not later than 90 calendar days after the receipt of such plan under [subparagraph (A)](#e-2-A); and
        - (III) to discuss the bases for the deferral under [subsection (a)(4)](#a-4) or a full or partial waiver under [subsection (a)(5)](#a-5);
      - (ii) may determine that a written response to the initial pediatric study plan is sufficient to communicate comments on the initial pediatric study plan, and that no meeting under [clause (i)(II)](#e-2-C-i-II) is necessary; and
      - (iii) if the [Secretary](/usc/21/321.md?p=d) determines that no meeting under [clause (i)(II)](#e-2-C-i-II) is necessary, shall so notify the applicant and provide written comments of the [Secretary](/usc/21/321.md?p=d) as soon as practicable, but not later than 90 calendar days after the receipt of the initial pediatric study plan.
  - (3) **Agreed initial pediatric study plan—** Not later than 90 calendar days following the meeting under [paragraph (2)(C)(i)(II)](#e-2-C-i-II) or the receipt of a written response from the [Secretary](/usc/21/321.md?p=d) under [paragraph (2)(C)(iii)](#e-2-C-iii), the applicant shall document agreement on the initial pediatric study plan in a submission to the [Secretary](/usc/21/321.md?p=d) marked “Agreed Initial Pediatric Study Plan”, and the [Secretary](/usc/21/321.md?p=d) shall confirm such agreement to the applicant in writing not later than 30 calendar days of receipt of such agreed initial pediatric study plan.
  - (4) **Deferral and waiver—** If the agreed initial pediatric study plan contains a request from the applicant for a deferral, partial waiver, or waiver under this section, the written confirmation under [paragraph (3)](#e-3) shall include a recommendation from the [Secretary](/usc/21/321.md?p=d) as to whether such request meets the standards under paragraphs [(3)](#a-3) or [(4)](#a-4) of subsection (a).
  - (5) **Amendments to the agreed initial pediatric study plan—** At the initiative of the [Secretary](/usc/21/321.md?p=d) or the applicant, the agreed initial pediatric study plan may be amended at any time. The requirements of [paragraph (2)(C)](#e-2-C) shall apply to any such proposed amendment in the same manner and to the same extent as such requirements apply to an initial pediatric study plan under [paragraph (1)](#e-1). The requirements of paragraphs [(3)](#e-3) and [(4)](#e-4) shall apply to any agreement resulting from such proposed amendment in the same manner and to the same extent as such requirements apply to an agreed initial pediatric study plan.
  - (6) **Internal committee—** The [Secretary](/usc/21/321.md?p=d) shall consult the internal committee under [section 355d of this title](/usc/21/355d.md) on the review of the initial pediatric study plan, agreed initial pediatric study plan, and any significant amendments to such plans.
  - (7) **Required rulemaking—** Not later than 1 year after July 9, 2012, the [Secretary](/usc/21/321.md?p=d) shall promulgate proposed regulations and issue guidance to implement the provisions of this subsection.
- (f) **Review of pediatric study plans, assessments, deferrals, deferral extensions, and waivers—**
  - (1) **Review—** Beginning not later than 30 days after September 27, 2007, the [Secretary](/usc/21/321.md?p=d) shall utilize the internal committee established under [section 355d of this title](/usc/21/355d.md) to provide consultation to reviewing divisions on initial pediatric study plans, agreed initial pediatric study plans, and any significant amendments to such plans, and assessments prior to approval of an application or supplement for which a pediatric assessment is required under this section and all deferral, deferral extension, and waiver requests granted pursuant to this section.
  - (2) **Activity by committee—** The committee referred to in [paragraph (1)](#f-1) may operate using appropriate members of such committee and need not convene all members of the committee.
  - (3) **Documentation of committee action—** For each [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13), the committee referred to in [paragraph (1)](#f-1) shall document, for each activity described in paragraph [(4)](#f-4) or [(5)](#f-5), which members of the committee participated in such activity.
  - (4) **Review of pediatric study plans, assessments, deferrals, deferral extensions, and waivers—** Consultation on initial pediatric study plans, agreed initial pediatric study plans, and assessments by the committee referred to in [paragraph (1)](#f-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, deferral extensions, 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.
  - (5) **Retrospective review of pediatric assessments, deferrals, and waivers—** Not later than 1 year after September 27, 2007, the committee referred to in [paragraph (1)](#f-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](/usc/21/321.md?p=d) 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.
  - (6) **Tracking of assessments and labeling changes—** The [Secretary](/usc/21/321.md?p=d), in consultation with the committee referred to in [paragraph (1)](#f-1), shall track and make available to the public in an easily accessible manner, including through posting on the Web site of the [Food](/usc/21/321.md?p=f) and [Drug](/usc/21/321.md?p=g-1) Administration—
    - (A) the number of assessments conducted under this section;
    - (B) the specific [drugs](/usc/21/321.md?p=g-1) and biological [products](/usc/21/360eee.md?p=13) 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) aggregated on an annual basis—
      - (i) the total number of deferrals and deferral extensions requested and granted under this section and, if granted, the reasons for each such deferral or deferral extension;
      - (ii) the timeline for completion of the assessments;
      - (iii) the number of assessments completed and pending; and
      - (iv) the number of postmarket non-compliance letters issued pursuant to [subsection (d)](#d), and the recipients of such letters;
    - (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](/usc/21/321.md?p=m) changes made as a result of assessments conducted under this section;
    - (H) an annual summary of [labeling](/usc/21/321.md?p=m) changes made as a result of assessments conducted under this section for [distribution](/usc/21/360eee.md?p=5) pursuant to [subsection (h)(2)](#h-2);
    - (I) an annual summary of information submitted pursuant to [subsection (a)(4)(C)](#a-4-C); and
    - (J) the number of times the committee referred to in [paragraph (1)](#f-1) made a recommendation to the [Secretary](/usc/21/321.md?p=d) under [paragraph (4)](#f-4) regarding priority review, the number of times the [Secretary](/usc/21/321.md?p=d) followed or did not follow such a recommendation, and, if not followed, the reasons why such a recommendation was not followed.
- (g) **Labeling changes—**
  - (1) **Dispute resolution—**
    - (A) **Request for labeling change and failure to agree—** If, on or after September 27, 2007, the [Commissioner](/usc/21/321.md?p=ee) determines that a [sponsor](/usc/21/360fff.md?p=8) and the [Commissioner](/usc/21/321.md?p=ee) have been unable to reach agreement on appropriate changes to the [labeling](/usc/21/321.md?p=m) for the [drug](/usc/21/321.md?p=g-1) 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 that receives a priority review or 330 days after the date of the submission of an application or supplement that receives a standard review—
      - (i) the [Commissioner](/usc/21/321.md?p=ee) shall request that the [sponsor](/usc/21/360fff.md?p=8) of the application make any [labeling](/usc/21/321.md?p=m) change that the [Commissioner](/usc/21/321.md?p=ee) determines to be appropriate; and
      - (ii) if the [sponsor](/usc/21/360fff.md?p=8) does not agree within 30 days after the [Commissioner](/usc/21/321.md?p=ee)’s request to make a [labeling](/usc/21/321.md?p=m) change requested by the [Commissioner](/usc/21/321.md?p=ee), the [Commissioner](/usc/21/321.md?p=ee) shall refer the matter to the Pediatric [Advisory Committee](/usc/21/360fff.md?p=1).
    - (B) **Action by the Pediatric Advisory Committee—** Not later than 90 days after receiving a referral under [subparagraph (A)(ii)](#g-1-A-ii), the Pediatric [Advisory Committee](/usc/21/360fff.md?p=1) shall—
      - (i) review the pediatric study reports; and
      - (ii) make a recommendation to the [Commissioner](/usc/21/321.md?p=ee) concerning appropriate [labeling](/usc/21/321.md?p=m) changes, if any.
    - (C) **Consideration of recommendations—** The [Commissioner](/usc/21/321.md?p=ee) shall consider the recommendations of the Pediatric [Advisory Committee](/usc/21/360fff.md?p=1) and, if appropriate, not later than 30 days after receiving the recommendation, make a request to the [sponsor](/usc/21/360fff.md?p=8) of the application or supplement to make any [labeling](/usc/21/321.md?p=m) changes that the [Commissioner](/usc/21/321.md?p=ee) determines to be appropriate.
    - (D) **Misbranding—** If the [sponsor](/usc/21/360fff.md?p=8) of the application or supplement, within 30 days after receiving a request under [subparagraph (C)](#g-1-C), does not agree to make a [labeling](/usc/21/321.md?p=m) change requested by the [Commissioner](/usc/21/321.md?p=ee), the [Commissioner](/usc/21/321.md?p=ee) may deem the [drug](/usc/21/321.md?p=g-1) that is the subject of the application or supplement to be misbranded.
    - (E) **No effect on authority—** Nothing in this subsection limits the authority of the United States to bring an enforcement action under this chapter when a [drug](/usc/21/321.md?p=g-1) lacks appropriate pediatric [labeling](/usc/21/321.md?p=m). Neither course of action (the Pediatric [Advisory Committee](/usc/21/360fff.md?p=1) 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.
  - (2) **Other labeling changes—** If, on or after September 27, 2007, the [Secretary](/usc/21/321.md?p=d) makes a determination that a pediatric assessment conducted under this section does or does not demonstrate that the [drug](/usc/21/321.md?p=g-1) that is the subject of such assessment is [safe](/usc/21/321.md?p=u) and effective in pediatric populations or subpopulations, including whether such assessment results are inconclusive, the [Secretary](/usc/21/321.md?p=d) shall order the [labeling](/usc/21/321.md?p=m) of such [product](/usc/21/360eee.md?p=13) to include information about the results of the assessment and a statement of the [Secretary](/usc/21/321.md?p=d)’s determination.
- (h) **Dissemination of pediatric information—**
  - (1) **In general—** Not later than 210 days after the date of submission of an application (or supplement to an application) that contains a pediatric assessment under this section, if the application (or supplement) receives a priority review, or not later than 330 days after the date of submission of an application (or supplement to an application) that contains a pediatric assessment under this section, if the application (or supplement) receives a standard review, the [Secretary](/usc/21/321.md?p=d) 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](/usc/21/321.md?p=f) and [Drug](/usc/21/321.md?p=g-1) Administration.
  - (2) **Dissemination of information regarding labeling changes—** Beginning on September 27, 2007, the [Secretary](/usc/21/321.md?p=d) shall require that the [sponsors](/usc/21/360fff.md?p=8) of the assessments that result in [labeling](/usc/21/321.md?p=m) changes that are reflected in the annual summary developed pursuant to [subsection (f)(6)(H)](#f-6-H) [distribute](/usc/21/360eee.md?p=5) such information to physicians and other health care providers.
  - (3) **Effect of subsection—** Nothing in this subsection shall alter or amend [section 331(j) of this title](/usc/21/331.md?p=j) or [section 552 of title 5](/usc/5/552.md) or [section 1905 of title 18](/usc/18/1905.md).
- (i) **Adverse event reporting—**
  - (1) **Reporting in first 18-month period—** Beginning on September 27, 2007, during the 18-month period beginning on the date a [labeling](/usc/21/321.md?p=m) change is made pursuant to [subsection (g)](#g), the [Secretary](/usc/21/321.md?p=d) shall ensure that all adverse event reports that have been received for such [drug](/usc/21/321.md?p=g-1) (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](/usc/21/360fff.md?p=1), including obtaining any recommendations of such committee regarding whether the [Secretary](/usc/21/321.md?p=d) should take action under this chapter in response to such reports.
  - (2) **Reporting in subsequent periods—** Following the 18-month period described in [paragraph (1)](#i-1), the [Secretary](/usc/21/321.md?p=d) shall, as appropriate, refer to the Office of Pediatric Therapeutics all pediatric adverse event reports for a [drug](/usc/21/321.md?p=g-1) 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](/usc/21/360fff.md?p=1), including obtaining any recommendation of such Committee regarding whether the [Secretary](/usc/21/321.md?p=d) should take action in response to such reports.
  - (3) **Preservation of authority—** Nothing in this subsection shall prohibit the Office of Pediatric Therapeutics from providing for the review of adverse event reports by the Pediatric [Advisory Committee](/usc/21/360fff.md?p=1) prior to the 18-month period referred to in [paragraph (1)](#i-1), if such review is necessary to ensure [safe](/usc/21/321.md?p=u) use of a [drug](/usc/21/321.md?p=g-1) in a pediatric population.
  - (4) **Effect—** The requirements of this subsection shall supplement, not supplant, other review of such adverse event reports by the [Secretary](/usc/21/321.md?p=d).
- (j) **Scope of authority—** Nothing in this section provides to the [Secretary](/usc/21/321.md?p=d) any authority to require a pediatric assessment of any [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13), or any assessment regarding other populations or uses of a [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13), other than the pediatric assessments described in this section.
- (k) **Relation to orphan drugs—**
  - (1) **In general; exemption for orphan indications—** Unless the [Secretary](/usc/21/321.md?p=d) requires otherwise by regulation and except as provided in [paragraph (2)](#k-2), this section does not apply to any [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) for an indication for which orphan designation has been granted under [section 360bb of this title](/usc/21/360bb.md).
  - (2) **Applicability despite orphan designation of certain indications—** This section shall apply with respect to a [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) for which an indication has been granted orphan designation under 360bb[^3] of this title if the investigation described in [subsection (a)(3)](#a-3) applies to the [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) as described in [subsection (a)(1)(B)](#a-1-B).
- (l) **New active ingredient—**
  - (1) **Non-interchangeable biosimilar biological product—** A biological [product](/usc/21/360eee.md?p=13) that is biosimilar to a reference [product](/usc/21/360eee.md?p=13) under [section 262 of title 42](/usc/42/262.md), and that the [Secretary](/usc/21/321.md?p=d) has not determined to meet the standards described in [subsection (k)(4)](/usc/42/262.md?p=k-4) of such section for interchangeability with the reference [product](/usc/21/360eee.md?p=13), shall be considered to have a new active ingredient under this section.
  - (2) **Interchangeable biosimilar biological product—** A biological [product](/usc/21/360eee.md?p=13) that is interchangeable with a reference [product](/usc/21/360eee.md?p=13) under [section 262 of title 42](/usc/42/262.md) shall not be considered to have a new active ingredient under this section.
- (m) **List of primary molecular targets—**
  - (1) **In general—** Within one year of August 18, 2017, the [Secretary](/usc/21/321.md?p=d) shall establish and update regularly, and shall publish on the internet website of the [Food](/usc/21/321.md?p=f) and [Drug](/usc/21/321.md?p=g-1) Administration—
    - (A) a list of molecular targets considered, on the basis of data the [Secretary](/usc/21/321.md?p=d) determines to be adequate, to be substantially relevant to the growth and progression of a pediatric cancer, and that may trigger the requirements under this section; and
    - (B) a list of molecular targets of new cancer [drugs](/usc/21/321.md?p=g-1) and biological [products](/usc/21/360eee.md?p=13) in development for which pediatric cancer study requirements under this section will be automatically waived.
  - (2) **Consultation—** In establishing the lists described in [paragraph (1)](#m-1), the [Secretary](/usc/21/321.md?p=d) shall consult the National Cancer Institute, members of the internal committee under [section 355d of this title](/usc/21/355d.md), and the Pediatric Oncology Subcommittee of the Oncologic [Drugs](/usc/21/321.md?p=g-1) [Advisory Committee](/usc/21/360fff.md?p=1), and shall take into account comments from the meeting under [subsection (c)](#c).
  - (3) **Rule of construction—** Nothing in [paragraph (1)](#m-1) shall be construed—
    - (A) to require the inclusion of a molecular target on the list published under such paragraph as a condition for triggering the requirements under [subsection (a)(1)(B)](#a-1-B) with respect to a [drug](/usc/21/321.md?p=g-1) or biological [product](/usc/21/360eee.md?p=13) directed at such molecular target; or
    - (B) to authorize the disclosure of confidential commercial information, as prohibited under [section 331(j) of this title](/usc/21/331.md?p=j) or [section 1905 of title 18](/usc/18/1905.md).

## Footnotes

[^1]: See Applicability of Amendment note below.
[^2]: So in original. Probably should be “of”.
[^3]: So in original. Probably should be preceded by “section”.

## Source credit

(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; Pub. L. 112–144, title V, §§ 501(b), 505–506(b), 509(b), July 9, 2012, 126 Stat. 1040–1044, 1048; Pub. L. 114–255, div. A, title III, §§ 3101(a)(2)(D), 3102(3), Dec. 13, 2016, 130 Stat. 1153, 1156; Pub. L. 115–52, title V, §§ 503–504(b), 505(e), Aug. 18, 2017, 131 Stat. 1038–1041, 1047; Pub. L. 117–328, div. FF, title II, § 2515(c), Dec. 29, 2022, 136 Stat. 5806; Pub. L. 119–75, div. J, title VI, §§ 6601(a), 6602(a), (b), Feb. 3, 2026, 140 Stat. 695, 698.)

## Notes

### Applicability of Amendment

Amendment of this section by section 6601(a) of Pub. L. 119–75 applicable with respect to any application under section 505(b) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(b)) and any application under section 351(a) of the Public Health Service Act (42 U.S.C. 262(a)), that is submitted on or after the date that is 3 years after Feb. 3, 2026. See 2026 Amendment notes below.

### Editorial Notes

### Amendments

2026—Subsec. (a)(1)(C). Pub. L. 119–75, § 6601(a)(3), added subpar. (C).

Subsec. (a)(3)(A), (B). Pub. L. 119–75, § 6601(a)(1), added subpars. (A) and (B) and struck out former subpar. (A). Prior to amendment, text of subpar. (A) read as follows: “With respect to a drug or biological product described in paragraph (1)(B), the investigation described in this paragraph is a molecularly targeted pediatric cancer investigation, which shall be designed to yield clinically meaningful pediatric study data, gathered using appropriate formulations for each age group for which the study is required, regarding dosing, safety, and preliminary efficacy to inform potential pediatric labeling.” Former subpar. (B) redesignated (C).

Subsec. (a)(3)(C). Pub. L. 119–75, § 6601(a)(1)(A), (4)(A), redesignated subpar. (B) as (C) and substituted “investigations referred to in subparagraph (A)” for “investigations described in this paragraph”. Former subpar. (C) redesignated (D).

Subsec. (a)(3)(D). Pub. L. 119–75, § 6601(a)(1)(A), (4)(B), redesignated subpar. (C) as (D) and substituted “the assessments required under paragraph (1)(A)” for “the assessments under paragraph (2)(B)”.

Subsec. (d)(1). Pub. L. 119–75, § 6602(a)(1), inserted heading.

Subsec. (d)(2). Pub. L. 119–75, § 6602(a)(2), inserted heading and substituted “(except that the drug or biological product shall be subject to action under section 333 of this title only if such person demonstrated a lack of due diligence in satisfying the applicable requirement)” for “(except that the drug or biological product shall not be subject to action under section 333 of this title)”.

Subsec. (d)(3). Pub. L. 119–75, § 6602(a)(3), added par. (3).

Subsec. (d)(4). Pub. L. 119–75, § 6602(b), added par. (4).

Subsec. (e)(1). Pub. L. 119–75, § 6601(a)(2), inserted at end “The Secretary shall determine whether subparagraph (A) or (B) of subsection (a)(1) applies with respect to an application before the date on which the applicant is required to submit the initial pediatric study plan under paragraph (2)(A).”

2022—Subsec. (f)(6)(I). Pub. L. 117–328 substituted “subsection (a)(4)(C)” for “subsection (a)(3)(B)”.

2017—Subsec. (a)(1). Pub. L. 115–52, § 504(a)(1)(A), designated existing provisions as subpar. (A) and inserted heading, substituted “Except with respect to an application for which subparagraph (B) applies, a person” for “A person”, redesignated former subpars. (A) and (B) as cls. (i) and (ii), respectively, of subpar. (A) and realigned margins, substituted “; or” for “, or” at end of subpar. (A)(i), and added subpar. (B).

Subsec. (a)(2)(A). Pub. L. 115–52, § 504(a)(1)(B), substituted “paragraph (1)(A)” for “paragraph (1)” in introductory provisions.

Subsec. (a)(3). Pub. L. 115–52, § 504(a)(1)(D), added par. (3). Former par. (3) redesignated (4).

Subsec. (a)(4). Pub. L. 115–52, § 504(a)(1)(C), redesignated par. (3) as (4). Former par. (4) redesignated (5).

Subsec. (a)(4)(A). Pub. L. 115–52, § 504(a)(1)(E)(i), substituted “assessments required under paragraph (1)(A) or reports on the investigation required under paragraph (1)(B)” for “assessments required under paragraph (1)” in introductory provisions.

Subsec. (a)(4)(A)(ii)(I). Pub. L. 115–52, § 504(a)(1)(E)(ii), inserted “or reports on the investigation” after “assessments”.

Subsec. (a)(4)(B)(i). Pub. L. 115–52, § 504(a)(1)(E)(i), substituted “assessments required under paragraph (1)(A) or reports on the investigation required under paragraph (1)(B)” for “assessments required under paragraph (1)” in introductory provisions.

Subsec. (a)(4)(B)(ii). Pub. L. 115–52, § 504(a)(1)(E)(iii), substituted “assessment under paragraph (1)(A) or reports on the investigation under paragraph (1)(B)” for “assessment under paragraph (1)”.

Subsec. (a)(4)(C)(ii)(II). Pub. L. 115–52, § 504(a)(1)(E)(iv), inserted “or investigation” after “assessment”.

Subsec. (a)(5). Pub. L. 115–52, § 504(a)(1)(C), redesignated par. (4) as (5).

Subsec. (a)(5)(A), (B). Pub. L. 115–52, § 504(a)(1)(F), inserted “or reports on the investigation” after “assessments” in introductory provisions.

Subsec. (d). Pub. L. 115–52, § 504(a)(2), inserted “and reports on the investigation” after “Submission of assessments” in heading and, in introductory provisions, inserted “or the investigation described in subsection (a)(3)” after “assessment described in subsection (a)(2)” and substituted “subsection (a)(4)” for “subsection (a)(3)”.

Subsec. (d)(1). Pub. L. 115–52, § 505(e), inserted at end “The Secretary shall inform the Pediatric Advisory Committee of letters issued under this paragraph and responses to such letters.”

Subsec. (d)(2). Pub. L. 115–52, § 504(a)(2)(A), (C), in introductory provisions, inserted “or the investigation described in subsection (a)(3)” after “assessment described in subsection (a)(2)” and substituted “subsection (a)(4)” for “subsection (a)(3)”.

Subsec. (e)(1). Pub. L. 115–52, § 504(a)(3)(A), inserted “or the investigation described in subsection (a)(3)” after “under subsection (a)(2)”.

Subsec. (e)(2). Pub. L. 115–52, § 503(b)(1), substituted “meetings” for “meeting” in heading.

Subsec. (e)(2)(A)(i). Pub. L. 115–52, § 504(a)(3)(B), inserted “or the investigation described in subsection (a)(3)” after “under subsection (a)(2)”.

Subsec. (e)(2)(C). Pub. L. 115–52, § 503(b)(2), substituted “Meetings” for “Meeting” in heading.

Subsec. (e)(2)(C)(i). Pub. L. 115–52, § 503(a), amended cl. (i) generally. Prior to amendment, cl. (i) read as follows: “shall meet with the applicant to discuss the initial pediatric study plan as soon as practicable, but not later than 90 calendar days after the receipt of such plan under subparagraph (A);”.

Subsec. (e)(2)(C)(ii), (iii). Pub. L. 115–52, § 503(b)(3), substituted “no meeting under clause (i)(II)” for “no meeting”.

Subsec. (e)(3). Pub. L. 115–52, § 503(b)(4), substituted “meeting under paragraph (2)(C)(i)(II)” for “meeting under paragraph (2)(C)(i)”.

Subsec. (k). Pub. L. 115–52, § 504(b), amended subsec. (k) generally. Prior to amendment, text read as follows: “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.”

Subsec. (m). Pub. L. 115–52, § 504(a)(4), added subsec. (m).

2016—Subsec. (e)(2)(A). Pub. L. 114–255, § 3101(a)(2)(D)(i)(I)(aa), inserted “study” after “initial pediatric” in introductory and concluding provisions.

Subsec. (e)(2)(B). Pub. L. 114–255, § 3101(a)(2)(D)(i)(I)(bb), substituted “Content of initial pediatric study plan” for “Content of initial plan” in heading.

Subsec. (e)(5). Pub. L. 114–255, § 3101(a)(2)(D)(i)(II), inserted “agreed initial pediatric study” before “plan” in heading.

Subsec. (e)(6). Pub. L. 114–255, § 3101(a)(2)(D)(i)(III), substituted “agreed initial pediatric study plan” for “agreed initial pediatric plan”.

Subsec. (f)(1). Pub. L. 114–255, § 3101(a)(2)(D)(ii), inserted “and any significant amendments to such plans,” after “agreed initial pediatric study plans,”.

Subsecs. (l), (m). Pub. L. 114–255, § 3102(3), redesignated subsec. (m) as (l) and struck out former subsec. (l) which related to Institute of Medicine study.

2012—Subsec. (a)(1). Pub. L. 112–144, § 509(b)(1)(A), inserted “for a drug” after “(or supplement to an application)” in introductory provisions.

Subsec. (a)(3)(A)(ii)(II). Pub. L. 112–144, § 506(b)(1), amended subcl. (II) generally. Prior to amendment, subcl. (II) read as follows: “a description of the planned or ongoing studies;”.

Subsec. (a)(3)(B), (C). Pub. L. 112–144, § 505(a)(1)(A), (B), added subpar. (B) and redesignated former subpar. (B) as (C).

Subsec. (a)(3)(C)(i)(III), (IV). Pub. L. 112–144, § 505(a)(1)(C)(i), added subcls. (III) and (IV).

Subsec. (a)(3)(C)(ii). Pub. L. 112–144, § 505(a)(1)(C)(ii), amended cl. (ii) generally. Prior to amendment, text read as follows: “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.”

Subsec. (a)(4)(C). Pub. L. 112–144, § 509(b)(1)(B), inserted “partial” after “If a” in first sentence and substituted “such a” for “either a full or” in second sentence.

Subsec. (b)(1). Pub. L. 112–144, § 509(b)(2), substituted “The” for “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” in introductory provisions.

Subsec. (d). Pub. L. 112–144, § 505(c)(1), amended subsec. (d) generally. Prior to amendment, subsec. (d) related to submission of assessments.

Subsec. (e). Pub. L. 112–144, § 506(a), amended subsec. (e) generally. Prior to amendment, text read as follows: “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.”

Subsec. (f). Pub. L. 112–144, § 506(b)(2)(A), substituted “pediatric study plans,” for “pediatric plans,” in heading.

Pub. L. 112–144, § 505(a)(2)(A), inserted “deferral extensions,” after “deferrals,” in heading.

Subsec. (f)(1). Pub. L. 112–144, § 506(b)(2)(B), substituted “initial pediatric study plans, agreed initial pediatric study plans,” for “all pediatric plans”.

Pub. L. 112–144, § 505(a)(2)(B), inserted “, deferral extension,” after “deferral”.

Subsec. (f)(4). Pub. L. 112–144, § 506(b)(2)(C), substituted “pediatric study plans,” for “pediatric plans,” in heading and “initial pediatric study plans, agreed initial pediatric study plans,” for “pediatric plans” in text.

Pub. L. 112–144, § 505(a)(2)(C), inserted “deferral extensions,” after “deferrals,” in heading and “, deferral extensions,” after “deferrals” in text.

Subsec. (f)(6)(D). Pub. L. 112–144, § 505(b), amended subpar. (D) generally. Prior to amendment, subpar. (D) read as follows: “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);”.

Subsec. (f)(6)(D)(iv). Pub. L. 112–144, § 505(c)(2), added cl. (iv).

Subsec. (g)(1)(A). Pub. L. 112–144, § 509(b)(3)(A), inserted “that receives a priority review or 330 days after the date of the submission of an application or supplement that receives a standard review” after “after the date of the submission of the application or supplement” in introductory provisions.

Subsec. (g)(2). Pub. L. 112–144, § 509(b)(3)(B), substituted “the labeling of such product” for “the label of such product”.

Subsec. (h)(1). Pub. L. 112–144, § 509(b)(4), inserted “an application (or supplement to an application) that contains” after “date of submission of” and “if the application (or supplement) receives a priority review, or not later than 330 days after the date of submission of an application (or supplement to an application) that contains a pediatric assessment under this section, if the application (or supplement) receives a standard review,” after “under this section,”.

Subsec. (i)(1). Pub. L. 112–144, § 509(b)(5)(A), substituted “first 18-month period” for “year one” in heading and “18-month” for “one-year” in text.

Subsec. (i)(2). Pub. L. 112–144, § 509(b)(5)(B), substituted “periods” for “years” in heading and “18-month period” for “one-year period” in text.

Subsec. (i)(3), (4). Pub. L. 112–144, § 509(b)(5)(C), (D), added par. (3) and redesignated former par. (3) as (4).

Subsecs. (m), (n). Pub. L. 112–144, § 501(b), redesignated subsec. (n) as (m) and struck out former subsec. (m). Prior to amendment, text of subsec. (m) read as follows: “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.”

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.

### Statutory Notes and Related Subsidiaries

### Effective Date of 2026 Amendment

Pub. L. 119–75, div. J, title VI, § 6601(c), Feb. 3, 2026, 140 Stat. 697, provided that: “The amendments made by this section [amending this section] apply with respect to any application under section 505(b) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(b)) and any application under section 351(a) of the Public Health Service Act (42 U.S.C. 262(a)), that is submitted on or after the date that is 3 years after the date of enactment of this Act [Feb. 3, 2026].”

### Effective Date of 2012 Amendment

Pub. L. 112–144, title V, § 506(c), July 9, 2012, 126 Stat. 1045, provided that: In general.—Subject to paragraph (2), the amendments made by this section [amending this section] shall take effect 180 calendar days after the date of enactment of this Act [July 9, 2012], irrespective of whether the Secretary [of Health and Human Services] has promulgated final regulations to carry out such amendments. Rule of construction.—Paragraph (1) shall not be construed to affect the deadline for promulgation of proposed regulations under section 505B(e)(7) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355c(e)(7)], as added by subsection (a) of this section.”

Notwithstanding any provision of this section stating that a provision applies beginning on Sept. 27, 2007, any amendment made by Pub. L. 112–144 to such a provision applies beginning on July 9, 2012, subject to a transitional rule, see section 509(g) of Pub. L. 112–144, set out as a note under section 355a of this title.

### Effective Date of 2007 Amendment

Pub. L. 110–85, title IV, § 402(b), Sept. 27, 2007, 121 Stat. 875, provided that: In general.—Notwithstanding subsection (h) of section 505B of the Federal Food, Drug and Cosmetic Act [21 U.S.C. 355c(h)], as in effect on the day before the date of the enactment of this Act [Sept. 27, 2007], a pending assessment, including a deferred assessment, required under such section 505B shall be deemed to have been required under section 505B of the Federal Food, Drug and Cosmetic Act as in effect on or after the date of the enactment of this Act. Certain assessments and waiver requests.—An assessment pending on or after the date that is 1 year prior to the date of the enactment of this Act shall be subject to the tracking and disclosure requirements established under such section 505B, as in effect on or after such date of enactment, except that any such assessments submitted or waivers of such assessments requested before such date of enactment shall not be subject to subsections (a)(4)(C), (b)(2)(C), (f)(6)(F), and (h) of such section 505B.”

### Effective Date

Pub. L. 108–155, § 4, Dec. 3, 2003, 117 Stat. 1942, provided that: In General.—Subject to subsection (b), this Act [enacting this section, amending sections 355, 355a, and 355b of this title and sections 262 and 284m of Title 42, The Public Health and Welfare, enacting provisions set out as a note under section 301 of this title, and amending provisions set out as notes under section 355a of this title and section 284m of Title 42] and the amendments made by this Act take effect on the date of enactment of this Act [Dec. 3, 2003].Applicability to New Drugs and Biological Products.— In general.—Subsection (a) of section 505B of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355c(a)] (as added by section 2) shall apply to an application described in paragraph (1) of that subsection submitted to the Secretary of Health and Human Services on or after April 1, 1999.Waivers and deferrals.— Waiver or deferral granted.—If, with respect to an application submitted to the Secretary of Health and Human Services between April 1, 1999, and the date of enactment of this Act [Dec. 3, 2003], a waiver or deferral of pediatric assessments was granted under regulations of the Secretary then in effect, the waiver or deferral shall be a waiver or deferral under subsection (a) of section 505B of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355c(a)], except that any date specified in such a deferral shall be extended by the number of days that is equal to the number of days between October 17, 2002, and the date of enactment of this Act. Waiver and deferral not granted.—If, with respect to an application submitted to the Secretary of Health and Human Services between April 1, 1999, and the date of enactment of this Act [Dec. 3, 2003], neither a waiver nor deferral of pediatric assessments was granted under regulations of the Secretary then in effect, the person that submitted the application shall be required to submit assessments under subsection (a)(2) of section 505B of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355c(a)(2)] on the date that is the later of— the date that is 1 year after the date of enactment of this Act; or 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. No Limitation of Authority.—Neither the lack of guidance or regulations to implement this Act or the amendments made by this Act nor the pendency of the process for issuing guidance or regulations shall limit the authority of the Secretary of Health and Human Services under, or defer any requirement under, this Act or those amendments.”

### Rule of Construction

Pub. L. 115–52, title V, § 504(e), Aug. 18, 2017, 131 Stat. 1045, provided that: “Nothing in this section [amending this section and section 355c–1 of this title and enacting provisions set out as a note below], including the amendments made by this section, shall limit the authority of the Secretary of Health and Human Services to issue written requests under section 505A of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a) or section 351(m) of the Public Health Service Act (42 U.S.C. 262(m)), or to negotiate or implement amendments to such requests proposed by the an [sic] applicant.”

### Guidance

Pub. L. 119–75, div. J, title VI, § 6601(b), Feb. 3, 2026, 140 Stat. 697, provided that: “The Secretary of Health and Human Services, acting through the Commissioner of Food and Drugs, shall— not later than 12 months after the date of enactment of this Act [Feb. 3, 2026], issue draft guidance on the implementation of the amendments made by subsection (a); and not later than 12 months after closing the comment period on such draft guidance, finalize such guidance.”

### Meeting, Consultation, and Guidance

Pub. L. 115–52, title V, § 504(c), Aug. 18, 2017, 131 Stat. 1041, provided that: Meeting.—The Secretary of Health and Human Services (referred to in this subsection as the ‘Secretary’), acting through the Commissioner of Food and Drugs and in collaboration with the Director of the National Cancer Institute, shall convene a public meeting not later than 1 year after the date of enactment of this Act [Aug. 18, 2017] to solicit feedback from physicians and researchers (including pediatric oncologists and rare disease specialists), patients, and other stakeholders to provide input on development of the guidance under paragraph (2) and the list under subsection (m) of section 505B of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355c), as added by subsection (a). The Secretary shall seek input at such meeting on— the data necessary to determine that there is scientific evidence that a drug or biological product is directed at a molecular target that is considered to be substantially relevant to the growth or progression of a pediatric cancer; the data necessary to determine that there is scientific evidence that a molecular target is considered to be substantially relevant to the growth or progression of a pediatric cancer; the data needed to meet the requirement of conducting an investigation described in section 505B(a)(3) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355c(a)(3)], as amended by subsection (a); considerations when developing the list under section 505B(m) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355c(m)] that contains molecular targets shared between different tumor types; the process the Secretary shall utilize to update regularly a list of molecular targets that may trigger a pediatric study under section 505B of the Federal Food, Drug, and Cosmetic Act, as so amended, and how often such updates shall occur; how to overcome the challenges related to pediatric cancer drug and biological product development, including issues related to the ethical, practical, and other barriers to conducting clinical trials in pediatric cancer with small patient populations; scientific or operational challenges associated with performing an investigation described in section 505B(a)(1)(B) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355c(a)(1)(B)], including the effect on pediatric studies currently underway in a pediatric patient population, treatment of a pediatric patient population, and the ability to complete adult clinical trials; the advantages and disadvantages of innovative clinical trial designs in addressing the development of cancer drugs or biological products directed at molecular targets in pediatric cancer patients; the ways in which the Secretary can improve the current process outlined under sections 505A and 505B of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a, 355c) to encourage additional research and development of pediatric cancer treatments; the ways in which the Secretary might streamline and improve the written request process, including when studies contained in a request under such section 505A are not feasible due to the ethical, practical, or other barriers to conducting clinical trials in pediatric cancer populations; how the Secretary will facilitate collaboration among pediatric networks, academic centers and experts in pediatric cancer to conduct an investigation described in such section 505B(a)(3); how the Secretary may facilitate collaboration among sponsors of same-in-class drugs and biological products that would be subject to the requirements for an investigation under such section 505B based on shared molecular targets; and the ways in which the Secretary will help to mitigate the risks, if any, of discouraging the research and development of orphan drugs when implementing such section 505B as amended. Guidance.—Not later than 2 years after the date of enactment of this Act [Aug. 18, 2017], the Secretary, acting through the Commissioner of Food and Drugs, shall issue final guidance on implementation of the amendments to section 505B of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355c) regarding molecularly targeted cancer drugs made by this section, including— the scientific criteria, types of data, and regulatory considerations for determining whether a molecular target is substantially relevant to the growth or progression of a pediatric cancer and would trigger an investigation under section 505B of the Federal Food, Drug, and Cosmetic Act, as amended; the process by which the Secretary will engage with sponsors to discuss determinations, investigation requirements, deferrals, waivers, and any other issues that need to be resolved to ensure that any required investigation based on a molecular target can be reasonably conducted; the scientific or operational challenges for which the Secretary may issue deferrals or waivers for an investigation described in subsection (a)(3) of such section 505B, including adverse impacts on current pediatric studies underway in a pediatric patient population, studies involving drugs designated as orphan drugs, treatment of a pediatric patient population, or the ability to complete adult clinical trials; how the Secretary and sponsors will facilitate collaboration among pediatric networks, academic centers, and experts in pediatric cancer to conduct an investigation described in subsection (a)(3) of such section 505B; scientific and regulatory considerations for study designs, including the applicability of innovative clinical trial designs for pediatric cancer drug and biological product developments under sections 505A and 505B of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a, 355c); approaches to streamline and improve the amendment process, including when studies contained in a request under such section 505A are not feasible due to the ethical, practical, or other barriers to conducting clinical trials in pediatric cancer populations; the process for submission of an initial pediatric study plan for the investigation described in section 505B(a)(3) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355c(a)(3)), including the process for a sponsor to meet and reach agreement with the Secretary on the initial pediatric study plan; and considerations for implementation of such section 505B, as so amended, and waivers of the requirements of such section 505B with regard to molecular targets for which several drugs or biological products may be under investigation.”