21 USC § 355c - Research into pediatric uses for drugs and biological products
(a)
New drugs and biological products
(1)
In general
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).
(2)
Assessments
(A)
In general
The assessments referred to in paragraph (1) shall contain data, gathered using appropriate formulations for each age group for which the assessment is required, that are adequate—
(B)
Similar course of disease or similar effect of drug or biological product
(i)
In general
If the course of the disease and the effects of the drug are sufficiently similar in adults and pediatric patients, the Secretary may conclude that pediatric effectiveness can be extrapolated from adequate and well-controlled studies in adults, usually supplemented with other information obtained in pediatric patients, such as pharmacokinetic studies.
(3)
Deferral
(A)
In general
On the initiative of the Secretary or at the request of the applicant, the Secretary may defer submission of some or all assessments required under paragraph (1) until a specified date after approval of the drug or issuance of the license for a biological product if—
(i)
the Secretary finds that—
(I)
the drug or biological product is ready for approval for use in adults before pediatric studies are complete;
(4)
Waivers
(A)
Full waiver
On the initiative of the Secretary or at the request of an applicant, the Secretary shall grant a full waiver, as appropriate, of the requirement to submit assessments for a drug or biological product under this subsection if the applicant certifies and the Secretary finds that—
(i)
necessary studies are impossible or highly impracticable (because, for example, the number of patients is so small or the patients are geographically dispersed);
(B)
Partial waiver
On the initiative of the Secretary or at the request of an applicant, the Secretary shall grant a partial waiver, as appropriate, of the requirement to submit assessments for a drug or biological product under this subsection with respect to a specific pediatric age group if the applicant certifies and the Secretary finds that—
(i)
necessary studies are impossible or highly impracticable (because, for example, the number of patients in that age group is so small or patients in that age group are geographically dispersed);
(ii)
there is evidence strongly suggesting that the drug or biological product would be ineffective or unsafe in that age group;
(C)
Pediatric formulation not possible
If a waiver is granted on the ground that it is not possible to develop a pediatric formulation, the waiver shall cover only the pediatric groups requiring that formulation. An applicant seeking either a full or partial waiver shall submit to the Secretary documentation detailing why a pediatric formulation cannot be developed and, if the waiver is granted, the applicant’s submission shall promptly be made available to the public in an easily accessible manner, including through posting on the Web site of the Food and Drug Administration.
(b)
Marketed drugs and biological products
(1)
In general
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)
(2)
Waivers
(A)
Full waiver
At the request of an applicant, the Secretary shall grant a full waiver, as appropriate, of the requirement to submit assessments under this subsection if the applicant certifies and the Secretary finds that—
(B)
Partial waiver
At the request of an applicant, the Secretary shall grant a partial waiver, as appropriate, of the requirement to submit assessments under this subsection with respect to a specific pediatric age group if the applicant certifies and the Secretary finds that—
(i)
necessary studies are impossible or highly impracticable (because, for example, the number of patients in that age group is so small or patients in that age group are geographically dispersed);
(ii)
there is evidence strongly suggesting that the drug or biological product would be ineffective or unsafe in that age group;
(C)
Pediatric formulation not possible
If a waiver is granted on the ground that it is not possible to develop a pediatric formulation, the waiver shall cover only the pediatric groups requiring that formulation. An applicant seeking either a full or partial waiver shall submit to the Secretary documentation detailing why a pediatric formulation cannot be developed and, if the waiver is granted, the applicant’s submission shall promptly be made available to the public in an easily accessible manner, including through posting on the Web site of the Food and Drug Administration.
(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) 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—
(d)
Submission of assessments
If a person fails to submit an assessment described in subsection (a)(2), or a request for approval of a pediatric formulation described in subsection (a) or (b), in accordance with applicable provisions of subsections (a) and (b)—
(1)
the drug or biological product that is the subject of the assessment or request may be considered misbranded solely because of that failure and subject to relevant enforcement action (except that the drug or biological product shall not be subject to action under section
333 of this title); but
(e)
Meetings
Before and during the investigational process for a new drug or biological product, the Secretary shall meet at appropriate times with the sponsor of the new drug or biological product to discuss—
(f)
Review of pediatric plans, assessments, deferrals, and waivers
(1)
Review
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.
(2)
Activity by committee
The committee referred to in paragraph (1) may operate using appropriate members of such committee and need not convene all members of the committee.
(3)
Documentation of committee action
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.
(4)
Review of pediatric plans, assessments, deferrals, and waivers
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.
(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) 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.
(6)
Tracking of assessments and labeling changes
The Secretary, in consultation with the committee referred to in paragraph (1), shall track and make available to the public in an easily accessible manner, including through posting on the Web site of the Food and Drug Administration—
(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;
(H)
an annual summary of labeling changes made as a result of assessments conducted under this section for distribution pursuant to subsection (h)(2);
(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.
(g)
Labeling changes
(1)
Dispute resolution
(A)
Request for labeling change and failure to agree
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—
(B)
Action by the Pediatric Advisory Committee
Not later than 90 days after receiving a referral under subparagraph (A)(ii), the Pediatric Advisory Committee shall—
(C)
Consideration of recommendations
The Commissioner shall consider the recommendations of the Pediatric Advisory Committee and, if appropriate, not later than 30 days after receiving the recommendation, make a request to the sponsor of the application or supplement to make any labeling changes that the Commissioner determines to be appropriate.
(D)
Misbranding
If the sponsor 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.
(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 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.
(2)
Other labeling changes
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.
(h)
Dissemination of pediatric information
(1)
In general
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.
(2)
Dissemination of information regarding labeling changes
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.
(i)
Adverse event reporting
(1)
Reporting in year one
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.
(2)
Reporting in subsequent years
Following the one-year period described in paragraph (1), the Secretary shall, as appropriate, refer to the Office of Pediatric Therapeutics all pediatric adverse event reports for a drug for which a pediatric study was conducted under this section. In considering such reports, the Director of such Office may provide for the review of such reports by the Pediatric Advisory Committee, including obtaining any recommendation of such Committee regarding whether the Secretary should take action in response to such reports.
(j)
Scope of authority
Nothing in this section provides to the Secretary any authority to require a pediatric assessment of any drug or biological product, or any assessment regarding other populations or uses of a drug or biological product, other than the pediatric assessments described in this section.
(k)
Orphan drugs
Unless the Secretary requires otherwise by regulation, this section does not apply to any drug for an indication for which orphan designation has been granted under section
360bb of this title.
(l)
Institute of Medicine study
(1)
In general
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.
(2)
Content of study
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.
(n)
New active ingredient
(1)
Non-interchangeable biosimilar biological product
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.
Source
(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.)
Amendments
2010—Subsec. (n). Pub. L. 111–148added subsec. (n).
2007—Pub. L. 110–85amended 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.
Effective Date of 2007 Amendment
Pub. L. 110–85, title IV, § 402(b),Sept. 27, 2007, 121 Stat. 875, provided that:
“(1) In general.—Notwithstanding subsection (h) ofsection
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.
“(2) 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:
“(a) 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].
“(b) Applicability to New Drugs and Biological Products.—
“(1) In general.—Subsection (a) ofsection
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.
“(2) Waivers and deferrals.—
“(A) 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) ofsection
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.
“(B) 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) ofsection
505B of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355c
(a)(2)] on the date that is the later of—
“(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) 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.”
The table below lists the classification updates, since Jan. 3, 2012, for this section. Updates to a broader range of sections may be found at the update page for containing chapter, title, etc.
The most recent Classification Table update that we have noticed was Wednesday, December 26, 2012
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| 21 USC | Description of Change | Session Year | Public Law | Statutes at Large |
|---|---|---|---|---|
| § 355c | 2012 | 112-144 [Sec.] 505-506(b) | 126 Stat. 1040-1044 | |
| § 355c | 2012 | 112-144 [Sec.] 509(b) | 126 Stat. 1048 | |
| § 355c | nt new | 2012 | 112-144 [Sec.] 506(c) | 126 Stat. 1045 |
| § 355c | 2012 | 112-144 [Sec.] 501(b) | 126 Stat. 1040 |
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