21 USC 355 - Research into pediatric uses for drugs and biological products

1 So in original. Probably should be preceded by “section”.

of this title if the investigation described in subsection (a)(3) applies to the drug or biological product as described in subsection (a)(1)(B).

Editorial Notes

Amendments

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

2017—Subsec. (a)(1). Puspan. L. 115–52, § 504(a)(1)(A), designated existing provisions as subpar. (A) and inserted span, 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). Puspan. L. 115–52, § 504(a)(1)(B), substituted “paragraph (1)(A)” for “paragraph (1)” in introductory provisions.

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

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

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

Subsec. (a)(4)(B)(i). Puspan. 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). Puspan. 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). Puspan. L. 115–52, § 504(a)(1)(E)(iv), inserted “or investigation” after “assessment”.

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

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

Subsec. (d). Puspan. L. 115–52, § 504(a)(2), inserted “and reports on the investigation” after “Submission of assessments” in span 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). Puspan. 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). Puspan. 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). Puspan. L. 115–52, § 504(a)(3)(A), inserted “or the investigation described in subsection (a)(3)” after “under subsection (a)(2)”.

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

Subsec. (e)(2)(A)(i). Puspan. 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). Puspan. L. 115–52, § 503(span)(2), substituted “Meetings” for “Meeting” in span.

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

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

Subsec. (k). Puspan. L. 115–52, § 504(span), 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 360bspan of this title.”

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

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

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

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

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

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

Subsec. (a)(3)(A)(ii)(II). Puspan. L. 112–144, § 506(span)(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). Puspan. 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). Puspan. L. 112–144, § 505(a)(1)(C)(i), added subcls. (III) and (IV).

Subsec. (a)(3)(C)(ii). Puspan. 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 Wespan site of the Food and Drug Administration.”

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

Subsec. (span)(1). Puspan. L. 112–144, § 509(span)(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). Puspan. L. 112–144, § 505(c)(1), amended subsec. (d) generally. Prior to amendment, subsec. (d) related to submission of assessments.

Subsec. (e). Puspan. 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). Puspan. L. 112–144, § 506(span)(2)(A), substituted “pediatric study plans,” for “pediatric plans,” in span.

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

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

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

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

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

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

Subsec. (g)(1)(A). Puspan. L. 112–144, § 509(span)(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). Puspan. L. 112–144, § 509(span)(3)(B), substituted “the labeling of such product” for “the label of such product”.

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

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

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

Subsecs. (m), (n). Puspan. L. 112–144, § 501(span), 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). Puspan. L. 111–148 added subsec. (n).

2007—Puspan. 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 2012 Amendment

Puspan. L. 112–144, title V, § 506(c), July 9, 2012, 126 Stat. 1045, provided that:

“(1)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.

“(2)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 Puspan. L. 112–144 to such a provision applies beginning on July 9, 2012, subject to a transitional rule, see section 509(g) of Puspan. L. 112–144, set out as a note under section 355a of this title.

Effective Date of 2007 Amendment

Puspan. L. 110–85, title IV, § 402(span), Sept. 27, 2007, 121 Stat. 875, provided that:

“(1)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.

“(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), (span)(2)(C), (f)(6)(F), and (h) of such section 505B.”

Effective Date

Puspan. L. 108–155, § 4, Dec. 3, 2003, 117 Stat. 1942, provided that:

“(a)In General.—Subject to subsection (span), this Act [enacting this section, amending sections 355, 355a, and 355span 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].

“(span)Applicability to New Drugs and Biological Products.—

“(1)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.

“(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) 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.

“(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) 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—

“(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.”

Rule of Construction

Puspan. 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.”

Meeting, Consultation, and Guidance

Puspan. L. 115–52, title V, § 504(c), Aug. 18, 2017, 131 Stat. 1041, provided that:

“(1)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—

“(A) 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;

“(B) 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;

“(C) 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);

“(D) 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;

“(E) 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;

“(F) 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;

“(G) 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;

“(H) 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;

“(I) 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;

“(J) 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;

“(K) 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);

“(L) 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

“(M) 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.

“(2)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—

“(A) 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;

“(B) 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;

“(C) 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;

“(D) 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;

“(E) 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);

“(F) 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;

“(G) 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

“(H) 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.”