§355a Pediatric Studies of Drugs

2021—Subsec. (c)(1)(A)(i)(II). Pub. L. 117–9 substituted “(c)(3)(E)” for “(c)(3)(D)”. 2017—Subsecs. (b), (c). Pub. L. 115–52, § 505(b)(2)(A), substituted “subsection (d)(4)” for “subsection (d)(3)” in introductory provisions of par. (1) and in par. (2). Subsec. (d)(3) to (6). Pub. L. 115–52, § 505(b)(1), added par. (3) and redesignated former pars. (3) to (5) as (4) to (6), respectively. Subsec. (f)(3). Pub. L. 115–52, § 505(b)(2)(A), substituted “subsection (d)(4)” for “subsection (d)(3)”. Subsec. (f)(7). Pub. L. 115–52, § 505(a), added par. (7). Subsec. (h). Pub. L. 115–52, § 505(b)(2)(A), substituted “subsection (d)(4)” for “subsection (d)(3)”. Subsec. (o). Pub. L. 115–52, § 608(1), struck out “under section 355(j)” after “approval of drugs” in heading. Subsec. (o)(1). Pub. L. 115–52, § 608(2), substituted “under subsection (b)(2) or (j) of section 355 of this title” for “under section 355(j) of this title” and “, or by exclusivity under clause (iii) or (iv) of section 355(j)(5)(F) of this title, clause (iii) or (iv) of section 355(c)(3)(E) of this title, or section 360cc(a) of this title, or by an extension of such exclusivity under this section or section 355f of this title” for “or by exclusivity under clause (iii) or (iv) of section 355(j)(5)(F) of this title”. Subsec. (o)(2). Pub. L. 115–52, § 608(3), in introductory provisions, inserted “clauses (iii) and (iv) of section 355(c)(3)(E) of this title, or section 360cc of this title,” after “section 355(j)(5)(F) of this title,” and substituted “drug approved pursuant to an application submitted under subsection (b)(2) or (j) of section 355 of this title” for “drug approved under section 355(j) of this title”. Subsec. (o)(3). Pub. L. 115–52, § 608(4), amended par. (3) generally. Prior to amendment, text read as follows: “This subsection does not affect— “(A) the availability or scope of exclusivity under this section; “(B) the availability or scope of exclusivity under section 355 of this title for pediatric formulations; “(C) the question of the eligibility for approval of any application under section 355(j) of this title that omits any other conditions of approval entitled to exclusivity under clause (iii) or (iv) of section 355(j)(5)(F) of this title; or “(D) except as expressly provided in paragraphs (1) and (2), the operation of section 355 of this title.” 2016—Subsec. (p). Pub. L. 114–255 struck out subsec. (p) which related to Institute of Medicine study. 2013—Subsec. (d)(5). Pub. L. 113–5, § 307(a)(1), added par. (5). Subsec. (n)(1)(C). Pub. L. 113–5, § 307(a)(2), added subpar. (C). 2012—Subsec. (d)(1)(A). Pub. L. 112–144, § 502(b), inserted at end “If a request under this subparagraph does not request studies in neonates, such request shall include a statement describing the rationale for not requesting studies in neonates.” Subsec. (h). Pub. L. 112–144, § 502(a)(1), amended subsec. (h) generally. Prior to amendment, text read as follows: “Notwithstanding any other provision of law, if any pediatric study is required by a provision of law (including a regulation) other than this section and such study meets the completeness, timeliness, and other requirements of this section, such study shall be deemed to satisfy the requirement for market exclusivity pursuant to this section.” Subsec. (k)(2). Pub. L. 112–144, § 509(a)(1), substituted “subsection (f)(6)(F)” for “subsection (f)(3)(F)”. Subsec. (l)(1). Pub. L. 112–144, § 509(a)(2)(A), substituted “first 18-month period” for “year one” in heading and “18-month” for “one-year” in text. Subsec. (l)(2). Pub. L. 112–144, § 509(a)(2)(B), substituted “periods” for “years” in heading and “18-month period” for “one-year period” in text. Subsec. (l)(3), (4). Pub. L. 112–144, § 509(a)(2)(C), (D), added par. (3) and redesignated former par. (3) as (4). Subsec. (n). Pub. L. 112–144, § 509(a)(3)(A), substituted “submitted” for “completed” in heading. Subsec. (n)(1). Pub. L. 112–144, § 509(a)(3)(B)(i), substituted “have not been submitted by the date specified in the written request issued or if the applicant or holder does not agree to the request” for “have not been completed” in introductory provisions. Subsec. (n)(1)(A). Pub. L. 112–144, § 509(a)(3)(B)(ii), inserted “, or for which a period of exclusivity eligible for extension under subsection (b)(1) or (c)(1) of this section or under subsection (m)(2) or (m)(3) of section 262 of title 42 has not ended” after “expired” and struck out at end “Prior to making such a determination, the Secretary may not take more than 30 days to certify whether the Foundation for the National Institutes of Health has sufficient funding at the time of such certification to initiate and fund all of the studies in the written request in their entirety within the timeframes specified within the written request. Only if the Secretary makes such certification in the affirmative, the Secretary shall refer all pediatric studies in the written request to the Foundation for the National Institutes of Health for the conduct of such studies, and such Foundation shall fund such studies. If no certification has been made at the end of the 30-day period, or if the Secretary certifies that funds are not sufficient to initiate and fund all the studies in their entirety, the Secretary shall consider whether assessments shall be required under section 355c(b) of this title for such drug.” Subsec. (n)(1)(B). Pub. L. 112–144, § 509(a)(3)(B)(iii), substituted “no unexpired listed patents and for which no unexpired periods of exclusivity eligible for extension under subsection (b)(1) or (c)(1) of this section or under subsection (m)(2) or (m)(3) of section 262 of title 42 apply,” for “no listed patents or has 1 or more listed patents that have expired,”. Subsec. (o)(2)(B). Pub. L. 112–144, § 509(a)(4), amended subpar. (B) generally. Prior to amendment, subpar. (B) read as follows: “a statement of any appropriate pediatric contraindications, warnings, or precautions that the Secretary considers necessary.” Subsec. (q). Pub. L. 112–144, § 501(a), struck out subsec. (q). Text read as follows: “A drug may not receive any 6-month period under subsection (b) or (c) unless— “(1) on or before

October 1, 2012, the Secretary makes a written request for pediatric studies of the drug; “(2) on or before

October 1, 2012, an application for the drug is accepted for filing under section 355(b) of this title; and “(3) all requirements of this section are met.” 2010—Subsec. (p)(4) to (6). Pub. L. 111–148 added pars. (4) to (6) and struck out former pars. (4) and (5) which read as follows: “(4) review and assess the pediatric studies of biological products as required under subsections (a) and (b) of section 355c of this title; and “(5) make recommendations regarding appropriate incentives for encouraging pediatric studies of biologics.” 2007—Pub. L. 110–85 amended section generally. Prior to amendment, text consisted of subsecs. (a) to (n) relating to pediatric studies of drugs, including market exclusivity, conduct of pediatric studies, delay of

promulgated by the Secretary” in text. Subsec. (i)(2). Pub. L. 108–155, § 3(b)(1), struck out “Advisory Subcommittee of the Anti-Infective Drugs” before “Advisory Committee” wherever appearing. Subsec. (l). Pub. L. 108–173, § 1104(3), substituted “355(j)(5)(F)” for “355(j)(5)(D)” wherever appearing. 2002—Subsec. (a). Pub. L. 107–109, § 19(2), (3), redesignated subsec. (g) as (a). Former subsec. (a) redesignated (b). Subsec. (a)(1)(A). Pub. L. 107–109, § 19(1)(A), (B), substituted “(j)(5)(D)(ii)” for “(j)(4)(D)(ii)” in two places in cl. (i) and “(j)(5)(D)” for “(j)(4)(D)” in cl. (ii). Subsec. (b). Pub. L. 107–109, § 19(2), (3), redesignated subsec. (a) as (b). Pub. L. 107–109, § 2(1), struck out heading and text of subsec. (b). Text read as follows: “Not later than 180 days after

November 21, 1997, the Secretary, after consultation with experts in pediatric research shall develop, prioritize, and publish an initial list of approved drugs for which additional pediatric information may produce health benefits in the pediatric population. The Secretary shall annually update the list.” Subsec. (c). Pub. L. 107–109, § 2(2), in introductory provisions, inserted “determines that information relating to the use of an approved drug in the pediatric population may produce health benefits in that population and” after “the Secretary” and struck out “concerning a drug identified in the list described in subsection (b) of this section” after “such studies)”. Subsec. (c)(1)(A). Pub. L. 107–109, § 19(1)(A), (B), substituted “(j)(5)(D)(ii)” for “(j)(4)(D)(ii)” in two places in cl. (i) and “(j)(5)(D)” for “(j)(4)(D)” in cl. (ii). Subsec. (d)(1). Pub. L. 107–109, § 19(4), substituted “subsection (b) or (c)” for “subsection (a) or (c)” in introductory provisions. Subsec. (d)(2). Pub. L. 107–109, §§ 18(a), 19(4), substituted “subsection (b) or (c)” for “subsection (a) or (c)” and inserted “In reaching an agreement regarding written protocols, the Secretary shall take into account adequate representation of children of ethnic and racial minorities.” after first sentence. Subsec. (d)(3). Pub. L. 107–109, § 19(4), substituted “subsection (b) or (c)” for “subsection (a) or (c)”. Subsec. (d)(4). Pub. L. 107–109, § 4, added par. (4). Subsec. (e). Pub. L. 107–109, § 19(1)(C), (4), substituted “section 355(j)(5)(D)” for “section 355(j)(4)(D)” and “subsection (b) or (c)” for “subsection (a) or (c)”. Subsec. (g). Pub. L. 107–109, § 19(2), (3), (5), redesignated subsec. (h) as (g) and substituted “subsection (b) or (c)” for “subsection (a) or (b)” in introductory provisions. Former subsec. (g) redesignated (a). Pub. L. 107–109, § 7, inserted “(including neonates in appropriate cases)” after “pediatric age groups”. Subsec. (h). Pub. L. 107–109, § 19(2), (3), redesignated subsec. (i) as (h). Former subsec. (h) redesignated (g). Subsec. (i). Pub. L. 107–109, § 19(2), (3), redesignated subsec. (l) as (i). Former subsec. (i) redesignated (h). Subsec. (j). Pub. L. 107–109, § 19(2), (3), redesignated subsec. (m) as (j). Former subsec. (j) redesignated (n). Pub. L. 107–109, § 8, added subsec. (j) and struck out heading and text of former subsec. (j). Text read as follows: “A drug may not receive any six-month period under subsection (a) or (c) of this section unless the application for the drug under section 355(b)(1) of this title is submitted on or before

January 1, 2002. After

January 1, 2002, a drug shall receive a six-month period under subsection (c) of this section if— “(1) the drug was in commercial distribution as of

November 21, 1997; “(2) the drug was included by the Secretary on the list under subsection (b) of this section as of

January 1, 2002; “(3) the Secretary determines that there is a continuing need for information relating to the use of the drug in the pediatric population and that the drug may provide health benefits in that population; and “(4) all requirements of this section are met.” Subsec. (k). Pub. L. 107–109, § 19(2), (3), redesignated subsec. (n) as (k). Former subsec. (k) redesignated (m). Subsec. (l). Pub. L. 107–109, § 19(2), (3), redesignated subsec. (o) as (l). Former subsec. (l) redesignated (i). Pub. L. 107–109, § 5(b)(2), added subsec. (l). Subsec. (m). Pub. L. 107–109, § 19(2), (3), redesignated subsec. (k) as (m). Former subsec. (m) redesignated (j). Pub. L. 107–109, § 9, added subsec. (m). Subsec. (n). Pub. L. 107–109, § 19(4), which directed substitution of “subsection (b) or (c)” for “subsection (a) or (c)” in subsec. (m), was executed by making the substitution in introductory provisions of subsec. (n), to reflect the probable intent of Congress. Pub. L. 107–109, § 19(2), (3), redesignated subsec. (j) as (n). Former subsec. (n) redesignated (k). Pub. L. 107–109, § 10, added subsec. (n). Subsec. (o). Pub. L. 107–109, § 19(2), (3), redesignated subsec. (o) as (l). Pub. L. 107–109, § 11(a), added subsec. (o).

of 2012 Amendment Pub. L. 112–144, title V, § 509(g),

July 9, 2012, 126 Stat. 1050, provided that: “(1) Application.—Notwithstanding any provision of section 505A and 505B of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a, 355c) stating that a provision applies beginning on the date of the enactment of the Best Pharmaceuticals for Children Act of 2007 [Sept. 27, 2007] or the date of the enactment of the Pediatric Research Equity Act of 2007 [Sept. 27, 2007], any amendment made by this Act to such a provision applies beginning on the date of the enactment of this Act [

July 9, 2012]. “(2) Transitional rule for adverse event reporting.—With respect to a drug for which a labeling change described under section 505A(l)(1) or 505B(i)(1) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a(l)(1); 355c(i)(1)) is approved or made, respectively, during the one-year period that ends on the day before the date of enactment of this Act [

July 9, 2012], the Secretary [of Health and Human Services] shall apply section 505A(l) and section 505B(i), as applicable, to such drug, as such sections were in effect on such day.”

made by this title may not be construed as affecting the authority of the Secretary of Health and Human Services to request pediatric studies under section 505A of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355a] or to require such studies under section 505B of such Act [21 U.S.C. 355c].” Plan for Earlier Submission of Pediatric Studies Pub. L. 115–52, title V, § 505(c), Aug. 18, 2017, 131 Stat. 1046, provided that: “The Secretary of Health and Human Services, acting through the internal review committee established under section 505C of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355d) shall, not later than one year after the date of enactment of this Act [Aug. 18, 2017], develop and implement a plan to achieve, when appropriate, earlier submission of pediatric studies 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)). Such plan shall include recommendations to achieve— “(1) earlier discussion of proposed pediatric study requests and written requests with sponsors, and if appropriate, discussion of such requests at the meeting required under section 505B(e)(2)(C) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355c(e)(2)(C)), as amended by section 503(a); “(2) earlier issuance of written requests for a pediatric study under such section 505A, including for investigational new drugs prior to the submission of an application under section 505(b)(1) of such Act (21 U.S.C. 355(b)(1)); and “(3) shorter timelines, when appropriate, for the completion of studies pursuant to a written request under such section 505A or such section 351(m).” Draft Guidance for Neonatal Studies Pub. L. 115–52, title V, § 505(d)(2), Aug. 18, 2017, 131 Stat. 1047, provided that: “Not later than 2 years after the date of enactment of this Act [Aug. 18, 2017], the Secretary shall issue draft guidance on clinical pharmacology considerations for neonatal studies for drugs and biological products.” Communication With Pediatric Review Committee Pub. L. 112–144, title V, § 503,

July 9, 2012, 126 Stat. 1040, provided that: “Not later than 1 year after the date of enactment of this Act [

July 9, 2012], the Secretary of Health and Human Services (referred to in this title [see Tables for classification] as the ‘Secretary’) shall issue internal standard operating procedures that provide for the review by the internal review committee established under section 505C of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355d) of any significant modifications to initial pediatric study plans, agreed initial pediatric study plans, and written requests under section 505A and 505B of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a, 355c). Such internal standard operating procedures shall be made publicly available on the Internet Web site of the Food and Drug Administration.” Access to Data Pub. L. 112–144, title V, § 504,

July 9, 2012, 126 Stat. 1040, provided that: “Not later than 3 years after the date of enactment of this Act [

July 9, 2012], the Secretary [of Health and Human Services] shall make available to the public, including through posting on the Internet Web site of the Food and Drug Administration, the medical, statistical, and clinical pharmacology reviews of, and corresponding written requests issued to an applicant, sponsor, or holder for, pediatric studies submitted between

January 4, 2002, and

September 27, 2007, under subsection (b) or (c) of section 505A of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a) for which 6 months of market exclusivity was granted and that resulted in a labeling change. The Secretary shall make public the information described in the preceding sentence in a manner consistent with how the Secretary releases information under section 505A(k) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a(k)).” Report on Pediatric Exclusivity Program Pub. L. 107–109, § 16, Jan. 4, 2002, 115 Stat. 1421, as amended by Pub. L. 108–155, § 3(b)(4), Dec. 3, 2003, 117 Stat. 1942, required the Comptroller General, not later than Oct. 1, 2006, and in consultation with the Secretary of Health and Human Services, to submit to Congress a report on specified issues concerning the effectiveness of the pediatric exclusivity program. Study by General Accounting Office Pub. L. 107–109, § 18(b), Jan. 4, 2002, 115 Stat. 1423, required the Comptroller General, not later than Jan. 10, 2003, to conduct a study relating to the representation of children of ethnic and racial minorities in studies under section 355a of this title and to submit a report to Congress describing the findings of the study.