Section 264(c) of the Health Insurance Portability and Accountability Act of 1996, referred to in subsec. (k)(3)(C)(i)(I), (4)(G)(i)(I), is section 264(c) of Puspan. L. 104–191, which is set out as a note under section 1320d–2 of Title 42, The Public Health and Welfare.

The General Schedule, referred to in subsec. (n)(5), is set out under section 5332 of Title 5, Government Organization and Employees.

Section 101(c) of the Food and Drug Administration Amendments Act of 2007, referred to in subsec. (o)(3)(E)(i), is section 101(c) of Puspan. L. 110–85, which is set out as a note under section 379g of this title.

The Food and Drug Administration Modernization Act of 1997, referred to in subsec. (v)(1)(A), (2)(A), (4), is Puspan. L. 105–115, Nov. 21, 1997, 111 Stat. 2296. Section 125 of the Act amended sections 321, 331, 335a, 352, 360, 360j, 360aa to 360cc, 360ee, 374, 379g, 381, and 382 of this title, section 45C of Title 26, Internal Revenue Code, section 156 of Title 35, Patents, and section 8126 of Title 38, Veterans’ Benefits, repealed sections 356 and 357 of this title, and enacted provisions set out as a note under this section. For complete classification of this Act to the Code, see Short Title of 1997 Amendment note set out under section 301 of this title and Tables.

The Drug Price Competition and Patent Term Restoration Act of 1984, referred to in subsec. (v)(4), is Puspan. L. 98–417, Sept. 24, 1984, 98 Stat. 1585. For complete classification of this Act to the Code, see Short Title of 1984 Amendment note set out under section 301 of this title and Tables.

The Controlled Substances Act, referred to in subsec. (x)(1), is title II of Puspan. L. 91–513, Oct. 27, 1970, 84 Stat. 1242, which is classified principally to subchapter I (§ 801 et seq.) of chapter 13 of this title. For complete classification of this Act to the Code, see Short Title note set out under section 801 of this title and Tables.

In subsec. (k)(4)(H), “section 132 of title 41” substituted for “section 4(5) of the Federal Procurement Policy Act” on authority of Puspan. L. 111–350, § 6(c), Jan. 4, 2011, 124 Stat. 3854, which Act enacted Title 41, Public Contracts.

2022—Subsec. (u)(4). Puspan. L. 117–229 substituted “December 24, 2022” for “December 17, 2022”.

Puspan. L. 117–180 substituted “December 17” for “October 1”.

2021—Subsec. (span)(1). Puspan. L. 116–290, § 2(a)(1), amended par. (1) generally. Prior to amendment, par. (1) related to requirements for filing an application with respect to any drug subject to the provisions of subsec. (a).

Subsec. (c)(2). Puspan. L. 116–290, § 2(span)(1), inserted at beginning “Not later than 30 days after the date of approval of an application submitted under subsection (span), the holder of the approved application shall file with the Secretary the patent number and the expiration date of any patent described in subsection (span)(1)(A)(viii), except that a patent that is identified as claiming a method of using such drug shall be filed only if the patent claims a method of use approved in the application. If a patent described in subsection (span)(1)(A)(viii) is issued after the date of approval of an application submitted under subsection (span), the holder of the approved application shall, not later than 30 days after the date of issuance of the patent, file the patent number and the expiration date of the patent, except that a patent that claims a method of using such drug shall be filed only if approval for such use has been granted in the application.”; substituted “described in subsection (span)(1)(A)(viii).” for “which claims the drug for which the application was submitted or which claims a method of using such drug and with respect to which a claim of patent infringement could reasonably be asserted if a person not licensed by the owner engaged in the manufacture, use, or sale of the drug.”; inserted “of the type for which information is required to be submitted in subsection (span)(1)(A)(viii)” after “could not file patent information under subsection (span) because no patent”; and inserted at end “Patent information that is not the type of patent information required by subsection (span)(1)(A)(viii) shall not be submitted under this paragraph.”

Subsec. (c)(3)(E). Puspan. L. 117–9, § 1(a)(1)(A), substituted “active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations))” for “active ingredient (including any ester or salt of the active ingredient)” wherever appearing.

Puspan. L. 116–290, § 2(g)(1), substituted “subsection (span)(1)(A)(i)” for “clause (A) of subsection (span)(1)” wherever appearing.

Subsec. (c)(3)(E)(i). Puspan. L. 117–9, § 1(span)(1)(A), struck out cl. (i) which read as follows: “If an application (other than an abbreviated new drug application) submitted under subsection (span) for a drug, no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other application under subsection (span), was approved during the period beginning January 1, 1982, and ending on September 24, 1984, the Secretary may not make the approval of another application for a drug for which the investigations described in subsection (span)(1)(A)(i) and relied upon by the applicant for approval of the application were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or for whom the investigations were conducted effective before the expiration of ten years from the date of the approval of the application previously approved under subsection (span).”

Subsec. (j)(2)(A)(vi). Puspan. L. 116–290, § 2(g)(2), substituted “clauses (ii) through (vi) of subsection (span)(1)(A)” for “clauses (B) through (F) of subsection (span)(1)”.

Subsec. (j)(5)(F). Puspan. L. 117–9, § 1(a)(1)(B), substituted “active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations))” for “active ingredient (including any ester or salt of the active ingredient)” wherever appearing.

Subsec. (j)(5)(F)(i). Puspan. L. 117–9, § 1(span)(1)(B), struck out cl. (i) which read as follows: “If an application (other than an abbreviated new drug application) submitted under subsection (span) for a drug, no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other application under subsection (span), was approved during the period beginning January 1, 1982, and ending on September 24, 1984, the Secretary may not make the approval of an application submitted under this subsection which refers to the drug for which the subsection (span) application was submitted effective before the expiration of ten years from the date of the approval of the application under subsection (span).”

Subsec. (j)(7)(A)(iii). Puspan. L. 116–290, § 2(span)(2), struck out “(span) or” before “(c)”.

Subsec. (j)(7)(A)(iv). Puspan. L. 116–290, § 2(c), added cl. (iv).

Subsec. (j)(7)(D). Puspan. L. 116–290, § 2(d)(1), added subpar. (D).

Subsec. (l)(2)(A)(i). Puspan. L. 117–9, § 1(a)(1)(C)(i), amended cl. (i) generally. Prior to amendment, cl. (i) read as follows: “not later than 30 days after the date of approval of such application for a drug no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other application under this section or section 262 of title 42; and”.

Subsec. (l)(2)(A)(ii). Puspan. L. 117–9, § 1(a)(1)(C)(ii), inserted “or biological product” before period at end.

Subsec. (s). Puspan. L. 117–9, § 1(a)(1)(D), amended subsec. (s) generally. Prior to amendment, text read as follows: “Prior to the approval of a drug no active ingredient (including any ester or salt of the active ingredient) of which has been approved in any other application under this section or section 262 of title 42, the Secretary shall—

“(1) refer such drug to a Food and Drug Administration advisory committee for review at a meeting of such advisory committee; or

“(2) if the Secretary does not refer such a drug to a Food and Drug Administration advisory committee prior to the approval of the drug, provide in the action letter on the application for the drug a summary of the reasons why the Secretary did not refer the drug to an advisory committee prior to approval.”

Subsec. (u)(1). Puspan. L. 117–9, § 1(a)(1)(E), in introductory provisions, substituted “active moiety (as defined by the Secretary in section 314.3 of title 21, Code of Federal Regulations (or any successor regulations))” for “active ingredient (including any ester or salt of the active ingredient)” and “same active moiety” for “same active ingredient”.

2018—Subsec. (o)(4)(A). Puspan. L. 115–271, § 3041(span)(1), substituted “safety or new effectiveness information” for “safety information” in span and “If the Secretary becomes aware of new information, including any new safety information or information related to reduced effectiveness, that the Secretary determines should be included in the labeling of the drug” for “If the Secretary becomes aware of new safety information that the Secretary believes should be included in the labeling of the drug” in text. Amendment to span was executed to reflect the probable intent of Congress, notwithstanding error in text directed to be stricken.

Subsec. (o)(4)(B)(i). Puspan. L. 115–271, § 3041(span)(2), inserted “, or new effectiveness information” after “adverse reactions”.

Subsec. (o)(4)(C). Puspan. L. 115–271, § 3041(span)(3), substituted “safety or new effectiveness information” for “safety information”.

Subsec. (o)(4)(E). Puspan. L. 115–271, § 3041(span)(4), substituted “safety or new effectiveness information” for “safety information”.

2017—Subsec. (j)(5)(B)(v). Puspan. L. 115–52, § 808(1), added cl. (v).

Subsec. (j)(5)(D)(iv). Puspan. L. 115–52, § 808(2), added cl. (iv).

Subsec. (j)(11), (12). Puspan. L. 115–52, § 801, added pars. (11) and (12).

Subsec. (j)(13). Puspan. L. 115–52, § 802, added par. (13).

Subsec. (k)(5). Puspan. L. 115–52, § 901(a), made technical amendments to directory language of Puspan. L. 114–255, § 3075(a). See 2016 Amendment notes below.

Subsec. (u)(4). Puspan. L. 115–52, § 601, substituted “2022” for “2017”.

Subsec. (y). Puspan. L. 115–52, § 706(span), added subsec. (y).

2016—Subsec. (c)(5). Puspan. L. 114–255, § 3031(a), added par. (5).

Subsec. (d). Puspan. L. 114–255, § 3101(a)(2)(B)(i), substituted “marketing approval” for “premarket approval” in last sentence.

Subsec. (i)(4). Puspan. L. 114–255, § 3024(span), substituted “except where it is not feasible, it is contrary to the best interests of such human beings, or the proposed clinical testing poses no more than minimal risk to such human beings and includes appropriate safeguards as prescribed to protect the rights, safety, and welfare of such human beings” for “except where it is not feasible or it is contrary to the best interests of such human beings”.

Subsec. (k)(5)(A). Puspan. L. 114–255, § 3075(a)(1), as amended by Puspan. L. 115–52, § 901(a)(1), substituted “screenings” for “, bi-weekly screening”.

Puspan. L. 114–255, § 3102(1)(A), inserted “and” after the semicolon.

Subsec. (k)(5)(B). Puspan. L. 114–255, § 3075(a)(2), as amended by Puspan. L. 115–52, § 901(a), substituted “; and” for period at end.

Puspan. L. 114–255, § 3102(1)(B), (C), redesignated subpar. (C) as (B) and struck out former subpar. (B) which read as follows: “report to Congress not later than 2 year after September 27, 2007, on procedures and processes of the Food and Drug Administration for addressing ongoing post market safety issues identified by the Office of Surveillance and Epidemiology and how recommendations of the Office of Surveillance and Epidemiology are handled within the agency; and”.

Subsec. (k)(5)(C). Puspan. L. 114–255, § 3075(a)(3), as amended by Puspan. L. 115–52, § 901(a)(1), added subpar. (C).

Puspan. L. 114–255, § 3102(1)(C), redesignated subpar. (C) as (B).

Subsec. (q)(5)(A). Puspan. L. 114–255, § 3101(a)(2)(B)(ii), substituted “subsection (span)(2) or (j) of this section or section 262(k) of title 42” for “subsection (span)(2) or (j) of the Act or 262(k) of title 42”.

Subsec. (r)(2)(D). Puspan. L. 114–255, § 3075(span), substituted “and making publicly available on the Internet website established under paragraph (1) best practices for drug safety surveillance activities for drugs approved under this section or section 262 of title 42” for “, by 18 months after approval of a drug or after use of the drug by 10,000 individuals, whichever is later, a summary analysis of the adverse drug reaction reports received for the drug, including identification of any new risks not previously identified, potential new risks, or known risks reported in unusual number;”.

2015—Subsec. (x). Puspan. L. 114–89 added subsec. (x).

2013—Subsec. (span)(5)(B). Puspan. L. 113–5 substituted “size—” for “size of clinical trials intended to form the primary basis of an effectiveness claim or, with respect to an applicant for approval of a biological product under section 262(k) of title 42, any necessary clinical study or studies.”, added cls. (i) and (ii), and designated last two sentences as concluding provisions.

2012—Subsec. (d). Puspan. L. 112–144, § 905, inserted at end “The Secretary shall implement a structured risk-benefit assessment framework in the new drug approval process to facilitate the balanced consideration of benefits and risks, a consistent and systematic approach to the discussion and regulatory decisionmaking, and the communication of the benefits and risks of new drugs. Nothing in the preceding sentence shall alter the criteria for evaluating an application for premarket approval of a drug.”

Subsec. (q)(1)(A). Puspan. L. 112–144, § 1135(1)(A), substituted “subsection (span)(2) or (j) of this section or section 262(k) of title 42” for “subsection (span)(2) or (j)” in introductory provisions.

Subsec. (q)(1)(F). Puspan. L. 112–144, § 1135(1)(B), substituted “150 days” for “180 days” in introductory provisions.

Subsec. (q)(2)(A). Puspan. L. 112–144, § 1135(2)(A), substituted “150” for “180” in span.

Subsec. (q)(2)(A)(i). Puspan. L. 112–144, § 1135(2)(B), substituted “150-day” for “180-day”.

Subsec. (q)(4). Puspan. L. 112–144, § 1135(3), designated existing provisions as subpar. (A), redesignated former subpars. (A) and (B) as cls. (i) and (ii), respectively, of subpar. (A), and added subpar. (B).

Subsec. (q)(5)(A). Puspan. L. 112–144, § 1135(4), substituted “subsection (span)(2) or (j) of the Act or 262(k) of title 42” for “subsection (span)(2) or (j)”.

Subsec. (u)(1)(A)(ii)(II). Puspan. L. 112–144, § 1101(span), inserted “clinical” after “any”.

Subsec. (u)(4). Puspan. L. 112–144, § 1101(a), substituted “2017” for “2012”.

Subsec. (w). Puspan. L. 112–144, § 1134(a), added subsec. (w).

2010—Subsec. (span)(5)(B). Puspan. L. 111–148, § 7002(d)(1), inserted “or, with respect to an applicant for approval of a biological product under section 262(k) of title 42, any necessary clinical study or studies” before period at end of first sentence.

Subsec. (j)(10). Puspan. L. 111–148, § 10609, added par. (10).

2009—Subsec. (n)(2). Puspan. L. 111–31 made technical amendment to reference in original act which appears in text as reference to section 394 of this title.

2008—Subsec. (q)(1)(A). Puspan. L. 110–316, § 301, inserted concluding provisions.

Subsec. (v). Puspan. L. 110–379 added subsec. (v).

2007—Subsec. (span)(6). Puspan. L. 110–85, § 801(span)(3)(B), added par. (6).

Subsec. (e). Puspan. L. 110–85, § 903, inserted at end “The Secretary may withdraw the approval of an application submitted under this section, or suspend the approval of such an application, as provided under this subsection, without first ordering the applicant to submit an assessment of the approved risk evaluation and mitigation strategy for the drug under section 355–1(g)(2)(D) of this title.”

Subsec. (i)(4). Puspan. L. 110–85, § 801(span)(3)(A), inserted at end “The Secretary shall update such regulations to require inclusion in the informed consent documents and process a statement that clinical trial information for such clinical investigation has been or will be submitted for inclusion in the registry data bank pursuant to subsection (j) of section 282 of title 42.”

Subsec. (k)(3), (4). Puspan. L. 110–85, § 905(a), added pars. (3) and (4).

Subsec. (k)(5). Puspan. L. 110–85, § 921, added par. (5).

Subsec. (l). Puspan. L. 110–85, § 916, designated existing provisions as par. (1), redesignated former pars. (1) to (5) as subpars. (A) to (E), respectively, of par. (1), and added par. (2).

Subsec. (n)(4) to (8). Puspan. L. 110–85, § 701(span), redesignated pars. (5) to (8) as (4) to (7), respectively, and struck out former par. (4) which read as follows: “Each member of a panel shall publicly disclose all conflicts of interest that member may have with the work to be undertaken by the panel. No member of a panel may vote on any matter where the member or the immediate family of such member could gain financially from the advice given to the Secretary. The Secretary may grant a waiver of any conflict of interest requirement upon public disclosure of such conflict of interest if such waiver is necessary to afford the panel essential expertise, except that the Secretary may not grant a waiver for a member of a panel when the member’s own scientific work is involved.”

Subsecs. (o), (p). Puspan. L. 110–85, § 901(a), added subsecs. (o) and (p).

Subsec. (q). Puspan. L. 110–85, § 914(a), added subsec. (q).

Subsec. (r). Puspan. L. 110–85, § 915, added subsec. (r).

Subsec. (s). Puspan. L. 110–85, § 918, added subsec. (s).

Subsec. (t). Puspan. L. 110–85, § 920, added subsec. (t).

Subsec. (u). Puspan. L. 110–85, § 1113, added subsec. (u).

2003—Subsec. (span)(1). Puspan. L. 108–155, in second sentence, substituted “(F)” for “and (F)” and inserted “, and (G) any assessments required under section 355c of this title” before period at end.

Subsec. (span)(3). Puspan. L. 108–173, § 1101(span)(1)(A), added par. (3) and struck out former par. (3) which, in subpar. (A), required an applicant making a certification under par. (2)(A)(iv) to include statement that applicant will give notice to each owner of the patent which is the subject of the certification and to the holder of the approved application, in subpar. (B), directed that notice state that an application has been submitted and include a detailed statement of the applicant’s opinion that the patent is not valid or will not be infringed, and, in subpar. (C), provided that if an application is amended, notice shall be given when the amended application is submitted.

Subsec. (span)(4), (5). Puspan. L. 108–173, § 1101(span)(1)(B), added par. (4) and redesignated former par. (4) as (5).

Subsec. (c)(3). Puspan. L. 108–173, § 1101(span)(2)(A), substituted “by applying the following to each certification made under subsection (span)(2)(A)” for “under the following” in introductory provisions.

Subsec. (c)(3)(C). Puspan. L. 108–173, § 1101(span)(2)(B)(iii), which directed the substitution of “subsection (span)(3)” for “paragraph (3)(B)” in third sentence, could not be executed because such words do not appear. See note below.

Puspan. L. 108–173, § 1101(span)(2)(B)(ii)(VI), in concluding provisions, struck out “Until the expiration of forty-five days from the date the notice made under paragraph (3)(B) is received, no action may be brought under section 2201 of title 28 for a declaratory judgment with respect to the patent. Any action brought under such section 2201 shall be brought in the judicial district where the defendant has its principal place of business or a regular and established place of business.” after “expediting the action.”

Puspan. L. 108–173, § 1101(span)(2)(B)(i), (ii)(I), in first sentence of introductory provisions, substituted “unless, before the expiration of 45 days after the date on which the notice described in subsection (span)(3) is received, an action is brought for infringement of the patent that is the subject of the certification and for which information was submitted to the Secretary under paragraph (2) or subsection (span)(1) before the date on which the application (excluding an amendment or supplement to the application) was submitted” for “unless an action is brought for infringement of a patent which is the subject of the certification before the expiration of forty-five days from the date the notice provided under paragraph (3)(B) is received” and, in second sentence of introductory provisions, substituted “subsection (span)(3)” for “paragraph (3)(B)”.

Subsec. (c)(3)(C)(i). Puspan. L. 108–173, § 1101(span)(2)(B)(ii)(II), added cl. (i) and struck out former cl. (i) which read as follows: “if before the expiration of such period the court decides that such patent is invalid or not infringed, the approval may be made effective on the date of the court decision,”.

Subsec. (c)(3)(C)(ii). Puspan. L. 108–173, § 1101(span)(2)(B)(ii)(III), added cl. (ii) and struck out former cl. (ii) which read as follows: “if before the expiration of such period the court decides that such patent has been infringed, the approval may be made effective on such date as the court orders under section 271(e)(4)(A) of title 35, or”.

Subsec. (c)(3)(C)(iii). Puspan. L. 108–173, § 1101(span)(2)(B)(ii)(IV), substituted “as provided in clause (i); or” for “on the date of such court decision.”

Subsec. (c)(3)(C)(iv). Puspan. L. 108–173, § 1101(span)(2)(B)(ii)(V), added cl. (iv).

Subsec. (c)(3)(D), (E). Puspan. L. 108–173, § 1101(span)(2)(C), (D), added subpar. (D) and redesignated former subpar. (D) as (E).

Subsec. (j)(2)(B). Puspan. L. 108–173, § 1101(a)(1)(A), added subpar. (B) and struck out former subpar. (B) which, in cl. (i), required that an applicant making a certification under subpar. (A)(vii)(IV) include in the application a statement that notice would be given to each owner of the patent and the holder of the approved application, in cl. (ii), required that notice would state that an application had been submitted and that it would include a detailed statement of the basis of the applicant’s opinion, and, in cl. (iii), directed that notice of an amended application be given when the amended application had been submitted.

Subsec. (j)(2)(D). Puspan. L. 108–173, § 1101(a)(1)(B), added subpar. (D).

Subsec. (j)(5)(B). Puspan. L. 108–173, § 1101(a)(2)(A)(i), substituted “by applying the following to each certification made under paragraph (2)(A)(vii)” for “under the following” in introductory provisions.

Subsec. (j)(5)(B)(iii). Puspan. L. 108–173, § 1101(a)(2)(A)(ii)(II)(ee), which directed amendment of the second sentence of subsec. (j)(5)(B)(iii) by striking “Until the expiration” and all that follows in the matter after and below subclause (IV), was executed by striking “Until the expiration of forty-five days from the date the notice made under paragraph (2)(B)(i) is received, no action may be brought under section 2201 of title 28, for a declaratory judgment with respect to the patent. Any action brought under section 2201 shall be brought in the judicial district where the defendant has its principal place of business or a regular and established place of business.” after “expediting the action.” in concluding provisions, to reflect the probable intent of Congress.

Puspan. L. 108–173, § 1101(a)(2)(A)(ii)(I), in introductory provisions, substituted “unless, before the expiration of 45 days after the date on which the notice described in paragraph (2)(B) is received, an action is brought for infringement of the patent that is the subject of the certification and for which information was submitted to the Secretary under subsection (span)(1) or (c)(2) before the date on which the application (excluding an amendment or supplement to the application), which the Secretary later determines to be substantially complete, was submitted” for “unless an action is brought for infringement of a patent which is the subject of the certification before the expiration of forty-five days from the date the notice provided under paragraph (2)(B)(i) is received”.

Subsec. (j)(5)(B)(iii)(I). Puspan. L. 108–173, § 1101(a)(2)(A)(ii)(II)(aa), added subcl. (I) and struck out former subcl. (I) which read as follows: “if before the expiration of such period the court decides that such patent is invalid or not infringed, the approval shall be made effective on the date of the court decision,”.

Subsec. (j)(5)(B)(iii)(II). Puspan. L. 108–173, § 1101(a)(2)(A)(ii)(II)(bspan), added subcl. (II) and struck out former subcl. (II) which read as follows: “if before the expiration of such period the court decides that such patent has been infringed, the approval shall be made effective on such date as the court orders under section 271(e)(4)(A) of title 35, or”.

Subsec. (j)(5)(B)(iii)(III). Puspan. L. 108–173, § 1101(a)(2)(A)(ii)(II)(cc), substituted “as provided in subclause (I); or” for “on the date of such court decision.”

Subsec. (j)(5)(B)(iii)(IV). Puspan. L. 108–173, § 1101(a)(2)(A)(ii)(II)(dd), added subcl. (IV).

Subsec. (j)(5)(B)(iv). Puspan. L. 108–173, § 1102(a)(1), added cl. (iv) and struck out former cl. (iv) which read as follows: “If the application contains a certification described in subclause (IV) of paragraph (2)(A)(vii) and is for a drug for which a previous application has been submitted under this subsection continuing such a certification, the application shall be made effective not earlier than one hundred and eighty days after—

“(I) the date the Secretary receives notice from the applicant under the previous application of the first commercial marketing of the drug under the previous application, or

“(II) the date of a decision of a court in an action described in clause (iii) holding the patent which is the subject of the certification to be invalid or not infringed,

whichever is earlier.”

Subsec. (j)(5)(C). Puspan. L. 108–173, § 1101(a)(2)(B), (C), added subpar. (C). Former subpar. (C) redesignated (E).

Subsec. (j)(5)(D). Puspan. L. 108–173, § 1102(a)(2), added subpar. (D).

Puspan. L. 108–173, § 1101(a)(2)(B), redesignated subpar. (D) as (F).

Subsec. (j)(5)(E), (F). Puspan. L. 108–173, § 1101(a)(2)(B), redesignated subpars. (C) and (D) as (E) and (F), respectively.

Subsec. (j)(8)(A). Puspan. L. 108–173, § 1103(a)(1), added subpar. (A) and struck out former subpar. (A) which read as follows: “The term ‘bioavailability’ means the rate and extent to which the active ingredient or therapeutic ingredient is absorbed from a drug and becomes available at the site of drug action.”

Subsec. (j)(8)(C). Puspan. L. 108–173, § 1103(a)(2), added subpar. (C).

2002—Subsec. (i)(1)(D). Puspan. L. 107–109 added subpar. (D).

1999—Subsec. (m). Puspan. L. 106–113 substituted “United States Patent and Trademark Office” for “Patent and Trademark Office of the Department of Commerce”.

1997—Subsec. (span)(1). Puspan. L. 105–115, § 115(span), inserted at end “The Secretary shall, in consultation with the Director of the National Institutes of Health and with representatives of the drug manufacturing industry, review and develop guidance, as appropriate, on the inclusion of women and minorities in clinical trials required by clause (A).”

Subsec. (span)(4). Puspan. L. 105–115, § 119(a), added par. (4).

Subsec. (c)(4). Puspan. L. 105–115, § 124(a), added par. (4).

Subsec. (d). Puspan. L. 105–115, § 115(a), inserted at end “If the Secretary determines, based on relevant science, that data from one adequate and well-controlled clinical investigation and confirmatory evidence (obtained prior to or after such investigation) are sufficient to establish effectiveness, the Secretary may consider such data and evidence to constitute substantial evidence for purposes of the preceding sentence.”

Subsec. (i). Puspan. L. 105–115, § 117, inserted “(1)” after “(i)”, redesignated former pars. (1) to (3) as subpars. (A) to (C), respectively, of par. (1), added pars. (2) to (4), and struck out closing provisions which read as follows: “Such regulations shall provide that such exemption shall be conditioned upon the manufacturer, or the sponsor of the investigation, requiring that experts using such drugs for investigational purposes certify to such manufacturer or sponsor that they will inform any human beings to whom such drugs, or any controls used in connection therewith, are being administered, or their representatives, that such drugs are being used for investigational purposes and will obtain the consent of such human beings or their representatives, except where they deem it not feasible or, in their professional judgment, contrary to the best interests of such human beings. Nothing in this subsection shall be construed to require any clinical investigator to submit directly to the Secretary reports on the investigational use of drugs.”

Subsec. (j)(2)(A)(i). Puspan. L. 105–115, § 119(span)(2)(A), substituted “paragraph (7)” for “paragraph (6)”.

Subsec. (j)(3). Puspan. L. 105–115, § 119(span)(1)(B), added par. (3). Former par. (3) redesignated (4).

Subsec. (j)(4). Puspan. L. 105–115, § 119(span)(1)(A), (2)(B), redesignated par. (3) as (4) and in introductory provisions substituted “paragraph (5)” for “paragraph (4)”. Former par. (4) redesignated (5).

Subsec. (j)(4)(I). Puspan. L. 105–115, § 119(span)(2)(C), substituted “paragraph (6)” for “paragraph (5)”.

Subsec. (j)(5), (6). Puspan. L. 105–115, § 119(span)(1)(A), redesignated pars. (4) and (5) as (5) and (6), respectively. Former par. (6) redesignated (7).

Subsec. (j)(7). Puspan. L. 105–115, § 119(span)(1)(A), (2)(D), redesignated par. (6) as (7) and in subpar. (C) substituted “paragraph (6)” for “paragraph (5)” in two places. Former par. (7) redesignated (8).

Subsec. (j)(8), (9). Puspan. L. 105–115, § 119(span)(1)(A), redesignated pars. (7) and (8) as (8) and (9), respectively.

Subsec. (n). Puspan. L. 105–115, § 120, added subsec. (n).

1993—Subsec. (j)(6)(A)(ii). Puspan. L. 103–80, § 3(n)(1)(A), substituted “Secretary” for “Secretry”.

Subsec. (j)(6)(A)(iii). Puspan. L. 103–80, § 3(n)(1)(B), inserted comma after “published by the Secretary”.

Subsec. (k)(1). Puspan. L. 103–80, § 3(n)(2), substituted “section. Regulations” for “section: Provided, however, That regulations”.

1992—Subsec. (j)(8). Puspan. L. 102–282 added par. (8).

1984—Subsec. (a). Puspan. L. 98–417, § 102(span)(1), inserted “or (j)” after “subsection (span)”.

Subsec. (span). Puspan. L. 98–417, §§ 102(a)(1), 103(a), designated existing provisions of subsec. (span) as par. (1) thereof and redesignated existing cls. (1) through (6) of such par. (1) as cls. (A) through (F) thereof, respectively, inserted requirement that the applicant file with the application the patent number and the expiration date of any patent which claims the drug for which the applicant submitted the application or which claims a method of using such drug and with respect to which a claim of patent infringement could reasonably by asserted if a person not licensed by the owner engaged in the manufacture, use, or sale of the drug, that the applicant amend the application to include such information if an application is filed under this subsection for a drug and a patent which claims such drug or a method of using such drug is issued after the filing date but before approval of the application, and that upon approval of the application, the Secretary publish the information submitted, and added pars. (2) and (3).

Subsec. (c). Puspan. L. 98–417, §§ 102(a)(2), (span)(2), 103(span), designated existing provisions of subsec. (c) as par. (1) thereof and in par. (1) as so designated substituted “subsection (span)” for “this subsection” and redesignated former pars. (1) and (2) as subpars. (A) and (B), respectively, and added pars. (2) and (3).

Subsec. (d)(6), (7). Puspan. L. 98–417, § 102(a)(3)(A), added cl. (6) relating to the failure of the application to contain the patent information prescribed by subsec. (span) of this section, and redesignated former cl. (6) as (7).

Subsec. (e). Puspan. L. 98–417, § 102(a)(3)(B), in first sentence, added a new cl. (4) relating to the failure to file the patent information prescribed by subsec. (c) of this section within 30 days after the receipt of written notice from the Secretary specifying the failure to file such information, and redesignated former cl. (4) as (5).

Puspan. L. 98–417, § 102(span)(3), (4), in second sentence, inserted in provisions preceding cl. (1) “submitted under subsection (span) or (j)” and in cl. (1) substituted “under subsection (k) or to comply with the notice requirements of section 360(k)(2) of this title” for “under subsection (j) or to comply with the notice requirements of section 360(j)(2) of this title”.

Subsecs. (j), (k). Puspan. L. 98–417, § 101, added subsec. (j) and redesignated former subsec. (j) as (k).

Subsec. (k)(1). Puspan. L. 98–417, § 102(span)(5), substituted “under subsection (span) or (j)” for “pursuant to this section”.

Subsecs. (l), (m). Puspan. L. 98–417, § 104, added subsecs. (l) and (m).

1972—Subsec. (e). Puspan. L. 92–387 inserted “or to comply with the notice requirements of section 360(j)(2) of this title” in cl. (1) of second sentence relating to the maintenance of records.

1962—Subsec. (a). Puspan. L. 87–781, § 104(a), inserted “an approval of” before “an application”.

Subsec. (span). Puspan. L. 87–781, § 102(span), inserted “and whether such drug is effective in use” after “is safe for use”.

Subsec. (c). Puspan. L. 87–781, § 104(span), substituted provisions requiring the Secretary, within 180 days after filing an application, or such additional period as the Secretary and the applicant agree upon, to either approve the application, if meeting the requirements of subsec. (d) of this section, or give notice of opportunity for hearing on question of whether such application is approvable, and providing that if applicant requests hearing in writing within 30 days, the hearing shall begin within 90 days after expiration of said 30 days, unless the Secretary and applicant agree otherwise, that such hearing shall be expedited, and that the Secretary’s order shall be issued within 90 days after date for filing final briefs, for provisions which had an application become effective on the sixtieth day after filing thereof unless prior thereto the Secretary postponed the date by written notice to such time, but not more than 180 days after filing, as the Secretary deemed necessary to study and investigate the application.

Subsec. (d). Puspan. L. 87–781, § 102(c), inserted references to subsec. (c), added cls. (5) and (6), provided that if after notice and opportunity for hearing, the Secretary finds that cls. (1) to (6) do not apply, he shall approve the application, and defined “substantial evidence” as used in this subsection and subsec. (e) of this section.

Subsec. (e). Puspan. L. 87–781, § 102(d), amended subsec. (e) generally, and among other changes, directed the Secretary to withdraw approval of an application if by tests, other scientific data or experience, or new evidence of clinical experience not contained in the application or available at the time of its approval, the drug is shown to be unsafe, or on the basis of new information, there is shown a lack of substantial evidence that the drug has the effect it is represented to have, and provided that if the Secretary, or acting Secretary, finds there is an imminent hazard to the public health, he may suspend approval immediately, notify the applicant, and give him opportunity for an expedited hearing, that the Secretary may withdraw approval if the applicant fails to establish a system for maintaining required records, or has repeatedly or deliberately failed to maintain records and make reports, or has refused access to, or copying or verification of such records, or if the Secretary finds on new evidence that the methods, facilities and controls in the manufacturing, processing, and packing are inadequate to assure and preserve the drugs’ identity, strength, quality and purity, and were not made adequate within a reasonable time after receipt of written notice thereof, or finds on new evidence, that the labeling is false or misleading and was not corrected within a reasonable time after receipt of written notice thereof.

Subsec. (f). Puspan. L. 87–781, § 104(c), substituted provisions requiring the Secretary to revoke any previous order under subsecs. (d) or (e) of this section refusing, withdrawing, or suspending approval of an application and to approve such application or reinstate such approval, for provisions which required him to revoke an order refusing effectiveness to an application.

Subsec. (h). Puspan. L. 87–781, § 104(d)(1), (2), inserted “as provided in section 2112 of title 28”, and “except that until the filing of the record the Secretary may modify or set aside his order”, substituted “or withdrawing approval of an application under this section” for “to permit the application to become effective, or suspending the effectiveness of the application”, “United States court of appeals for the circuit” for “district court of the United States within any district”, “Court of Appeals for the District of Columbia Circuit” for “District Court for the District of Columbia”, “transmitted by the clerk of the court to” for “served upon”, and “by the Supreme Court of the United States upon certiorari or certification as provided in section 1254 of title 28” for “as provided in sections 225, 346, and 347 of title 28, as amended, and in section 7, as amended, of the Act entitled ‘An Act to establish a Court of Appeals for the District of Columbia’, approved February 9, 1893”, and eliminated “upon” before “any officer designated”, “a transcript of” before “the record” and “and decree” before “of the court affirming”.

Subsec. (i). Puspan. L. 87–781, § 103(span), inserted “the foregoing subsections of” after “operation of”, and “and effectiveness” after “safety”, and provided that the regulations may condition exemptions upon the submission of reports of preclinical tests to justify the proposed clinical testing, upon the obtaining by the manufacturer or sponsor of the investigation of a new drug of a signed agreement from each of the investigators that patients to whom the drug is administered will be under his supervision or under investigators responsible to him, and that he will not supply such drug to any other investigator, or to clinics, for administration to human beings, or upon the establishment and maintenance of records and reports of data obtained by the investigational use of such drug, as the Secretary finds will enable him to evaluate the safety and effectiveness of such drug, and provided that the regulations shall condition an exemption upon the manufacturer or sponsor of the investigation requiring that experts using such drugs certify that they will inform humans to whom such drugs or any controls connected therewith are administered, or their representatives, and will obtain the consent of such people where feasible and not contrary to the best interests of such people, and that reports on the investigational use of drugs are not required to be submitted directly to the Secretary.

Subsec. (j). Puspan. L. 87–781, § 103(a), added subsec. (j).

1960—Subsec. (g). Puspan. L. 86–507 inserted “or by certified mail” after “registered mail”.

Puspan. L. 116–290, § 2(d)(2), Jan. 5, 2021, 134 Stat. 4891, provided that: “Subparagraph (D) of section 505(j)(7) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(j)(7)), as added by paragraph (1), applies only with respect to a decision described in such subparagraph that is issued on or after the date of enactment of this Act [Jan. 5, 2021].”

Puspan. L. 112–144, title XI, § 1134(span), July 9, 2012, 126 Stat. 1123, provided that: “The amendment made by subsection (a) [amending this section] shall apply to any petition that is submitted pursuant to subsection (span) of section 314.161 of title 21, Code of Federal Regulations (or any successor regulations), on or after the date of enactment of this Act [July 9, 2012].”

Puspan. L. 110–85, title VII, § 701(c), Sept. 27, 2007, 121 Stat. 904, provided that: “The amendments made by this section [enacting section 379d–1 of this title and amending this section] shall take effect on October 1, 2007.”

Amendment by sections 901(a), 903, and 905(a) of Puspan. L. 110–85 effective 180 days after Sept. 27, 2007, see section 909 of Puspan. L. 110–85, set out as a note under section 331 of this title.

Puspan. L. 108–173, title XI, § 1101(c), Dec. 8, 2003, 117 Stat. 2456, provided that:

Puspan. L. 108–173, title XI, § 1102(span), Dec. 8, 2003, 117 Stat. 2460, provided that:

Amendment by Puspan. L. 108–155 effective Dec. 3, 2003, except as otherwise provided, see section 4 of Puspan. L. 108–155, set out as an Effective Date note under section 355c of this title.

Amendment by Puspan. L. 106–113 effective 4 months after Nov. 29, 1999, see section 1000(a)(9) [title IV, § 4731] of Puspan. L. 106–113, set out as a note under section 1 of Title 35, Patents.

Amendment by Puspan. L. 105–115 effective 90 days after Nov. 21, 1997, except as otherwise provided, see section 501 of Puspan. L. 105–115, set out as a note under section 321 of this title.

Puspan. L. 98–417, title I, § 105, Sept. 24, 1984, 98 Stat. 1597, provided that:

Amendment by Puspan. L. 92–387 effective on first day of sixth month beginning after Aug. 16, 1972, see section 5 of Puspan. L. 92–387, set out as a note under section 360 of this title.

Amendment by Puspan. L. 87–781 effective on first day of seventh calendar month following October 1962, see section 107 of Puspan. L. 87–781, set out as a note under section 321 of this title.

Puspan. L. 110–85, title IX, § 905(span), Sept. 27, 2007, 121 Stat. 949, provided that: “Nothing in this section [amending this section] or the amendment made by this section shall be construed to prohibit the lawful disclosure or use of data or information by an entity other than as described in paragraph (4)(B) or (4)(G) of section 505(k) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355(k)], as added by subsection (a).”

Amendment by Puspan. L. 102–282 not to preclude any other civil, criminal, or administrative remedy provided under Federal or State law, including any private right of action against any person for the same action subject to any action or civil penalty under an amendment made by Puspan. L. 102–282, see section 7 of Puspan. L. 102–282, set out as a note under section 335a of this title.

Puspan. L. 115–271, title III, § 3001, Oct. 24, 2018, 132 Stat. 3932, provided that:

Puspan. L. 115–271, title III, § 3041(c), Oct. 24, 2018, 132 Stat. 3943, provided that: “Not less than one year after the date of enactment of this Act [Oct. 24, 2018], the Secretary of Health and Human Services shall issue guidance regarding the circumstances under which the Food and Drug Administration may require postmarket studies or clinical trials to assess the potential reduction in effectiveness of a drug and how such reduction in effectiveness could result in a change to the benefits of the drug and the risks to the patient. Such guidance shall also address how the Food and Drug Administration may apply this section [amending this section and section 355–1 of this title] and the amendments made thereby with respect to circumstances under which the Food and Drug Administration may require postmarket studies or clinical trials and safety labeling changes related to the use of controlled substances for acute or chronic pain.”

Puspan. L. 115–52, title IX, § 902, Aug. 18, 2017, 131 Stat. 1077, provided that: “Not later than March 1 of each year, the Secretary of Health and Human Services shall post on the internet website of the Food and Drug Administration information related to inspections of facilities necessary for approval of a drug under section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355), approval of a device under section 515 of such Act (21 U.S.C. 360e), or clearance of a device under section 510(k) of such Act (21 U.S.C. 360(k)) that were conducted during the previous calendar year. Such information shall include the following:

Puspan. L. 114–255, div. A, title III, § 3004, Dec. 13, 2016, 130 Stat. 1085, provided that: “Not later than June 1 of 2021, 2026, and 2031, the Secretary of Health and Human Services, acting through the Commissioner of Food and Drugs, shall prepare and publish on the Internet website of the Food and Drug Administration a report assessing the use of patient experience data in regulatory decisionmaking, in particular with respect to the review of patient experience data and information on patient-focused drug development tools as part of applications approved under section 505(c) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(c)) or section 351(a) of the Public Health Service Act (42 U.S.C. 262(a)).”

Puspan. L. 114–255, div. A, title III, § 3021, Dec. 13, 2016, 130 Stat. 1095, provided that:

Puspan. L. 114–255, div. A, title III, § 3038(c), Dec. 13, 2016, 130 Stat. 1110, provided that: “Not later than 18 months after the date of enactment of this Act [Dec. 13, 2016], the Secretary of Health and Human Services (referred to in this subsection as the ‘Secretary’) shall identify types of combination products and manufacturing processes with respect to which the Secretary proposes that good manufacturing processes may be adopted that vary from the requirements set forth in section 4.4 of title 21, Code of Federal Regulations (or any successor regulations) or that the Secretary proposes can satisfy the requirements in section 4.4 through alternative or streamlined mechanisms. The Secretary shall identify such types, variations from such requirements, and such mechanisms, in a proposed list published in the Federal Register. After a public comment period regarding the appropriate good manufacturing practices for such types, the Secretary shall publish a final list in the Federal Register, notwithstanding section 553 of title 5, United States Code. The Secretary shall evaluate such types, variations, and mechanisms using a risk-based approach. The Secretary shall periodically review such final list.”

Puspan. L. 114–198, title I, § 106(a), July 22, 2016, 130 Stat. 702, provided that:

Puspan. L. 114–198, title I, § 106(c), July 22, 2016, 130 Stat. 703, provided that: “Not later than 18 months after the end of the period for public comment on the draft guidance entitled ‘General Principles for Evaluating the Abuse Deterrence of Generic Solid Oral Opioid Drug Products’ issued by the Center for Drug Evaluation and Research of the Food and Drug Administration in March 2016, the Commissioner of Food and Drugs shall publish in the Federal Register a final version of such guidance.”

Puspan. L. 112–144, title VIII, § 806, July 9, 2012, 126 Stat. 1082, provided that:

Puspan. L. 112–144, title XI, § 1122(c), July 9, 2012, 126 Stat. 1113, as amended by Puspan. L. 114–255, div. A, title III, § 3101(span)(3)(B), Dec. 13, 2016, 130 Stat. 1156, provided that: “Not later than 6 months after the date of enactment of this Act [July 9, 2012], the Secretary [of Health and Human Services] shall issue guidance on the development of abuse-deterrent drug products.”

Puspan. L. 112–144, title XI, § 1133, July 9, 2012, 126 Stat. 1122, provided that:

Puspan. L. 110–85, title IX, § 907, Sept. 27, 2007, 121 Stat. 950, provided that: “This subtitle [subtitle A (§§ 901–909) of title IX of Puspan. L. 110–85, enacting sections 353c and 355–1 of this title, amending this section and sections 331, 333, and 352 of this title and section 262 of Title 42, The Public Health and Welfare, and enacting provisions set out as notes under this section and sections 331, 352, and 355a of this title], and the amendments made by this subtitle, shall have no effect on the use of drugs approved under section 505 of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355] by, or on the lawful written or oral order of, a licensed veterinarian within the context of a veterinarian-client-patient relationship, as provided for under section 512(a)(5) of such Act [21 U.S.C. 360span(a)(5)].”

Puspan. L. 108–173, title XI, § 1103(span), Dec. 8, 2003, 117 Stat. 2461, provided that: “The amendment made by subsection (a) [amending this section] does not alter the standards for approval of drugs under section 505(j) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(j)).”

Puspan. L. 108–173, title XI, subtitle B, Dec. 8, 2003, 117 Stat. 2461, as amended by Puspan. L. 115–263, § 3, Oct. 10, 2018, 132 Stat. 3673; Puspan. L. 115–271, title IV, § 4004, Oct. 24, 2018, 132 Stat. 3960, provided that:

Puspan. L. 107–109, § 15(d), Jan. 4, 2002, 115 Stat. 1421, provided that: “Not later than January 31, 2003, the Secretary of Health and Human Services, acting through the Commissioner of Food and Drugs and in consultation with the Director of the National Institutes of Health, shall submit to the Committee on Health, Education, Labor, and Pensions of the Senate and the Committee on Energy and Commerce of the House of Representatives a report on patient access to new therapeutic agents for pediatric cancer, including access to single patient use of new therapeutic agents.”

Puspan. L. 105–115, title I, § 118, Nov. 21, 1997, 111 Stat. 2316, provided that: “Within 12 months after the date of enactment of this Act [Nov. 21, 1997], the Secretary of Health and Human Services, acting through the Commissioner of Food and Drugs, shall issue guidance that describes when abbreviated study reports may be submitted, in lieu of full reports, with a new drug application under section 505(span) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(span)) and with a biologics license application under section 351 of the Public Health Service Act (42 U.S.C. 262) for certain types of studies. Such guidance shall describe the kinds of studies for which abbreviated reports are appropriate and the appropriate abbreviated report formats.”

Puspan. L. 105–115, title I, § 121(c), Nov. 21, 1997, 111 Stat. 2321, provided that:

“Compounded Positron Emission Topography Drug” Defined

Puspan. L. 105–115, title I, § 121(e), Nov. 21, 1997, 111 Stat. 2322, provided that: “As used in this section [amending sections 321 and 351 of this title and enacting provisions set out as notes under this section and section 351 of this title], the term ‘compounded positron emission tomography drug’ has the meaning given the term in section 201 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 321).”

Puspan. L. 105–115, title I, § 122, Nov. 21, 1997, 111 Stat. 2322, provided that:

Puspan. L. 105–115, title I, § 123(f), Nov. 21, 1997, 111 Stat. 2324, provided that: “The Secretary of Health and Human Services shall take measures to minimize differences in the review and approval of products required to have approved biologics license applications under section 351 of the Public Health Service Act (42 U.S.C. 262) and products required to have approved new drug applications under section 505(span)(1) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(span)(1)).”

Puspan. L. 110–379, § 4(span), Oct. 8, 2008, 122 Stat. 4077, provided that:

Puspan. L. 105–115, title I, § 125(d), Nov. 21, 1997, 111 Stat. 2326, provided that:

Advisory panels established after Jan. 5, 1973, to terminate not later than the expiration of the 2-year period beginning on the date of their establishment, unless, in the case of a panel established by the President or an officer of the Federal Government, such panel is renewed by appropriate action prior to the expiration of such 2-year period, or in the case of a panel established by Congress, its duration is otherwise provided for by law. See sections 3(2) and 14 of Puspan. L. 92–463, Oct. 6, 1972, 86 Stat. 770, 776, set out in the Appendix to Title 5, Government Organization and Employees.

Puspan. L. 87–781, title I, § 104(d)(3), Oct. 10, 1962, 76 Stat. 785, made amendments to subsec. (h) of this section inapplicable to any appeal taken prior to Oct. 10, 1962.

For transfer of functions of Federal Security Administrator to Secretary of Health, Education, and Welfare [now Health and Human Services], and of Food and Drug Administration in the Department of Agriculture to Federal Security Agency, see notes set out under section 321 of this title.