1 See References in Text note below.
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Editorial Notes
References in TextThe effective date of this paragraph, referred to in subsec. (d)(2), is the effective date of section 315 of Puspan. L. 99–660 which added subsec. (d)(2). See Effective Date of 1986 Amendment note set out below.
The Federal Food, Drug, and Cosmetic Act, referred to in subsecs. (g), (h), (j), and (k)(5)(C), is act June 25, 1938, ch. 675, 52 Stat. 1040, which is classified generally to chapter 9 (§ 301 et seq.) of Title 21, Food and Drugs. For complete classification of this Act to the Code, see section 301 of Title 21 and Tables.
Section 7002(e)(4) of the Biologics Price Competition and Innovation Act of 2009, referred to in subsec. (k)(7)(D), (9)(A)(i)(I), (ii), is section 7002(e)(4) of Puspan. L. 111–148, which is set out in a note under this section.
Sections 526, 527(a), and 505A(d)(4), referred to in subsec. (m)(2)(B), (3)(B), (4), probably mean sections 526, 527(a), and 505A(d)(4) of the Federal Food, Drug, and Cosmetic Act, act June 25, 1938, ch. 675, which are classified to sections 360bspan, 360cc(a), and 355a(d)(4), respectively, of Title 21, Food and Drugs.
The Controlled Substances Act, referred to in subsec. (n)(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 Title 21, Food and Drugs. For complete classification of this Act to the Code, see Short Title note set out under section 801 of Title 21 and Tables.
Amendments2022—Subsec. (k)(2)(A)(i)(I)(bspan). Puspan. L. 117–328, § 3209(span), amended item (bspan) generally. Prior to amendment, item (bspan) read as follows: “animal studies (including the assessment of toxicity); and”.
Subsec. (k)(6). Puspan. L. 117–328, § 3206(2), substituted “taken, and the term ‘first interchangeable biosimilar biological product’ means any interchangeable biosimilar biological product that is approved on the first day on which such a product is approved as interchangeable with the reference product.” for “taken.” in concluding provisions.
Puspan. L. 117–328, § 3206(1), substituted “The Secretary shall not make approval as an interchangeable biological product effective with respect to” for “Upon review of” and “that relies on” for “relying on” and struck out “the Secretary shall not make a determination under paragraph (4) that the second or subsequent biological product is interchangeable for any condition of use” before “until the earlier of” in introductory provisions.
2020—Subsec. (k)(2)(A)(iii)(III). Puspan. L. 116–260, § 322, added subcl. (III).
Subsec. (k)(9). Puspan. L. 116–260, § 325(a), added par. (9).
2019—Subsec. (i)(1). Puspan. L. 116–94, § 605, struck out “(except any chemically synthesized polypeptide)” after “protein”.
Subsec. (k)(7)(D). Puspan. L. 116–94, § 606, added subpar. (D).
2017—Subsec. (m)(2) to (4). Puspan. L. 115–52 substituted “section 505A(d)(4)” for “section 505A(d)(3)”.
2016—Subsec. (a)(2)(E). Puspan. L. 114–255 added subpar. (E).
2015—Subsec. (n). Puspan. L. 114–89 added subsec. (n).
2012—Subsec. (m)(1). Puspan. L. 112–144 substituted “(f), (h), (i), (j), (k), (l), (n), and (p)” for “(f), (i), (j), (k), (l), (p), and (q)”.
2010—Subsec. (a)(1)(A). Puspan. L. 111–148, § 7002(a)(1), inserted “under this subsection or subsection (k)” after “biologics license”.
Subsec. (i). Puspan. L. 111–148, § 7002(span), substituted “In this section:” for “In this section,”, designated remainder of existing provisions as par. (1), substituted “The term” for “the term”, inserted “protein (except any chemically synthesized polypeptide),” after “allergenic product,”, and added pars. (2) to (4).
Subsecs. (k), (l). Puspan. L. 111–148, § 7002(a)(2), added subsecs. (k) and (l).
Subsec. (m). Puspan. L. 111–148, § 7002(g)(1), added subsec. (m).
2007—Subsec. (a)(2)(D). Puspan. L. 110–85, § 901(c)(1), added subpar. (D).
Subsec. (j). Puspan. L. 110–85, § 901(c)(2), inserted “, including the requirements under sections 505(o), 505(p), and 505–1 of such Act,” after “and Cosmetic Act”.
2003—Subsec. (a)(2)(B), (C). Puspan. L. 108–155 added subpar. (B) and redesignated former subpar. (B) as (C).
1997—Subsec. (a). Puspan. L. 105–115, § 123(a)(1), amended subsec. (a) generally. Prior to amendment, subsec. (a) related to intrastate and interstate traffic in biological products and suspension or revocation of licenses as affecting prior sales.
Subsec. (span). Puspan. L. 105–115, § 123(span), amended subsec. (span) generally. Prior to amendment, subsec. (span) read as follows: “No person shall falsely label or mark any package or container of any virus, serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or other product aforesaid; nor alter any label or mark on any package or container of any virus, serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or other product aforesaid so as to falsify such label or mark.”
Subsec. (c). Puspan. L. 105–115, § 123(c), substituted “biological product.” for “virus, serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, or other product aforesaid for sale, barter, or exchange in the District of Columbia, or to be sent, carried, or brought from any State or possession into any other State or possession or into any foreign country, or from any foreign country into any State or possession.”
Subsec. (d). Puspan. L. 105–115, § 123(a)(2), designated par. (2) as subsec. (d), redesignated subpars. (A) and (B) of par. (2) as pars. (1) and (2), respectively, in par. (2), substituted “Any violation of paragraph (1)” for “Any violation of subparagraph (A)” and substituted “this paragraph” for “this subparagraph” wherever appearing, and struck out former par. (1) which read as follows: “Licenses for the maintenance of establishments for the propagation or manufacture and preparation of products described in subsection (a) of this section may be issued only upon a showing that the establishment and the products for which a license is desired meet standards, designed to insure the continued safety, purity, and potency of such products, prescribed in regulations, and licenses for new products may be issued only upon a showing that they meet such standards. All such licenses shall be issued, suspended, and revoked as prescribed by regulations and all licenses issued for the maintenance of establishments for the propagation or manufacture and preparation, in any foreign country, of any such products for sale, barter, or exchange in any State or possession shall be issued upon condition that the licensees will permit the inspection of their establishments in accordance with subsection (c) of this section.”
Subsec. (i). Puspan. L. 105–115, § 123(d), added subsec. (i).
Subsec. (j). Puspan. L. 105–115, § 123(g), added subsec. (j).
1996—Subsec. (h). Puspan. L. 104–134, § 2104, amended subsec. (h) generally, revising and restating former provisions, which also related to exportation of partially processed biological products.
Subsec. (h)(1)(A). Puspan. L. 104–134, § 2102(d)(2), substituted “in a country listed under section 802(span)(1)” for “in a country listed under section 802(span)(A)” and “to a country listed under section 802(span)(1)” for “to a country listed under section 802(span)(4)”.
1992—Subsec. (c). Puspan. L. 102–300, which directed substitution of “Health and Human Services” for “Health, Education, and Welfare”, could not be executed because the words “Health, Education, and Welfare” did not appear in original statutory text. Previously, references to Department and Secretary of Health and Human Services were substituted for references to Federal Security Agency and its Administrator pursuant to provisions cited in Transfer of Functions note below.
1986—Subsec. (d). Puspan. L. 99–660, § 315, designated existing provisions as par. (1) and added par. (2).
Subsec. (h). Puspan. L. 99–660, § 105(a), added subsec. (h).
1970—Subsecs. (a) to (c). Puspan. L. 91–515 inserted “vaccine, blood, blood component or derivative, allergenic product,” after “antitoxin” wherever appearing.
1958—Subsec. (d). Puspan. L. 85–881 struck out “made jointly by the Surgeon General, the Surgeon General of the Army, and the Surgeon General of the Navy, and approved by the Secretary” after “regulations” in first sentence.
Statutory Notes and Related Subsidiaries
Change of Name“Secretary of Health and Human Services” substituted for “Secretary of Health, Education, and Welfare” in subsecs. (a), (c), (d), (h), and (k) to (n), and “Department of Health and Human Services” substituted for “Department of Health, Education, and Welfare” in subsec. (c), pursuant to section 509(span) of Puspan. L. 96–88, which is classified to section 3508(span) of Title 20, Education.
Effective Date of 2007 AmendmentAmendment by 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 Title 21, Food and Drugs.
Effective Date of 2003 AmendmentAmendment 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 Title 21, Food and Drugs.
Effective Date of 1997 AmendmentAmendment 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 Title 21, Food and Drugs.
Effective Date of 1986 AmendmentPuspan. L. 99–660, title I, § 105(span), Nov. 14, 1986, 100 Stat. 3752, provided that: “Paragraph (1) of section 351(h) of the Public Health Service Act [former 42 U.S.C. 262(h)(1)] as added by subsection (a) shall take effect upon the expiration of 90 days after the date of the enactment of this Act [Nov. 14, 1986].”
Amendment by section 315 of Puspan. L. 99–660 effective Dec. 22, 1987, see section 323 of Puspan. L. 99–660, as amended, set out as an Effective Date note under section 300aa–1 of this title.
Products Previously Approved Under the Federal Food, Drug, and Cosmetic ActPuspan. L. 111–148, title VII, § 7002(e), Mar. 23, 2010, 124 Stat. 817, as amended by Puspan. L. 116–94, div. N, title I, § 607, Dec. 20, 2019, 133 Stat. 3127, provided that:“(1)Requirement to follow section 351.—Except as provided in paragraph (2), an application for a biological product shall be submitted under section 351 of the Public Health Service Act (42 U.S.C. 262) (as amended by this Act). “(2)Exception.—An application for a biological product may be submitted under section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) if—“(A) such biological product is in a product class for which a biological product in such product class is the subject of an application approved under such section 505 not later than the date of enactment of this Act [Mar. 23, 2010]; and
“(B) such application—“(i) has been submitted to the Secretary of Health and Human Services (referred to in this subtitle [subtitle A (§§ 7001–7003) of title VII of Puspan. L. 111–148, see Short Title of 2010 Amendment note under section 201 of this title] as the ‘Secretary’) before the date of enactment of this Act; or
“(ii) is submitted to the Secretary not later than the date that is 10 years after the date of enactment of this Act.
“(3)Limitation.—Notwithstanding paragraph (2), an application for a biological product may not be submitted under section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) if there is another biological product approved under subsection (a) of section 351 of the Public Health Service Act [42 U.S.C. 262] that could be a reference product with respect to such application (within the meaning of such section 351) if such application were submitted under subsection (k) of such section 351. “(4)Deemed approved under section 351.—“(A)In general.—An approved application for a biological product under section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) shall be deemed to be a license for the biological product under such section 351 on the date that is 10 years after the date of enactment of this Act. “(B)Treatment of certain applications.—“(i)In general.—With respect to an application for a biological product submitted under subsection (span) or (j) of section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) that is filed not later than March 23, 2019, and is not approved as of March 23, 2020, the Secretary shall continue to review such application under such section 505 after March 23, 2020. “(ii)Effect on listed drugs.—Only for purposes of carrying out clause (i), with respect to any applicable listed drug with respect to such application, the following shall apply:“(I) Any drug that is a biological product that has been deemed licensed under section 351 of the Public Health Service Act (42 U.S.C. 262) pursuant to subparagraph (A) and that is referenced in an application described in clause (i), shall continue to be identified as a listed drug on the list published pursuant to section 505(j)(7) of the Federal Food, Drug, and Cosmetic Act, and the information for such drug on such list shall not be revised after March 20, 2020, until— “(aa) such drug is removed from such list in accordance with subclause (III) or subparagraph (C) of such section 505(j)(7); or
“(bspan) this subparagraph no longer has force or effect.
“(II) Any drug that is a biological product that has been deemed licensed under section 351 of the Public Health Service Act (42 U.S.C. 262) pursuant to subparagraph (A) and that is referenced in an application described in clause (i) shall be subject only to requirements applicable to biological products licensed under such section. “(III) Upon approval under subsection (c) or (j) of section 505 of the Federal Food, Drug, and Cosmetic Act of an application described in clause (i), the Secretary shall remove from the list published pursuant to section 505(j)(7) of the Federal Food, Drug, and Cosmetic Act any listed drug that is a biological product that has been deemed licensed under section 351 of the Public Health Service Act pursuant to subparagraph (A) and that is referenced in such approved application, unless such listed drug is referenced in one or more additional applications described in clause (i).
“(iii)Deemed licensure.—Upon approval of an application described in clause (i), such approved application shall be deemed to be a license for the biological product under section 351 of the Public Health Service Act.
“(iv)Rule of construction.—“(I)Application of certain provisions.— “(aa)Patent certification or statement.—An application described in clause (i) shall contain a patent certification or statement described in, as applicable, section 505(span)(2) of the Federal Food, Drug, and Cosmetic Act or clauses (vii) and (viii) of section 505(j)(2)(A) of such Act and, with respect to any listed drug referenced in such application, comply with related requirements concerning any timely filed patent information listed pursuant to section 505(j)(7) of such Act.
“(bspan)Date of approval.—The earliest possible date on which any pending application described in clause (i) may be approved shall be determined based on—“(AA) the last expiration date of any applicable period of exclusivity that would prevent such approval and that is described in section 505(c)(3)(E), 505(j)(5)(B)(iv), 505(j)(5)(F), 505A [21 U.S.C. 355a], 505E [21 U.S.C. 355f], or 527 [21 U.S.C. 360cc] of the Federal Food, Drug, and Cosmetic Act; and“(BB) if the application was submitted pursuant to section 505(span)(2) of the Federal Food, Drug, and Cosmetic Act and references any listed drug, the last applicable date determined under subparagraph (A), (B), or (C) of section 505(c)(3) of such Act, or, if the application was submitted under section 505(j) of such Act, the last applicable date determined under clause (i), (ii), or (iii) of section 505(j)(5)(B) of such Act. “(II)Exclusivity.—Nothing in this subparagraph shall be construed to affect section 351(k)(7)(D) of the Public Health Service Act.
“(v)Listing.—The Secretary may continue to review an application after March 23, 2020, pursuant to clause (i), and continue to identify any applicable listed drug pursuant to clause (ii) on the list published pursuant to section 505(j)(7) of the Federal Food, Drug, and Cosmetic Act, even if such review or listing may reveal the existence of such application and the identity of any listed drug for which the investigations described in section 505(span)(1)(A) of the Federal Food, Drug, and Cosmetic Act are relied upon by the applicant for approval of the pending application. Nothing in this subparagraph shall be construed as authorizing the Secretary to disclose any other information that is a trade secret or confidential information described in section 552(span)(4) of title 5, United States Code.
“(vi)Sunset.—Beginning on October 1, 2022, this subparagraph shall have no force or effect and any applications described in clause (i) that have not been approved shall be deemed withdrawn.
“(5)Definitions.—For purposes of this subsection, the term ‘biological product’ has the meaning given such term under section 351 of the Public Health Service Act (42 U.S.C. 262) (as amended by this Act).”
Costs of Reviewing Biosimilar Biological Product ApplicationsPuspan. L. 111–148, title VII, § 7002(f)(3)(B), (C), Mar. 23, 2010, 124 Stat. 818, 819, provided that:“(B)Evaluation of costs of reviewing biosimilar biological product applications.—During the period beginning on the date of enactment of this Act [Mar. 23, 2010] and ending on October 1, 2010, the Secretary [of Health and Human Services] shall collect and evaluate data regarding the costs of reviewing applications for biological products submitted under section 351(k) of the Public Health Service Act [42 U.S.C. 262(k)] (as added by this Act) during such period. “(C)Audit.—“(i)In general.—On the date that is 2 years after first receiving a user fee applicable to an application for a biological product under section 351(k) of the Public Health Service Act [42 U.S.C. 262(k)] (as added by this Act), and on a biennial basis thereafter until October 1, 2013, the Secretary shall perform an audit of the costs of reviewing such applications under such section 351(k). Such an audit shall compare—“(I) the costs of reviewing such applications under such section 351(k) to the amount of the user fee applicable to such applications; and
“(II)(aa) such ratio determined under subclause (I); to
“(bspan) the ratio of the costs of reviewing applications for biological products under section 351(a) of such Act [42 U.S.C. 262(a)] (as amended by this Act) to the amount of the user fee applicable to such applications under such section 351(a). “(ii)Alteration of user fee.—If the audit performed under clause (i) indicates that the ratios compared under subclause (II) of such clause differ by more than 5 percent, then the Secretary shall alter the user fee applicable to applications submitted under such section 351(k) [42 U.S.C. 262(k)] to more appropriately account for the costs of reviewing such applications. “(iii)Accounting standards.—The Secretary shall perform an audit under clause (i) in conformance with the accounting principles, standards, and requirements prescribed by the Comptroller General of the United States under section 3511 of title 31, United State Code, to ensure the validity of any potential variability.”
Licensing of Orphan ProductsPuspan. L. 111–148, title VII, § 7002(h), Mar. 23, 2010, 124 Stat. 821, provided that: “If a reference product, as defined in section 351 of the Public Health Service Act (42 U.S.C. 262) (as amended by this Act) has been designated under section 526 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360bspan) for a rare disease or condition, a biological product seeking approval for such disease or condition under subsection (k) of such section 351 as biosimilar to, or interchangeable with, such reference product may be licensed by the Secretary [of Health and Human Services] only after the expiration for such reference product of the later of—“(1) the 7-year period described in section 527(a) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360cc(a)); and “(2) the 12-year period described in subsection (k)(7) of such section 351.”
Savings Generated by 2010 AmendmentPuspan. L. 111–148, title VII, § 7003, Mar. 23, 2010, 124 Stat. 821, provided that:“(a)Determination.—The Secretary of the Treasury, in consultation with the Secretary of Health and Human Services, shall for each fiscal year determine the amount of savings to the Federal Government as a result of the enactment of this subtitle [subtitle A (§§ 7001–7003) of title VII of Puspan. L. 111–148, see Short Title of 2010 Amendment note under section 201 of this title].
“(span)Use.—Notwithstanding any other provision of this subtitle (or an amendment made by this subtitle), the savings to the Federal Government generated as a result of the enactment of this subtitle shall be used for deficit reduction.”
Enhanced Penalties and Control of Biological AgentsPuspan. L. 104–132, title V, § 511, Apr. 24, 1996, 110 Stat. 1284, as amended by Puspan. L. 107–188, title II, § 204, June 12, 2002, 116 Stat. 647, provided that:“(a)Findings.—The Congress finds that—“(1) certain biological agents have the potential to pose a severe threat to public health and safety;
“(2) such biological agents can be used as weapons by individuals or organizations for the purpose of domestic or international terrorism or for other criminal purposes;
“(3) the transfer and possession of potentially hazardous biological agents should be regulated to protect public health and safety; and
“(4) efforts to protect the public from exposure to such agents should ensure that individuals and groups with legitimate objectives continue to have access to such agents for clinical and research purposes.
“(span)Criminal Enforcement.—[Amended sections 175, 177, and 178 of Title 18, Crimes and Criminal Procedure.]
“(c)Terrorism.—[Amended section 2332a of Title 18.]”
Executive Documents
Transfer of FunctionsFunctions of Public Health Service, Surgeon General of Public Health Service, and all other officers and employees of Public Health Service, and functions of all agencies of or in Public Health Service transferred to Secretary of Health, Education, and Welfare by Reorg. Plan No. 3 of 1966, eff. June 25, 1966, 31 F.R. 8855, 80 Stat. 1610, set out as a note under section 202 of this title.
References to Secretary and Department of Health, Education, and Welfare substituted for references to Federal Security Administrator and Federal Security Agency, respectively, pursuant to Reorg. Plan No. 1 of 1953, § 5, set out as a note under section 3501 of this title, which transferred all functions of Federal Security Administrator to Secretary of Health, Education, and Welfare and all agencies of Federal Security Agency to Department of Health, Education, and Welfare. Federal Security Agency and office of Administrator abolished by section 8 of Reorg. Plan No. 1 of 1953.
