42 U.S.C. § 262 — Regulation of biological products

Page 456 TITLE 42—THE PUBLIC HEALTH AND WELFARE § 258a § 258a. Transferred Editorial Notes CODIFICATION Section, act July 8, 1947, ch. 210, title II, § 201, 61 Stat. 269, which related to transfer of balances in working capital fund, narcotic hospitals, to surplus fund, was transferred and is set out as a note under section 290aa of this title. §§ 259 to 261a. Repealed. Pub. L. 106–310, div. B, title XXXIV, § 3405(a), Oct. 17, 2000, 114 Stat. 1221, as amended by Pub. L. 114–198, title I, § 110(b), July 22, 2016, 130 Stat. 710 Section 259, acts July 1, 1944, ch. 373, title III, § 343, 58 Stat. 699; Pub. L. 91–513, title I, § 2(a)(2)(A), (3), (4), Oct. 27, 1970, 84 Stat. 1240; Pub. L. 92–293, § 3, May 11, 1972, 86 Stat. 136; Pub. L. 98–473, title II, § 232(b), Oct. 12, 1984, 98 Stat. 2031, related to convict addicts or other persons with drug abuse or drug dependence problems. Section 260, acts July 1, 1944, ch. 373, title III, § 344, 58 Stat. 701; June 25, 1948, ch. 654, § 5, 62 Stat. 1018; July 24, 1956, ch. 676, title III, § 302(b), 70 Stat. 622; Pub. L. 91–513, title I, § 2(a)(2)(A), (3), (4), Oct. 27, 1970, 84 Stat. 1240, re- lated to addicts and persons with drug abuse or drug dependence problems. Section 260a, act July 1, 1944, ch. 373, title III, § 345, as added May 8, 1954, ch. 195, § 2, 68 Stat. 79; amended July 24, 1956, ch. 676, title III, § 302(c), 70 Stat. 622; Pub. L. 91–358, title I, § 155(c)(32), July 29, 1970, 84 Stat. 572, re- lated to admission of addicts committed from District of Columbia. Section 261, acts July 1, 1944, ch. 373, title III, § 346, formerly § 345, 58 Stat. 701; renumbered § 346, May 8, 1954, ch. 195, § 2, 68 Stat. 79; amended Pub. L. 91–513, title I, § 2(a)(2)(A), (5), Oct. 27, 1970, 84 Stat. 1240, related to penalties for introducing prohibited articles and sub- stances into hospitals and escaping from, or aiding and abetting escape from hospitals. Section 261a, act July 1, 1944, ch. 373, title III, § 347, as added May 8, 1954, ch. 195, § 4, 68 Stat. 80; amended Pub. L. 91–513, title I, § 2(a)(4), Oct. 27, 1970, 84 Stat. 1240, re- lated to release of patients and determination by Sur- geon General. Statutory Notes and Related Subsidiaries EFFECTIVE DATE OF 2016 AMENDMENT Pub. L. 114–198, title I, § 110(b), July 22, 2016, 130 Stat. 710, provided that the amendment made by section 110(b) (amending directory language of section 3405(a) of Pub. L. 106–310, which repealed sections 259 to 261a of this title) is effective as if included in the enactment of Pub. L. 106–310. PART F—LICENSING OF BIOLOGICAL PRODUCTS AND CLINICAL LABORATORIES SUBPART 1—BIOLOGICAL PRODUCTS § 262. Regulation of biological products (a) Biologics license (1) No person shall introduce or deliver for in- troduction into interstate commerce any bio- logical product unless— (A) a biologics license under this subsection or subsection (k) is in effect for the biological product; and (B) each package of the biological product is plainly marked with— (i) the proper name of the biological prod- uct contained in the package; (ii) the name, address, and applicable li- cense number of the manufacturer of the bi- ological product; and (iii) the expiration date of the biological product. (2)(A) The Secretary shall establish, by regula- tion, requirements for the approval, suspension, and revocation of biologics licenses. (B) PEDIATRIC STUDIES.—A person that submits an application for a license under this paragraph shall submit to the Secretary as part of the ap- plication any assessments required under sec- tion 505B of the Federal Food, Drug, and Cos- metic Act [21 U.S.C. 355c]. (C) The Secretary shall approve a biologics li- cense application— (i) on the basis of a demonstration that— (I) the biological product that is the sub- ject of the application is safe, pure, and po- tent; and (II) the facility in which the biological product is manufactured, processed, packed, or held meets standards designed to assure that the biological product continues to be safe, pure, and potent; and (ii) if the applicant (or other appropriate person) consents to the inspection of the facil- ity that is the subject of the application, in accordance with subsection (c). (D) POSTMARKET STUDIES AND CLINICAL TRIALS; LABELING; RISK EVALUATION AND MITIGATION STRATEGY.—A person that submits an applica- tion for a license under this paragraph is subject to sections 505(o), 505(p), and 505–1 of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355(o), (p), 355–1]. (E)(i) The Secretary may rely upon qualified data summaries to support the approval of a supplemental application, with respect to a qualified indication for a drug, submitted under this subsection, if such supplemental applica- tion complies with the requirements of subpara- graph (B) of section 505(c)(5) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355(c)(5)]. (ii) In this subparagraph, the terms ‘‘qualified indication’’ and ‘‘qualified data summary’’ have the meanings given such terms in section 505(c)(5) of the Federal Food, Drug, and Cos- metic Act. (3) The Secretary shall prescribe requirements under which a biological product undergoing in- vestigation shall be exempt from the require- ments of paragraph (1). (b) Falsely labeling or marking package or con- tainer; altering label or mark No person shall falsely label or mark any package or container of any biological product or alter any label or mark on the package or container of the biological product so as to fal- sify the label or mark. (c) Inspection of establishment for propagation and preparation Any officer, agent, or employee of the Depart- ment of Health and Human Services, authorized by the Secretary for the purpose, may during all reasonable hours enter and inspect any estab- lishment for the propagation or manufacture and preparation of any biological product. (d) Recall of product presenting imminent haz- ard; violations (1) Upon a determination that a batch, lot, or other quantity of a product licensed under this Page 457 TITLE 42—THE PUBLIC HEALTH AND WELFARE § 262 section presents an imminent or substantial hazard to the public health, the Secretary shall issue an order immediately ordering the recall of such batch, lot, or other quantity of such product. An order under this paragraph shall be issued in accordance with section 554 of title 5. (2) Any violation of paragraph (1) shall subject the violator to a civil penalty of up to $100,000 per day of violation. The amount of a civil pen- alty under this paragraph shall, effective De- cember 1 of each year beginning 1 year after the effective date of this paragraph, be increased by the percent change in the Consumer Price Index for the base quarter of such year over the Con- sumer Price Index for the base quarter of the preceding year, adjusted to the nearest 1⁄10 of 1 percent. For purposes of this paragraph, the term ‘‘base quarter’’, as used with respect to a year, means the calendar quarter ending on Sep- tember 30 of such year and the price index for a base quarter is the arithmetical mean of such index for the 3 months comprising such quarter. (e) Interference with officers No person shall interfere with any officer, agent, or employee of the Service in the per- formance of any duty imposed upon him by this section or by regulations made by authority thereof. (f) Penalties for offenses Any person who shall violate, or aid or abet in violating, any of the provisions of this section shall be punished upon conviction by a fine not exceeding $500 or by imprisonment not exceed- ing one year, or by both such fine and imprison- ment, in the discretion of the court. (g) Construction with other laws Nothing contained in this chapter shall be construed as in any way affecting, modifying, repealing, or superseding the provisions of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 301 et seq.]. (h) Exportation of partially processed biological products A partially processed biological product which— (1) is not in a form applicable to the preven- tion, treatment, or cure of diseases or injuries of man; (2) is not intended for sale in the United States; and (3) is intended for further manufacture into final dosage form outside the United States, shall be subject to no restriction on the export of the product under this chapter or the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 301 et seq.] if the product is manufactured, processed, packaged, and held in conformity with current good manufacturing practice requirements or meets international manufacturing standards as certified by an international standards organiza- tion recognized by the Secretary and meets the requirements of section 801(e)(1) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 381(e)). (i) ‘‘Biological product’’ defined In this section: (1) The term ‘‘biological product’’ means a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein, or analogous prod- uct, or arsphenamine or derivative of arsphen- amine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings. (2) The term ‘‘biosimilar’’ or ‘‘biosimi- larity’’, in reference to a biological product that is the subject of an application under sub- section (k), means— (A) that the biological product is highly similar to the reference product notwith- standing minor differences in clinically in- active components; and (B) there are no clinically meaningful dif- ferences between the biological product and the reference product in terms of the safety, purity, and potency of the product. (3) The term ‘‘interchangeable’’ or ‘‘inter- changeability’’, in reference to a biological product that is shown to meet the standards described in subsection (k)(4), means that the biological product may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product. (4) The term ‘‘reference product’’ means the single biological product licensed under sub- section (a) against which a biological product is evaluated in an application submitted under subsection (k). (j) Application of Federal Food, Drug, and Cos- metic Act The Federal Food, Drug, and Cosmetic Act [21 U.S.C. 301 et seq.], including the requirements under sections 505(o), 505(p), and 505–1 of such Act [21 U.S.C. 355(o), (p), 355–1], applies to a bio- logical product subject to regulation under this section, except that a product for which a li- cense has been approved under subsection (a) shall not be required to have an approved appli- cation under section 505 of such Act. (k) Licensure of biological products as biosimilar or interchangeable (1) In general Any person may submit an application for licensure of a biological product under this subsection. (2) Content (A) In general (i) Required information An application submitted under this sub- section shall include information dem- onstrating that— (I) the biological product is biosimilar to a reference product based upon data derived from— (aa) analytical studies that dem- onstrate that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components; (bb) an assessment of toxicity (which may rely on, or consist of, a study or studies described in item (aa) or (cc)); and (cc) a clinical study or studies (in- cluding the assessment of Page 458 TITLE 42—THE PUBLIC HEALTH AND WELFARE § 262 immunogenicity and pharmacokinetics or pharmacodynamics) that are suffi- cient to demonstrate safety, purity, and potency in 1 or more appropriate conditions of use for which the ref- erence product is licensed and intended to be used and for which licensure is sought for the biological product; (II) the biological product and ref- erence product utilize the same mecha- nism or mechanisms of action for the condition or conditions of use prescribed, recommended, or suggested in the pro- posed labeling, but only to the extent the mechanism or mechanisms of action are known for the reference product; (III) the condition or conditions of use prescribed, recommended, or suggested in the labeling proposed for the biologi- cal product have been previously ap- proved for the reference product; (IV) the route of administration, the dosage form, and the strength of the bio- logical product are the same as those of the reference product; and (V) the facility in which the biological product is manufactured, processed, packed, or held meets standards designed to assure that the biological product continues to be safe, pure, and potent. (ii) Determination by Secretary The Secretary may determine, in the Secretary’s discretion, that an element de- scribed in clause (i)(I) is unnecessary in an application submitted under this sub- section. (iii) Additional information An application submitted under this sub- section— (I) shall include publicly-available in- formation regarding the Secretary’s pre- vious determination that the reference product is safe, pure, and potent; (II) may include any additional infor- mation in support of the application, in- cluding publicly-available information with respect to the reference product or another biological product; and (III) may include information to show that the conditions of use prescribed, recommended, or suggested in the label- ing proposed for the biological product have been previously approved for the reference product. (B) Interchangeability An application (or a supplement to an ap- plication) submitted under this subsection may include information demonstrating that the biological product meets the stand- ards described in paragraph (4). (3) Evaluation by Secretary Upon review of an application (or a supple- ment to an application) submitted under this subsection, the Secretary shall license the bio- logical product under this subsection if— (A) the Secretary determines that the in- formation submitted in the application (or the supplement) is sufficient to show that the biological product— (i) is biosimilar to the reference product; or (ii) meets the standards described in paragraph (4), and therefore is inter- changeable with the reference product; and (B) the applicant (or other appropriate per- son) consents to the inspection of the facil- ity that is the subject of the application, in accordance with subsection (c). (4) Safety standards for determining inter- changeability Upon review of an application submitted under this subsection or any supplement to such application, the Secretary shall deter- mine the biological product to be interchange- able with the reference product if the Sec- retary determines that the information sub- mitted in the application (or a supplement to such application) is sufficient to show that— (A) the biological product— (i) is biosimilar to the reference product; and (ii) can be expected to produce the same clinical result as the reference product in any given patient; and (B) for a biological product that is admin- istered more than once to an individual, the risk in terms of safety or diminished effi- cacy of alternating or switching between use of the biological product and the reference product is not greater than the risk of using the reference product without such alter- nation or switch. (5) General rules (A) One reference product per application A biological product, in an application submitted under this subsection, may not be evaluated against more than 1 reference product. (B) Review An application submitted under this sub- section shall be reviewed by the division within the Food and Drug Administration that is responsible for the review and ap- proval of the application under which the reference product is licensed. (C) Risk evaluation and mitigation strategies The authority of the Secretary with re- spect to risk evaluation and mitigation strategies under the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 301 et seq.] shall apply to biological products licensed under this subsection in the same manner as such authority applies to biological products li- censed under subsection (a). (6) Exclusivity for first interchangeable bio- logical product The Secretary shall not make approval as an interchangeable biological product effective with respect to an application submitted under this subsection that relies on the same reference product for which a prior biological product has received a determination of inter- changeability for any condition of use, until the earlier of— (A) 1 year after the first commercial mar- keting of the first interchangeable bio- Page 459 TITLE 42—THE PUBLIC HEALTH AND WELFARE § 262 similar biological product to be approved as interchangeable for that reference product; (B) 18 months after— (i) a final court decision on all patents in suit in an action instituted under sub- section (l)(6) against the applicant that submitted the application for the first ap- proved interchangeable biosimilar biologi- cal product; or (ii) the dismissal with or without preju- dice of an action instituted under sub- section (l)(6) against the applicant that submitted the application for the first ap- proved interchangeable biosimilar biologi- cal product; or (C)(i) 42 months after approval of the first interchangeable biosimilar biological prod- uct if the applicant that submitted such ap- plication has been sued under subsection (l)(6) and such litigation is still ongoing within such 42-month period; or (ii) 18 months after approval of the first interchangeable biosimilar biological prod- uct if the applicant that submitted such ap- plication has not been sued under subsection (l)(6). For purposes of this paragraph, the term ‘‘final court decision’’ means a final decision of a court from which no appeal (other than a petition to the United States Supreme Court for a writ of certiorari) has been or can be 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. (7) Exclusivity for reference product (A) Effective date of biosimilar application approval Approval of an application under this sub- section may not be made effective by the Secretary until the date that is 12 years after the date on which the reference prod- uct was first licensed under subsection (a). (B) Filing period An application under this subsection may not be submitted to the Secretary until the date that is 4 years after the date on which the reference product was first licensed under subsection (a). (C) First licensure Subparagraphs (A) and (B) shall not apply to a license for or approval of— (i) a supplement for the biological prod- uct that is the reference product; or (ii) a subsequent application filed by the same sponsor or manufacturer of the bio- logical product that is the reference prod- uct (or a licensor, predecessor in interest, or other related entity) for— (I) a change (not including a modifica- tion to the structure of the biological product) that results in a new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device, or strength; or (II) a modification to the structure of the biological product that does not re- sult in a change in safety, purity, or po- tency. (D) Deemed licenses (i) No additional exclusivity through deem- ing An approved application that is deemed to be a license for a biological product under this section pursuant to section 7002(e)(4) of the Biologics Price Competi- tion and Innovation Act of 2009 shall not be treated as having been first licensed under subsection (a) for purposes of sub- paragraphs (A) and (B). (ii) Application of limitations on exclu- sivity Subparagraph (C) shall apply with re- spect to a reference product referred to in such subparagraph that was the subject of an approved application that was deemed to be a license pursuant to section 7002(e)(4) of the Biologics Price Competi- tion and Innovation Act of 2009. (iii) Applicability The exclusivity periods described in sec- tion 527, section 505A(b)(1)(A)(ii), and sec- tion 505A(c)(1)(A)(ii) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 360cc and 355a(b)(1)(A)(ii), (c)(1)(A)(ii)] shall con- tinue to apply to a biological product after an approved application for the biological product is deemed to be a license for the biological product under subsection (a) pursuant to section 7002(e)(4) of the Bio- logics Price Competition and Innovation Act of 2009. (8) Guidance documents (A) In general The Secretary may, after opportunity for public comment, issue guidance in accord- ance, except as provided in subparagraph (B)(i), with section 701(h) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 371(h)] with respect to the licensure of a bio- logical product under this subsection. Any such guidance may be general or specific. (B) Public comment (i) In general The Secretary shall provide the public an opportunity to comment on any pro- posed guidance issued under subparagraph (A) before issuing final guidance. (ii) Input regarding most valuable guid- ance The Secretary shall establish a process through which the public may provide the Secretary with input regarding priorities for issuing guidance. (C) No requirement for application consider- ation The issuance (or non-issuance) of guidance under subparagraph (A) shall not preclude the review of, or action on, an application submitted under this subsection. Page 460 TITLE 42—THE PUBLIC HEALTH AND WELFARE § 262 (D) Requirement for product class-specific guidance If the Secretary issues product class-spe- cific guidance under subparagraph (A), such guidance shall include a description of— (i) the criteria that the Secretary will use to determine whether a biological product is highly similar to a reference product in such product class; and (ii) the criteria, if available, that the Secretary will use to determine whether a biological product meets the standards de- scribed in paragraph (4). (E) Certain product classes (i) Guidance The Secretary may indicate in a guid- ance document that the science and expe- rience, as of the date of such guidance, with respect to a product or product class (not including any recombinant protein) does not allow approval of an application for a license as provided under this sub- section for such product or product class. (ii) Modification or reversal The Secretary may issue a subsequent guidance document under subparagraph (A) to modify or reverse a guidance docu- ment under clause (i). (iii) No effect on ability to deny license Clause (i) shall not be construed to re- quire the Secretary to approve a product with respect to which the Secretary has not indicated in a guidance document that the science and experience, as described in clause (i), does not allow approval of such an application. (9) Public listing (A) In general (i) Initial publication Not later than 180 days after December 27, 2020, the Secretary shall publish and make available to the public in a search- able, electronic format— (I) a list of each biological product, by nonproprietary name (proper name), for which, as of December 27, 2020, a bio- logics license under subsection (a) or this subsection is in effect, or that, as of such date of enactment, is deemed to be licensed under this section pursuant to section 7002(e)(4) of the Biologics Price Competition and Innovation Act of 2009; (II) the date of licensure of the mar- keting application and the application number; and (III) with respect to each biological product described in subclause (I), the li- censure status, and, as available, the marketing status. (ii) Revisions Every 30 days after the publication of the first list under clause (i), the Sec- retary shall revise the list to include each biological product which has been licensed under subsection (a) or this subsection during the 30-day period or deemed li- censed under this section pursuant to sec- tion 7002(e)(4) of the Biologics Price Com- petition and Innovation Act of 2009. (iii) Patent information Not later than 30 days after a list of pat- ents under subsection (l)(3)(A), or a supple- ment to such list under subsection (l)(7), has been provided by the reference product sponsor to the subsection (k) applicant re- specting a biological product included on the list published under this subparagraph, the reference product sponsor shall provide such list of patents (or supplement there- to) and their corresponding expiry dates to the Secretary, and the Secretary shall, in revisions made under clause (ii), include such information for such biological prod- uct. Within 30 days of providing any subse- quent or supplemental list of patents to any subsequent subsection (k) applicant under subsection (l)(3)(A) or (l)(7), the ref- erence product sponsor shall update the in- formation provided to the Secretary under this clause with any additional patents from such subsequent or supplemental list and their corresponding expiry dates. (iv) Listing of exclusivities For each biological product included on the list published under this subparagraph, the Secretary shall specify each exclu- sivity period under paragraph (6) or para- graph (7) for which the Secretary has de- termined such biological product to be eli- gible and that has not concluded. (B) Revocation or suspension of license If the license of a biological product is de- termined by the Secretary to have been re- voked or suspended for safety, purity, or po- tency reasons, it may not be published in the list under subparagraph (A). If such revoca- tion or suspension occurred after inclusion of such biological product in the list pub- lished under subparagraph (A), the reference product sponsor shall notify the Secretary that— (i) the biological product shall be imme- diately removed from such list for the same period as the revocation or suspen- sion; and (ii) a notice of the removal shall be pub- lished in the Federal Register. (l) Patents (1) Confidential access to subsection (k) appli- cation (A) Application of paragraph Unless otherwise agreed to by a person that submits an application under sub- section (k) (referred to in this subsection as the ‘‘subsection (k) applicant’’) and the sponsor of the application for the reference product (referred to in this subsection as the ‘‘reference product sponsor’’), the provisions of this paragraph shall apply to the ex- change of information described in this sub- section. (B) In general (i) Provision of confidential information When a subsection (k) applicant submits an application under subsection (k), such Page 461 TITLE 42—THE PUBLIC HEALTH AND WELFARE § 262 applicant shall provide to the persons de- scribed in clause (ii), subject to the terms of this paragraph, confidential access to the information required to be produced pursuant to paragraph (2) and any other information that the subsection (k) appli- cant determines, in its sole discretion, to be appropriate (referred to in this sub- section as the ‘‘confidential information’’). (ii) Recipients of information The persons described in this clause are the following: (I) Outside counsel One or more attorneys designated by the reference product sponsor who are employees of an entity other than the reference product sponsor (referred to in this paragraph as the ‘‘outside counsel’’), provided that such attorneys do not en- gage, formally or informally, in patent prosecution relevant or related to the reference product. (II) In-house counsel One attorney that represents the ref- erence product sponsor who is an em- ployee of the reference product sponsor, provided that such attorney does not en- gage, formally or informally, in patent prosecution relevant or related to the reference product. (iii) Patent owner access A representative of the owner of a patent exclusively licensed to a reference product sponsor with respect to the reference prod- uct and who has retained a right to assert the patent or participate in litigation con- cerning the patent may be provided the confidential information, provided that the representative informs the reference product sponsor and the subsection (k) ap- plicant of his or her agreement to be sub- ject to the confidentiality provisions set forth in this paragraph, including those under clause (ii). (C) Limitation on disclosure No person that receives confidential infor- mation pursuant to subparagraph (B) shall disclose any confidential information to any other person or entity, including the ref- erence product sponsor employees, outside scientific consultants, or other outside coun- sel retained by the reference product spon- sor, without the prior written consent of the subsection (k) applicant, which shall not be unreasonably withheld. (D) Use of confidential information Confidential information shall be used for the sole and exclusive purpose of deter- mining, with respect to each patent assigned to or exclusively licensed by the reference product sponsor, whether a claim of patent infringement could reasonably be asserted if the subsection (k) applicant engaged in the manufacture, use, offering for sale, sale, or importation into the United States of the bi- ological product that is the subject of the application under subsection (k). (E) Ownership of confidential information The confidential information disclosed under this paragraph is, and shall remain, the property of the subsection (k) applicant. By providing the confidential information pursuant to this paragraph, the subsection (k) applicant does not provide the reference product sponsor or the outside counsel any interest in or license to use the confidential information, for purposes other than those specified in subparagraph (D). (F) Effect of infringement action In the event that the reference product sponsor files a patent infringement suit, the use of confidential information shall con- tinue to be governed by the terms of this paragraph until such time as a court enters a protective order regarding the informa- tion. Upon entry of such order, the sub- section (k) applicant may redesignate con- fidential information in accordance with the terms of that order. No confidential infor- mation shall be included in any publicly- available complaint or other pleading. In the event that the reference product sponsor does not file an infringement action by the date specified in paragraph (6), the reference product sponsor shall return or destroy all confidential information received under this paragraph, provided that if the reference product sponsor opts to destroy such infor- mation, it will confirm destruction in writ- ing to the subsection (k) applicant. (G) Rule of construction Nothing in this paragraph shall be con- strued— (i) as an admission by the subsection (k) applicant regarding the validity, enforce- ability, or infringement of any patent; or (ii) as an agreement or admission by the subsection (k) applicant with respect to the competency, relevance, or materiality of any confidential information. (H) Effect of violation The disclosure of any confidential infor- mation in violation of this paragraph shall be deemed to cause the subsection (k) appli- cant to suffer irreparable harm for which there is no adequate legal remedy and the court shall consider immediate injunctive relief to be an appropriate and necessary remedy for any violation or threatened vio- lation of this paragraph. (2) Subsection (k) application information Not later than 20 days after the Secretary notifies the subsection (k) applicant that the application has been accepted for review, the subsection (k) applicant— (A) shall provide to the reference product sponsor a copy of the application submitted to the Secretary under subsection (k), and such other information that describes the process or processes used to manufacture the biological product that is the subject of such application; and (B) may provide to the reference product sponsor additional information requested by or on behalf of the reference product spon- sor. Page 462 TITLE 42—THE PUBLIC HEALTH AND WELFARE § 262 (3) List and description of patents (A) List by reference product sponsor Not later than 60 days after the receipt of the application and information under para- graph (2), the reference product sponsor shall provide to the subsection (k) appli- cant— (i) a list of patents for which the ref- erence product sponsor believes a claim of patent infringement could reasonably be asserted by the reference product sponsor, or by a patent owner that has granted an exclusive license to the reference product sponsor with respect to the reference prod- uct, if a person not licensed by the ref- erence product sponsor engaged in the making, using, offering to sell, selling, or importing into the United States of the bi- ological product that is the subject of the subsection (k) application; and (ii) an identification of the patents on such list that the reference product spon- sor would be prepared to license to the subsection (k) applicant. (B) List and description by subsection (k) ap- plicant Not later than 60 days after receipt of the list under subparagraph (A), the subsection (k) applicant— (i) may provide to the reference product sponsor a list of patents to which the sub- section (k) applicant believes a claim of patent infringement could reasonably be asserted by the reference product sponsor if a person not licensed by the reference product sponsor engaged in the making, using, offering to sell, selling, or import- ing into the United States of the biological product that is the subject of the sub- section (k) application; (ii) shall provide to the reference product sponsor, with respect to each patent listed by the reference product sponsor under subparagraph (A) or listed by the sub- section (k) applicant under clause (i)— (I) a detailed statement that describes, on a claim by claim basis, the factual and legal basis of the opinion of the sub- section (k) applicant that such patent is invalid, unenforceable, or will not be in- fringed by the commercial marketing of the biological product that is the subject of the subsection (k) application; or (II) a statement that the subsection (k) applicant does not intend to begin com- mercial marketing of the biological product before the date that such patent expires; and (iii) shall provide to the reference prod- uct sponsor a response regarding each pat- ent identified by the reference product sponsor under subparagraph (A)(ii). (C) Description by reference product sponsor Not later than 60 days after receipt of the list and statement under subparagraph (B), the reference product sponsor shall provide to the subsection (k) applicant a detailed statement that describes, with respect to each patent described in subparagraph (B)(ii)(I), on a claim by claim basis, the fac- tual and legal basis of the opinion of the ref- erence product sponsor that such patent will be infringed by the commercial marketing of the biological product that is the subject of the subsection (k) application and a response to the statement concerning validity and en- forceability provided under subparagraph (B)(ii)(I). (4) Patent resolution negotiations (A) In general After receipt by the subsection (k) appli- cant of the statement under paragraph (3)(C), the reference product sponsor and the subsection (k) applicant shall engage in good faith negotiations to agree on which, if any, patents listed under paragraph (3) by the subsection (k) applicant or the reference product sponsor shall be the subject of an ac- tion for patent infringement under para- graph (6). (B) Failure to reach agreement If, within 15 days of beginning negotiations under subparagraph (A), the subsection (k) applicant and the reference product sponsor fail to agree on a final and complete list of which, if any, patents listed under paragraph (3) by the subsection (k) applicant or the ref- erence product sponsor shall be the subject of an action for patent infringement under paragraph (6), the provisions of paragraph (5) shall apply to the parties. (5) Patent resolution if no agreement (A) Number of patents The subsection (k) applicant shall notify the reference product sponsor of the number of patents that such applicant will provide to the reference product sponsor under sub- paragraph (B)(i)(I). (B) Exchange of patent lists (i) In general On a date agreed to by the subsection (k) applicant and the reference product spon- sor, but in no case later than 5 days after the subsection (k) applicant notifies the reference product sponsor under subpara- graph (A), the subsection (k) applicant and the reference product sponsor shall simul- taneously exchange— (I) the list of patents that the sub- section (k) applicant believes should be the subject of an action for patent in- fringement under paragraph (6); and (II) the list of patents, in accordance with clause (ii), that the reference prod- uct sponsor believes should be the sub- ject of an action for patent infringement under paragraph (6). (ii) Number of patents listed by reference product sponsor (I) In general Subject to subclause (II), the number of patents listed by the reference prod- uct sponsor under clause (i)(II) may not exceed the number of patents listed by the subsection (k) applicant under clause (i)(I). Page 463 TITLE 42—THE PUBLIC HEALTH AND WELFARE § 262 (II) Exception If a subsection (k) applicant does not list any patent under clause (i)(I), the reference product sponsor may list 1 pat- ent under clause (i)(II). (6) Immediate patent infringement action (A) Action if agreement on patent list If the subsection (k) applicant and the ref- erence product sponsor agree on patents as described in paragraph (4), not later than 30 days after such agreement, the reference product sponsor shall bring an action for patent infringement with respect to each such patent. (B) Action if no agreement on patent list If the provisions of paragraph (5) apply to the parties as described in paragraph (4)(B), not later than 30 days after the exchange of lists under paragraph (5)(B), the reference product sponsor shall bring an action for patent infringement with respect to each patent that is included on such lists. (C) Notification and publication of complaint (i) Notification to Secretary Not later than 30 days after a complaint is served to a subsection (k) applicant in an action for patent infringement de- scribed under this paragraph, the sub- section (k) applicant shall provide the Sec- retary with notice and a copy of such com- plaint. (ii) Publication by Secretary The Secretary shall publish in the Fed- eral Register notice of a complaint re- ceived under clause (i). (7) Newly issued or licensed patents In the case of a patent that— (A) is issued to, or exclusively licensed by, the reference product sponsor after the date that the reference product sponsor provided the list to the subsection (k) applicant under paragraph (3)(A); and (B) the reference product sponsor reason- ably believes that, due to the issuance of such patent, a claim of patent infringement could reasonably be asserted by the ref- erence product sponsor if a person not li- censed by the reference product sponsor en- gaged in the making, using, offering to sell, selling, or importing into the United States of the biological product that is the subject of the subsection (k) application, not later than 30 days after such issuance or licensing, the reference product sponsor shall provide to the subsection (k) applicant a sup- plement to the list provided by the reference product sponsor under paragraph (3)(A) that includes such patent, not later than 30 days after such supplement is provided, the sub- section (k) applicant shall provide a statement to the reference product sponsor in accordance with paragraph (3)(B), and such patent shall be subject to paragraph (8). (8) Notice of commercial marketing and pre- liminary injunction (A) Notice of commercial marketing The subsection (k) applicant shall provide notice to the reference product sponsor not later than 180 days before the date of the first commercial marketing of the biological product licensed under subsection (k). (B) Preliminary injunction After receiving the notice under subpara- graph (A) and before such date of the first commercial marketing of such biological product, the reference product sponsor may seek a preliminary injunction prohibiting the subsection (k) applicant from engaging in the commercial manufacture or sale of such biological product until the court de- cides the issue of patent validity, enforce- ment, and infringement with respect to any patent that is— (i) included in the list provided by the reference product sponsor under paragraph (3)(A) or in the list provided by the sub- section (k) applicant under paragraph (3)(B); and (ii) not included, as applicable, on— (I) the list of patents described in para- graph (4); or (II) the lists of patents described in paragraph (5)(B). (C) Reasonable cooperation If the reference product sponsor has sought a preliminary injunction under subpara- graph (B), the reference product sponsor and the subsection (k) applicant shall reasonably cooperate to expedite such further discovery as is needed in connection with the prelimi- nary injunction motion. (9) Limitation on declaratory judgment action (A) Subsection (k) application provided If a subsection (k) applicant provides the application and information required under paragraph (2)(A), neither the reference prod- uct sponsor nor the subsection (k) applicant may, prior to the date notice is received under paragraph (8)(A), bring any action under section 2201 of title 28 for a declara- tion of infringement, validity, or enforce- ability of any patent that is described in clauses (i) and (ii) of paragraph (8)(B). (B) Subsequent failure to act by subsection (k) applicant If a subsection (k) applicant fails to com- plete an action required of the subsection (k) applicant under paragraph (3)(B)(ii), para- graph (5), paragraph (6)(C)(i), paragraph (7), or paragraph (8)(A), the reference product sponsor, but not the subsection (k) appli- cant, may bring an action under section 2201 of title 28 for a declaration of infringement, validity, or enforceability of any patent in- cluded in the list described in paragraph (3)(A), including as provided under para- graph (7). (C) Subsection (k) application not provided If a subsection (k) applicant fails to pro- vide the application and information re- quired under paragraph (2)(A), the reference product sponsor, but not the subsection (k) applicant, may bring an action under section 2201 of title 28 for a declaration of infringe- ment, validity, or enforceability of any pat- Page 464 TITLE 42—THE PUBLIC HEALTH AND WELFARE § 262 1 See References in Text note below. ent that claims the biological product or a use of the biological product. (m) Pediatric studies (1) Application of certain provisions The provisions of subsections (a), (d), (e), (f), (h), (i), (j), (k), (l), (n), and (p) of section 505A of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355a(a), (d), (e), (f), (h), (i), (j), (k), (l), (n), (p)] shall apply with respect to the ex- tension of a period under paragraphs (2) and (3) to the same extent and in the same manner as such provisions apply with respect to the ex- tension of a period under subsection (b) or (c) of section 505A of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355a(b), (c)]. (2) Market exclusivity for new biological prod- ucts If, prior to approval of an application that is submitted under subsection (a), the Secretary determines that information relating to the use of a new biological product in the pedi- atric population may produce health benefits in that population, the Secretary makes a written request for pediatric studies (which shall include a timeframe for completing such studies), the applicant agrees to the request, such studies are completed using appropriate formulations for each age group for which the study is requested within any such timeframe, and the reports thereof are submitted and ac- cepted in accordance with section 505A(d)(4) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355a(d)(4)]— (A) the periods for such biological product referred to in subsection (k)(7) are deemed to be 4 years and 6 months rather than 4 years and 12 years and 6 months rather than 12 years; and (B) if the biological product is designated under section 526 1 [21 U.S.C. 360bb] for a rare disease or condition, the period for such bio- logical product referred to in section 527(a) 1 [21 U.S.C. 360cc(a)] is deemed to be 7 years and 6 months rather than 7 years. (3) Market exclusivity for already-marketed bi- ological products If the Secretary determines that informa- tion relating to the use of a licensed biological product in the pediatric population may produce health benefits in that population and makes a written request to the holder of an approved application under subsection (a) for pediatric studies (which shall include a time- frame for completing such studies), the holder agrees to the request, such studies are com- pleted using appropriate formulations for each age group for which the study is requested within any such timeframe, and the reports thereof are submitted and accepted in accord- ance with section 505A(d)(4) of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355a(d)(4)]— (A) the periods for such biological product referred to in subsection (k)(7) are deemed to be 4 years and 6 months rather than 4 years and 12 years and 6 months rather than 12 years; and (B) if the biological product is designated under section 526 1 [21 U.S.C. 360bb] for a rare disease or condition, the period for such bio- logical product referred to in section 527(a) 1 [21 U.S.C. 360cc(a)] is deemed to be 7 years and 6 months rather than 7 years. (4) Exception The Secretary shall not extend a period re- ferred to in paragraph (2)(A), (2)(B), (3)(A), or (3)(B) if the determination under section 505A(d)(4) 1 [21 U.S.C. 355a(d)(4)] is made later than 9 months prior to the expiration of such period. (n) Date of approval in the case of recommended controls under the CSA (1) In general In the case of an application under sub- section (a) with respect to a biological product for which the Secretary provides notice to the sponsor that the Secretary intends to issue a scientific and medical evaluation and rec- ommend controls under the Controlled Sub- stances Act [21 U.S.C. 801 et seq.], approval of such application shall not take effect until the interim final rule controlling the biological product is issued in accordance with section 201(j) of the Controlled Substances Act [21 U.S.C. 811(j)]. (2) Date of approval For purposes of this section, with respect to an application described in paragraph (1), ref- erences to the date of approval of such appli- cation, or licensure of the product subject to such application, shall mean the later of— (A) the date an application is approved under subsection (a); or (B) the date of issuance of the interim final rule controlling the biological product. (July 1, 1944, ch. 373, title III, § 351, 58 Stat. 702; 1953 Reorg. Plan No. 1, §§ 5, 8, eff. Apr. 11, 1953, 18 F.R. 2053, 67 Stat. 631; Pub. L. 85–881, § 2, Sept. 2, 1958, 72 Stat. 1704; Pub. L. 91–515, title II, § 291, Oct. 30, 1970, 84 Stat. 1308; Pub. L. 96–88, title V, § 509(b), Oct. 17, 1979, 93 Stat. 695; Pub. L. 99–660, title I, § 105(a), title III, § 315, Nov. 14, 1986, 100 Stat. 3751, 3783; Pub. L. 102–300, § 6(b)(1), June 16, 1992, 106 Stat. 240; Pub. L. 104–134, title II, §§ 2102(d)(2), 2104, Apr. 26, 1996, 110 Stat. 1321–319, 1321–320; Pub. L. 105–115, title I, § 123(a)–(d), (g), Nov. 21, 1997, 111 Stat. 2323, 2324; Pub. L. 108–155, § 2(b)(3), Dec. 3, 2003, 117 Stat. 1941; Pub. L. 110–85, title IX, § 901(c), Sept. 27, 2007, 121 Stat. 939; Pub. L. 111–148, title VII, § 7002(a), (b), (g)(1), Mar. 23, 2010, 124 Stat. 804, 814, 819; Pub. L. 112–144, title V, § 502(a)(2), July 9, 2012, 126 Stat. 1040; Pub. L. 114–89, § 2(a)(2), Nov. 25, 2015, 129 Stat. 698; Pub. L. 114–255, div. A, title III, § 3031(b), Dec. 13, 2016, 130 Stat. 1100; Pub. L. 115–52, title V, § 505(b)(2)(B), Aug. 18, 2017, 131 Stat. 1046; Pub. L. 116–94, div. N, title I, §§ 605, 606, Dec. 20, 2019, 133 Stat. 3127; Pub. L. 116–260, div. BB, title III, §§ 322, 325(a), Dec. 27, 2020, 134 Stat. 2933, 2936; Pub. L. 117–328, div. FF, title III, §§ 3206, 3209(b), Dec. 29, 2022, 136 Stat. 5820, 5822.) Editorial Notes REFERENCES IN TEXT The effective date of this paragraph, referred to in subsec. (d)(2), is the effective date of section 315 of Pub. Page 465 TITLE 42—THE PUBLIC HEALTH AND WELFARE § 262 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 Pub. L. 111–148, which is set out in a note under this section. Sections 526, 527(a), and 505A(d)(4), referred to in sub- sec. (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 clas- sified to sections 360bb, 360cc(a), and 355a(d)(4), respec- tively, of Title 21, Food and Drugs. The Controlled Substances Act, referred to in subsec. (n)(1), is title II of Pub. 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. AMENDMENTS 2022—Subsec. (k)(2)(A)(i)(I)(bb). Pub. L. 117–328, § 3209(b), amended item (bb) generally. Prior to amend- ment, item (bb) read as follows: ‘‘animal studies (in- cluding the assessment of toxicity); and’’. Subsec. (k)(6). Pub. L. 117–328, § 3206(2), substituted ‘‘taken, and the term ‘first interchangeable biosimilar biological product’ means any interchangeable bio- similar biological product that is approved on the first day on which such a product is approved as inter- changeable with the reference product.’’ for ‘‘taken.’’ in concluding provisions. Pub. L. 117–328, § 3206(1), substituted ‘‘The Secretary shall not make approval as an interchangeable biologi- cal 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 bio- logical product is interchangeable for any condition of use’’ before ‘‘until the earlier of’’ in introductory provi- sions. 2020—Subsec. (k)(2)(A)(iii)(III). Pub. L. 116–260, § 322, added subcl. (III). Subsec. (k)(9). Pub. L. 116–260, § 325(a), added par. (9). 2019—Subsec. (i)(1). Pub. L. 116–94, § 605, struck out ‘‘(except any chemically synthesized polypeptide)’’ after ‘‘protein’’. Subsec. (k)(7)(D). Pub. L. 116–94, § 606, added subpar. (D). 2017—Subsec. (m)(2) to (4). Pub. L. 115–52 substituted ‘‘section 505A(d)(4)’’ for ‘‘section 505A(d)(3)’’. 2016—Subsec. (a)(2)(E). Pub. L. 114–255 added subpar. (E). 2015—Subsec. (n). Pub. L. 114–89 added subsec. (n). 2012—Subsec. (m)(1). Pub. 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). Pub. L. 111–148, § 7002(a)(1), in- serted ‘‘under this subsection or subsection (k)’’ after ‘‘biologics license’’. Subsec. (i). Pub. L. 111–148, § 7002(b), substituted ‘‘In this section:’’ for ‘‘In this section,’’, designated remain- der 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). Pub. L. 111–148, § 7002(a)(2), added subsecs. (k) and (l). Subsec. (m). Pub. L. 111–148, § 7002(g)(1), added subsec. (m). 2007—Subsec. (a)(2)(D). Pub. L. 110–85, § 901(c)(1), added subpar. (D). Subsec. (j). Pub. 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). Pub. L. 108–155 added sub- par. (B) and redesignated former subpar. (B) as (C). 1997—Subsec. (a). Pub. 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 af- fecting prior sales. Subsec. (b). Pub. L. 105–115, § 123(b), amended subsec. (b) generally. Prior to amendment, subsec. (b) read as follows: ‘‘No person shall falsely label or mark any package or container of any virus, serum, toxin, anti- toxin, 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). Pub. L. 105–115, § 123(c), substituted ‘‘bio- logical product.’’ for ‘‘virus, serum, toxin, antitoxin, vaccine, blood, blood component or derivative, aller- genic product, or other product aforesaid for sale, bar- ter, 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). Pub. 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), sub- stituted ‘‘Any violation of paragraph (1)’’ for ‘‘Any vio- lation of subparagraph (A)’’ and substituted ‘‘this para- graph’’ 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, pu- rity, and potency of such products, prescribed in regu- lations, 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). Pub. L. 105–115, § 123(d), added subsec. (i). Subsec. (j). Pub. L. 105–115, § 123(g), added subsec. (j). 1996—Subsec. (h). Pub. L. 104–134, § 2104, amended sub- sec. (h) generally, revising and restating former provi- sions, which also related to exportation of partially processed biological products. Subsec. (h)(1)(A). Pub. L. 104–134, § 2102(d)(2), sub- stituted ‘‘in a country listed under section 802(b)(1)’’ for ‘‘in a country listed under section 802(b)(A)’’ and ‘‘to a country listed under section 802(b)(1)’’ for ‘‘to a country listed under section 802(b)(4)’’. 1992—Subsec. (c). Pub. L. 102–300, which directed sub- stitution of ‘‘Health and Human Services’’ for ‘‘Health, Education, and Welfare’’, could not be executed because the words ‘‘Health, Education, and Welfare’’ did not ap- pear in original statutory text. Previously, references to Department and Secretary of Health and Human Services were substituted for references to Federal Se- curity Agency and its Administrator pursuant to provi- sions cited in Transfer of Functions note below. 1986—Subsec. (d). Pub. L. 99–660, § 315, designated ex- isting provisions as par. (1) and added par. (2). Subsec. (h). Pub. L. 99–660, § 105(a), added subsec. (h). 1970—Subsecs. (a) to (c). Pub. L. 91–515 inserted ‘‘vac- cine, blood, blood component or derivative, allergenic product,’’ after ‘‘antitoxin’’ wherever appearing. 1958—Subsec. (d). Pub. L. 85–881 struck out ‘‘made jointly by the Surgeon General, the Surgeon General of Page 466 TITLE 42—THE PUBLIC HEALTH AND WELFARE § 262 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’’ sub- stituted for ‘‘Secretary of Health, Education, and Wel- fare’’ in subsecs. (a), (c), (d), (h), and (k) to (n), and ‘‘Department of Health and Human Services’’ sub- stituted for ‘‘Department of Health, Education, and Welfare’’ in subsec. (c), pursuant to section 509(b) of Pub. L. 96–88, which is classified to section 3508(b) of Title 20, Education. EFFECTIVE DATE OF 2007 AMENDMENT Amendment by Pub. L. 110–85 effective 180 days after Sept. 27, 2007, see section 909 of Pub. L. 110–85, set out as a note under section 331 of Title 21, Food and Drugs. EFFECTIVE DATE OF 2003 AMENDMENT Amendment by Pub. L. 108–155 effective Dec. 3, 2003, except as otherwise provided, see section 4 of Pub. L. 108–155, set out as an Effective Date note under section 355c of Title 21, Food and Drugs. EFFECTIVE DATE OF 1997 AMENDMENT Amendment by Pub. L. 105–115 effective 90 days after Nov. 21, 1997, except as otherwise provided, see section 501 of Pub. L. 105–115, set out as a note under section 321 of Title 21, Food and Drugs. EFFECTIVE DATE OF 1986 AMENDMENT Pub. L. 99–660, title I, § 105(b), 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 en- actment of this Act [Nov. 14, 1986].’’ Amendment by section 315 of Pub. L. 99–660 effective Dec. 22, 1987, see section 323 of Pub. L. 99–660, as amend- ed, set out as an Effective Date note under section 300aa–1 of this title. PRODUCTS PREVIOUSLY APPROVED UNDER THE FEDERAL FOOD, DRUG, AND COSMETIC ACT Pub. L. 111–148, title VII, § 7002(e), Mar. 23, 2010, 124 Stat. 817, as amended by Pub. 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 biologi- cal 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 prod- uct 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 sub- title [subtitle A (§§ 7001–7003) of title VII of Pub. 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 sub- mitted under section 505 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355) if there is another biologi- cal 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 appli- cation (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 bi- ological 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 (b) 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 re- view 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 appli- cable 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 pub- lished pursuant to section 505(j)(7) of the Federal Food, Drug, and Cosmetic Act, and the informa- tion 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 ‘‘(bb) 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 Cos- metic Act of an application described in clause (i), the Secretary shall remove from the list pub- lished 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 con- tain a patent certification or statement de- scribed in, as applicable, section 505(b)(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 re- lated requirements concerning any timely filed patent information listed pursuant to section 505(j)(7) of such Act. ‘‘(bb) DATE OF APPROVAL.—The earliest pos- sible date on which any pending application de- Page 467 TITLE 42—THE PUBLIC HEALTH AND WELFARE § 262 scribed in clause (i) may be approved shall be determined based on— ‘‘(AA) the last expiration date of any appli- cable 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 pur- suant to section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act and references any listed drug, the last applicable date deter- mined under subparagraph (A), (B), or (C) of section 505(c)(3) of such Act, or, if the applica- tion 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 subpara- graph shall be construed to affect section 351(k)(7)(D) of the Public Health Service Act. ‘‘(v) LISTING.—The Secretary may continue to re- view an application after March 23, 2020, pursuant to clause (i), and continue to identify any applica- ble listed drug pursuant to clause (ii) on the list published pursuant to section 505(j)(7) of the Fed- eral Food, Drug, and Cosmetic Act, even if such re- view or listing may reveal the existence of such ap- plication and the identity of any listed drug for which the investigations described in section 505(b)(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 subpara- graph shall be construed as authorizing the Sec- retary to disclose any other information that is a trade secret or confidential information described in section 552(b)(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 Serv- ice Act (42 U.S.C. 262) (as amended by this Act).’’ COSTS OF REVIEWING BIOSIMILAR BIOLOGICAL PRODUCT APPLICATIONS Pub. 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 ‘‘(bb) the ratio of the costs of reviewing applica- tions 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 ap- plications under such section 351(a). ‘‘(ii) ALTERATION OF USER FEE.—If the audit per- formed under clause (i) indicates that the ratios com- pared 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 re- quirements prescribed by the Comptroller General of the United States under section 3511 of title 31, United State Code, to ensure the validity of any po- tential variability.’’ LICENSING OF ORPHAN PRODUCTS Pub. L. 111–148, title VII, § 7002(h), Mar. 23, 2010, 124 Stat. 821, provided that: ‘‘If a reference product, as de- fined in section 351 of the Public Health Service Act (42 U.S.C. 262) (as amended by this Act) has been des- ignated under section 526 of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 360bb) 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 Sec- retary [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 AMENDMENT Pub. 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 Pub. L. 111–148, see Short Title of 2010 Amendment note under section 201 of this title]. ‘‘(b) 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 AGENTS Pub. L. 104–132, title V, § 511, Apr. 24, 1996, 110 Stat. 1284, as amended by Pub. 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 do- mestic or international terrorism or for other crimi- nal purposes; ‘‘(3) the transfer and possession of potentially haz- ardous biological agents should be regulated to pro- tect 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 pur- poses. ‘‘(b) 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 FUNCTIONS Functions of Public Health Service, Surgeon General of Public Health Service, and all other officers and em- Page 468 TITLE 42—THE PUBLIC HEALTH AND WELFARE § 262a ployees 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 Secu- rity Administrator to Secretary of Health, Education, and Welfare and all agencies of Federal Security Agen- cy 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. § 262a. Enhanced control of dangerous biological agents and toxins (a) Regulatory control of certain biological agents and toxins (1) List of biological agents and toxins (A) In general The Secretary shall by regulation estab- lish and maintain a list of each biological agent and each toxin that has the potential to pose a severe threat to public health and safety. (B) Criteria In determining whether to include an agent or toxin on the list under subpara- graph (A), the Secretary shall— (i) consider— (I) the effect on human health of expo- sure to the agent or toxin; (II) the degree of contagiousness of the agent or toxin and the methods by which the agent or toxin is transferred to hu- mans; (III) the availability and effectiveness of pharmacotherapies and immuniza- tions to treat and prevent any illness re- sulting from infection by the agent or toxin; and (IV) any other criteria, including the needs of children and other vulnerable populations, that the Secretary con- siders appropriate; and (ii) consult with appropriate Federal de- partments and agencies and with scientific experts representing appropriate profes- sional groups, including groups with pedi- atric expertise. (2) Biennial review The Secretary shall review and republish the list under paragraph (1) biennially, or more often as needed, and shall by regulation revise the list as necessary in accordance with such paragraph. (b) Regulation of transfers of listed agents and toxins The Secretary shall by regulation provide for— (1) the establishment and enforcement of safety procedures for the transfer of listed agents and toxins, including measures to en- sure— (A) proper training, including with respect to notification requirements under this sec- tion, of— (i) individuals who are involved in the handling and use of such agents and tox- ins, including appropriate skills to handle such agents and toxins; (ii) individuals whose responsibilities routinely place them in close proximity to laboratory facilities in which such agents and toxins are being transferred, pos- sessed, or used; and (iii) individuals who perform administra- tive or oversight functions of the facility related to the transfer, possession, or use of such agents and toxins on behalf of reg- istered persons; (B) proper laboratory facilities to contain and dispose of such agents and toxins; (2) the establishment and enforcement of safeguard and security measures to prevent access to such agents and toxins for use in do- mestic or international terrorism or for any other criminal purpose; (3) the establishment of procedures to pro- tect the public safety in the event of a trans- fer or potential transfer of such an agent or toxin in violation of the safety procedures es- tablished under paragraph (1) or the safeguard and security measures established under para- graph (2); and (4) appropriate availability of biological agents and toxins for research, education, and other legitimate purposes. (c) Possession and use of listed agents and toxins The Secretary shall by regulation provide for the establishment and enforcement of standards and procedures governing the possession and use of listed agents and toxins, including the provi- sions described in paragraphs (1) through (4) of subsection (b), in order to protect the public health and safety. (d) Registration; identification; database (1) Registration Regulations under subsections (b) and (c) shall require registration with the Secretary of the possession, use, and transfer of listed agents and toxins, and shall include provisions to ensure that persons seeking to register under such regulations have a lawful purpose to possess, use, or transfer such agents and toxins, including provisions in accordance with subsection (e)(6). (2) Identification; database Regulations under subsections (b) and (c) shall require that registration include (if available to the person registering) informa- tion regarding the characterization of listed agents and toxins to facilitate their identifica- tion, including their source. The Secretary shall maintain a national database that in- cludes the names and locations of registered persons, the listed agents and toxins such per- sons are possessing, using, or transferring, and information regarding the characterization of such agents and toxins. (e) Safeguard and security requirements for reg- istered persons (1) In general Regulations under subsections (b) and (c) shall include appropriate safeguard and secu-