42 U.S.C. § 262 (THE PUBLIC HEALTH AND WELFARE)
§ 262. Regulation of biological products
(a) Biologics license
(1) No person shall introduce or deliver for introduction into interstate commerce any biological 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 product contained in the package;
(ii) the name, address, and applicable license number of the manufacturer of the biological product; and
(iii) the expiration date of the biological product.
(2)
(A) The Secretary shall establish, by regulation, 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 application any assessments required under section 505B of the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 355c].
(C) The Secretary shall approve a biologics license application—
(i) on the basis of a demonstration that—
(I) the biological product that is the subject of the application is safe, pure, and potent; 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 facility 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 application 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 application complies with the requirements of subparagraph (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 Cosmetic Act.
(3) The Secretary shall prescribe requirements under which a biological product undergoing investigation shall be exempt from the requirements of paragraph (1).
(b) Falsely labeling or marking package or container; 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 falsify the label or mark.
(c) Inspection of establishment for propagation and preparation
Any officer, agent, or employee of the Department of Health and Human Services, authorized by the Secretary for the purpose, may during all reasonable hours enter and inspect any establishment for the propagation or manufacture and preparation of any biological product.
(d) Recall of product presenting imminent hazard; violations
(1) Upon a determination that a batch, lot, or other quantity of a product licensed under this 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 penalty under this paragraph shall, effective December 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 Consumer Price Index for the base quarter of the preceding year, adjusted to the nearest ⅒ 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 September 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 performance 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 exceeding one year, or by both such fine and imprisonment, 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 prevention, 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 organization 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 (except any chemically synthesized polypeptide), or analogous product, or arsphenamine or derivative of arsphenamine (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 “biosimilarity”, in reference to a biological product that is the subject of an application under subsection (k), means—
(A) that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components; and
(B) there are no clinically meaningful differences between the biological product and the reference product in terms of the safety, purity, and potency of the product.
(3) The term “interchangeable” or “interchangeability”, 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 subsection (a) against which a biological product is evaluated in an application submitted under subsection (k).
(j) Application of Federal Food, Drug, and Cosmetic 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 biological product subject to regulation under this section, except that a product for which a license has been approved under subsection (a) shall not be required to have an approved application 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 subsection shall include information demonstrating that—
(I) the biological product is biosimilar to a reference product based upon data derived from—
(aa) analytical studies that demonstrate that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components;
(bb) animal studies (including the assessment of toxicity); and
(cc) a clinical study or studies (including the assessment of immunogenicity and pharmacokinetics or pharmacodynamics) that are sufficient to demonstrate safety, purity, and potency in 1 or more appropriate conditions of use for which the reference product is licensed and intended to be used and for which licensure is sought for the biological product;
(II) the biological product and reference product utilize the same mechanism or mechanisms of action for the condition or conditions of use prescribed, recommended, or suggested in the proposed 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 biological product have been previously approved for the reference product;
(IV) the route of administration, the dosage form, and the strength of the biological 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 described in clause (i)(I) is unnecessary in an application submitted under this subsection.
(iii) Additional information
An application submitted under this subsection—
(I) shall include publicly-available information regarding the Secretary’s previous determination that the reference product is safe, pure, and potent; and
(II) may include any additional information in support of the application, including publicly-available information with respect to the reference product or another biological product.
(B) Interchangeability
An application (or a supplement to an application) submitted under this subsection may include information demonstrating that the biological product meets the standards described in paragraph (4).
(3) Evaluation by Secretary
Upon review of an application (or a supplement to an application) submitted under this subsection, the Secretary shall license the biological product under this subsection if—
(A) the Secretary determines that the information 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 interchangeable with the reference product; and
(B) the applicant (or other appropriate person) consents to the inspection of the facility that is the subject of the application, in accordance with subsection (c).
(4) Safety standards for determining interchangeability
Upon review of an application submitted under this subsection or any supplement to such application, the Secretary shall determine the biological product to be interchangeable with the reference product if the Secretary determines that the information submitted 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 administered more than once to an individual, the risk in terms of safety or diminished efficacy 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 alternation 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 subsection shall be reviewed by the division within the Food and Drug Administration that is responsible for the review and approval of the application under which the reference product is licensed.
(C) Risk evaluation and mitigation strategies
The authority of the Secretary with respect 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 licensed under subsection (a).
(6) Exclusivity for first interchangeable biological product
Upon review of an application submitted under this subsection relying on the same reference product for which a prior biological product has received a determination of interchangeability for any condition of use, the Secretary shall not make a determination under paragraph (4) that the second or subsequent biological product is interchangeable for any condition of use until the earlier of—
(A) 1 year after the first commercial marketing of the first interchangeable biosimilar 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 subsection (l)(6) against the applicant that submitted the application for the first approved interchangeable biosimilar biological product; or
(ii) the dismissal with or without prejudice of an action instituted under subsection (l)(6) against the applicant that submitted the application for the first approved interchangeable biosimilar biological product; or
(C)
(i) 42 months after approval of the first interchangeable biosimilar biological product if the applicant that submitted such application 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 product if the applicant that submitted such application 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.
(7) Exclusivity for reference product
(A) Effective date of biosimilar application approval
Approval of an application under this subsection may not be made effective by the Secretary until the date that is 12 years after the date on which the reference product 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 product that is the reference product; or
(ii) a subsequent application filed by the same sponsor or manufacturer of the biological product that is the reference product (or a licensor, predecessor in interest, or other related entity) for—
(I) a change (not including a modification 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 result in a change in safety, purity, or potency.
(8) Guidance documents
(A) In general
The Secretary may, after opportunity for public comment, issue guidance in accordance, 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 biological 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 proposed guidance issued under subparagraph (A) before issuing final guidance.
(ii) Input regarding most valuable guidance
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 consideration
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.
(D) Requirement for product class-specific guidance
If the Secretary issues product class-specific 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 described in paragraph (4).
(E) Certain product classes
(i) Guidance
The Secretary may indicate in a guidance document that the science and experience, 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 subsection 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 document under clause (i).
(iii) No effect on ability to deny license
Clause (i) shall not be construed to require 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.
(l) Patents
(1) Confidential access to subsection (k) application
(A) Application of paragraph
Unless otherwise agreed to by a person that submits an application under subsection (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 exchange of information described in this subsection.
(B) In general
(i) Provision of confidential information
When a subsection (k) applicant submits an application under subsection (k), such applicant shall provide to the persons described 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) applicant determines, in its sole discretion, to be appropriate (referred to in this subsection 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 engage, formally or informally, in patent prosecution relevant or related to the reference product.
(II) In-house counsel
One attorney that represents the reference product sponsor who is an employee of the reference product sponsor, provided that such attorney does not engage, 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 product and who has retained a right to assert the patent or participate in litigation concerning the patent may be provided the confidential information, provided that the representative informs the reference product sponsor and the subsection (k) applicant of his or her agreement to be subject to the confidentiality provisions set forth in this paragraph, including those under clause (ii).
(C) Limitation on disclosure
No person that receives confidential information pursuant to subparagraph (B) shall disclose any confidential information to any other person or entity, including the reference product sponsor employees, outside scientific consultants, or other outside counsel retained by the reference product sponsor, 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 determining, 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 biological 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 continue to be governed by the terms of this paragraph until such time as a court enters a protective order regarding the information. Upon entry of such order, the subsection (k) applicant may redesignate confidential information in accordance with the terms of that order. No confidential information 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 information, it will confirm destruction in writing to the subsection (k) applicant.
(G) Rule of construction
Nothing in this paragraph shall be construed—
(i) as an admission by the subsection (k) applicant regarding the validity, enforceability, 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 information in violation of this paragraph shall be deemed to cause the subsection (k) applicant 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 violation 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 sponsor.
(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 paragraph (2), the reference product sponsor shall provide to the subsection (k) applicant—
(i) a list of patents for which the reference 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 product, if a person not licensed by the reference product sponsor engaged 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; and
(ii) an identification of the patents on such list that the reference product sponsor would be prepared to license to the subsection (k) applicant.
(B) List and description by subsection (k) applicant
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 subsection (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 importing into the United States of the biological product that is the subject of the subsection (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 subsection (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 subsection (k) applicant that such patent is invalid, unenforceable, or will not be infringed 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 commercial marketing of the biological product before the date that such patent expires; and
(iii) shall provide to the reference product sponsor a response regarding each patent 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 factual and legal basis of the opinion of the reference 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 enforceability provided under subparagraph (B)(ii)(I).
(4) Patent resolution negotiations
(A) In general
After receipt by the subsection (k) applicant 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 action for patent infringement under paragraph (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 reference 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 subparagraph (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 sponsor, but in no case later than 5 days after the subsection (k) applicant notifies the reference product sponsor under subparagraph (A), the subsection (k) applicant and the reference product sponsor shall simultaneously exchange—
(I) the list of patents that the subsection (k) applicant believes should be the subject of an action for patent infringement under paragraph (6); and
(II) the list of patents, in accordance with clause (ii), that the reference product sponsor believes should be the subject 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 product sponsor under clause (i)(II) may not exceed the number of patents listed by the subsection (k) applicant under clause (i)(I).
(II) Exception
If a subsection (k) applicant does not list any patent under clause (i)(I), the reference product sponsor may list 1 patent under clause (i)(II).
(6) Immediate patent infringement action
(A) Action if agreement on patent list
If the subsection (k) applicant and the reference 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 described under this paragraph, the subsection (k) applicant shall provide the Secretary with notice and a copy of such complaint.
(ii) Publication by Secretary
The Secretary shall publish in the Federal Register notice of a complaint received 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 reasonably believes that, due to the issuance of such patent, 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 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 supplement 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 subsection (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 preliminary 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 subparagraph (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 decides the issue of patent validity, enforcement, 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 subsection (k) applicant under paragraph (3)(B); and
(ii) not included, as applicable, on—
(I) the list of patents described in paragraph (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 subparagraph (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 preliminary 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 product 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 declaration of infringement, validity, or enforceability 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 complete an action required of the subsection (k) applicant under paragraph (3)(B)(ii), paragraph (5), paragraph (6)(C)(i), paragraph (7), or paragraph (8)(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 infringement, validity, or enforceability of any patent included in the list described in paragraph (3)(A), including as provided under paragraph (7).
(C) Subsection (k) application not provided
If a subsection (k) applicant fails to provide the application and information required 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 infringement, validity, or enforceability of any patent 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 extension 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 extension 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 products
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 pediatric 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 accepted 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 biological 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 biological products
If the Secretary determines that information 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 timeframe for completing such studies), the holder 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 accepted 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 biological 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 referred 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 subsection (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 recommend controls under the Controlled Substances 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), references to the date of approval of such application, 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.)
heading: References in Text
text: The effective date of this paragraph, referred to in subsec. (d)(2), is the effective date of section 315 of Pub. 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.
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 360bb, 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 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.
heading: Amendments
text: 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), inserted “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 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). 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 subpar. (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 affecting 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, 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). Pub. 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). 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), 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). 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 subsec. (h) generally, revising and restating former provisions, which also related to exportation of partially processed biological products.
Subsec. (h)(1)(A). Pub. L. 104–134, § 2102(d)(2), substituted “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 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). Pub. L. 99–660, § 315, designated existing 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 “vaccine, 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 the Army, and the Surgeon General of the Navy, and approved by the Secretary” after “regulations” in first sentence.
heading: Effective Date of 2007 Amendment
text: 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.
heading: Effective Date of 2003 Amendment
text: 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.
heading: Effective Date of 1997 Amendment
text: 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.
heading: Effective Date of 1986 Amendment
text: 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 enactment 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 amended, set out as an Effective Date note under section 300aa–1 of this title.
heading: Transfer of Functions
text: Functions 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. Secretary of Health, Education, and Welfare redesignated Secretary of Health and Human Services by section 509(b) of Pub. L. 96–88 which is classified to section 3508(b) of Title 20, Education.
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. Secretary and Department of Health, Education, and Welfare redesignated Secretary and Department of Health and Human Services by section 509(b) of Pub. L. 96–88 which is classified to section 3508(b) of Title 20.
heading: Products Previously Approved Under the Federal Food, Drug, and Cosmetic Act
text: Pub. L. 111–148, title VII, § 7002(e), Mar. 23, 2010, 124 Stat. 817, 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 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 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.—
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.
“(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).”
heading: Costs of Reviewing Biosimilar Biological Product Applications
text: 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 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.”
heading: Licensing of Orphan Products
text: Pub. 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. 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 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.”
heading: Savings Generated by 2010 Amendment
text: 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.”
heading: Enhanced Penalties and Control of Biological Agents
text: 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 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.
“(b) Criminal Enforcement.—
[Amended sections 175, 177, and 178 of Title 18, Crimes and Criminal Procedure.]
“(c) Terrorism.—
[Amended section 2332a of Title 18.]”