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

submitted 82 years ago by ch. 373 to r/title-42-THE-PUBLIC-HEALTH-AND-WELFARE · 6,848 words · no verdicts yet

in plain englishAI-generated · not legal advice

This law requires biological products, like vaccines and blood, to get an FDA license. It sets separate rules for biosimilar and interchangeable products, including patent-dispute procedures. It also covers labeling, inspections, recalls, penalties, and exclusivity periods for original and pediatric research.

(a) Biologics license. No one may ship a biological product across state lines, or bring it in from outside the state, unless it has a "biologics license" from the FDA and each package is clearly marked with the product's proper name, the maker's name, address, and license number, and the expiration date. The Secretary of Health and Human Services must write rules for approving, suspending, and revoking these licenses. Anyone applying for a license must also submit any required pediatric-study assessments. The Secretary must approve a license application if the product is shown to be "safe, pure, and potent," the facility that makes it meets standards designed to keep it that way, and the applicant agrees to let the facility be inspected. Certain Food, Drug, and Cosmetic Act rules on postmarket studies, labeling, and risk management plans also apply to license applicants. In limited cases, the Secretary may approve a supplemental application for a new use of an already-approved drug using "qualified data summaries" instead of full new studies, if the summaries meet the standard set for approved drugs. The Secretary must also create rules exempting biological products that are still being investigated (not yet on the market) from the licensing requirement. (b) False labeling. No one may falsely label or mark a biological product's package, or alter a label to make it false. (c) Inspections. HHS officers, agents, or employees who are authorized to do so may enter and inspect, during all reasonable hours, any facility that makes or prepares biological products. (d) Recalls and violations. If the Secretary decides that a batch, lot, or other quantity of a licensed product is an immediate or serious danger to public health, the Secretary must order it recalled right away, following the hearing procedures in Title 5, Section 554. Anyone who violates a recall order can be fined up to $100,000 for each day the violation continues. That $100,000 cap goes up every December 1st based on the change in the Consumer Price Index from one year to the next. (e) Interference with officers. No one may interfere with an officer, agent, or employee of the Public Health Service while they are doing their job under this section or its regulations. (f) Penalties. Anyone who violates, or helps someone else violate, any part of this section can be fined up to $500, imprisoned up to one year, or both, at the court's discretion. (g) Relation to other laws. Nothing in this chapter changes, weakens, or replaces the Federal Food, Drug, and Cosmetic Act. (h) Exporting partly finished products. A partly processed biological product can be exported freely — without the restrictions in this chapter or the Food, Drug, and Cosmetic Act — if it is not yet ready to treat or prevent disease, is not meant to be sold in the United States, and will be finished into its final form outside the United States. This only applies if the product is made under current good manufacturing practices (or certified international standards) and meets a specific Food, Drug, and Cosmetic Act export requirement. (i) Definitions. A "biological product" means things like a virus, therapeutic serum, toxin, antitoxin, vaccine, blood or blood parts, an allergenic product, a protein, arsphenamine (or a similar arsenic compound), or a similar product used to prevent, treat, or cure a human disease or condition. A product is "biosimilar" to a reference product if it is highly similar to it (small differences in inactive ingredients are okay) and there are no clinically meaningful differences in safety, purity, or potency. A product is "interchangeable" if it meets the stricter standard in subsection (k)(4), meaning a pharmacist could substitute it for the reference product without asking the prescribing doctor. The "reference product" is the original licensed biological product that a biosimilar or interchangeable product is compared against. (j) How the FDCA applies. The Food, Drug, and Cosmetic Act, including its rules on postmarket studies, labeling, and risk management plans, applies to biological products too — except that a product already licensed under subsection (a) doesn't also need separate FDCA approval. (k) Licensing biosimilar or interchangeable products. Anyone may apply for a license under this subsection. The application must show, using analytical studies, a toxicity assessment, and clinical studies, that the product is biosimilar to a reference product; that it works the same way as the reference product (as far as that mechanism is known); that its approved uses were already approved for the reference product; that its route of use, dosage form, and strength match the reference product's; and that the manufacturing facility meets safety standards. The Secretary can decide that some of this biosimilarity evidence isn't needed. The application must also include public information about why the Secretary found the reference product safe, pure, and potent, and may include other supporting information. If the applicant wants the product declared "interchangeable," the application (or a later supplement) can include the extra proof required for that. The Secretary must license the product if the evidence shows it is biosimilar, or that it meets the interchangeability standard, and the applicant agrees to a facility inspection. To be found interchangeable, the evidence must show the product is biosimilar, can be expected to produce the same clinical result as the reference product in any given patient, and — for products given more than once — that switching between it and the reference product isn't riskier than just using the reference product alone. A few general rules apply: an application can compare a product to only one reference product; the same FDA division that reviewed the reference product must review the biosimilar; and the Secretary's risk management authority applies the same way it does to reference products. The first product found interchangeable with a given reference product gets an exclusivity period before a second interchangeable product for the same reference product can be approved — generally 1 year after the first one goes on sale, though this can shift to 18 months after certain patent lawsuits end (or are dismissed), or up to 42 months after approval if a lawsuit is still ongoing. Separately, the reference product itself is protected: a biosimilar application can't even be filed until 4 years after the reference product was first licensed, and can't be approved until 12 years after that licensing date. This 4-year/12-year protection doesn't apply to a supplement for the reference product itself, or to certain follow-on applications by the same maker that change the product's form, delivery, or structure without changing its safety, purity, or potency. Products "deemed" to be licensed under a 2009 transition law don't get this protection extended, though other related exclusivity periods still apply to them going forward. The Secretary may issue public guidance — after taking public comments — about how these biosimilar rules will be applied, including guidance specific to a class of products, and must set up a way for the public to suggest which guidance is most needed. Not issuing guidance doesn't block the Secretary from reviewing applications anyway. The Secretary may also say in guidance that current science doesn't yet support approving biosimilars for a certain product class (except recombinant proteins), though that doesn't force the Secretary to reject an application either. Finally, the Secretary must publish and keep updating (at least every 30 days) a public, searchable list of every licensed biological product, including its license date, application number, licensing and marketing status, patent information supplied by reference product sponsors, and any exclusivity periods still running. A product's license is taken off this list if it's revoked or suspended for safety, purity, or potency reasons, and the sponsor must tell the Secretary to remove it and have that removal published in the Federal Register. (l) Patent disputes ("the patent dance"). This subsection sets up a detailed, step-by-step process for resolving patent disputes between a biosimilar applicant (the "subsection (k) applicant") and the maker of the reference product (the "reference product sponsor"), unless they agree to handle things differently. First, the applicant must give certain designated outside or in-house lawyers (and, in some cases, a patent owner's representative) confidential access to its application and manufacturing information, under strict rules: that information can't be shared further without permission, can only be used to assess possible patent infringement, stays the property of the applicant, and any misuse is treated as causing harm serious enough to justify a court injunction. Within 20 days of the FDA accepting the application for review, the applicant must give the sponsor a copy of the application and manufacturing details. Then a series of exchanges happens on strict deadlines: within 60 days, the sponsor lists patents it believes could be infringed and says which ones it would license; within another 60 days, the applicant responds with its own possible patent list and, for each patent, either a detailed non-infringement/invalidity argument or a promise not to sell before the patent expires; within another 60 days, the sponsor responds in detail to those arguments. The two sides must then negotiate in good faith over which patents will actually be litigated. If they can't agree within 15 days, a fallback process kicks in: the applicant says how many patents it will list, then within 5 days both sides simultaneously exchange lists (the sponsor's list can't have more patents than the applicant's, unless the applicant listed none, in which case the sponsor may list one). Once a list is settled — either by agreement or through the fallback process — the sponsor must sue for patent infringement over each listed patent within 30 days, and must tell the FDA within 30 days after being served, after which the FDA publishes notice of the lawsuit. If the sponsor gets or licenses a new patent after its original list, it must add that patent within 30 days if it reasonably believes the patent could be infringed, and the same response process applies to it. The applicant must notify the sponsor at least 180 days before it starts selling the product commercially; after that notice, the sponsor may ask a court for a preliminary injunction covering any listed patent that wasn't part of the earlier lawsuit, and both sides must cooperate on the discovery needed for that injunction request. Generally, neither side can bring an early "declaratory judgment" lawsuit about a patent before the 180-day notice is given — except that if the applicant fails to complete its required steps in this process, only the sponsor may bring such a suit (and if the applicant never even shares its application at all, only the sponsor may sue over any patent covering the product). (m) Pediatric study exclusivity. Several rules from a similar Food, Drug, and Cosmetic Act pediatric-study section apply here the same way. If, before a biological product is first licensed, the Secretary decides that studying its use in children could help kids' health, and asks the maker in writing to do pediatric studies (with a deadline), and the maker agrees, completes the studies for each requested age group in time, and the results are accepted — then the product's exclusivity periods described in subsection (k)(7) grow: 4 years becomes 4 years and 6 months, and 12 years becomes 12 years and 6 months. If the product is also designated for a rare disease, its 7-year exclusivity becomes 7 years and 6 months. The same extension applies to already-licensed products if the Secretary makes the same kind of request to the current license holder and the same conditions are met. But the Secretary can't grant this extension if the pediatric-study decision comes less than 9 months before the original exclusivity period would have ended anyway. (n) Products that also need drug-scheduling review. If the Secretary tells an applicant that a biological product will need a scientific and medical evaluation and possible controls under the Controlled Substances Act, the license approval doesn't take legal effect until the related drug-scheduling rule is issued. For this section, the product's "date of approval" is whichever comes later: the date the license itself is approved, or the date the drug-scheduling rule is issued.

the actual law source: uscode.house.gov ↗public domain

(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.

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, 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)

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 (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;

(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; and

(III)

may include information to show that the conditions of use prescribed, recommended, or suggested in the labeling proposed for the biological product have been previously approved for the reference 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.

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

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 interchangeability 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, 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 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).

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.

(D) Deemed licenses

(i) No additional exclusivity through deeming

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 Competition and Innovation Act of 2009 shall not be treated as having been first licensed under subsection (a) for purposes of subparagraphs (A) and (B).

(ii) Application of limitations on exclusivity

Subparagraph (C) shall apply with respect 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 Competition and Innovation Act of 2009.

(iii) Applicability

The exclusivity periods described in section 527, section 505A(b)(1)(A)(ii), and section 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 continue 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 Biologics Price Competition and Innovation Act of 2009.

(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.

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.

(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 searchable, electronic format—

(I)

a list of each biological product, by nonproprietary name (proper name), for which, as of December 27, 2020, a biologics 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 marketing application and the application number; and

(III)

with respect to each biological product described in subclause (I), the licensure status, and, as available, the marketing status.

(ii) Revisions

Every 30 days after the publication of the first list under clause (i), the Secretary 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 licensed under this section pursuant to section 7002(e)(4) of the Biologics Price Competition and Innovation Act of 2009.

(iii) Patent information

Not later than 30 days after a list of patents under subsection (l)(3)(A), or a supplement to such list under subsection (l)(7), has been provided by the reference product sponsor to the subsection (k) applicant respecting a biological product included on the list published under this subparagraph, the reference product sponsor shall provide such list of patents (or supplement thereto) and their corresponding expiry dates to the Secretary, and the Secretary shall, in revisions made under clause (ii), include such information for such biological product. Within 30 days of providing any subsequent or supplemental list of patents to any subsequent subsection (k) applicant under subsection (l)(3)(A) or (l)(7), the reference product sponsor shall update the information 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 exclusivity period under paragraph (6) or paragraph (7) for which the Secretary has determined such biological product to be eligible and that has not concluded.

(B) Revocation or suspension of license

If the license of a biological product is determined by the Secretary to have been revoked or suspended for safety, purity, or potency reasons, it may not be published in the list under subparagraph (A). If such revocation or suspension occurred after inclusion of such biological product in the list published under subparagraph (A), the reference product sponsor shall notify the Secretary that—

(i)

the biological product shall be immediately removed from such list for the same period as the revocation or suspension; and

(ii)

a notice of the removal shall be published in the Federal Register.

(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).

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).

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.

(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).

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).

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.

Source credit: (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.)

history & why it existsrecord from the source credit

1944Enacted · Act of July 1, 1944, ch. 373 · 58 Stat. 702
1958Amended · Pub. L. 85-881 · 72 Stat. 1704
1970Amended · Pub. L. 91-515 · 84 Stat. 1308
1979Amended · Pub. L. 96-88 · 93 Stat. 695
1986Amended · Pub. L. 99-660 · 100 Stat. 3751, 3783
1992Amended · Pub. L. 102-300 · 106 Stat. 240
1996Amended · Pub. L. 104-134 · 110 Stat. 1321
1997Amended · Pub. L. 105-115 · 111 Stat. 2323, 2324
2003Amended · Pub. L. 108-155 · 117 Stat. 1941
2007Amended · Pub. L. 110-85 · 121 Stat. 939
2010Amended · Pub. L. 111-148 · 124 Stat. 804, 814, 819
2012Amended · Pub. L. 112-144 · 126 Stat. 1040
2015Amended · Pub. L. 114-89 · 129 Stat. 698
2016Amended · Pub. L. 114-255 · 130 Stat. 1100
2017Amended · Pub. L. 115-52 · 131 Stat. 1046
2019Amended · Pub. L. 116-94 · 133 Stat. 3127
2020Amended · Pub. L. 116-260 · 134 Stat. 2933, 2936
2022Amended · Pub. L. 117-328 · 136 Stat. 5820, 5822

A history note hasn’t been published yet. The record shows enactment by ch. 373 on 1944-07-01.

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