Because No One is Immune to the Law
September 09, 2020 - United States, FDA, Biotech, Healthcare, Pharma, Intellectual Property, Cell + Gene Therapy

Pediatric Exclusivity for Biologics

A New Year's Gift for Patent Applicants?

The U.S. Food and Drug Administration’s six-month pediatric exclusivity rules that apply to drugs also largely apply to biologics (albeit with certain distinctions), which may become a valuable life cycle management strategy for biopharmaceutical companies (hereinafter “Sponsors”) in addition to patent exclusionary rights.

At the outset, it is important to recognize that the patent term of a biologic product is distinct from the FDA’s regulatory market exclusivity period for the same product; these two public policies are governed by entirely separate laws and regulations. Patent term and the FDA’s exclusivity programs run concurrently and in parallel. As such, pediatric exclusivities (or other FDA exclusivities) do not formally extend the term of any patent rights. However, both of these legal frameworks have the same effect of extending the biologic product’s market monopoly and preventing competitors from introducing biosimilar products into the marketplace. In the event that certain patents rights are invalidated prior to the expiration of the full patent term, FDA exclusivities provide an additional safeguard against competitors seeking to enter the market. Thus, Sponsors should consider using both patent rights and FDA exclusivities to recoup research and development investments.

Biologics are eligible to participate in the FDA’s pediatric exclusivity program.[i] Under Section 351 of the Public Health Service Act, in order to receive six months of pediatric exclusivity in addition to the 12-year exclusivity period granted under the Biologics Price Competition and Innovation Act,[ii] the FDA must issue a Written Request for the Sponsor to conduct specific pediatric studies for a given biological product.[iii] The Sponsor may choose (but is not required) to conduct the pediatric studies outlined in the Written Request, at its own expense, in exchange for an additional six months of exclusivity for its biological product. The exclusivity grant is based on whether the applicant complied with the terms of the Written Request and is not conditioned on approval of a pediatric indication.[iv] Any unauthorized deviation from the Written Request may result in non-compliance and can jeopardize the Sponsor’s ability to earn pediatric exclusivity. The FDA maintains discretion over issuing Written Requests for pediatric studies, and thereby controls the Sponsor’s ability to obtain multiple pediatric exclusivities. The FDA may issue multiple Written Requests, which are each eligible for an additional six-month exclusivity period, provided that the Sponsor appropriately complies with each Written Request.[v] Examples of previous Written Requests for biologics can be found on the FDA’s List of Determinations Including Written Request web page (see, e.g., ipilimumab and tocilizumab). It appears that the FDA has not yet issued multiple Written Requests for a single biologic. In fact, it appears rare for the FDA to issue multiple Written Requests for the same drug.


In a previous Guidance, the FDA explained that a Sponsor of a new drug under Section 505A of the Federal Food, Drug, and Cosmetic Act (FDCA) may submit a detailed proposal to the FDA for a Written Request, which is equally applicable to the holder of an approved Biologics License Application under Section 351 of the Public Health Service Act.[vi] The proposal for a Written Request should substantially follow the template that the FDA has previously used for a Written Request (see, e.g., ipilimumab and tocilizumab). The proposal should contain sufficient information to execute the studies such as the objective of the study, trial design, number and kinds of patients and other relevant patient characteristics, inclusion and exclusion criteria for the study, drug dosing for the treatment arm, statistical information for analyzing the results, and other pertinent information.[vii] The FDA will then evaluate the proposal and decide whether to issue a formal Written Request based on the information submitted. In addition, the FDA maintains a FAQ web page dedicated to qualifying for pediatric exclusivity under Section 505A of the FDCA. To qualify for pediatric exclusivity, the pediatric studies conducted to satisfy the requirements of the Pediatric Research Equity Act (PREA) must also satisfy all of the requirements for pediatric exclusivity under Section 505A of the FDCA.[viii]

Fulfilling the Written Request for pediatric exclusivity is separate from meeting the Sponsor’s PREA obligations or any other requirements to perform phase 4 post-market surveillance studies.[ix] PREA requires that all applications for new active ingredients, new indications, new dosage forms, new dosing regimens, or new routes of administration contain an assessment of the safety and effectiveness of the product for the claimed indication(s) in pediatric patients, unless this requirement is waived, deferred, or inapplicable.[x] In terms of scope, PREA is more limited and requires a pediatric assessment of those indications included in the pending biologics license application (BLA), which addresses the safety and effectiveness of the claimed indications with respect to the drug or biological product. The FDA’s authority to issue a Written Request for pediatric exclusivity extends to the use of an active moiety for all indications that occur in the pediatric population, regardless of whether the indications have been previously approved in adults or approval for those indications is being sought in adults.[xi] The FDA has previously advised that an applicant seeking to qualify for pediatric exclusivity should obtain a Written Request for studies from FDA before submitting the pediatric studies to satisfy PREA.[xii] 


[i] See 42 U.S.C. § 262(m) (Section 351 of the Public Health Service Act). Notice that under § 262(m)(1), the rules for submitting pediatric studies are the same for both drugs and biologics under § 505A of the Federal Food, Drug, and Cosmetic Act (FDCA) (codified as 21 U.S.C. § 355a). More precisely, § 262(m)(1) carves out the exclusivity benefits in §§ 505A (b)-(c) for drugs, which are then re-inserted as §§ 262(m)(2)-(3) as applicable to biologics given the different exclusivity periods.

[ii] See 42 U.S.C. § 262(k). 

[iii] See 42 U.S.C. § 262(m) (Section 351 of the Public Health Service Act). Under both §§ 262(m)(2) and m(3), the Secretary makes a written request to the applicant to perform additional pediatric studies, and the applicant accepts that request (at its own expense), the applicant is rewarded another six months of exclusivity. Note that under 21 U.S.C § 355a(h) (carried over into 42 U.S.C. § 262(m)(1) for biologics), pediatric exclusivity shall only be granted for a study or studies that are the subject of a Written Request from the FDA and prior to nine months from expiration.

[iv] See

[v] See Guidance for Industry, Qualifying for Pediatric Exclusivity Under Section 505(A) of the Federal Food, Drug, and Cosmetic Act (June 1998, revised Sept. 1999). 

[vi] See id. (listing specific requirements for a Proposed Pediatric Study Request).

[vii] See id.

[viii] See Sections 505A(d) and 505A(h) of the FDCA (codified as 21 U.S.C. §§ 355a(d) and (h), respectively).

[ix] See Section 505B of the FDCA (codified as 21 U.S.C. § 355c). PREA also authorized the FDA to waive the required assessments when the drug or biological product (1) does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients and (2) is not likely to be used in a substantial number of pediatric patients.

[x] See id.

[xi] See Section 505A(a) of the FDCA, codified as 21 U.S.C. § 355a(b)(1).

[xii] See Draft Guidance for Industry: How to Comply with the Pediatric Research Equity Act (Sept. 2005).