A biosimilar is a biological product that is highly similar to and has no clinically meaningful differences from an FDA-approved reference biological product. Biosimilar applicants have a number of choices to make on the path to a commercial biosimilar product. To start, the biosimilar applicant can either launch at risk or try to clear the patent rights controlled by the reference product sponsor (“RPS”) before launch. If a biosimilar applicant chooses to clear the RPS’s patent rights, it may (or may not) engage in a procedure called the “patent dance” and optionally participate in multiple waves of litigation, as set forth in the Biologics Price Competition and Innovation Act (“BPCIA”). This blog outlines the path to biosimilar approval and launch and explains some of the decisions that a biosimilar applicant must make along the way.
The discussion here focuses on one possible scenario (illustrated in the timeline below) in which a biosimilar applicant chooses to engage in the patent dance. In this example, the biosimilar applicant leaves patents on the table for a second wave of litigation. Each step of the timeline is explained in more detail below.
Steps 1–4: Reference Product is Approved and Patented
Just as a generic drug undergoes an abbreviated regulatory review process that references an approved “brand-name” drug, a biosimilar undergoes an abbreviated regulatory review process that references an approved “reference product” or “reference biological drug.” The discussion of a biosimilar’s lifecycle necessarily starts with the reference product—what happens during the approval and patenting process of a reference product impacts how and when a biosimilar is launched.
Step 1. A Reference Product Sponsor Makes and Tests a Biological Drug
Biologics are a diverse category of pharmaceutical products that are often produced or isolated from living sources, such as cells. When developing a biological drug, the RPS must perform clinical trials to show the drug is safe and effective.
Step 2. The Reference Product Sponsor Patents the Biological Drug
An RPS may seek patents directed to the biological drug, including patents covering drug composition, methods of manufacturing the drug, and methods of using the drug for treatment. Patents do not give the RPS an affirmative right to practice the patented invention, but do give the RPS the right to exclude others from making, selling, and offering to sell an infringing biosimilar in the United States—even if the FDA has approved the biosimilar.
Step 3. The Reference Product Sponsor Files a Section 351(a) Biologics License Application with the FDA
An RPS submits a Section 351(a)[1] Biologics License Application (“BLA”) to obtain FDA approval of its biological drug. 42 U.S.C. § 262(a). The RPS must submit to the FDA clinical and non-clinical study information showing that the drug is safe, pure, and potent. 21 C.F.R. § 601.2.
Step 4. The FDA Approves the Biological Drug
When the FDA approves a biological drug, it triggers an exclusivity period for that drug. Under the BPCIA, new biological drugs currently enjoy at least 12 years of market exclusivity. Until this exclusivity period expires, the FDA may not approve an application for a biosimilar version of that drug. 42 U.S.C. § 262(k)(7)(A). In addition, a biosimilar applicant may not submit a Section 351(k) BLA until 4 years after the FDA approves the reference biological drug. Id. § 262(k)(7)(B).
Steps 5–6: A Biosimilar is Developed and Submitted to the FDA
Step 5. The Biosimilar Applicant Makes and Tests a Biosimilar
A potential biosimilar applicant may begin making and testing a biosimilar drug even before a reference product’s exclusivity period expires.
Can the RPS sue a potential biosimilar applicant for developing a biosimilar? Generally no. The Patent Statute includes a safe harbor provision that protects a potential biosimilar applicant engaged in drug development activity from being sued for patent infringement, as long as the potential biosimilar applicant is performing otherwise infringing activities “solely for uses reasonably related to the development and submission of information” to the FDA. 35 U.S.C. § 271(e)(1). However, certain pre-launch activities, such as stockpiling commercial inventory, might not be protected by the safe harbor provision. See Amgen Inc. v. Hospira, Inc., 944 F.3d 1327, 1339–40 (Fed. Cir. 2019).
Step 6. The Biosimilar Applicant Files a Section 351(k) Biologics License Application with the FDA
Under the BPCIA, a biosimilar applicant may rely on the reference product’s safety and efficacy data to seek biosimilar approval with the FDA. Specifically, a biosimilar applicant submits a Section 351(k) BLA to seek FDA approval of its biosimilar drug. 42 U.S.C. § 262(k). The biosimilar applicant may file a Section 351(k) BLA four years (or more) after the FDA approves the reference product. Id. § 262(k)(7)(B).
Under the BPCIA, the biosimilar applicant must show that its product is highly similar to, and has no clinically meaningful differences from, the FDA-approved reference product. Id. § 262(i)(2); see id. § 262(k)(2)(A)(i)(I). The applicant need not submit the same safety and efficacy data found in a Section 351(a) BLA—instead, the biosimilar applicant submits data such as biosimilarity studies, toxicity studies, and condition of use studies. Id. § 262(k)(2)(A)(i)(I). In addition, the biosimilar applicant must show:
- that its product “utilize[s] 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”;
- that “the condition or conditions of use prescribed, recommended, or suggested in the labeling proposed for the [biosimilar] have been previously approved for the reference product”;
- that “the route of administration, the dosage form, and the strength of the [biosimilar] are the same as those of the reference product”; and
- that “the facility in which the [biosimilar] is manufactured, processed, packed, or held meets standards designed to assure that the [biosimilar] continues to be safe, pure, and potent.”
Id. § 262(k)(2)(A)(i)(II)–(V).
The biosimilar applicant may also apply for interchangeable status by showing that its product is “expected to produce the same clinical result as [its] reference product in any given patient,” and if the product will be administered more than once, it will not increase safety risks or decrease...
