Guidance for Industry on Biosimilars: Q & As Regarding Implementation of the BPCI Act of 2009: Background
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The BPCI Act was enacted as part of the Affordable Care Act on March 23, 2010. The BPCI Act creates an abbreviated licensure pathway for biological products shown to be biosimilar to, or interchangeable with, an FDA-licensed biological reference product. The objectives of the BPCI Act are conceptually similar to those of the Drug Price Competition and Patent Term Restoration Act of 1984 (Pub. L. 98–417) (commonly referred to as the “Hatch-Waxman Act”), which established abbreviated pathways for the approval of drug products under the Federal Food, Drug, and Cosmetic Act (FD&C Act).The implementation of an abbreviated licensure pathway for biological products can present challenges given the scientific and technical complexities that may be associated with the larger and typically more complex structure of biological products, as well as the processes by which such products are manufactured. Most biological products are produced in a living system such as a microorganism, or plant or animal cells, whereas small molecule drugs are typically manufactured through chemical synthesis.
Section 351(k) of the PHS Act (42 U.S.C. 262(k)), added by the BPCI Act, sets forth the requirements for an application for a proposed biosimilar product and an application or a supplement for a proposed interchangeable product. Section 351(i) defines biosimilarity to mean “that the biological product is highly similar to the reference product notwithstanding minor differences in clinically inactive components” and that “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” (see section 351(i)(2) of the PHS Act). A 351(k) application must contain, among other things, information demonstrating that the biological product is biosimilar to a reference product based upon data derived from analytical studies, animal studies, and a clinical study or studies, unless FDA determines, in its discretion, that certain studies are unnecessary in a 351(k) application (see section 351(k)(2) of the PHS Act). To meet the higher standard of “interchangeability,” an applicant must provide sufficient information to demonstrate biosimilarity, and also to demonstrate that the biological product can be expected to produce the same clinical result as the reference product in any given patient and, if the biological product is administered more than once to an individual, the risk in terms of safety or diminished efficacy of alternating or switching between the 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 (see section 351(k)(4) of the PHS Act). Interchangeable products may be substituted for the reference product by a pharmacist without the intervention of the prescribing healthcare provider (see section 351(i)(3) of the PHS Act).
The BPCI Act also includes, among other provisions:
- A 12-year exclusivity period from the date of first licensure of the reference product, during which approval of a 351(k) application referencing that product may not be made effective (see section 351(k)(7) of the PHS Act);
- A 4-year exclusivity period from the date of first licensure of the reference product, during which a 351(k) application referencing that product may not be submitted (see section 351(k)(7) of the PHS Act);
- An exclusivity period for the first biological product determined to be interchangeable with the reference product for any condition of use, during which a second or subsequent biological product may not be determined interchangeable with that reference product (see section 351(k)(6) of the PHS Act);
- An exclusivity period for certain biological products for which pediatric studies are conducted in accordance with a written request (see section 351(m) of the PHS Act);
- A transition provision for biological products that have been or will be approved under section 505 of the FD&C Act (21 U.S.C. 355) before March 23, 2020 (see section 7002(e) of the Affordable Care Act); and
- A provision stating that a 351(k) application for a biosimilar product contains a “new active ingredient” for purposes of the Pediatric Research Equity Act (PREA) (see section 505B(n) of the FD&C Act).
The BPCI Act also establishes procedures for identifying and resolving patent disputes involving applications submitted under section 351(k) of the PHS Act.
 See section 505(b)(2) and 505(j) of the FD&C Act (21 U.S.C. 355(b)(2) and 355(j)).