SILVER SPRING, Md.—Biosimilars are biological products that, according to the U.S. Food and Drug Administration (FDA), are “highly similar to and [have] no clinically meaningful differences from an existing FDA-approved reference product.” Of key interest for companies pursuing the development of biosimilar products is how to have their product determined to be interchangeable with the original reference product. On May 10, the FDA finalized its guidance to clarify what steps developers will need to take for their biosimilars to be deemed interchangeable.
Interchangeable biologics, as noted in a statement by FDA Acting Commissioner of Food and Drugs Dr. Norman E. Sharpless, are compounds “which may be substituted without the involvement of the prescriber, similar to how generic drugs are routinely substituted for brand name drugs when they are prescribed for patients.”
Thus far, the FDA has not approved any interchangeable biosimilars, and Zachary Brennan of the Regulatory Affairs Professionals Society notes that at present, Boehringer Ingelheim is the only company pursuing approval for an interchangeable. Boehringer Ingelheim has announced the initiation of an interchangeability study for its biosimilar for AbbVie’s adalimumab, also known as Humira.
As noted in a piece by Locke Lord LLP, “This new FDA Guidance provides important considerations for biosimilar applicants desiring to prove that a biosimilar product satisfies the requirements for receiving an interchangeability designation under Section 351(k)(4)(A)—that the applied for biologic product is:
- “biosimilar to the reference product;”
- “can be expected to produce the same clinical result as the reference product in any given patient;”
- and “for a biosimilar 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.”
This final guidance comes after a comment period and consideration of the issues that commenters pointed out. Compared to the original draft, the final guidance sought to further clarify the guidelines for determining interchangeability and eliminated two appendices regarding comparative use human factors studies, according to Brennan. The FDA also amended a requirement in the draft that dictated that companies had to use U.S.-licensed reference products in the switching studies.
Ronny Gal, a Bernstein biotech analyst, explained in a note to investors that “The main added requirement is a two-arm switching trial where all patients start on the reference product. In one arm, the patients will remain on the reference product throughout. On the other, they will switch back and forth twice, ending on the biosimilar product. Critically, the main comparison is on PK/PD markers, not efficacy markers (which FDA considers less sensitive). This will materially lower costs of doing these trials.”
While biosimilars in any indication are expected to help drive competition and drop drug prices, Sharpless noted that in particular, this final guidance “will help enable biosimilar or interchangeable insulin products to come to market in the future. There are currently no approved insulin products that can be substituted at the pharmacy level. But, under the BPCI Act, on March 23, 2020, insulin and other biological products that were approved as drugs under the Federal Food, Drug, and Cosmetic Act will be deemed biological products licensed and regulated under the PHS Act … An interchangeable insulin product may be substituted at the pharmacy, potentially leading to increased access and lower costs for patients.”
“[The Association for Accessible Medicines] and the Biosimilars Council applauds the FDA’s timely guidance on interchangeability for biosimilars, particularly its streamlined data and study design requirements that allow flexibility and the use of global comparator products to support applications. While the interchangeability designation does not confer any additional quality or safety attributes for FDA-approved biosimilars, we look forward to continue working with the agency to bring biosimilar medicines to America’s patients,” said Christine Simmon, executive director of the Biosimilars Council.