Can the new FDA guidance on biosimilarity expedite development and approval?
Part 1 of a 2-part feature on the nuances of biosimilarity
Since the approval of Zarxio in March, the biosimilars race has been heating up. But one major challenge for all contenders has been a lack of clarity regarding the approval pathway. And new regulations published by the FDA this week promise to change the rules once again, potentially making it easier for all participants.
It is widely believed that generic small-molecule drugs and biosimilars are subject to the same scientific and regulatory considerations with just a few tweaks.
However, there are significant differences between generics and biosimilars. Under Hatch-Waxman, approval of generic, small-molecule drugs require that manufacturers conduct bioequivalence studies in order to be considered therapeutically equivalent, as well as substitutable at the pharmacy level.
"Based on Hatch-Waxman, generic drugs have to demonstrate sameness in terms of having the same active ingredient, route of administration, dosage form, strength and intended use," explained Ralph Neas, President and CEO of the Generic Pharmaceutical Association (GPhA), in an interview with BioPharma Dive.
New guidance clarifies BPCIA
According to new guidance issued by the FDA on April 28, "Guidance for Industry - Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009," biosimilars may be formulated differently than the pioneer drug (reference biologic), however, in order to be approvable, they must be supported by data showing that these differences do not result in "meaningful differences" in safety, purity and potency.
This guidance also clarifies other ways in which a biosimilar product can be different from the reference biologic, yet still approvable as a biosimilar. For example, the FDA deems it acceptable for a biosimilar to have a different delivery device or container system. As long, of course, as there are no "clinically meaningful differences" as a result—and the route of administration must be the same.
In addition, according to the new guidance, a biosimilar product must be approved for some of the strengths for which the pioneer product is approved—but the biosimilar product does not have to be formulated or available in all of the original-product strengths.
Flexibility, costs and approvability
In light of the new guidance clarifying what makes a product biosimilar in the eyes of the FDA, some companies involved in biosimilar R&D may be able to decrease costs, while potentially expediting the approval process associated with biosimilar development, according to David Rosen, FDA Practice Group Leader, Co-Chair of Life Sciences Industry and former FDA staff member.
"The new Guidances provide developers of biosimilar products with a framework that provides an organized, systemic approach for the development of these types of products," said Rosen in an interview. "By providing the Guidances, the Companies can gain a better understanding of FDA’s expectations which can lead to more efficient and lower development costs."
The cost factor
According to the IMS, the cost of developing a biosimilar ranges from $100 million to $250 million, compared with the cost of developing a generic small-molecule drug, which ranges from $1 million to $4 million.
However, just as new guidance suggests, there may be built-in flexibility that could bring development costs down. "One way to reduce costs is by doing as few trials as possible," Kate Keeping, senior director of biosimilars research at Decision Resources Group, told BioPharma Dive. "One possibility would be to design a three-arm trial, comparing the biosimilar in development with a U.S. reference product, and an E.U. reference product."
In fact, the new guidance explicitly states that sponsors may rely on clinical data using a non-licensed product to support an indication of biosimilarity, though the guidance also stipulates that “analytical studies and at least one clinical PK study and, if appropriate, at least one PD study, intended to support a demonstration of biosimilarity for purposes of section 351(k) of the PHS Act must include an adequate comparison of the proposed biosimilar product directly with the U.S.-licensed reference product unless it can be scientifically justified that such a study is not needed.”
Pushing the limits
Keeping notes that some companies are pushing the envelope even further by trying to demonstrate that their molecules are so similar to the reference biologic that phase III trials are not needed. Clearly, the parameters surrounding biosimilar R&D, approval and marketing continue to be in flux, but the impact of the new guidance cannot be discounted, and bodes especially well for Amgen, Sandoz, and others actively involved in developing biosimilars.
Be sure to catch part 2 of this feature next week on BioPharma Dive.
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