The AAM GRx+Biosims meeting was in progress when word came down that, within minutes, a new guidance document would be released by the FDA to outline conditions under which comparative efficacy studies (CES) may not be required for biosimilar applications. The draft Guidance for Industry (here) is titled Scientific Considerations in Demonstrating Biosimilarity to a Reference Product: Updated Recommendations for Assessing the Need for Comparative Efficacy Studies. This is a big deal as the Agency has been talking about this issue for a few years. Based on review and approval of the more than eighty biosimilar products that have been approved to date and the European experience with biosimilars, the FDA will rely, in many cases, on comparative analytical assessment (CAA) to support approval for products that have been shown to be highly similar. In addition, there was a hint from some senior FDA presenters that switching studies for highly similar biosimilar products may soon not be required. Marty Makary, M.D., Commissioner of the FDA, also noted in his remarks that he believes there should be no distinction between biosimilar products once approved and they should be treated like generics for the purpose of substitution. I want to point out that, while it is new ground for the FDA to come out and say this in writing, it not new to many of the biosimilars that the FDA has approved over the past couple of years. There are hints that the FDA may be moving quickly to reverse its requirements for interchangeability studies as well, and the wind is whispering that another, companion guidance may be on the way! The FDA has been applying the principle expressed in the new guidance for highly similar biosimilar products, and the time has come for the Agency to recognize this fact in writing.
Getting back to the analytical sameness issue, this concept has even been applied to a few complex generic products. Enoxaparin and Glatiramer are two very complex injectable products. The FDA approved the generic versions as bioequivalent based on the same criteria that is posited for biosimilar products. The highly specific analytics developed over time showed that they were highly similar. The products also demonstrated bioequivalence (albeit through rigorous in vitro testing). The road to approval for generics of these two products was paved with intense analytical developmental work and development of complex mathematical simulations to demonstrate that the products were highly similar. And it took a long time. The Enoxaparin application took six years and three months while Glatiramer application took eight years and four months back and forth with the FDA to satisfy the Agency that the products were the same (highly similar) to their respective RLDs. Evolution of the biosimilar program and analytical capability over the years has brought the Agency to the same conclusion for biosimilars.
The perhaps the next guidance document that the FDA will issue will be on biosimilar interchangeability and perhaps it will be coupled with a revision of the Biologics Price Competition and Innovation Act (BPCIA) to amend its interchangeability language to better protect the FDA’s revised thinking on how it views interchangeability of biosimilars with their reference products.
