BIOSIMILARITY

Biosimilar proponents and innovators took similarly discordant stances when arguing about biosimilarity standards. Innovators argued for clinical trials for all indications with no surrogate endpoints. Innovators opposed extrapolating biosimilarity across indications (even with the same mechanism of action) and equivalence rather than noninferiority as the standard for efficacy. Innovators stressed that "product is process," and they argued that complexity of molecules, changes introduced during processing and purification and the risk of immunogenicity necessitate complete clinical trials for all biosimilars.

Biosimilar proponents argued against strict standards, asserting that current technologies for detecting structural differences obviate the need for long clinical trials for some biosimilars. In such instances, they asserted that abbreviated clinical trials could suffice. Others argued for concurrent animal and human trials for biosimilars with nontoxic reference products. Still others argued for abbreviated analysis of structure instead, as sameness in efficacy rather than structure is the ultimate goal. Biosimilar proponents also argued for the use of surrogate endpoints and single clinical studies in key sensitive indications to extrapolate to other indications with the same mechanism of action. Biosimilar proponents also relied on the concept of drift to argue that the "goalposts" for biosimilarity should be based on the variability of innovator products over time and across lots and batches. Most importantly, biosimilar proponents advocated for a case-by-case approach to approval, rather than product or even biosimilar-wide standards and rules.

The above issues present an area in which any biologics company should determine its standpoint and develop clear and cogent arguments for approval standards and implementation of the BPCI Act. The fact that FDA needs to develop a view on each issue shows the potential influence any company can have on the biologics landscape. At least initially, FDA is likely to adopt a product-specific model, with requirements varying from product-to-product. Whatever FDA ultimately comes up with, we can expect to see numerous disputes and likely court actions in relation to FDA's bisimilar approval requirements.

REFERENCE

1. Approval Pathway for Biosimilar and Interchangeable Biological Products Public Meeting (FDA, Silver Spring, MD, Nov. 2-3, 2010).