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 non-toxic 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.
Biosimilar proponents also supported looking to the European Medicines Agency for data. Biosimilar proponents advocated strongly
for approval standards that allow reliance on data comparing their products to foreign-licensed products, with little to no
bridging data required. Innovators opposed this reliance, arguing that potential differences between the foreign-licensed
product and the US-licensed reference product, even if based simply on different manufacturing sites, should limit any reliance
on foreign data and require significant bridging data.
Each of the above issues presents an area in which any biologics company—whether an innovator or biosimilar proponent—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 if it succeeds in lobbying for its position early and often.
At least initially, FDA is likely to adopt a product-specific model, with requirements varying from product-to-product. The
companies that will be successful in launching the first biosimilar products will be those who advocate effectively in relation
to FDA's requirements. Whatever FDA ultimately comes up with, we can certainly expect to see numerous disputes and likely
court actions in relation to FDA's approval requirements for biosimilars.
Chad Landmon is a partner at Axinn, Veltrop & Harkrider LLP, where he chairs the firm's FDA Practice Group, tel. 860.275.8170 or 202.721.5415,
or by e-mail at email@example.com
. Elizabeth Retersdorf is an associate at Axinn, Veltrop & Harkrider LLP, tel. 860.275.8126, firstname.lastname@example.org
1. Approval Pathway for Biosimilar and Interchangeable Biological Products Public Meeting (FDA, Silver Spring, MD, Nov. 2–3,