If Everyone’s Unhappy, Maybe You’re Doing Something Right… Comment Period on FDA’s Biosimilar Interchangeability Guidance Closes

By Sara W. Koblitz

The comment period on FDA’s Draft Guidance Considerations in Demonstrating Interchangeability With a Reference Product recently closed (Docket No. FDA-2017-D-0154), and it seems like everyone has something to say about the guidance. With over 50 comments submitted, some very technical in nature, FDA has some deep reading to do before finalizing anything. Commenters ranged from biologics and biosimilar manufacturers to third-party payers and trade associations.

Most commenters addressed the same points: the distinction between interchangeability and biosimilar, switching studies, use of foreign reference products, and the necessity of demonstrating interchangeability in all indications or uses and in all presentations. Questions are raised throughout the comments about what interchangeability actually means: is it a higher standard or just an additional data requirement? Is it therapeutic equivalence? And everyone is nervous about whether FDA will use labeling or nonproprietary naming or something totally new to indicate that a biosimilar is interchangeable. The commenters were also torn on the use of foreign reference products – mostly breaking down into a cost compared to safety argument.

Interestingly, almost all of the comments complimented FDA on its “flexible approach” to interchangeability, but proceeded to ask FDA for more precise testing requirements. Some want more human factor requirements while others want more in-depth switching study requirements. And comments really want FDA to lay out its plan for post-marketing changes to innovators after findings of interchangeability.

A lot of these questions are familiar to commenters, as they echo the questions that have arisen during the rocky implementation of the Hatch-Waxman Act and the abbreviated new drug pathway. Questions about whether interchangeability needs to apply to all conditions of use seem like they are a direct response to the common practice of skinny-labeled generics. And questions about exclusivity when multiple applications for interchangeability are submitted and ready for approval on the same day smacks of post-MMA questions that have taken FDA years to address. There is a lot of overlap in the biologic and drug industry, so a lot of these players have been burned before. Hence, the push for clarity, I presume.

It’s clear that FDA is not going to be able to please everyone with its interchangeable procedures. With so many commenters asking for diametrically opposed standards, there will be some tough decisions to make. And as we have seen in the Hatch-Waxman context, the trade-off between innovation and access is complicated. The one thing that all of the commenters have made pretty clear though is that they want FDA to take action and give some clear direction to manufacturers here. With the plain language of the BPCIA already subject to multiple interpretations, industry is really relying on FDA for some semblance of clarity here. As the Rolling Stones so eloquently said “you can’t always get what you want, but if you try sometimes, well you just might find, you get what need.” Maybe these comments will push FDA to give industry the clarity it needs, but one can only hope.