OTBB Director Discusses FDA's Roadmap for Biosimilars

Highlighting challenges and ongoing efforts, Sarah Yim, MD, director of the Office of Therapeutic Biologics and Biosimilars (OTBB) delivered a progress report on the FDA’s Biosimilars Action Plan (BAP) at the Association for Accessible Medicine (AAM) GRx+Biosims annual conference.

The BAP was created in 2018 to support biosimilar development by improving efficiency of the development and approval process; improving scientific and regulatory guidance; improving education about biosimilars for patients, clinicians, and payers; and improving the competitive environment by “reducing gaming of FDA requirements or other attempts to unfairly delay competition,” Yim said.

The FDA continues work to develop indices of critical quality attributes for biosimilars, identify pharmacodynamic (PD) biomarkers, and investigate in silico modeling, in which computers are used to model pharmacologic or physiologic processes. Each of these qualifies as a potential development tool, “but because of resource limitations related to [coronavirus disease 2019], we are not yet ready to release the first batch of biosimilar product recommendations. Hopefully, we’re close,” Yim said.

Setting the Exclusivity Clock

In 2014, the FDA released draft guidance to help biologics developers and other stakeholders to understand at what point the exclusivity protection clock begins to tick for a reference product. The guidance was also intended to help innovator companies know what information to provide the FDA to help the agency decide when product exclusivity begins. Six years later, that guidance is still in draft form, although progress continues, Yim said. “We’re still working on biologic product regulatory modernization and finalizing guidance on reference product exclusivity and post-approval manufacturing.”​

The FDA would like to make various improvements to improve biosimilar development, and these include optimizing review staff time, exploring PD markers and assays that can help ascertain biosimilarity between biosimilar candidates and reference products, providing product specific guidance, and partnering with international regulatory authorities to reduce redundant activities. “To take product development and review to the next level in efficiency, more will need to be done,” Yim said.

“We’ll need to improve the status of biosimilar-related knowledge management and expand its scope to ensure not only consistency but provide space for ideas regarding improvements in best practices to be easily known and shared,” she said.

Another area of focus that could lead to important gains for biosimilars is patient education and reduction of anticompetitive messaging, she said. This can be achieved, in part, “by figuring out how to best exploit the educational gold mine of information that’s already available from real world experience with biosimilars. More than a decade of experience is available for some biosimilars in Europe, and at least several years of information should be available for some of the US-approved biosimilars.”

Purple Book Achievement

Yim noted the FDA’s achievement in modernizing the Purple Book, which originally was a bare bones listing of FDA-licensed biological products and now is an expanded, searchable, online database.

Also, in 2019, the FDA published guidance on biosimilar interchangeability with reference products and on the design and evaluation of comparative analytical studies for determining biosimilarity.

“We’ve made significant strides in advancing educational resources and activities and have recently begun a 2-year curriculum development project,” Yim said. “We also plan to begin work this year on developing additional, wide-reach education forums.”

Yim also said the FDA and the Federal Trade Commission have made “significant progress” combating anticompetitive behaviors by innovator companies and others that seek to oppose the advancement of biosimilars.

“Moving forward, we will be looking toward identifying and expanding high value activities that could help take biosimilar and interchangeable product access to the next level in the 2020s,” she said.