FDA officials discuss biosimilar inspections, BsUFA enhancements

A US Food and Drug Administration (FDA) official said that sites making biosimilars will be inspected in person, as opposed to virtual methods, as these products are relatively new and involve novel manufacturing processes. She also noted that the facilities making these products are generally new to biosimilar manufacturing.

Jacqueline Corrigan-Curay, principal deputy center director for FDA’s Center for Drug Evaluation and Research (CDER), made the remarks at the Association for Accessible Medicines’ (AAM) GRx+Biosim conference in Bethesda, MD on Monday.

In the biosimilar preapproval space, the agency continues to see “inspection challenges” at sites with prior inspectional and marketing histories that are seeking their first approval of a biologics license application (BLA), according to Corrigan-Curay and other officials who spoke at the event.

The officials also discussed some of the major enhancement in reviewing biosimilars present in the third iteration of its Biosimilar User Fee Amendments (BsUFA III) program, which will run from FY 2023-2027. They also discussed some of the ongoing research in the biosimilar field and provided an update on upcoming guidances to look for affecting the industry.

Officials noted slow but steady uptake in biosimilar approvals and touted the cost savings biosimilars provide. Corrigan-Curay said that as of November 2022, FDA has approved 39 biosimilars, 23 of which are currently marketed.

Of the 39 approvals, three are interchangeable biosimilars: Mylan’s Semglee (insulin glargine-yfgn), approved in July 2021; Boehringer Ingelheim’s Cyltezo (adalimumab-adbm), approved in September 2021; and Coherus Biosciences’ Cimeril (ranibizumab-eqrn), approved in August 2022. She said consumers saved $7 billion in 2021 by using biosimilars.

She also observed that BsUFA is “still a relatively new program” compared to PDUFA, which has been around for three decades.

Biosimilar inspections less amenable to virtual audits

Because of the different nature of biosimilar manufacturing, the agency tends to conduct these inspections onsite.

Corrigan-Curay said there is a “lower rate of alternative facility assessment approaches” for biosimilar products, as “these facilities are generally new to biotechnology products or processes.”

These products pose risks that are unique to biological products, such as using new cell lines, and firms may have limited experience with mammalian cell cultures or with novel manufacturing processes.

On the preapproval side, the agency “continues to see inspection challenges with sites with prior inspections and marketing history that are seeking first BLA approval.” These issues sometimes occur despite repeat inspections.

“We encourage industry to focus their efforts on understanding FDA expectations for biologics manufacturing and increasing [their] quality of operations to support biologics approvals,” Corrigan-Curay said.

Timetable for releasing guidances

Corrigan-Curay discussed the agency’s timetable for releasing guidance documents related to the biosimilar program. FDA plans to publish guidance on the use of alternative tools to assess manufacturing facilities named in pending applications by September 2023. This pledge was made in the BsUFA III commitment letter. (RELATED: BsUFA III commitment letter details FDA, industry goals for biosimilars program, Regulatory Focus 21 September 2021)

The agency is planning to update its biosimilar labeling guidance to include interchangeable products and is scheduled to be released by 30 September 2023. It also plans to issue a guidance on formal meetings with industry by 30 September 2023.

New research discussed

FDA also aims to spur the development of biosimilar drugs by sponsoring research, and it recently awarded grants to the United States Pharmacopeia (USP) to study the performance of multi-attribute methods (MAS) with traditional quality control (QC) methods in evaluating the product quality attributes of adalimumab and etanercept.

A second grant was awarded to the National Institute for Pharmaceutical Technology and Education to evaluate the comparability of biosimilar drug products in lyophilized and liquid formulations. A third grant was awarded to the University of Michigan to conduct research to study multiple biosimilar and innovator pairs and evaluate technical and regulatory hurdles.

Funding for this research was made available under the regulatory science pilot for biosimilar under the BsUFA III program via a $5 million funding opportunity announced in March. (RELATED: FDA offers funding for biosimilar regulatory science pilot, Regulatory Focus 7 March 2022).

Major BsUFA enhancements

According to Sarah Yim, director of the FDA’s Office of Therapeutic Biologics and Biosimilars, one of the “biggest changes” in the BsUFA III enhancements was accommodating shorter timelines for reviewing labeling supplements. Another major change was the new focused Type 2a limited meetings.

Yim also described efforts being made by FDA in working with other agencies to implement policies potentially impacting biosimilars and interchangeable products. For example, the agency is meeting with the Center for Medicare and Medicaid Services (CMS) to work out policies under the Inflation Reduction Act. FDA is also working with the US Patent and Trademark Office (USPTO) in response to an Executive Order (EO 14036) on drug pricing.

The biosimilar marketplace is at an “inflection point” with “good progress” being made for products administered in the hospital setting, such as Medicare Part B drugs. It is still too early to predict the progress being made with respect to patient self-administered drugs through the Medicare Part D drugs. She added, however, that that 2023 could be a “big opportunity” for these products.

AAM GRx+Biosims meeting

FDA officials discuss biosimilar inspections, BsUFA enhancements

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