Alvotech’s Adalimumab BLA Tripped Up by FDA

Alvotech and Teva plan to launch ATV02, their high-concentration, citrate-free, interchangeable biosimilar version of Humira® in July 2023. However, the US Food and Drug Administration (FDA) issued the company a complete response letter this week, citing Alvotech’s manufacturing issues, which could delay those plans.

The FDA has been catching up on facility inspections (see also Biocon’s issue, below), after COVID-19 related delays.  According to Alvotech, its manufacturing facility in Reykjavik, Iceland, was visited in March 2022 by inspectors, and the review “noted certain deficiencies.” The complete response letter does not seem to cite any clinical issues with study data or comparability between AVT02 and the reference drug.

According to a company press release, Mark Levick, Chief Executive Officer of Alvotech, stated, “Alvotech looks forward to addressing the deficiencies outlined in the post-application action letter and continuing to work with the FDA to close out the facility inspection. We aim to satisfactorily address the issues before the [BsUFA] goal date for the interchangeable biosimilar BLA in December.”

Receiving an initial complete response letter (considered akin to a rejection letter) from the FDA is not unusual for biosimilar manufacturers. However, they are rarely resolved within a couple of months and can cause significant delays in obtaining FDA approval. In this case, the launch date is still 10 months away, which gives Alvotech a bit of a buffer. Mr. Levick stated that despite Alvotech’s manufacturing issues, the company anticipates being “ready by our expected launch date in the US of July 1, 2023.”

Biocon’s FDA Inspection Issues

Biocon Biologics has had its own issues with the FDA’s inspections. On August 31, the company was cited for manufacturing issues at two plants in Bengaluru, India, and one at Johor, Malaysia, where it would produce a biosimilar forms of bevacizumab, trastuzumab, and two insulins. The company was issued citations for a total of 22 problems in the Indian facilities and six deficiencies in the Malaysian plant.

According to Biocon, “The observations primarily relate to the need for improving strategies for microbial control, enhancing quality oversight, augmenting the use of software applications & computerized tools to aid risk assessment & investigations and other procedural & facility upgrades.”

The FDA was conducting preapproval inspections for Biocon’s insulins and bevacizumab (MYL-1402O), and for an expansion of biosimilar trastuzumab (Ogivri®) production.

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