The Biocon sterile manufacturing plant that got spanked by European and FDA regulators earlier this year has taken another whipping by the FDA, raising new questions about its efforts to get a Herceptin biosimilar approved with partner Mylan in both markets.
The plant in Bangalore was written up in an 8-page, 10-observation Form 483, which the FDA posted (PDF) last week. The inspection, conducted in late May and early June, found problems across the entire range of processes, including in aseptic processing and filling, environmental monitoring, data recording, cleaning procedures, and even in its processes for buying sterile gloves for employees.
In one case, FDA inspectors faulted the company for not fully investigating an injection product after particulate was documented in a batch of the drug. They noted Biocon did not go ahead and evaluate what impact there might have been on other batches. Inspectors remarked that this is a product that Biocon was still selling in Russia and the Dominican Republic.
The FDA had already hit the site with a Form 483 this year over issues it found in its drug substance processing.
Wells Fargo Securities analyst David Maris in a note to clients Monday said the newly disclosed problems are likely to come up in a discussion with Mylan execs when the company reports Q2 earnings on Wednesday.
“On the one hand, inspections show progress toward action on filings, and oftentimes observations are easy to address, which is good news,” Maris told clients. “On the other hand, observations which are not corrected can result in costly delays.”
Biocon last month indicated that the approval of its biosimilar of trastuzumab and another biosimilar could be affected in Europe after the European Medicines Agency withheld a certificate of compliance for the plant when a pre-approval inspection turned up problems. Biocon and Mylan have applications for the biosimilar pending in both the U.S. and Europe.
Biocon downplayed the seriousness of the issues, but a copy of the report from French inspectors showed they found nearly three dozen deficiencies, 11 of them major, ranging from management of out-of-spec results to cross-contamination risks. It pointed out the agency had approved two Biocon API plants connected to its biosimilar program.
Biocon said at the time that it had already started its correction actions for the sterile plant and that it and Mylan were working with “French and European regulatory authorities with regard to the follow-up inspection of the drug product facility and the Marketing Authorization Applications with the goal of an early reinspection.”
The plant problems have implications for several of the biosimilar products that Biocon has been counting on. The pre-inspection by EU regulators also was for Mylan's and Biocon’s biosimilar of Amgen’s Neulasta and the pen assembly for some of the insulin products Biocon intends to launch in Europe.
Biocon last year got approval in Japan for a biosimilar of Sanofi's blockbuster Lantus (insulin glargine), which it also hopes to launch in the EU and U.S. It also is working on a biosimilar of Humira, the world’s best-selling drug.