Memorandum

FDA issues Form 483 outlining manufacturing violations at Biocon’s Bangalore facility – May 14, 2018

Biocon recently disclosed that its manufacturing facility in Bangalore, India received a Form 483 from the FDA, citing seven violations observed during a recent FDA inspection.

According to Regulatory Focus, this follows a March 2018 preliminary report from a congruent EMA inspection listing six violations, a previous Form 483 from an FDA inspection in June 2017, and a statement of non-compliance with good manufacturing practices from French regulatory authorities in March 2017. FDA issued a Complete Response Letter (CRL) in October 2017 for Biocon’s Neulasta (pegfilgrastim), a biosimilar bone marrow stimulant used as an adjunct cancer treatment; the CRL mentioned concerns surrounding chemistry, manufacturing, and control data from the Bangalore plant.

This controversy is not isolated to Biocon’s Bangalore facility – the company’s new plant in Malaysia also received a Form 483 from the FDA in March 2018.

Needless to say, this does not inspire confidence in Biocon’s Mylan-partnered biosimilar insulin glargine, which is currently under FDA review and is pending launch in the EU under brand name Semglee (expected in 2H18, following EMA approval in March). We can’t emphasize enough how crucial safety and quality assurance are for insulin products (and really, all medicines). We note that neither Biocon nor Mylan has longstanding experience as an insulin manufacturer, which may exacerbate the general manufacturing-related concerns from FDA and EMA.

Biocon management has been fairly quiet on these regulatory challenges during past earning calls, citing only the more rigorous standards for biosimilars and biologics vs. conventional small molecule drugs as an explanation for these less-than-successful inspections. While this is certainly new territory, we are skeptical about Biocon’s capabilities and wouldn’t be surprised if FDA approval of the company’s biosimilar insulin glargine is delayed due to these concerns.

Notably, Lilly/BI and Merck did not raise any of these regulatory red flags with the development of their respective biosimilar insulin glargine products, Basaglar and tentatively-approved Lusunda.

 

-- by Abigail Dove, Payal Marathe, and Kelly Close