FDA Issues Another Form 483 to Biocon Over Bangalore Facility

The FDA has issued a new Form 483 to Biocon over the Bangalore, India, facility where it produces its biosimilars. The document makes 2 inspection observations that stem from a February 2019 inspection.

The FDA first notes that procedures designed to prevent microbiological contamination are not established or followed. In particular, the document points out a lack of appropriate procedures to prevent contamination on the drug product fill line.

The inspector writes in the partially redacted document that he observed an operator failing to sanitize a restricted access barrier system despite Biocon’s having a written procedure that requires such a sanitization process be carried out. He also notes inadequate procedures for aseptic behaviors in the processing area, environmental sampling, aseptic process simulation, and visual inspection of vials. Further, he identifies problems with inadequately labeled and stored rejected vials.

The second observation states that written records of investigations into unexplained discrepancies sometimes lacked adequate conclusions or follow-up. Some environmental monitoring investigations and corrective actions over “several months” lacked appropriate Corrective and Preventive Actions.

In a February statement, Biocon acknowledged the Form 483, saying that it was related to a preapproval inspection of a new injectable manufacturing line. A representative from Biocon said that the company has already addressed the observations and made a response to the FDA.

The Form 483 is the latest communication from regulators in a long line of such documents for Biocon’s Bangalore plant, which is used to produce biosimilars in partnership with Mylan; in May 2018, Biocon received a Form 483 noting 7 observations, and in the same week, Biocon revealed that it had received a preliminary report from a European regulatory inspection of the same facility that resulted in 6 “major” observations. The plant was also the subject of a 2017 Form 483 and a 2017 French National Agency for Medicines and Health Products Safety noncompliance statement.

Troubles with the plant resulted in the delayed approval of Mylan and Biocon’s pegfilgrastim biosimilar, Fulphila; according to Biocon, the FDA’s initial Complete Response Letter for the proposed drug relates to “data from facility requalification activities” after modifications to the Bangalore facility. The biosimilar was later approved by the FDA, making Fulphila the first pegfilgrastim biosimilar to gain authorization in the United States.