Biocon has received two US FDA 483s with two and six observations at a drug product plant and an insulin API plant, respectively.

The first 483 came following a pre-approval inspection of a new injectable manufacturing line for a biologic drug product at the firm’s site in Bangalore, India conducted between February 7 and 15.

The Form has since been published by the US Food and Drug Administration (FDA) and the two observations relate to issues with microbial prevention procedures and the firm’s failure to fully investigate unexplained discrepancies.

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“These two observations have been addressed and we have responded to the US FDA,” a Biocon spokesperson told Bioprocess Insider.

The second Form 483 with six observations came following a pre-approval inspection of Biocon’s insulin drug substance manufacturing facility, also in Bangalore, triggered by a New Drug Application (NDA) submitted by a customer.

The firm told us it does not comment on individual observations but is “confident of responding to the agency expeditiously and hence see no business impact on our insulin business in the US or elsewhere.”

History of compliance

Biocon is India’s largest biomanufacturer and makes biosimilar products for the local and international market marketed by both itself and partners.

The site in Bangalore has been subject to compliance issues in the past, being hit with a Form 483 with eight observations in 2017, while a French National Agency for Medicines and Health Products Safety issued Biocon a non-compliance statement after finding 35 issues relating to environmental monitoring, training, cross-contamination risks, cleaning validation, and process validation.

One of the biosimilars produced at the site is Mylan’s Fulphila, a biosimilar version of Amgen’s cancer drug Neulasta (pegfilgrastim). While the biosimilar was approved in the US in June 2018,  it took two tries with the first attempt resulting in a complete response letter (CRL) citing manufacturing issues.

Despite the regulatory history, the spokesperson told us: “We do not view the [latest] observations as systemic issues within our manufacturing network. This inspection was for a new injectable manufacturing line being inspected by the USFDA for the first time.

“We are committed to global standards of Quality and Compliance and have demonstrated our agility in addressing 483 observations in the past in an expeditious manner.”