French regulator finds GMP violations at Biocon's Bengaluru plant

Moneycontrol verified a copy of the non-compliance report (NCR) posted on EMA website.

The French regulator found GMP deficiencies, environmental monitoring-training, OOS (out-of-specification) results management, cleaning validation, process validation, vendors' qualification, media fill test, cross contamination risks, batch manufacturing record, differential pressure alarms' management in classified areas, and access management in SAP for batch certification.

ANSM in its report proposed suspension of marketing authorisation and prohibition of supply of the three products until the deficiencies are resolved.

The agency said a follow-up GMP inspection is requested in order to ensure that the entire corrective and preventive actions (CAPA) plan has been implemented and finalised by the site and that a robust quality system is in place.

“The French inspecting authority (ANSM) conducted pre-approval inspection audits of our Bengaluru drug substance and drug product sites related to the pending EMA Marketing Authorization Applications for Trastuzumab, Pegfilgrastim, and related to Insulin Glargine (pen assembly only)," said Biocon in a statement.

"While there were no critical observations mentioned in the final report, ANSM notified Biocon that the receipt of a GMP compliance certificate for the drug product facility will require a follow-up inspection from ANSM to verify implementation of the proposed corrective and preventive actions (CAPAs). ANSM has reviewed the proposed CAPA plan and Biocon is progressing towards completion of the implementation of these CAPAs," the statement added.

Biocon said, along with its partner Mylan, it will work with the 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 re-inspection.

In a related development, ANSM has issued GMP compliance certificates for Biocon's two facilities in Bengaluru that manufacture active substance of Trastuzumab and Pegfilgrastim.

"This is important as the drug substance manufacture is core to the production of the actual biologic product in GMP compliance," Biocon said.

Biocon said it is committed to ensuring the highest level of quality in all of its products.

"The regulatory expectations will generally be much higher for biotech products," said an analyst tracking Biocon, on condition of anonymity. "Biocon's hopes of launching biosimilars in highly regulated markets such as Europe and US now hinge on how quickly it will be able to respond and resolve the issues raised by the French regulator."

Biocon has teamed up with the US-based generic maker Mylan to develop five biosimilars — pegfilgrastim, trastuzumab, bevacizumab, adalimumab and insulin glargine — for regulated markets such as Europe and the US.

Pegfilgrastim is used to stimulate the level of neutrophils, a type of white blood cell, in cancer patients undergoing chemotherapy. Trastuzumab is used in the treatment of HER2-positive metastatic breast cancer.

Three of Biocon’s biosimilars including trastuzumab, pegfilgrastim and insulin Glargine are currently under review with the European drug regulator, European Medicines Agency (EMA), while pegfilgrastim and trastuzumab are now being reviewed by the US regulator.

Biocon is expected to roll out its biosimilar products in the US and Europe starting FY19.