French Inspectors Find Major Deficiencies at Biocon's Manufacturing Facility

France’s health regulatory body, the French National Agency for Medicines and Health Products Safety (ANSM), found that Biocon has failed to comply with good manufacturing practice requirements for 3 of its biosimilar products manufactured at the company’s Bommasandra facility in Bangalore, India.

In a non-compliance statement (NCS) issued on July 5, the ANSM identified a wide array of concerns with the drug product manufacturing activities for Biocon’s pegfilgrastim (Fulphila), trastuzumab (Ogivri), and insulin glargine (Semglee).

The French inspection, a pre-approval audit related to pending European Medicines Agency (EMA) marketing authorization applications for the 3 biosimilars, was conducted from March 13 to March 17 of this year. During the course of that inspection, the ANSM found 35 problems related to drug product manufacturing and quality control operations for the 3 biosimilars. Of those problems, the agency deemed the following 11 to be “major deficiencies:”

• Environmental monitoring
• Training
• Out-of-specification results management
• Cleaning validation
• Process validation
• Vendor qualification
• Media fill test
• Cross-contamination risks
• Batch manufacturing record
• Differential pressure alarms’ management in classified areas
• Access management in systems, applications, and products (SAP) for batch certification

The agency recommended to the EMA that no batch of any of the 3 biosimilars that was manufactured prior to the issuance of the NCS should be supplied to the European marketplace. Furthermore, the agency proposed that the EU revoke the marketing authorization applications for all 3 products while the NCS remains in force.

ANSM has requested a follow-up inspection in order to ensure that the entirety of its recommendations to the facility have been implemented by the manufacturer, and to ensure that a robust quality system has been implemented.

In its statement on the ANSM’s findings, Biocon said that it would, “with its partner Mylan, 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.” The company also noted that the ANSM had issued 2 compliance certificates for the company related to other inspections, and said that it was committed to ensuring the highest level of quality for all of its products.

That commitment aside, news of the NCS had a swift impact on Biocon’s stock price; shares of the company were down approximately 9.5% on Monday.

As Biocon works to address its manufacturing lapses for ANSM’s re-inspection, the FDA is still evaluating Biocon and Mylan’s trastuzumab (MYL-1401O), and regulatory action for the drug is expected in September of this year. If approved, this treatment will be the first biosimilar trastuzumab approved in the United States.