Biocon Biologics Limited – FDA 483, Aug 26, 2022

This FDA Form 483 details significant deficiencies at a drug substance (DS) manufacturing facility.

**Facility and Operations:** The DS manufacturing facilities, including fermentation and downstream processing (DSP) areas, are deemed inadequate. Fermentation areas are "unclassified and uncontrolled" (UNC), with open windows observed. Raw materials are weighed in uncontrolled LAF units and added to open vessels. The DSP facility exhibits poor maintenance and cleanliness, with soiled/cracked floors, damaged walls, and excessive caulking.

**Violations and Observations:** * **Contamination Control (Observation 1):** Uncontrolled environments in fermentation areas led to at least four microbial contamination failures since FY2020. No microbial monitoring is performed on certain vessels. * **Aseptic Technique & Contamination (Observation 2):** DSP operations lack assurance against microbiological contamination. Operators were observed touching intermediates with gowns/gloves, blocking LAF, and using unsanitized tools. Dynamic smoke studies showed operators compromising aseptic conditions and airflow. * **Supervisory Oversight & Data Integrity (Observation 3):** Deficient supervisory oversight of laboratory and manufacturing systems. The firm failed to follow its SOP for audit trail review of electronic data since June 2020, impacting data integrity. A deviation for this was not initiated promptly. * **Complaint Handling (Observation 4):** Written procedures for complaints lack quality unit review provisions. Similar customer concerns regarding filter clogging were