Biocon Malaysia facility USFDA 483 – Eight observations including inadequacy of microbial contamination control procedures of sterile drug products, OOS investigations, method transfer, cGMP refresher training, inadequate risk analysis of device and CAPA. The facility was audited by USFDA in July 2023 Read More..

Biocon Malaysia was inspected by USFDA Investigators Eileen A. Liu, Patty P. Kaewussdangkul, Daniel Lahar, Rong Guo in July 2023. Following the inspection Biocon was issued USFDA 483 with eight observations

1. Procedures and practices of aseptic area operators in Grade A area / RABS are inadequate to prevent microbial contamination of sterile drug products. Operators Head, Shoulder, Chest, Arm were seen inside the Grade A area, sterile scissors were held in non sterile holders, cleaning and sanitisation of Grade A area are deficient, integrity testing are not performed.
2. Inadequate Failure investigations – OOS, OOTs, Out of trend (OOT) batch of drug substance used for manufacture of drug product failed in stability; but drug product reserve samples were not evaluated
3. Inadequate investigations into discrepancies – OOS, OOTs
   • OOS attributed to system breakdown, though system suitability and standards were conforming, manufacturing investigation not performed
   • In OOS for laboratory error (analyst error), root cause not scientifically justified, manufacturing investigation not performed
   • Remeasurement followed by retest of sample to invalidate OOS, though Phase 1 investigation did not identify any laboratory errors
   • Attributing TOC (Total Organic Carbon) failure of sampling point (water) to disinfectant use is not scientifically sound
   • Procedures for pre and post (filter) integrity test and investigation of integrity test failures (leaks, physical defects, tears) are inadequate
4. Inadequate procedures to handle loss of differential pressures in aseptic areas during operation to mitigate viable /non viable contamination
5. Failure to establish accuracy and validity of test methods for vial stoppers, perform method transfer study for methods transferred from Biocon Bangalore.
6. No cGMP refresher training for Process Research & Development personnel who support manufacture of drug substance (DS) and drug products (DP).
7. Inadequate Risk analysis – Control of Injection force on drug product device; 1620 complaints on the issue since 2020.
8. Inadequate CAPA; Failure to test injection force on retention samples for complaint lots.