FDA 483 - Sun Pharmaceutical Medicare Limited - February 27, 2024

During an inspection from February 19-27, 2024, the U.S. Food and Drug Administration (FDA) issued a Form 483 to Sun Pharmaceutical Medicare Ltd. in Halol, Gujarat, India, a sterile drug manufacturer. The inspection revealed significant deficiencies concerning manufacturing controls and quality systems, critical for ensuring the sterility and quality of drug products.

Key violations included a failure to establish and follow procedures preventing microbiological contamination. Specifically, the facility’s processes for manufacturing a terminally sterilized injection lacked controls to minimize bioburden, resulting in out-of-specification (OOS) mold contamination (Aspergillus sydowii) in exhibit batches. Deficiencies encompassed inadequate bioburden acceptance criteria for Active Pharmaceutical Ingredients (API), unsterilized primary containers and components, and un-disinfected manufacturing equipment. Additionally, filling operations lacked proper environmental controls and aseptic practices.

The FDA also cited the company for failing to thoroughly investigate discrepancies. Investigations into OOS bioburden results were incomplete, overlooking non-sterile API as a root cause and delaying the implementation of necessary API testing changes for years. Similarly, atypical visual inspection results on exhibit batches were not promptly investigated, leading to significant delays in identifying the source of black particles and implementing corrective actions related to API screening.

Finally, essential production equipment, specifically packaging and printing machinery for the injection, was decommissioned in July 2022 without a qualified replacement being identified, impacting commercial manufacturing readiness. Sun Pharmaceutical Medicare Ltd. is required to address these observations by developing comprehensive corrective and preventive action plans to comply with Good Manufacturing Practices.