On July 11, 2024, the U.S. Food and Drug Administration (FDA) issued a warning letter to Brassica Pharma Pvt. Ltd. following an inspection that uncovered significant violations of Current Good Manufacturing Practice (CGMP) regulations at their facility in Thane, India. The inspection, conducted from January 15-19, 2024, revealed numerous compliance issues that led to the adulteration of their drug products under the Federal Food, Drug, and Cosmetic Act.
Key Violations:
- Data Integrity Issues: The company failed to test every batch for sterility, with many records found to be fabricated. Environmental and personnel monitoring data were also falsified, leading to inaccurate records of sterility and environmental control.
- Inadequate Sterility Testing and Validation: The sterility test methods were not adequately validated for all product formulations. There were multiple steps and materials used during testing that were not part of the initial validation process.
- Poor Aseptic Practices: The FDA observed numerous poor practices in the aseptic processing areas, including operators touching sterile surfaces without proper precautions, inadequate gowning, and insufficient media fill programs that failed to simulate actual manufacturing conditions.
- Environmental Monitoring Deficiencies: The facility’s environmental monitoring program was found lacking, with insufficient data to ensure the sterility of their products. Non-viable particulate monitoring was not performed during filling operations, and sampling locations were chosen at random without proper documentation.
- Inadequate Cleaning Practices: The cleaning and maintenance of aseptic processing line equipment were found inadequate, with significant discrepancies in cleaning validation processes. This posed a high risk of contamination between batches of different drug products.
FDA’s Requirements and Recommendations:
- Comprehensive Investigation: Brassica Pharma is required to conduct a detailed investigation into the extent of data inaccuracies, including retrospective reviews and risk assessments.
- Corrective Actions and Preventive Actions (CAPA): The company must develop a global CAPA plan addressing all identified deficiencies and ensuring the reliability of their data.
- Enhanced Oversight: The FDA recommends ongoing management oversight and regular audits by a qualified consultant to ensure CGMP compliance.
- Environmental and Sterility Controls: Improvements in environmental monitoring and sterility testing practices are necessary, including better aseptic techniques and proper gowning procedures.
Impact on Operations:
Brassica Pharma has suspended manufacturing and distribution of all drugs for the U.S. market and initiated a voluntary recall of all affected products. The company must address all violations and systemic flaws to resume operations and regain FDA approval for their drug products