December 4, 2023


The FDA recently issued a warning letter to pharmaceutical company Cipla, citing multiple violations of Current Good Manufacturing Practice (CGMP). The letter highlighted issues at Cipla’s Indian manufacturing facility, particularly concerning the handling of customer complaints, contamination controls, and inadequate oversight of CGMP records.

  1. Poor Complaint Handling:
    • Cipla received over 3,000 customer complaints regarding its Albuterol Sulfate Inhalation Aerosol, primarily related to product performance issues.
    • The company’s investigation into quality defects was deemed inadequate due to a lack of timely corrective actions and failure to extend investigations to potentially affected batches.
    • Recommendations include developing a standardized electronic tracking system for logging complaints, training staff on detailed complaint analysis techniques, establishing a clear chain of command for escalating serious complaints, and ensuring thorough investigations for potential impacts on other batches.
    Relevant FDA Regulation: 21 CFR 211.192 (Unexplained Discrepancies; Failures Investigation)
  2. Contamination Controls:
    • Cipla lacked adequate controls to prevent microbiological contamination, posing a risk to the quality of its products.
    • The warning letter emphasized the importance of addressing deficiencies promptly and thoroughly, considering market actions to prevent patient exposure to defective products.
    Supplementary Guidelines/Frameworks: FDA Guidance on Investigating Out-of-Specification (OOS) Test Results, ICH Q9 (Quality Risk Management)
  3. Minimizing Problems with Defective Inhalers:
    • Cipla identified critical issues with the container-closure system of its inhalers but classified them as non-critical, leading to defective batches remaining on the market.
    • The warning underscores the need for adequate attention to the integrity and functionality of container-closure systems, prompt resolution of identified deficiencies, and consideration of market actions if necessary.

The warning letter resulted from a 12-day inspection of Cipla’s facility in Pithampur, India, in February 2023, and was made public on the FDA’s website on November 21, 2023. This follows a Form 483 report issued to the company in March 2023.

In summary, the FDA’s warning letter to Cipla highlights critical issues in complaint handling, contamination controls, and minimizing problems tied to defective inhalers. The outlined recommendations provide insights for pharmaceutical companies to avoid similar compliance issues and ensure the quality and safety of their products.