Inadequate Cleaning Validation Cited in FDA Warning Letter

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FDA's Warning Letter to an Indian API manufacturer alleges cGMP violations and improper cleaning and validation

On January 18, 2017, Thomas Cosgrove, director of FDA’s Office of Manufacturing Quality, sent a Warning Letter to the CEO of CTX Life Sciences in Gujarat, India.  The API manufacturing facility and its equipment and processes deviated from current good manufacturing practices (cGMPs), the letter said, raising doubts as to the safety and cleanliness of product produced and released at the facility and sold. In addition, the letter noted that the company’s responses to regulator’s observations were inadequate. 

Among the problems that FDA inspection noted were:

  • Inadequate cleaning and contamination prevention measures.

  • Failure to ensure compliance with cGMPs regarding material testing

  • Insufficient quality requirements for batch release.

Manufacturing equipment was found to contain rust and insects, while some pieces were damaged, and drug residue was found on equipment surfaces, suggesting that product batches were contaminated with small levels of previous batches of other APIs. The company’s corrective and preventive action plans were inadequate, FDA inspectors said, because they did not outline cleaning procedures and equipment maintenance procedures  in detail. FDA asked for assurance of cleanliness, as well as evidence of thorough cleaning validation tests, maintenance programs, and risk assessment of released batches.

Part of the problem, the company said, stemmed from the fact that its uv spectrometer was out of order when inspectors visited the facility.

As a result, FDA alleges, CTX released product batches without testing identity or content.  The letter asked CTX to develop a method validation study for HPLC, and to report and evaluate deviations for all products. It also demanded that the company  identify and summarize the batches that had been released without testing. It also asked for an itemized report on impacts to batch release and testing efforts, as well as evaluation of all production deviations, including an analysis of eight critical process parameter failures that could be traced to deviations from proscribed time limits.