Inadequate Cleaning and Batch Release in spite of Incomplete Quality Control - Warning Letter to an Indian API Manufacturer

Recommendation

23-25 April 2024
Barcelona, Spain

Global Registration and Life Cycle Management for APIs

The company CTX Life Sciences Pvt., Ltd - a manufacturer of APIs based in the state of Gujarat in India received the visit of FDA inspectors in February 2016. The outcome of this inspection was the issuance of a Warning Letter on 18 January 2017. This letter  presents a range of serious deficiencies. Those deficiencies violate fundamental requirements and show that there is hardly any awareness of GMP-compliant manufacturing and controlling at this site. The Warning Letter lists the following deficiencies:

• Failure to have adequate cleaning procedures to prevent contamination or carry-over material that would alter API quality

During their tour, the inspectors observed rust, insects, damaged interiors and product residues on the manufacturing equipment which had the "clean" status. As this equipment was in use and partly in direct contact with products, the inspectors saw a considerable risk of contamination.

• Failure of your quality unit to exercise its responsibility to ensure the API manufactured at your facility are in compliance with CGMP, and meet established specifications for quality and purity.

Diverse product batches had been released without performing the required UV spectrometry test. The reason for that was that the UV spectrophotometer was defective. In its response, the company states that according to the quality department the batch release was justified since all other release tests had been passed. For the FDA, this argument was definitely unacceptable.

• Failure to ensure all production deviations are reported and evaluated, and that critical deviations are investigated and conclusions are recorded.

The inspectors discovered a customer complaint who had measured in a product batch a higher water content deviating from the specification. This measurement was also higher than the value calculated by the quality control. The reason for that was due to the fact that the QC was not using a validated testing method.

In the Warning Letter, the FDA requires statements on the deficiencies criticised coupled with the provision of extensive information on improvement measures and data on the already delivered batches. All theses actions are expected to avoid the threatening import ban in the USA on APIs manufactured by this company.

Please also see the FDA's Warning Letter to CTX Lifescience Private Ltd.