Warning Letter: API Testing still in the Focus of the U.S. FDA

Recommendation

28-30 March 2023

Global Registration and Life Cycle Management of APIs - Live Online Training
Contents of the regulatory information in the ASMF and CEP

In January 2022, the U.S. FDA issued a Warning Letter to an Indian drug manufacturing site called "Aurobindo Pharmaceutical Limited" due to significant violations of cGMP regulations for active pharmaceutical ingredients (APIs).

Amongst other deficiencies listed in the Warning Letter, the firm failed to verify for their APIs and intermediates the influence and effect changes could have on the quality. In this case, the firm increased their specified limits for impurities for an API starting material before evaluating that this change would not influence the quality of the API. According to the U.S. FDA the change management needs to be improved and the effectiveness needs to be checked and specified.   

For APIs and intermediates, a formal change control system, which ensures the compliance with the regulatory filing as well the GMP requirements, is a key aspect of the ICH Q7 requirements and need to be considered in order to maintain GMP compliant systems in manufacturing facilities.

Furthermore, it is mentioned that the Quality Unit of the manufacturer failed to ensure that critical deviations are investigated adequately – as an example, the process of investigation was shown during the method transfer for a gas chromatography-mass spectrometry (GC-MS).

Coming to the final conclusion mentioned in the Warning Letter, the U.S. FDA strongly recommends engaging a cGMP consultant to support the company in aligning their systems with cGMP requirements. The U.S. FDA may refuse new applications until the Indian manufacturer has addressed all observations and fully complies with cGMP requirements, which might be checked by a further inspection.

To view the complete list of violations and the conclusion given by the U.S. FDA, please see the Warning Letter to Aurobindo Pharmaceutical Limited.