FDA Warning Letter: Key Aspects of the ICH Q7 Guideline disregarded

In February 2022, the U.S. FDA issued a Warning Letter (WL) to an Indian drug manufacturing site called "Indiana Chem-Port" due to significant violations of cGMP regulations for active pharmaceutical ingredients (APIs).

The five observations listed in the Warning Letter are as follows:

  • "Failure to ensure that equipment surfaces in contact with API do not alter the quality of the API beyond the official or other established specifications"
  • "Failure to demonstrate that the manufacturing process can reproducibly manufacture an API meeting its predetermined quality attributes"
  • "Failure to adequately validate written procedures for the cleaning and maintenance of equipment and failure to establish adequate written procedures for cleaning equipment and its release for use in manufacture of API"
  • "Failure to design a documented, on-going stability testing program to monitor the stability characteristics of API and to use the results to conform appropriate storage conditions and retest or expiry dates"
  • "Failure to have a quality unit that is independent of production and fulfills quality assurance (QA) and quality control (QC) duties"

One of the most important statements made in the U.S. FDA Warning Letter is that the firm failed to establish an independent Quality Unit (QC and QA responsibilities), which led to an enormous lack of Good Documentation Practices. As an example, it is mentioned that batch records were not adequately signed and completed. As a consequence to this finding, the U.S. FDA expects that an appropriate system of record retention throughout the retest period of the API is implemented and followed.

According to chapter 2 "Quality Management" of the "ICH Q7 Good manufacturing practice for active pharmaceutical ingredients" guideline, the quality unit needs to be independent of production and a clearly defined Quality Management System (QMS) needs to be established to ensure the quality of the API.

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 import alert, effective since December 2021, will remain until the Indian manufacturer has closed all observations and fully comply 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 Indiana Chem-Port.

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