Here are the observed deviations:
- Failure to implement a system managing quality regarding the organizational structure, procedures, processes and resources
- Failure to ensure confidence that the API will meet its intended specifications for quality and purity
- Failure to define and document all quality-related activities
- Lack of written procedures for the receipt, identification, quarantine, storage, sampling, testing, handling, and approval or rejection of raw materials
FDA noted, “For example, when our investigator asked for a list of your critical raw materials and your sampling requirements, you told our investigator that you had no written procedures for testing and sampling incoming materials. Instead, you explained, your warehouse employees accounted for incoming raw material handling, sampling, and testing “in their heads”.”
- Lack of laboratory control records that ensure compliance with established specifications and standards
FDA comments, “For example, our investigator reviewed the audit trail from your assay testing and found that you tested the same sample set three times over several days without documentation or investigation. You reported only the result of the third and final test for purposes of completing your certificate of analysis and releasing this batch of API.”
- Failure to prepare adequate batch production records and record the activities at the time they are performed
FDA writes “Our investigator found that your operator used process parameter values from previous batches to complete new batch records when she was too tired to immediately record the data and had forgotten the values.”
Even though the company was manufacturing and shipping drugs to the United States, there were no quality procedures in place before August 2016. By the time of the second inspection in February 2017, there were just some procedures drafted ahead but not implemented by the time of inspection.
This circumstance alone is absolutely unacceptable, regarding that at the end of the line the patient safety is at stake. Considering that data integrity issues are cited in more than 60% of the GMP warning letters of the FDA, the question arises how to really exercise control over those untrustworthy manufacturing practices.
FDA has now placed the firm on import alert. A cGMP consultant is strongly recommended to the Chinese API manufacturer to meet the expectations outlined in ICH Q7.
FDA Warning Letter