Production of APIs without any Minimal GMP Standards leads to a Warning Letter for a Chinese Manufacturer

Recommendation

22/23 February 2024
Munich, Germany

API Regulatory Starting Materials
Definition, Manufacture, Assessment and handling post-approval Changes

When a company manufactures APIs without a QM system and the associated written instructions and records and ships those APIs to the USA, it is merely a matter of time until problems with the FDA arise. The Chinese API manufacturer Changzhou Jintan Qianyao can testify that. Indeed, inspectors discovered that even the minimal GMP requirements with regard to production and quality control hadn't been complied with. The Warning Letter issued thereupon contains a list of the following deficiencies:

• Non-existent quality management system defining all processes and procedures and ensuring that the APIs are manufactured according to predefined specifications regarding quality and purity.
  At the time of the inspection, a few written working instructions were available. Those have been obviously created at the last minute and to "show off" during the inspection.
• No existing written procedures for the receipt, identification, quarantine, storage, sampling, testing, handling, and approval or rejection of raw materials
  Upon request of the inspectors, the warehouse personnel explained that the activities performed such as sampling and testing are done "in their heads".
• Laboratory control records are not available.
  After reviewing the audit trail, the inspectors discovered that one sample had been analysed three times over several days. Only the final test result was reported in the certificate of analysis: records of the prior tests couldn't be found.
• Batch records have been filled out incorrectly.

Production steps and process parameters haven't been entered promptly in the batch record. The operator was too tired to immediately record the current data and forgot the values. Instead, she entered the process parameters of the previous batch in the protocol.

In this Warning Letter issued to Changzhou Jintan Qianyao as well as in a few others with regard to companies violating basic GMP requirements, the FDA refers to the provisions laid down in the ICH Q7 Guideline on the GMP-compliant manufacture of APIs.