Tuesday, 3 November 2020 14.00 - 15.30 h
On 7 July 2014 the US FDA has issued a Warning Letter for Zhejiang Jiuzhou Pharmaceutical Co., Ltd. located in Taizhou, Zhejiang Province in China. The company is a producer of APIs and failed to establish basic GMP principles.
The Warning Letter can be considered a "perfect" but negative example for a company which has not established basic GMP principles on the shop floor level. The critical deviations found by the FDA inspector show that fundamental principles of GMP are not understood or management is not willing to implement them by means of GMP training and necessary resources (e.g. enough personal).
1) Zhejiang Jiuzhou did not review all batch production records prior to distribution of the API batches. This practice did not happen by mistake as FDA Inspectors found out that several employees were aware of the problem.
2) The company did not document manufacturing operations at the time when they were performed. This fundamental GMP principle should be understood by all employees. But according to the FDA Warning Letter it was common practice in the manufacturing report to leave lines blank to fill in information later. Moreover, the company was found responsible for data falsification. During an inspection an employee had to admit that he had falsified records. According to the records he signed a batch as a QA reviewer but never did so.
3) The FDA Warning Letter also lists that the company did not maintain the manufacturing equipment as required by the cGMP regulation. Again this is a basic GMP principle. Everyone should also know that FDA investigators will usually check whether deviations identified at previous inspections have been addressed as requested by the FDA. But the firm had to admit that leaks in the purified water system which had been found during the last FDA inspections were not all detected and repaired.
The FDA inspection revealed that management is responsible for the identified problems. The workload was too large for the current staff. This is again a problem which can be observed in many companies. It is a basic GMP principle that management is responsible for providing the necessary resources.
Finally the company was found responsible for selling APIs which were not manufactured by Zhejiang Jiuzhou. The company purchased APIs from an outside supplier and relabeled them without oversight of a quality unit. The FDA writes:
"The information from the original certificate of analysis, generated by the actual manufacturer, was transferred to a new certificate of analysis on Zhejiang Jiuzhou Pharmaceutical Co. letterhead with no information about the original manufacturer or analytical laboratory performing the analyses. In addition, a new label identifying Zhejiang Jiuzhou Pharmaceutical Co. as the manufacturer was added to drums. In doing so, your firm essentially obscured the supply chain of these APIs."
Zhejiang Jiuzhou Pharmaceutical explained to the FDA investigator that a company called Zonebanner has been responsible for this falsification. However, FDA Inspectors found out that Zonebanner is not only located in the same building, but organisation charts were found showing that the Zonebanner management was reporting to the CEO of Zhejiang Jiuzhou Pharmaceutical Co.