FDA criticizes Lack of Compliance with ICH Q7 Guidance

In August, the U.S. FDA issued a Warning Letter to a Chinese API distributor due to the failure to establish, document and implement an effective system to manage quality of the APIs handled by the firm.

For the FDA a robust quality system, including an adequate organizational structure, is very important. The failure to establish such a system compromises the assurance that the released APIs meet required specifications of quality and purity.

In addition, according to the FDA, the company re-labels active pharmaceutical ingredients (APIs) manufactured by other manufacturers and distributes the APIs to other facilities, also located in the United States. The Warning Letter mentions that the Chinese company failed to transfer all quality or regulatory information received from the API manufacturers to their customers. As an example, the generation of COAs by the Chinese company is described and found to be not in compliance with the ICH Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients. The U. S. FDA recommends to follow the provisions outlined in the ICH Q7 Guidance. They also define how APIs from original manufacturers as well as API re-packagers and re-labelers should be labeled to clearly identify the original API manufacturer and to ensure the traceability of each API throughout the entire supply chain.

According to the Warning Letter, the U.S. FDA has not received a response to the inspection deficiencies yet.

FDA expectations

The FDA now expects:

• a plan to establish, document, and implement an effective system for managing quality, including written procedures for CGMP-related activities and the roles of personnel responsible for oversight.

• a written procedure regarding generation of COAs, including controls demonstrating that the COAs include the required information about original manufacturers.

• a retrospective review to determine how the failure to provide required information may have affected drug quality.

• a plan mentioning any actions that have been taken or will be taken, such as notifying customers, recalling drugs, or invalidating previously issued COAs for any drugs still within their labeled retest dates; and a recently issued COA that includes the required information, as well as a batch certificate.

The FDA strongly recommends engaging a GMP consultant to rectify the deficiencies and placed the firm on Import Alert on August 1, 2019.

To find out more, please see the FDA's Warning Letter to Yino.