Warning Letter regarding serious Deficiencies in Equipment, Documentation and Contamination Control

In September 2025, the FDA inspected a Chinese active pharmaceutical ingredient manufacturer and identified serious non-compliance with GMP requirements. The violations relate to the structural condition of the facilities, manufacturing procedures and risks of cross-contamination.

The main focus of the warning letter is the poor condition of the building and equipment. For example, severe corrosion was observed on the piping of a production tank. In addition, there were repeated instances of water leaks in the ceilings in various areas of the facility, including the warehouse, production areas and packaging areas. These leaks resulted in puddles of water on the floor in Zone D areas. According to the FDA, such conditions pose a significant risk to product quality, as moisture can promote both chemical degradation and microbial growth.
The FDA considers the corrective measures submitted by the company to be inadequate. Although individual repairs have been carried out, photographs have been sent and a maintenance programme has been outlined, there is a lack of detailed information regarding the nature and scope of the measures, as well as a comprehensive investigation into whether other facilities and buildings are also affected by leaks. In particular, the FDA has not conducted a risk assessment to determine whether batches of active ingredients that have already been manufactured have been affected by moisture, or to what extent. 

Another significant shortcoming relates to the manufacturing specifications. The FDA has raised concerns that the master batch records are incomplete and that key process parameters are missing. For example, individual process steps were described without defined time limits, quantities were not specified, and critical process conditions were not adequately defined. In the FDA’s view, without this information, it is not possible to exercise sufficient control over the manufacturing process. Here too, the FDA considers the manufacturer’s response to be inadequate. The corrective measures taken are limited to individual processes and have not been extended to all active substances manufactured. Furthermore, there has been no retrospective review of batches already manufactured.

Furthermore, the FDA found that the separation of different production areas is inadequate, thereby posing a risk of cross-contamination. The agency has expressed particular concern regarding the potential mixing of different active ingredients during future production for the US market.

The FDA is calling for comprehensive measures to address the identified deficiencies. These include, in particular, a detailed risk assessment regarding the potential impact on batches already on the market, a fundamental overhaul of the maintenance system, the completion and standardisation of manufacturing procedures, and appropriate measures to prevent cross-contamination.

You can find the full text warning letter on the FDA website.