Warning Letter to Chinese Manufacturer due to serious Sterility and Hygiene Deficiencies

The FDA found serious GMP deficiencies during an inspection of a Chinese pharmaceutical manufacturer in November 2024. These include, above all, inadequate hygiene and assurance of product sterility. For example, medicinal products were labelled as 'sterile' although neither sterilisation nor sterility tests were carried out.

1. Insanitary manufacturing conditions

The FDA inspectors assessed the manufacturing facility as ina state of disrepair, not cleaned and not maintained. Specifically, the following deficiencies were found, among others:

• Numerous dead insects in tubing used to transfer active ingredients and in the storage containers of these tubings. 
• Unknown foreign particles in a solution that was fed into the filling line 
• Product transfer hoses were cracked, leaking, discoloured or had residues 
• Contamination of bulk containers of ingredients or intermediates with hair, particles or insects 
• The ceilings above open filling and packaging systems were visibly soiled and damaged.

2. Inadequate aseptic procedures and lack of sterilisation

Although the products were declared as 'sterile', the company had discontinued the sterilisation previously used without introducing a new validated method. There was neither a validated sterilisation method nor environmental monitoring. Basic requirements for hygienic clothing were also not met.

3. No sterility testing

According to the FDA, no sterility testing was carried out for the products labelled as 'sterile'. This means that there is no assurance that the products actually fulfil the sterility and pyrogen-free requirements.

4. No identity check and lack of testing of raw materials

The company relied entirely on manufacturer certificates (COAs) without carrying out its own identity checks or verifying the quality specifications. The suppliers were not qualified. In addition, the water used for production was not tested for microbial contamination.

5. Inadequate stability programme

Despite a declared expiry date, data was only available for a shorter period. The company did not have an ongoing stability programme to prove the shelf life.

Consequences

On 21 January, the FDA asked the company to recall affected products from the market, which it did on 11 February 2025. The FDA assessed the manufacturer's entire quality system as inadequate and demanded extensive corrective measures to restore GMP compliance.

The Warning Letter to the Chinese manufacturer can be found on the FDA website.