Pharmaceutical Manufacturer obstructs FDA Inspection

A pharmaceutical manufacturer in China received an FDA Warning Letter after significantly restricting the FDA's inspection of its facility in March 2024. This violation constitutes a serious impediment to regulatory control for the FDA and may result in the manufacturer's products being classified as 'adulterated'. This classification means that the manufactured medicinal products do not meet the legal requirements of the Federal Food, Drug, and Cosmetic Act (FD&C Act), which would have significant consequences for the manufacturer and its products. This includes a distribution ban for the US market, an import ban, but fines are also possible. The FDA refers here to its guideline 'Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug or Device Inspection'.

Restricted access to documents

The manufacturer denied the FDA inspectors unrestricted access to important manufacturing documents. For example, process validation reports and batch documents were only provided with significant redactions. Critical information such as the weight of the components used and process parameters were made illegible. The qualification report for the equipment used was also only made available with redactions. The manufacturer explained that this was required by management guidelines in order to protect sensitive information. However, the FDA saw this as a significant hindrance to the inspection and documented this as a refusal.

Prohibition of photo documentation

The inspectors attempted to take photos of filling machines that were labelled as clean but were visibly dirty and in poor condition. Management prohibited the inspectors from taking photos, even though this was an essential part of the inspection. The FDA also considered this a denial.

Restricted access to production areas

The FDA inspectors were not allowed to enter certain production areas where critical manufacturing processes took place. Management refused access despite being told that this would significantly hinder the inspection. This was also documented as a refusal.

Further GMP violations

Despite these obstructions, the FDA inspectors were able to observe further deficiencies, which are also reflected in the Warning Letter:

According to the FDA, the manufacturer's cleaning is not sufficient to remove contamination from the manufacturing equipment. Residues were found on filling machines even though they were labelled as cleaned. In addition, the filling machines were in poor condition, including missing screws, defective parts and improvised repairs. The FDA therefore judged the equipment to be unsuitable for its intended use.
In addition, the manufacturer was unable to provide sufficient evidence that the production processes had been validated.
According to the FDA, the analytical methods for the release and stability tests of the product are not suitable for accompanying stability studies. In addition, no studies were conducted to identify potential degradation products that need to be monitored during stability testing.

The manufacturer's products remain on the import warning list and their import into the USA can be refused until the FDA confirms GMP compliance. If the deficiencies are not corrected, the FDA may continue to deny importation, classify products as adulterated and block the approval of new products.

The detailed warning letter can be found on the FDA website.