GMP Violations by Chinese OTC Manufacturer

A Chinese manufacturer of OTC products (such as alcohol swabs) received a warning letter from the FDA due to serious violations. The warning letter is not based on an on-site inspection, but on a review of documents that the pharmaceutical manufacturer submitted to the FDA upon request. This is a typical approach for manufacturers outside the US, especially when on-site inspections are not possible due to resources or other priorities. The deficiencies include the areas of quality control and quality assurance, process validation and the water system.

Inadequate testing of raw materials (21 CFR 211.84(d))

The manufacturer did not adequately test incoming raw materials for identity, purity and quality. This particularly affects the ingredients glycerin and ethanol, which pose a high risk of diethylene glycol (DEG) and ethylene glycol (EG) or methanol contamination. DEG or EG contamination in glycerine and methanol contamination in ethanol have in the past led to fatal poisonings worldwide. The manufacturer relied on suppliers' certificates (Certificates of Analysis, COAs) without verifying their plausibility through their own tests.

Inadequate process validation (21 CFR 211.100(a))

The process validation documents submitted to the FDA only contained analytical test results, but no comprehensive consideration of the manufacturing processes. The FDA refers to its guidance on process validation here.

According to the FDA, water is a component of the manufactured OTC drugs. However, the Chinese manufacturer has not demonstrated that the water system has been adequately designed and validated for its intended purpose. The validation report of the water system submitted to the FDA does not include information on total organic carbon (TOC), which is a requirement by the United States Pharmacopeia (USP) for suitable water quality.

Inadequate laboratory procedures and microbiological testing (21 CFR 211.160(b))

Based on the documentation submitted, FDA could not verify that appropriate testing methods for microbiological testing were used in the stability program. For example, the microbiological tests of the stability testing are not based on USP <51> Antimicrobial Effectiveness Testing. Although the manufacturer tested for microbiological contamination, they used the wrong methods according to the FDA. For the FDA, this does not ensure that the products are safe throughout their shelf life.

Deficiencies in the quality management system (21 CFR 211.22(a))

According to the FDA, the Quality Unit (QU) does not exercise sufficient control over material flows, laboratory systems and manufacturing processes. For the FDA, the QU has failed to ensure that processes, materials, and finished products meet the established specifications. The FDA recommends reading its guidance on implementing quality systems in order to comply with CGMP requirements under CFR 210 & 211.

As a result of the warning letter, the FDA has issued an import ban for the USA (Import Alert 66-40). Before resuming exports to the US, an inspection will be necessary to verify the implementation of the required corrective actions.

The full warning letter to the Chinese OTC manufacturer is available on the FDA website.