Contamination at Facility of US OTC Manufacturer

Contaminated equipment, OOS results in microbiological testing, and failures in testing of incoming goods led to an FDA Warning Letter being issued to a US manufacturer of over-the-counter (OTC) products.

Identitiy testing

The FDA criticizes that not every batch of glycerin was tested according to USP specifications. Thus, the absence of the impurities diethlyene glycol (DEG) and ethylene glycol (EG) was not ensured.

DEG contamination has led to several fatal cases of human poisoning worldwide. The drug manufacturer is responsible for this specific testing prior to release for use in production.

In addition, glycerin batches from unqualified suppliers were used for manufacturing.

Contaminated equipment

According to FDA, the manufacturer failed to adequately clean and maintain the equipment used to manufacture their drug products.

For instance, an unidentified residue was observed on the product-contact surface of a mixing tank during the inspection. However, the tank was labeled as "cleaned." Associated cleaning documents were not available.

Furthermore, the manufacturer had on several occasions observed microbial contamination of a finished drug product that had been manufactured using the aforementioned equipment. The CAPA protocol identified inadequate cleaning of valves and lack of quality assurance monitoring as likely causes. The FDA criticized the absence of operations management, who were not able to satisfactorily monitor daily cleaning. Also, investigations were not extended to other equipment to identify possible cases of cross-contamination.

Microbiological OOS results

The FDA criticizes the inadequate testing of OOS results for Burkholderia cepacia, yeasts, and molds in finished drug product.

For example, the manufacturer recovered OOS results in testing for Burkholderia cepacia or yeasts and molds in finished drug product batches from February through to September 2020. The relevant batches were manufactured using non-dedicated equipment where other drug products are also manufactured. One opened CAPA case was closed as successful after 8 months without extending the investigation to other potentially affected drug batches manufactured during the mentioned period. In addition, no action was taken to prevent the recurrence of bioburden OOS results.

Given the nature of the violations, the FDA strongly recommends hiring a qualified consultant to assist the company in complying with GMP requirements.

The original Warning Letter can be found on the FDA's website.

Glycerin in Warning Letters

There's been an influx of FDA Warning Letters due to inadequate testing of glycerin and other high-risk drug components this year. Learn more about this topic in our live webinar "Ethylene Glycol and Diethylene Glycol" on Thursday, 16 November 2023 (15.00 - 16.30 h CET) and in the following articles:

• Series of FDA Warning Letters due to inadequate Testing of Glycerin and Other High-Risk Drug Components
• Identity Testing of Glycerin in Focus of an FDA Warning Letter