Stability Testing Program as a Common Problem in recent FDA Warning Letters

Stability testing of drug products is mandatory by 21 CFR 211.166 of the cGMP guidelines and is a fundamental GMP requirement. A stability testing program should demonstrate that the chemical properties of the drug products remain acceptable throughout their labeled expiry period. Inadequate stability studies that do not provide the shelf life of the product may cause the facility to fail an FDA inspection and receive a Warning Letter.

A recently published evaluation has shown that complaints regarding inadequate stability testing can be found in about every fifth Warning Letter in the fiscal years 2016, 2018, and 2019. This trend seems to continue for 2020, as three of the Warning Letters posted in January 2020 also deal with this problem. 

In a Warning Letter dated January 9, 2020, to Huaian Zongheng Bio-Tech Co., Ltd., the FDA criticizes, among others, that the "firm did not have an adequate stability testing program to demonstrate that the chemical [...] properties [...] remain acceptable throughout their labeled expiry period." - as recently covered in "Identity Testing and Stability Studies criticised in an FDA Inspection".

A second example is the Warning Letter to CGA Limited posted on the FDA website on January 21, 2020. According to the FDA, the company could not provide stability data to demonstrate that the properties of the product remain acceptable throughout its assigned shelf-life.

FDA Warns German Company

Among the companies that received a Warning Letter in January 2020 is Dental-Kosmetik GmbH & Co. KG, located in Dresden, Germany. Besides an inadequate control of the manufacturing process as one of the key findings, the stability program was in focus.

According to the FDA, the company did not have long-term stability test data to support the expiration date assigned to the products. The FDA states that "the product expiration dates were based on only three months of accelerated stability testing" and that the accelerated stability testing data is inadequate because the firm tested the samples not at appropriate intervals. Furthermore, the "stability program did not include an adequate number of batches of each drug product." and "no additional batches were placed on stability throughout the lifecycle".

In the accelerated stability data, a reduction of the concentration of one of the components was observed. Dental-Kosmetik GmbH & Co. KG could not provide an adequate explanation for this observation. For that reason, the FDA requested the company to perform a more in-depth investigation "and an assessment of the impact of this degradation on distributed drug product."

The original warning letter to Dental-Kosmetik GmbH & Co. KG can be found on the FDA website.