FDA Warning Letter: No Adequate Quality Unit, Laboratory Controls, Sampling Plans, and Stability Program

The U.S. Food and Drug Administration (FDA) sent a Warning Letter dated 3 December 2020 to Clientele, Inc. The firm produces OTC topical drug products that include sunscreen active ingredients and pain-relieving active ingredients. During an inspection from 3 to 7 February 2020, significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals were observed.

No Adequate QU Oversight

According to the FDA, the company’s Quality Unit (QU) did not provide adequate oversight for the manufacture of the OTC drug products. For example, no microbiological testing was performed and reviewed for each batch before release, and suppliers were not adequately qualified. In conclusion, the FDA considers the firm’s quality systems are inadequate. 

Failure to Adequately Validate the Processes

In the Warning Letter, it is stated that Clientele, Inc. failed to adequately validate the processes used to manufacturer the drug products. In response to the letter, the FDA requires, besides others, „an assessment of each drug product process to ensure that there is a data-driven and scientifically sound program that identifies and controls all sources of variability“ to make sure that „the production processes will consistently meet appropriate specifications and manufacturing standards.“

Insufficient Laboratory Controls

The company failed to routinely monitor the water used in production. The FDA concluded that it was not ensured that the water meets minimum microbiological and chemical standards suitable for the manufacture of the drug products. In response to the Warning Letter, the FDA requires a retrospective assessment to ensure that products on the market were adequately tested for their quality attributes, as well as a summary of all results obtained from testing retain samples from each batch.

No Adequate Stability Data Available

During the inspection, the company could not provide adequate stability data to show that the chemical and microbiological properties of the products remain acceptable throughout the claimed expiry period. For this reason, the FDA expects an improvement of the stability program including „stability studies for each drug product in its marketed container-closure system before distribution is permitted“ and „an ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid“.

Conclusion

The company has already committed in a statement to cease manufacturing drug products and to deregister the facility as a drug manufacturer. Clientele, Inc. plans to outsource the production of the OTC drugs to a third-party facility. The FDA points out that it regards contractors as extensions of the manufacturer. For this reason, a company is still responsible for the quality of its drugs regardless of agreements in place with their contract facilities.

For further details, please see the original Warning Letter to Clientele, Inc., published on the FDA’s website.