FDA Warning Letter: Incoming Analysis of Raw Materials - Performing only an Appearance Test is not enough

The U.S. Food and Drug Administration (FDA) has issued a Warning Letter dated March 10, 2020, to DermaPharm A/S, a Danish drugmaker. The FDA placed the firm on Import Alert 66-40 on March 9, 2020.

During an inspection from September 16 to 19, 2019, the FDA inspector observed significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. All in all, the FDA considers the company's quality system to be inadequate.

The observations noted in the Warning Letter published on the FDA website can be divided into three thematic areas:

1. Testing of finished products

According to the FDA, DermaPharm A/S failed to test a specific over-the-counter (OTC) drug product for the identity and strength of the active ingredient prior to release for distribution. In this context, the FDA particularly emphasizes that this drug product is labeled for use on children. Because the company lacked adequate testing of each batch of these drug products, it was not ensured that they conform to all appropriate finished product specifications and are suitable for release to consumers.

Among other things, the FDA is now demanding "an action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States within expiry as of the date of this letter."

2. Testing of raw materials

During the inspection, it turned out that a raw material, containing the active ingredient in the finished drug product, was sampled by the company's quality unit but was not fully tested. Only an appearance test was performed. The company considered that incoming testing of this material was not necessary because the supplier of this component was qualified, and the material was received with a certificate of analysis from the supplier.

In the response to the Warning Letter, the FDA is asking the company - among other things - to include a commitment to always conduct at least one specific identity test for each incoming component lot.

3. Validation of manufacturing process

The company did not validate the process used to manufacture one of the drug products in the focus of the inspection. The company itself had to admit this during the inspection.

The FDA is now requiring a detailed summary of the validation program for ensuring a state of control throughout the product lifecycle as well as a timeline for performing a process performance qualification (PPQ) for each of the company's marketed drug products.

Please also read the FDA's Warning Letter to DermaPharm for more detailed information.