FDA’s warning letters cite firms over inadequate testing, BIMO violations

The US Food and Drug Administration (FDA) recently sent three warning letters to companies based in China and the United States, as well as a warning letter to a clinical investigator. The letter directed to an investigator who received criticism for clinical research violations, while two over-the-counter (OTC) drugmakers were warned for failing to conduct adequate testing and validation of their manufacturing processes.

Clinical investigator Amy Lightner received a warning letter from the FDA for three violations related to the clinical research stemming from a 2023 inspection. These violations concern the handling of patients enrolled in a study for an investigational drug.

According to the warning letter, patients were not screened or evaluated for eligibility before enrollment in clinical studies, which was out of line with the study protocol.

Lightner’s response letter indicated that some participants in the studies lived out of town, which left the study team with insufficient time to complete the laboratory and imaging assessments before dosing. However, the FDA was not satisfied with this explanation and did not accept it. “This explanation does not justify your failure to evaluate subjects’ eligibility in accordance with the protocol,” the agency wrote.

FDA also chastised the investigator for failing to submit adverse event reports related to the study, which was required under the study protocol and the Data and Safety Monitoring Board (DSMB) charter.

Another violation was the failure to retain study records and reports for the 2-year time required by 21 CFR § 312.57(c).

 “Your failures to ensure that enrolled subjects met protocol-specified eligibility criteria and that adverse events were documented and reported as required by the protocol and applicable FDA regulations risked jeopardizing the rights, safety, and welfare of enrolled subjects. Additionally, your lack of supervision and oversight, and failure to conduct the clinical studies in accordance with the respective protocols raises significant concerns about the validity and integrity of all the data collected at your site in the course of your investigations,” FDA wrote.

FDA said the investigator has 15 days to describe remedial actions taken to prevent similar violations in the future.

Huangshi Hygienic Material Medicine Co.

Huangshi Hygienic Material Medicine Co., a manufacturer of OTC drugs in Huangshi City, China, was cited in a warning letter for several good manufacturing practice (GMP) violations, including failing to test products prior to their release and failing to affix the current expiration dates on products.

The agency stated that the company did not test products, including the identity and strength of each active pharmaceutical ingredient (API), before their release.

FDA reminded the company that “full release testing, including for identity, strength, and purity, must be performed prior to batch release and distribution. Without adequate finished product release testing, you do not have scientific evidence that each batch of drug product conforms to appropriate specifications before release.”

The company also allegedly failed to include the correct expiration dates on the product labeling. The expiration dates were assigned based on stability testing conducted in China, without considering that the formulations for products aimed at the US market differ from those used in domestic products.

The company was advised to hire a consultant. FDA stated that the company has 15 days to respond to the violations noted in the warning letter.

CTK OTC Laboratories

CTK OTC Labs, located in Corona, California, received an FDA warning letter for failing to conduct thorough investigations into batch failures associated with its manufacturing of OTC topical creams, including sunscreens.

Investigators said the company failed to conduct adequate investigations into out-of-specification (OOS) results for a batch which had a low potency value for one of the active pharmaceutical ingredients (APIs). The root cause of the low potency was not determined. Also, batch failures tied to high viscosity of the products were reportedly not investigated.

The company was also taken to task for not validating its manufacturing process for its OTC topical creams and sunscreens.

Additionally, it was unable to provide studies on blend uniformity to demonstrate that its mixing processes could achieve consistent uniformity and homogeneity. These issues contributed to the out-of-specification (OOS) results.

FDA said that failure to address these violations may result in the withholding of export certificates. The company was also advised to hire a GMP consultant and has 15 days to respond to the warning letter.

CTK Labs, Huangshi Hygienic, Amy Lightener