FDA warns API manufacturer, OTC maker for sloppy GMP oversight

The US Food and Drug Administration (FDA) recently sent warning letters to a supplier of active pharmaceutical ingredients (APIs) in India for data integrity lapses tied to poor control of documents, and to an over-the-counter (OTC) drugmaker in the US for not adequately testing the final product or evaluating the purity of incoming ingredients.

Both these lapses were tied to a larger problem of inadequate quality control unit (QCU) oversight.

Centaur earns failing grades for document controls

FDA cited a multitude of examples of Centaur’s failings to maintain adequate oversight over its paper and electronic records. The supplier is based in Mumbai.

Investigators found that analytical worksheets, incident report forms, non-conformance reports, batch release copies, and pre-printed blank forms were kept in laboratory drawers and cabinets with “unrestricted access.” Two analytical worksheets were submitted with the same control number.

The firm also shredded original GMP documents “without a review and a meaningful description in the logbook.” The firm acknowledged in its response that it “destroyed CGMP documents without adequate controls and accountability.”

Centaur was also criticized for its lax control over products in the testing labs. As an example, “an HPLC [high-performance liquid chromatography] system processed unlabeled vials of solution. You could not provide evidence that these unlabeled vials contained the solution described in the HPLC system sequences. Reliability of data is compromised when there is a failure to maintain complete records of the conditions and data associated with all tests. Furthermore, the lack of complete data compromises the QU’s ability to exercise its function of ensuring compliance to applicable standards.”

The firm also failed to keep equipment clean. While manufacturing equipment was labeled as clean, investigators found peeling material on equipment as well as residue on the inner surfaces of equipment.

FDA told the company to promptly correct these deviations and said it may withhold approving new applications or supplements until they are addressed.

Fuller earns poor grades for testing products and ingredients

A similarly weak quality control unit was also observed in FDA’s 28 June warning letter to Fuller Industries in Great Bend, KS, following a February 2023 inspection. The company makes OTC topicals, including antibacterial hand soaps and hand sanitizers.

FDA said the firm’s quality control unit “failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity.”

The firm did not perform assay testing for the active ingredient, chloroxylenol (PCMX) used in its antibacterial foam hand soap prior to batch release and distribution.

The company also failed to have procedures in place for investigating out-of-specification (OOS).

In addition, the company lacked a stability program, failed to identify samples on test records, and perform annual product reviews.

FDA reminded the firm that “an adequate QU overseeing all manufacturing operations is necessary to consistently ensure drug quality.”

The company also failed to test incoming ingredients for propylene glycol, and FDA advised the company to consult its May 2023 guidance “Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycol,” when manufacturing drugs containing ingredients at risk for DEG or EG contamination.

Fuller also did not test incoming ethanol APIs for methanol. FDA reminded the company that “the use of ethanol contaminated with methanol has resulted in various lethal poisoning incidents in humans worldwide.” The company was advised to consult its January 2021 guidance document, “Policy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanol, Including During the Public Health Emergency (COVID-19)” to ensure that such testing is completed.

FDA said the company also lacked a “scientifically sound” program for testing its antibacterial hand soap. The company provided the investigator with non-validated tests methods from an internet search which “did not appear to be specific for your drug products, nor appropriate for any drug product.”

FDA advised the company to hire a GMP consultant based on the nature of the findings of the letter.

FDA said that corrective actions must be taken within 15 days of receiving the letter. Failure to address violations may also cause FDA to withhold the issuance of export certificates.

Warning letter to Centaur

Warning letter to Fuller

FDA warns API manufacturer, OTC maker for sloppy GMP oversight

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