14/15 June 2021
The FDA has recently issued a Warning Letter describing serious GMP deficiencies to a US manufacturer of over-the-counter (OTC) topical products. The deficiencies concerned, among others, the water system, the QC (chemical, microbial and stability tests), and the process validation.
The company manufactures and distributes topical sunscreen and anti-blemish OTC drug products. During FDA´s inspection performed in September last year the agency found that the company did not test the finished drug products to confirm their identity or potency prior to releasing those products. In particular there was a lack of data showing that identity and potency testing was performed for the active ingredients in the OTC topical products. In addition, the company lacked adequate testing for microbial attributes (e.g. no adequate program for growth promotion testing of media used for microbial testing).
The FDA criticized the missing validation of the processes used to manufacture the topical drugs. For example, no process qualification studies were performed. In addition, no ongoing program for monitoring process control to ensure stable manufacturing operations and consistent drug quality was established. Therefore the FDA stated that the company has not demonstrated that they can consistently deliver quality products.
During the inspection FDA observed that the water system contained a dead leg, which can foster the development of biofilms. However, water from this system is a component in the topical drugs. According to FDA, the firm has not demonstrated that they can effectively design, control, maintain, and monitor the water system so it consistently produces pharmaceutical grade water that, at a minimum, meets the USP monograph for purified water and appropriate microbial limits.
According to the FDA, the firm could not provide sufficient data demonstrating that the chemical and microbial attributes of the drug products remain acceptable throughout their assigned shelf life (three-year expiration dates). The agency also missed an adequate stability program to confirm that the drug products continue to meet established specifications and all pre-determined quality criteria throughout their shelf life. In addition the company failed to provide data to support the “period after opening policy.”
The QU did not adequately test or evaluate raw materials prior to releasing them as components used in the manufacturing of drug products. During the inspection, the company told FDA´s investigator the QU did not have the resources to perform this operation on every incoming shipment, and occasionally compares the manufacturer’s labels with the label printed by the receiving warehouse.
Due to the numerous and fundamental GMP deficiencies, the FDA does not consider the Quality Unit (QU) to be sufficiently authorized to ensure a QA Oversight. The QU should be provided with sufficient resources and authorities to perform their function. The FDA also strongly recommends that the company engages a GMP consultant to address the deficiencies and to bring the company up to a GMP compliant status.
Please also see the FDA Warning Letter to the OTC topical products manufacturer.