FDA reprimands two firms for missing validation programs, poor facility maintenance

Regulatory NewsRegulatory News | 29 March 2022 |  By 

Inadequate validation of manufacturing processes, failure to conduct microbiological testing of drugs and keeping a facility in a poor state of repair, prompted the US Food and Drug Administration (FDA) to issue warning letters for good manufacturing practice (GMP) violations to two over-the-counter (OTC) drug manufacturers, one based in the US and one in Poland.
The recipients of the warning letters, which were posted on 29 March include Puerto Rican firm Agropharma Laboratories, a manufacturer of OTC antiseptics and hand sanitizers and Dr Retter Ec Wladyslaw Retter, a manufacturer of homeopathic creams based in Warsaw, Poland.
The warning letter to Agropharma found the drug manufacturing areas at its facility were in “disrepair.” Investigators observed “facility damage such as broken walls in the production area, filth, and pooling water in close proximity to open manufacturing equipment.”
The warning letter, dated 25 March, was sent to the Salinas, Puerto Rico-based manufacturer following an inspection from October to November 2021. Investigators also took issue with a missing validation program and reminded the company that this program is necessary to ensure that products are manufactured in a state of control throughout its lifecycle.
FDA told the company that “each significant stage of a manufacturing process must be designed appropriately and ensure the quality of raw materials inputs, in-process materials, and finished drugs. Process qualification studies determine whether an initial state of control has been established.”
The firm also failed to validate that its water system “consistently produced water suitable for its intended use.” FDA said, “Your firm uses water from your water systems as a component to manufacture your drug product; however, you have not established that the water system is adequately designed, controlled, maintained, and monitored to ensure that it consistently produced water for its intended use.”
The company was also chastised for failing to follow its stability program, failing to perform annual product reviews, and failing to ensure that incoming components were tested for identity, purity, and strength.
The company has stopped manufacturing products. The agency recommended the company engage a consultant if intending to resume manufacturing operations for the US market.
Products distributed “without adequate process validation
Similar validation problems bedeviled Dr Retter Ec, a manufacturer of OTC homeopathic ointments and creams in a warning letter issued 14 March.
FDA said the company’s products are distributed to the US “without adequate process validation” to demonstrate that the manufacturing process can produce a homeopathic drug product of its “purported quality and safety.”
The drug is diluted four times the number indicated on the label, yet the firm lacks documentation attesting that the drug has been tested at the amount listed on the label.
FDA was further told by the company that a validation protocol and report for products “did not exist,” in response to a request for these documents.
The agency said “each significant step of a manufacturing process must be controlled to ensure that in-process materials and finished drugs meet their quality attributes and specifications. Unvalidated product processes increase the probability that your products will vary in strength, quality, and purity. Your failure to validate your drug manufacturing process signifies that you cannot ensure consistency, which may result in variable levels of ingredients in finished drug products.”
The firm also failed to conduct microbiological testing before releasing products to the market.
FDA’s review of the product’ certificate of analysis (COA) for batches shipped to the US “indicate that you have failed to establish appropriate specifications for microbiological testing … your COA does not dictate that you test for total aerobic count according to the United States Pharmacopoeia (USP) General Chapter <61> Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests, or an equivalent validation method.”
The firm was also criticized for failing to conduct identity tests to verify drug components, as well as for having batch records that lacked such details as the identity of equipment, the duration of each manufacturing step and the total duration of manufacturing.
FDA placed the company on an import alert, and recommended that the firm hire a GMP consultant
Agropharma warning letter
Dr Retter warning letter


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