FDA warns three US OTC drugmakers for lax component testing, missing validation programs

Regulatory NewsRegulatory News | 16 March 2023 |  By 

Three domestic drug manufacturers were chastised in recent warning letters sent by the US Food and Drug Administration (FDA) for similar good manufacturing practice (GMP) violations related to failure to test incoming components and missing validation programs to ensure products remain in a state of control.
Another problem found at two sites were lax or nonexistent stability testing programs. One company was lambasted for “filthy conditions” at its facility, including the discovery of insects found inside bottles and caps and “rust-like residues” on equipment.
All three letters were posted to the agency’s website this week.
Formology Lab Inc.
Formology Lab Inc., a contract manufacturer of OTC products in Chatsworth, CA, was cited for a multitude of GMP violations, including failing to test active pharmaceutical ingredients (API) in manufacturing drug products.
FDA told the firm that “component testing is fundamental to drug product quality. Without adequate testing, you do not have scientific evidence that your incoming components conform to appropriate specifications before use in the manufacture of drug products.”
The company did not have an ongoing monitoring program to ensure stable manufacturing operations. “Specifically, you did not provide documentation to show that the manufacturing processes for your over-the-counter (OTC) sunscreen drug products have been validated.” FDA referred the manufacturer to read the agency’s guidance on process validation.
The firm’s quality unit also failed to have procedures in place to oversee “critical oversight responsibilities” such as investigations, change management, customer complaints, training, corrective actions and preventive actions (CAPAs), deviations, annual product reviews and written procedures for quality unit operations.
The company also lacked stability data to show that products met established specifications throughout their assigned shelf-life. The firm also did not set aside an appropriate number of batches for stability testing.
The company also reminded of its responsibilities as a contractor. “The FDA regards contractors as extensions of the manufacturer. You are responsible for the quality of drugs you produce as a contract facility regardless of agreements in place with product owners.”
Profounda, Inc.
Similar lax stability testing programs were identified by FDA investigators during the agency’s inspection of Orlando, FL-based OTC drugmaker Profounda, Inc.
FDA said the firm lacked the necessary data to support the storage conditions and expiration dates of its Rhinase D drug product. The company set a five-year expiration date for this product using only real-time and accelerated data to support these dates. The firm “lacked sufficient stability data to substantiate” the product’s five-year expiration period.
Profounda said it based the expiration date on its other drug product, Rhinase, which had a five-year expiration. FDA pointed out that Rhinase is a different product from Rhinase D and does not contain the same active ingredient, oxymetazoline hydrochloride.
The firm also lacked any kind of validation program, said FDA. The company “firm failed to provide data to demonstrate that you have validated manufacturing processes for your over-the-counter (OTC) drug products, including but not limited to “Rhinase D.” Your firm lacked qualification protocols, reports, or studies to determine if manufacturing processes were in a state of control and appropriate acceptance criteria were met.”
Another problem was the firm lacked a specific identity test to detect diethylene glycol (DEG) and ethylene glycol (EG) in shipments, containers, and lots of glycerin before they are used in manufacturing drug products.
FDA reminded the firm that “DEG contamination in glycerin has resulted in various lethal poisoning incidents in humans worldwide. In addition, we note that both glycerin and propylene glycol are ingredients used in your drug products. As a drug manufacturer, you are responsible for performing specific identity tests for all incoming shipments of component lots prior to release for use in manufacturing.”
FDA said that corrective actions must be taken within 15 days of receiving the letter.
Frenda Corporation
Poor sanitary conditions were observed by investigators prompted a warning letter to Frenda Corporation in Trujillo Alto, Puerto Rico. The firm manufactures OTC products, including hand sanitizers.
Investigators observed the presence of “insects and filthy conditions” at the facility. “There were several instances of insects found inside your supply of container closures (bottles and caps) in the facility. We are also aware of a consumer complaint of an insect observed in a hand sanitizer product,” FDA wrote.
Equipment was in a state of disrepair, with “rust-like residues” on the surfaces of the filling equipment and “dirty and damaged” seals on the filling line injector nozzles that contact the product.
In addition, the firm did not adequately design and validate its water system to ensure it was suitable for use in drug products. FDA said “you lacked water system validation, chemical and microbiological limits for component water, and routine morning for chemical and microbiological quality. Inadequate control and monitoring of our water system pose a potential risk for the presence of objectional microbiological contamination in your drug products.”
The firm also failed to separate drug manufacturing operation from industrial chemicals and failed to protect products from the external environment. The same warehouse and production areas were used for both products, and the facility doors were open to the outside environment during production.
FDA told the firm that “it is unacceptable as a matter of CGMP to continue manufacturing drugs using the same equipment that you use to manufacture industrial chemicals due to the risk of cross-contamination and potential for mix-ups.”
In addition, inspectors said the firm failed to conduct identity tests on components, including the active ingredient isopropyl alcohol. Instead, the company relied on the certificates of analysis (COA) from its suppliers and did not independently establish the reliability of each of its suppliers’ COAs.
FDA said that “the use of ethanol contaminated with methanol has resulted in various lethal poisoning incidents in humans worldwide,” and advised the manufacturer to consult its guidance document on testing alcohol (ethanol) and isopropyl alcohol for methanol.
The company has since stopped manufacturing drugs at the facility.
Warning letters: Formology, Profounda, Frenda


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