FDA warns drugmakers over contamination controls, inadequate investigations
The US Food and Drug Administration (FDA) recently issued two warning letters to a sterile drug manufacturer and an over-the-counter (OTC) drug maker in the US for multiple violations of good manufacturing practices (GMPs). These violations included inadequate contamination controls, failure to investigate batch issues, and insufficient testing of components.
Additionally, the FDA's Center for Biologics Evaluation and Research (CBER) sent an untitled letter to Fenwal International, a subsidiary of Fresenius Kabi, highlighting GMP deficiencies related to the manufacturing of blood-pack units (BPUs) and component solutions intended for the collection and storage of whole blood and blood components. The letter emphasized the need for the facility and equipment to be maintained in a proper state of repair.
International Medication Systems
FDA issued a warning letter to International Medication Systems Limited, located in South El Monte, CA, due to numerous GMP violations in their cleanrooms. These violations included insufficient investigations of batch failures and inadequate environmental monitoring procedures. The company produces active pharmaceutical ingredients (APIs) and sterile injectable drug products, including epinephrine injections.
Investigators said the company failed to adequately address multiple too-numerous-to-count (TNTC) microbial findings during the manufacturing of epinephrine injection.
For example, a viable air environmental monitoring plate, located next to the ISO 5 aseptic filling area, yielded a TNTC result “with confluent bacterial growth and numerous insect larvae.” The same day, personnel monitoring plates for an individual in the adjacent ISO 7 aseptic filling area also yielded TNTC results; insect larvae were also found in both cleanroom areas.
FDA said the company’s investigation failed to identify a root cause, instead attributing these “exceedingly high” environmental monitoring findings to an “unsubstantiated hypothesis” alleging insect infiltration of sealed monitoring plates.
FDA stated that “the presence of insect larvae and gross microbial contamination in your aseptic processing area demonstrates a critical failure of your contamination control program. The decision to release a lot manufactured under these conditions also demonstrates that your quality unit failed to exercise its responsibility to ensure drug products are manufactured under appropriate conditions and to reject any lot produced under conditions that compromise its quality.”
The company’s restricted access barrier systems (RABS) also came under criticism for lacking the necessary “fundamental design elements” to minimize or eliminate direct gowned personnel interventions. For example, operators must manually cut open numerous stopper bags and transfer stoppers using a scoop. FDA said that “these manually-intensive interventions pose a significant and repeated risk of microbial contamination.”
FDA told the company that “your firm’s aseptic processing lines and operations were inadequately designed, controlled, and monitored to prevent microbiological contamination.”
The agency also noted that between March 2021 and March 2026, the company submitted three field alert reports for contamination issues for its sterile drug products. In addition, the company received over 90 customer complaints related to container-closure deficiencies such as glass breakages and cracked vials since December 2023. Many of these investigations were closed without finding a root cause.
Following FDA recommendations, the company decided to recall its epinephrine injection USP due to lack of sterility assurance on 1 April 2026.
Spa De Soleil kept testing to obtain passing results
FDA issued a warning letter to Spa De Soleil, Inc., located in Sun Valley, CA, highlighting several violations of GMPs. These violations included the company's failure to investigate batch failures, insufficient testing of components, and a weak quality control system. Spa De Soleil, Inc. produces topical OTC products.
Between May 2024 and July 2025, the company did not properly investigate 51 out-of-limit (OOL) and out-of-specification results related to its products. This included tests for conductivity, total organic carbon, and the detection of gram-negative microorganisms. The investigations failed to identify the recovered microorganisms. Furthermore, the company resampled and retested the products for microbiological quality in an attempt to obtain passing results.
“Following an OOL recovery, you also placed certain point-of-use valves on hold until you obtained a passing result. However, this practice did not prevent you from using other valves on the same system,” FDA wrote.
FDA stated that the company also failed to verify the identity of the components used to manufacture the drug product, relying instead on the certificates of analysis from their suppliers without establishing the reliability of those results.
The agency stated the company's choice not to properly test incoming components for methanol contamination before using them in APIs poses a significant risk.
FDA notes that products “contaminated with methanol has resulted in various lethal poisoning incidents in humans worldwide.”
The agency added similar cGMP violations were found in a previous inspection in September 2021. It warned that “repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.”
Fenwal International
CBER investigators observed similar GMP violations in an untitled letter to Fenwal International, a subsidiary of Fresenius Kabi, located in Maricao, Puerto Rico. The company was criticized for not maintaining its facility and equipment in an adequate state of repair.
The company makes blood-pack units (BPUs) as well as component solutions intended for collecting and storing whole blood and blood components.
Investigators said that the company failed to clean and maintain equipment to prevent malfunctions or contamination. FDA said it found “white and black residues as well as apparent corrosion” inside its equipment used to formulate the solutions for its products. In addition, black, yellow, and green residues and “apparent corrosion” were observed inside the equipment.
The agency also said the facility was in a poor state of repair. In one of the filling rooms, black material was observed on the surfaces of HEPA filters in the ceiling in the room where products are filled. In the mixing rooms, there were cracked ceiling light fixtures with missing light panels, and peeling stickers. In addition, “apparently biological, residue and standing pools of water” were found near and inside of the air handling unit (AHU) that supplies air to the filling room where the product is filled.
FDA previously issued a warning letter to the company in September 2023, and noted that the most recent inspection “identified new or continued deficiencies related to your facilities and equipment.”
Spa DeSoleil; International Medication Systems; Untitled letter to Fenwal
