FDA cites firms for CGMP violations, failure to submit PMA application
The US Food and Drug Administration (FDA) has issued warning letters to several firms that have violated current good manufacturing practice (CGMP) requirements, and one firm that has failed to submit an approved application for premarket approval (PMA).
CareFusion 213
In its warning letter to CareFusion 213, LLC, a subsidiary of Becton Dickinson, FDA said the company has received “more than 2,500 customer complaints” since September 2023 that their drug products contained foreign matter, missing components, and compromised package seals, among other issues. They noted the company has amassed “significant violations” of CGMP regulations for finished pharmaceuticals, and the investigations conducted by the company in response to the agency’s 483 form failed to “adequately identify root causes, provide scientific rationale for your conclusions, and extend investigations to other potentially affected batches.”
The agency also cited CareFusion 213 for deficient corrective actions and preventive actions (CAPAs) and out-of-specification (OOS) investigations and stated the company’s response that they hired a consultant to investigate these issues was inadequate. CareFusion 213 also chose to perform the extended investigation when FDA investigators pointed out the gaps in the original investigation. “You have not adequately explained how your quality unit failed in its oversight of numerous investigations associated with repeated and systemic product quality deficiencies that led to customer complaints,” FDA said.
FDA said that the company “has a history of sterility-related quality issues including multiple recalls and Field Alert Reports.”
“To ensure proper root cause analysis and appropriate CAPA implementation, investigations must be thorough, well-documented, scientifically sound, and timely,” the agency wrote. “Procedural updates and training alone do not address the systemic failures that allowed deficient investigations to persist undetected by quality unit oversight.”
In addition, FDA cited CareFusion 213 for a failure to create and follow written procedures for equipment cleaning and maintenance. Agency investigators identified personnel in the company’s facility were improperly wearing face masks, and observed a residue in air vents, on the walls, and on equipment in several areas across the facility, including the main production area.
Unetixs Vascular, Inc.
FDA’s warning letter to Unetixs Vascular, Inc., notes that the company’s vascular diagnostic ultrasound systems do not currently have an approved application for PMA. While previous versions of the firm’s ROODRA and 2CP vascular diagnostic devices had 510(k) clearance, FDA stated their review found the design and labeling modifications made to the devices would warrant a new 510(k) application.
“Our review found that the change was implemented to significantly mitigate a known risk in response to an adverse event,” the agency explained. “Specifically, the device design, construction materials and labeling changes, to physically prevent device misconnections, were implemented to address a complaint of a death caused by air embolism.”
This is not the first time the company has received a warning letter from the agency. FDA said it sent a warning letter to Unetixs Vascular in February 2020 for “significant quality system violations related to your vascular diagnostic ultrasound systems.”
FDA also reminded the firm that it needs to comply with the Quality Management System Regulation as of 2 February 2026.
“We understand that while you have made progress in implementing corrective actions, deficiencies remain as documented during the recent inspection. You should continue to ensure that you are making further progress to be in compliance with all of our regulations,” FDA wrote.
Other CGMP violations
The agency cited several other firms with significant CGMP violations, including Ava Inc., which FDA said did not have appropriate controls over their master production and control records. Ava Inc. reportedly used a shared username and password for their equipment that conducted impurity testing, and the agency noted analysts had the ability to modify and delete company data.
The firm also had inadequate data in their laboratory records from testing and did not have an adequate quality control unit responsible for the manufacture, testing, and release of their drug products.
“You fail to adequately address how the various issues associated with the unstable laboratory equipment will be handled by your deviation system in the future, and how you will ensure stability is restored only through appropriate systems suitability approaches,” the agency wrote. “You lack an adequate retrospective review to determine the scope and impact of your data integrity issues throughout your facility.”
A warning letter was also issued to Active Cosmetics Manufacturing Inc., for failing to properly investigate OOS microbiological test results for its over-the-counter topical drug products. “You released batches for commercial distribution based on passing retest results, without conducting thorough investigations to determine the root causes of the original results,” the agency explained.
The rapid microbiological test methods were also not validated, FDA said, using a pass/fail testing methodology that “not provide sufficient data on contamination levels, which are essential for trend analysis and evidence-based risk assessment to support quality evaluations and patient safety.”
Active Cosmetics Manufacturing also did not test each lot for contamination and relied on its supplier’s certificate of analysis “without establishing the reliability of each of your component suppliers’ analyses at appropriate intervals.”
FDA’s warning letter to Respilon Production S.R.O., concerned the company’s failure to perform testing to verify the components in their drug product, and to verify their suppliers’ test analyses. Respilon also did not create and conduct a testing program to evaluate the stability of their drug products.
“Without the appropriate stability studies, you do not have scientific evidence to support whether your drug product’s active ingredient maintains its strength, purity, and quality throughout the shelf life of the product,” the agency wrote.
FDA cited the company for not creating written procedures for production and process control, a lack of complete data in their laboratory records, and for not taking steps to create test methods with appropriate accuracy, sensitivity, specificity, and reproducibility.
“[Y]ou have not validated your overall manufacturing process or conducted stability studies to determine if microbial contamination proliferates throughout the shelf life of the product,” the agency said.
FDA recommended all three firms hire consultants to evaluate their company’s operations and help them meet CGMP requirements.
