The FDA has issued a warning letter to German pharma company Fresenius Kabi after finding "serious violations" at its Melrose Park, Illinois facility.
In the letter, dated September 22, the FDA said that it had identified significant CGMP violations relating to sterile injectable manufacturing during its inspection of the site earlier this year.
The agency added that the deficiencies included inadequate investigations, aseptic processing controls and visual inspection, resulting in drug products that are considered adulterated under the FD&C Act.
The warning comes shortly after the FDA raised separate CGMP concerns at Fresenius Medical Care’s Ogden, Utah facility, including issues involving leaking sterile dialysis solution bags and inadequate quality investigations.
The site
Fresenius' Illinois facility manufactures sterile injectable products, primarily through aseptic processing.
The campus previously underwent a $250m expansion starting in 2017 to expand automation, cleanrooms and aseptic filling lines, which was scheduled for completion by the end of this year.
The location also became Fresenius' first site to implement virtual reality (VR) cleanroom training for new employees.
Bioburden and endotoxin failures
The Warning Letter details multiple bioburden action-limit failures during famotidine injection manufacturing, detected after reports were received that patients were experiencing adverse events, including apparent pyrogenic reactions.
The FDA said that the company "failed to sufficiently investigate this critical deviation," instead releasing affected batches based on passing finished-product sterility/endotoxin tests.
Subsequent testing of retained product found an endotoxin failure and ultimately, three famotidine batches were recalled.
The FDA criticised the company's investigation and reliance on finished-product testing, saying that the company had seen an upstream warning sign and treated it as though a passing finished-product test made the warning sign irrelevant.
The letter added that atypical bioburden levels should be treated as a signal requiring "prompt attention."
Aseptic processing failures
The FDA said that Fresenius also had media-fill failures on multiple aseptic manufacturing lines, with one line experiencing failures in September and October 2024 and another restricted-access barrier system line in April and October 2025.
Fresenius identified the most probable contributing factor as deficient aseptic technique by operators, but the FDA has argued that the firm had failed to adequately consider why it didn't detect poor practices during commercial production.
The FDA did also identify poor aseptic practices during the inspection but, more fundamentally, said some lines have design flaws, including inadequate barrier protection, excessive interventions and ergonomic/layout problems.
The agency explained that the manufacturing lines required excessive intervention and had inadequate barrier protection; thus, the problem isn't necessarily something that can be solved through operator retraining alone.
Visual inspection and contamination
The Warning Letter mentions that, beginning in May 2022, Fresenius documented at least nine incidents of extrinsic contamination, including hair, during visual inspection, with contamination described as free-floating and in direct contact with the drug product.
The FDA said the firm's visual inspection programme failed to detect this particulate contamination and that Fresenius did not initiate timely investigations in response or adequately assess potentially affected products.
Remediations
The FDA has given Fresenius a comprehensive list of remediation measures, including an independent assessment of its investigation and CAPA systems and a retrospective review of critical investigations from the previous three years.
The company must also review its endotoxin and environmental monitoring programmes, conduct comprehensive assessments of its aseptic processes and media-fill programme and remediate its visual inspection systems.
Fresenius Kabi has also been asked to provide an updated plan to accelerate the transfer of manufacturing away from certain aseptic filling lines, along with a list of backup contract manufacturing organisations that could protect supply in the event of disruption.
The company stated that no patient-safety concerns have been linked to distributed products and that the Melrose Park site remains fully operational while remediation plans are underway.
The firm said that it does "not anticipate significant disruptions to the supply of products currently on the market."
