The U.S. Food and Drug Administration (FDA) has issued a warning letter to Fresenius Kabi after identifying deficiencies in the company’s handling of manufacturing deviations associated with reports of adverse events tied to famotidine injections. The warning follows an inspection of the company’s sterile injectables facility in Melrose Park, Illinois, conducted between Jan. 27 and Feb. 18 this year.
According to the FDA, patients reported adverse reactions after receiving famotidine injections manufactured at the site between 2025 and 2026. Famotidine is an H2 blocker used to treat heartburn and stomach ulcers. The agency said some reports involved apparent pyrogenic reactions, a medical term for fever, which can occur when injectable products are contaminated by pyrogens.
FDA Findings on Famotidine Production
The FDA stated that multiple bioburden action limits were exceeded during the production of famotidine injections. Inspectors concluded that Fresenius Kabi did not adequately investigate the deviations and allowed batches to be released after finished-product testing initially showed acceptable results.
Subsequent testing conducted after adverse event reports and customer complaints identified endotoxin contamination, leading to the recall of three famotidine batches. According to the FDA, the company did not sufficiently investigate the manufacturing deviations despite signs of elevated bioburden levels.
In its response to an FDA Form 483 issued after the inspection, Fresenius Kabi acknowledged that bioburden samples had shown Gram-negative confluent growth. However, the FDA said the company failed to adequately consider the associated endotoxin risk despite the elevated bacterial findings.
Agency Seeks Broader Corrective Measures
While Fresenius Kabi committed to increasing endotoxin sampling and testing, the FDA said the response did not fully address broader quality concerns. The agency called on the company to strengthen its complaint handling system and corrective and preventive action processes.
The FDA emphasized the importance of maintaining upstream manufacturing controls and stated that atypical bioburden findings require prompt attention. The agency also said Fresenius Kabi had not committed to a comprehensive review of its complaint system to improve vigilance.
A Fresenius Kabi spokesperson said no patient safety concerns have been identified and that the Melrose Park facility remains operational. The spokesperson added that the company does not currently expect significant disruptions to product supply and is taking steps to address the FDA’s observations. The spokesperson also said remediation activities are underway at the site.
Concerns Over Aseptic Practices and Hair Contamination
The warning letter also cited deficiencies related to aseptic manufacturing practices. Fresenius Kabi determined that deficient operator techniques could have contributed to media fill failures, but the FDA said the company’s investigations did not adequately examine why those practices were not detected by its aseptic observer program during commercial operations.
Inspectors also reviewed incidents involving visible particulate contamination. Beginning in May 2022, the company documented at least nine cases of extrinsic contamination during product inspection, including hair found in drug products.
“This contamination was described as free-floating and in direct contact with the drug product,” the FDA said.
The agency stated that drug products contaminated with hair can have microbial contamination and are generally considered adulterated. It also said Fresenius Kabi did not initiate timely investigations in response to the contamination events.
Warning Letter and Recent Regulatory Scrutiny
The FDA’s Sept. 22 warning letter gave Fresenius Kabi 15 business days to respond. The agency also recommended that the company engage a current good manufacturing practice consultant to assist with corrective actions.
The letter marks the second FDA warning letter issued to a company within the Fresenius group in less than a month. Fresenius Medical Care, which specializes in renal care and dialysis, received a separate warning letter in late August concerning its facility in Ogden, Utah.
The latest action also follows several recalls involving Fresenius Kabi products during the summer, including recalls related to contamination concerns and product labeling issues.
Kabi is facing regulatory scrutiny after the U.S. Food and Drug Administration identified manufacturing deviations at a facility producing famotidine products. The FDA warning highlights concerns about production controls and reports of adverse events associated with affected products.
Kabi Manufacturing Issues Draw FDA Attention
The FDA’s inspection identified deficiencies involving manufacturing and quality-control practices at the facility. For Kabi, the findings underscore the importance of maintaining strict production standards for injectable and other pharmaceutical products.
Manufacturing deviations can become significant regulatory concerns when they have the potential to affect a medicine’s identity, strength, quality, purity or safety. The FDA uses facility inspections to determine whether manufacturers are consistently following current good manufacturing practices.
