Fujifilm Diosynth Cited Over NC Plant’s Microbial Contamination Controls

FDA has cited Fujifilm Diosynth Biotechnologies USA for significant manufacturing deficiencies at its drug substance facility in Research Triangle Park, NC, raising concerns about microbial contamination controls, environmental monitoring and investigations into repeated contamination events, according to a Form FDA 483 issued following a March inspection.

The inspection came on the heels of a separate FDA-483 released in April (see earlier story). That document covered an inspection at the Fujifilm’s drug manufacturing facility in College Station, TX, which resulted in eight inspection observations.

The inspection, conducted 3/23-27, resulted in four observations involving the contract development and manufacturing organization's quality systems. FDA investigators concluded that facility design and manufacturing controls did not provide adequate assurance against microbial contamination and cross-contamination risks for drug substances intended for commercial distribution.

The agency's most significant observation focused on what inspectors described as persistent microbial contamination problems. According to FDA, Fujifilm had isolated about 80 bacterial spore-forming organisms and about six mold isolates from classified manufacturing areas between 1/2025 and the inspection, while at least eight manufacturing batches had been rejected since 2024 because of contamination.

Despite those recurring events, investigators said the company had not determined the root causes or implemented adequate corrective and preventive actions. FDA criticized the firm's repeated conclusion in contamination investigations that there was "no impact to process performance or product quality," calling that position unacceptable given the contamination risks associated with sterile drug production.

A second observation addressed the company's handling of contamination investigations. FDA said multiple investigations into mold recoveries from processing rooms, raw materials and in-process products failed to identify root causes or implement effective corrective actions. In several cases, contaminated batches were either released or rejected without investigators determining how the contamination occurred or preventing recurrence.

The agency also criticized Fujifilm for failing to investigate at least 26 recoveries of bacterial spore-forming organisms in drug substance samples since January 2025 because company procedures did not require such investigations. FDA said the firm therefore had not identified the sources or routes by which the organisms entered the manufacturing process.

In addition, investigators highlighted repeated recoveries of water-system contaminants, including Ralstonia pickettii and Burkholderia lata, organisms capable of forming biofilms in pharmaceutical water systems. FDA said the company's responses — including replacing components, sanitizing systems and repeating sampling — were not supported by adequate validation or risk assessments demonstrating that biofilms had been eliminated or that the systems remained in a validated state.

The third observation cited deficiencies in procedures governing testing of process equipment after use. FDA said the company's procedure allowed managers to approve an undefined number of additional tests beyond the established limit, which inspectors said could fail to detect equipment failures.

Finally, FDA concluded that Fujifilm had not demonstrated that its microbiological testing methods were suitable for recovering organisms that could pose risks to patients, particularly in light of the facility's repeated recoveries of bacterial and mold spore-formers. Investigators noted that company officials acknowledged having "no tolerance for spore-formers," yet the firm's testing program did not specifically screen for those organisms or require reassessment of testing methods after approval.