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Regulatory Focus™ > News Articles > FDA Warns German Contract Manufacturer Over API Stability Concerns

FDA Warns German Contract Manufacturer Over API Stability Concerns

Posted 24 May 2016 | By Zachary Brennan 

FDA Warns German Contract Manufacturer Over API Stability Concerns

The US Food and Drug Administration (FDA) has warned Baesweiler, Germany-based contract manufacturer BBT Biotech GMBH over deviations from good manufacturing practices (GMPs), including the failure to provide stability data to support expiration dates for active pharmaceutical ingredients (APIs).

The warning letter, sent 16 May and released Tuesday, follows an inspection at the API manufacturing facility in May 2015 during which FDA inspectors found BBT Biotech did not provide any stability data to support expiration dates on APIs shipped to the US in 2012.

“We acknowledge your commitment to follow your SOP [standard operating procedure] and perform the required stability testing on future batches. However, your response was inadequate because you failed to include any retesting of the API already distributed,” FDA said.

The company was also cited for failing to provide change management documentation or any other documentation for raw material supplier changes.

In addition, BBT’s investigation into a failed in-process control test for a certain lot of API identified that the supplier change was a possible root cause for the failure, though FDA notes the company “did not evaluate other lots made with crude [redacted] from the same supplier.”

The company says on its website that it supplies a range of live microorganisms, with batch sizes up to several kilograms, as well as proteins, including thrombolytica, fertility hormones and inhibitors. The company also produces APIs for early phase clinical trials with 30- to 500-liter fermenters and GMP commercial production on a scale up to 18,000 liters.

Data integrity was another issue that cropped up for FDA’s inspectors.

For example, all BBT employees, according to the letter, had administrator privileges and shared one user name, so actions could not be attributed or traced to specific individuals, which also means that the electronic data could be manipulated and/or deleted without traceability.

“Our investigator also noted that your firm copied raw data to a CD,” the letter says, “and then deleted the data from the [redacted] system to free space on the hard drive. Files copied to the CD were selected manually; the selection process was not supervised. Without audit trail capabilities or supervised file selection, there was no assurance that all raw data files were copied to the CD before they were permanently deleted from the system.”

Warning Letter

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