Ben Venue Labs Receives Warning Letter

Bedford, OH (Nov. 16)-The US Food and Drug Administration has issued Ben Venue Laboratories a Warning Letter resulting from CGMP deviations found during an inspection of the company’s “Propofol” injectable emulsion manufacturing facility earlier this year. Ben Venue Laboratories is a contract developer and manufacturer of sterile pharmaceuticals and a subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT).

The Warning Letter cited the following deviations:

• Failure to establish written control procedures to monitor the output and validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product, 21 CFR 211.110(a)

• A failure of the quality control unit to reject in-process materials during the production process that were tested for identity, strength, quality and purity, 21 CFR 211.110(c)

• A failure to thoroughly investigate any unexplained discrepancy or the failure of a batch or any of its components to meet any of its specifications whether or not the batch has already been distributed, 21 CFR 211.192.

The letter specifically referred to the company’s failure to conduct a thorough investigation to determine the source of exceeded levels of in-process endotoxin of multiple lots of Propofol. The investigators found that although these lots “passed final product testing for endotoxin” the company’s quality control unit “determined these lots to be acceptable for release without determining the source of the contamination.” In addition, the letter stated that the company’s “investigation of these lots concluded that since the in-process test for endotoxin was for investigational purposes, full investigations were not required.”

FDA concluded that it was “concerned that [the company] may lack an adequate understanding of the product and the process for manufacturing Propofol” and recommended a review of process design and entoxin controls for the manufacturing process.

The detailed Warning Letter may be viewed here.