The FDA issued an import alert in April banning all human and veterinary antibiotics and other drugs coming out of a plant in the Czech Republic. A warning letter the FDA posted this week to its website explains why. Vuab Pharma was shipping active pharmaceutical ingredients (APIs) to the U.S. that were contaminated with bacteria and didn't even have tests that were capable of detecting it.
The FDA discovered the problems during an inspection at the company's plant in Roztoky near Prague a year ago, but just sent the warning letter last week after receiving several responses from the drugmaker. According to the FDA warning, inspectors found that in January 2014, a Vuab customer complained it had discovered that one of the APIs it bought from Vuab was contaminated by Clostridium sphenoides. Vuab's checked returned samples but didn't find any bacteria. The problem, according to the FDA, is that the test Vuab used was "inadequate to detect" the C. sphenoides. The customer pointed that out to Vuab during an on-site audit it conducted after detecting the contamination.
According to FDA inspectors, the issue with the C. sphenoides contamination was not an isolated incident. Another customer found an API that was contaminated with Bacillus. And that was only one of a number of issues inspectors found, including ongoing problems with data integrity that the agency noted as far back as 2008.
The FDA pointed out in its warning letter that not all companies will be as diligent as those that complained to Vuab, making it essential that the API maker thoroughly samples for contamination before it ships products to the U.S. Not only that, inspectors said that when Vuab did confirm the the problems, it still didn't investigate the source of the contamination so it could be avoided going forward.
The "objectionable microbiological contamination in your API … indicates a significant failure in your capability to prevent microbiological contamination in your operation," the FDA told the company. It said it not only wants Vuab to produce a plan for testing going forward, but also to hear how it intends to determine what other batches may have been affected by the problems already uncovered and what Vuab intends to do about those.
On top of that, the FDA found that Vuab's testing equipment was unable to produce an audit trail and that when inspectors asked for backup data from disks, the company claimed they were unreadable and had been for sometime. Inspectors also noted there were no controls in place with passwords to prevent employees from deleting data that indicated failed batches. The agency pointed out that during an inspection in September 2008, FDA employees uncovered problems with the company's handling of raw analytical data, including discrepancies between laboratory notebooks and printed chromatograms.
"This lack of control over the integrity of your data raises questions about your analytical data's authenticity and reliability, and about the quality of your APIs." The agency said that until it is satisfied that Vuab has resolved all of the problems it laid out in the warning letter, it may not approve any applications for new products and that the ban is likely to remain in place.
The FDA has been stepping up its foreign inspections since Congress in 2013 approved new fees to help the agency cover the costs of sending employees around the world. But the challenges it faces were apparent in a report made recently to Congress by the Office of the Inspector General. The OIG said that in 2013, the FDA was able to conduct surveillance inspections of all generic manufacturers that it had identified as high risk. But it also pointed out that while the FDA performed 142 ANDA pre-approval inspections of foreign manufacturers in 2013, up 40% from the 101 it did in 2011, the share of foreign manufacturers inspected fell to 50% that year from 60% two years earlier.