UPDATED: FDA ravages Sanofi vaccine sterility process in warning letter

An FDA warning letter that lays out two dozen observations at a Sanofi Pasteur plant in Canada explains some of the mold and contamination problems that led the company to close some operations, a move that it says will lead to a shortage of BCG tuberculosis vaccine.

Sanofi Pasteur, the largest operation devoted to human vaccines in the world, in June recalled four batches of the tuberculosis vaccine BCG and suspended production at a plant in Canada after Australian regulators found problems with sterility. The result will be a shortage there, as well as perhaps in Canada. There were also worries that the halt in production could lead to a global shortage of the bladder cancer drug ImmuCyst, but spokesman Len Lavenda said that "As of today, this notification does not impact our ability to supply the market, except for our BCG products manufactured in Toronto."

An FDA warning letter posted Tuesday on the agency's website lays out a particularly long list of observations, 24 at the plant in Toronto inspected in April, as well as a couple more found during a routine March inspection of a plant in Marcy l'Etoile, France. Among other problems at the Toronto plant, the FDA says, "there have been no less than 58 documented non-conformances relating to the isolation of mold within the BCG aseptic processing areas" since August 2010.

In an emailed response to FiercePharmaManufacturing, the company says it is moving as quickly as possible to address FDA issues at both plants, and has responded to the FDA with the actions it has already initiated. It says it has "full confidence in the products released from its facilities" and that manufacturing safe and effective vaccines and biological products "remains Sanofi Pasteur's highest priority."

"Sanofi Pasteur takes the observations outlined in the recent FDA Warning Letter seriously," said Olivier Charmeil, president and CEO, Sanofi Pasteur. "We are working diligently with the FDA to implement a series of immediate and ongoing steps to address their concerns and further strengthen our global manufacturing operations and quality systems. I have full confidence in our products in the market."

The FDA sounds less confident. In the warning letter it also says that because of testing issues, the company can't be sure that all lots of the BCG vaccine manufactured in one building since the last successful sterility test in 2000 are safe. It says there are questions whether the test the company has used is capable of detecting mold in the product.

In addition, FDA investigators had issues with vial handling in the aseptic processing area in the filling and packaging building, the fact that employees were allowed to move unchallenged from the live vaccine area into the washing and sterilizing area, had questions about its disinfection practices, and observed on April 18 that there were "nesting birds" in the air handling units.

In France, problems included not thoroughly investigating what caused some lots of Conjugated Haemophilus Vaccine and typhoid vaccines to test out of specifications.

The agency has ordered the company to do a "comprehensive and global assessment of all of its manufacturing operations to ensure that all products conform to FDA requirements" and suggested a meeting with Sanofi ($SNY) executives to discuss the company's responses and plans. The agency also said that all warning letters about biological products"are passed along to federal agencies "so that they may take this information into account when considering the award of contracts."

- here's the FDA warning letter