In a warning letter last year, the FDA told Australian vaccine maker CSL that it should have thoroughly investigated whether its manufacturing processes had something to do with children having convulsions after getting its Fluvax vaccine. The company on Thursday said a two-year study found a linkage between the seizures and the vaccine but couldn't determine what in the manufacturing could have caused it.
A CSL executive reports the study found excessive viral components in the drug, triggering convulsions in some children, Bloomberg reports. CSL has been unable to get Fluvax licensed for children under 5 since health authorities in Australia suspended its use in response to reports of hospitalized children. Doctors reported at the time that there were two or three children hospitalized from reactions to Fluvax for every one flu-related admission avoided, Bloomberg says.
The final conclusion from the company was that its manufacturing left higher vaccine component levels than other vaccines makers but it couldn't determine why. The company says the increased levels of seizures may be related to characteristics of the virus unique to the 2010 strain.
While the vaccines must contain virus components, "it appears that components of the inactivated virus retained in Fluvax in 2010 overstimulated the developing immune systems of some young children compared to previous seasons," Darryl Maher, vice president of medical and research at CSL's biotherapies division, said in a statement.
The FDA in 2010 summoned CSL executives after inspectors found problems at the manufacturing plant. It then sent a warning letter chastising the company, for among other things, doing only a limited analysis of the manufacturing process to determine why the adverse events spiked in 2010 relative to previous seasons. "There was no analysis of all critical parameters and critical processing steps to try to determine differences in the 2010 lots compared to lots from previous seasons," the letter says.
The agency found lacking a separate investigation into dark particles found in thimerosal-containing multi-dose vials. The investigation focused only on multi-dose vials based on a review of data for syringes, rather than a visual examination to determine whether particles formed in syringes since release. And in another particle-related investigation, the company tested just one multi-dose vial lot and one syringe lot representing product distributed to the U.S. The FDA refuted the company's contention that "the dark particles are not foreign to the product." The FDA said, "direct analysis indicates they are discolored influenza split virus," possibly containing other compounds.
The statement says CSL is doing further studies to determine how to adjust its processes so it doesn't happen again. Until "CSL and the regulators are fully confident that our manufacturing process can consistently produce a safe and effective influenza vaccine for children," CSL will support age restrictions in all markets, Maher said.