Flu vaccine maker CSL has been cited by the FDA for GMP failures spanning a lack of follow-through on raw material test failures to half-hearted investigations into adverse reactions suffered by hundreds of Australian children after they received the Fluvax shot last year. Twenty-three of those children landed in the hospital with seizures and fever. The Australian government ultimately withdrew the flu vaccine for use in children.
Exec VP Jeff Davies attempts to minimize the impact of the letter in an interview with ABC News Australia. "I think [the FDA] is just concerned about how we documented that process...the FDA has identified flaws in the methodology we use to look at these investigations and I think we're working with them to address that.... FDA is really questioning the methodology we used around some initial testing that we do on product."
But the Therapeutic Goods Administration, Australia's drug regulator, sides with the FDA and says it has conducted special audits of the vax maker's facility as part of its investigation into the adverse reactions.
The FDA warning letter, sent to CEO Brian McNamee, says inspectors found no documentation of the company's April 2010 investigation into the fever and convulsions in the children. Regulations require documentation of activities and decisions for traceability of corrective actions, from the initial identification of problems to the implementation of solutions and the follow up to evaluate effectiveness.
The regulator says also that it found 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."
A separate investigation into dark particles found in thimerosal-containing multi-dose vials also was deemed inadequate. The investigation focused only on multi-dose vials based on a review of data for syringes, rather than an 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. "There is no statistical rationale for use of this sample size."
The FDA refutes the company's finding that "the dark particles are not foreign to the product." Instead, says the regulator, "direct analysis indicates they are discolored influenza split virus," possibly containing other compounds
Last year CSL sold $53 million worth of flu vaccine in the U.S., according to an ABC report, nearly half of its worldwide flu vax sales.