MELBOURNE, Australia- A warning letter from the Food and Drug Administration (FDA) to Australian vaccine manufacturer CSL Biotherapies has shaken confidence in the country's biotechnology superstar. The letter dated June 15 accuses CSL not properly investigate why its vaccine against influenza Fluvax last year caused a strongly higher rate of febrile convulsions in children under five. "There was no analysis of all critical parameters and critical processing steps to try to determine differences in the 2010 batch associated with adverse event reports compared to lots from previous seasons" the letter. The CSL letter has 15 days to respond to its concerns or risk losing its license to sell Fluvax the United States, where it is marketed under the name Afluria.
"We take very warning letter serious, "said Jeff Davies, executive vice president of CSL Biotherapies, in a prepared statement. "Our technical team is preparing more substantive detail about our corrective actions to meet the requirements of the FDA."
CSL Biotherapies is one of the best interpreters of biotechnology Australia, with 2010 revenues of $ 4.8 billion; Fluvax global sales were $ 130 million, including $ 56 million in the United States. After adverse reactions to the vaccine against influenza reported in 2010, the FDA sent inspectors in June to CSL manufacturing plant in Melbourne. After a second visit last March, the FDA issued its warning letter, which stated that the quality control unit of CSL had failed to "assume its responsibility to ensure the identity, strength, quality and the purity of your monovalent bulk of the flu and the final products of the drug. "
a recent study by Paul Armstrong at the Ministry of Health, Western Australia, and colleagues reported that the rate of seizures fever in young children was 3.3 per 1000 doses 0 times that reported in a study on the safety of vaccines against influenza in the United States. the same study found that febrile seizures were related to the CSL vaccine but not to similar such as vaccines Influvac and Vaxigrip.
in the June issue of the journal vaccine , Christopher Blyth at the University of Western Australia and colleagues found that Fluvax (but not other vaccines against influenza) have triggered the release of high levels of cytokines in isolated blood cells from children who had febrile seizures. Cytokines are natural immune system molecules that induce fever. Investigations by independent laboratories and CSL failed to determine why Fluvax appears strongly raise the cytokine levels.
According to the letter from the FDA, the CSL manufacturing methods hampered the ability to root out the cause of adverse effects. CSL vaccine prepared by killing the flu virus and divide. The degree of separation could influence how the vaccine triggers an immune response, said a vaccine against influenza expert who requested anonymity. But the FDA said the degree of separation has not been determined in the different lots. "You failed to determine the optimal separation conditions for new virus strains before the strains are used in the production," said the FDA's letter to CSL. The FDA also said that the release agent used to fragment the virus, sodium taurodeoxycholate (TDOC) had failed a test to confirm the identity of the chemical. Another criticism is that the FDA CSL failed to identify what the FDA calls "dark particles" in some vials. In addition, the FDA said that CSL failed to properly document its procedures for investigating why the vaccine caused the adverse reactions.
A spokesman said CSL Science Insider in an email that the investigations by the company and by the regulatory body of drugs in Australia, the Authority Therapeutic Goods (TGA), currently identified no contaminant in the manufacturing process. In addition, they stressed that although TDOC failed a first test, he spent a further test of his identity. "We hope to be able to draw conclusions [about the cause of the elevated rate of febrile convulsions] in the coming months and will be totally transparent about our results," wrote the CSL spokesman.
Concerns about Fluvax cause the anxiety in the community of biomedical research in Australia. "I've never been convinced by the cost-benefit equations for the vaccination of healthy people or children against the flu, but one of the things that I do not think that there was a problem with the manufacturing process, "says Peter Collignon, director of infectious diseases at the medical school of the Australian national University in Canberra. He says he is concerned that the FDA not TGA, broadcast for the first concerns about the vaccine. "This raises questions about the transparency of our own regulator," he said.
On June 21, TGA revealed that he had sent letters in May 2010 after five audits CSL reported problems ranging from "inadequate investigation" to "poor management of corrective and preventive actions", and cleaning "insufficient" and testing regimes. CSL Davies told the media that TGA was "fully aware" of the problems, but did not consider it appropriate to publish the correspondence with the regulator.
the FDA warning letter raises the stakes. It "means that they will be doing things rather quickly or they will not make these more vaccine," says Collignon. "If you can not market in the United States because it is not enough safe, then it will not be very satisfactory for Australia either."
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