SECRET audits by the powerful US Food and Drug Administration have revealed a multitude of manufacturing flaws at Australia’s biggest pharmaceutical company, CSL. The FDA’s 2010 and 2011 audits, released to The Australian yesterday after a Freedom of Information request, cite a string of “objectionable conditions and practices” used by CSL to make vaccines.
The FDA allegations – which CSL said yesterday had been or were in the process of being resolved – include the failure of laboratory staff to wear masks while dispensing and mixing vaccines, “deficient” tests to check whether viruses were properly split to prevent side-effects and “inadequate” investigations into product failures.
The FDA documents reveal that CSL took six months to start investigating the cause of mysterious dark particles in the national stockpile of swine flu vaccine.
The most recent audit, in March, branded as “inadequate” CSL’s investigation of febrile fits among children immunised with Fluvax, its seasonal flu vaccine.
Eleven months after Fluvax was banned for young children, the FDA audit discovered CSL had not compiled an investigations report or even designated anyone to be in charge of the investigation.
Australia’s pharmaceutical regulator, the Therapeutic Goods Administration, refused to release the findings of its own audits into CSL.
And CSL insisted the FDA audits contained “observations only” rather than any final determination of compliance.
CSL, the privatised Commonwealth Serum Laboratories, has also been under fire this week after being forced to ration supplies of penicillin in its role as sole Australian supplier of the medicine.
The FDA audit findings form the basis of a “warning letter” the US regulator sent to CSL in June, threatening to revoke its US licence if it failed to address outstanding issues.
This year’s audit described as “inadequate” CSL’s investigation into the high rate of fever and convulsions among children given the Fluvax shot last year. “There was limited analysis of the manufacturing process to determine why there was a substantial increase of adverse-event reports of fever and convulsions in the 2010 southern hemisphere influenza season in comparison to previous seasons. “There was no evaluation of testing of raw material and potential impact on manufacturing,” it said.
The audit found 15 lots of a key ingredient in CSL’s flu vaccines, the detergent sodium taurodeoxycholate, failed an “identity test” but were used regardless.
The detergent is used to split the flu viruses used to make vaccines to minimise side-effects.
The Medical Journal of Australia reported last week that CSL was “one of only a few manufacturers globally” to use the ingredient.
The FDA audit also criticised CSL’s “inadequate” investigation into the cause of dark particles that appeared in multi-dose vials of vaccines against swine and seasonal flu, produced for the US market in 2009.
“The investigation is ongoing and a root cause has not been determined,” its report said.
It also noted that CSL had manufactured products “outside the validated processes” without determining if they would remain stable until their expiry date.
It cited a “formulation error” discovered in July last year, when not enough swine flu virus was used in the vaccine against seasonal flu.
The FDA inspectors raised the problem of black particles in multi-dose vials during an inspection of the Parkville laboratory in April last year.
The same discolouration had been detected in Australia’s stockpile of swine flu vaccine, Panvax, for which the federal government paid CSL $131 million of taxpayer funds. Half the stockpile – 10 million doses – had to be destroyed after passing their use-by date last year, while the paediatric version was withdrawn early because the medication lost potency before the expiry date.
The FDA’s 2010 audit found CSL’s supplier of rubber stoppers had told the company they could react with the mercury in multi-dose vials and should not be used.
The TGA said it agreed with the FDA findings, but it refused to release its own audits.
UPDATE: from the Australian Broadcasting Corporation