CSL pays heed to FDA observations on faulty manufacturing processes

By Dr. Ananya Mandal, MDOct 2 2011

Australia’s biggest pharmaceutical company CSL has taken steps to address most manufacturing flaws highlighted by the US Food and Drug Administration (FDA) and promised that the remaining concerns are being resolved.

Audits carried out by the FDA last year and this year revealed, what was described as, objectionable conditions and practices in CSL. Allegations include the failure of laboratory staff to wear masks while dispensing and mixing vaccines, and deficient tests to check whether viruses were properly split to prevent side-effects.

CSL says the FDA's inspection reports contained observations only, and were not final determinations on a manufacturer's compliance with regulations.

The FDA sent a warning letter to CSL in June, raising concerns about its manufacturing operations, and warning if they were not fixed it may withdraw the company's license to sell products in the US.

Those potential problems include the unexplained rise in the number of children suffering a high fever and convulsions after they were given the seasonal flu shot last year. In response, the FDA says, CSL engaged in “limited analysis” of the manufacturing process and “no evaluation of the testing of raw material”.

But the problems are not just confined to the seasonal flu vaccine. The FDA audit also criticized the drug company's “inadequate investigation” into the cause of dark particles in multi-use vials of the swine flu vaccine produced for the US and Australia. The Australian Therapeutic Goods Administration (TGA) says its investigations have found that the dark particles disappear when the vaccine is stored at room temperature, and that they may have resulted from an interaction between the vaccine and the vial's rubber stoppers.

The Australian drug regulator referred to a statement it issued at the beginning of July. “While both the TGA and the FDA are of the view that, based on the information currently available, the deficiencies don't represent a risk to public health, they are of a nature that, if left unaddressed, could have future public safety implications,” an extract from the statement reads. “Therefore, it is important that CSL actively works to rectify all the concerns raised adequately. In the meantime, the TGA is closely monitoring the situation to ensure that neither Australian nor American consumers of CSL products are exposed to unnecessary risk.”

Dr Peter Howard is an honorary research fellow specializing in immunization at the University of Melbourne. “It's clear that [the company] needs to take a very long look at their safety and monitoring procedures, particularly during the manufacturing process,” he said. But Dr Howard says patients should not worry about the safety of vaccines in Australia. “You're talking about major international companies, of which CSL is one, who produce vaccines, and it is their responsibility to ensure safety…That's the first priority for any medicine: to do no harm,” he said.

Health Minister Nicola Roxon last week said the TGA held similar concerns to the FDA. “The concerns raised by the FDA are similar to those raised by the TGA with CSL through several audits since a number of children had febrile reactions following immunization with CSL's flu vaccine, Fluvax, last year. It's important to note that neither regulator found product safety issues,” she said.