The report, a "483 form" obtained by The San Francisco Chronicle under a Freedom of Information Act request, reveals that just three months before Chiron was given approval on October 17 to deliver its much in demand influenza vaccine, its English facility was far from ready to produce the vaccine in line with the standards the FDA expects.
In the summer of 2004, Chiron's 48m dose production of Fluvirin flu vaccine was judged unacceptable for use by the FDA, and British regulators shut down the Liverpool facility, so questions now arise as to how Chiron spent the ten-month period between the site closure and a nine-day FDA inspection in July 2005.
After the July inspection and a report sent to Chiron, the vaccine manufacturer responded with proposed corrective actions which the agency deemed "generally acceptable."
But the report, whose contents are described in a Chronicle article, shows how big a mountain plant operators had to climb in a short period of time, as bacterial contamination testing was still not reliable and dozens of reports that ought to have been filled to report errors were not submitted.
The FDA inspectors wrote that Chiron had yet to develop a useful test that could spot Serratia marcescens bacteria, the strain that contaminated Chiron's vaccine and led to the temporary loss of its licence.
The report found that Chiron had isolated Serratia marcescens bacteria in five lots of vaccine during manufacturing last year and eleven times in routine environmental sampling.
What is more, Chiron's new system for handling deviations from current good manufacturing practice (cGMP) failed to document corrective and preventive action on 29 of 40 reports involving the plant environment.
The inspectors also found ten of 31 reports involving water in the sterile manufacturing process were either incomplete or not finished until after the FDA inspectors arrived in July.
There were also instances where Chiron failed to investigate serious problems, such as a major deviation in the acceptable level of bacteria in a batch of vaccine.
Disturbingly, a plant worker was even observed wearing eye makeup, a well-known source for bacterial contamination of sterile areas.Leftover labels from last year's product, that was never sold because of contamination, were also found.
The inspection report also raises concern about a batch of vaccine that was stored longer than the allowable time during processing. The batch was reprocessed and retested for contamination, but apparently not for potency, which can fall over time.
"Much of the report in the newspaper article is without context, without knowing the history of the facility," company spokeswoman Alison Marquiss told In-PharmaTechnogist.com, refusing to provide a copy of the FDA report or Chiron's response.
"The FDA inspection in question was important in helping us to get the plant back online and restoring its licence."
Nevertheless, these problems are in the past and today Chiron, which was bought by Novartis for $5.4bn (€4.2bn) last April, insists it is on track to make 40m flu shots for the upcoming influenza season.
Last October, the Emeryville-based company bagged a $62.5m contract from the US government to produce avian flu vaccine from the Liverpool facility, while in March it announced a similar contract with the UK government to make 1.5m doses of the vaccine.
But these revelations, together with this week's warning letter to sanofi pasteur's pivotal vaccine manufacturing plant in Pennsylvania, carry echoes of the 2004/2005 shortage, when thousands of Americans stood in line for hours to get vaccinated.