The Chiron Case: Good Manufacturing

Practice Gone Bad

British regulators suspended the license of Chiron's manufacturing plant in
Liverpool, England, in October 2004, the move caught the US Food and Drug
Administration by surprise and triggered an international vaccine crisis. The FDA
had inspected the plant in the past, and Chiron was slated to provide nearly half of
the US vaccine supply for 2004–2005: 48 million doses of Fluvirin.

reason for such failure : When they closed the plant, the UK's Medicines
and Healthcare Products Regulatory Agency (MHRA) cited bacterial
contamination in some lots of vaccine, and a failure to follow good manufacturing
practice.

The Chiron episode has led some to scrutinize not only Chiron's failings, but also
those of the regulatory community. Some ask, for instance, whether the FDA
adequately regulates plants outside the United States, and if other companies,
especially those with overseas operations, are at risk for similar GMP problems.

The good news is that the MHRA gave Chiron the go-ahead to resume flu vaccine
production in March, which was earlier than expected. This ended the company's
five-month suspension and greatly increased its chances of being able to produce
flu vaccine for the 2005–2006 season.

After British authorities closed the plant, the FDA followed with its own
investigation and sent a warning letter to Chiron in December 2004 that listed 20
separate problems with manufacturing and record keeping. Known in the industry
as FDA Form 483, the FDA warned that the plant had failed to follow its own
procedures to investigate sterility problems. For instance, bacterial contamination
was found in a room that was supposed to be sterile, even after the room was
fumigated. Even then, the company failed to document the impact of this sterility
failure on its product. The company also failed to use proper storage temperatures
for its vaccine, failed to properly follow procedures for cleaning and maintaining
equipment, failed to properly review production records for accuracy, and failed to
take corrective action after experiencing alerts of contamination.
Ultimately, the company found Serratia bacteria in nine of its 100 flu vaccine lots.
Because the plant had failed to keep adequate records of each vaccine batch, it
could not trace where the problem started, nor determine if the other 91 lots were
contaminated. As a result, none of the batches was safe to use. The discovery
meant the loss of half of the flu shots for the United States and about 10% to 20%
of the United Kingdom's doses.

The FDA knew about Chiron's contamination problems from previous inspections,
according to congressional testimony from FDA Commissioner Lester Crawford.
In August, Chiron informed the FDA that some lots of vaccine, equaling about 4.5
million doses, were contaminated with bacteria. But the agency apparently became
aware of the severity of the problems only after British regulators suspended the
Liverpool plant's license in October. This suggests there could be better
communication between the FDA and regulators outside the country.

SOLUTION : The new cGMP (current GMP) initiative will "build quality into the
manufacturing process" and "modernize our manufacturing regulatory
responsibilities," he says. Under the initiative, there will be advanced training for
manufacturing investigators, in hopes this will lead to greater consistency in
inspections and a quicker response to deficiencies. The FDA will also promote
better communication with the firms it regulates to help manufacturers anticipate
and avoid production problems "before they occur,"

"Companies do not need to do anything new," he says. "Rigorous compliance with

the well-known [FDA] regulations is quite sufficient to prevent these kinds of
problems from arising."