BY STEVE SMITH
EMERYVILLE, Calif. – Corrections to contamination-control issues that halted vaccine production last fall at Chiron Corp.’s Liverpool, U.K., facility are being met with general approval by the Food and Drug Administration (FDA; www.fda.gov), but it remains to be seen whether the manufacturer can fully satisfy regulatory requirements in time for the upcoming flu season.
Dr. Jesse Goodman, director of the FDA’s Center for Biologics Evaluation and Research (CBER), says the agency is pleased with the steps Chiron has taken to address deviations from current good manufacturing practice (cGMP) that halted production at the Liverpool plant last fall, but cautions, “Additional work is needed to determine the amount of vaccine Chiron may be able to supply the U.S. market for the upcoming flu season.”
Although specific details are not known, the FDA says it will need to make subsequent inspection of the facility to “further evaluate the implementation and effectiveness of [Chiron’s] corrective actions going forward.” The FDA also says that any Fluvirin vaccine produced by Chiron for the U.S. must first pass “all tests for safety and potency” before it can be marketed.
Production of Fluvirin was halted last October when an internal investigation discovered bacterial contamination had found its way into a manufacturing cleanroom, affecting nearly 46 million doses of the vaccine. The serratia marcescens microbe causes urinary tract infections and is often resistant to antibiotic treatment. The bacteria are often found growing on medical equipment, in petri dishes, and sometimes in “sterile” solutions.
In its warning letter to Chiron following an inspection of the Liverpool site, the FDA cited several manufacturing and procedural failures that may have led to the contamination, including failure to fully investigate aseptic filling area environmental monitoring, several failures to establish and follow written procedures designed to prevent microbial contamination, and failing to establish separate or defined areas or control systems for aseptic processing operations to prevent contamination or mix-ups.
Chiron’s remediation plan has involved a number of unspecified improvements to the Liverpool manufacturing facilities, equipment and processes, which means the company must receive supplemental approvals from the FDA in response to filing of these changes before it can market Fluvirin to the U.S.
The vaccine fill process at Chiron Corp.’s Liverpool, U.K., facility may soon be back up to speed once manufacturing remediation steps have been fully approved by the FDA.
The steps for final approval can be time-consuming, however, and while Chiron CEO Howard Pien said his company “remained focused on our objective of delivering Fluvirin to the U.S. market…to prepare for the upcoming influenza season,” the FDA has taken measures to assure that there will be no flu vaccine shortage this year by approving Fluarix, developed by GlaxoSmithKline (www.gsk.com). The vaccine is new to the U.S. market but has previously been used in other countries.
Fluarix is the first vaccine approved with the FDA’s accelerated approval process, which allows products that treat serious or life-threatening illnesses to be approved based on “successfully achieving an endpoint that is reasonably likely to predict ultimate clinical benefit.” The agency says that GlaxoSmithKline successfully demonstrated that, following Fluarix vaccination, adults 18 and older made levels of protective antibodies in the blood that the FDA believes are likely to be effective in preventing flu.
To help increase vaccine production in the U.S., the British pharmaceutical giant has acquired a 90-acre research and production facility in Marietta, Pa., previously owned by Wyeth. The facility will be used to develop next-generation vaccines as well as for development and production of tissue culture technology to be used for seasonal and pandemic flu vaccines. Once a new flu vaccine based on tissue culture is developed, GlaxoSmithKline says it will make further investments at the Marietta facility. The site has freeze-drying technology that will be used to enhance vaccine shelf life and stability.
“We expect to develop new flu vaccine technology at our Marietta facility that we hope will enhance our ability to rapidly produce flu vaccines for the nation in response to a pandemic,” says GlaxoSmithKline CEO J. P. Garnier.
Meanwhile, Chiron may continue Fluvirin manufacturing, even if not in time for this year’s U.S. flu season. The Medicines and Healthcare products Regulatory Agency (MHRA), which has regulatory jurisdiction for the United Kingdom and had suspended Fluvirin production in the U.K. following an on-site investigation last fall, ruled earlier this year that Chiron could resume operations there, although the agency may again inspect the Liverpool manufacturing site before vaccine shipment is allowed to begin.