Anthrax Drug
Supplier Fails FDA
Manufacturing Inspection

By Deborah Funk
The Air Force Times
The second phase of the Pentagon's anthrax vaccination program will be delayed six months to a year while the sole supplier of the vaccine corrects deficiencies in its newly renovated manufacturing plant.
BioPort Inc. of Lansing, Mich., needs certification from the Food and Drug Administration before it can send new batches of vaccine to the Defense Department. But it failed to meet FDA standards for the manufacturing process during a November inspection.
Continuing efforts to meet those standards could add $7 million to $10 million to the program's cost and delay the program up to a year, said David Oliver Jr., principal deputy undersecretary of defense for acquisition.
Since the controversial vaccination program began about two years ago, inoculations for 383,000 active-duty and reserve service members have begun. About 11,000 have completed the series of six shots, administered over 18 months. Defense officials say "several hundred" service members have refused the shots because of concerns about the manufacturer, short- and long-term health effects, and whether the vaccine will, in fact, protect against anthrax, a biological agent that defense officials regard as one of the greatest threats to U.S. forces.
Eventually, the Defense Department plans to inoculate all 2.4 million active and reserve troops. For now, however, it will continue to vaccinate only those going to Korea or the Persian Gulf, or those who have already begun the shots. Vaccinations for early deployers, those who would be among the first to be called up for a contingency, were expected to begin in January. But that portion of the program has been delayed until BioPort can ensure a continuous supply.
The FDA already has approved 430,000 doses of the vaccine kept at BioPort, which were manufactured before the renovation of the plant took place. The Defense Department expects another 600,000 previously manufactured doses to be approved. The stock is expected to meet demands of the immunization program through the end of 2000.
Another million doses are in storage but defense officials expect the plant to be certified before they would need to use those, Oliver said.
BioPort purchased the anthrax vaccine manufacturing facility from the state of Michigan 15 months ago and completely renovated it to meet the Defense Department's substantially increased need for the vaccine.
In its recertification inspection, the FDA examined such issues as whether the facility could reliably produce the vaccine, maintain consistent potency, maintain records in accordance with FDA standards, and identify and prevent the introduction of possible contaminants in the manufacturing process.
"Frankly, it has been more difficult than either the department or BioPort expected to move from a small, state-regulated production facility to a large, modern production facility that meets the state-of-the-art FDA requirements," Dr. Sue Bailey, assistant secretary of defense for health affairs, said Dec. 13.
"BioPort has recently beefed up its management and production teams. At the same time, the department has augmented the team that supervises this program," she said.
The FDA identified 30 problem areas. Among them:
* The FDA could not verify whether the company's parameters for manufacturing temperatures, stirring speed, refrigeration times and holding times would guarantee that each batch would be identical.
* The company did not report that it failed potency-test results on some samples when using an FDA-approved calculation method, rather than an unapproved method company officials thought was acceptable.
* BioPort has not completely demonstrated it can always manufacture the vaccine without bacterial contamination.
* The company's internal procedures for reporting deviations from the normal manufacturing process lacked a timeframe for concluding investigations, and did not fully address when the deviation reports should be written.
Robert Myers, BioPort's chief operating officer, said he welcomes the federal oversight. BioPort is fully cooperating with the FDA, he said.
"We're working aggressively to resolve the issues identified in the pre-approval inspection and any other concerns for the renovated facility," Myers said.
At least eight of the problems the FDA found last month were also cited in February 1998, around the time the plant closed for the much-needed renovation.
The FDA frowns on repeat problems, industry experts say.
The deviations don't mean the company didn't try to correct the problems, Myers said, only that the corrective action was insufficient for the new inspection.
Oliver noted that some government tests have changed since the new facility was built. Therefore, new company procedures need to be written, tested and established.
"Good manufacturing practices are always evolving and it's incumbent upon the manufacturer to stay abreast of any changes," Myers said.
One critic of BioPort and the current vaccine who works in the biotech industry said the FDA observations reflect an inattention to rules.
"It's one thing to have new observations," said George Robertson, an Army Reserve colonel and an executive with a Maryland biotech firm. "But it's altogether a different level of noncompliance to have repeat observations."
Robertson worked on a possible second-generation anthrax vaccine developed at the U.S. Army Medical Research Institute for Infectious Disease at Fort Detrick, Md., in the 1990s.
The news that the Pentagon will spend up to $10 million more on BioPort comes just four months after it announced it was revising its contract with the company and would pay $24.1 million more for the vaccine, $18.7 million in advance.
Defense officials said they and BioPort representatives underestimated the cost of making the vaccine because Michigan was subsidizing the plant's costs.
Copyright 1999 Army Times Publishing Company. All Rights Reserved.

This Site Served by TheHostPros