FDA NABS ANTHRAX SUPPLIER ON VIOLATIONS
By Deborah Funk
The sole supplier of the anthrax vaccine now being given to thousands of troops has been cited for quality control problems by the Food and Drug Administration.
FDA inspectors visited the plant in Lansing, Mich., in February and documented more than two dozen shortcomings, including lapses in the manufacturing process, laboratory controls, record keeping, and testing of potency of the vaccine.
Michigan Biologic Products Institute, owned and controlled by the state of Michigan, says it is addressing the problems.
The company almost lost its license last year for other unrelated quality problems, and the FDA acknowledged after its February visit that progress has been made.
Still, its findings on the anthrax vaccine included criticism on many fronts:
* Anthrax vaccine that had been stored for long periods of time was re-dated without written justification. There was no evidence that analytical testing had been done to verify the vaccine had not degraded.
* Potency tests on various lots of anthrax vaccine did not include sufficient documentation. "There is no data demonstrating that these samples are representative of the lot."
* Numerous potency tests produced "invalid" results, but the company never investigated why.
* There are no specifications for how long the product can be exposed to room temperature during filling, labeling and packaging.
* Inspectors observed "peeling paint, exposed duct and pipe work, insulation peeling off the pipes, and rusty steam and gas lines" in the buildings where the vaccine is manufactured.
* Logs for the refrigerators and freezers that keep some of the substances used in the manufacturing process were "incomplete" and in some cases did not match the contents of the refrigerator and freezer. Some vials were unlabeled in one anthrax production refrigerator-freezer.
* Formulation tanks had not been qualified for long-term storage of bulk anthrax and sublots had been held longer than three years prior to use without being tested to ensure the stability of the substances.
"The manufacturing process for anthrax is not validated," the FDA concluded.John M. Taylor III, FDA's senior adviser for regulatory operations, outlined the "deviations" in an April 7 letter to the institute. He urged management there to "make every effort to expedite changes and improvements to its vaccine manufacturing facility and correct the inspectional findings."
FDA did not threaten to pull the laboratory's license, as it had a year earlier, but Taylor did write that "significant improvements are not only in the interest of (Michigan Biologic Products Institute), but also affect our ability to protect the public health and DoD's ability to protect military personnel."
Still safe, DoD says
Despite the problems at the institute, the Pentagon's health affairs chief, both lab and military officials say the anthrax vaccine is safe and effective for troops.
Acting Assistant Secretary of Defense for Health Affairs Gary Christopherson said he had personally talked to the FDA commissioner.
"He and I are both sure the vaccine is safe, effective."
The vaccine in use today has already undergone supplemental testing by an independent lab, Christopherson said.
Geralyn Lasher, spokeswoman for the Michigan Department of Community Health, which oversees the state-owned laboratory, also said the vaccine is safe. "The anthrax vaccine has more testing done on it than pediatric vaccines," she said.
Renovating production line
Meanwhile, the laboratory has stopped making the anthrax vaccine while the Defense Department spends $2.6 million renovating the lab's manufacturing line, Lasher said. Production is expected to resume in 18 months and the department has adequate supplies to inoculate troops until then, she said.
Defense Secretary William Cohen announced plans in December to begin inoculating U.S. troops against anthrax because of its potential to be used as a biological weapon. While the program was not expected to begin until this summer, in March defense officials accelerated the vaccinations for those deployed to high-risk areas.
The vaccine is given in six shots, over 18 months. An annual booster maintains the vaccine's effectiveness. Sailors, Marines, soldiers and airmen deployed in the Persian Gulf theater have already begun receiving the six-shot series.
More than 31,000 troops had begun the injections as of mid-April.
A history of problems
FDA notified Michigan Biologic Products Institute in March 1997 that it would revoke its license because it showed "numerous significant deviations" in the making of some of its products -- particularly rabies vaccine and immune globulin -- during an inspection in November 1996. That pattern had been demonstrated during previous inspections in 1993, 1994 and 1995. But with its license threatened, the Michigan lab drafted a plan in April 1997 to correct matters.
Lasher said the lab has hired quality-control experts from the pharmaceutical industry. Previously bookkeeping was sloppy and things weren't recorded properly, she said.
Inspectors reviewing the plant in February acknowledge that the firm has made progress toward meeting FDA requirements. "However, a lot of work remains to correct the deficiencies related to the manufacture of the anthrax and the experimental botulinum toxoid vaccines," Taylor wrote.
Michigan officials say they have been working closely with FDA to improve. They see the latest findings as a recognition of their efforts.
"There are still things that need to be addressed but we were very pleased they recognized the progress," Lasher said. "We've always said that there is remaining work to be done out there."
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