- 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
- 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
- * 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
- * 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." ----------------------- NOTE: In accordance with
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