ANTHRAX VACCINE MIRED IN RED TAPE
27 Nov 2002
Source: Atlanta Journal-Constitution, November 11, 2001.
Anthrax vaccine mired in red tape
It's quarantined, but maker says it's safe and effective
By MIKE TONER, Atlanta Journal-Constitution Staff Writer
Lansing, Mich. -- Concrete crash barriers and coils of razor-sharp concertina wire surround the 12-acre cluster of drab institutional brick buildings. Armed guards check all vehicles entering the gate.
The company logo has been removed to assure a small measure of anonymity for the unremarkable corporate campus of BioPort Corp., a company with one product, one customer and one very big headache.
BioPort makes anthrax vaccine for the U.S. military. As the sole manufacturer of vaccine for bioterrorism's bug du jour, the company could be basking in the warm glow of public acclaim these days.
Instead it is stuck in a bureaucratic quagmire. Virtually every dose of the vaccine BioPort has produced during the last three years -- a number the company won't disclose but that may be as high as 3 million -- is under a tight federal quarantine, waiting for the Food and Drug Administration to decide whether the manufacturing facility, and the vaccine produced there, meet federal standards.
FDA officials have stated publicly that they view the vaccine as "safe and effective for individuals at high risk of exposure to anthrax." But until the company corrects what the agency calls "significant deviations" from new federal requirements for vaccine production, and revalidates the manufacturing process used to produce the vaccine for 30 years, the quarantine will remain in force.
The lockup leaves the military, which hoped to have immunized every service member by now, with a critical shortage of vaccine. It also leaves the Centers for Disease Control and Prevention, which recommends vaccinating some lab technicians and investigators at sites contaminated by anthrax, pleading with the Pentagon to liberate for civilian use 800 doses from its dwindling stocks.
Unlike the antibiotics used in recent weeks to treat potential anthrax exposure, the vaccine offers lasting protection before exposure. Among high-risk workers in the livestock industry, it is highly effective in preventing the disease.
For all the vaccine's promise, production at the Lansing complex now owned by BioPort has been dogged for a decade by questions of quality control, safety, efficacy and other issues. Most of the problems date to the time when Michigan owned the facility, and BioPort inherited many of them when it bought the operation in 1998.
Buoyed by Secretary of Health and Human Services Tommy Thompson's recent assurances that the company would be making vaccine again by Nov. 22, BioPort President Robert Kramer said he now hopes that "the nightmare" soon will be over.
"We now have a significant stockpile of vaccine ready to be released," he said. "It is safe. It is effective. And in light of recent events, there is clearly a need for it."
But even as the company prepares for the December FDA inspection that could decide the fate of the plant and its vaccine, old controversies are bubbling to the surface.
Anti-vaccine protesters -- mostly military personnel who attribute a host of illnesses and several deaths to side effects of the vaccine, or those who quit the service rather than undergo compulsory vaccination -- will rally today on the steps of Michigan's Capitol to oppose the resumption of vaccine production. Some oppose the vaccine because they don't think it works; others because it causes nasty side effects.
Adding to the impasse: The company has been sued by two vaccine recipients, a former Army helicopter pilot from Michigan who claims she was sickened, and a soldier from Washington state who died from aplastic anemia allegedly caused by her vaccination. A second group of vaccine opponents, including two Air Force reserve majors and a retired colonel, have asked the FDA to revoke the company's license and declare all existing stocks of the vaccine to be adulterated.
Those actions, filed in October, come on the heels of a federal class-action suit by two Air Force officers who contend that the FDA should be treating the vaccine, when used against inhaled anthrax, as an investigational drug and that it should be administered to military personnel only if they volunteer to take it.
More than a dozen scientific studies have failed to find any unusual rate of severe reactions among military personnel. Because everyone's immune system is different, all vaccines have adverse effects in some people. In most cases it is only a temporary reddening of the skin. In a few cases per million, reactions may be fatal.
The FDA says the 1,561 reports of reactions recorded in the last three years by its Vaccine Adverse Event Reporting System "do not raise any specific concerns about the safety of the vaccine."
"That's not a large number of adverse events," explains Phillip Brachman, professor of public health at Emory University, who conducted the only clinical trials of anthrax vaccine in the 1960s. "There are a handful of people making a lot of noise, but there have been very few serious problems with the vaccine."
How the vaccine is administered has also been called into question. On at least one occasion, the FDA cautioned the military against its use of a four-shot regimen for vaccinations, instead of the six shots over 18 months that the FDA says are needed to induce full immunity.
Reduced dosages are considered likely to confer substantial immunity, but anthrax is so rare, that major questions about the vaccine are still unanswered.
A planned $20 million study funded by the CDC in Atlanta will attempt to determine whether fewer than six doses will protect a person from inhalation anthrax and whether deeper, intra-muscular injections can reduce some of the side effects. But in the interim, the FDA maintains that six half-milliliter doses of the milky vaccine are the only way to assure immunity.
When the Defense Department's $130 million Anthrax Vaccination Program was launched in 1998, the department had hoped to vaccinate all 2.4 million active duty personnel within 18 months. So far, only 511,000 have received at least one of the six doses required and as stocks of approved vaccine have dwindled, the Pentagon has been forced to slow its vaccination schedule three times.
And BioPort's only customer has no reservations about the vaccine itself; each new delay has made it increasingly restive about how to protect its troops.
Disagreement over what to do about the logjam surfaced this summer within the Pentagon. In August, Undersecretaries of Defense Peter Aldridge and David Chu hinted in a memo to Secretary Donald Rumsfeld that the military might need to develop its own vaccine production capabilities. Gen. Henry Shelton, chairman of the Joint Chiefs of Staff, leaped to the company's defense, urging Rumsfeld to stick with Bioport's vaccine.
Although all of BioPort's vaccine is currently earmarked for military use, the company would eventually like to make enough vaccine to serve a wider market. That wider market may not wait. Wary of the continuing delays, U.S. public health officials are already shopping for someone to produce anthrax vaccines in Great Britain, Russia and China.
The storm of controversy is a decided contrast to the sleepy history of a vaccine that almost no one wanted to make -- and has never turned a significant profit.
Pharmaceutical giant Merck manufactured anthrax vaccine on a trial basis in the early 1960s, but quickly lost interest. With only a handful of anthrax cases in the United States since the turn of the century, it didn't look like a money maker.
When no other company was willing to produce it, the federal government asked the Michigan Department of Health, which was already making pediatric DPT -- diphteria-pertussis-tetanus vaccine -- to assume the task. The FDA licensed the current anthrax vaccine in 1970 and over the next 20 years, Michigan distributed 68,000 doses, mostly to laboratory workers, , textile workers and livestock handlers who ran the risk of anthrax exposure.
Faced with increasingly rigorous FDA regulations and growing complaints of adverse reactions from military personnel who had received it during and after the Persian Gulf War, Michigan decided to get out of the business.
BioPort, whose board of directors includes former Chairman of the Joint Chiefs of Staff Rear Admiral William J. Crowe, was the sole bidder. The company negotiated a new vaccine price with the Pentagon -- $10.64 a dose, up from $5 -- and committed to right the regulatory deficiencies -- a host of citations for inadequate sanitation and unauthorized changes in equipment -- that it had inherited from the state.
Three months later, the FDA threatened to revoke the company's license if the deficiencies weren't corrected. BioPort halted operations and renovated the facility. Kramer says the company has produced "significant quantities" of vaccine since manufacturing was resumed last year, but none have yet been approved by the FDA.
Kramer says the company welcomes the FDA scrutiny and is confident it will soon have all of the approval it needs to begin producing the vaccine. But he says BioPort's experience explains why other vaccines, notably for influenza and tetanus, have been in short supply in recent years as manufacturers opt out of the business.
"The FDA is exactly right in imposing higher standards on vaccine manufacturers," he says. "But it reflects how hard it has become to make biologic products in a climate where there is no margin for error."