Mark A. DeSorbo
SPOKANE, WA- A biotechnology laboratory established 80 years ago as a result of a summer cold that plagued one of the founding chemists has begun aseptically filling vials with one of the most highly profiled vaccines on the market.
In late February, workers at Hollister-Stier Laboratories donned masks, gloves and bunnysuits to enter ISO Class 5 and ISO Class 6 cleanrooms, where small glass vials are filled with the anthrax vaccine.
Packaging began once the vaccine's manufacturer, BioPort Corp. (Lansing, MI), met U.S. Food and Drug Administration (FDA) process validation requirements. Violations of current good manufacturing practices (cGMPs) dated back nearly four years, long before BioPort's mid-1998 acquisition of the facility, known then as the Michigan Biologics Products Institute (MBPI), which was owned by the Michigan Department of Public Health.
“When they acquired MBPI, they inherited a real challenging situation,” says Anthony Bonanzino, Hollister-Stier's president and chief executive officer. “They have taken some very negative press, but they have worked very hard to get to the point they are at today, and we are pleased to be part of it.”
Contract manufacturing
Aseptically filling ampoules with BioPort's anthrax vaccine is definitely a change of pace of for a biotechnology laboratory that made a name for itself extracting antigens for allergies and bee stings in the grassy fields of Washington.
Bonanzino describes the allergy extract market as viable, yet finite enough to warrant a move to diversify, which is why Hollister-Stier branched into contract manufacturing for the pharmaceutical, biopharmaceutical and biotechnology industries a little more than a year ago.
“The allergy extract market is very stable, but it has less growth potential than contract manufacturing,” he says. “In order to supplement our business in the allergy area, we determined that we would diversify to become a contract manufacturer and it has been a major area of growth for us.”
On the contract manufacturing side, Bonanzino says Hollister-Stier works with multiple products from 18 companies and has the capability to fill 150,000 vials in a 10-hour shift. “We deal with small lots of [FDA] Phase I clinical trials to large Phase III clinical trial lots to commercial products that have been FDA approved.”
“We hold FDA licenses for pharmaceutical drug products, biological products and medical devices,” he says.
Hollister-Stier also produces about 6,000 allergy immunotherapy items and about 70 pharmaceuticals in its cleanrooms. “BioPort is not our largest client and it is not our smallest either, but it is one of the most profiled,” Bonanzino adds.
Conversing with Couric
BioPort hired Hollister-Stier to fill vaccine vials when its procedures kept failing. BioPort's renovated laboratory repeatedly failed to pass inspections conducted by the FDA, which found contamination, inadequate record-keeping and unapproved procedures that yielded several batches that flunked sterility tests.
In early February, Robert Kramer, president of BioPort told The Today Show's Katie Couric that a detailed plan for FDA compliance was established when BioPort took over the facility from the state of Michigan in late 1998.
“[BioPort] worked very closely with the FDA through 1999, 2000, 2001 and shared with them our progress with that plan for compliance,” he says. “When the FDA came in late last year to do the inspection, they found that we could clearly demonstrate that we can manufacture this vaccine consistently and in control.”
Bonanzino adds that discussions with BioPort started in September 2000 and a contract was signed that December. “We began trial validation in May 2001, and we have filled quite a bit to reach the point we are at now,” he says. “We are producing regular production now, and those registered batches are now available to the military.”
BioPort spokesperson Kim Brennen Root noted Hollister-Stier's FDA compliance record, saying there are “shared values in terms of commitment to quality, the size of the companies and the willingness to work together to meet the need for a very high-profile product.”
The anthrax vaccine, Bonanzino says, is a cell-free liquid filtrate that is shipped to Hollister-Stier from BioPort in stainless steel containers. The vaccine is then aseptically filled into 10-milliliter glass vials, which are then shipped back to BioPort for labeling and distribution. Because the vaccine is inert, the liquid “poses no threat to employees or our neighbors, or anyone in the vicinity.”
Licensed for production in 1970, vaccine caches were beefed up during the Persian Gulf War, when Iraq was said to have developed anthrax weapons.
Health and Human Services Secretary Tommy Thompson has said BioPort will produce 2 million vaccine doses this year, and between 3 million and 8 million next year for the U.S. Department of Defense (DOD).
A great deal of controversy, however, still plagues the vaccine.
Along with NBC's Today Show, The Associated Press reports that the Pentagon is waffling on its previous commitment to inoculate the nation's 2.4 million men and women in uniform. Meanwhile, many soldiers have refused the shots, worried they, too, could come down with chronic fatigue, memory loss and other problems of complaint.
BioPort's Kramer noted numerous government studies that maintain the safety and efficacy of the vaccine, which he says has already been administered to 500,000 service men and women. The government has said the vaccine is safe, with rare, but severe side effects such as dangerous allergic reactions.
“We feel extremely confident the product is safe and we stand behind its efficacy,” Kramer says, adding that the DOD has enough vaccine to immunize troops and that BioPort remains poised to provide a civilian stockpile if it is called upon to do so.
Interest in the vaccine was renewed last fall when envelopes containing the bacteria were mailed to media and congressional offices, killing five people on the East Coast. A vaccination protects against anthrax exposure through skin, inhalation and other forms. The inhaled version is particularly lethal, killing victims within days.
Bonanzino says the vaccine is shipped and handled under “fairly tight security.” Barbed wire fences surround Hollister-Stier, guards are stationed at the front gate and security cameras have recently been installed.
“We have upgraded security very substantially, however, we still are a pharmaceutical plant and not a military installation,” he adds.
The heightened security, Bonanzino says, has not had a negative impact on employees. In fact, it's quite the opposite. “We are very pleased, in our own way, to participate and contribute in the fashion that we are able,” he adds.