Bioport: Approval Process For Anthrax Vaccine Production On Track

by Keith Costa

Inside The Pentagon

November 16, 2000

Despite problems uncovered by Food and Drug Administration officials during an inspection last month at BioPort's vaccine manufacturing plant in Lansing, MI, company officials are confident they will obtain FDA approval to start new anthrax vaccine production as early as April next year.

"We're still on track to get FDA approval in the second quarter of calendar year 2001," a company source told Inside the Pentagon Nov. 11. "Once approved, production could begin within a matter of weeks."

BioPort's vaccine plant is the only facility contracted by the Pentagon to make vaccine for the U.S. military. The company also manufactures rabies vaccines and various blood products for other customers.

The Oct. 10-26 FDA inspection was conducted by its so-called Team Biologics, the name given to a group of investigators who specialize in reviewing good manufacturing practices for vaccine manufacturers. The group identified several problems with the design and construction of the facility's filling suite and uncovered employee practices that question "the sterility of products filled in the suite," according to an Oct. 26 FDA "483" report obtained by ITP that summarizes the team's findings.

The inspection team examined BioPort's production practices for all its products, not just the anthrax vaccine. "It was a biennial inspection of the entire facility," the source said. "It was not a surprise, but it was unannounced."

Company officials are downplaying any concern about problems raised by the inspection, which they say are already being addressed and will not impact efforts to get FDA approval for anthrax vaccine production.

The 483 report also faults the company for incomplete investigations of anthrax vaccine lots that failed "initial sterility testing." In addition, the report says BioPort "does not trend data" it receives on adverse events related to its vaccines, nor has it "investigated adverse events for anthrax vaccine that are different from those stated in the package insert," as required by FDA guidelines.

When it issued the 483 report, FDA had yet to receive documentation from BioPort about the death of an individual who had taken anthrax vaccine from lot No. 31, the agency says.

"The individual was inoculated on [March 14, 2000] and died on [June 14, 2000]," the report states. "The cause of death is reported as Aplastic Anemia and Invasive Aspergillosis. The firm [BioPort] received information in a Vaccine Adverse Event Reporting System form, but there is no documentation as to when that report was received by" BioPort.

BioPort was required to submit a so-called "15-day report" on the incident, the report says. The BioPort source said that the company learned about the death on Oct. 10 and already has notified FDA that it is reviewing the VAERS information.

To track and review adverse events related to the vaccines it produces -- which could include nausea, vomiting, double vision and memory loss -- the company started to purchase software for the job before the inspection took place, according to BioPort officials. The company also has purchased a subscription to VAERS and appointed a medical officer to oversee investigations of VAERS reports.

In 1998, BioPort purchased the vaccine plant from the state-owned Michigan Biologic Products Institute, which owned an FDA license for anthrax vaccine production. The Defense Department announced its mandatory anthrax vaccine program in December 1997 and has maintained that only FDA-approved vaccine would be administered to service members.

The next month, the plant was shut down to renovate and expand the facility. The renovation was planned, in part, to address production problems identified by previous FDA inspections. MBPI came under scrutiny after a February 1998 inspection uncovered stability, sterility and validation problems with the vaccine production process (ITP, March 26, 1998, p1). FDA Inspections in 1993, 1994, 1995 and 1996 revealed "significant deviations" from agency standards at the facility. Because of those problems, Defense Secretary William Cohen ordered supplemental testing for all MBPI-produced anthrax vaccine before giving doses to military personnel.

Since its 1998 purchase of the MBPI facility, BioPort has sought an amended license -- called a biologics license application -- from FDA, allowing the company to distribute vaccine produced at the renovated plant. BioPort submitted the application for FDA approval in August last year. Typically, it takes 18 to 24 months for FDA to approve BLAs, according to a company spokeswoman.

In the meantime, an unanticipated number of MBPI-produced vaccine lots failed supplemental testing, making them off-limits for DOD use. The result was a shortage of FDA-approved vaccine, which led Pentagon officials to scale back vaccinations in July.

Administration of the vaccine was suspended for all troops except those deploying for an extended time to high-risk regions (ITP, July 20, p1). Deputy Defense Secretary Rudy de Leon said at the time that defense officials should work toward getting the program back on track by January 2001.

But doing so depends on FDA approval of BioPort's biologics license application. Before it is approved, BioPort must correct problems identified last year by FDA during a Nov. 15-23 inspection of the renovated plant (ITP, Dec. 16, 1999, p1). A 483 report of that inspection said the manufacturing process for making anthrax vaccine "is not validated."

BioPort had hoped to address all 30 problems outlined in the report by last August, but officials at the company found the self-imposed deadline "unrealistic," the spokeswoman said. Also that month, the company announced it expects to get BLA approval in the second quarter of calendar year 2001.

BioPort has worked out an arrangement with FDA that allows the company to address each problem in turn with "rolling submissions," she said. "We're still within the average amount of time it takes to get a BLA approved."

The Anthrax Vaccine Immunization Program office was unable to respond by press time (Nov. 15) about the amount of anthrax vaccine available to continue the scaled-down program until mid-2001.