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Testimony of Dr. Robert C. Myers

Chief Operating Officer, BioPort Corporation

Lansing, Michigan

Presented to the Subcommittee on National Security, Veterans Affairs, and International Relations

April 29, 1999

INTRODUCTION AND BACKGROUND

Chairman Shays, Representative Blagojevich and distinguished committee members, my name is Dr. Bob Myers and I am the Chief Operating Officer of BioPort Corporation.

I am proud to come before you today to tell you about our experiences as the manufacturer of the first and only routinely used defense vaccine in the country. I am pleased to have this opportunity to personally assure you of our vaccine's safety and effectiveness. Indeed, this vaccine, instead of being criticized, should be welcomed as a safe and effective counter in today's highly threatening global environment.

I have worked for the lab since 1977, when it was owned by the Michigan Department of Public Health, later known as the Michigan Biologic Products Institute (MBPI). I have been involved in the manufacture of all doses of the anthrax vaccine being used by the Department of Defense (DoD) in its Anthrax Vaccination Immunization Program (AVIP).

Let me be clear at the outset. I don't set policy. I make vaccines. And I am totally committed to providing the very best protection possible against the threat of anthrax. BioPort has worked closely with the FDA to license and manufacture a quality vaccine and we're working closely with the DoD to build and test a stockpile of vaccine that meets their important force protection requirements.

Anthrax is a very real threat that is virtually always fatal. Anthrax is also considered a low-tech bioweapon — it’s easy to get, it’s easy to grow, and it's not too difficult to weaponize. As a result, anthrax is by far the most likely bioweapon we will face as we move into the new millennium.

That anthrax is a potential bioweapon has long been known — long before the recent resurgence of concern on the likely use of bio-weapons by terrorists or aggressor nations. The National Centers for Disease Control (now the CDC) and the DoD came to the Michigan Department of Public Health some 35 years ago and asked them to develop and produce an anthrax vaccine. They asked the Michigan group for three reasons:

• First, Michigan had a long and outstanding history as one of the leading vaccine developers in the country.

• Second, Michigan had an excellent working relationship with the CDC and the DoD as a well-respected, highly reliable, pre-eminent biologics lab.

• Last but by no means least, the Michigan Department of Public Health was willing to work on a vaccine that would protect people against anthrax at a time when no one else would. We stepped up to the plate when we were needed, and worked in tandem with scientists from Fort Detrick and the Public Health Service to develop an improved, safe and more highly effective anthrax vaccine during the years 1965-1970.

 

EFFICACY OF ANTHRAX VACCINE

The anthrax vaccine was first licensed by the FDA in 1970. At that time, it was badly needed in the textile industry, as well as to protect laboratory workers studying anthrax. In fact, the only time anthrax vaccine was tested for efficacy in controlled trials in humans was in four textile mills in the northeastern United States. That vaccine — less potent but very similar to ours — was tested from 1955 to 1959 in these textile mills because anthrax occurred regularly in mill workers — especially in mills processing imported goat hair. (On average, 1.2 cases of anthrax, mostly cutaneous, were reported per 100 employees per year.)

In that study, the vaccine was determined to be 93 percent effective against cutaneous anthrax. Twenty-one cases of cutaneous anthrax were reported — 18 in people who either received the placebo or no vaccine, two cases in people who had received three doses of vaccine with 5-13 months elapsing since the last dose, and one case in which the individual had received two doses of the vaccine with less than two weeks elapsing since the last dose.

Although the cases of inhalation anthrax were insufficient in number to obtain a measure of efficacy, five cases did occur during the study -- none in fully vaccinated individuals. Four of the five individuals died. This single, controlled trial of vaccine efficacy was the basis of efficacy upon which the federal government licensed the anthrax vaccine in 1970.

The efficacy of Bioport's vaccine was confirmed in 1985 by an expert FDA panel, which found that from 1962 through 1974, NO cases — let me repeat, NO CASES— occurred in fully vaccinated individuals despite continued cases in unvaccinated mill workers. The FDA concluded that there was sufficient evidence that the anthrax vaccine is safe and effective under its licensed conditions.

Because it would be unethical to conduct placebo-controlled human studies, the only available method to show the effectiveness of the vaccine today is through animal studies. While several studies in guinea pigs about ten years ago found mixed results in the vaccine's ability to protect against some strains of anthrax, recent studies in rhesus monkeys and rabbits have proven that our vaccine is highly effective in preventing inhalational anthrax, even with so-called vaccine resistant strains. In those studies, groups of monkeys were protected against anthrax aerosol challenges at doses between 100 and 1000 times the amount lethal to unvaccinated animals, up to two years after being given only two doses. The superior effectiveness that has been demonstrated in these studies is the basis for the current work under an approved Investigational New Drug (IND) application aimed at reducing the number of doses required.

Finally, Dr. Arnold Kaufmann, a highly regarded epidemiologist who followed anthrax infection in the United States for the CDC and is now retired, in April of 1998 stated the following: "To the present date, I am unaware of any person who has developed any form of anthrax after receiving either two doses of the current vaccine with seven or more days elapsing since the last dose, or three doses of the current vaccine, regardless of time elapsed since the third dose." We are also unaware of occurrence of any anthrax in vaccinated individuals, but a few cases of cutaneous anthrax continue to occur sporadically in the U.S. in people who have not received the vaccine.

 

SAFETY OF ANTHRAX VACCINE, INCLUDING ADVERSE EVENTS

Certainly the safety of a vaccine must be assured. Yet anthrax vaccine is a perfect example of a safe vaccine that is still being unfairly criticized. It baffles me that someone going to the Middle East would actually refuse protection against a disease that is virtually always fatal. You get inhalation anthrax, you don’t get better. You die. Vaccines given by injection don’t get any safer than the anthrax vaccine. The side effects — a sore arm, an occasional slight fever — occur less frequently than they do with common childhood vaccines like DTP (diphtheria-tetanus-pertussis) and MMR (measles-mumps-rubella).

As a requirement for licensure, the safety of our anthrax vaccine was studied between 1965 and 1970 under an approved IND, sponsored by the CDC. During that five-year period, some 16,500 doses of anthrax vaccine were administered. This included the initiation of vaccination of at least 4,000 individuals and the administration of approximately 6,500 booster doses. Reactions and rates of reactions identified in those studies served as the basis for the discussion of reactions now found in the prescribing information for anthrax vaccine.

These reactions to our anthrax vaccine — which, by the way, are common reactions to ANY injected vaccine — are as follows:

Between licensure in 1970 and May 1994, adverse events reported to the Michigan Labs from the 65,000 doses distributed were few in number. The adverse events reported were similar in nature to those found during clinical trials of the vaccine and none were associated with chronic or permanent local or systemic effects. Through May 1994, no reports of adverse events were received by the Michigan Labs during or after the Persian Gulf conflict. No reports of adverse events were received by Michigan in any of the four yearly reporting periods beginning in April 1994 and ending in April 1998. Since that time BioPort has received directly two reports of adverse events and is now processing a report from a Michigan National Guardsman, concerning reactions in 12 individuals.

Additionally, BioPort is aware of 101 adverse events reported through the Vaccine Adverse Event Reporting System (VAERS). The VAERS reports run from November 1990 through now. Of the 101, only 9 were classified as serious. Serious adverse events for any vaccine are defined as those that are life-threatening, result in a chronic illness or condition, or require hospitalization. It is my understanding that the FDA has assessed that none of these 9 events were caused by the anthrax vaccine and do not represent any trend in adverse health effects associated with the vaccine. From the 49 adverse events reported to VAERS by the DoD, the most serious was in a young man who developed Guillian-Barre Syndrome, temporally associated with his third dose of anthrax vaccine. We are informed that this individual fully recovered. I am also told that all others have been resolved and all individuals have returned to duty. I am sure the GAO, FDA and the DoD have more to say about the safety profile of the anthrax vaccine in their testimonies.

I personally have had many doses of the vaccine over the years and have had nothing worse than the sore arm experienced by many others. If the anthrax vaccine were available for my wife, children and my grandson, I would have absolutely no reservation in administering it to them, including to my oldest daughter who is of childbearing age.

 

FDA COMPLIANCE AND RELATED MATTERS

Our records show that our labs have been inspected by the FDA and its predecessor, the Division of Biological Standards of NIH, at least 48 times since 1969. Each inspection focused on one or more of three manufacturing activities: bacterial vaccines and toxoids, viral vaccines, or plasma derivatives. Examined during each of these inspections were elements common to the manufacturing of all products at our site, including the manufacture of anthrax vaccine. Such common elements included: policies and procedures, recordkeeping, analytical laboratories, quality control practices, raw materials handling, filling and packaging, and storage, warehousing and distribution.

The purpose of these inspections is to determine if we are operating according to our license and according to current Good Manufacturing Practices (GMP). Recent inspections and accompanying detailed establishment inspection reports are largely a matter of public record.

It's no secret that we and others in the biologics industry have had some pretty negative findings from the FDA inspections in recent years. Just before that string of inspections, in January 1993, the anthrax vaccine manufacturing facility was inspected and a renovation to the facility was subsequently approved in July of 1993. Contrary to some reports, that's not so very long ago. Most recently:

• In 1994, we received a rigorous inspection of our plasma derivatives operation, that included several serious deviations from GMP.

• In 1995, we received a warning letter following another inspection of plasma operations and rabies vaccine manufacturing.

• A 1996 inspection showed that we had not yet fully implemented the corrections we had promised.

• This inspection was followed, in March 1997, by a "Notice of Intent to Revoke" (NOIR) letter--threatening to initiate proceedings to revoke our license.

Immediately after receiving the NOIR letter, we met with our clients, including the DoD, to rapidly develop and execute a comprehensive plan to resolve FDA concerns about our operation. We formally responded to FDA with our Strategic Plan for Compliance, which we are executing with oversight from the FDA.

Two inspections in 1998, one in February and another in October, concentrated heavily on the anthrax vaccine, the lots in the stockpile and related GMP issues. We expect another inspection this summer, as part of FDA's review of our anthrax vaccine fermentation and purification facility renovation. This renovation, for which planning was initiated in 1996 with construction beginning in early 1998, is now completed and new lots are in production. The release of these new lots will be dependent upon the FDA's approval of the renovated facility.

After the February 1998 FDA inspection, we immediately participated in a conference call, initiated by the FDA, to discuss several of the lots mentioned in the inspection report. As a result of that telephone call, we voluntarily quarantined, as a precautionary measure, 10 lots previously released by the FDA, pending resolution of those issues through our internal investigations and performance of any necessary additional analyses. Six lots were quarantined over concerns about the potency test (FAV018, FAV021, FAV022, FAV023, FAV025, FAV028), three for sterility assurance issues (FAV029, FAV032, FAV035) and one because of a high rejection rate for the presence of particles (FAV016), now known to be inert gasket material. An eleventh lot (FAV026) discussed with the FDA had already been quarantined and rejected by MBPI Quality Assurance for sterility assurance issues. These 10 lots will remain in quarantine until any outstanding issues are resolved to the satisfaction of BioPort and the FDA. If satisfactory resolution is not obtained, the lots will be rejected.

It should be pointed out that when lots are released by the FDA, the DoD has traditionally paid for them, but has not taken possession of the doses in the lot. Rather, the DoD has requested that we store these lots, on-site, creating, over time, a vaccine "stockpile." This is very different than a normal commercial manufacturing situation in which lots are made in accordance with a market forecast and in consideration of the expiration dating period. In that scenario, those lots would be actually administered to recipients on a regular basis. Now, with the AVIP program, manufacturing will be more closely tied to annual forecasts. However, there is a great deal of discussion regarding stockpiling vaccines such as anthrax and smallpox for both civilian and military use. I do not sense that a consensus has been reached across and within federal agencies on how stockpiling can be acceptably achieved in an acceptable and timely fashion.

All 32 lots of the existing vaccine in this stockpile, owned by the DoD but stored by us, were essentially quarantined by DoD as part of Secretary Cohen's announcement of implementation of the program to vaccinate all service personnel. In his December 15, 1997 announcement, the Secretary specified, among other things that each of the lots must be additionally tested (the so-called supplemental testing) by the manufacturer with audit oversight by an independent DoD contractor who would report back to the DoD on the acceptability of each lot. At that time, MBPI agreed to cooperate with the DoD in this effort and began testing the lots. To date, eight lots have been tested and released through this program for distribution in support of the AVIP. Due to the suspension of potency testing in the fall of 1998 because of a greatly increased number of non-valid tests additional lots were not released. An amendment to our product license to address these non-valid tests and other aspects of the potency test was originally filed several years ago. Since February of 1998, BioPort has worked closely with FDA to achieve approval of this amendment. Additionally, investigations by BioPort and JPO contractors revealed possible causes for the testing difficulties. These difficulties were evaluated and steps have been taken to address them. The test is now functioning as it was originally intended. With this consistent test performance and approval of the potency test amendment, we expect additional lots to be released from the stockpile.

 

CONCLUSION

No one is more committed to making a safe and effective vaccine than we are. I am greatly concerned about the unsubstantiated comments made by those who, for whatever reason, are opposed to this important protection against one of the most serious and deadly biological threats in the world today. The fact that the senior defense leaders of our country have been inoculated with our anthrax vaccine is an indication of their confidence in its safety, and their belief in its effectiveness and necessity. The anthrax vaccine is an essential component of force protection in our military and we at BioPort are committed to providing the men and women who serve our country with the highest quality vaccine.

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