In December of 1997, the anthrax vaccine manufacturer was shut down and could not manufacture anything related to the AVA. Notwithstanding that hurdle, Secretary of Defense William Cohen announced that before the mandatory program would begin, it would have to meet four prerequisites:
- Supplemental testing, consistent with Food and Drug Administration standards, to assure sterility, safety, potency and purity of the vaccine;
- Implementation of a system for fully tracking personnel who receive the anthrax vaccinations;
- Approval of appropriate operational plans to administer the immunizations and communications plans to inform military personnel of the overall program;
- Review of health and medical issues of the program by an independent expert.
(My emphasis added). One cannot help but wonder why condition number one would need to be in place if the DoD was confident in the safety and potency of the AVA, as it had started saying publicly. In fact, this appears to have been nothing more than a media campaign to assuage fears because none of these four “prerequisites” were ever met before the program kicked off, which is exactly why the manufacturer had been shut down in the first instance. Each of these factors revealed fundamental flaws with the program from its inception.
With regard to point 1, “supplemental testing” may well have been the worst idea for the DoD could have ever come up with because what it demonstrated, unequivocally, was failure of lot, after lot, after lot of the vaccine.[1] One of the first findings in CBER’s February 1998 inspection was that “there is no validation of the length of time sublots are held until they are used in a lot. Sublots have been held longer than three years prior to use. There is no stability data to support this hold time.”[i] Lest this seem picayune, consider a little more history of one particular Sublot:
Sublot AV456 was produced . . . in 5/95 [and stored] until 3/97 at which time it was transported to the formulation room . . . with other sublots to make FAV039. Here it was discovered that AV456 was contaminated with mold, and it was destroyed.[ii]
While some may say that the fact that it was caught is good news, it ignores the other, older sublots where mold or other impurities were not caught. One finding (among many like this) is particularly noteworthy:
Lot FAV023 was filled on 12/13/93 and passed a potency test on 3/29/94. It was submitted for redating on 4/2/97 and was placed in the stability program (zero time) at the same time. It is reported as failing potency on 4/2/97. It was tested again on 8/12/97 and is reported as failing potency. A fourth potency test conducted on 10/6/97 is listed as passing by 0.01. There is no investigation into the original result and justifying the additional testing.[iii]
This finding is most disturbing because it indicates a testing regime that ignores negative test results – twice! – and somehow chooses to validate a subsequent positive after two negatives. How can one know which test result is correct with two failing and two passing results? And how many people would like to line up, roll up their sleeve, and take their shots from that particular vial of the vaccine? Stability testing of biological products is crucial because of the possibility for these products to break down over time. Note that this lot was “filled” in 1993. Four years later it passes a test by .01 after having failed twice previously. This particular finding is in no way isolated: Lots FAV 010, 011, 018, 021, 022, 025, 028, 040, 041, 042, 043, and 044 all had at least one failed potency test that was not investigated and then a passing result was somehow chosen over the negative one.
FAV016 has its own uniquely disturbing history.
Lot FAV016 had 6579 vials rejected due to particulates during post-filling inspection. These particulates were not identified, nor was an investigation conducted. The batch was released.
Someone, somewhere, had unidentified “particulates” injected into them. As a practical aside, one has to wonder how those individuals will get VA compensation if they have an illness as a result of this contaminated product being injected into them in light of the DoD’s positions that there had only been 74 adverse events from the vaccine.
The list of violations goes on and on and includes several different lots being tested and found with such contaminants as “penicillum species” – a danger to anyone allergic to penicillin; cladosporium – a fungus that can cause infections leading to “rough skin, black lesions on the hands, and sometimes a brain abscess”; altenaria – a fungus that can cause dermatitis in humans; micrococcus – a contaminant that is relatively harmless to humans; staphylococcus saprophyticus – a significant cause of urinary tract infections; staphylococcus epidermis – a significant cause of opportunistic infections, usually for those with some skin puncturing, such as needle/IV intrusions, medical appliances, or surgery; and staphylococcus capitis – another infection causing bacteria.
Despite all of these findings and more in February of 1998, the program was launched on May 15, 1998, with Secretary Cohen claiming, with a straight face, that “all conditions for implementing the anthrax vaccination program for the total force have now been met.”[iv] There is simply no possible way Secretary Cohen could have said that in good conscience if he was aware of the inspection results in February. And given everything going on around the program, it is impossible to imagine that he didn’t know – because he manufacturer “voluntarily” shut down for “renovations” in January 1998. In reality it shut down as a result of the Notice of Intent to Revoke letter by the FDA, otherwise the February inspection results would have resulted in the facility’s license revocation.
The second condition of the program was tracking of immunizations. Two DoD briefers talked extensively on November 6th, 1997, about a new program that would be used to track immunizations and of the terrific job the new system had done in Bosnia.[v] At a March 1998 Senate Armed Services Committee hearing, however, Dr. Randolph Wykoff, the Associate Commissioner for operations at the FDA, and Mark Gebicke of the GAO, pointed out that the Bosnia experience left a lot to be desired, particularly of the tracking of immunizations under an IND protocol for an investigational encephalitis vaccine.[vi] In fact, one report used the word “abysmal” to describe it.[vii] Once again, the Assistant Secretary of Defense for Health Affairs promised to get better, but also talked about a new procedure for getting relief from the FDA from the requirements of an IND. The FDA associate director maintained that the “FDA firmly believes the IND process, as defined in our rules and regulations, is sufficiently flexible [for DoD’s needs]. Additionally, FDA is convinced the Department of Defense has the scientific, clinical, and logistic capability necessary to comply with the requirements of the IND process.”[viii] Evidently, however, they could not and did not do it in Bosnia. A GAO report issued the same day stressed the importance of being able to track vaccine immunizations in order to ensure “that (1) sufficient supplies of vaccines will be available at the various worldwide immunization sites; (2) vaccines that are older than their 1-year shelf life are destroyed; and (3) records of vaccines received, administered, and destroyed are kept to allow for monitoring and tracking.”[ix] Worse yet, the GAO found that during the “Bosnia deployment in 1997 . . . DOD could not account for more than 3,000 (20 percent) of the total number of doses sent to Bosnia.”[x]
Requirement number three was that there would be approved operational plans to communicate to service members about the anthrax vaccine program. Whatever the operational plans were, in May 1999, the Department of the Air Force circulated a memo to its judge advocates, specifically defense counsel, telling them that “a small number of military members have refused to follow their commander’s direct order to take the [anthrax] vaccine” and that the cause of their fear in taking the shot is “misinformation obtained from web sites set up by special interest groups[.]”[xi] This was a frequent refrain of the DoD, in front of Congress and in the press. The memo also points members to the DoD’s own website, which was established after the program had begun, in order to “counter” in DoD parlance “internet misinformation.” Evidently then, in March of 1998, when the program was about to begin, prong number three hadn’t been met, either.
It is worth noting that the Army’s AVIP Agency existed solely for the promotion of the anthrax vaccine. It was budgeted at $74 million over a six-year period (FY99-FY05).[xii] No other military medicine program has ever needed to be forced on servicemembers with an orchestrated campaign of this type. William Arkin, a defense writer and former Army intelligence officer observed that “. . . this is the Pentagon versus its own service members. It is a depressing window into the breakdown of discipline and basic confidence in the political and military leadership. That has nothing to do with the Web.”[xiii]
Criterion number four probably cost the DoD as much credibility (if one can say it had any to begin with) as number one. It would be comical were it not for the stakes involved. Secretary of Defense Cohen announced that there would be a “review of the health and medical aspects of the program by an independent expert.”[xiv]
Doctor Gerard N. Burrow was the doctor who allegedly reviewed the program at the request of Deputy Secretary of Defense Rudy DeLeon. Dr. Burrow concluded that “[t]he anthrax vaccine appears to be safe and offers the best available protection against wild-type anthrax as a biological warfare agent.”[xv] Unfortunately, Dr. Burrow is a professor of gynecology at Yale University School of Medicine, a specialty that one would not normally associate with some expertise in weaponized anthrax toxins. When that unfortunate snippet from his CV leaked out, Dr. Burrow was subsequently asked by Congress to testify about his review at a 29 Apr 1999 hearing. He declined to appear. Instead, in a 26 Apr 1999 letter to Representative Christopher Shays (R-CT), Burrow stated that
“[t]he Defense Department was looking for some [sic] to review the program in general and make suggestions, and I accepted out of patriotism. I was very clear that I had no expertise in Anthrax and they were very clear they were looking for a general oversight of the vaccination program.”[xvi]
The DoD’s claims of misinformation on the internet had a particularly hollow ring in light of its blatant lack of honesty and candor in having something as simple as an independent review conducted. Nothing was ever done about this lie that was foisted off on American servicemembers. No one has ever been taken to task for this laughably blatant fraud perpetrated on U.S. military members and the broader American public.
Thus, in the end, the DoD’s four-point plan to reassure the public and servicemembers of the safety of the anthrax program – as a prerequisite to beginning inoculation – was nothing more than a PR campaign that ultimately cost the DoD credibility that it did not have to spare. As the truth came out, and was certainly made available on the internet and elsewhere, the DoD’s cries of “misinformation” went unheeded. Service members on active duty and in the reserves began to refuse or leave the service rather than take the anthrax shot.
If the DoD’s actions appear incredible, the FDA’s inaction is equally baffling. The FDA is charged, under the Administrative Procedures Act, with the duty and authority to regulate, among many other things, the safety of drugs and biologic products. The FDA has had no hesitation in cracking down on manufacturers who do not comply with its regulations or decisions. The cases in the D.C circuit are legion with the FDA disciplining manufacturers who try to market a drug for a purpose not clearly delineated on the approved labeling or who otherwise fail to comply with IND protocols. For some reason, however, in the case of the AVA, the FDA had an absolutely incestuous relationship with the DoD, a third-party who was NOT even the manufacturer! Letters were exchanged between the two agencies regarding non-compliance with IND protocols after the IND protocol was not properly administered in Bosnia. At the March 17, 1998, hearing, the following colloquy took place on this issue between Senator Rockefeller and Dr. Wykoff, the FDA’s associate director for operations.
Rockefeller: . . . It’s also not clear to me that FDA’s shoes are entirely clear or clean on this matter. In fact, some would say lax. I think that FDA and DoD have been exchanging letters about all of this for some months now. And the fact is that seven years after the Gulf War, the situation is still not resolved. If DoD does not adequately answer FDA’s questions with respect to these matters and others, what is FDA going to do about it? . . . And why, for example, was it necessary for the Presidential Advisory Commission to address the waived informed consent matter six years after the end of the war? So I put to you what FDA would recommend and would do if DoD does not come in compliance more?
Wykoff: . . . We have tried very hard to make sure that they are absolutely clear what our rules and regulations are and what our expectations are. We believe that they understand that. We believe that they have the capability of complying with all of our IND rules and regulations. As to whether they will comply in the next deployment situation, obviously we can’t predict that.
Rockefeller: And if they don’t, is there anything that you can do about it?
Wykoff: Yes, sir. Obviously, there are a range of options that we have. We would have to determine what the specific concerns are. That drives what are specific actions would be.
Rockefeller: What are some of the options?
Wykoff: Well, as we interact with any trial sponsor, we learn more about their ability to conduct IND trials, we would be more or less willing to grant waivers or exemptions to particular requirements. We could hold them to more – all of the requirements as outlined in the rules and regulations – based on their performance.[xviii]
It boggles the mind to think that the first words out of the FDA’s mouth are talk of waivers for non-compliance with regulations, particularly in light of DoD’s history in this area. There was, and is, a clearly documented squeamishness on the part of the FDA to step in and bring the DoD into compliance. In downright shocking testimony before a House Committee, Dr. Kathryn Zoon of CBER was questioned by Rep. Christopher Shays (R-CT) about the FDA’s regulatory responsibility.
ZOON: This is a licensed vaccine. If a physician uses it or DoD uses it, that does not really fall under our jurisdiction.
SHAYS: So it’s your statement before us now that if DoD doesn’t abide by the protocol, you have no responsibility? That you have set out a requirement? Who is responsible then? Who’s going to make sure that DoD abides by the protocol, if you don’t do it?
ZOON: We don’t have the authority.
SHAYS: I can’t believe – I just want to say, Dr. Zoon, I cannot believe that you have just said under oath that you do not have the responsibility to deal with this issue or the authority. You said you don’t have the authority.
ZOON: I said – yes, that’s correct.
SHAYS: That is your testimony.
ZOON: We don’t have the authority.
SHAYS: Well then who is going to protect our men and women if you aren’t going to do it? Who? Who has the authority?
The tricky part of this testimony is that it is partly correct. The FDA does not regulate end-users of a product, normally. That is, they do not tell a doctor that he cannot use a drug off-label. However, if the end-user is participating in a clinical protocol, then the FDA does regulate that user. Thus, the DoD’s participation in BioPort’s IND application in order to get an indication against aerosolized anthrax should make them subject to FDA regulation, just as the DoD was during the Gulf War when applying for a Rule 23(d) waiver. FDA’s willingness to accede to DoD’s interpretation essentially allowed the DoD to slide. This is an open abdication of the FDA’s regulatory role.
FDA officials have repeatedly acceded to DoD doctors’ interpretations of the anthrax vaccine label, as well. This is an absurdity. It is particularly appalling in light of the DoD’s involvement in the manufacturing process. The DoD fundamentally became a manufacturer, for all intents and purposes, and the FDA looked the other way, hiding behind the fiction that the DoD was an “end-user” when convenient. The DoD was involved from the very beginning in the development of the anthrax vaccine. Additionally, when problems arose with the manufacturer, the DoD sent in its own ‘inspection’ teams to ensure the supply of the vaccine. The DoD had paramount liens on every piece of equipment that the manufacturer has. A GAO report in June 1999 found that
DOD has made a significant investment in renovating BioPort’s biologic facility to meet the military’s requirements for anthrax vaccine . . . Since 1988, DOD has provided about $112 million in contracts, including options, to help ensure the viability of the anthrax vaccine biologic facility. As shown in figure 1, DoD’s contracts provided monies to (1) produce the vaccine, (2) renovate and expand the production facility, (3) provide various support services, and (4) purchase equipment to enhance production capacity. DoD has also provided contract terms and conditions to help ensure the success of the anthrax vaccine program. For example, under Public Law 85-804, which allows for government indemnification of contractors for unusually hazardous risks, DoD indemnified BioPort against product liability. In addition, DoD agreed to allow the company to sell up to 200,000 doses of anthrax vaccine to others, using government-furnished equipment rent-free, after DoD’s requirements are met.[xix]
Amazingly, this is chump change compared to what the Defense Contract Auditing Agency found in 2000! That report led to an Inspector General Investigation.
Notwithstanding numerous audits that found that the company was not financially viable, BioPort requested contract amendments that included $1.28 million in bonuses for senior management that amounted to 109% of the managers’ base salary. This was deemed an “unreasonable expenditure” by the DCAA in light of “BioPort’s current financial condition.”[xx] Okay, so someone disapproved, right? Well, sort of, because the manufacturer had almost no real financial incentive to produce an FDA approved vaccine under its contracts with DoD: the contract paid the manufacturer 90% of the contract price before the FDA inspected the vaccine. Yes, read that again.
Put another way, BioPort only gets paid 10% more for the product being approved by the FDA. At one point, the Department of Justice was looking into criminal charges as some $6 to $8 Million of the money provided to the manufacturer was unaccounted for. Additionally, the fact the former Chairman of the Joint Chiefs of Staff was a co-owner of the facility, as well as Dr. Robert Myers (formerly of MDPH and MBPI) can hardly escape attention. While both have disavowed any “inside” preferential treatment from the DoD, one must wonder if the decision to award BioPort the contract had anything to do with either’s presence as an owner. Finally, emails from inside the DoD suggest that the agency actually had its own people “on site.” During hearings held by Representative Christopher Shays in May 1999, an email was sent from Brigadier General Eddie Cain, the Director of the Joint Program Office for Biological Defense, to an Army Colonel John V. Wade. In the email Cain warned that “[I]f you think Congressman Shays was critical of the current relationship between FDA & DOD, wait until he finds out that DOD is calling the shots on-sight.” [sic][xxi] When this email surfaced during the court-martial of Air Force Captain (and medical Doctor) John Buck, the FDA had “no comment.”
The FDA has, for whatever reasons, backed down from the DoD to the point that after the warning letters, the notice of intent to revoke, and a failed inspection thereafter, the agency still withheld pulling the manufacturer’s license because the DoD interceded on behalf of the company. In a June 25, 2000, interview with the Vancouver newspaper The Province, Mark Elengold, the Deputy Director for CBER, explained what happened.
The FDA held off pulling the licence, in part because it would have left the U.S. Department of Defence [sic] – which had just announced that all soldiers were to receive anthrax vaccine – with no domestic source.
“This is a one-source product so we tend to try to work with firms and put additional monitoring steps in to avoid revoking the licence,” said Elengold. The prestigious British medical journal Lancet reported at the time that ‘a plea from the Pentagon has prevented an ‘eleventh-hour’ closure of the only U.S. producer of anthrax vaccine,” according to an e-mail to DND [DOD?] medical headquarters in February 1998.
Elengold confirmed the Pentagon sat in on a crucial call to the company in which he discussed revoking the licence.”[xxii]
Electronic mails surfaced in and around 2000 show not only did the DoD convince the FDA not to revoke the license, but DoD also attempted to bully both the manufacturer and the Government Accounting Office at the same time. In one e-mail, a Pentagon official discusses how other agency supervisors were urging the U.S. Food and Drug Administration and the manufacturer of the vaccine to release lots that had been held up for scrutiny by them (the FDA). This despite Secretary Cohen’s public insistence on supplemental testing to ensure safety of the vaccine, one should remember.
On Feb. 22. 1999, Dr. Michael Gilbreath, a civilian Pentagon biological defense employee sent an email to U.S. Army Brig. Gen. Eddie Cain, then Director of the Joint Program Office of Biological Defense (JPOBD). Gilbreath wrote that he had “received information this morning from BioPort that individuals within the DOD contacted them and threatened that DOD would circumvent BioPort and contact the FDA regarding availability of anthrax vaccine lots currently under review at the FDA . . . Any such actions by DOD would be inappropriate.”[xxiii]
E-mails also reveal that the Pentagon was having trouble countering the U.S. General Accounting Office’s assertion that the vaccine is improperly licensed, and that it has not been proven safe and effective. Cain indicated in one e-mail that then Secretary of Defense William Cohen would be writing to the GAO, whose findings have consistently gone against the Pentagon, to protest “the expertise put on this (vaccine) project” by the watchdog agency.
“If we cannot answer these questions, we (DOD and the Administration) are in big time trouble,” Cain said in the May 3 e-mail. “…We are digging ourselves a hole that will be too difficult to crawl out of.”[xxiv]
The FDA also stood by when adulterated vaccine was shipped to the Canadian military and when 59 Marines were given shots from expired lots of the vaccine.[xxv] The FDA’s complicity with the DoD’s actions has left service members with no recourse but to either take the shot, be court-martialed for refusing, or leave the service somehow if their commitment allows it. If the service member simply will not take the chance on the vaccine’s safety, the penalty for refusing is court-martial with a certain conviction. Military Judges simply would not hear that the vaccine is investigational, nor would they even allow service members to present that information to a jury. The FDA’s refusal to act leaves the judge with an out: if the FDA thought it was investigational, why wouldn’t they just issue an opinion to that effect? Worse yet, some military judges would not wade through the necessary materials in order to understand the FDA regulatory process and what an IND is, or they would find that the Secretary of Defense’s actions were in legal parlance “non-justiciable” disputes between “co-equal branches of government.”
The member who fights will be convicted and punished. When an Air Force Doctor, John Buck, tried to submit evidence that the specific lot that he was to have received, FAV044, was subject to a recall because it was expired, the judge did not allow the evidence to come into court. The only option left for service members was to resign quietly, leave at the end of a service obligation, or fight behind the scenes to ensure that the law is followed. That is what a group of persistent officers had been doing from the word go.
[1] It would take up too much space to detail all of the failed lots, for their various reasons during the February 20, 1998, CBER inspection on the lots of AVA. Some of the more egregious violations are listed. See CBER Inspection report dtd 2/20/98 for a complete listing.
[i] FDA Form 483 Inspectional Observations Feb. 4-20, 1998.
[ii] Id.
[iii] Id.
[iv] May 15, 1998, SecDef memo.
[v] Nov 6, 1997, background briefing
[vi] Mar 17, 1998 Senate Hearing, Committee on Veterans Affairs Holds Hearing on the Nomination of Togo West as Secretary of Veterans Affairs and on U.S. Biologic Vaccines for Gulf War Veterans.
[vii] “Abysmal” tracking job quote ????
[viii] Id.
[ix] GAO Report T–NSIAD-98-83 p.8 (March 17, 1998).
[x] Id.
[xi] 18 May 99 AF memo
[xii] Charles Cragin, PDASD Reserve Affairs, testimony, 3 Oct 2000. See: http://www.house.gov/reform/hearings/healthcare/00.10.03/cragin.htm
[xiii] William Arkin, “Bugged by the Net”, Washington Post online, 27 Sep 1999. See: http://www.washingtonpost.com/wp-srv/national/dotmil/arkin092799.htm
[xiv] AVIP Impl ltr 18 May 98
[xv] See: http://www.defenselink.mil/other_info/burrows.html
[xvi] Id.
[xviii] Mar 17, 1998 Senate Hearing, Committee on Veterans Affairs Holds Hearing on the Nomination of Togo West as Secretary of Veterans Affairs and on U.S. Biologic Vaccines for Gulf War Veterans.
[xix] GAO Report GAO T-NSIAD-99-214, (June 30, 1999)
[xx] IG Report dtd March 22, 2000.
[xxi] Dave Eberhart, Stars and Stripes, May, 2001.
[xxii] Ann Rees, “Their Dangerous Dose”, The Province [Vancouver, Canada], 25 Jun 2000
[xxiii] E-mails Suggest Pentagon Pressured FDA On Anthrax Vaccine, Thomas D. Williams, Hartford Courant, May 17, 2001.
[xxiv] Id.
[xxv] See “Their Dangerous Dose”, Ann Rees; also see GAO report T-NSIAD-00-36.
