From: Kathy Hubbell [hkathryn7@qwest.net] Sent: Sunday, February 27, 2005 7:47 PM To: Dockets, FDA Subject: Docket No. 1980N-0208 Military Vaccine Action Committee, L.L.C. P.O. Box 8168 • Missoula, MT 59807 • contact@mvacpac.org http://www.mvacpac.org • PH: (406) 531-9355 February 27, 2005 Division of Dockets Management 5630 Fishers Lane, rm. 1061 Rockville, MD 20852 RE: Docket No. 1980N-0208 Cc: To members of the original Panel advising on this rule; To the Hon. Judge Emmet G. Sullivan, U.S. District Court, Washington, D.C. Published online at www.mvacpac.org and www.milvacs.org To Whom It May Concern: I am writing this letter to you as President of the Military Vaccine Action Committee, L.L.C., a non-connected Political Action Committee. On behalf of this organization and the individuals it represents, we request that you classify the anthrax vaccine as Category II - unsafe, ineffective, or misbranded – and withdraw its license. We have solid reasons for this request, completely apart from the many letters you have already received documenting the devastating illnesses and conditions suffered by our troops and veterans as a result of this vaccine. (Further information is available at the Anthrax Vaccine Education Center at http://www.milvacs.org.) The proposed rule in the Federal Register is seriously flawed. It documents a process full of inaccuracies, half-truths, and slipshod science. It reveals knowledge of laws broken and ignored – knowledge documented in a 1997 letter from Health & Human services to DOD, which will be further discussed later in this document. What follows are specific errors in the proposed rule, and our rebuttals. Either attached, or linked to this document, are two other critical documents. The first is a chronology compiled by Lt. Col. Russell E. Dingle and Major Thomas L. Rempfer of the Connecticut Air National Guard, outlining the original development and use of the current anthrax vaccine (http://www.milvacs.org/anthrax/chrono.pdf). It contains information we can only assume you have not seen before, all of which is documented and referenced. We supply it to assist you in carrying out your responsibilities concerning the approval process for a vaccine, and to more thoroughly understand why it should never have been licensed in the first place – let alone used to the great detriment of the Armed Forces of our nation. The second document is one with which you are definitely familiar. It is a copy of the 1997 letter from Health & Human Services and FDA, documenting DOD’s complete inability to administer, track, or comply with the rules regarding use of an Investigational New Drug, clearly stating that it expects the problems to continue if there is no resolution. If you are reading this electronically, you may find this document at http://www.milvacs.org/append~1.pdf. A few of the main points in our rebuttal include: a.. FDA admits more than once in the Proposed Rule that two different vaccines were manufactured and used – but does not acknowledge that the vaccine used on members of the armed forces is not the same vaccine that was licensed in 1970. b.. FDA relies on the Institute of Medicine Report as to the safety and efficacy of the anthrax vaccine, despite the exclusion in the report of evidence to the contrary, including the Army’s own studies and statements, and despite numerous other problems with the report as noted below. c.. FDA extrapolates statistics which cannot be validated or substantiated, and which represent shoddy science – but uses those statistics to justify use of the vaccine. d.. FDA lumps studies of both vaccines together, assuming that the results from one can be automatically applied to both, even though the vaccines are materially different. e.. FDA continually quotes the Brachman Study as proving the safety and efficacy of the anthrax vaccine, despite the fact that the Brachman Study was done on the original vaccine, not on the vaccine that has been used on members of the armed forces. f.. FDA has not followed its own rules in ensuring that the anthrax vaccine is safe, pure and potent before it is licensed; this lack is a matter of public record, as noted. g.. FDA relies upon the VAERS reporting system as justification that it is researching and tracking the anthrax vaccine, when the VAERS system cannot be considered more than anecdotal research in the military for reasons noted in this report. h.. FDA claims that because the two anthrax vaccines are comparable, it is all right to treat them in both research and results as being the same, completely ignoring the fact that, in many classes of drugs, there are comparable vaccines and medicines, but that there are material differences – as becomes obvious when one realizes each has its own patent. i.. FDA and HHS clearly state in the 1997 letter to DOD that DOD has a clear inability to handle Investigational New Drugs. In light of the recent declaration by HHS that there is some kind of “anthrax emergency” facing our troops, this is puzzling indeed, and needs a great deal of explanation to our troops as well as to the general public. HHS and FDA are clearly aware of DOD’s terrible track record with Investigational New Drugs, yet seemingly work to clear all obstacles in the path of DOD as if resolution has been accomplished, when it has not. Because FDA has consistently ignored its own policies and procedures; has ignored reports even from the Dept. of Defense indicating that the anthrax vaccine is highly reactogenic and dangerous, and not likely to protect against all strains of anthrax; because FDA has consistently ignored the differences between two materially different vaccines, and assumed that the safety study of one applies to the other, that the use and results for one apply to the other, and that they can be lumped together for statistical purposes; because FDA has not encouraged or demanded that DoD conduct a long-term study of the effects of the anthrax vaccine, and, in fact, has been shown by Health & Human Services as well as FDA to be incapable of handling an Investigational New Drug responsibly and in compliance with FDA rules and procedures; and because FDA does not rely upon valid research; we therefore request that FDA classify the anthrax vaccine as a Category II drug -- unsafe, ineffective and misbranded -- and withdraw its license. The following pages explain the errors in the Proposed Rule and our rebuttals in more details, and are an integral part of these comments, as are the attached or linked documents noted above. Following our formal rebuttals are some of the major points made in the 1997 letter to DOD from Health & Human Services, documenting DOD’s inability and unwillingness to comply with the laws and procedures governing Investigational New Drugs. We thank you for your time. Sincerely, Kathryn D. Hubbell President, Military Vaccine Action Committee, L.L.C. P.O. Box 8168 Missoula, MT 59803 Cell: (406) 531-9355 contact@mvacpac.org www.mvacpac.org ERRORS AND REBUTTALS from the Military Vaccine Action Committee, L.L.C. Concerning FDA Proposed Rule: Dec. 29, 2004 Docket No. 1980N-0208 Page 5, Part IV: Anthrax Vaccine Adsorbed: Proposed Order A. The Panel Recommendation that Anthrax Vaccine Adsorbed be Placed in Category I (Safe, Effective, and Not Misbranded) In its report, the Panel found that Anthrax Vaccine Adsorbed (AVA), manufactured by Michigan Department of Public Health (MDPH now BioPort) was safe and effective for its intended use and recommended that the vaccine be placed in Category I. In the December 1985 proposal, FDA agreed with the Panel’s recommendation. During the comment period for the December 1985 proposal, FDA received no comments opposing the placement of AVA into Category 2. The Panel based its evaluation of the safety and efficacy of AVA on two studies: A well controlled field study conducted in the 1950s, ‘‘the Brachman study,’’ (Ref. 1) and an open-label safety study conducted by the National Center for Disease Control (CDC, now the Centers for Disease Control and Prevention) (50 FR 51002 at 51058). The Panel also considered surveillance data on the occurrence of anthrax disease in the United States in at-risk industrial settings as supportive of the effectiveness of the vaccine (50 FR 51002 at 51059). In its determination that the data support the safety and efficacy of AVA, FDA has identified points of disagreement with statements in the Panel report. However, FDA has determined that the data do support the safety and efficacy of the vaccine and, thus, the agency continues to accept the Panel’s recommendation and places AVA in Category I.3 Response: The following excerpts are from the Rempfer/Dingle timeline attached, and portray what actually happened. The oft-quoted Brachman study was actually done on the original anthrax vaccine, not on the later vaccine used on members of the Armed Forces. In addition, safety and efficacy of a vaccine intended for licensed for use only against cutaneous anthrax – anthrax absorbed through the skin by contact with a contaminated carcass or other direct contact -- is not the same as studying the safety and efficacy of a reconfigured vaccine used off-label for inhalation anthrax. As is obvious below, there was not enough data regarding the efficacy of the anthrax vaccine either before or after its licensing; and in 1985, contrary to the above statements that FDA decided the anthrax vaccine was safe and effective, the Army itself stated that “that there was no vaccine in current use that safely and effectively protects military personnel against exposure to anthrax and that the current anthrax vaccine was highly reactogenic, required multiple boosters to maintain immunity, and may not protect against all strains of anthrax.[i]” The footnotes refer to the references in the full timeline. Italics and bold emphasis added. 1. January 1955. An anthrax vaccine supplied by the U.S. Army Chemical Corps was used in the first human field trial. During this clinical trial five workers contracted inhalation anthrax and four died in the first anthrax epidemic of the 20th Century.[ii] 2. September 1965. A human anthrax vaccine patent was awarded to Milton Puziss and George Wright, representing the U.S. Army.[iii] (The vaccine described in this patent was materially different from the vaccine used in the 1955 to 1959 New Hampshire field trial.) 3. July 1967. An application is made with the Health Education and Welfare’s Division of Biologic Standards to license an anthrax vaccine based on the patented vaccine production method.[iv] 4. July 1967. First required annual progress report submitted to the Division of Biologic Standards.[v] 5. February 1969. The Division of Biologic Standards recommended license approval, but noted that clinical data establishing efficacy had not been submitted and requested data be gathered to establish efficacy.[vi] 6. November 1970. The Division of Biologic Standards approved the anthrax vaccine.[vii] 7. February 1972. Final Progress Report on the anthrax vaccine was submitted to the Division of Biologic Standards. [viii] (Data establishing efficacy of this vaccine as requested in February 1969 had yet to be generated, collected, submitted or reviewed by the Division of Biologic Standards.) 8. June 1972. The responsibility of regulating biologic products, including vaccines, is transferred from the Division of Biologic Standards to the Food and Drug Administration.[ix] 9. August 1972. The Food and Drug Administration announced a review of all products transferred from the Division of Biologic Standards for safety, effectiveness and labeling.[x] AVA was one such product. 10. May 1985. The DOD (through the Department of the Army) issued a Request for Proposals (DAMD17-85-R-0078) to the pharmaceutical industry soliciting the development of a new anthrax vaccine. The reasons stated in the Request for Proposals was that there was no vaccine in current use that safely and effectively protects military personnel against exposure to anthrax and that the current anthrax vaccine was highly reactogenic, required multiple boosters to maintain immunity, and may not protect against all strains of anthrax.[xi] 11. December 1985. The review required by the Food and Drug Administration in 1972 was published in the Federal Register as a Proposed Rule. The review panel recommended that AVA be placed in Category I as safe, effective and not mislabeled. The review panel did note the lack of efficacy data: “the vaccine…has not been employed in a controlled field trial.” The panel also noted the inability to determine the vaccine’s use in preventing inhalation anthrax: “efficacy against inhalation anthrax is not well documented . . . no meaningful assessment of its value against inhalation anthrax is possible due to its low incidence.” Finally, based on the extremely limited use of the vaccine the panel felt the possible benefit outweighed the risk: “In general, safety of this product is not a concern especially considering its very limited distribution and the benefit-to-risk aspects of occupational exposure in those individuals for whom it is indicated.”[xii] A. Continued… October 12, 2001, a group of individuals filed a citizen petition requesting that FDA find AVA, as currently manufactured by BioPort, ineffective for its intended use, classify the product as Category II, and revoke the license for the vaccine. The petitioners complained that the December 1985 proposal that placed AVA in Category I had not been finalized. FDA responded separately in a written response to the petitioners and will not further address those issues in this final rule. In October 2000, the Institute of Medicine (IOM) convened the Committee to Assess the Safety and efficacy of the Anthrax Vaccine. In March 2002, the Committee issued its report: The Anthrax Vaccine: Is It Safe? Does It Work? (Ref. 2). The report concluded that the vaccine is acceptably safe and effective in protecting humans against anthrax. Responses: The Institute of Medicine Study was seriously flawed and incomplete, and is inadequate as a basis for declaring that the anthrax vaccine is safe. 1.. ”In April 2002, the prestigious Institute of Medicine of the National Academy of Sciences issued a final report on the safety and effectiveness of the anthrax vaccine currently in use by the United States military. It concluded that the present vaccine was completely safe and effective, but ignored evidence of several recent research studies from three different nations that have implicated vaccines, often including anthrax vaccine, in the epidemiology of Gulf War illnesses. Omissions and limitations of that report are discussed.” Schumm WR, Webb FJ, Jurich AP, Bollman SR. School of Family Studies and Human Services, Kansas State University, Manhattan 66506-1403, USA. Schumm@Humec.ksu.edu 2.. "The anthrax vaccine is effective and safe enough to use to protect U.S. soldiers, says a panel of medical experts. But there are not enough studies to assure its safety for wide use by the public, and a better vaccine is needed, according to a report released Wednesday by the Institute of Medicine." Anthrax vaccine found safe for troops - More study needed before public use By Anita Manning, USA TODAY – 3/07/2002 USA Today's statement is an accurate assessment of the IOM's analysis, but it also defines the ethical dilemma we're engaged in -- i.e., the laws are no different for soldiers vs. citizens. If the troops receive a vaccine in a mandatory program that doesn't meet the requirements for use by the general population, they are by definition being "experimented" upon. We have laws, executive orders, and DOD directives that deal with these situations, all which have been violated in the anthrax vaccine program -- 10 USC 1107, EO 13139, and DOD Directive 6200.2. There is no double standard under the law unless the President directs one based on an imminent threat or a national emergency. 3. Further responses to the IOM report, written in 2002: a. The IOM report fails to address regulatory problems that render the vaccine improperly licensed. The vaccine licensed in 1970 is not the vaccine being used on the troops. This is buried in the back of the report in the appendix H. b. The IOM report fails to address the fact that the Manufacturer / DOD failed to get the vaccine properly approved for "inhalation anthrax" with the FDA. Their application was never approved by the FDA, and IOM's view based on animal data is legally irrelevant. c. The IOM report fails to address the significant 1990 change in filtering and fermenting equipment reported by the General Accounting Office in their testimony to Congress on 23 OCT 01. The report reveals an up-to-100-fold increase in the potency of the vaccine, but has never been studied as a possible cause of Gulf War Illness. 4.. The IOM report summarily dismisses all previous reports highly critical of the vaccine's high reactogenic nature and unproven efficacy against inhalation anthrax. All dissenting information is omitted from the report despite the hundreds of pages of critical documents provided, many on FDA and DOD letterhead. 5.. The IOM report disregards the severe reactions listed on the new, FDA-mandated, label for the vaccine -- documented birth defects, deaths and adverse reaction rates up to 175 times greater than advertised before, show a vaccine that is either new, or one that was previously falsely advertised. 6.. There is no admission in the report that, in fact, adverse reactions to the vaccine are vastly underreported because soldiers are worried about forced retirement or other repercussions from their superiors - as a result, they either try to live with their reactions, or seek help elsewhere. 7.. Most of the documentation used to support the IOM report comes from the Dept. of Defense itself, and was created after the mandatory vaccination policy became controversial. The preliminary report in appendix H admits that in Mar of 2000 there was a "paucity of data" which is prima fascia evidence that the new data was crafted to support the policy. 8.. The committee finds that, despite limited data on long-term effects, reports of serious illnesses and reports of links to Gulf War Syndrome, no special follow-up efforts should be made. This program has always been a 'no bad news' effort by the DOD, and the IOM report is an attempt to gloss over serious legal, medical and regulatory problems. 9.. Both the approval of the manufacturer by the FDA and this IOM report are cosmetic attempts to protect government and DOD bureaucrats that used an illegal vaccine in an illegal vaccination program. Digging the hole of after-the-fact science will only make the problems worse and further tarnish the integrity of our military and erode the morale and trust of our troops. 10.. The truth is in the fine print. The new FDA mandated product label shows death, birth defects and adverse reaction rates up to 175 times greater than previously acknowledged. The IOM report also recommends a new vaccine and justifies the old vaccine based on animal data, which doesn't satisfy the requirements of the law. The vaccine is experimental and illegal to mandate unless President Bush waives our soldiers’ rights. We expect our President will follow the rule of law. From a March 11, 2002 original document by Major Thomas Rempfer and Kathryn D. Hubbell B. Efficacy of Anthrax Vaccine Adsorbed The Brachman study included 1,249 workers in four textile mills in the northeastern United States that processed imported goat hair. Of these 1,249 workers, 379 received anthrax vaccine, 414 received placebo, 116 received incomplete inoculations of either vaccine or placebo, and 340 received no treatment but were monitored for the occurrence of anthrax disease as an observational group. The Brachman study used an earlier version of the protective antigen-based anthrax vaccine administered subcutaneously at 0, 2, and 4 weeks and 6, 12, and 18 months. Response: Exactly. The Brachman study was done on the original vaccine, not on the vaccine that has been used on members of the Armed Services. During the trial, 26 cases of anthrax were reported across the four mills: 5 inhalation and 21 cutaneous anthrax cases. Prior to vaccination, the yearly average number of human anthrax cases was 1.2 cases per 100 employees in these mills. Of the five inhalation anthrax cases (four of which were fatal), two received placebo and three were in the observational group. Of the 21 cutaneous anthrax cases, 15 received placebo, 3 were in the observational group, and 3 received anthrax vaccine. Of the three cases in the vaccine group, one case occurred just prior to administration of the third dose, one case occurred 13 months after the individual received the third of the six doses (but no subsequent doses), and one case occurred prior to receiving the fourth dose of vaccine. In its report, the Panel stated that the Brachman study results demonstrate ‘‘a 93 percent (lower 95 percent confidence limit = 65 percent) protection against cutaneous anthrax’’ and that ‘‘inhalation anthrax occurred too infrequently to assess the protective effect of vaccine against this form of the disease’’ (50 FR 51002 at 51058). On the latter point, FDA does not agree with the Panel report. Because the Brachman comparison of anthrax cases between the placebo and vaccine groups included both inhalation and cutaneous cases, FDA has determined that the calculated efficacy of the vaccine to prevent all types of anthrax disease combined was, in fact, 92.5 percent. Response: This is playing fast and loose with statistics, and is in no way a credible statement. First of all, the small number of samples represented by the inhalation anthrax cases – just 5 – can in no way be used to extrapolate any kind of percentage rate to hundreds of thousands of service members. This is completely invalid from a statistical standpoint. Secondly, the Panel was entirely correct in stating that inhalation anthrax occurred too infrequently to assess the protective value of the vaccine. It is completely invalid from a statistical standpoint to lump one category into another and therefore declare all categories to be fairly represented in a statistical study. FDA’s determination in this case is without merit. The Panel noted that it would be very difficult, if not impossible, to clinically study the efficacy of any anthrax vaccine (50 FR 51058). Further study raises ethical considerations, and the low incidence and sporadic occurrence of anthrax disease also makes further adequate and well-controlled clinical studies of effectiveness not possible. For example: The Brachman study (Ref. 1); the CDC epidemiological data described in the December 1985 proposal; Fellows (2001) (Ref. 3); Ivins (1996) (Ref. 4); Ivins (1998) (Ref. 5). (lower 95 percent confidence interval = 65 percent). The efficacy analysis in the Brachman study includes all cases of anthrax disease regardless of the route of exposure or manifestation of disease. FDA agrees that the five cases of inhalation anthrax reported in the course of the Brachman study are too few to support an independent statistical analysis. However, of these cases, two occurred in the placebo group, three occurred in the observational group, and no cases occurred in the vaccine group. Therefore, the indication section of the labeling for AVA does not specify the route of exposure, and the vaccine is indicated for active immunization against Bacillus anthracis, independent of the route of exposure. Response: In fact, the Brachman study was done on the original vaccine, not the vaccine since given to members of the Armed Services; and neither vaccine has ever been licensed for use against inhalational anthrax, regardless of how the numbers and concepts in the Brachman study are manipulated. Please note the reference to Fellows (2001) (Ref.3). This reference is a follows: 3. Fellows, P. F., M. K. Linscott, B. E. Ivins, M. L. Pitt, C. A. Rossi, P. H. Gibbs, and A M. Friedlander, ‘‘Efficacy of a Human Anthrax Vaccine in Guinea Pigs, Rabbits, and Rhesus Macaques Against Challenge by Bacillus Anthracis Isolates of Diverse Geographical Origin,’’ Vaccine, 19(23– 24):3241–3247, 2001. The referenced report came out in 2001. It is therefore of no small import that in 1994, U.S. Army officer and researcher Col. Arthur M. Friedlander, one of the authors of that report, co-authored a chapter on the anthrax vaccine for the medical reference textbook “Vaccines”. Friedlander wrote that: "No assessment of the effectiveness of the vaccine against inhalation anthrax could be made because there were too few cases. … There have been no controlled clinical trials in humans of the efficacy of the currently licensed U.S. vaccine. … The current vaccine against anthrax is unsatisfactory for several reasons. The vaccine is composed of an undefined crude culture supernatant absorbed to aluminum hydroxide. There has been no quantification of the protective antigen content of the vaccine or of any of the other constituents, so the degree of purity is unknown. … The vaccine is also less than optimal in that six doses are required over 18 months, followed by annual boosters. There is also evidence in experimental animals that the vaccine may be less effective against some strains of anthrax."[xiii] From the Rempfer/Dingle Timeline To date, there has been no explanation for Col. Friedlander’s 180° change of position. As stated previously in this document, the Panel also considered epidemiological data—sometimes called surveillance data—on the occurrence of anthrax disease in at-risk industrial settings collected by the CDC and summarized for the years 1962–1974 as supportive of the effectiveness of AVA. In that time period, individuals received either vaccine produced by MDPH, now BioPort, or an earlier version of anthrax vaccine. Response: This certainly is an admission by FDA that two different vaccines were in use. The study referenced below obviously lumps them together, and, despite the differences in makeup between these two vaccines, does not look for results that may be specific to one vaccine as compared with another. In addition, this study was for cutaneous anthrax, not inhalational anthrax. Twenty-seven cases of anthrax disease were identified. Three cases were not mill employees but people who worked in or near mills; none of these cases were vaccinated. Twenty-four cases were mill employees; three were partially immunized (one with one dose, two with two doses); the remainder (89 percent) were unvaccinated (50 FR 51002 at 51058). These data provide confirmation that the risk of disease still existed for those persons who were not vaccinated and that those persons who had not received the full vaccination series (six doses) were susceptible to anthrax infection, while no cases occurred in those who had received the full vaccination series. In 1998, the Department of Defense (DOD) initiated the Anthrax Vaccination Program, calling for mandatory vaccination of service members. Thereafter, concerns about the vaccine caused the U.S. Congress to direct DOD to support an independent examination of AVA by the IOM. The IOM committee reviewed all available data, both published and unpublished, heard from Federal agencies, the manufacturer, and researchers. The committee in its published report concluded that AVA, as licensed, is an effective vaccine to protect humans against anthrax including inhalation anthrax (Ref. 2). Response: Please see section above (pp. 8-9) for a listing of the specific failures and bias of the IOM report. FDA agrees with the report’s finding that studies in humans and animal models support the conclusion that AVA is effective against B. anthracis strains that are dependent upon the anthrax toxin as a mechanism of virulence, regardless of the route of exposure. Response: FDA would seem to be ignoring some studies and admissions by the DOD, while paying attention only to those which seem to support its view. The following excerpts are from the Rempfer/Dingle timeline (with references). 12. February 1986. Dr. Gregory B. Knudsen published an article in Military Medicine on anthrax in man. Knudsen concluded that by extrapolating animal studies, which demonstrate that vaccination is not protective against all anthrax strains or concentrations to humans, we can expect that the vaccine will not protect humans against all strains or concentrations as well.[xiv] 13. March 1988. USAMRIID researcher Bruce Ivins wrote in the European Journal of Epidemiology of the inability of the anthrax vaccine to adequately protect against certain strains of anthrax.[xv] 14. May 1989. When asked by the U.S. Senate Committee on Governmental Affairs to explain the DOD’s assessment that the U.S. cannot adequately defend its service personnel against anthrax, Assistant Secretary of Defense Robert B. Barker answered, “The assessment in the 1986 report is accurate. Current vaccines, particularly the anthrax vaccine, do not readily lend themselves to use in mass troop immunization for a variety of reasons: …a higher than desirable rate of reactogenicity, and, in some cases, lack of strong enough efficacy against the aerosol route of exposure.”[xvi] In addition, even the Army has admitted that there is no known correlate between animal data and human data regarding the anthrax vaccine. C. Safety of Anthrax Vaccine Adsorbed CDC conducted an open-label study under an investigational new drug application (IND) between 1967 and 1971 in which approximately 7,000 persons, including textile employees, laboratory workers, and other at-risk individuals, were vaccinated with anthrax vaccine and monitored for adverse reactions to vaccination. The vaccine was administered in 0.5 ml. doses according to a 0, 2, and 4 week initial dose schedule followed by additional doses at 6, 12, and 18 months with annual boosters thereafter. Several lots, approximately 15,000 doses, of AVA manufactured by MDPH were used in this study period. In its report, the Panel found that the CDC data ‘‘suggests that this product is fairly well tolerated with the majority of reactions consisting of local erythema and edema. Severe local reactions and systemic reactions are relatively rare’’ (50 FR 51002 at 51059). Subsequent to the publication of the Panel’s recommendations, DOD conducted a small, randomized clinical study of the safety and immunogenicity of AVA. These more recent DOD data as well as post licensure adverse event surveillance data available from the Vaccine Adverse Event Reporting System (VAERS) further support the safety of AVA. These data were reviewed by FDA and provided the basis for a description of the types and severities of adverse events associated with administration of AVA included in labeling revisions approved by FDA in January 2002 (Ref. 6). Response: The VAERS reporting system is a passive, voluntary reporting system that cannot be replied upon for statistics when it comes to members of the Armed Forces. Most service members who receive anthrax shots are never even told about the VAERS system; others were assured by their military physicians that VAERS reports would be filed on their behalf, only to find out later that nothing was ever submitted. To reply upon this data is to come to false conclusions. The fact is that there have never been a long-term study on the effects of the anthrax vaccine; and no study has been done on the current vaccine which involves both a vaccinated group and a control group. If DOD did conduct a “small, randomized clinical study,” its results have neither been peer-reviewed nor released. The lack of such valid follow-up study and reporting concerning Investigational New Drugs is, in fact, one of the major criticisms leveled at the DOD by Health and Human Services in its 1997 letter. D. the Panel’s General Statement: Anthrax Vaccine, Adsorbed, Description of Product The Panel report states: ‘‘Anthrax vaccine is an aluminum hydroxide adsorbed, protective, proteinaceous, antigenic fraction prepared from a nonproteolytic, nonencapsulated mutant of the Vollum strain of Bacillus anthracis’’ (50 FR 51002 at 51058). FDA would like to clarify that while the B. anthracis strain used in the manufacture of BioPort’s AVA is the nonproteolytic, nonencapsulated strain identified in the Panel report, it is not a mutant of the Vollum strain but was derived from a B. anthracis culture originally isolated from a case of bovine anthrax in Florida. Response: The discrepancy here is no doubt reflective of the fact that there were two vaccines: the Brachman vaccine and the subsequent vaccine which reflected manufacturing and configuration changes for use by the military. E. The Panel’s Specific Product Review: Anthrax Vaccine Adsorbed: Efficacy The Panel report states: 3. Analysis—a. Efficacy—(2) Human. The vaccine manufactured by the Michigan Department of Public Health has not been employed in a controlled field trial. A similar vaccine prepared by Merck Sharp & Dohme for Fort Detrick was employed by Brachman * * * in a placebo-controlled field trial in mills processing imported goat hair * * *. The Michigan Department of Public Health vaccine is patterned after that of Merck Sharp & Dohme with various minor production changes. (50 FR 51002 at 51059). Response: The vaccine may have been similar; and may have been pattered after that of Merck Sharp & Dohme; but the simple fact is that it was now a different vaccine, as FDA itself notes above. FDA has found that contrary to the Panel’s statement, the vaccine used in the Brachman study was not manufactured by Merck Sharp & Dohme, but instead this initial version was provided to Dr. Brachman by Dr. G. Wright of Fort Detrick, U.S. Army, DoD (Ref. 1). The DOD version of the anthrax vaccine used in the Brachman study was manufactured using an aerobic culture method (Ref. 7). Subsequent to the Brachman trial, DOD modified the vaccine’s manufacturing process to, among other things, optimize production of a stable and immunogenic formulation of vaccine antigen and to increase the scale of manufacture. Response: Again, this is an admission that a different vaccine was manufactured. To assume the results of the Brachman study apply to this different vaccine, and to continually quote the Brachman study as proof that the vaccine is safe, is fraudulent science. In the early 1960s, DOD entered into a contract with Merck Sharp & Dohme to standardize the manufacturing process for large-scale production of the anthrax vaccine and to produce anthrax vaccine using an anaerobic method. Thereafter, in the 1960s, DOD entered into a similar contract with MDPH to further standardize the manufacturing process and to scale up production for further clinical testing and immunization of persons at risk of exposure to anthrax spores. This DoD-MDPH contract resulted in the production of the anthrax vaccine that CDC used in the open-label safety study and that was licensed in 1970. Response: Please look at the timeline of events leading up to 1970, with particular note of the entries for September, 1965, and February, 1969. In 1965, a new vaccine was formulated and produced. In 1969, the Division of Biologic Standards recommend license approval, but noted that clinical data establishing efficacy had not been submitted – and it recommend that such data be gathered. To reiterate: The vaccine licensed in 1970 was no longer the original anthrax vaccine. It was materially different from the original, and safety studies from the original cannot be applied. While the Panel attributes the manufacture of the vaccine used in the Brachman study to Merck Sharp & Dohme, FDA has reviewed the historical development of AVA and concluded that DOD’s continuous involvement with, and intimate knowledge of, the formulation and manufacturing processes of all of these versions of the anthrax vaccine provide a foundation for a determination that the MDPH anthrax vaccine is comparable to the original DoD vaccine. See Berlex Laboratories, Inc. v. FDA, 942 F. Supp. 19 (D.D.C. 1996). The comparability of the MDPH anthrax vaccine to the DOD vaccine has been verified through potency data that demonstrate the ability of all three versions of the vaccine to protect guinea pigs and rabbits against challenge with virulent B. anthracis. In addition, there are data comparing the safety and immunogenicity of the MDPH vaccine with the DOD vaccine. These data, while limited in the number of vaccines and samples evaluated, reveal that the serological responses to the MDPH vaccine and the DOD vaccine were similar with respect to peak antibody response and seroconversion. Response: If these criteria were used for all drugs on the market, we’d have no separate patents or licenses. There are certain classes of drugs which currently cause alarm, specifically the COX2 inhibitors such as Vioxx and Celebrex. But to say these are the same drug is ridiculous; if they were not materially different, they would not each have their own patent. So to say that the DoD vaccine is comparable to the MDPH vaccine because the potency is similar, or because there is data comparing the two in regard to safety and immunogenicity, does nothing to address the fact that one vaccine may, indeed, cause more serious and frequent adverse reactions than the other, particularly if used off-label. In addition, in section “K” below, FDA makes its own statement that seroconversion rates are not an indicator as to the comparability of vaccines: “The current package insert for this product states that ‘although the rates of seroconversion are essentially equivalent with either type of tetanus toxoid, the adsorbed toxoids induce more persistent antitoxin titers than fluid products.’” Statements of seroconversion rates, potency, etc. are specific to each vaccine / drug and the recipes being used. Furthermore, the form used and the concentration of the primary ingredients and adjuvants/ vehicles range from somewhat to significantly different, in the batches prepared. The route of administration is a “wild-card” in the reactivity, especially since the IM, IV routes are not considered valid routes for administering the original licensed anthrax vaccine, let alone the multiple versions. F. The Panel’s Specific Product Review: Anthrax Vaccine Adsorbed: Labeling The Panel report states: 3. Analysis—d. Labeling. The labeling seems generally adequate. There is a conflict, however, with additional standards for anthrax vaccine. Section 620.24(a) (21 CFR 620.24(a)) defines a total primary immunizing dose as 3 single doses of 0.5 ml. The labeling defines primary immunization as 6 doses (0, 2, and 4 weeks plus 6, 12, and 18 months). (50 FR 51002 at 51059). The labeling of AVA since at least 1978 has described the vaccination schedule as three ‘‘primary’’ doses followed by three ‘‘booster’’ doses for a total of six doses followed by annual boosters. This labeling is not inconsistent with § 620.24(a) before it was revoked by FDA in 1996 as part of a final rule that revoked 21 CFR part 620 and other biologics regulations because they were obsolete or no longer necessary (Ref. 8). VI. FDA’s Responses to Additional Panel Recommendations. In the December 1985 proposal, FDA responded to the Panel’s general recommendations regarding the products under review and to the procedures involved in their manufacture and regulation. Below, FDA responds in final to the general recommendations. Response: The labeling certainly is in conflict and is a problem. Referring back to the timeline, here is the entry for December, 1985: December 1985. The review required by the Food and Drug Administration in 1972 was published in the Federal Register as a Proposed Rule. The review panel recommended that AVA be placed in Category I as safe, effective and not mislabeled. The review panel did note the lack of efficacy data: “the vaccine…has not been employed in a controlled field trial.” The panel also noted the inability to determine the vaccine’s use in preventing inhalation anthrax: “efficacy against inhalation anthrax is not well documented . . . no meaningful assessment of its value against inhalation anthrax is possible due to its low incidence.” Finally, based on the extremely limited use of the vaccine the panel felt the possible benefit outweighed the risk: “In general, safety of this product is not a concern especially considering its very limited distribution and the benefit-to-risk aspects of occupational exposure in those individuals for whom it is indicated.”[xvii] This panel also found the dosage of the anthrax vaccine to be incorrect, and recommended a correction to the labeling to only 3 shots. V. FDA’s Response to Additional Panel Recommendations B. Periodic Review of Product Labeling - page 8 In its report the Panel noted a number of labeling deficiencies. To improve the labeling, the Panel recommended that labeling be reviewed and revised as necessary at intervals of no more than every 2 years. As discussed in the December 1985 proposal, FDA believes the current system of labeling review will adequately assure accurate labeling. Periodic review of labeling on a set schedule is unnecessary. Section 601.12(f) prescribes when revised labeling must be submitted, either as a supplement for FDA’s review or, if changes are minor, in an annual report. In addition, the agency may request revision of labeling when indicated by current scientific knowledge. FDA believes that, by these mechanisms, product labeling is kept up to date, and a scheduled, routine review of labeling is unnecessary and burdensome for both the agency and manufacturers. Response: If anyone were doing a comprehensive, long-term study of the effects of the anthrax vaccine on service members, we would agree that FDA would probably be informed of the resulting data and revise the label accordingly. However, that is not being done, despite HHS’ letter to DOD in 1997 clearly requiring follow-up studies and correct labeling for Investigational New Drugs. As a result, information comes in randomly and from various quarters, and in light of ongoing reports of adverse reactions, we believe a scheduled, routine review of the anthrax vaccine label is absolutely necessary. It will force FDA to look for the new data that will invariably be available as reports of adverse reactions continue to mount. It might interest FDA to monitor the Data Base of the Ill on the web site of the Military Vaccine Education Center at http://www.milvacs.org. Entries continue to grow. C. Improvement in the Reporting of Adverse Reactions The Panel recommended that actions be taken to improve the reporting and documentation of adverse reactions to biological products. The Panel particularly noted the need to improve the surveillance systems to identify adverse reactions to pertussis vaccine. Since publication of the Panel’s report, the Vaccine Adverse Event Reporting System (VAERS) was created as an outgrowth of the National Childhood Vaccine Injury Act (NCVIA) and is administered by FDA and CDC. VAERS accepts from health care providers, manufacturers, and the public reports of adverse events that may be associated with U.S.-licensed vaccines. Health care providers must report certain adverse events included in a Reportable Events Table (Ref. 9) and any event listed in the vaccine’s package insert as a contraindication to subsequent doses of the vaccine. Health care providers also may report other clinically significant adverse events. FDA and CDC receive an average of 800 to 1,000 reports each month under the VAERS program. A guidance document is available which explains how to complete the VAERS form (Ref. 10). To facilitate electronic reporting, FDA is currently revising the reporting form Response: Again, the VAERS system is a passive, voluntary system; it depends upon people’s willingness to participate. It can in no way be considered adequate for reporting rates of adverse reactions, particularly in the military. As already stated, most service members are not even told of the existence of VAERS; the military’s standard procedure is to deny any relation between a person’s illness and the vaccines taken just prior to the illness; and, even though some service members have been assured that they physicians will file a VAERS report on their behalf, too frequently they have gone back to check and nothing has been done. If adverse reactions in the military are to be adequately and accurately reported, then a proactive, not passive, research study needs to be done, as clearly spelled out in the HHS letter. That will be impossible so long as physicians routinely deny what might cause the adverse reaction, or, in some cases, are not in any way educated as to what the adverse reactions to the anthrax vaccine might be. The fact that DOD routinely ignored the HHS requirements begs the question as to who is genuinely protecting the troops – and with what. D. Periodic Review of Product Licenses The Panel recommended that all licensed vaccines be periodically reviewed to assure that data concerning the safety and effectiveness of these products are kept current and that licenses be revoked for products which have not been marketed for years or which have never been marketed in the licensed form. The Panel noted that, by limiting the period for which specific vaccines may be licensed, older products would be assured periodic review, and new products for which additional efficacy data are required could be provisionally licensed for a limited time period during which additional data can be generated. In its proposed response, FDA noted that licensing policies in effect at the time of the review resulted in licenses being held for some products which were never intended to be marketed as individual products or which were no longer being marketed as individual products. FDA had required that manufacturers licensed for a combination vaccine also hold a license for each individual vaccine contained in the combination. For example, a manufacturer of diphtheria, tetanus, and pertussis (DTP) vaccine would also be required to have a license for Diphtheria Toxoid, Tetanus Toxoid, and Pertussis Vaccines. Because this policy is no longer in effect, most licenses are for currently marketed products. In a few cases, there may be no current demand for a product but, for public health reasons, a license continues to be held for the product. There are some vaccines for which there is little current demand but continued licensure could expedite the manufacture and availability of the product in the event an outbreak of the targeted disease should occur. FDA believes that the routine inspection of licensed facilities adequately assures that the information held in product licenses is current and that a routine review of safety and efficacy data is unnecessary and burdensome. The Panel’s recommendation that some new vaccines be provisionally licensed for only limited periods of time while additional data are generated is inconsistent with the law that requires a determination that a biologic product is safe, pure, and potent before it is licensed. Response: If the FDA followed its own rules in determining that a biologic product was safe, pure and potent before it was licensed, the Panel would not have needed to make this recommendation. Go back to the facts before and after the 1970 license for the anthrax vaccine was granted by looking at specific entries in the timeline again: February 1969. The Division of Biologic Standards recommended license approval, but noted that clinical data establishing efficacy had not been submitted and requested data be gathered to establish efficacy.[xviii] May 1989. When asked by the U.S. Senate Committee on Governmental Affairs to explain the DOD’s assessment that the U.S. cannot adequately defend its service personnel against anthrax, Assistant Secretary of Defense Robert B. Barker answered, “The assessment in the 1986 report is accurate. Current vaccines, particularly the anthrax vaccine, do not readily lend themselves to use in mass troop immunization for a variety of reasons: …a higher than desirable rate of reactogenicity, and, in some cases, lack of strong enough efficacy against the aerosol route of exposure.”[xix] March 1990. Army Colonels E.T. Takafuji and P. K. Russell published an article describing the human anthrax vaccine as a "limited use vaccine" and an "unlicensed experimental vaccine". [xx] It puzzles us, in light of these known and public facts, why the FDA continues to say that it does not need to follow the Panel’s recommendations. To make matters worse, FDA has ignored the HHS letter to DOD, which carries the FDA name at the top of the letterhead, demanding that proper procedures and studies be conducted on Investigational New Drugs. This somehow all conveniently disappears from view. E. Compensation for Individuals Suffering Injury from Vaccination The Panel recommended that compensation from public funds be provided to individuals suffering injury from vaccinations that were recommended by competent authorities, carried out with approved vaccines, and where the injury was not a consequence of defective or inappropriate manufacture or administration of the vaccines. A compensation program has been implemented consistent with the Panel’s recommendation. The NCVIA established the National Vaccine Injury Compensation Program (NVICP) designed to compensate individuals, or families of individuals, who have been injured by childhood vaccines, whether administered in the private or public sector. The NVICP, administered under the Health Resources and Services Administration, Department of Health and Human Services (DHHS), is a no-fault alternative to the tort system for resolving claims resulting from adverse reactions to routinely recommended childhood vaccines. The specific vaccines and injuries covered by NVICP are identified in a Vaccine Injury Table that may periodically be revised as new vaccines come into use or new types of potential injuries are identified. The NVICP has resulted in a reduction in the amount of litigation related to injury from childhood vaccines while assuring adequate liability coverage and protection. The NVICP applies only to vaccines routinely recommended for infants and children. Vaccines recommended for adults are not covered unless they are routinely recommended for children as well, e.g., Hepatitis B Vaccine. Response: Nor is there any compensation for service members, despite the fact that there are “individuals suffering injury from vaccinations that were recommended by competent authorities (not competent in the service, since these vaccinations are ordered by the chain of command, not by military physicians), carried out with approved vaccines (not approved in the military, since the anthrax vaccine was, for over 18 years, an Investigational New Drug, and its license is now – and should be – in question), and where the injury was not a consequence of defective or inappropriate manufacture or administration of the vaccines (FDA surely remembers the number of times it sanctioned BioPort, the anthrax vaccine’s only manufacturer, and finally shut it down for four years. In addition, the administration of the anthrax vaccine in the military is haphazard at best, rarely if ever according to the instructions on the label – instructions, as we have seen, that were wrong in the first place.). A 1950 body of law called the Feres Doctrine prevents service members from suing the government for any injuries resulting from such malpractice or carelessness – leaving the way open for unregulated and unethical medical experimentation, a horrifying byproduct of a well-intended law. H. Consistency of Efficacy Protocols The Panel recommended that the protocols for efficacy studies be reasonably consistent throughout the industry for any generic product. To achieve this goal, the Panel recommended the development of industry guidelines that provide standardized methodology for adducing required information. FDA believes that the standardization of clinical testing methodology for a group of vaccines is often not practical or useful. Because of the variety of possible vaccine types, e.g., live vaccines, killed vaccines, toxoids, bioengineered vaccines, acellular vaccines, and the diversity of populations in which the vaccine may be studied, it is difficult to develop guidance that would apply to more than one or two studies. Response: Once again, it FDA would be advised to follow its own advice. It lumped studies for cutaneous anthrax and inhalation anthrax together and extrapolated the results to apply to both; furthermore, it assumed that the results for people working in mills and various industries would be the same as for members of the armed forces; and finally, it did not study one anthrax vaccine as separate from another, even though, in this very document, it has acknowledged the differences. If a standardized method of testing is neither practical nor useful in light of these differences, then FDA and DOD are severely remiss and ethically challenged to have NOT conducted individualized studies on the different anthrax vaccines; and individualized studies on how the vaccines affected cutaneous vs. inhalational anthrax. Furthermore, DOD is in direct violation of requirements put forth by HHS and FDA. I. The Effect of Regulations Protecting and Informing Human Study Subjects on the Ability to Conduct Clinical Trials The Panel expressed concern that the regulations governing informed consent and the protection of human subjects involved in clinical investigations should not establish unnecessary impediments to the goal of obtaining adequate evidence for the safety and effectiveness of a product. FDA believes that the regulations and policies applying to informed consent and the protection of human subjects do not inhibit the adequate clinical study of a product. FDA notes that whenever the regulations or guidance documents related to these subjects are modified or amended, FDA offers an opportunity for public comment on the revisions. FDA particularly welcomes comments on how appropriate informed consent and protection of human subjects can be maintained while assuring that the development and study of useful products is not inhibited. Response: FDA is particularly reminded that appropriated informed consent and protection of human subjects has never been accorded to members of the armed forces, as is their constitutional right, and as has been stipulated in the 1997 letter from HHS/FDA to DOD. Unless there is strict enforcement of the law within the DOD, these legal and medical abuses will continue. K. Immunogenic Superiority of Adsorbed Toxoids Over Fluid Toxoids The Panel recommended that the immunogenic superiority of the adsorbed DTs over the fluid (plain) preparations be strongly emphasized in product labeling, especially with regard to the duration of protection. Tetanus Toxoid fluid, manufactured by Aventis Pasteur, Inc., is the only fluid toxoid product that remains licensed in the United States in 2003. This product is licensed for booster use only in persons over 7 years of age. The current package insert for this product states that ‘‘although the rates of seroconversion are essentially equivalent with either type of tetanus toxoid, the adsorbed toxoids induce more persistent antitoxin titers than fluid products.’’ Response: This very interesting statement reflects that fact that while two drugs may indeed have similar rates of seroconversion, the drugs may still have materially different effects. This is certainly inconsistent with FDA’s statement that the two anthrax vaccines are similar because, in part, they share similar seroconversion rates. VI. FDA’s Response to General Research Recommendations In its report, the Panel identified many areas in which there should be further investigation to improve existing products, develop new products, develop new testing methodologies, and monitor the population for its immune status against bacterial disease. In the December 1985 proposal, FDA responded to these recommendations in the responses identified as items 11, 17 (in part), 21, 25, and 27. As discussed in the December 1985 proposal, FDA considered the Panel’s recommendations in defining its research priorities at the time the recommendations were made. Because a considerable amount of time has elapsed since these recommendations were made and FDA initially responded to the recommendations, FDA is not providing specific responses to each recommendation in this final rule. As in any area of scientific research, new discoveries and new concerns require a continual reevaluation of research priorities and objectives to assure their relevance to current concerns. FDA recognizes the Panel’s desire to have FDA’s research program evolve with the significant issues and findings of medical science. In order to assure the continued relevance of its research program, CBER’s research program for vaccines, including bacterial vaccines and related biological products, is subject to peer review by the Panel’s successor, the Vaccines and Related Biological Products Advisory Committee (see, for example, the transcripts from the meetings of June 11 (Ref. 15) and November 29, 2001 (Refs. 16 and 17), and March 6, 2002 (Ref. 18)). In addition, CBER has defined as part of its mission statement a strategic goal of assuring a high quality research program that contributes directly to its regulatory mission. This goal includes a plan to assure that CBER’s research program continues to support the regulatory review of products and timely development of regulatory policy, and to have a significant impact on the evaluation of biological products for safety and efficacy. Because of limited resources, FDA also supports the leveraging of resources to create effective collaborations in the advancement of science. FDA has issued a ‘‘Guidance for FDA Staff: The Leveraging Handbook, an Agency Resource for Effective Collaborations.’’ (Ref. 19). Through cooperation with international, other Federal, and State health care agencies and the industry and academia, the agency intends that its research resources will reap the benefits of a wide range of experience, expertise, and energy from the greater scientific community while the agency maintains its legal and regulatory obligations. FDA invites comment at any time on ways it may improve its research program and set its objectives. Response: Wonderful. Insist that the DOD follow the law as laid down by HHS in 1997, and conduct full-scale, proactive research on the effects of the anthrax vaccine on its service members, and release all findings and reports to the FDA as well as to the general public, since there are plans for public use of this vaccine. Insist that if all vaccines are to be researched and studied, the anthrax vaccine must be included in this research by those who are using it. The July 22, 1997 letter from the Dept. of Health and Human Services With FDA on its letterhead To Edward D. Martin, M.D., Acting Assistant Secretary of Defense for Health Affairs If FDA were truly concerned about the anthrax vaccine license and the vaccine’s effects upon members of the Armed Forces, it would go back to this letter – obviously written under the double auspices of FDA and HHS – and enforce it. This letter refers specifically to problems with the use of the Investigational New Drug TBE (tick-borne encephalitis) vaccine in Bosnia and the use of PB bills (pyridostigmine bromide) in the Persian Gulf, and repeatedly voices concerns about the military’s ability to handle Investigational New Drugs in the future. At the time this letter was written, the anthrax vaccine was still on Investigational New Drug status with FDA – as it was for a total of 18 years. The letter cites the following: 1) Failure to meet the conditions set by the Commissioner for granting a waiver of informed consent concerning the PB pills; 2) Failure to collect, review, and make reports of adverse experiences attributed to the use of same; 3) Clarification as to whether or not PB bills were labeled with language granted in the informed consent waiver (i.e., whether it carried the “military use” labeling); 4) Failure to insure that the investigation was conducted in accordance with the general investigational plan for the botulinum toxoid vaccine (the Army simply replied that who received the vaccine was classified information, and no notation was made in the permanent record … “however, unit records may have been kept.”) Emphasis added 5) Failure to maintain adequate records showing the receipt, shipment and disposition of the investigational product botulinum toxoid vaccine; 6) Clarification as to whether DOD met the conditions granting a waiver from the informed consent requirements for the botulinum toxoid vaccine, and whether informed consent was given at all. The letter states in its summary on page 10: “These regulatory deviations, taken as a whole, point to an underlying inability for DoD to carry out its obligations under INDs for drugs and biologics intended to provide potential protection to deployed military personnel. … We suggest that DOD’s difficulties may result, in part, from a discontinuity between the military command that planned the IND study and provides assurances to this agency and the command that ultimately must carry out the study. This discontinuity in command appears to occur within the Army itself…and may occur DoD-wide…” The letter goes on to make certain minimum requests, including: · a statement outlining how the DoD will ensure that IND commitments are fulfilled in combat or deployment situations; · who will be responsible for informing the FDA that these commitments have been met; · how DoD will ensure that adequate records have been kept concerning the receipt, shipment and disposition of investigational products as well as the inclusion of immunizations in all service members’ permanent medical records; · how the DOD will ensure that collection, review and reporting of adverse clinical consequences attributed to the use of an investigational product are timely and complete; · how military personnel will be provided with information on investigational products; · how those products are correctly labeled; and · how DOD will ensure that the use of such products immediately conforms to FDA’s IND requirements. We respectfully submit to FDA that nothing has changed. Appropriate records are still not entered on service members’ shot records; DoD still does not track adverse reactions to the anthrax vaccine; DoD has never provided either service members or military physicians with information on the adverse effects of the anthrax vaccine, let alone conducted a follow-up study and reported such to FDA (all of FDA’s quoted research in the Proposed Rule, one will note, is from 20 and 30 years ago, not from any current administration of Anthrax Vaccine Adsorbed – with “current” defined as meaning from 1990 to the present day.) DOD has not complied with FDA requirements concerning the administration or labeling of the vaccine, nor with record keeping, or with the legal requirements of informed consent or a Presidential Waiver of that consent. In short, for FDA to use faulty statistics; research based on a different vaccine other than the one currently used on members of the Armed Forces; fraudulent scientific reasoning in comparing the two different anthrax vaccines; biased reporting via the Institute of Medicine (an Institute which has itself come under attack for conflicts of interest); a complete denial of its own rules and procedures, as evidenced by the casual language and flawed reasoning in the Proposed Rule as well as by the 1997 HHS/FDA letter to the DoD; and finally, a more than casual approach to the law, all speaks to a dysfunctional system in complete disarray. It is essential to confront reality and to force DOD to comply with the principles of hard science and with the letter of the law by withdrawing the license for the anthrax vaccine and classifying the anthrax vaccine as a Category II drug: unsafe, unproven, and misbranded. If there is, indeed, an anthrax emergency, it lies within the anthrax vaccine itself. Kathryn D. Hubbell, President Military Vaccine Action Committee, L.L.C. P.O. Box 8168 Missoula, MT 59807 PH: (406) 531-9355 (cell) e-mail: contact@mvacpac.org web site: www.mvacpac.org --------------------------------------------------------------------------------