LEGAL MEMORANDUM

  • RE: Legality of Orders to Submit to Anthrax Vaccination

    FROM: Lt. Col. John J. Michels, Jr., USAFR; Major Bruce Smith, USAFR

    "I think medicine is based on trust. If for whatever reason, in any individual’s mind he loses trust in his medicine, in his doctor, or he loses trust in his government, then those sorts of feelings will fall on more fertile ground… Our job is to regain that trust and make sure that our message is clear, that we are protecting our people, that we are doing everything we possibly can to make sure we are not harming them with the thing we give them to protect them."

    1. Unidentified Defense Department Spokesman at Department of Defense ("DoD") Background Briefing on the Anthrax Vaccine, August 5, 1999.
    1. ISSUE PRESENTED:

      Are orders currently being given to members of the U.S. Armed Forces to submit to anthrax vaccinations consistent with federal law?
    2. SHORT ANSWER:

      Orders currently being given to members of the United States Armed Forces to submit to anthrax vaccinations are illegal because they contradict the express terms of Presidential Executive Order 13139 (1999) and 10 U.S.C. ¤ 1107. Because the anthrax vaccine is being used in a manner inconsistent with both its original licensing and for a purpose for which it has never been tested, the vaccine is properly considered an Investigational New Drug under Food and Drug Administration ("FDA") regulations and federal court decisions. Both the Executive Order and the statute mandate that informed consent is a prerequisite to all vaccinations with an Investigational New Drug. It is undisputed that service members are not giving their informed consent to the vaccination process.
    3. ANALYSIS:
      1. Introduction

        Members of the Armed Forces of the United States are currently being vaccinated against anthrax (Bacillus anthracis), a relatively common, spore-forming soil bacterium that can cause death within 1-6 days of exposure to a lethal dose. Anthrax is postulated as a likely biological warfare (BW) agent because it is relatively easy to synthesize, exists naturally as spores that are readily dispersed in the atmosphere and because a variety of second and third world nations are known to have at least attempted to create BW versions of the disease. See Atch. 1, Excerpt of Dept. of Defense Background Briefing p. 13 (August 5, 1999).

        There are essentially two ways to medically counter anthrax BW – antibiotics and vaccines. Antibiotics must be administered shortly before or after anthrax exposure to be effective. Antibiotics cannot prevent a lethal infection once the anthrax spore has produced signs of illness. Vaccines, on the other hand, can be administered years before exposure, are theoretically effective as long as the victim has enough immunity to neutralize the bacillus, and generally do not provide the kind of logistics problems associated with long-term, forward storage of antibiotics.

        In December 1997, Secretary of Defense William Cohen announced a multi-service vaccination program for all active duty and Reserve and National Guard service members. Cohen’s directive, requiring that all active and Reserve component members receive anthrax vaccinations was ostensibly based on a threat to U.S. Forces from second and third world nations who sought ready access to a weapon of mass destruction ("WMD").

        The sole production facility for anthrax vaccine was originally owned by the Michigan Department of Public Health ("MDPH"). In the mid 1990s the facility was sold to a corporation known as Michigan Biologic Products, Inc. ("MBPI"). In September 1998, MBPI was sold to a group of investors heading up a company called Bioport, Inc.

        MDPH obtained approval for the anthrax vaccine in 1970 from the National Institute of Health ("NIH") Bureau of Biologics. This was some two years before efficacy and safety data were required by the FDA for drug approval and licensing. Long-term safety data for the vaccine was not supplied with the original license application and none has ever been supplied to the FDA. In addition, the vaccine now being produced by MBPI’s successor, Bioport, is produced under a different procedure and is apparently chemically different from the original vaccine approved by the NIH.

        The license to produce anthrax vaccine was originally the property of MDPH and later, MBPI and Bioport. The original license for the anthrax vaccine reflects its use in agricultural and veterinary settings as a protection against cutaneous (skin) contact anthrax. See Atch. 2, Anthrax Vaccine Adsorbed, various package inserts, Michigan Dept. of Pub. Health, 1978. The vaccine has never been licensed as a prophylaxis against airborne anthrax, the most likely BW variant.

      2. The Anthrax Vaccine Used By DoD Is An Investigational New Drug

        The key to understanding why current Defense Department policy is illegal is the recognition that the anthrax vaccine as currently used by DoD is properly characterized under FDA regulations as an "Investigational New Drug" ("IND"). The vaccine (hereafter referred to as "AVA" for "anthrax vaccine adsorbed") was originally approved only for protection against cutaneous anthrax. However, it is undisputed that the DoD vaccination program is aimed at protecting vaccine recipients from pulmonary, or airborne, anthrax. In addition, the DoD vaccination regimen differs from the regimen originally approved by the NIH.

        These substantive changes in the way the vaccine is used and the purpose for which it is used render the vaccine an IND under current federal law. As an IND, the vaccine may not be administered to service members without their informed consent, as directed by President Clinton’s Executive Order 13139 and 10 U.S.C. ¤ 1107. Accordingly, orders to military personnel to submit to the vaccine without their consent are per se violative of a direct order from the President in his role as Commander-in-Chief.

        1. Investigational New Drug Status.

          Vaccines, like other medical drugs, are closely monitored by the FDA and are licensed for production and marketing. The Center for Biologics Evaluation and Research ("CBER") is the FDA agency charged with oversight of the four-stage licensing process. See Bascom & Sutton, New Generation Vaccines, Center for Biologics Evaluation and Research, U.S. Food and Drug Administration (1997), at Atch. 3. The process consists of a pre-clinical stage, followed by an IND stage, followed by a Product License Application process, and finally, a post-licensure stage. See generally 21 C.F.R. ¤ 312. The FDA and CBER govern a vaccine license applicant in both its manufacturing and marketing procedures. The FDA does not govern the behavior of the end user, in this case, the Department of Defense. (1)

          It is clear that the term "investigational" drugs also embraces so-called "new" drugs as defined by the FDA itself. See 21 C.F.R. ¤ 312.3(b) (cited in EO 13139). The determination of what is a "new" drug for purposes of FDA regulatory coverage (and coverage under EO 13139) hinges on a variety of factors. A drug is "new", even if it has been in use for years, if there is a proposed change in the target use of the product, a change in the formula, dilution of the drug, a change in its route of administration, or even repackaging of the drug product. See generally What Is A "New Drug" Within the Meaning of ¤ 201(p) of the Federal Drug and Cosmetic Act, 133 ALR Fed 229 (1999), and cases cited therein.

          Court decisions reinforce FDA’s interpretation. For example, in Hoffman v. Sterling Drug, Inc., 485 F.2d 132 (3d Cir. 1973) the court held that marketing a drug that had been approved by the FDA for the treatment of malaria as suitable for use in treating lupus caused the already approved drug to be considered a "new" drug, at least as far as the lupus treatment was concerned. Similarly, in U.S. v. Articles of Drug, etc., 442 F. Supp. 1236 (S.D.N.Y. 1978) the court found that a drug may be considered "new" if there is a change in the dosage, or method or duration of administration or application, or other condition of use prescribed, recommended or suggested in the labeling of such drug, despite the fact that the drug had previously had been approved, albeit with a different dosage and for a different purpose.

          In addition, drugs that are not adequately tested are also considered "new" and investigational, regardless of usage. In U.S. v. Articles of Drug Consisting of the Following: 5906 Boxes, 745 F.2d 105 (1st Cir. 1984) the court found that a nausea-suppressing drug was a "new" drug in the absence of substantial evidence that it was recognized by experts as safe and effective. The court defined "substantial evidence" to mean consisting of adequate and well-controlled investigations, including clinical investigations conducted by experts. The court noted that substantial evidence that a drug is generally recognized by experts as safe and effective means adequate and well-controlled investigations including clinical investigations conducted by experts.

          Finally, in U.S. v. Rutherford, 442 U.S. 544 (1979) the Supreme Court held that under 21 U.S.C. ¤ 321(p)(1) the term "new drug" described a drug not generally recognized as being safe and effective for use under the conditions prescribed, recommended or suggested in the labeling. Rutherford, 442 U.S. at 552-3.

          Clearly then, federal statutes, regulations and case law show indisputably that even an established and licensed drug that is modified with regard to its dosage regimen, or the purpose for which it is being offered, is an "investigational new drug", covered by the requirements of EO 13139 and 10 U.S.C. ¤ 1107.

        2. The Current Use of AVA for Pulmonary Anthrax and the Altered Vaccine Schedule for U.S. Soldiers Makes the AVA an Investigational Drug under FDA Regulations.

        The 1970 NIH-approved license for AVA indicates that it was approved as a prophylaxis only against cutaneous exposure to anthrax for a specific methodology of administration, and a specific vaccination schedule. See Atch. 2.

        Recognizing the need for certification for pulmonary infections, in 1995 MDPH and the Army discussed establishing a plan for Investigational New Drug approval by the FDA. See Atch. 4, Anthrax Vaccine License Amendment Project Plan briefing slides (October 20, 1995). The briefing slides clearly show that the Army was well-aware that the AVA, in order to meet the above-described legal requirements for licensure, had to pass through the IND application process in order to become fully licensed as a prophylaxis for pulmonary anthrax. The focus of the proposed plan was to get approval from the FDA for a change to the immunization schedule (in this case to a series of three doses of vaccine versus the prescribed six) and to change the labeling to reflect that the vaccine was properly administered as protection against pulmonary or airborne anthrax. Id.

        In fact, less than one year from the date of the briefing, on September 20, 1996, MBPI filed an Investigational New Drug application with the FDA. The application identified the three areas where the current license would be modified – showing a new designation for "inhalation anthrax", changing the "route of administration", and changing the "vaccination schedule". The application indicates that it is an "initial" investigational new drug application. See Atch. 5, IND Application (September 20, 1996).

        Thus, as the DoD was preparing to kick-off its anthrax vaccination program, the sole producer of anthrax vaccine recognized that its product, as labeled, was not legally viable and undertook the appropriate steps to change product use labeling, method of administration, and vaccination schedule. These substantial changes in how this drug was to be used rendered it an IND. This is explicitly acknowledged by the September 20, 1996 application by MBPI. That application has never been withdrawn by MBPI or Bioport, nor has it ever been modified or acted on in any way.

        The formal record of the anthrax program is littered with references to the vaccine’s IND status. For example, as the Army began to move forward to try and license the vaccine as a prophylaxis against inhaled or pulmonary anthrax, it followed up its October 1995 meeting with a series of meetings designed to request that MBPI file an IND application for the vaccine. On November 13, 1995 the Joint Program Manager for Biological Defense, Army Brigadier General Walter L. Busbee, instructed the Joint Program Office for Biological Defense that the DoD needed to "…develop a … package for initiating and completing an amendment to MDPH anthrax license for: (1) reduced immunization schedule, (2) immunization by the intramuscular route, and (3) indication for protection against an aerosol challenge". Minutes of the Meeting on Changing the Food and Drug Administration License for the Michigan Department of Public Health (MDPH) Anthrax Vaccine to Meet Military Requirements (November 13, 1995), Atch. 6. As late as June 30, 1999, in testimony before the House Subcommittee on National Security, Veterans Affairs and International Relations, Atch. 7, at 12, Mr. Fuad El-Hibiri, President and CEO of Bioport, stated

        [w]e continue to hold an Investigational New Drug application - IND 6847 – to improve administration of the anthrax vaccine.

        The use of the AVA as currently contemplated by DoD is a clear change in how the drug was to be originally used and for which it was licensed, rendering the AVA an IND. There can be no doubt that "administration of the anthrax vaccine for mass prophylaxis in Biological Warfare should be considered an off-label use of the product to treat an indication for which it is not explicitly licensed… both the new indication and the new schedule should be undertaken only pursuant to FDA regulations governing clinical trials on investigational new drugs". The Department of Defense Anthrax Vaccination Immunization Program: Unproven Force Protection, p.3, House of Representatives Government Oversight Committee (March 9, 2000) Atch. 8.

        This current vaccine is obviously a "new" drug under any FDA standard. Moreover, the Anthrax Vaccine is apparently is not even the same substance originally tested and approved by NIH. This bizarre conclusion is borne out in a GAO report dated April 29, 1999, entitled Medical Readiness: Safety and Efficacy of the Anthrax Vaccine, Atch. 9 where, at p. 3, it was revealed that the AVIP vaccine being administered to DoD members is not the same vaccine as originally tested prior to 1970. The import of this fact cannot be emphasized enough; the vaccine in current DoD inventories is NOT the same chemical compound as the original compound tested in advance of the 1970 NIH approval.

        Finally, the AVA’s IND status is further bolstered by the fact that there is no reputable study or clinical evidence supporting the AVA’s use as safe and effective protection against pulmonary anthrax. In 5906 Boxes, the court held that a drug was a "new drug" in the absence of substantial evidence that it was generally recognized by experts as safe and effective. 5906 Boxes, 745 F.2d at 108. The manufacturer conceded that no investigations of any kind had ever been conducted to test the particular product’s efficacy; at trial it attempted to introduce three studies that had been conducted using a drug that was similar to the product in question containing the same amounts of active ingredients. Even though an expert testified that his theoretical opinion was that tests of a similar drug would lead to results identical to the drug in question, the court rejected the evidence and found that the material was a "new drug". 5906 Boxes, 745 F.2d at 118.

        In United States v. Sene X Eleemosynary Corp., 479 F. Supp. 970 (S.D. Fla. 1979) the court found an orally administered solution of buffered novocaine originally used as a cardiovascular medicine was a "new drug" under 21 U.S.C. ¤ 321(p) when marketed for the treatment of arthritis and other geriatric diseases. The court noted that its conclusion was based in part in a letter written by the defendant stating that the defendant and others were currently conducting clinical trials of the drug to determine its effectiveness. The court specifically pointed out that anecdotal evidence by numerous individual patients or doctors concerning the efficacy of the medicine could not be used to establish general recognition of safety and efficacy. Sene X, 479 F. Supp. at 977, citing Weinberger v. Hynson, Westcott & Dunning, Inc., 412 U.S. 609 (1973).

        There is no question that the claims of efficacy of the vaccine against pulmonary anthrax are unproven. In its March 9, 2000 report, the House Government Oversight Committee specifically noted that "no adequate and well-controlled investigations, including clinical investigations conducted by experts, have been performed regarding either the safety or the efficacy of the vaccine in humans". Unproven Force Protection, Atch. 8, supra.(2)

        In what is generally regarded as the seminal test of the efficacy of the AVA as a prophylaxis against cutaneous or skin contract anthrax, there were no indications that the AVA provided significant protection against aerosolized anthrax. Brachman, Gold, et al., Field Evaluation of a Human Anthrax Vaccine, American Journal of Public Health, Vol. 52, No. 4, at 632 (April, 1962). Nothing has changed this early assessment of the AVA’s role, at least regarding human beings. The AVA is still considered untested as a mechanism for protecting human beings from aerosol anthrax exposure. See Col. Stanley L. Weinner, Strategies for the Prevention of a Successful Biological Warfare Aerosol Attack, Military Medicine, Vol. 161, No. 5 at 251-254 (May, 1996); Letter of Dr. Claire V. Broome, M.D., Deputy Director for Science and Public Health, Center for Disease Control, U.S. Department of Heath and Human Services, December 14, 1998, Atch. 11.(3)

        Accordingly, there can be absolutely no claim by DoD that the AVA is anything but an IND. This fact is recognized by the AVA’s manufacturer, Bioport, in its IND application, which is still current and pending, and by the complete failure of Bioport, DoD or any other entity to provide verifiable clinical testing showing that the AVA is either safe or effective, in humans, as a prophylaxis to pulmonary anthrax. The FDA testing regimen, which has not been waived or excepted for the AVA, federal statutes, and federal case law, all point to the inescapable determination that the AVA is an IND as it is currently being used on members of the Armed Forces without their informed consent.(4)

      3. Federal Statutes, A Presidential Order, And Air Force Regulations Require Informed Consent From Service Members Prior To The Administration Of The Anthrax Vaccine

        A determination that the AVA is an IND renders inescapable the conclusion that service members as a consequence of federal law and service regulations must give their informed consent prior to submitting to vaccinations.
        1. The Federal Statute.

          10 U.S.C. ¤ 1107 (1999) entitled "Notice of Use of an Investigational New Drug or a Drug Unapproved for its Applied Use" specifically provides:

          1. Notice Required. - (1) Whenever the Secretary of Defense requests or requires a member of the armed forces to receive an investigational new drug or a drug unapproved for its applied use, the Secretary shall provide the member with notice containing the information specified in subsection (d).
          2. Time of Notice. - The notice required to be provided to a member under subsection (a)(1) shall be provided before the investigational new drug or drug unapproved for its applied use is first administered to the member.
          3. Form of Notice. - The notice required under subsection (a)(1) shall be provided in writing.
          4. Content of Notice. - The notice required under subsection (a)(1) shall include the following:
            1. Clear notice that the drug being administered is an investigational new drug or a drug unapproved for its applied use.

            2. The reasons why the investigational new drug or drug unapproved for its applied use is being administered.

            3. Information regarding the possible side effects of the investigational new drug or drug unapproved for its applied use, including any known side effects possible as a result of the interaction of such drug with other drugs or treatments being administered to the members receiving such drug.

            * * *

          5. Limitation and Waiver. - (1) In the case of the administration of an investigational new drug or a drug unapproved for its applied use to a member of the armed forces in connection with the member's participation in a particular military operation, the requirement that the member provide prior consent to receive the drug in accordance with the prior consent requirement imposed under section 505(i)(4) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(i)(4)) may be waived only by the President. The President may grant such a waiver only if the President determines, in writing, that obtaining consent –
            1. is not feasible;
            2. is contrary to the best interests of the member; or
            3. is not in the interests of national security.

          (emphasis added).

        2. The Order of the President.

          An Executive Order is a lawful order of the Commander-in-Chief of the United States Armed Forces. On September 30, 1999, the President issued Executive Order 13139, entitled "Improving Health Protection of Military Personnel Participating in Particular Military Operations". EO 13139 provides in pertinent part:

          Sec. 2. Administration of Investigational New Drugs to Members of the Armed Forces. (a) The Secretary of Defense (Secretary) shall collect intelligence on potential health threats that might be encountered in an area of operations. The Secretary shall work together with the Secretary of Health and Human Services to ensure appropriate countermeasures are developed. When the Secretary considers an investigational new drug or a drug unapproved for its intended use (investigational drug) to represent the most appropriate countermeasure, it shall be studied through scientifically based research and development protocols to determine whether it is safe and effective for its intended use. (b) It is the expectation that the United States Government will administer products approved for their intended use by the Food and Drug Administration (FDA). However, in the event that the Secretary considers a product to represent the most appropriate countermeasure for diseases endemic to the area of operations or to protect against possible chemical, biological, or radiological weapons, but the product has not yet been approved by the FDA for its intended use, the product may, under certain circumstances and strict controls, be administered to provide potential protection for the health and well-being of deployed military personnel in order to ensure the success of the military operation. The provisions of 21 CFR Part 312 contain the FDA requirements for investigational new drugs.

          Sec. 3. Informed Consent Requirements and Waiver Provisions.

          1. Before administering an investigational drug to members of the Armed Forces, the Department of Defense (DoD) must obtain informed consent from each individual unless the Secretary can justify to the President a need for a waiver of informed consent in accordance with 10 U.S.C. 1107(f). Waivers of informed consent will be granted only when absolutely necessary.

          (emphasis added).

          In addition, the provisions of 21 C.F.R. ¤¤ 50, 312 (October 5, 1999) support both the federal statute and the Executive Order by specifically noting situations where the informed consent requirements may be waived. Echoing 10 U.S.C. ¤ 1107, the Regulations note that only the President of the United States may waive the informed consent requirements mandated by his Executive Order and federal law. Waiver is allowed only if one of three preconditions is met – if obtaining informed consent is not feasible; if obtaining informed consent is contrary to the best interests of the recipient; or if informed consent is contrary to national security interests. The President has yet to issue any such waivers, or even initiate action to do so regarding the AVA.

        3. Air Force Instruction 40-403.

        Air Force Instruction ("AFI") 40-403, "Clinical Investigations in Medical Research Guidance and Procedures" (May 19, 1994) deals directly with Air Force mandated policies on use of INDs on Air Force personnel. AFI 40-403 dictates that Air Force members must provide "informed consent" before any clinical use of an IND. Pertinent portions of that AFI follow:

        CLINICAL INVESTIGATIONS IN MEDICAL RESEARCH GUIDANCE AND PROCEDURES

        THE SCOPE OF THIS INSTRUCTION

        2.1. Investigations Covered by This Instruction:

        2.1.1. Clinical investigations...

        2.1.1.1. Examples of clinical investigations are:
        Field trials of vaccines and prophylactic drugs.

        2.1.2 Use of drugs...that are not approved by the FDA, or use of FDA approved drugs...in a manner not provided for in the FDA approved indications. Using FDA approved drugs, devices or radiopharmaceuticals for therapeutic effects that are widely reported and are generally accepted within the scope of normal medical practice, does not constitute clinical investigation or research in the sense of this instruction.

        All medications or devices will be used within the FDA approved indications for the drug ...

        3.1.3. The investigator must avoid all unnecessary physical or mental discomfort to human subjects, by planning for adequate facilities and making proper research preparations. Studies are not permitted if there is significant possibility that the subject could suffer disease, injury, or death. The investigator must: Conduct an evaluation of the subject before the study begins and record the results.

        3.1.6. Before a subject is permitted to give consent, the investigator or associate investigator must accurately explain the investigation in language the subject can understand. This explanation must be made a part of the informed consent document.

        3.1.6.1. The informed consent document should contain, in addition to the components identified in 32 CFR 219, the following statements:

        Any medical misadventure or unanticipated medical event will be brought immediately to the attention of the subject, or the subject's guardian or next of kin, if the subject is not competent at the time to understand the nature of the misadventure or unanticipated medical event.

        Records of the study may be inspected by the FDA or sponsoring institution, if appropriate.

        3.1.7. Informed Consent. The subject must give consent in writing. The investigator must attach a copy of the voluntary consent form to the protocol using these procedures:

        3.1.7.1. The subject must sign the consent form in the presence of at least one witness, who attests to the subject's signature by signing in the place provided. If the subject is military (whether active duty or retired), enter the social security number (SSN) of the subject on the form under the subject's signature...

        3.1.7.2. The investigator or associate investigator gives the advice that forms the basis for the informed consent. This individual must sign the consent form in the presence of the same witness.

        3.1.7.3. Sign or reproduce the consent document in at least four copies.

        3.4. Active Duty Personnel as Human Subjects. The investigator, in consultation with the subject, should determine whether participation in a study would affect the ability of the subject to mobilize for readiness, to perform duties, or to be available for duty. Normally, if their participation could affect their performance, they should not be considered for the clinical investigation.

        Terms

        Informed Consent:

        Informed Consent Process. The informed consent process is intended to give a subject all the information that he or she reasonably would want about a study; to ensure that the subject understands this information; and to give the subject an opportunity to agree or decline to participate in the study. The process provides for interaction between the investigator and the subject.

        Investigational Drugs or Devices--Drugs or devices that are not FDA approved for marketing. These include drugs or devices for which the FDA has provided either a notice of exemption as an Investigational New Drug (IND), or an Investigational Device Exemption (IDE), as appropriate…

        2. Additional Information. If you will be using investigational drugs or devices, the following additional information is required:

        a. The drug or device to be used, including the trade and generic name and the manufacturer.

        b. If the drug or device is FDA approved, but it will be used outside of its approved labeling, indicate that this is an "investigational use" and give rationale (for example, route of administration, higher dose level, or treatment of another condition not approved by FDA).

        c. FDA compliance. If an investigational new drug (IND) number or an investigational device exemption (IDE) number has been assigned, indicate the number and identify the holder; that is, Principal/or Associate Investigator, Medical Center, or manufacturer.

        d. Side effects of the proposed drug or device, from most common to rarest.

        e. Dosage rate schedule.

        f. Modifications in treatment, if side effects occur.

        g. Patient selection, including inclusion and exclusion criteria.

        h. Schedule of patient evaluation studies to be performed before, during, and after completing the study.

        5. Use of Investigational Drugs. If the investigation concerns human studies of treatment or diagnostic procedures involving the use of medications or radiopharmaceuticals not approved by the FDA, include the approved IND number and the following information about the investigational drug. (5)

      The overwhelming authority cited above is concisely summarized in a February 18, 1997 memorandum written by Dr. Karen L. Goldenthal of the FDA CBER Office of Biologics, Atch. 12:

      …if the military is interested in using a vaccine time schedule different from the currently licensed schedule for a mass vaccination effort, then informed consent would appropriate…

      The same holds true, presumably, for the military’s use of a vaccine for a purpose different from the original licensing, as well as using a different route to administer the vaccine….a fact most recently recognized by the Army in a November 1997 briefing. Atch. 13.

      It is abundantly clear that failure to get informed consent from Armed Forces’ members prior to the administration of the AVA, an IND, violates federal law and supporting regulations, Presidential Order, and, in the case of the Air Force, service regulations. An order to submit to the DoD anthrax vaccination program, as it is currently constructed, is therefore illegal.

      1. The DoD Vaccination Program May Violate International Law

        1. The AVA program is experimental under FDA regulations.

        In Atch. 8, Unproven Force Protection, at 72, Congress said plainly:

        Use of the anthrax vaccine for force protection against biological warfare should be considered experimental and undertaken only pursuant to FDA regulations governing investigational testing for a new indication. (emphasis added).

        The findings and recommendations of the Congressional report were underscored in a GAO report dated April 29, 1999, entitled Medical Readiness: Safety and Efficacy of the Anthrax Vaccine, supra, at Atch. 9. Therein, at 3, the report specifically reveals that: The long-term safety of the vaccine has not yet been studied.

        The same conclusion was reached in an October 1999 GAO report entitled, Medical Readiness: DoD Faces Challenges in Implementing Its Anthrax Vaccine Immunization Program, p. 8, Atch. 14. The GAO reiterated that the effectiveness of the AVA against inhalational anthrax in humans has not been proven as it would be unethical to conduct such studies on humans. The report continued, noting that while some studies had proven that the vaccine was effective in animals no valid scientific evidence exists to link the results of animal studies to proof of efficacy in humans.

        The most significant indictment of DoD’s repeated assurances that the AVA is effective against weaponized anthrax is contained in a March 13, 1997 letter from Michael A. Friedman, M.D., Lead Deputy Commissioner, Food and Drug Administration, Department of Health and Human Services (Atch. 15) which plainly said:

        …there is a paucity of data regarding the effectiveness of the Anthrax Vaccine for prevention of inhalation anthrax.

        Even more troubling to the AVA program is the statement in 21 C.F.R. Part 312.3(b) that an experiment is any use of a drug except for the use of a marketed drug in the course of medical practice. Clearly, as evidenced by the 1996 investigational new drug application and the failure to show its effectiveness, the AVA is investigational only and has never been licensed for marketing by the FDA. The AVA is, therefore, experimental and its use falls within the ambit of both the Nuremberg Code, Atch. 16 and 50 U.S.C. ¤1520a. and 50 U.S.C. ¤1520a, Atch. 17. Both proscribe, inter alia, the inoculation of military members with the AVA without their prior expressed and informed consent.

        1. Nuremberg Code
          The Nuremberg Code provides assurance that human beings will not be used as unwilling subjects of chemical or biological experimentation without their specific and informed consent. The Code arose as part of the trials Karl Brandt and others at Nuremberg for crimes against humanity committed in their roles as the Nazi high command.

          It is indisputable that such international law is an integral part of United States domestic law, via treaties, executive agreements and customary international law. Paquete Habana, 175 U.S. 677 (1900). And, it is equally well grounded that the Nuremberg Code is a part of our domestic law. See dissent, Gibbons, Circuit Judge, Jaffee v. United States, 663 F. 2d 1226 (3rd. Cir., 1981) (Per the Nuremberg Code, "The international consensus against involuntary human experimentation is clear;" See also, Annas, GJ., Protecting Soldiers from Friendly Fire: The Consent Requirement for Using Investigational Drugs and Vaccines in Combat, 24 Am. J. Law & Med. 245-260 (1998), Atch. 18.

          The Code has ten requirements, but the essence of the Code prohibits medical experimentation on human subjects without their expressed informed consent.

          Congress has only recently declared that the AVA program is nothing more than an experiment. As such, it must meet the requirements of the Nuremberg Code which requires, absent the fully informed consent of military members. See Annas, CG, Changing The Consent Rules for Desert Storm, Am. J. Law & Med., Vol. 326, No. 11 at 770 (March 12, 1992).

        2. 50 U.S.C. ¤1520a.

      The principles of the Nuremberg Code are codified in 50 U.S.C. ¤1520a (which also prohibits the Department of Defense from conducting a grand-scale experiment of the AVA drug on its members.

      50 U.S.C. ¤1520a provides in pertinent part:

      Sec. 1520a. Restrictions on use of human subjects for testing of chemical or biological agents

      (a) Prohibited activities

      The Secretary of Defense may not conduct (directly or by contract)

      (1) any test or experiment involving the use of a chemical
      agent or biological agent on a civilian population; or
      (2) any other testing of a chemical agent or biological agent on human subjects.

      (b) Exceptions
      Subject to subsections (c), (d), and (e) of this section, the prohibition in subsection (a) of this section does not apply to a test or experiment carried out for any of the following purposes:
      (1) Any peaceful purpose that is related to a medical, therapeutic, pharmaceutical, agricultural, industrial, or research activity.

      (2) Any purpose that is directly related to protection against toxic chemicals or biological weapons and agents.

      (3) Any law enforcement purpose, including any purpose related to riot control.

      (c) Informed consent required

      The Secretary of Defense may conduct a test or experiment described in subsection (b) of this section only if informed consent to the testing was obtained from each human subject in advance of the testing on that subject. (emphasis added).

      The government’s use of a drug that has never been proven effective against preliminary BW anthrax is properly construed as a large-scale test. The fact that the government is attempting to field the drug on a wide scale does not, a fortiori, determine that the vaccinations are routine medical treatment. Indeed, even the anecdotal evidence regarding the questionable safety of the drug dictates otherwise. The informed consent provisions of 50 U.S.C. ¤1520a, therefore, mandate that the government administer the anthrax drug to military member’s only after receiving their informed and voluntary consent.

    4. CONCLUSION:

    The purpose of this Memorandum has been to clearly delineate the legal requirements surrounding the use of an unproven and unapproved vaccine on members of the Armed Forces. Whatever the original intent of the DoD anthrax vaccination program, its originators and proponents have not followed the law in carrying out the Secretary of Defense’s instructions. The legal requirements described in this Memorandum may seem onerous to a military commander worried about the safety of her troops, however, the law provides adequate mechanisms to bypass the regulatory requirements established by the FDA for the protection of American forces in the event a real threat exists.

    Simply put, federal law requires certain steps to be taken before the AVA legally can be administered without getting informed consent from service members. DoD has not taken those steps, nor has DoD or any other entity gone to the trouble of getting applicable waivers for the informed consent requirement.

    Before Congress takes this matter completely out of the services’ hands, a prudent course of action for DoD would be to immediately suspend the AVA program until:

    1. Bioport or other suitable contractor secures a full FDA license and approval for marketing of AVA as a prophylaxis against pulmonary anthrax (Note: the DoD is presently seeking a change to those FDA regulations to allow animal surrogate testing, vice the present requirement for two studies, in humans, to prove safety and efficacy. Atch. 19);
    2. The Surgeon General designs and implements a scientifically and medically valid and appropriate adverse reaction reporting system for service members presently suffering reactions to the AVA; and
    3. The DoD Inspector General, together with the Veterans Administration, openly investigates and reports on all adverse reactions involving Air Force members past and present, to date.

    Such a response would cure the current aura of illegality that surrounds the anthrax program orders as well as provide a mechanism for accounting for the variety of reactions that may or may not be related to the vaccine. It is undeniable that certain units have been hit hard by what appear to be adverse vaccine reactions. The situation needs to be fully investigated by competent authorities in an environment free from political pressure to approve the program. The proposed steps will result in a better and efficacious vaccine, and will allow the Air Force to properly deal with whatever lasting damage has been done to its personnel and its morale as a result of this ill-considered program.

    Footnotes:
    (1) It is important to note that the FDA approval is not a prerequisite for use by a medical practitioner or the DoD. The FDA regulates the manufacturer in the marketing of drugs, vaccines and devices, not the use of the products. In fact, the FDA does not have jurisdiction to regulate the administration of the AVA. It is commonplace in the practice of medicine for physicians to make use of drugs and devices that do not bear FDA approval. (See e.g. FTC v. Simeon Mgmt. Corp., 391 F. Supp. 697 aff'd. 532 F.2d 708 (9th Cir. 1978); Talley v. Danek Medical Inc., 179 F.3d 154 (4th Cir. 1999); In re: Orthopedic Bone Screw Products Liability Litigation, 159 F.3d 817 (3d Cir. 1998).

    (2) Indeed, it is unlikely that any BW vaccine could pass muster under the current FDA testing regimen. In a particularly frank article in Military Medicine, Vol. 157, (August 1992), attached as Atch. 10, Army physicians Col. Garland E. McCarty and Lt. Col. Gregory P. Berezuk said :

    the studies of new drug or vaccine products are initiated in the appropriate animal species in order to define a safe and effective dose. The results of those studies are then submitted to the [FDA] as part of an Investigational New Drug (IND) application, and acceptance of the IND by the FDA a l lows for the initiation of studies in humans. Human studies are designed to demonstrate safety and efficacy of the investigational product. Once sufficient human data are collected, the sponsor of the IND may file a New Drug Application (NDA) for the pr o duct, and this can lead to approval or licensure for marketing. Approval of the NDA by the FDA is dependent upon the results of at least two adequate and well-controlled studies that demonstrate the efficacy of the product in humans. For products design ed to product against chemical and biological agents, a clear demonstration of efficacy would require exposure to humans to these lethal agents. Since this practice would be unethical and immoral, these products never advanced beyond the investigational stage.

    (3)In fact, there have been only a few relevant animal studies regarding the efficacy of the AVA. These are widely touted by DoD officials as proving the efficacy of the vaccine. However, the Senate Committee on Veterans' Affairs in a 1994 report evaluating an anthrax program study stated

    "although the results of this study suggest the vaccine might protect against anthrax that has been sprayed, it is not sufficient to prove that anthrax vaccine is safe and effective as used in the Persian Gulf. The vaccine should therefore be considered investigational when used as a protection against biological warfare. (emphasis added).

    U.S. Senate Committee on Veterans\rquote Affairs Report at 14 (December 8, 1994) (citations omitted).

    (4) DoD has produced two letters that it relies on in an effort to show that the AVA is not an IND when used for inhalation anthrax. The first is a letter from Dr. Michael Friedman to former DoD ASD/HA Dr. Joseph, dated March 13, 1997. The second letter was written to Representative D an Burton by FDA Associate Commissioner Melinda Plaisier on November 26, 1999. Both letters are circumspect in their assessment of the status of the AVA as an IND, but indicate that the AVA is not investigational. However, such letters have absolutely n o effect on the legal status of the AVA. FDA regulations specifically note that:

    a statement made or advice provided by an FDA employee constitutes an advisory opinion only if it is issued in writing under this Section. A statement or advice given by an FDA employee orally, or given in writing but not under this Section or ¤10.90 is an informal communication that represents the best judgment of that employee at that time but does not constitute an advisory opinion, does not necessarily represent the formal position of the FDA, and does not bind or otherwise obligate or commit the agency to the views expressed.

    21 CFR ¤10.85

    Neither of the letters referenced by DoD were issued pursuant to the above Section. They do not bind the agency, they do not carry the weight of law and they cannot constitute a change in the legal status of the AVA from an IND to something else.

    (5) Note that the AFI is completely consistent with FDA definitions as to what compromises an IND. Of particular note is the text identifying an "investigational use" - use outside of approved labeling, route of administration, higher dose level, or treatment of another con dition not approved by the FDA. Obviously, even under Air Force regulations, the AVA is an IND requiring consent from the service member prior to its application.