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."
-- Unidentified Defense Department Spokesman at Department
of Defense ("DoD") Background Briefing on the Anthrax
Vaccine, August 5, 1999.
ISSUE PRESENTED:
Are orders currently being given to members of the U.S. Armed
Forces to submit to anthrax vaccinations consistent with federal
law?
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
and 10 U.S.C. § 1107 (1999). 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.
ANALYSIS:
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.
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.
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.
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.
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.
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.
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.
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.
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:
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).
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.
Form of Notice. - The notice required under subsection (a)(1)
shall be provided in writing.
Content of Notice. - The notice required under subsection (a)(1)
shall include the following:
Clear notice that the drug being administered is an investigational
new drug or a drug unapproved for its applied use.
The reasons why the investigational new drug or drug unapproved
for its applied use is being administered.
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.
* * *
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 -
is not feasible;
is contrary to the best interests of the member; or
is not in the interests of national security.
(emphasis added).
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.
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.
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.
(emphasis added).
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.
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.
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).
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.
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:
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);
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
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.
Contents
Official Documents
Congressional Testimony
Position Papers
Troop Experiences
News Articles
Government Contact Information
Opinion
Informative WWW Sites
Benefit versus Risk
Last revised: September 2000