Authorization of Emergency Use of Anthrax Vaccine Adsorbed for Prevention of Inhalation Anthrax by Individuals at Heightened Risk of Exposure Due to Attack With Anthrax; Availability, 5452-5456 [05-2028]
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Federal Register / Vol. 70, No. 21 / Wednesday, February 2, 2005 / Notices
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
SUPPLEMENTARY INFORMATION:
Administration for Children and
Families
Food and Drug Administration
Delegation of Authority
Authorization of Emergency Use of
Anthrax Vaccine Adsorbed for
Prevention of Inhalation Anthrax by
Individuals at Heightened Risk of
Exposure Due to Attack With Anthrax;
Availability
Section 564 of the act (21 U.S.C.
360bbb–3), as amended by the Project
BioShield Act of 2004 (Public Law 108–
276), allows FDA to strengthen the
public health protections against
biological, chemical, nuclear, and
radiological agents. Among other things,
section 564 of the act allows FDA to
authorize the use of an unapproved
medical product or an unapproved use
of an approved medical product during
a declared emergency involving a
heightened risk of attack on the public
or U.S. military forces. With this EUA
authority, FDA can help assure that
medical countermeasures may be used
in an emergency to diagnose, treat, or
prevent serious or life-threatening
diseases or conditions caused by such
agents, when there are no adequate,
approved, and available alternatives to
protect the American people and the
U.S. military.
Section 564(b)(1) of the act provides
that, before an EUA may be issued, the
Secretary must declare an emergency
based on one of the following grounds:
[Docket No. 2005N–0040]
Notice is hereby given that, under the
authority vested in me by the Secretary,
Department of Health and Human
Services, I have redelegated to the
Commissioner, Administration on
Children, Youth and Families, with the
authority to further redelegate to the
Director, Family Youth Services Bureau,
the authority to approve/disapprove
cooperative research or demonstration
projects under Section 1110 of the
Social Security Act, and as amended
hereafter, when such projects pertain to
the abstinence education activities
referenced in Public Law 108–447 at
Title II, Division F.
This delegation excludes the authority
to submit reports to Congress. Further,
this delegation shall be exercised under
the Department’s existing delegation
and policy on regulations and under
financial and administrative
requirements applicable to all
Administration for Children and
Families authorities. In addition, where
all or part of any research or
demonstration project is wholly
financed with Federal funds made
available under section 1110 of the
Social Security Act, without any State,
local, or other non-Federal financial
participation, that project must be
approved by the Secretary of Health and
Human Services.
I have ratified any actions taken by
the Commissioner, Administration on
Children, Youth and Families, or any
other Administration on Children,
Youth and Families officials, which, in
effect, involved the exercise of this
authority prior to the effective date of
this delegation. This delegation was
effective on the date of signature.
Dated: January 21, 2005.
Wade F. Horn,
Assistant Secretary for Children and Families.
[FR Doc. 05–1896 Filed 2–1–05; 8:45 am]
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AGENCY:
Food and Drug Administration,
HHS.
ACTION:
Notice.
SUMMARY: The Food and Drug
Administration (FDA) is announcing the
issuance of an Emergency Use
Authorization (EUA) (the Authorization)
for Anthrax Vaccine Adsorbed (AVA)
for prevention of inhalation anthrax for
individuals between 18 and 65 years of
age who are deemed by the Department
of Defense (DoD) to be at heightened
risk of exposure due to attack with
anthrax. FDA is issuing this
Authorization under the Federal Food,
Drug, and Cosmetic Act (the act), as
requested by DoD. The Authorization
contains, among other things,
conditions on the emergency use of
AVA. The Authorization follows the
determination by DoD that there is a
significant potential for a military
emergency involving a heightened risk
to U.S. military forces of attack with
anthrax. On the basis of such
determination, Secretary of Health and
Human Services Tommy G. Thompson
(the Secretary) declared an emergency
justifying the authorization of the
emergency use of AVA. The
Authorization, which includes an
explanation of the reasons for its
issuance, is reprinted in this Notice.
DATES: The Authorization is effective as
of January 27, 2005.
ADDRESSES: Submit written requests for
single copies of the Emergency Use
Authorization to the Office of
Counterterrorism Policy and Planning
(HF–29), Food and Drug
Administration, 5600 Fishers Lane,
Rockville, MD 20857. Send one selfaddressed adhesive label to assist that
office in processing your request or
include a fax number to which the
Authorization may be sent. See the
SUPPLEMENTARY INFORMATION section for
electronic access to the Authorization.
FOR FURTHER INFORMATION CONTACT:
Margaret O’K. Glavin, Office of
Counterterrorism Policy and Planning
(HF–29), Food and Drug
Administration, 5600 Fishers Lane,
Rockville, MD 20857, 301–827–4067.
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I. Background
(1) a determination by the Secretary of
Homeland Security that there is a domestic
emergency, or a significant potential for a
domestic emergency, involving a heightened
risk of attack with a specified biological,
chemical, radiological, or nuclear agent or
agents;
(2) a determination by the Secretary of
Defense that there is a military emergency, or
a significant potential for a military
emergency, involving a heightened risk to
United States military forces of attack with a
specified biological, chemical, radiological,
or nuclear agent or agents; or
(3) a determination by the Secretary of a
public health emergency under section 319 of
the Public Health Service Act (PHS Act) that
affects, or has a significant potential to affect,
national security, and that involves a
specified biological, chemical, radiological,
or nuclear agent or agents, or a specified
disease or condition that may be attributable
to such agent or agents.
Once the Secretary has declared an
emergency justifying an authorization
under section 564 of the act, FDA may
authorize the emergency use of a drug,
device, or biological product if the
agency concludes, based on the
information and data available to the
agency, that the statutory criteria of
section 564(c) of the act are satisfied.
Under section 564(h)(1) of the act FDA
is required to publish in the Federal
Register notice of each authorization,
and each termination or revocation of an
authorization, and an explanation of the
reasons for the action. The explanation
may include a summary of data
submitted to FDA in an application
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Federal Register / Vol. 70, No. 21 / Wednesday, February 2, 2005 / Notices
under section 505(i) or 520(g) of the act
(21 U.S.C. 355(i) or 21 U.S.C. 360j(g)).
Section 564 of the act permits FDA to
authorize, during the effective period of
the declaration, the introduction into
interstate commerce of a drug, device, or
biological product intended for use in
an actual or potential emergency.
Products appropriate for emergency use
may include products and uses that are
not approved, cleared, or licensed under
sections 505, 510(k), and 515 of the act
(21 U.S.C. 355, 21 U.S.C. 360(k), 21
U.S.C. 360e) or section 351 of the PHS
Act (42 U.S.C. 262). FDA may issue an
EUA only if, after consultation with the
National Institutes of Health (NIH) and
the Centers for Disease Control and
Prevention (CDC) (to the extent feasible
and appropriate given the circumstances
of the emergency), FDA concludes:
(1) That the agent specified in the
declaration of emergency can cause a
serious or life-threatening disease or
condition;
(2) That, based on the totality of
scientific evidence available, including
data from adequate and well-controlled
clinical trials, if available, it is
reasonable to believe that the product
may be effective in diagnosing, treating,
or preventing—(a) the serious or lifethreatening disease or condition referred
to in paragraph (1); or (b) a serious or
life-threatening disease or condition
caused by a product authorized under
section 564, or approved, cleared, or
licensed under the act or PHS Act, for
diagnosing, treating, or preventing the
disease or condition referred to in
paragraph (1) and caused by the agent
specified in the declaration of
emergency;
(3) That the known and potential
benefits of the product outweigh the
known and potential risks of the
product when used to diagnose,
prevent, or treat the serious or lifethreatening disease or condition that is
the subject of the declaration; and
(4) That there is no adequate,
approved, and available alternative to
the product for diagnosing, preventing,
or treating such serious or lifethreatening disease or condition.
II. EUA Request for AVA
On December 10, 2004, pursuant to
section 564(b)(1)(B) of the act (21 U.S.C.
360bbb–3(b)(1)(B)), the Deputy
Secretary of Defense determined that
there is a significant potential for a
military emergency involving a
heightened risk to United States military
forces of attack with anthrax. On
January 14, 2005, pursuant to section
564(b) of the act, and on the basis of
such determination, Secretary of Health
and Human Services Tommy G.
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Thompson declared an emergency
justifying the authorization of the
emergency use of AVA. Notice of the
determination of the Deputy Secretary
of Defense and the declaration of the
Secretary of Health and Human Services
is published elsewhere in this issue of
the Federal Register.
III. Significance of Notice
The issuance of this Authorization for
the emergency use of AVA is the first
time that the EUA authority is being
used. FDA intends to explain clearly the
reasons for each issuance, termination,
or revocation of an EUA. The agency
wishes to make its decision-making
understandable to help ensure that
members of the public, and particularly
those individuals who may be eligible to
receive a medical product authorized for
emergency use, are informed about the
basis of an EUA determination. The
amount of information that will be
provided regarding each authorization
will depend on the circumstances of the
emergency. We anticipate that in some
circumstances, an EUA will be issued
very quickly, and time may not permit
the agency to prepare supplementary
documents beyond the letter of
authorization and the notice required by
section 564(h)(1) of the act. Other
circumstances may afford greater
opportunity to produce materials in
addition to those prepared and
disseminated as a condition of
authorization under section 564(e) of
the act. Thus, the amount of additional
information that we will provide will
necessarily vary on a case-by-case basis.
The agency will publish notice of each
EUA and intends also to make the
notice and certain supplementary
information available on its website and
in the Division of Dockets Management
(HFA–305), Food and Drug
Administration, 5630 Fishers Lane, rm.
1061, Rockville, MD 20852, which is
open to the public between 9 a.m. and
4 p.m., Monday through Friday.
Because the statute is self-executing,
FDA does not require regulations or
guidance to implement the EUA
authority. However, we believe that it
would be helpful for stakeholders and
the public to have more information
about the EUA authority, and the
process that the agency is proposing to
adopt for the consideration of EUA
requests. Accordingly the agency is
planning to issue draft guidance on this
topic in the near future.
IV. Electronic Access
An electronic version of this notice
and the full text of the Authorization are
available on the Internet at https://
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www.fda.gov/ohrms/dockets/
default.htm.
V. The Authorization
Having consulted with NIH and CDC,
and having concluded that the criteria
for issuance of this Authorization under
section 564(c) of the act are met, FDA
has authorized the emergency use of
AVA for prevention of inhalation
anthrax for individuals between 18 and
65 years of age who are deemed by DoD
to be at heightened risk of exposure due
to attack with anthrax. The
Authorization follows and provides an
explanation of the reasons for its
issuance, as required by section
564(h)(1) of the act:
William Winkenwerder, Jr., M.D.
Assistant Secretary of Defense for Health
Affairs
The Pentagon
Washington, D.C. 20301–1200
Re: Request for Emergency Use
Authorization for the Armed Forces Pending
Re-determination on the Licensed Use of
Anthrax Vaccine Adsorbed for Protection
Against Inhalational Anthrax
Dear Dr. Winkenwerder:
This is in response to your letter of
December 22, 2004, requesting that the Food
and Drug Administration (FDA) issue an
Emergency Use Authorization (EUA)
regarding the use of Anthrax Vaccine
Adsorbed (AVA) for the prevention of
inhalational anthrax, pursuant to section 564
of the Federal Food, Drug, and Cosmetic Act
(the Act).
On December 10, 2004, pursuant to section
564(b)(1)(B) of the Act, 21 U.S.C. § 360bbb–
3(b)(1)(B), the Deputy Secretary of Defense
determined that there is a significant
potential for a military emergency involving
a heightened risk to U.S. military forces of
attack with anthrax.1 On January 14, 2005,
pursuant to section 564(b) of the Act, and on
the basis of such determination, Secretary of
Health and Human Services, Tommy G.
Thompson declared an emergency justifying
the authorization of the emergency use of
AVA. Having consulted with the National
Institutes of Health (NIH) and the Centers for
Disease Control and Prevention (CDC), and
having concluded that the criteria for
issuance of this authorization under section
564(c) of the Act are met, I am authorizing
the emergency use of AVA for prevention of
inhalation anthrax,2 subject to the conditions
established herein.3
1 You state in your letter that the Deputy
Secretary of Defense has assigned authority from
the Secretary of Defense to make the statutory
determination under section 564(b)(1)(B) of the Act.
2 The Secretary of Health and Human Services
has delegated his authority to issue an EUA under
section 564 to the FDA Commissioner.
3 The terms ‘‘inhalation anthrax’’ and
‘‘inhalational anthrax’’ are used interchangeably.
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I. Background
AVA was first licensed by NIH in
November 1970.4 Upon the delegation of
vaccine regulation to FDA in 1972, FDA
undertook a comprehensive review of the
safety, effectiveness, and labeling of all
vaccines licensed prior to July 1, 1972.5
Under this review, independent advisory
panels evaluated the safety and effectiveness
data of vaccines to assure that they met
appropriate standards. The advisory panel
that reviewed AVA concluded that it is safe,
effective, and not misbranded, and FDA
issued a proposal to adopt the panel’s
recommendation (the Bacterial Vaccines and
Toxoids Efficacy Review).6
In March 2003, six plaintiffs, known as
John and Jane Doe 1 through 6, filed suit in
the United States District Court for the
District of Columbia (the Court) seeking the
Court to enjoin the Anthrax Vaccine
Immunization Program (AVIP) of the
Department of Defense (DoD), and to declare
AVA an investigational drug when used for
protection against inhalation anthrax. On
December 22, 2003, the Court issued a
preliminary injunction barring inoculations
under the AVIP in the absence of informed
consent or a Presidential waiver of the
informed consent requirement.
In the Federal Register of January 5, 2004,7
FDA published a final rule and final order in
response to the report and recommendations
of the independent advisory panel that
reviewed the safety and effectiveness data
pertaining to AVA. Following FDA’s issuance
of the final rule and final order, the Court
lifted the preliminary injunction on January
7, 2004, except as it applied to the six Doe
plaintiffs.
On October 27, 2004, the Court issued a
memorandum opinion vacating and
remanding the January 2004 final rule and
final order to FDA for reconsideration,
following an appropriate notice and
comment period. The Court also enjoined
operation of the AVIP for inoculation using
AVA to prevent inhalation anthrax. On
December 29, 2004, FDA published a
proposed rule and proposed order reopening
the comment period on the Bacterial Vaccine
and Toxoids Efficacy Review for 90 days.8 As
a result of the Court’s order of October 27,
2004, the use of AVA by DoD for the
prevention of inhalation anthrax under the
AVIP is deemed an unapproved use of an
approved product for purposes of section
564(a)(2) of the Act. But for the Court’s order,
FDA would not consider the use of AVA for
inhalation anthrax to be an unapproved use.
4 Biological products are licensed under section
351 of the Public Health Service Act (42 U.S.C.
262).
5 See 21 C.F.R. § 601.25.
6 Biological Products; Bacterial Vaccines and
Toxoids; Implementation of Efficacy Review, 50
Fed. Reg. 51002 (Dec. 13, 1985).
7 Biological Products; Bacterial Vaccines and
Toxoids; Implementation of Efficacy Review, 69
Fed. Reg. 255 (Jan. 5, 2004).
8 Biological Products; Bacterial Vaccines and
Toxoids; Implementation of Efficacy Review;
Proposed Rule and Proposed Order, 69 Fed. Reg.
78281 (Dec. 29, 2004).
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II. Criteria for Issuance of Authorization
Having considered the December 10, 2004,
determination by the Deputy Secretary of
Defense that there is a significant potential
for a military emergency involving a
heightened risk to U.S. military forces of
attack with anthrax, and the January 14,
2005, declaration of emergency by the
Secretary of Health and Human Services, and
after consultation with NIH and CDC, I have
concluded that the use of AVA to prevent
inhalation anthrax meets the criteria for
issuance of an authorization under section
564(c) of the Act, because I have concluded
that:
(1) anthrax (Bacillus anthracis) can cause
a serious or life-threatening disease or
condition;
(2) based on the totality of scientific
evidence available to FDA, AVA is effective
in preventing inhalation anthrax; therefore, it
is reasonable to believe that AVA may be
effective in preventing inhalation anthrax
pursuant to section 564(c)(2)(A) of the Act;
and that the known and potential benefits of
AVA, when used to prevent inhalation
anthrax, outweigh the known and potential
risks of the product; and
(3) there is no adequate, approved, and
available alternative to AVA for preventing
inhalation anthrax.9
Specifically, I have concluded, pursuant to
section 564(c)(1) of the Act, that anthrax
(Bacillus anthracis) can cause inhalation
anthrax, which is a serious or life-threatening
disease or condition. The fatality rate for
inhalation anthrax in the United States is
estimated to be approximately 45 percent to
90 percent. From 1900 to October 2001, there
were 18 identified cases of inhalation anthrax
in the United States, the latest of which was
reported in 1976, with an 89 percent (16/18)
mortality rate. Most of these exposures
occurred in industrial settings, i.e., textile
mills. From October 4, 2001, to December 5,
2001, a total of 11 cases of inhalation anthrax
linked to intentional dissemination of
Bacillus anthracis spores were identified in
the United States. Five of these cases were
fatal. These fatalities occurred despite
aggressive medical care, including
antibiotics.
I have concluded that, based on the totality
of scientific evidence available to FDA,
including data from at least one wellcontrolled field study, AVA is effective in
preventing inhalation anthrax; therefore, it is
reasonable to believe that AVA may be
effective in preventing inhalation anthrax
pursuant to section 564(c)(2)(A) of the Act. In
addition, pursuant to section 564(c)(2)(B) of
the Act, I have concluded that it is reasonable
to believe that the known and potential
benefits of AVA outweigh the known and
potential risks of the product. The available
scientific evidence that supports these
conclusions includes the following:
• A well-controlled efficacy field study
using an earlier version of a protective
antigen-based anthrax vaccine was
conducted in mill workers from 1955-1959.
In a comparison of anthrax cases between the
placebo and vaccine groups, including both
9 No other criteria of issuance have been
prescribed by regulation under section 564(c)(4).
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inhalation and cutaneous cases in those who
were completely vaccinated, the calculated
vaccine efficacy level against all reported
cases of anthrax combined was 92.5 percent
(lower 95 percent CI = 65 percent). The
efficacy analysis included all cases of anthrax
disease regardless of the route of exposure or
manifestation of disease.
• Epidemiological surveillance data on the
occurrence of anthrax disease in at-risk
industrial settings for the years 1962-1974
provides further supportive evidence of the
effectiveness of AVA. In that time period,
individuals received either AVA, or an
earlier version of anthrax vaccine. Of the 24
anthrax cases that occurred in mill
employees during that period, no cases
occurred in those who had received the full
vaccination series.
• The safety of AVA was evaluated in a 5year (1967-1971) open-label safety study in
which 15,907 doses of AVA were
administered to approximately 7,000 textile
employees, laboratory workers, and other atrisk individuals. Severe local reactions were
reported in 0.15 percent of doses
administered (24 reports). There were 150
reports (0.94 percent of doses administered)
of moderate local reactions and 1,373 reports
(8.63 percent of doses administered) of mild
local reactions. In the same open label study,
four cases of systemic reactions were
reported during a 5-year reporting period
(<0.06 percent of doses administered). These
reactions, which were reported to have been
transient, included fever, chills, nausea, and
general body aches.
• Recently (1996-1999), an assessment of
safety was conducted as part of a randomized
clinical study conducted by the U.S. Army
Medical Research Institute of Infectious
Diseases. Four of the 28 volunteers reported
seven acute adverse events within 30
minutes after the subcutaneous
administration of AVA. These adverse events
included erythema (3), headache (2), fever
(1), and elevated temperature (1). Of these
events, a single patient reported the
simultaneous occurrence of headache, fever,
and elevated temperature (100.7°F). The most
common local reactions reported after the
first dose in this study were tenderness (71
percent), erythema (43 percent),
subcutaneous nodule (36 percent), induration
(21 percent), warmth (11 percent), and local
pruritus (7 percent). Local reactions were
found to occur more often in women. No
abscess or necrosis was observed at the
injection site.
I have concluded, pursuant to section
564(c)(3) of the Act, that there is no adequate,
approved, and available alternative to AVA
for preventing inhalation anthrax. No other
drugs are approved for the prevention (preexposure) of anthrax infection. Antibiotics
are effective against the germinated form of
Bacillus anthracis, but are not effective
against the spore form of the organism.
Although antibiotics are available to treat
anthrax infection, their effectiveness is
limited, in part due to delays from the time
of exposure to the initiation of treatment.
Delays in the treatment of exposed persons
are possible, considering the potential
scenarios of exposure, and the difficulties
that exist in identifying anthrax as the
etiology of illness.
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III. Scope of Authorization
Pursuant to section 564(d)(1) of the Act,
this authorization is limited to the use of
AVA for the prevention of inhalation anthrax
for individuals between 18 and 65 years of
age who are deemed by DoD to be at
heightened risk of exposure due to attack
with anthrax.
I have concluded, pursuant to section
564(d)(2) of the Act, that it is reasonable to
believe that the known and potential benefits
of AVA, when used to prevent inhalation
anthrax, outweigh the known and potential
risks of the product for the population
described above.
I have concluded, pursuant to section
564(d)(3) of the Act, based on the totality of
scientific evidence available to FDA, that
AVA is effective in preventing inhalation
anthrax, and therefore, it is reasonable to
believe that AVA may be effective in
preventing inhalation anthrax pursuant to
section 564(c)(2)(A) of the Act. FDA has
reviewed the scientific information available,
including the studies described in Section II
above, and concludes that AVA, when used
for preventing inhalation anthrax, meets the
standards set forth in section 564(c) of the
Act.
FDA understands that DoD recognizes that
the current AVA license describes an
immunization schedule consisting of six
doses. Certain details of DoD’s EUA request
are not specifically addressed in the package
insert, however. DoD notes that for some
personnel, the vaccination schedule was
unavoidably disrupted, and DoD intends for
such personnel to resume vaccinations at the
point in the dosing schedule where they left
off, for individuals eligible under the EUA.
While this practice is not addressed in the
package insert, the practice is consistent with
the general recommendations of the Advisory
Committee on Immunization Practices. When
it is impracticable to provide a dose on a
specific date recommended by the schedule,
DoD intends to provide the vaccine dose as
soon as practicable thereafter. Based on the
totality of the scientific evidence available to
FDA, it is reasonable to believe that such
administration of AVA may be effective in
preventing inhalation anthrax. Furthermore,
the known and potential benefits of AVA,
when used to prevent inhalation anthrax in
the manner described above, outweigh the
known and potential risks of the product.
DoD also acknowledges that during the
course of the EUA, the risk status of
individuals initially eligible for vaccination
under the EUA may change (e.g., changes in
deployment or other circumstances). In such
cases, DoD must determine whether such
individuals continue to be at heightened risk
of exposure due to attack with anthrax, and
therefore, whether they continue to be
eligible for vaccination with AVA under this
EUA.
The use of AVA under this EUA must be
consistent with and not contrary to the
conditions of authorization set forth below.
Subject to the foregoing limitations and
under the circumstances set forth in the
Deputy Secretary of Defense’s determination
of military emergency, AVA may be
administered for the prevention of inhalation
anthrax to individuals determined by DoD to
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be at heightened risk of exposure due to
attack with anthrax.
IV. Conditions of Authorization
Pursuant to section 564 of the Act, I am
establishing the following conditions on this
authorization:
Conditions Designed to Ensure that Health
Care Providers or Authorized Dispensers
Administering the Product Are Informed.
DoD will conduct an educational and
information program under appropriate
conditions designed to ensure that health
care providers or authorized dispensers
administering AVA under this authorization
are informed:
(1) that FDA has authorized the emergency
use of AVA for preventing inhalation
anthrax;
(2) of the significant known and potential
benefits and risks of the emergency use of
AVA, and the extent to which such benefits
and risks are unknown; and
(3) of the alternatives to AVA that are
available, and of their benefits and risks.
With respect to condition (2), above,
relating to provision of the significant known
and potential benefits and risks of the
emergency use of AVA, DoD will assure that
the manufacturer’s package insert is available
to all health care providers or authorized
dispensers who administer AVA. DoD will
also provide to all such health care providers
or authorized dispensers the same
information provided to potential vaccine
recipients described immediately below.
Conditions Designed to Ensure that
Individuals to Whom the Product is
Administered Are Informed. DoD will
conduct an educational and information
program under appropriate conditions
designed to ensure that individuals to whom
AVA is administered are informed:
(1) that FDA has authorized the emergency
use of AVA for preventing inhalation
anthrax;
(2) of the significant known and potential
benefits and risks of the emergency use of
AVA, and of the extent to which such
benefits and risks are unknown; and
(3) of the option to accept or refuse
administration of AVA; of the consequences,
if any, of refusing administration of the
product; and of the alternatives to AVA that
are available, and of their benefits and risks.
With respect to condition (3), above,
relating to the option to accept or refuse
administration of AVA, the AVIP will be
revised to give personnel the option to refuse
vaccination. Individuals who refuse anthrax
vaccination will not be punished. Refusal
may not be grounds for any disciplinary
action under the Uniform Code of Military
Justice. Refusal may not be grounds for any
adverse personnel action. Nor would either
military or civilian personnel be considered
non-deployable or processed for separation
based on refusal of anthrax vaccination.
There may be no penalty or loss of
entitlement for refusing anthrax vaccination.
This information shall read in the trifold
brochure provided to potential vaccine
recipients as follows:
You may refuse anthrax vaccination under
the EUA, and you will not be punished. No
disciplinary action or adverse personnel
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action will be taken. You will not be
processed for separation, and you will still be
deployable. There will be no penalty or loss
of entitlement for refusing anthrax
vaccination.
Other information, as outlined in your
request, is not a condition of this EUA, but
may be provided, including: That
unvaccinated people are more vulnerable to
lethal anthrax infection; morbidity or
mortality due to anthrax could threaten the
lives of others in the unit who depend on
each other; and anthrax infections could
jeopardize the success of the mission.
Individuals subject to the vaccination
program may be informed that their military
and civilian leaders strongly recommend
anthrax vaccination, but such individuals
may not be forced to be vaccinated. In
addition, the issue of mandatory vaccination
will be reconsidered by DoD after FDA
completes its administrative process, which
DoD expects to occur later this year.10
As a condition of this authorization, DoD
will provide to each potential AVA recipient,
prior to vaccination, information that meets
the requirements set forth above. FDA has
reviewed DoD’s trifold brochure, submitted
on January 19, 2005, and concludes that this
brochure meets such requirements. DoD will
obtain FDA’s prior approval of any revision
to the trifold brochure.
Conditions for the Monitoring and
Reporting of Adverse Events Associated with
the Emergency Use of AVA. DoD will, as a
condition of this authorization, actively
encourage health care providers or
authorized dispensers and vaccine recipients
to report adverse events to the Vaccine
Adverse Events Reporting System (VAERS).
In addition, we understand that DoD will
conduct systematic monitoring of the health
of recipients of AVA, e.g., cohort studies
using the Defense Medical Surveillance
System databases of active-duty military
personnel; such monitoring is not a condition
of this authorization.
Conditions Concerning Recordkeeping and
Reporting, Including Records Access by FDA.
DoD will, as a condition of authorization,
record in individual medical records,
including electronic immunization tracking
systems, the names of individual recipients
of AVA and the dates of vaccination. DoD
will provide FDA access to such records.
Advertising and Promotional Descriptive
Printed Matter. FDA has the authority, under
section 564(e)(4) of the Act to establish
conditions on advertisements and other
promotional descriptive printed matter that
relate to the emergency use of AVA under
this authorization. As a condition of this
EUA, all advertising and promotional
descriptive printed matter relating to the use
of AVA shall be consistent with the trifold
as well as the standards and requirements set
forth in this authorization.
V. Duration of Authorization
This EUA will be effective for 6 months
from the date of issuance. However, this EUA
may be extended within the duration of the
declaration of emergency if the criteria under
section 564(c) of the Act for issuance of such
10 See
E:\FR\FM\02FEN1.SGM
Section I of this authorization.
02FEN1
5456
Federal Register / Vol. 70, No. 21 / Wednesday, February 2, 2005 / Notices
authorization are still met. Moreover, the
EUA will cease to be effective when the
declaration of emergency is terminated under
section 564(b) of the Act or the EUA is
revoked under section 564(g) of the Act.
Thank you in advance for your cooperation
in implementing this EUA.
Sincerely,
Lester M. Crawford, D.V.M., Ph.D.
Dated: January 28, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05–2028 Filed 1–31–05; 11:39 am]
Place: Sugarloaf Room, 1 Choke Cherry
Road, Rockville, MD 20857.
Type: Open: February 16, 2005, 9 a.m.—5
p.m.; February 17, 2005, 9:30 a.m.—1 p.m.
Closed: February 17, 2005, 9 a.m.—9:30
a.m.
Contact: Diane Abbate, MA, Acting
Executive Secretary, 1 Choke Cherry Road,
Room 6–1075, Rockville, Maryland 20857.
Telephone: (240) 276–1830, and FAX (240)
276–1850. E-mail: dabbate@hhs.samhsa.gov.
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Dated: January 26, 2005.
Toian Vaughn,
Committee Management Officer, Substance
Abuse and Mental Health Services
Administration.
[FR Doc. 05–1923 Filed 2–1–05; 8:45 am]
BILLING CODE 4162–20–P
Substance Abuse and Mental Health
Services Administration
Center for Mental Health Services;
Notice of Meeting
Transportation Security Administration
Pursuant to Pub. L. 92–463, notice is
hereby given of the meeting of the
Center for Mental Health Services
(CMHS) National Advisory Council in
February 2005.
A portion of the meeting will be open
and will include a roll call, general
announcements, Director’s and
Administrator’s Reports, as well as
presentations and discussions about
Mental Health System Transformation.
Attendance by the public will be
limited to space available. Public
comments are welcome. Please
communicate with the individual listed
below as contact to make arrangements
to comment or to request special
accommodations for persons with
disabilities.
The meeting also will include the
review, discussion, and evaluation of
grant applications. Therefore a portion
of the meeting will be closed to the
public as determined by the
Administrator, SAMHSA, in accordance
with Title 5 U.S.C. 552b(c)(6) and 5
U.S.C. App. 2 Section 10(d).
Substantive program information, and
a roster of Council members may be
obtained by accessing the SAMHSA
Advisory Committee website (https://
www.samhsa.gov) or by communicating
with the contact whose name and
telephone number are listed below. A
summary of the meeting and the
transcript for the open session will also
be available on the SAMHSA Advisory
Committee Web site as soon as possible
after the meeting.
Committee Name: Substance Abuse and
Mental Health Services Administration,
Center for Mental Health Services National
Advisory Council.
Meeting Date: February 16–17, 2005.
VerDate jul<14>2003
14:19 Feb 01, 2005
Jkt 205001
DEPARTMENT OF HOMELAND
SECURITY
Notice of Intent To Request Renewal
From the Office of Management and
Budget (OMB) of One Current Public
Collection of Information; Flight Crew
Self-Defense Training—Registration
and Evaluation
Transportation Security
Administration (TSA), DHS.
ACTION: Notice.
AGENCY:
SUMMARY: TSA invites public comment
on an existing information collection
requirement, abstracted below, that will
be submitted to OMB for renewal in
compliance with the Paperwork
Reduction Act.
DATES: Send your comments by April 4,
2005.
ADDRESSES: Comments to be delivered
to Katrina Wawer, Information
Collection Specialist, TSA
Headquarters, East Tower, Floor 7,
TSA–9, 601 South 12th Street,
Arlington, VA 22202–4220; facsimile
(571) 227–2594; email
katrina.wawer@dhs.gov.
FOR FURTHER INFORMATION CONTACT:
Katrina Wawer, Information Collection
Specialist (571) 227–1995.
SUPPLEMENTARY INFORMATION: In
accordance with the Paperwork
Reduction Act of 1995, (44 U.S.C. 3501
et seq.), an agency may not conduct or
sponsor, and a person is not required to
respond to a collection of information,
unless it displays a valid OMB control
number. Therefore, in preparation for
submission of the specified information
collection for renewal, TSA solicits
comments in order to—
(1) Evaluate whether the proposed
information requirement is necessary for
the proper performance of the functions
PO 00000
Frm 00045
Fmt 4703
Sfmt 4703
of the agency, including whether the
information will have practical utility;
(2) Evaluate the accuracy of the
agency’s estimate of the burden;
(3) Enhance the quality, utility, and
clarity of the information to be
collected; and
(4) Minimize the burden of the
collection of information on those who
are to respond, including through the
use of appropriate automated,
electronic, mechanical, or other
technological collection techniques or
other forms of information technology
where appropriate.
1652–0028, Flight Crew Self-Defense
Training—Registration and Evaluation.
TSA is seeking to renew information
collection request number 1652–0028 to
continue compliance with statutory
mandate. Section 603 of Vision 100—
Century of Aviation Reauthorization
Act, Public Law 108–176, requires TSA
to develop and provide a voluntary
advanced self-defense training program
for flight and cabin crew members of air
carriers providing scheduled passenger
air transportation. TSA collects limited
biographical information from flight
crew members to confirm their
eligibility for training. TSA also asks
participants to complete an anonymous
and voluntary evaluation form after the
training is completed to assess the
quality of the training. TSA requests this
renewal to continue confirming
participants’ eligibility and attendance
for the training program, as well as to
continue to assess training quality. The
estimated number of annual
respondents is 3,000 and estimated
annual burden is 750 hours. There is no
estimated annual cost burden to
respondents.
The approval of this information
collection expires on April 30, 2005.
Issued in Arlington, Virginia, on January
25, 2005.
Lisa S. Dean,
Privacy Officer.
[FR Doc. 05–1926 Filed 2–1–05; 8:45 am]
BILLING CODE 4910–62–P
DEPARTMENT OF HOMELAND
SECURITY
Transportation Security Administration
Notice of Intent To Request Renewal
From the Office of Management and
Budget (OMB) of a Current Public
Collection of Information; Airport
Security
Transportation Security
Administration (TSA), Department of
Homeland Security (DHS).
ACTION: Notice.
AGENCY:
E:\FR\FM\02FEN1.SGM
02FEN1
]]>Agencies
[Federal Register Volume 70, Number 21 (Wednesday, February 2, 2005)]
[Notices]
[Pages 5452-5456]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: 05-2028]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2005N-0040]
Authorization of Emergency Use of Anthrax Vaccine Adsorbed for
Prevention of Inhalation Anthrax by Individuals at Heightened Risk of
Exposure Due to Attack With Anthrax; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing the
issuance of an Emergency Use Authorization (EUA) (the Authorization)
for Anthrax Vaccine Adsorbed (AVA) for prevention of inhalation anthrax
for individuals between 18 and 65 years of age who are deemed by the
Department of Defense (DoD) to be at heightened risk of exposure due to
attack with anthrax. FDA is issuing this Authorization under the
Federal Food, Drug, and Cosmetic Act (the act), as requested by DoD.
The Authorization contains, among other things, conditions on the
emergency use of AVA. The Authorization follows the determination by
DoD that there is a significant potential for a military emergency
involving a heightened risk to U.S. military forces of attack with
anthrax. On the basis of such determination, Secretary of Health and
Human Services Tommy G. Thompson (the Secretary) declared an emergency
justifying the authorization of the emergency use of AVA. The
Authorization, which includes an explanation of the reasons for its
issuance, is reprinted in this Notice.
DATES: The Authorization is effective as of January 27, 2005.
ADDRESSES: Submit written requests for single copies of the Emergency
Use Authorization to the Office of Counterterrorism Policy and Planning
(HF-29), Food and Drug Administration, 5600 Fishers Lane, Rockville, MD
20857. Send one self-addressed adhesive label to assist that office in
processing your request or include a fax number to which the
Authorization may be sent. See the SUPPLEMENTARY INFORMATION section
for electronic access to the Authorization.
FOR FURTHER INFORMATION CONTACT: Margaret O'K. Glavin, Office of
Counterterrorism Policy and Planning (HF-29), Food and Drug
Administration, 5600 Fishers Lane, Rockville, MD 20857, 301-827-4067.
SUPPLEMENTARY INFORMATION:
I. Background
Section 564 of the act (21 U.S.C. 360bbb-3), as amended by the
Project BioShield Act of 2004 (Public Law 108-276), allows FDA to
strengthen the public health protections against biological, chemical,
nuclear, and radiological agents. Among other things, section 564 of
the act allows FDA to authorize the use of an unapproved medical
product or an unapproved use of an approved medical product during a
declared emergency involving a heightened risk of attack on the public
or U.S. military forces. With this EUA authority, FDA can help assure
that medical countermeasures may be used in an emergency to diagnose,
treat, or prevent serious or life-threatening diseases or conditions
caused by such agents, when there are no adequate, approved, and
available alternatives to protect the American people and the U.S.
military.
Section 564(b)(1) of the act provides that, before an EUA may be
issued, the Secretary must declare an emergency based on one of the
following grounds:
(1) a determination by the Secretary of Homeland Security that
there is a domestic emergency, or a significant potential for a
domestic emergency, involving a heightened risk of attack with a
specified biological, chemical, radiological, or nuclear agent or
agents;
(2) a determination by the Secretary of Defense that there is a
military emergency, or a significant potential for a military
emergency, involving a heightened risk to United States military
forces of attack with a specified biological, chemical,
radiological, or nuclear agent or agents; or
(3) a determination by the Secretary of a public health
emergency under section 319 of the Public Health Service Act (PHS
Act) that affects, or has a significant potential to affect,
national security, and that involves a specified biological,
chemical, radiological, or nuclear agent or agents, or a specified
disease or condition that may be attributable to such agent or
agents.
Once the Secretary has declared an emergency justifying an
authorization under section 564 of the act, FDA may authorize the
emergency use of a drug, device, or biological product if the agency
concludes, based on the information and data available to the agency,
that the statutory criteria of section 564(c) of the act are satisfied.
Under section 564(h)(1) of the act FDA is required to publish in the
Federal Register notice of each authorization, and each termination or
revocation of an authorization, and an explanation of the reasons for
the action. The explanation may include a summary of data submitted to
FDA in an application
[[Page 5453]]
under section 505(i) or 520(g) of the act (21 U.S.C. 355(i) or 21
U.S.C. 360j(g)).
Section 564 of the act permits FDA to authorize, during the
effective period of the declaration, the introduction into interstate
commerce of a drug, device, or biological product intended for use in
an actual or potential emergency. Products appropriate for emergency
use may include products and uses that are not approved, cleared, or
licensed under sections 505, 510(k), and 515 of the act (21 U.S.C. 355,
21 U.S.C. 360(k), 21 U.S.C. 360e) or section 351 of the PHS Act (42
U.S.C. 262). FDA may issue an EUA only if, after consultation with the
National Institutes of Health (NIH) and the Centers for Disease Control
and Prevention (CDC) (to the extent feasible and appropriate given the
circumstances of the emergency), FDA concludes:
(1) That the agent specified in the declaration of emergency can
cause a serious or life-threatening disease or condition;
(2) That, based on the totality of scientific evidence available,
including data from adequate and well-controlled clinical trials, if
available, it is reasonable to believe that the product may be
effective in diagnosing, treating, or preventing--(a) the serious or
life-threatening disease or condition referred to in paragraph (1); or
(b) a serious or life-threatening disease or condition caused by a
product authorized under section 564, or approved, cleared, or licensed
under the act or PHS Act, for diagnosing, treating, or preventing the
disease or condition referred to in paragraph (1) and caused by the
agent specified in the declaration of emergency;
(3) That the known and potential benefits of the product outweigh
the known and potential risks of the product when used to diagnose,
prevent, or treat the serious or life-threatening disease or condition
that is the subject of the declaration; and
(4) That there is no adequate, approved, and available alternative
to the product for diagnosing, preventing, or treating such serious or
life-threatening disease or condition.
II. EUA Request for AVA
On December 10, 2004, pursuant to section 564(b)(1)(B) of the act
(21 U.S.C. 360bbb-3(b)(1)(B)), the Deputy Secretary of Defense
determined that there is a significant potential for a military
emergency involving a heightened risk to United States military forces
of attack with anthrax. On January 14, 2005, pursuant to section 564(b)
of the act, and on the basis of such determination, Secretary of Health
and Human Services Tommy G. Thompson declared an emergency justifying
the authorization of the emergency use of AVA. Notice of the
determination of the Deputy Secretary of Defense and the declaration of
the Secretary of Health and Human Services is published elsewhere in
this issue of the Federal Register.
III. Significance of Notice
The issuance of this Authorization for the emergency use of AVA is
the first time that the EUA authority is being used. FDA intends to
explain clearly the reasons for each issuance, termination, or
revocation of an EUA. The agency wishes to make its decision-making
understandable to help ensure that members of the public, and
particularly those individuals who may be eligible to receive a medical
product authorized for emergency use, are informed about the basis of
an EUA determination. The amount of information that will be provided
regarding each authorization will depend on the circumstances of the
emergency. We anticipate that in some circumstances, an EUA will be
issued very quickly, and time may not permit the agency to prepare
supplementary documents beyond the letter of authorization and the
notice required by section 564(h)(1) of the act. Other circumstances
may afford greater opportunity to produce materials in addition to
those prepared and disseminated as a condition of authorization under
section 564(e) of the act. Thus, the amount of additional information
that we will provide will necessarily vary on a case-by-case basis. The
agency will publish notice of each EUA and intends also to make the
notice and certain supplementary information available on its website
and in the Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852, which
is open to the public between 9 a.m. and 4 p.m., Monday through Friday.
Because the statute is self-executing, FDA does not require
regulations or guidance to implement the EUA authority. However, we
believe that it would be helpful for stakeholders and the public to
have more information about the EUA authority, and the process that the
agency is proposing to adopt for the consideration of EUA requests.
Accordingly the agency is planning to issue draft guidance on this
topic in the near future.
IV. Electronic Access
An electronic version of this notice and the full text of the
Authorization are available on the Internet at https://www.fda.gov/
ohrms/dockets/default.htm.
V. The Authorization
Having consulted with NIH and CDC, and having concluded that the
criteria for issuance of this Authorization under section 564(c) of the
act are met, FDA has authorized the emergency use of AVA for prevention
of inhalation anthrax for individuals between 18 and 65 years of age
who are deemed by DoD to be at heightened risk of exposure due to
attack with anthrax. The Authorization follows and provides an
explanation of the reasons for its issuance, as required by section
564(h)(1) of the act:
William Winkenwerder, Jr., M.D.
Assistant Secretary of Defense for Health Affairs
The Pentagon
Washington, D.C. 20301-1200
Re: Request for Emergency Use Authorization for the Armed Forces
Pending Re-determination on the Licensed Use of Anthrax Vaccine
Adsorbed for Protection Against Inhalational Anthrax
Dear Dr. Winkenwerder:
This is in response to your letter of December 22, 2004,
requesting that the Food and Drug Administration (FDA) issue an
Emergency Use Authorization (EUA) regarding the use of Anthrax
Vaccine Adsorbed (AVA) for the prevention of inhalational anthrax,
pursuant to section 564 of the Federal Food, Drug, and Cosmetic Act
(the Act).
On December 10, 2004, pursuant to section 564(b)(1)(B) of the
Act, 21 U.S.C. Sec. 360bbb-3(b)(1)(B), the Deputy Secretary of
Defense determined that there is a significant potential for a
military emergency involving a heightened risk to U.S. military
forces of attack with anthrax.\1\ On January 14, 2005, pursuant to
section 564(b) of the Act, and on the basis of such determination,
Secretary of Health and Human Services, Tommy G. Thompson declared
an emergency justifying the authorization of the emergency use of
AVA. Having consulted with the National Institutes of Health (NIH)
and the Centers for Disease Control and Prevention (CDC), and having
concluded that the criteria for issuance of this authorization under
section 564(c) of the Act are met, I am authorizing the emergency
use of AVA for prevention of inhalation anthrax,\2\ subject to the
conditions established herein.\3\
---------------------------------------------------------------------------
\1\ You state in your letter that the Deputy Secretary of
Defense has assigned authority from the Secretary of Defense to make
the statutory determination under section 564(b)(1)(B) of the Act.
\2\ The Secretary of Health and Human Services has delegated his
authority to issue an EUA under section 564 to the FDA Commissioner.
\3\ The terms ``inhalation anthrax'' and ``inhalational
anthrax'' are used interchangeably.
---------------------------------------------------------------------------
[[Page 5454]]
I. Background
AVA was first licensed by NIH in November 1970.\4\ Upon the
delegation of vaccine regulation to FDA in 1972, FDA undertook a
comprehensive review of the safety, effectiveness, and labeling of
all vaccines licensed prior to July 1, 1972.\5\ Under this review,
independent advisory panels evaluated the safety and effectiveness
data of vaccines to assure that they met appropriate standards. The
advisory panel that reviewed AVA concluded that it is safe,
effective, and not misbranded, and FDA issued a proposal to adopt
the panel's recommendation (the Bacterial Vaccines and Toxoids
Efficacy Review).\6\
---------------------------------------------------------------------------
\4\ Biological products are licensed under section 351 of the
Public Health Service Act (42 U.S.C. 262).
\5\ See 21 C.F.R. Sec. 601.25.
\6\ Biological Products; Bacterial Vaccines and Toxoids;
Implementation of Efficacy Review, 50 Fed. Reg. 51002 (Dec. 13,
1985).
---------------------------------------------------------------------------
In March 2003, six plaintiffs, known as John and Jane Doe 1
through 6, filed suit in the United States District Court for the
District of Columbia (the Court) seeking the Court to enjoin the
Anthrax Vaccine Immunization Program (AVIP) of the Department of
Defense (DoD), and to declare AVA an investigational drug when used
for protection against inhalation anthrax. On December 22, 2003, the
Court issued a preliminary injunction barring inoculations under the
AVIP in the absence of informed consent or a Presidential waiver of
the informed consent requirement.
In the Federal Register of January 5, 2004,\7\ FDA published a
final rule and final order in response to the report and
recommendations of the independent advisory panel that reviewed the
safety and effectiveness data pertaining to AVA. Following FDA's
issuance of the final rule and final order, the Court lifted the
preliminary injunction on January 7, 2004, except as it applied to
the six Doe plaintiffs.
---------------------------------------------------------------------------
\7\ Biological Products; Bacterial Vaccines and Toxoids;
Implementation of Efficacy Review, 69 Fed. Reg. 255 (Jan. 5, 2004).
---------------------------------------------------------------------------
On October 27, 2004, the Court issued a memorandum opinion
vacating and remanding the January 2004 final rule and final order
to FDA for reconsideration, following an appropriate notice and
comment period. The Court also enjoined operation of the AVIP for
inoculation using AVA to prevent inhalation anthrax. On December 29,
2004, FDA published a proposed rule and proposed order reopening the
comment period on the Bacterial Vaccine and Toxoids Efficacy Review
for 90 days.\8\ As a result of the Court's order of October 27,
2004, the use of AVA by DoD for the prevention of inhalation anthrax
under the AVIP is deemed an unapproved use of an approved product
for purposes of section 564(a)(2) of the Act. But for the Court's
order, FDA would not consider the use of AVA for inhalation anthrax
to be an unapproved use.
---------------------------------------------------------------------------
\8\ Biological Products; Bacterial Vaccines and Toxoids;
Implementation of Efficacy Review; Proposed Rule and Proposed Order,
69 Fed. Reg. 78281 (Dec. 29, 2004).
---------------------------------------------------------------------------
II. Criteria for Issuance of Authorization
Having considered the December 10, 2004, determination by the
Deputy Secretary of Defense that there is a significant potential
for a military emergency involving a heightened risk to U.S.
military forces of attack with anthrax, and the January 14, 2005,
declaration of emergency by the Secretary of Health and Human
Services, and after consultation with NIH and CDC, I have concluded
that the use of AVA to prevent inhalation anthrax meets the criteria
for issuance of an authorization under section 564(c) of the Act,
because I have concluded that:
(1) anthrax (Bacillus anthracis) can cause a serious or life-
threatening disease or condition;
(2) based on the totality of scientific evidence available to
FDA, AVA is effective in preventing inhalation anthrax; therefore,
it is reasonable to believe that AVA may be effective in preventing
inhalation anthrax pursuant to section 564(c)(2)(A) of the Act; and
that the known and potential benefits of AVA, when used to prevent
inhalation anthrax, outweigh the known and potential risks of the
product; and
(3) there is no adequate, approved, and available alternative to
AVA for preventing inhalation anthrax.\9\
---------------------------------------------------------------------------
\9\ No other criteria of issuance have been prescribed by
regulation under section 564(c)(4).
---------------------------------------------------------------------------
Specifically, I have concluded, pursuant to section 564(c)(1) of
the Act, that anthrax (Bacillus anthracis) can cause inhalation
anthrax, which is a serious or life-threatening disease or
condition. The fatality rate for inhalation anthrax in the United
States is estimated to be approximately 45 percent to 90 percent.
From 1900 to October 2001, there were 18 identified cases of
inhalation anthrax in the United States, the latest of which was
reported in 1976, with an 89 percent (16/18) mortality rate. Most of
these exposures occurred in industrial settings, i.e., textile
mills. From October 4, 2001, to December 5, 2001, a total of 11
cases of inhalation anthrax linked to intentional dissemination of
Bacillus anthracis spores were identified in the United States. Five
of these cases were fatal. These fatalities occurred despite
aggressive medical care, including antibiotics.
I have concluded that, based on the totality of scientific
evidence available to FDA, including data from at least one well-
controlled field study, AVA is effective in preventing inhalation
anthrax; therefore, it is reasonable to believe that AVA may be
effective in preventing inhalation anthrax pursuant to section
564(c)(2)(A) of the Act. In addition, pursuant to section
564(c)(2)(B) of the Act, I have concluded that it is reasonable to
believe that the known and potential benefits of AVA outweigh the
known and potential risks of the product. The available scientific
evidence that supports these conclusions includes the following:
A well-controlled efficacy field study using an earlier
version of a protective antigen-based anthrax vaccine was conducted
in mill workers from 1955-1959. In a comparison of anthrax cases
between the placebo and vaccine groups, including both inhalation
and cutaneous cases in those who were completely vaccinated, the
calculated vaccine efficacy level against all reported cases of
anthrax combined was 92.5 percent (lower 95 percent CI = 65
percent). The efficacy analysis included all cases of anthrax
disease regardless of the route of exposure or manifestation of
disease.
Epidemiological surveillance data on the occurrence of
anthrax disease in at-risk industrial settings for the years 1962-
1974 provides further supportive evidence of the effectiveness of
AVA. In that time period, individuals received either AVA, or an
earlier version of anthrax vaccine. Of the 24 anthrax cases that
occurred in mill employees during that period, no cases occurred in
those who had received the full vaccination series.
The safety of AVA was evaluated in a 5-year (1967-1971)
open-label safety study in which 15,907 doses of AVA were
administered to approximately 7,000 textile employees, laboratory
workers, and other at-risk individuals. Severe local reactions were
reported in 0.15 percent of doses administered (24 reports). There
were 150 reports (0.94 percent of doses administered) of moderate
local reactions and 1,373 reports (8.63 percent of doses
administered) of mild local reactions. In the same open label study,
four cases of systemic reactions were reported during a 5-year
reporting period (<0.06 percent of doses administered). These
reactions, which were reported to have been transient, included
fever, chills, nausea, and general body aches.
Recently (1996-1999), an assessment of safety was
conducted as part of a randomized clinical study conducted by the
U.S. Army Medical Research Institute of Infectious Diseases. Four of
the 28 volunteers reported seven acute adverse events within 30
minutes after the subcutaneous administration of AVA. These adverse
events included erythema (3), headache (2), fever (1), and elevated
temperature (1). Of these events, a single patient reported the
simultaneous occurrence of headache, fever, and elevated temperature
(100.7[deg]F). The most common local reactions reported after the
first dose in this study were tenderness (71 percent), erythema (43
percent), subcutaneous nodule (36 percent), induration (21 percent),
warmth (11 percent), and local pruritus (7 percent). Local reactions
were found to occur more often in women. No abscess or necrosis was
observed at the injection site.
I have concluded, pursuant to section 564(c)(3) of the Act, that
there is no adequate, approved, and available alternative to AVA for
preventing inhalation anthrax. No other drugs are approved for the
prevention (pre-exposure) of anthrax infection. Antibiotics are
effective against the germinated form of Bacillus anthracis, but are
not effective against the spore form of the organism. Although
antibiotics are available to treat anthrax infection, their
effectiveness is limited, in part due to delays from the time of
exposure to the initiation of treatment. Delays in the treatment of
exposed persons are possible, considering the potential scenarios of
exposure, and the difficulties that exist in identifying anthrax as
the etiology of illness.
[[Page 5455]]
III. Scope of Authorization
Pursuant to section 564(d)(1) of the Act, this authorization is
limited to the use of AVA for the prevention of inhalation anthrax
for individuals between 18 and 65 years of age who are deemed by DoD
to be at heightened risk of exposure due to attack with anthrax.
I have concluded, pursuant to section 564(d)(2) of the Act, that
it is reasonable to believe that the known and potential benefits of
AVA, when used to prevent inhalation anthrax, outweigh the known and
potential risks of the product for the population described above.
I have concluded, pursuant to section 564(d)(3) of the Act,
based on the totality of scientific evidence available to FDA, that
AVA is effective in preventing inhalation anthrax, and therefore, it
is reasonable to believe that AVA may be effective in preventing
inhalation anthrax pursuant to section 564(c)(2)(A) of the Act. FDA
has reviewed the scientific information available, including the
studies described in Section II above, and concludes that AVA, when
used for preventing inhalation anthrax, meets the standards set
forth in section 564(c) of the Act.
FDA understands that DoD recognizes that the current AVA license
describes an immunization schedule consisting of six doses. Certain
details of DoD's EUA request are not specifically addressed in the
package insert, however. DoD notes that for some personnel, the
vaccination schedule was unavoidably disrupted, and DoD intends for
such personnel to resume vaccinations at the point in the dosing
schedule where they left off, for individuals eligible under the
EUA. While this practice is not addressed in the package insert, the
practice is consistent with the general recommendations of the
Advisory Committee on Immunization Practices. When it is
impracticable to provide a dose on a specific date recommended by
the schedule, DoD intends to provide the vaccine dose as soon as
practicable thereafter. Based on the totality of the scientific
evidence available to FDA, it is reasonable to believe that such
administration of AVA may be effective in preventing inhalation
anthrax. Furthermore, the known and potential benefits of AVA, when
used to prevent inhalation anthrax in the manner described above,
outweigh the known and potential risks of the product. DoD also
acknowledges that during the course of the EUA, the risk status of
individuals initially eligible for vaccination under the EUA may
change (e.g., changes in deployment or other circumstances). In such
cases, DoD must determine whether such individuals continue to be at
heightened risk of exposure due to attack with anthrax, and
therefore, whether they continue to be eligible for vaccination with
AVA under this EUA.
The use of AVA under this EUA must be consistent with and not
contrary to the conditions of authorization set forth below. Subject
to the foregoing limitations and under the circumstances set forth
in the Deputy Secretary of Defense's determination of military
emergency, AVA may be administered for the prevention of inhalation
anthrax to individuals determined by DoD to be at heightened risk of
exposure due to attack with anthrax.
IV. Conditions of Authorization
Pursuant to section 564 of the Act, I am establishing the
following conditions on this authorization:
Conditions Designed to Ensure that Health Care Providers or
Authorized Dispensers Administering the Product Are Informed. DoD
will conduct an educational and information program under
appropriate conditions designed to ensure that health care providers
or authorized dispensers administering AVA under this authorization
are informed:
(1) that FDA has authorized the emergency use of AVA for
preventing inhalation anthrax;
(2) of the significant known and potential benefits and risks of
the emergency use of AVA, and the extent to which such benefits and
risks are unknown; and
(3) of the alternatives to AVA that are available, and of their
benefits and risks.
With respect to condition (2), above, relating to provision of
the significant known and potential benefits and risks of the
emergency use of AVA, DoD will assure that the manufacturer's
package insert is available to all health care providers or
authorized dispensers who administer AVA. DoD will also provide to
all such health care providers or authorized dispensers the same
information provided to potential vaccine recipients described
immediately below.
Conditions Designed to Ensure that Individuals to Whom the
Product is Administered Are Informed. DoD will conduct an
educational and information program under appropriate conditions
designed to ensure that individuals to whom AVA is administered are
informed:
(1) that FDA has authorized the emergency use of AVA for
preventing inhalation anthrax;
(2) of the significant known and potential benefits and risks of
the emergency use of AVA, and of the extent to which such benefits
and risks are unknown; and
(3) of the option to accept or refuse administration of AVA; of
the consequences, if any, of refusing administration of the product;
and of the alternatives to AVA that are available, and of their
benefits and risks.
With respect to condition (3), above, relating to the option to
accept or refuse administration of AVA, the AVIP will be revised to
give personnel the option to refuse vaccination. Individuals who
refuse anthrax vaccination will not be punished. Refusal may not be
grounds for any disciplinary action under the Uniform Code of
Military Justice. Refusal may not be grounds for any adverse
personnel action. Nor would either military or civilian personnel be
considered non-deployable or processed for separation based on
refusal of anthrax vaccination. There may be no penalty or loss of
entitlement for refusing anthrax vaccination.
This information shall read in the trifold brochure provided to
potential vaccine recipients as follows:
You may refuse anthrax vaccination under the EUA, and you will
not be punished. No disciplinary action or adverse personnel action
will be taken. You will not be processed for separation, and you
will still be deployable. There will be no penalty or loss of
entitlement for refusing anthrax vaccination.
Other information, as outlined in your request, is not a
condition of this EUA, but may be provided, including: That
unvaccinated people are more vulnerable to lethal anthrax infection;
morbidity or mortality due to anthrax could threaten the lives of
others in the unit who depend on each other; and anthrax infections
could jeopardize the success of the mission. Individuals subject to
the vaccination program may be informed that their military and
civilian leaders strongly recommend anthrax vaccination, but such
individuals may not be forced to be vaccinated. In addition, the
issue of mandatory vaccination will be reconsidered by DoD after FDA
completes its administrative process, which DoD expects to occur
later this year.\10\
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\10\ See Section I of this authorization.
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As a condition of this authorization, DoD will provide to each
potential AVA recipient, prior to vaccination, information that
meets the requirements set forth above. FDA has reviewed DoD's
trifold brochure, submitted on January 19, 2005, and concludes that
this brochure meets such requirements. DoD will obtain FDA's prior
approval of any revision to the trifold brochure.
Conditions for the Monitoring and Reporting of Adverse Events
Associated with the Emergency Use of AVA. DoD will, as a condition
of this authorization, actively encourage health care providers or
authorized dispensers and vaccine recipients to report adverse
events to the Vaccine Adverse Events Reporting System (VAERS). In
addition, we understand that DoD will conduct systematic monitoring
of the health of recipients of AVA, e.g., cohort studies using the
Defense Medical Surveillance System databases of active-duty
military personnel; such monitoring is not a condition of this
authorization.
Conditions Concerning Recordkeeping and Reporting, Including
Records Access by FDA. DoD will, as a condition of authorization,
record in individual medical records, including electronic
immunization tracking systems, the names of individual recipients of
AVA and the dates of vaccination. DoD will provide FDA access to
such records.
Advertising and Promotional Descriptive Printed Matter. FDA has
the authority, under section 564(e)(4) of the Act to establish
conditions on advertisements and other promotional descriptive
printed matter that relate to the emergency use of AVA under this
authorization. As a condition of this EUA, all advertising and
promotional descriptive printed matter relating to the use of AVA
shall be consistent with the trifold as well as the standards and
requirements set forth in this authorization.
V. Duration of Authorization
This EUA will be effective for 6 months from the date of
issuance. However, this EUA may be extended within the duration of
the declaration of emergency if the criteria under section 564(c) of
the Act for issuance of such
[[Page 5456]]
authorization are still met. Moreover, the EUA will cease to be
effective when the declaration of emergency is terminated under
section 564(b) of the Act or the EUA is revoked under section 564(g)
of the Act.
Thank you in advance for your cooperation in implementing this
EUA.
Sincerely,
Lester M. Crawford, D.V.M., Ph.D.
Dated: January 28, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-2028 Filed 1-31-05; 11:39 am]
BILLING CODE 4160-01-S
