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[Federal Register: August 3, 2005 (Volume 70, Number 148)]
[Notices]
[Page 44657-44660]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr03au05-160]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. 2005N-0299]
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; Extension; Availability
AGENCY: Food and Drug Administration, HHS.
ACTION: Notice.
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SUMMARY: The Food and Drug Administration (FDA) is announcing an
extension of the Emergency Use Authorization (EUA) (the Authorization)
for Anthrax Vaccine Adsorbed (AVA), issued on January 27, 2005, 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. The FDA
Commissioner is extending the term of this Authorization on the request
of DoD.
DATES: The extension of the Authorization was effective as of July 22,
2005.
ADDRESSES: Submit written requests for single copies of the extension
of the 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: Boris D. Lushniak, 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 Federal Food, Drug, and Cosmetic Act (the act)
(21 U.S.C. 360bbb-3), as amended by the Project BioShield Act of 2004
(Public Law 108-276), allows the FDA Commissioner, by delegation from
the Secretary of Health and Human Services (the Secretary), 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. As a
result of an October 27, 2004, order by the U.S. District Court for the
District of Columbia, the use of AVA by DoD for the prevention of
inhalation anthrax is deemed an unapproved use of an approved product
for purposes of section 564(a)(2) of the act.
On December 10, 2004, under section 564(b)(1)(B) of the act, 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. On December 22, 2004, DoD
requested an EUA for AVA for protection against inhalation anthrax. DoD
asked for a 6-month authorization and indicated that, if necessary, it
might ask for an extension of the duration of the EUA.
Under section 564(b) of the act, and on the basis of the Deputy
Secretary of Defense's determination of a significant potential for a
military emergency, on January 14, 2005, the 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
[[Page 44658]]
was published in the Federal Register of February 2, 2005 (70 FR 5450).
On January 27, 2005, after consulting with the National Institutes
of Health (NIH) and the Centers for Disease Control and Prevention
(CDC), and after concluding that the criteria for issuance of an
authorization under section 564(c) of the act were met, the FDA
Commissioner 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. As requested, the Authorization was effective for 6
months from the date of issuance on January 27, 2005. Notice of the
Authorization was published in the Federal Register of February 2, 2005
(70 FR 5452).
II. Request for Extension
On July 11, 2005, DoD requested an extension of the Authorization
and stated that the information presented in its December 22, 2004,
request for an EUA for AVA is still accurate.
III. Electronic Access
An electronic version of this notice is available on the Internet
at http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.fda.gov/ohrms/dockets/default.htm.
IV. Extension of the Authorization
Having confirmed that the declaration of emergency issued under
section 564(b)(1) of the act currently remains in effect and having
concluded that the criteria for issuance of the Authorization under
section 564(c) of the act continue to be met, the FDA Commissioner, on
July 22, 2005, granted DoD's request for an extension of the
Authorization for the emergency use of AVA for prevention of inhalation
anthrax. This EUA will be effective for the duration of the declaration
of emergency issued on January 14, 2005.
The letter granting the extension follows:
William Winkenwerder, Jr., M.D.
Assistant Secretary of Defense for Health Affairs
The Pentagon
Washington, D.C. 20301-1200
Re: Request for Extension of the 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 July 11, 2005, requesting
an extension of the above-referenced Emergency Use Authorization
(EUA), which was issued on January 27, 2005,\1\ pursuant to section
564 of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C.
Sec. 360bbb-3.\2\ You requested an extension of the EUA ``for such
time as necessary pending the upcoming FDA re-determination of the
licensed use of AVA for protection against inhalational anthrax.''
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\1\Notice of the issuance of the EUA for AVA was published in
the Federal Register on February 2, 2005 (70 Fed. Reg. 5452).
\2\The Secretary of Health and Human Services (HHS) has
delegated the authority to issue an EUA under section 564 of the Act
to the Commissioner of Food and Drugs.
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The declaration of emergency\3\ justifying the EUA for AVA
remains in effect. The Secretary of Health and Human Services, Tommy
G. Thompson, issued this declaration of emergency on January 14,
2005.\4\ Pursuant to section 564(b)(2)(A)(ii) of the Act, the
declaration of emergency will terminate by expiration on January 14,
2006, which is the end of the one year period that began on the date
that the declaration was made.\5\
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\3\Notice of the HHS Secretary's declaration of emergency and of
the Deputy Secretary of Defense's determination of military
emergency under section 564(b)(1) of the Act was published in the
Federal Register on February 2, 2005 (70 Fed. Reg. 5450).
\4\The declaration of emergency was not issued on January 10,
2005, as is stated in your letter of July 11, 2005.
\5\It is possible, under section 564(b)(2) of the Act, that the
declaration of emergency may terminate or be renewed prior to its
expiration.
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Having confirmed that the declaration of emergency, issued under
section 564(b)(1) of the Act, currently remains in effect and having
concluded that the criteria for issuance of this authorization under
section 564(c) of the Act continue to be met, I am granting your
request to extend the authorization for the emergency use of AVA for
prevention of inhalation anthrax.\6\ The extension of the EUA is for
the duration of the existing declaration of emergency,\7\ subject to
the conditions established herein. These conditions shall be the
same as those that currently apply to the EUA for AVA, issued on
January 27, 2005.
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\6\The terms ``inhalation anthrax'' and ``inhalational anthrax''
are used interchangeably.
\7\The EUA may be revoked, pursuant to section 564(g) of the
Act, prior to the termination of the declaration of emergency if the
criteria for issuance of the authorization are no longer met or
other circumstances make revocation appropriate to protect the
public health or safety.
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I. Background
AVA was first licensed by the National Institutes of Health
(NIH) in November 1970.\8\ 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.\9\ Under this review, independent advisory panels evaluated
the safety and effectiveness data of vaccines to ensure 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).\10\
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\8\Biological products are licensed under section 351 of the
Public Health Service Act, 42 U.S.C. Sec. 262.
\9\See 21 C.F.R. Sec. 601.25.
\10\Biological Products; Bacterial Vaccines and Toxoids;
Implementation of Efficacy Review, 50 Fed. Reg. 51002 (Dec. 13,
1985).
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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,\11\ FDA published a
final rule and final order (January 2004 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.
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\11\Biological Products; Bacterial Vaccines and Toxoids;
Implementation of Efficacy Review, 69 Fed. Reg. 255 (Jan. 5, 2004).
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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.\12\ 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.
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\12\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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On December 10, 2004, pursuant to section 564(b)(1)(B) of the
Act, 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.\13\
On December 22, 2005, you requested an EUA to use AVA for protection
against inhalation anthrax. You requested an authorization for a
period of six months, pending completion of FDA's Bacterial Vaccine
and Toxoids Efficacy Review.\14\ You also indicated that, if
necessary, you might ask for an extension of the duration of the
EUA.
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\13\See supra note 3.
\14\See supra note 12.
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On January 14, 2005, pursuant to section 564(b) of the Act, and
on the basis of the Deputy Secretary of Defense's determination
[[Page 44659]]
of a significant potential for a military emergency, the Secretary
of Health and Human Services, Tommy G. Thompson, declared an
emergency justifying the authorization of the emergency use of
AVA.\15\ On January 27, 2005, after consulting with the NIH and the
Centers for Disease Control and Prevention (CDC), and after
concluding that the criteria for issuance of an authorization under
section 564(c) of the Act were met, I authorized the emergency use
of AVA for prevention of inhalation anthrax, subject to conditions
of authorization set out in the authorization.\16\
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\15\See supra note 3.
\16\See supra note 1.
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II. Criteria for Issuance of Authorization
The January 14, 2005, declaration of emergency by the Secretary
of Health and Human Services remains in effect. After consultation
with NIH and CDC, I have concluded that the use of AVA to prevent
inhalation anthrax continues to meet 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.\17\
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\17\No other criteria of issuance have been prescribed by
regulation under section 564(c)(4) of the Act.
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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. FDA incorporates by reference the information concerning
inhalation anthrax contained in Section II, p. 3, of the
authorization issued on January 27, 2005. 70 Fed. Reg. 5454
(February 2, 2005).
I have concluded that, based on the totality of scientific
evidence available to FDA,\18\ 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 data and
information described in Section II of the authorization issued on
January 27, 2005,\19\ which is hereby incorporated by reference.
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\18\ The available scientific evidence includes FDA's review of
adverse event reports concerning AVA submitted to the Vaccine
Adverse Event Reporting System
\19\70 Fed. Reg. 5454 (February 2, 2005).
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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.
III. Scope of Authorization
Pursuant to section 564(d)(1) of the Act, this authorization
continues to be 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 available scientific evidence reviewed by
FDA,\20\ 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.
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\20\The scientific evidence available to the Agency includes
studies referred to in Section II above.
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Accordingly, I have concluded 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 December 22, 2004, 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 of the following:
(1) that FDA has authorized the emergency use of AVA for
preventing inhalation anthrax;
(2) that significant known and potential benefits and risks
exist with the emergency use of AVA, and that the extent to which
such benefits and risks exist is unknown; and
(3) that alternatives to AVA are available, and that there are
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 ensure 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 of:
(1) the fact that FDA has authorized the emergency use of AVA
for preventing inhalation anthrax;
(2) 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) the option to accept or refuse administration of AVA; of the
consequences,
[[Page 44660]]
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.
The trifold brochure provided to potential vaccine recipients
also shall state the following:
On October 27, 2004, the U.S. District Court for the District of
Columbia issued an Order declaring unlawful and prohibiting
mandatory anthrax vaccinations to protect against inhalation
anthrax, pending further FDA action. The Court's injunction means
you have the right to refuse to take the vaccine without fear of
retaliation. A copy of the Court's Order and Opinion is available at
http://frwebgate.access.gpo.gov/cgi-bin/leaving.cgi?from=leavingFR.html&log=linklog&to=http://www.anthrax.mil or from the vaccination clinic.
Other information, as outlined in your request of December 22,
2004, 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 January 27, 2005, authorization notes
that the issue of mandatory vaccination will be reconsidered by DoD
after FDA completes its administrative process.\21\
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\21\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. Based on a review of DoD's
trifold brochure, dated April 5, 2005,\22\ I have concluded that
this brochure continues to meet such requirements. DoD will obtain
FDA's prior approval of any revision to the trifold brochure.
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\22\FDA approved a revision to the trifold brochure on February
15, 2005, and on April 6, 2005.
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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 the duration of the declaration
of emergency issued by Secretary of Health and Human Services, Tommy
G. Thompson, on January 14, 2005. The EUA will cease to be effective
when the declaration of emergency is terminated under section
564(b)(2) of the Act or the EUA is revoked under section 564(g) of
the Act.
Thank you in advance for your continued cooperation in
implementing this EUA.
Sincerely,
Lester M. Crawford, D.V.M., Ph.D.
Commissioner of Food and Drugs
Dated: July 27, 2005.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. 05-15233 Filed 7-28-05; 2:51 pm]
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