
[Federal Register: October 21, 2008 (Volume 73, Number 204)]
[Notices]               
[Page 62507-62514]
From the Federal Register Online via GPO Access [wais.access.gpo.gov]
[DOCID:fr21oc08-66]                         

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DEPARTMENT OF HEALTH AND HUMAN SERVICES

Food and Drug Administration

[Docket No. FDA-2008-N-0548]

 
Authorization of Emergency Use of Doxycycline Hyclate Tablet 
Emergency Kits for Eligible United States Postal Service Participants 
in the Cities Readiness Initiative and Their Household Members; 
Availability

AGENCY: Food and Drug Administration, HHS.

ACTION: Notice.

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SUMMARY: The Food and Drug Administration (FDA) is announcing the 
issuance of an Emergency Use Authorization (EUA) (the Authorization) 
for doxycycline hyclate tablet emergency kits for eligible United 
States Postal Service (USPS) participants in the Cities Readiness 
Initiative (CRI) and their household members. FDA is issuing this 
Authorization under the Federal Food, Drug, and Cosmetic Act (the act), 
as requested by the Biomedical Advanced Research and Development 
Authority (BARDA), Office of the Assistant Secretary for Preparedness 
and Response, HHS. The Authorization contains, among other things, 
conditions on the emergency use of doxycycline hyclate tablet emergency 
kits. The Authorization follows the determination by the Secretary of 
the Department of Homeland Security that there is a significant 
potential for a domestic emergency, involving a heightened risk of 
attack with a specified biological, chemical, radiological, or nuclear 
agent or agents--in this case, Bacillus anthracis. On the basis of such 
determination, Secretary of Health and Human Services Michael O. 
Leavitt (the Secretary) declared an emergency justifying the 
authorization of the emergency use of doxycycline hyclate tablets 
accompanied by emergency use information subject to the terms of any 
authorization issued under 21 U.S.C. 360bbb-3(a). The Authorization, 
which includes an explanation of the reasons for its issuance, is 
reprinted in this Notice.

DATES: The Authorization is effective as of October 3, 2008.

ADDRESSES: Submit written requests for single copies of the Emergency 
Use Authorization to the Office of Counterterrorism and Emerging 
Threats (HF-29), Food and Drug Administration, 5600 Fishers Lane (HF-
29), rm. 14C-26, 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 Lushniak, Office of 
Counterterrorism and Emerging Threats (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 
domestic emergency, or a significant

[[Page 62508]]

potential for a domestic emergency, involving a heightened risk of 
attack with a specified biological, chemical, radiological, or nuclear 
agent or agents. 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.
    Section 564(b)(1) of the act provides that, before an EUA may be 
issued, the Secretary must declare an emergency justifying the 
authorization 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 that the statutory criteria are satisfied. Under section 
564(h)(1) of the act, FDA is required to publish in the Federal 
Register a notice of each authorization, and each termination or 
revocation of an authorization, and an explanation of the reasons for 
the action. 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, 
360(k), and 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\1\ concludes:
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    \1\ The Secretary has delegated his authority to issue an EUA 
under section 564 of the act to the Commissioner of Food and Drugs.
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    (1) That an agent specified in a declaration [of emergency] can 
cause a serious or life-threatening disease or condition;
    (2) That, based on the totality of scientific evidence available to 
[FDA], including data from adequate and well-controlled clinical 
trials, if available, it is reasonable to believe that:
    (A) The product may be effective in diagnosing, treating, or 
preventing--
    (1) Such disease or condition; or
    (2) A serious or life-threatening disease or condition caused by a 
product authorized under [Section 564], approved or cleared under this 
Act, or licensed under Section 351 of the [PHS] Act, for diagnosing, 
treating, or preventing such a disease or condition caused by such an 
agent; and
    (B) the known and potential benefits of the product, when used to 
diagnose, prevent, or treat such disease or condition, outweigh the 
known and potential risks of the product;
    (3) That there is no adequate, approved, and available alternative 
to the product for diagnosing, preventing, or treating such disease or 
condition; and
    (4) That such other criteria as the Secretary may by regulation 
prescribe are satisfied.
    No other criteria of issuance have been prescribed by regulation 
under Section 564(c)(4) of the act. Because the statute is self-
executing, FDA does not require regulations or guidance to implement 
the EUA authority. However, FDA published guidance in July 2007 
entitled ``Emergency Use Authorization of Medical Products'' to provide 
more information for stakeholders and the public about the EUA 
authority and the agency's process for the consideration of EUA 
requests.

II. EUA Request for Doxycycline Hyclate Tablets in Emergency Kits

    On September 23, 2008, under section 564(b)(1)(A) of the act, the 
Secretary of Homeland Security determined that there is a significant 
potential for a domestic emergency, involving a heightened risk of 
attack with a specified biological, chemical, radiological, or nuclear 
agent or agents--in this case, Bacillus anthracis. On October 1, 2008, 
under section 564(b) of the act, and on the basis of such 
determination, Secretary of Health and Human Services Michael O. 
Leavitt declared an emergency justifying the authorization of the 
emergency use of doxycycline hyclate tablets accompanied by emergency 
use information subject to the terms of any authorization issued under 
21 U.S.C. 360bbb-3(a). Notice of the determination of the Secretary of 
Homeland Security and the declaration of the Secretary of Health and 
Human Services was published in the Federal Register of October 6, 2008 
(73 FR 58242). On October 1, 2008, BARDA requested an EUA for 
doxycycline hyclate tablet emergency kits for eligible USPS 
participants in CRI and their household members. Doxycycline hyclate 
tablets are not approved with certain written information, including 
emergency use instructions, which are authorized under this EUA.

III. Electronic Access

    An electronic version of this document and the full text of the 
Authorization are available on the Internet at http://
www.regulations.gov.

IV. 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 doxycycline 
hyclate tablet emergency kits for eligible USPS participants in the CRI 
and their household members. The Authorization follows and provides an 
explanation of the reasons for its issuance, as required by section 
564(h)(1) of the act:
    The letter of authorization follows:

Robin Robinson, Ph.D.
Director
Biomedical Advanced Research and Development Authority (BARDA)
330 Independence Avenue SW
Room G640
Washington, DC 20201
Dear Dr. Robinson:
    This letter is in response to BARDA's October 1, 2008 
submission, as amended,\2\ requesting that the Food and Drug 
Administration (FDA) issue an Emergency Use Authorization (EUA) for 
the pre-event provision and potential use of doxycycline hyclate 
tablet emergency kits\3\ for

[[Page 62509]]

inhalational anthrax, pursuant to section 564 of the Federal Food, 
Drug, and Cosmetic Act (the Act). Your request is specifically for 
eligible\4\ United States Postal Service (USPS) participants in the 
Cities Readiness Initiative (CRI) (hereinafter USPS participants) 
and their household members.\5\
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    \2\ BARDA's amendment was submitted on October 3, 2008.
    \3\ Your submissions refer to a Household Antibiotic Kit (HAK), 
which would be stored in an eligible United States Postal Service 
(USPS) participant's home and would contain unit-of-use bottles of 
doxycycline hyclate tablets (100 mg) and both emergency use 
instructions and home preparation instructions. Your submissions 
also refer to an individual Household Antibiotic Kit (iHAK), which 
would be stored at an eligible USPS participant's workplace and 
would contain only one unit-of-use bottle of doxycycline hyclate 
tablets (100 mg) and emergency use instructions. For ease of 
reference, this letter of authorization will use the term 
``doxycycline hyclate tablet emergency kit(s)'' to refer to both 
types of kits, unless otherwise specified. When referring to the 
kits separately, this letter will use the term ``household 
doxycycline hyclate tablet emergency kit to refer to the HAK and the 
term ``individual doxycycline hyclate tablet emergency kit'' to 
refer to the iHAK.
    \4\ The term ``eligible'' refers to USPS participants who have 
agreed in writing to participate in the Postal Module of CRI, have 
been screened for fitness to receive OSHA-required personal 
protective equipment, have (including household members) been 
medically screened for contraindications based on completed health 
assessment forms, have (including household members) been given a 
valid prescription, and have (including household members) not 
otherwise been determined to be ineligible to receive doxycycline 
hyclate tablet emergency kits.
    \5\ Your submissions define ``household member'' as ``anyone 
that considers that address as his or her permanent place of 
residence.''
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    On September 23, 2008, pursuant to section 564(b)(1)(A) of the 
Act, 21 U.S.C. Sec.  360bbb-3(b)(1)(A), the Secretary of the 
Department of Homeland Security determined that there is a 
significant potential for a domestic emergency, involving a 
heightened risk of attack with a specified biological, chemical, 
radiological, or nuclear agent or agents--in this case, Bacillus 
anthracis.\6\ On October 1, 2008, pursuant to section 564(b) of the 
Act, and on the basis of such determination, the Secretary of the 
Department of Health and Human Services declared an emergency 
justifying the authorization of the emergency use of doxycycline 
hyclate tablets accompanied by emergency use information subject to 
the terms of any authorization issued under 21 U.S.C. Sec.  360bbb-
3(a).\7,8\ 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 doxycycline hyclate tablet 
emergency kits for the post-exposure prophylaxis of inhalational 
anthrax for eligible USPS participants and their household 
members,\9\ subject to the terms of this authorization.
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    \6\ Memorandum from Michael Chertoff to Michael O. Leavitt, 
Determination Pursuant to Sec.  564 of the Federal Food, Drug, and 
Cosmetic Act (Sept. 23, 2008).
    \7\ Declaration of Emergency Pursuant to Section 564 of the 
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. 360bbb-3(b) (Oct. 1, 
2008).
    \8\ The doxycycline hyclate tablet emergency kits for eligible 
USPS participants and their household members referenced and 
authorized in this letter fall within the scope of the Secretary of 
the Department of Health and Human Services' declaration.
    \9\ Doxycycline hyclate tablets are indicated for treatment of 
infections caused by ``Anthrax due to Bacillus anthracis, including 
inhalational anthrax (post-exposure): to reduce the incidence or 
progression of disease following exposure to aerosolized Bacillus 
anthracis.'' This indication generally means that drug 
administration is expected to start after a known or suspected 
exposure to aerosolized Bacillus anthracis spores, but before 
clinical symptoms of the disease develop. The indication includes 
presumed exposure, since it is often difficult to know whether and 
when exposure has actually occurred. The indication also encompasses 
instances where Bacillus anthracis exposure via inhalation is 
expected and will be imminent. In such cases, the first few doses of 
prophylaxis may be taken pre-exposure, but the remainder of the 
course would be taken post-exposure. The indication is commonly 
referred to as ``post-exposure prophylaxis of inhalational 
anthrax,'' and this term will be used throughout this letter for 
ease of reference.
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    The remainder of this letter is organized into four sections: 
Background, Criteria for Issuance of Authorization, Scope of 
Authorization, Conditions of Authorization, and Duration of 
Authorization.

I. Background

    CRI involves 72 major metropolitan areas and all 50 states. The 
primary goal of CRI is to develop the ability to provide mass 
prophylaxis to 100% of the identified population within 48 hours of 
notification to do so.
    On February 18, 2004, the Secretary of the Department of Health 
and Human Services (HHS), the Secretary of the Department of 
Homeland Security (DHS), and the Postmaster General signed a 
Memorandum of Agreement to explore how the resources of the USPS 
could be made available to help deliver oral antibiotics in response 
to a biological terrorism incident. Subsequently, HHS launched CRI 
and asked the USPS to participate in what has been referred to as 
the CRI Postal Module (or Postal Plan). The Postal Module involves 
the delivery of antibiotics to residential households within pre-
determined zip codes by USPS participants where there may be an 
intentional release of Bacillus anthracis in their geographic area. 
The CRI Postal Module could be activated and executed while the 
municipality is establishing its points-of-dispensing (POD) network 
for the remainder of the emergency response which, in the case of a 
wide-area anthrax event, could continue for 1-2 months. The postal 
carriers' role is voluntary because emergency response is neither 
part of the basic mission of USPS nor a provision of the contracts 
between USPS and the unions representing the carriers. USPS has made 
its participation in the CRI Postal Module contingent on the pre-
event provision of prescription antibiotic countermeasures to USPS 
participants and their household members.
    Your request relates to a potential EUA for the pre-event 
provision and potential use of doxycycline hyclate tablets (100 mg) 
in the form of emergency kit(s) for eligible USPS participants and 
their household members. Although doxycycline hyclate tablets are 
approved for the post-exposure prophylaxis of inhalational anthrax, 
the emergency kits you describe in your submissions would require an 
EUA because they would include certain written information that is 
not currently part of the approved new drug applications (NDAs) or 
abbreviated new drug applications (ANDAs) for doxycycline hyclate 
tablets (100 mg). Specifically, you indicated that the following 
pieces of written information would accompany the doxycycline 
hyclate tablets:
     Fact Sheet for Recipients
     For the household doxycycline hyclate tablet emergency 
kit, home preparation instructions for recipients who cannot swallow 
pills (hereinafter home preparation instructions)
     Information placard (unless the bag is pre-printed with 
placard information)
     MedWatch Form 3500 for the reporting of any adverse 
events associated with the doxycycline hyclate tablet emergency kit
    In addition, a Fact Sheet for Health Care Providers would be 
distributed to health care providers and authorized dispensers of 
the doxycycline hyclate tablet emergency kits.
    You propose to use doxycycline hyclate tablets (100 mg) that 
were manufactured by West-Ward Pharmaceutical Corp., and repackaged 
by PD-Rx Pharmaceuticals into unit-of-use bottles containing 20 oral 
tablets each, a 10-day supply.\10\
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    \10\ We note that the full course of doxycycline hyclate tablets 
for adults for the post-exposure prophylaxis of inhalational anthrax 
is 100 mg twice daily for 60 days. The corresponding oral dosing 
regimen for children under 100 pounds is 1 mg per pound of body 
weight twice daily for 60 days.
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    The doxycycline hyclate tablet emergency kit(s) that are the 
subject of your request would come in two forms. The first, which 
you describe as a Household Antibiotic Kit (HAK), would contain a 
unit-of-use bottle of doxycycline hyclate tablets for each eligible 
USPS participant and each eligible household member, as well as the 
Fact Sheet for Recipients, home preparation instructions, MedWatch 
Form 3500, and information placard (unless bag is pre-printed with 
placard information) described above. All of these items would be 
placed in one tamper-evident, clear plastic bag for home storage. 
The second, which you describe as an individual Household Antibiotic 
Kit (iHAK), would contain one unit-of-use bottle of doxycycline 
hyclate tablets for the eligible USPS participant and the Fact Sheet 
for Recipients, MedWatch Form 3500, and information placard (unless 
the bag is pre-printed with placard information) described above. 
All of these items would be placed in a separate tamper-evident, 
clear plastic bag for secure storage at the USPS participant's 
workplace, should the USPS participant need to deploy emergently.

II. Criteria for Issuance of Authorization

    Having considered the September 23, 2008 determination by the 
Secretary of the Department of Homeland Security that there is a 
significant potential for a domestic emergency, involving a 
heightened risk of attack with a biological, chemical, radiological, 
or nuclear agent or agents--in this case, Bacillus anthracis, and 
the October 1, 2008 declaration of emergency by the Secretary of 
Health and Human Services, and having consulted with NIH and CDC, I 
have concluded that the emergency use of doxycycline hyclate tablet 
emergency kits for

[[Page 62510]]

the post-exposure prophylaxis of inhalational anthrax for eligible 
USPS participants and their household members meets the criteria for 
issuance of an authorization under section 564(c) of the Act, 
because I have concluded that:
    (1) Bacillus anthracis can cause anthrax, a serious or life-
threatening disease or condition;
    (2) based on the totality of scientific evidence available to 
FDA, it is reasonable to believe that doxycycline hyclate tablet 
emergency kits may be effective for post-exposure prophylaxis of 
inhalational anthrax,\11\ and that the known and potential benefits 
of doxycycline hyclate tablet emergency kits, when used for the 
post-exposure prophylaxis of inhalational anthrax in the specified 
population, outweigh the known and potential risks of the product; 
and
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    \11\ The Act uses the terms ``diagnosing, treating, or 
preventing'' in Section 564(c)(2)(A). Post-exposure prophylaxis is 
encompassed by these statutory terms.
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    (3) there is no adequate, approved, and available alternative to 
doxycycline hyclate tablet emergency kits for the post-exposure 
prophylaxis of inhalational anthrax.\12\
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    \12\ 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 Bacillus anthracis can cause inhalational anthrax, 
which is a serious or life-threatening disease or condition. The 
fatality rate for inhalational 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 inhalational 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 inhalational 
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 treatment with antimicrobial drugs.
    I have also concluded that, based on the totality of the 
scientific evidence available to FDA, including data supporting the 
safe and effective use of doxycycline hyclate tablets (100 mg) for 
the post-exposure prophylaxis of inhalational anthrax, the results 
of CDC's home MedKit study, and information associated with the 
development of the home preparation instructions, it is reasonable 
to believe that doxycycline hyclate tablet emergency kits may be 
effective for the post-exposure prophylaxis of inhalational anthrax 
pursuant to section 564(c)(2)(A) of the Act.
    The above conclusion is largely based on the fact that FDA has 
previously approved a number of NDAs and ANDAs for doxycycline 
hyclate tablets for the treatment and post-exposure prophylaxis of 
inhalational anthrax, as summarized below.
    In November 2001, as part of a public health response to the use 
of anthrax spores as a bioterrorism agent, the Agency published a 
notice in the Federal Register that clarified the dosing 
recommendations for, among others, doxycycline hyclate products, in 
the management of patients with inhalational anthrax who had been 
exposed to spores of Bacillus anthracis, but who did not manifest 
clinical disease.\13\ In that notice, FDA announced that it had 
determined that the language in the labeling of certain drug 
products, including those containing doxycycline hyclate, is 
intended to, and does, cover all forms of anthrax, including 
inhalational anthrax (post-exposure): to reduce the incidence or 
progression of disease exposure to aerosolized B. anthracis. FDA 
also announced that the appropriate dosing regimen for adults is 100 
mg of doxycycline, taken orally twice daily for 60 days; and the 
corresponding oral dosing regimen for children under 100 pounds is 1 
mg per pound (1 mg/lb) of body weight (2.2 mg/kilogram (kg)), given 
twice daily for 60 days.\14\ FDA based these conclusions on the 
following:
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    \13\ See 66 Fed. Reg. 55679 (Nov. 2, 2001); Docket 01N-0494.
    \14\Id. The Federal Register notice further requested that 
applicants for these products submit labeling supplements to update 
their package inserts with this information.
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     Effectiveness was supported by minimal inhibitory 
concentration (MIC) data for the tetracycline class and Bacillus 
anthracis, pharmacokinetic data, data from the Sverdlovsk incident, 
and the outcome data from a study of inhalational exposure to 
Bacillus anthracisin rhesus monkeys.
     With respect to safety, FDA noted that doxycycline drug 
products have been used for over 30 years and the literature on the 
products is voluminous. FDA previously reviewed the literature 
dealing with the long-term administration of doxycycline for 
treatment of diseases other than anthrax. Several articles reported 
the results of studies involving the administration of doxycycline 
in amounts comparable to the recommended doses. They also involved 
administration of doxycycline for 60 days and periods approaching 
and exceeding 60 days. FDA also reviewed data from the Adverse Event 
Reporting System (AERS). Analysis of these articles and data 
indicated no pattern of unlabeled adverse events associated with the 
long-term use of doxycycline.
     FDA also noted that doxycycline and other members of 
the tetracycline class of antibiotics are not generally indicated 
for the treatment of any patients under the age of 8 years. 
Tetracyclines are known to be associated with teeth discoloration 
and enamel hypoplasia in children and delays in bone development in 
premature infants after prolonged use. FDA balanced the nature of 
the effect on teeth and the fact that this delay in bone development 
is apparently reversible against the lethality of inhalational 
anthrax, and concluded that doxycycline drug products can be labeled 
with a pediatric dosing regimen for inhalational anthrax (post-
exposure).
    As noted above, FDA has approved, under section 505(j) of the 
Act, a number of abbreviated new drug applications (ANDAs), 
including West-Ward's ANDA (65-095) for doxycycline hyclate 
tablets (100 mg) for treatment and post-exposure prophylaxis of 
inhalational anthrax on July 2, 2003. West-Ward's doxycycline 
hyclate tablets (100 mg), which have been repackaged and re-labeled 
by PD-Rx Pharmaceuticals, are the subject of this emergency use 
authorization. This product is the same as the reference listed 
drug, Vibra-Tabs (doxycycline hyclate tablets, 100 mg; NDA 
50-333), within the meaning of section 505(j) of the Act.
    I have also considered CDC's home MedKit study and information 
associated with the development of the home preparation instructions 
as part of the totality of the scientific evidence available to FDA, 
and have determined that this information helps to support the 
conclusion that it is reasonable to believe that doxycycline hyclate 
tablet emergency kits may be effective for post-exposure prophylaxis 
of inhalational anthrax, as summarized below.
    The CDC study evaluated the ability of study participants to 
receive what was referred to as a MedKit--doxycycline\15\ with 
certain written information, including emergency use instructions 
and home preparation instructions similar to those being authorized 
here. A convenience sample of 4,250 St. Louis area households, 
divided among three cohorts, was enrolled in the study after medical 
screening and informed consent. The primary outcomes for this 
evaluation were to determine the extent to which participants would 
follow instructions for appropriately keeping the MedKits intact and 
reserving them for emergency use until directed by a local 
government official. Although this study had a number of limitations 
as explained below, approximately 97% of all study respondents 
returned the MedKits upon completion of the study.
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    \15\ In this study, participants who were allergic to 
doxycycline or for whom doxycycline was otherwise contraindicated 
received ciprofloxacin.
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    Finally, FDA considered information associated with the 
development of the home preparation instructions for doxycycline 
hyclate tablets. FDA had previously developed home preparation 
instructions and these instructions were tested by the Chicago 
Department of Public Health, which provided its results to FDA. The 
Agency revised the home preparation instructions based on these 
findings and performed additional laboratory tests and limited 
palatability testing. FDA also worked with CDC to improve the 
readability of the instructions.
    Although FDA has approved a number of NDAs and ANDAs for 
doxycycline hyclate tablets (100 mg) for the treatment and post-
exposure prophylaxis of inhalational anthrax, these products are not 
approved with emergency use instructions and home preparation 
instructions. The amount and nature of the scientific evidence 
regarding the ability to use emergency use instructions and home 
preparation instructions is more limited than the scientific 
evidence supporting the approval of doxycycline hyclate tablets for 
the post-exposure prophylaxis of inhalational anthrax. However, 
taking into consideration the potentially fatal nature of anthrax 
disease, the CDC home MedKit study and the information associated 
with the development

[[Page 62511]]

of the home preparation instructions also helps to support a 
conclusion that it is reasonable to believe that doxycycline hyclate 
tablet emergency kits may be effective for the post-exposure 
prophylaxis of inhalational anthrax. Accordingly, based on the 
totality of the scientific evidence available to FDA, it is 
reasonable to believe that doxycycline hyclate tablet emergency kits 
may be effective for the post-exposure prophylaxis of inhalational 
anthrax.
    I have also concluded, pursuant to section 564(c)(2)(B) of the 
Act, that it is reasonable to believe that the known and potential 
benefits of doxycycline hyclate tablet emergency kits outweigh the 
known and potential risks of the product for USPS participants and 
their household members. The available scientific evidence that 
supports this conclusion is summarized below.
    We have already concluded, as evidenced by the previous NDA and 
ANDA approvals discussed above, that the known and potential 
benefits of the approved doxycycline hyclate tablets (100 mg) for 
post-exposure prophylaxis of inhalational anthrax outweigh the known 
and potential risks of the product. Under this EUA, doxycycline 
hyclate tablets will be packaged with additional written information 
(including emergency use instructions and home preparation 
instructions) that has not been approved by FDA as part of a new 
drug application. CDC's home MedKit study and the process by which 
home preparation instructions were developed, as discussed above, 
help to further inform the requisite risk-benefit analysis under 
section 564(c)(2)(B).
    The CDC home MedKit study was somewhat limited in its ability to 
address certain questions about home storage and use since the 
participants were not required to follow any directions for 
preparation or use of doxycycline hyclate tablets in an actual 
emergency. The effect of the actual storage conditions on the stored 
drug product was not tested and the instructions for storage did not 
provide the temperature conditions for storage on the outside of the 
bag. Despite the limitations of the CDC home MedKit study, it is 
important to note that approximately 97% of all study respondents 
returned the MedKits upon completion of the study.
    As described above, the development of the home preparation 
instructions has been informed by limited testing and input from 
CDC. However, the current version of the home preparation 
instructions has not been subjected to formal independent testing 
procedures for an assessment of an individual's understanding or 
his/her ability to follow the directions.
    Because of the limitations of the CDC study and the lack of 
formal independent testing on the home preparation instructions, FDA 
cannot conclude without further testing and information that the 
emergency use instructions and home preparation instructions pose no 
additional risks to eligible USPS participants and their household 
members. Inappropriate use and the development of doxycycline 
resistant microorganisms could be a potential issue if a 
considerable number of eligible USPS participants take the product 
for an unintended purpose.
    The known and potential risks of eligible USPS participants and 
their household members not being able to store, prepare, and use 
doxycycline hyclate tablets in accordance with the emergency use 
instructions and home preparation instructions, and of experiencing 
adverse reactions, is outweighed by the known and potential benefits 
of using doxycycline hyclate tablets as a safe and effective 
treatment against an otherwise potentially fatal aerosolized anthrax 
attack. For the foregoing reasons, it is reasonable to believe that 
the known and potential benefits of the doxycycline hyclate tablet 
emergency kits (including emergency instructions and home 
preparation instructions as authorized) for the post-exposure 
prophylaxis of inhalational anthrax in the specified population 
outweigh the known and potential risks of the product under the 
terms of this letter of authorization.\16\
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    \16\ The terms of this letter of authorization, including its 
scope and conditions, are integral to the conclusions regarding the 
known and potential risks and benefits of the emergency use of this 
product in eligible USPS participants and their household members.
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    I have also concluded, pursuant to section 564(c)(3) of the Act, 
that there is no adequate, approved, and available alternative to 
the doxycycline hyclate tablet emergency kits for post-exposure 
prophylaxis of inhalational anthrax in the specified population. 
Although doxycycline hyclate is approved for treatment and post-
exposure prophylaxis of inhalational anthrax, the emergency use 
instructions and home preparation instructions included here as part 
of the doxycycline hyclate tablet emergency kits are not approved by 
FDA.
    Other products approved for treatment and post-exposure 
prophylaxis of inhalational anthrax include penicillin G procaine, 
ciprofloxacin, and levofloxacin. However, none of these products is 
approved with emergency use instructions. In addition, penicillin G 
procaine is administered by injection and fluoroquinolones 
(ciprofloxacin and levofloxacin) have additional significant adverse 
events reported following their use, including adverse tendon 
effects and rupture, peripheral neuropathy, and central nervous 
system disorders.
    Further, Biothrax (Anthrax Vaccine Adsorbed) is indicated for 
the active immunization against Bacillus anthracis of individuals 
between 18 and 65 years of age who come in contact with animal 
products such as hides, hair or bones that come from anthrax endemic 
areas, and that may be contaminated with Bacillus anthracis spores. 
This product is not considered an ``adequate, approved, and 
available'' alternative for several reasons including: (1) the 
license for Biothrax does not extend to post exposure use; (2) the 
immunization consists of three subcutaneous injections given 2 weeks 
apart followed by three additional subcutaneous injections given at 
6, 12 and 18 months; and (3) following the initial injections, time 
is needed to develop the antibodies. Therefore, I have concluded 
that there is no adequate, approved, and available alternative to 
doxycycline hyclate tablet emergency kits for the post-exposure 
prophylaxis of inhalational anthrax for the specified population.

III. Scope of Authorization

    Pursuant to section 564(d)(1) of the Act, this authorization is 
limited to the use of doxycycline hyclate tablet emergency kits for 
the post-exposure prophylaxis of inhalational anthrax\17\ for 
eligible\18\ USPS participants in the Postal Module of CRI and their 
household members.
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    \17\ See footnote 8.
    \18\ See footnote 3.
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    The doxycycline hyclate tablets authorized under this EUA were 
manufactured by West-Ward Pharmaceutical Corp. and have been 
repackaged into unit-of-use bottles containing 20 tablets (a 10-day 
supply) by PD-Rx Pharmaceuticals, consistent with current Good 
Manufacturing Practice (CGMP) and the Draft Guidance entitled 
``Expiration Dating of Unit-Dose Repackaged Drugs; Compliance Policy 
Guide.'' The product has been stored under conditions consistent 
with the manufacturer's labeled storage conditions and CGMP and is 
within its labeled expiration date. Once doxycycline hyclate tablets 
covered by this EUA have passed their expiration date, they are 
outside the scope of this EUA.
    HHS will determine whether to initiate distribution of product 
under this EUA to particular CRI locations based on:
    (a) whether the municipality has submitted a Strategic Security 
Plan acceptable to USPS and HHS;
    (b) whether the municipality, in collaboration with pertinent 
State public health officials, local law enforcement agencies, USPS, 
HHS, and other appropriate entities, has developed a mutually 
acceptable set of policies and procedures for recruiting USPS 
participants, screening them for fitness to receive doxycycline 
hyclate tablets, providing the doxycycline hyclate tablet emergency 
kits to eligible USPS participants and their household members, and 
maintaining the readiness of the participant force. Policies and 
procedures must also include screening for fitness to receive OSHA-
required personal protective equipment (PPE) (i.e., N95 masks) and 
provision of PPE to eligible USPS participants;\19\
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    \19\ The emergency use of unapproved, unlicensed, or uncleared 
PPE or the unapproved use of approved, licensed, or cleared PPE is 
not authorized as part of this EUA.
---------------------------------------------------------------------------

    (c) whether HHS has determined that it has sufficient funds to 
cover the costs of CRI Postal Module implementation in that 
location.
    After the distribution decision has been made by HHS and 
conveyed to FDA, the unit-of-use bottles will be delivered to secure 
site(s), where USPS and/or local public health authorities will 
assume control over them. Under this EUA, the unit-of-use bottles 
will be repackaged and relabeled\20\ into doxycycline hyclate tablet 
emergency kits by

[[Page 62512]]

licensed health care providers under the auspices of local public 
health authorities.
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    \20\ The term ``repackaged and relabeled'' will be used to refer 
to the activity of putting unit-of-use bottles into clear, tamper-
evident bags with the addition of certain written information.
---------------------------------------------------------------------------

    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 
the doxycycline hyclate tablet emergency kits, when used for the 
post-exposure prophylaxis of inhalational 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 
it is reasonable to believe that the doxycycline hyclate tablet 
emergency kits may be effective for the post-exposure prophylaxis of 
inhalational anthrax pursuant to section 564(c)(2)(A) of the Act. 
FDA has reviewed the scientific information available, including the 
information described in Section II above, and concludes that the 
doxycycline hyclate tablet emergency kits, when used for the post-
exposure prophylaxis of inhalational anthrax in the specified 
population, meet the criteria set forth in section 564(c) of the Act 
concerning safety and potential effectiveness.
    The pre-event distribution and use of doxycycline hyclate tablet 
emergency kits under this EUA must conform to and may not exceed the 
terms of this letter of authorization, including the scope and the 
conditions of authorization set forth below. Subject to the terms of 
this EUA and under the circumstances set forth in the Secretary of 
Homeland Security's determination under section 564(b)(1)(A) 
described above and the Secretary of HHS's corresponding declaration 
under section 564(b)(1), doxycycline hyclate tablet emergency kits 
are authorized for the post-exposure prophylaxis of inhalational 
anthrax for eligible USPS participants and their household members.
    This EUA will cease to be effective when the declaration of 
emergency is terminated under section 564(b)(2) of the Act or when 
the EUA is revoked under section 564(g) of the Act. When the EUA 
ceases to be effective, doxycycline hyclate tablet emergency kits 
will no longer be authorized for emergency use under this EUA, and 
doxycycline hyclate tablet emergency kits that have been distributed 
under this EUA must be collected as described in this letter of 
authorization.

IV. Conditions of Authorization

    Pursuant to section 564 of the Act, I am establishing the 
following conditions on this authorization:
    A. BARDA will conduct an educational and information program 
under appropriate conditions designed to ensure that health care 
providers or other authorized dispensers (hereinafter health care 
providers) distributing doxycycline hyclate tablet emergency kits 
are informed:
    (1) that FDA has authorized the emergency use of doxycycline 
hyclate tablet emergency kits for the post-exposure prophylaxis of 
inhalational anthrax for eligible USPS participants and their 
household members;
    (2) of the significant known and potential benefits and risks of 
the emergency use of doxycycline hyclate tablet emergency kits, and 
of the extent to which such benefits and risks are unknown for 
eligible USPS participants and their household members; and
    (3) of the alternatives to doxycycline hyclate tablet emergency 
kits for eligible USPS participants and their household members, 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 doxycycline hyclate tablet emergency kits, BARDA 
will ensure that the manufacturer's package insert is provided to 
all health care providers who distribute doxycycline hyclate tablet 
emergency kits to eligible USPS participants and their household 
members. With respect to conditions (1)-(3), BARDA will ensure that 
health care providers are provided with the authorized Fact Sheet 
for Health Care Providers. Any revision to the authorized Fact Sheet 
for Health Care Providers is subject to FDA's prior approval. BARDA 
will also ensure that all such health care providers are provided 
with the same information as that provided to eligible recipients 
described immediately below.
    B. BARDA will conduct an educational and information program 
under appropriate conditions designed to ensure that individuals to 
whom doxycycline hyclate tablet emergency kits are distributed are 
informed:
    (1) that FDA has authorized the emergency use of doxycycline 
hyclate tablet emergency kits for the post-exposure prophylaxis of 
inhalational anthrax for eligible USPS participants and their 
household members;
    (2) of the significant known and potential benefits and risks of 
the emergency use of doxycycline hyclate tablet emergency kits for 
eligible USPS participants and their household members, and of the 
extent to which such benefits and risks are unknown; and
    (3) of the option to accept or refuse administration of 
doxycycline hyclate tablet emergency kits, of the consequences, if 
any, of refusing administration of the product, and of the 
alternatives to the product that are available, and of their 
benefits and risks.
    As a condition of this authorization, BARDA will ensure that, 
prior to distribution of doxycycline hyclate tablet emergency kits, 
the authorized information that meets the requirements set forth 
above is provided to each eligible recipient (i.e., in the case of 
the household doxycycline hyclate emergency kit, the Fact Sheet for 
Recipients, home preparation instructions, and information placard 
(or bag pre-printed with placard information); in the case of the 
individual doxycycline hyclate emergency kit, the Fact Sheet for 
Recipients, and information placard (or bag pre-printed with placard 
information)). Any revision to the authorized information for 
potential recipients is subject to FDA's prior approval.
    C. USPS, in conjunction with appropriate local public health 
authorities, will also be responsible for ensuring that health care 
providers distributing doxycycline hyclate tablet emergency kits, 
and individuals to whom such emergency kits are dispensed, receive 
the authorized information described respectively in sections A and 
B above.
    USPS, in conjunction with appropriate local public health 
authorities, will distribute doxycycline hyclate tablet emergency 
kits to eligible recipients through health care providers who are 
qualified and licensed under applicable state law to dispense 
prescription drugs. The health care providers will distribute 
doxycycline hyclate tablet emergency kits under conditions that 
assure that otherwise eligible\21\ recipients are screened for 
medical eligibility (including contraindications) and are issued 
prescriptions for the doxycycline hyclate tablet emergency kit. Such 
conditions shall include exclusion of a USPS participant if:
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    \21\ USPS postal carriers are not eligible to receive a 
doxycycline hyclate tablet emergency kit if they have not passed 
their N95 mask fit test. See Section III, Scope of Authorization, 
above.
---------------------------------------------------------------------------

     No medical history and Health Assessment Form is 
available for the USPS participant or any member of their household; 
or
     Doxycycline hyclate is contraindicated for the USPS 
participant.
    USPS, in conjunction with appropriate public health authorities, 
must ensure documentation of eligibility or ineligibility to receive 
doxycycline hyclate tablet emergency kits. If doxycycline hyclate 
tablets are contraindicated for any of the USPS participant's 
household members, the USPS participant can still receive the 
doxycycline hyclate tablet emergency kit if s/he consents in writing 
to accept an incomplete kit and acknowledges that the household 
member(s) will have the same dependence on whatever community-based 
mass prophylaxis is available to the general public in an emergency.
    USPS, in conjunction with appropriate local public health 
authorities, will ensure that the authorized Health Assessment Form 
will be provided to and completed by potential recipients and then 
reviewed for eligibility by qualified health care providers, prior 
to dispensing to eligible recipients the doxycycline hyclate tablet 
emergency medical kits. Any revision of the authorized Health 
Assessment Form is subject to FDA's prior approval. A health care 
provider will review with each USPS participant his/her Health 
Assessment Form and the Health Assessment Form corresponding to each 
family member and will comply with applicable state prescribing laws 
before authorizing the filling of one unit-of-use bottle for each 
eligible USPS participant and household member. See Section D below 
for requirements regarding repackaging and relabeling of doxycycline 
hyclate tablet emergency kits prior to dispensing to eligible 
recipients.
    D. Doxycycline hyclate tablet emergency kits must be 
manufactured, (re)packaged, (re)labeled, and held according to 
applicable good manufacturing practice requirements, except that 
with respect to the doxycycline hyclate tablet emergency kits that 
will be repackaged and relabeled by appropriate local public health 
authorities using the doxycycline unit-of-use bottles manufactured 
by West-Ward Pharmaceutical Corp. and repackaged by PD-Rx 
Pharmaceuticals described in this EUA, the Secretary waives good 
manufacturing practice requirements applicable to the repackaging 
and relabeling

[[Page 62513]]

of such kits, subject to the following requirements
     USPS, in conjunction with appropriate local public 
health authorities, will be responsible for repackaging and 
relabeling doxycycline hyclate unit-of-use bottles into doxycycline 
hyclate tablet emergency kits through health care providers 
qualified and licensed under state law to dispense prescription 
drugs.
     The packaging and relabeling described below should be 
performed in a controlled environment such that there is adequate 
space, lighting, and freedom from debris and from other drug 
products to prevent mix-ups or cross-contamination.
     A health care provider who initially assembles the 
doxycycline hyclate tablet emergency kits will do the following:
    [cir] The health care provider will determine the number of 
authorized individuals in a household eligible to receive the 
product using the completed Health Assessment Form. The health care 
provider will document the prescription number, lot number, and 
expiration date of doxycycline hyclate for each authorized 
individual.
    [cir] The health care provider will record all prescription 
numbers for the household on the Healthcare Provider Quality 
Checklist.
    [cir] The health care provider will be responsible for 
maintaining an inventory/drug accountability record. At a minimum, 
this record will contain a running total/balance, the date filled, 
household name, and number of unit-of-use bottles dispensed to a 
household. The prescription number, lot number, and expiration date 
of the doxycycline hyclate tablets for each authorized individual 
will also be recorded.
    [cir] For the household doxycycline hyclate tablet emergency 
kit, the health care provider will place the correct number of unit-
of-use bottles of doxycycline hyclate (corresponding to the 
authorized USPS participant and each authorized household member) in 
one clear, tamper-evident plastic bag. Each unit-of-use bottle will 
be labeled with the appropriate authorized individual's name.
    [cir] For an individual doxycycline hyclate tablet emergency 
kit, the health care provider will place one unit-of-use bottle of 
doxycycline hyclate tablets in a separate clear, tamper-evident 
plastic bag for the authorized USPS participant for secure storage 
by the USPS at work. The unit-of-use bottle will be labeled with the 
authorized USPS participant's name.
    [cir] For the household doxycycline hyclate tablet emergency 
kit, the health care provider will place the Fact Sheet for 
Recipients, home preparation instructions, and MedWatch Form 3500 
inside and in the outer pocket of the clear, tamper-evident plastic 
bag; and, if the bag is not pre-printed with placard information, 
the health care provider will place the information placard inside 
the bag facing out so the wording is plainly visible.
    [cir] For the individual doxycycline hyclate tablet emergency 
kit, the health care provider will place the Fact Sheet for 
Recipients and MedWatch Form 3500 Form inside and in the outer 
pocket of the clear, tamper-evident plastic bag; and, if the bag is 
not pre-printed with placard information, the health care provider 
will place the information placard inside the bag facing out so the 
wording is plainly visible.
    [cir] The health care provider will complete the first page of 
the Healthcare Provider Quality Checklist, including signature and 
date.
    [cir] The health care provider will not seal the bag, and will 
give it to the identified health care provider to check the contents 
of the bags as described below.
     Before dispensing, a different health care provider 
will check each doxycycline hyclate tablet emergency kit that has 
been assembled as follows:
    [cir] Review and verify Health Assessment Forms for eligibility 
of USPS participant and each household member to receive the 
doxycycline hyclate tablet emergency kit.
    [cir] Verify that each unit-of-use bottle is labeled with the 
authorized individual's name.
    [cir] Verify the prescription number, lot number, and expiration 
date of the doxycycline hyclate tablets for each authorized 
individual on the Health Assessment Forms.
    [cir] Verify prescription numbers for each authorized individual 
on the Healthcare Provider Quality Checklist.
    [cir] For the household doxycycline hyclate tablet emergency 
kit, verify that the correct number of unit-of-use bottles of 
doxycycline hyclate tablets have been placed in the tamper-evident 
bag for that household based on the number of household members 
eligible. For the individual doxycycline hyclate tablet emergency 
kit, verify that the correct unit-of-use bottle of doxycycline 
hyclate tablets has been placed in the tamper-evident bag for the 
USPS participant for secure storage by USPS at work.
    [cir] Verify that the appropriate written information is inside 
the tamper-evident bags.
    [cir] Verify that the appropriate written information is in the 
outer pocket of the tamper-evident bags.
    [cir] If the information placard is not pre-printed on the 
outside of the tamper-evident bags, verify that the information 
placard is inside the tamper-evident bags and plainly visible.
    [cir] Complete the second page of the Healthcare Provider 
Quality Checklist, including signature and date.
    [cir] Seal the bags.
    [cir] Attach the Healthcare Provider Quality Checklist to the 
Health Assessment Forms for the household.
    [cir] The doxycycline hyclate tablet emergency kits may then be 
dispensed to the USPS participant along with review of the 
instructions and information.
    The authorized Healthcare Provider Quality Checklist and placard 
information will be used. Any revision of the authorized Healthcare 
Provider Quality Checklist or placard information is subject to 
FDA's prior approval.
    E. BARDA will record the amount of unit-of-use bottles of 
doxycycline hyclate tablets (including lot numbers) shipped under 
this EUA to the USPS/local public health authorities for use by 
eligible USPS participants and their households. Such records will 
be made available to FDA for inspection upon request. However, the 
appropriate public health authority responsible for distributing the 
doxycycline hyclate tablet emergency kits will prepare, maintain, 
and make available records and provide reports as directed by HHS/
FDA.
    F. Once an individual doxycycline hyclate tablet emergency kit 
has been dispensed to an eligible USPS participant, USPS will store 
the individual doxycycline hyclate tablet emergency kit in a secure 
location for the eligible USPS participant.
    G. BARDA, USPS, and appropriate local public health authorities 
may only provide written materials as included in BARDA's October 1, 
2008 submission, as amended on October 3, 2008, and authorized under 
this EUA. Any revisions or additional written materials to be 
provided by BARDA, USPS, or appropriate local public health 
authorities are subject to FDA's prior approval, except that USPS 
may provide additional materials for recruitment purposes to the 
extent that those materials are consistent with the materials 
included in BARDA's October 1, 2008 submission, as amended on 
October 3, 2008, that are authorized under this EUA.
    H. USPS, in conjunction with appropriate local public health 
authorities, will conduct an adverse event monitoring and reporting 
program designed to ensure that adverse events and medication errors 
associated with the use of the doxycycline hyclate tablet emergency 
kit are documented and reported within 15 days to MedWatch through 
www.fda.gov/medwatch, by submitting MedWatch Form 3500 in hard copy, 
or by calling 1-800-FDA-1088; and that any such report identifies 
the product as ``doxycycline hyclate tablet emergency kit'' and 
includes in the description of the event the designation ``USPS-CRI 
EUA'' or ``USPS-CRI Emergency Use Authorization.'' As part of this 
program, health care providers will be provided copies of MedWatch 
Form 3500, recipients will be instructed to report if they take any 
of the doxycycline hyclate tablets in their emergency kit and 
experience an adverse event or medication error, MedWatch Form 3500 
will be included in each doxycycline hyclate tablet emergency kit, 
and recipients will be provided with a toll-free number for 
contacting a health care provider if they experience an adverse 
event or medication error. USPS, in conjunction with appropriate 
local public health authorities, will maintain associated records 
until notified by FDA and will make such records available to FDA 
for inspection upon request.
    I. Appropriate local public health authorities will periodically 
verify and document that any undistributed doxycycline hyclate is 
within its labeled expiration date. Appropriate local public health 
authorities will maintain any

[[Page 62514]]

associated records until notified by FDA and will make such records 
available to FDA for inspection upon request. Appropriate local 
public health authorities will periodically verify and reconcile 
drug accountability records.
    J. USPS will obtain information from participating USPS carriers 
every six months documenting whether (a) they have stored their kits 
as instructed; (b) they are able to locate their kits readily; (c) 
their kits are intact; and (d) the doxycycline hyclate in their kits 
has not expired. USPS will ascertain the circumstances surrounding 
non-compliance for USPS participants who report (a) loss of a kit or 
(b) use of doxycycline hyclate from the emergency kit in the absence 
of instructions to do so. Depending on its findings, USPS may 
disqualify an individual from further participation. If the 
doxycycline hyclate emergency kit will expire before the next 6-
month follow-up, a new doxycycline hyclate emergency kit will be 
prescribed for eligible participants in accordance with paragraph D 
and the other terms of this letter. In such cases, USPS, in 
conjunction with local public health authorities, will be 
responsible for ensuring that such kits are collected, accounted 
for, and disposed of, as instructed by HHS. Drug accountability 
records will be maintained. USPS will also ascertain whether there 
have been any adverse events or medication errors associated with 
the doxycycline hyclate tablet emergency kit. If any such adverse 
events or medication errors have not previously been reported to FDA 
as outlined in paragraph H, they must be reported within 15 days to 
FDA. FDA has authorized BARDA's Form entitled ``Questions to 
Determine Status of Your Household Antibiotic Kit (HAK) or 
Individual Household Antibiotic Kit (iHAK)'' (Kit Status form). Any 
revision of the Kit Status form is subject to FDA's prior approval. 
USPS, in conjunction with appropriate local public health 
authorities, will be responsible for ensuring that completed Kit 
Status forms are maintained until notified by FDA. A report 
summarizing the information collected on Kit Status forms under this 
paragraph will be submitted to FDA within 30 days of gathering such 
information. Associated records will be made available to FDA for 
inspection upon request.
    K. USPS, in conjunction with appropriate public health 
authorities, will be responsible for collecting any expired 
doxycycline hyclate tablet emergency kits. USPS and/or appropriate 
local public health authorities will be responsible for disposing of 
expired doxycycline hyclate tablet emergency kits as instructed by 
HHS at that time. USPS, in conjunction with appropriate local public 
health authorities, will ensure that drug accountability records are 
maintained and reconciled. Such records shall be made available to 
FDA for inspection upon request.
    L. USPS, in conjunction with appropriate local public health 
authorities, will be responsible for ensuring that completed Health 
Assessment Forms, Healthcare Provider Quality Checklists, and any 
other records associated with this EUA are maintained until notified 
by FDA. Such records will be made available to FDA for inspection 
upon request.
    M. As a condition of this EUA, all advertising and promotional 
descriptive printed matter relating to the use of doxycycline 
hyclate tablet emergency kits authorized under this EUA shall be 
consistent with the Fact Sheets, home preparation instructions, and 
placard information, as well as the terms set forth in this EUA and 
other requirements set forth in the Act and FDA regulations.
    N. Upon termination of the declaration of emergency under 
section 564(b)(2) of the Act or upon revocation of this EUA under 
section 564(g) of the Act, USPS, in conjunction with appropriate 
public health authorities, will be responsible for collecting all 
doxycycline hyclate tablet emergency kits. USPS and/or local public 
health authorities will dispose of doxycycline hyclate emergency 
kits as instructed by HHS at that time. USPS, in conjunction with 
appropriate local public health authorities, will ensure that drug 
accountability records are maintained and reconciled. Such records 
will be made available to FDA for inspection upon request.
    O. HHS will notify FDA of its decision to add a CRI location and 
its decision to initiate distribution of doxycycline hyclate tablet 
emergency kits under this EUA to particular CRI locations.
    The emergency use of doxycycline hyclate tablet emergency kits 
as described in this letter of authorization must comply with the 
conditions above and all other terms of this authorization.

V. Duration of Authorization

    This EUA will be effective until 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.
Sincerely,
Randall W. Lutter, Ph.D.
Deputy Commissioner for Policy

    Dated: October 15, 2008.
Randall W. Lutter,
Deputy Commissioner for Policy.
[FR Doc. E8-25062 Filed 10-20-08; 8:45 am]

BILLING CODE 4160-01-S
