Amended 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, 30577-30584 [E9-15044]
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Federal Register / Vol. 74, No. 122 / Friday, June 26, 2009 / Notices
proposed information collections must
be received by the OMB desk officer at
the address below, no later than 5 p.m.
on July 27, 2009.
OMB, Office of Information and
Regulatory Affairs, Attention: CMS Desk
Officer, Fax Number: (202) 395–6974, Email: OIRA_submission@omb.eop.gov.
Dated: June 18, 2009.
Michelle Shortt,
Director, Regulations Development Group,
Office of Strategic Operations and Regulatory
Affairs.
[FR Doc. E9–15189 Filed 6–25–09; 8:45 am]
BILLING CODE 4120–01–P
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
National Institutes of Health
Proposed Collection; Comment
Request; NCCAM Customer Service
Data Collection
Summary: In compliance with the
requirement of Section 3506(c)(2)(A) of
the Paperwork Reduction Act of 1995,
for opportunity for public comment on
proposed data collection projects, the
National Center for Complementary and
Alternative Medicine (NCCAM), at the
National Institutes of Health (NIH), will
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projects to be submitted to the Office of
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review and approval.
Proposed Collection: Title: NCCAM
Customer Service Data Collection. Type
of Information Collection Request:
Revision. Need and Use of Information
Collection: NCCAM provides the public,
patients, families, health care providers,
complementary and alternative
medicine (CAM) practitioners, and
others with the latest scientifically
based information on CAM and
information about NCCAM’s programs
through a variety of channels, including
its toll-free telephone information
service and its quarterly newsletter. To
ensure that NCCAM is effectively
serving all audiences, NCCAM needs to
continue to measure customer
Estimated number of respondents
Type of respondents
Telephone survey:
Individuals or households .................................................................
The annualized cost to respondents is
estimated at $1,770 for the telephone
survey. There are no Capital Costs to
report. There are no Operating or
Maintenance Costs to report.
Request for Comments: Written
comments and/or suggestions from the
public and affected agencies are invited
on the following points: (1) Whether the
proposed collection of information is
necessary for the proper performance of
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whether the information will have
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including the validity of the
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collected; and (4) Ways to minimize the
burden of the collection of information
on those who are to respond, including
the use of appropriate automated,
electronic, mechanical, or other
technological collection techniques or
other forms of information technology.
For Further Information Contact: To
request more information on the
proposed project or to obtain a copy of
the data collection plans and
instruments, contact Christy Thomsen,
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satisfaction with NCCAM telephone
interactions. This effort involves a
telephone survey consisting of 10
questions, which are asked of 25 percent
of all callers, for an annual total of
approximately 1,210 respondents.
NCCAM uses the data collected from the
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measure service use among special
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effective media and messages to reach
these audiences. Frequency of Response:
Once. Affected Public: Individuals and
households. Type of Respondents:
Patients, spouses/family/friends of
patients, health care providers,
physicians, CAM practitioners, or other
individuals contacting the NCCAM
Clearinghouse.
The annual reporting burden is as
follows.
Estimated number of responses per respondent
1,210
Average burden
hours per
response
1
Estimated total
annual burden
hours requested
0.075
Director, Office of Communications and
Public Liaison, NCCAM, 31 Center
Drive, Room 2B11, Bethesda, MD
20892–2182; or fax your request to 301–
402–4741; or e-mail
thomsenc@mail.nih.gov. Ms. Thomsen
can be contacted by telephone at 301–
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Comments Due Date: Comments
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best assured of having their full effect if
received within 60 days of the date of
this publication.
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Dated: June 18, 2009.
Christy Thomsen,
Director, Office of Communications and
Public Liaison, National Center for
Complementary and Alternative Medicine,
National Institutes of Health.
[FR Doc. E9–15058 Filed 6–25–09; 8:45 am]
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HHS.
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Food and Drug Administration
[Docket No. FDA–2009–N–0264]
Amended 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:
ACTION:
Food and Drug Administration,
Notice.
SUMMARY: The Food and Drug
Administration (FDA) is announcing an
amendment to the Emergency Use
Authorization (EUA) (the Authorization)
for doxycycline hyclate tablet
emergency kits for eligible U.S. Postal
Service (USPS) participants in the Cities
Readiness Initiative (CRI) and their
household members issued on October
3, 2008, 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 (ASPR),
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Health and Human Services (HHS).
Following issuance of FDA’s October 3,
2008, Authorization letter, on February
19, 2009, BARDA submitted a request
on behalf of ASPR, to amend the
Authorization. In response to BARDA’s
request, FDA amended the
Authorization letter and reissued the
Authorization letter in its entirety on
February 25, 2009. The Authorization,
as amended and reissued in its entirety,
is reprinted in this document.
DATES: The amended Authorization is
effective as of February 25, 2009.
ADDRESSES: Submit written requests for
single copies of the EUA to the Office
of Counterterrorism and Emerging
Threats (HF–29), Food and Drug
Administration, 5600 Fishers Lane, 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. Amendment to the October 3, 2008,
Authorization for Doxycycline Hyclate
in Emergency Kits
On September 23, 2008, under section
564(b)(1)(A) of the the act (21 U.S.C.
360bbb-3(b)(1)(A)), as amended by the
Project BioShield Act of 2004 (Public
Law 108–276), 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, the Secretary of
HHS, 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 HHS was published
in the Federal Register on 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
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household members. As required under
section 564(h)(1) of the act, on October
21, 2008, FDA published in the Federal
Register notice of the Authorization for
doxycycline hyclate tablet emergency
kits for eligible USPS participants in the
CRI and their household members,
including an explanation of the reasons
for its issuance (73 FR 62057, October
21, 2008). On February 19, 2009,
BARDA submitted a request on behalf of
ASPR to amend the Authorization to
make certain changes to the written
information authorized to accompany
the doxycycline hyclate tablets and to
the roles and responsibilities provided
for in the Authorization. On February
25, 2009, in response to BARDA’s
request, FDA amended the
Authorization letter and reissued the
Authorization letter in its entirety.
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 kits2 for
inhalational anthrax, pursuant to section 564
of the Federal Food, Drug, and Cosmetic Act
(the Act). Your request is specifically for
eligible3 United States Postal Service (USPS)
participants in the Cities Readiness Initiative
(CRI) (hereinafter USPS participants) and
their household members.4
On September 23, 2008, pursuant to
section 564(b)(1)(A) of the Act, 21 U.S.C.
§ 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.5 On October 1, 2008,
pursuant to section 564(b) of the Act, and on
II. Electronic Access
An electronic version of this notice
and the full text of the Authorization are
available on the Internet at https://
www.regulations.gov.
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.
3 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.
4 Your submissions define ‘‘household member’’
as ‘‘anyone that considers that address as his or her
permanent place of residence.’’
5 Memorandum from Michael Chertoff to Michael
O. Leavitt, Determination Pursuant to § 564 of the
Federal Food, Drug, and Cosmetic Act (Sept. 23,
2008).
6 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).
7 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.
8 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 preexposure, 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.
III. The Authorization
After 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 were met, on October 3, 2008,
FDA authorized the emergency use of
doxycycline hyclate tablet emergency
kits for eligible USPS participants in the
CRI and their household members. The
letter of authorization in its entirety, as
amended on February 25, 2009, follows:
February 25, 2009
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,1
1 BARDA submitted an amendment on October 3,
2008. Following issuance of FDA’s October 3, 2008,
authorization letter, BARDA submitted a request on
behalf of the Office of the Assistant Secretary for
Preparedness and Response (ASPR) on February 19,
2009, to further amend the authorization. This
amended authorization letter responds to that
request.
2 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
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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. § 360bbb-3(a).6,7 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,8 subject to the
terms of this authorization.
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-ofdispensing (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
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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.9
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 preprinted 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 tamperevident, 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
9 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 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,10 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
(3) there is no adequate, approved, and
available alternative to doxycycline
hyclate tablet emergency kits for the
post-exposure prophylaxis of
inhalational anthrax.11
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 postexposure 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 postexposure prophylaxis of inhalational anthrax,
as summarized below.
In November 2001, as part of a public
health response to the use of anthrax spores
10 The Act uses the terms ‘‘diagnosing, treating, or
preventing’’ in Section 564(c)(2)(A). Post-exposure
prophylaxis is encompassed by these statutory
terms.
11 No other criteria of issuance have been
prescribed by regulation under section 564(c)(4) of
the Act.
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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.12 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.13 FDA based these conclusions on the
following:
• 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
anthracis in 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
12 See 66 Fed. Reg. 55679 (Nov. 2, 2001); Docket
01N-0494.
13 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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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. WestWard’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 postexposure 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 -- doxycycline14 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.
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 postexposure 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
14 In this study, participants who were allergic to
doxycycline or for whom doxycycline was
otherwise contraindicated received ciprofloxacin.
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Fmt 4703
Sfmt 4703
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
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 postexposure 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
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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 postexposure 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.15
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
15 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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16:39 Jun 25, 2009
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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
anthrax16 for eligible17 USPS participants in
the Postal Module of CRI and their household
members.
The doxycycline hyclate tablets authorized
under this EUA were manufactured by WestWard 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.
ASPR 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 ASPR;
(b) whether the municipality, in
collaboration with pertinent State public
health officials, local law enforcement
agencies, USPS, ASPR, 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;18
(c) whether ASPR 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 ASPR and conveyed to FDA, the
unit-of-use bottles will be delivered to secure
site(s), where the participating public health
16 See
footnote 8.
footnote 3.
18 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.
30581
authority(ies) will assume control over them.
Under this EUA, the unit-of-use bottles will
be repackaged and relabeled19 into
doxycycline hyclate tablet emergency kits by
licensed health care providers under the
auspices of the participating public health
authority(ies).
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 provide to the participating
public health authority(ies) the written
materials included in BARDA’s October 3,
2008 submission, as amended on February
19, 2009, and authorized under this EUA.
B. The participating public health
authority(ies) will conduct an educational
and information program under appropriate
17 See
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19 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.
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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, the participating public
health authority(ies) 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), the participating public
health authority(ies) 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. The
participating public health authority(ies) will
also ensure that all such health care
providers are provided with the same
information as that provided to eligible
recipients described immediately below.
C. The participating public health
authority(ies) 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, the
participating public health authority(ies) will
ensure that, prior to distribution of
doxycycline hyclate tablet emergency kits,
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16:39 Jun 25, 2009
Jkt 217001
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.
D. The participating public health
authority(ies) 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
eligible20 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:
• 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.
The participating public health
authority(ies) 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 will be responsible for providing
copies of the authorized Health Assessment
Form to potential USPS participants. If they
elect to apply for participation, potential
USPS participants and their household
members should complete Health
Assessment Forms and mail them to the
participating public health authority(ies) at
the address provided. Qualified health care
providers, under the auspices of the
participating public health authority(ies),
will be responsible for reviewing the
completed Health Assessment Forms to
determine whether potential recipients are
eligible to receive doxycycline hyclate tablet
emergency kits prior to dispensing such kits
to eligible USPS recipients . 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
20 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.
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Fmt 4703
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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.
E. 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 participating
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
of such kits, subject to the following
requirements
• The participating public health
authority(ies) 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 crosscontamination.
• A health care provider who initially
assembles the doxycycline hyclate tablet
emergency kits will do the following:
Æ 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.
Æ The health care provider will record all
prescription numbers for the household
on the Healthcare Provider Quality
Checklist.
Æ 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-ofuse 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.
Æ 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
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household member) in one clear, tamperevident plastic bag. Each unit-of-use
bottle will be labeled with the
appropriate authorized individual’s
name.
Æ 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.
Æ 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.
Æ 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.
Æ The health care provider will complete
the first page of the Healthcare Provider
Quality Checklist, including signature
and date.
Æ 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:
Æ Review and verify Health Assessment
Forms for eligibility of USPS participant
and each household member to receive
the doxycycline hyclate tablet emergency
kit.
Æ Verify that each unit-of-use bottle is
labeled with the authorized individual’s
name.
Æ Verify the prescription number, lot
number, and expiration date of the
doxycycline hyclate tablets for each
authorized individual on the Health
Assessment Forms.
Æ Verify prescription numbers for each
authorized individual on the Healthcare
Provider Quality Checklist.
Æ 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
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16:39 Jun 25, 2009
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tablets has been placed in the tamperevident bag for the USPS participant for
secure storage by USPS at work.
Æ Verify that the appropriate written
information is inside the tamper-evident
bags.
Æ Verify that the appropriate written
information is in the outer pocket of the
tamper-evident bags.
Æ If the information placard is not preprinted on the outside of the tamperevident bags, verify that the information
placard is inside the tamper-evident bags
and plainly visible.
Æ Complete the second page of the
Healthcare Provider Quality Checklist,
including signature and date.
Æ Seal the bags.
Æ Attach the Healthcare Provider Quality
Checklist to the Health Assessment
Forms for the household.
Æ 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.
F. ASPR will record the amount of unit-ofuse bottles of doxycycline hyclate tablets
(including lot numbers) shipped under this
EUA to the participating public health
authority(ies) for use by eligible USPS
participants and their households. Such
records will be made available to FDA for
inspection upon request. However, the the
participating public health authority(ies)
responsible for distributing the doxycycline
hyclate tablet emergency kits will prepare,
maintain, and make available records and
provide reports as directed by ASPR/FDA.
G. 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.
H. ASPR, USPS, and the participating
public health authority(ies) may only provide
written materials as included in BARDA’s
October 3, 2008 submission, as amended on
February 19, 2009, and authorized under this
EUA. Any revisions or additional written
materials to be provided by ASPR, USPS, or
the participating public health authority(ies)
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 3,
2008 submission, as amended on February
19, 2009, that are authorized under this EUA.
The participating public health authority(ies)
may evaluate activities undertaken pursuant
to this authorization. To ensure consistency
with this authorization, the participating
public health authority(ies) must consult
with FDA before conducting such
evaluations.
I. The participating public health
authority(ies) will conduct an adverse event
monitoring and reporting program designed
to ensure that adverse events and medication
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30583
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 ‘‘USPSCRI 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 tollfree number for contacting a health care
provider if they experience an adverse event
or medication error. The participating public
health authority(ies) will maintain associated
records until notified by FDA and will make
such records available to FDA for inspection
upon request.
J. The participating public health
authority(ies) will periodically verify and
document that any undistributed
doxycycline hyclate is within its labeled
expiration date. The participating public
health authority(ies) will maintain any
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.
K. USPS will be responsible for providing
USPS participants every six months with the
Form entitled ‘‘Questions to Determine
Status of Your Household Antibiotic Kit
(HAK)’’ (Kit Status form) to document
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 participants should complete
these forms and mail them to the
participating public health authority(ies) at
the address provided. The participating
public health authority(ies) will ascertain the
circumstances surrounding non-compliance
for USPS participants who (a) report loss of
a kit; (b) report use of doxycycline hyclate
from the emergency kit in the absence of
instructions to do so; or (c) fail to return a
completed Kit Status Form. Depending on its
findings, the participating public health
authority(ies) 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 will be responsible for
collecting such kits and turning them over to
the participating public health authority(ies),
which then will be responsible for
accounting for them and disposing ofthem as
instructed by ASPR. The participating public
health authority(ies) will maintain drug
accountability records. The participating
public health authority(ies) will also
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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 ASPR’s
Form entitled ‘‘Questions to Determine
Status of Your Household Antibiotic Kit
(HAK)’’ (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.
L. USPS will be responsible for collecting
any expired doxycycline hyclate tablet
emergency kits and turning them over to the
participating public health authority(ies).
The participating public health authority(ies)
will be responsible for disposing of expired
doxycycline hyclate tablet emergency kits as
instructed by ASPR at that time. The
participating public health authority(ies) will
ensure that drug accountability records are
maintained and reconciled. Such records
shall be made available to FDA for inspection
upon request.
M. USPS and the participating public
health authority(ies) 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.
N. 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.
O. 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 will be responsible
for collecting all doxycycline hyclate tablet
emergency kits and turning them over to the
participating public health authority(ies).
The participating public health authority(ies)
will dispose of doxycycline hyclate
emergency kits as instructed by ASPR at that
time. The participating public health
authority(ies) will ensure that drug
accountability records are maintained and
reconciled. Such records will be made
available to FDA for inspection upon request.
P. 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
VerDate Nov<24>2008
16:39 Jun 25, 2009
Jkt 217001
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.
Randall W. Lutter, Ph.D.
Deputy Commissioner for Policy
Dated: June 17, 2009.
Randall W. Lutter,
Deputy Commissioner for Policy.
[FR Doc. E9–15044 Filed 6–25–09; 8:45 am]
BILLING CODE 4160–01–S
DEPARTMENT OF HEALTH AND
HUMAN SERVICES
Centers for Medicare & Medicaid
Services
[CMS–2896–FN2]
Medicare and Medicaid Programs;
Approval of the Joint Commission’s
Continued Deeming Authority for
Critical Access Hospitals
AGENCY: Centers for Medicare &
Medicaid Services (CMS), HHS.
ACTION: Final Notice of Removal of
Conditional Probationary Status.
SUMMARY: Based on our review and
observations, we have determined that
the Joint Commission’s accreditation
standards for critical access hospitals
(CAHs) meet or exceed our
requirements. Therefore, this final
notice announces our decision to
approve without condition the Joint
Commission’s request for continued
recognition as a national accreditation
program for CAHs seeking to participate
in the Medicare or Medicaid programs.
DATES: Effective Date: This final notice
of approval is effective November 21,
2008 through November 21, 2011.
FOR FURTHER INFORMATION CONTACT:
Cindy Melanson, (410) 786–0310.
Patricia Chmielewski, (410) 786–6899.
SUPPLEMENTARY INFORMATION:
I. Background
Under the Medicare program, eligible
beneficiaries may receive covered
services in a Critical Access Hospital
(CAH) provided certain requirements
are met. Sections 1820(c)(2)(B) and
1861(mm) of the Social Security Act
(the Act) establish distinct criteria for
facilities seeking designation as a CAH.
Under this authority, the minimum
requirements that a CAH must meet to
participate in Medicare are set forth in
regulations at 42 CFR part 485, subpart
F (Conditions of Participation: Critical
Access Hospitals (CAHs)) which
PO 00000
Frm 00085
Fmt 4703
Sfmt 4703
determine the basis and scope of CAH
covered services. Conditions for
Medicare payment for CAHs are set
forth at § 413.70. Applicable regulations
concerning provider agreements are
located in 42 CFR part 489 (Provider
Agreements and Supplier Approval) and
those pertaining to facility survey and
certification are located in 42 CFR part
488, subparts A and B.
In general, we approve a CAH for
participation in the Medicare program if
it is participating as a hospital at the
time it applies for CAH designation, and
it is in compliance with part 482
(Conditions of Participation for
Hospitals) and part 485, subpart F
(Conditions of Participation: Critical
Access Hospital (CAHs)).
For a CAH to enter into a provider
agreement, a State survey agency must
certify that the CAH is in compliance
with the conditions or standards set
forth in section 1820 of the Act and part
485 of our regulations. Thereafter, the
CAH is subject to ongoing review by a
State survey agency to determine
whether it continues to meet the
Medicare requirements. There is,
however, an alternative to State
compliance surveys. Accreditation by a
nationally-recognized accreditation
program can substitute for ongoing State
review.
Section 1865(a)(1) of the Act provides
that, if a provider entity demonstrates
through accreditation by an approved
national accreditation organization (AO)
that all applicable Medicare conditions
are met or exceeded, we may ‘‘deem’’
that provider entity as having met the
requirements. Accreditation by an AO is
voluntary and is not required for
Medicare participation.
A national AO applying for approval
of deeming authority under part 488,
subpart A must provide us with
reasonable assurance that the AO
requires the accredited provider entities
to meet requirements that are at least as
stringent as the Medicare conditions of
participation. Our regulations
concerning re-approval of AOs are set
forth at § 488.4 and § 488.8(d)(3). The
regulations at § 488.8(d)(3) require AOs
to reapply for continued approval of
deeming authority every 6 years, or
sooner as we determine. The regulations
at § 488.8(f)(3)(i) provide CMS the
authority to grant conditional approval
of an AO’s deeming authority, with a
180-day probationary period, if the AO
has not adopted comparable standards
during the reapplication process.
We received a complete application
from the Joint Commission for
continued recognition as a national
accrediting organization for CAHs on
March 28, 2008. In accordance with the
E:\FR\FM\26JNN1.SGM
26JNN1
Agencies
[Federal Register Volume 74, Number 122 (Friday, June 26, 2009)]
[Notices]
[Pages 30577-30584]
From the Federal Register Online via the Government Printing Office [www.gpo.gov]
[FR Doc No: E9-15044]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-2009-N-0264]
Amended 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.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is announcing an
amendment to the Emergency Use Authorization (EUA) (the Authorization)
for doxycycline hyclate tablet emergency kits for eligible U.S. Postal
Service (USPS) participants in the Cities Readiness Initiative (CRI)
and their household members issued on October 3, 2008, 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 (ASPR),
[[Page 30578]]
Health and Human Services (HHS). Following issuance of FDA's October 3,
2008, Authorization letter, on February 19, 2009, BARDA submitted a
request on behalf of ASPR, to amend the Authorization. In response to
BARDA's request, FDA amended the Authorization letter and reissued the
Authorization letter in its entirety on February 25, 2009. The
Authorization, as amended and reissued in its entirety, is reprinted in
this document.
DATES: The amended Authorization is effective as of February 25, 2009.
ADDRESSES: Submit written requests for single copies of the EUA to the
Office of Counterterrorism and Emerging Threats (HF-29), Food and Drug
Administration, 5600 Fishers Lane, 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. Amendment to the October 3, 2008, Authorization for Doxycycline
Hyclate in Emergency Kits
On September 23, 2008, under section 564(b)(1)(A) of the the act
(21 U.S.C. 360bbb-3(b)(1)(A)), as amended by the Project BioShield Act
of 2004 (Public Law 108-276), 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, the Secretary of HHS,
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
HHS was published in the Federal Register on 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. As required under section 564(h)(1) of the act, on
October 21, 2008, FDA published in the Federal Register notice of the
Authorization for doxycycline hyclate tablet emergency kits for
eligible USPS participants in the CRI and their household members,
including an explanation of the reasons for its issuance (73 FR 62057,
October 21, 2008). On February 19, 2009, BARDA submitted a request on
behalf of ASPR to amend the Authorization to make certain changes to
the written information authorized to accompany the doxycycline hyclate
tablets and to the roles and responsibilities provided for in the
Authorization. On February 25, 2009, in response to BARDA's request,
FDA amended the Authorization letter and reissued the Authorization
letter in its entirety.
II. Electronic Access
An electronic version of this notice and the full text of the
Authorization are available on the Internet at https://www.regulations.gov.
III. The Authorization
After 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 were met, on October 3, 2008, FDA authorized
the emergency use of doxycycline hyclate tablet emergency kits for
eligible USPS participants in the CRI and their household members. The
letter of authorization in its entirety, as amended on February 25,
2009, follows:
February 25, 2009
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,\1\ 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\2\ for inhalational anthrax, pursuant to
section 564 of the Federal Food, Drug, and Cosmetic Act (the Act).
Your request is specifically for eligible\3\ United States Postal
Service (USPS) participants in the Cities Readiness Initiative (CRI)
(hereinafter USPS participants) and their household members.\4\
---------------------------------------------------------------------------
\1\ BARDA submitted an amendment on October 3, 2008. Following
issuance of FDA's October 3, 2008, authorization letter, BARDA
submitted a request on behalf of the Office of the Assistant
Secretary for Preparedness and Response (ASPR) on February 19, 2009,
to further amend the authorization. This amended authorization
letter responds to that request.
\2\ 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.
\3\ 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.
\4\ Your submissions define ``household member'' as ``anyone
that considers that address as his or her permanent place of
residence.''
---------------------------------------------------------------------------
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.\5\ On October 1, 2008, pursuant to section 564(b) of the
Act, and on
[[Page 30579]]
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).\6,7\ 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,\8\ subject to the terms of
this authorization.
---------------------------------------------------------------------------
\5\ Memorandum from Michael Chertoff to Michael O. Leavitt,
Determination Pursuant to Sec. 564 of the Federal Food, Drug, and
Cosmetic Act (Sept. 23, 2008).
\6\ 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).
\7\ 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.
\8\ 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.
---------------------------------------------------------------------------
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.\9\
---------------------------------------------------------------------------
\9\ 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.
---------------------------------------------------------------------------
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 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,\10\ 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
---------------------------------------------------------------------------
\10\ The Act uses the terms ``diagnosing, treating, or
preventing'' in Section 564(c)(2)(A). Post-exposure prophylaxis is
encompassed by these statutory terms.
---------------------------------------------------------------------------
(3) there is no adequate, approved, and available alternative to
doxycycline hyclate tablet emergency kits for the post-exposure
prophylaxis of inhalational anthrax.\11\
---------------------------------------------------------------------------
\11\ No other criteria of issuance have been prescribed by
regulation under section 564(c)(4) of the Act.
---------------------------------------------------------------------------
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
[[Page 30580]]
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.\12\
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.\13\
FDA based these conclusions on the following:
---------------------------------------------------------------------------
\12\ See 66 Fed. Reg. 55679 (Nov. 2, 2001); Docket 01N-0494.
\13\ Id. The Federal Register notice further requested that
applicants for these products submit labeling supplements to update
their package inserts with this information.
---------------------------------------------------------------------------
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 anthracis in 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\14\ 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.
---------------------------------------------------------------------------
\14\ In this study, participants who were allergic to
doxycycline or for whom doxycycline was otherwise contraindicated
received ciprofloxacin.
---------------------------------------------------------------------------
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 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
[[Page 30581]]
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.\15\
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\15\ 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.
---------------------------------------------------------------------------
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\16\ for
eligible\17\ USPS participants in the Postal Module of CRI and their
household members.
---------------------------------------------------------------------------
\16\ See footnote 8.
\17\ See footnote 3.
---------------------------------------------------------------------------
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.
ASPR 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 ASPR;
(b) whether the municipality, in collaboration with pertinent State
public health officials, local law enforcement agencies, USPS, ASPR,
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;\18\
---------------------------------------------------------------------------
\18\ 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 ASPR 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 ASPR and
conveyed to FDA, the unit-of-use bottles will be delivered to secure
site(s), where the participating public health authority(ies) will
assume control over them. Under this EUA, the unit-of-use bottles
will be repackaged and relabeled\19\ into doxycycline hyclate tablet
emergency kits by licensed health care providers under the auspices
of the participating public health authority(ies).
---------------------------------------------------------------------------
\19\ 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 provide to the participating public health
authority(ies) the written materials included in BARDA's October 3,
2008 submission, as amended on February 19, 2009, and authorized
under this EUA.
B. The participating public health authority(ies) will conduct
an educational and information program under appropriate
[[Page 30582]]
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, the
participating public health authority(ies) 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), the participating public health
authority(ies) 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. The participating public health
authority(ies) will also ensure that all such health care providers
are provided with the same information as that provided to eligible
recipients described immediately below.
C. The participating public health authority(ies) 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, the participating public
health authority(ies) 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.
D. The participating public health authority(ies) 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\20\ 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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\20\ 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.
The participating public health authority(ies) 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 will be responsible for providing copies of the authorized
Health Assessment Form to potential USPS participants. If they elect
to apply for participation, potential USPS participants and their
household members should complete Health Assessment Forms and mail
them to the participating public health authority(ies) at the
address provided. Qualified health care providers, under the
auspices of the participating public health authority(ies), will be
responsible for reviewing the completed Health Assessment Forms to
determine whether potential recipients are eligible to receive
doxycycline hyclate tablet emergency kits prior to dispensing such
kits to eligible USPS recipients . 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.
E. 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 participating 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 of such kits, subject to the following requirements
The participating public health authority(ies) 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
[[Page 30583]]
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.
F. ASPR will record the amount of unit-of-use bottles of
doxycycline hyclate tablets (including lot numbers) shipped under
this EUA to the participating public health authority(ies) for use
by eligible USPS participants and their households. Such records
will be made available to FDA for inspection upon request. However,
the the participating public health authority(ies) responsible for
distributing the doxycycline hyclate tablet emergency kits will
prepare, maintain, and make available records and provide reports as
directed by ASPR/FDA.
G. 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.
H. ASPR, USPS, and the participating public health
authority(ies) may only provide written materials as included in
BARDA's October 3, 2008 submission, as amended on February 19, 2009,
and authorized under this EUA. Any revisions or additional written
materials to be provided by ASPR, USPS, or the participating public
health authority(ies) 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 3, 2008 submission, as amended on
February 19, 2009, that are authorized under this EUA. The
participating public health authority(ies) may evaluate activities
undertaken pursuant to this authorization. To ensure consistency
with this authorization, the participating public health
authority(ies) must consult with FDA before conducting such
evaluations.
I. The participating public health authority(ies) 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. The participating public health authority(ies)
will maintain associated records until notified by FDA and will make
such records available to FDA for inspection upon request.
J. The participating public health authority(ies) will
periodically verify and document that any undistributed doxycycline
hyclate is within its labeled expiration date. The participating
public health authority(ies) will maintain any 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.
K. USPS will be responsible for providing USPS participants
every six months with the Form entitled ``Questions to Determine
Status of Your Household Antibiotic Kit (HAK)'' (Kit Status form) to
document 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 participants should complete these forms and mail them
to the participating public health authority(ies) at the address
provided. The participating public health authority(ies) will
ascertain the circumstances surrounding non-compliance for USPS
participants who (a) report loss of a kit; (b) report use of
doxycycline hyclate from the emergency kit in the absence of
instructions to do so; or (c) fail to return a completed Kit Status
Form. Depending on its findings, the participating public health
authority(ies) 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 will be responsible for collecting such kits and
turning them over to the participating public health authority(ies),
which then will be responsible for accounting for them and disposing
ofthem as instructed by ASPR. The participating public health
authority(ies) will maintain drug accountability records. The
participating public health authority(ies) will also
[[Page 30584]]
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 ASPR's Form
entitled ``Questions to Determine Status of Your Household
Antibiotic Kit (HAK)'' (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.
L. USPS will be responsible for collecting any expired
doxycycline hyclate tablet emergency kits and turning them over to
the participating public health authority(ies). The participating
public health authority(ies) will be responsible for disposing of
expired doxycycline hyclate tablet emergency kits as instructed by
ASPR at that time. The participating public health authority(ies)
will ensure that drug accountability records are maintained and
reconciled. Such records shall be made available to FDA for
inspection upon request.
M. USPS and the participating public health authority(ies) 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.
N. 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.
O. 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 will be responsible for collecting
all doxycycline hyclate tablet emergency kits and turning them over
to the participating public health authority(ies). The participating
public health authority(ies) will dispose of doxycycline hyclate
emergency kits as instructed by ASPR at that time. The participating
public health authority(ies) will ensure that drug accountability
records are maintained and reconciled. Such records will be made
available to FDA for inspection upon request.
P. 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.
Randall W. Lutter, Ph.D.
Deputy Commissioner for Policy
Dated: June 17, 2009.
Randall W. Lutter,
Deputy Commissioner for Policy.
[FR Doc. E9-15044 Filed 6-25-09; 8:45 am]
BILLING CODE 4160-01-S