Public Health Authorities; Unapproved EUA Product

Contains Nonbinding Recommendations

GUIDANCE
Emergency Use Authorization of
Medical Products
For single copies of this guidance, please contact:
OfJice of Counterterrorism Policy and Planning (HF-29)
OfJice of the Commissioner
Food and Drug Administration
5600 Fishers Lane, Room 14C-26
Rockville, MD 2085 7
(Phone 301-82 7-4067)

U.S. Department of Health and Human Sewices
Food and Drug Administration
Office of the Commissioner
Office of Counterterrorism Policy and Planning
July 2007

Contains Nonbinding Recommendations

TABLE OF CONTENTS
I. INTRODUCTION .......

........................................................................................................1

I1. DECLARATION O F EMERGENCY .................................................................................. 3

Publication .........................................................................................................................5
I11. ELIGIBILITY FOR AN EMERGENCY USE AUTHORIZATION (EUA) ................... 5

Categories of Products ......................................................................................................6
Effectiveness ...................................................................................................................... 7
Risk-Benefit Analysis ..................................................................................................... 8
Alternatives to the Product .............................................................................................. 9
IV . REQUEST FOR CONSIDERATION FOR AN EUA ...................................................... 9
Pre-Emergency Activities ............................................................................................ 10
Emergency Activities ..................................................................................................... 11
Submission of a Request for Consideration ................................................................11
Summary of Recommended Data to Support a Request for Consideration ............. 12
Recommended Safety Data ............................................................................................ 13
Recommended Effectiveness Data ............................................................................. 14
Other Data Considerations ............................................................................................15
Discussion of Risks and Benefits .................................................................................... 17
Format of Submissions ................................................................................................... 17
V . PROCESSING O F AN EUA .......................................................................................... 19
Prioritization of Pre-Emergency Activities .................................................................. 19
Review of Pre-Emergency Submissions ........................................................................ 20
Prioritization of Requests for Consideration for an EUA During a Declared
Emergency .......................................................................................................................21
Review Process for a Request for Consideration for an EUA .................................... 22
Timelines for Review .............................................................................................. 23

Contains Nonbinding Recommendations

VI . CONDITIONS O F AUTHORIZATION ..........................................................................24
Conditions of Authorization for Emergency Use of an Unapproved Product .......... 25
Conditions of Authorization for Emergency Use of an Approved Product for an
Unapproved Use ...........................................................................................................25
Additional Conditions of Authorization ....................................................................... 27
Summary of Conditions of Described in Section 564(e) ..............................................34
Option To Carry Out Authorized Activities ................................................................ 35
Rules of Statutory Construction ....................................................................................35
VII . REVOCATION OR TERMINATION OF AN EUA ......................................................35
Revocation ..................................................................................................................... 36
Termination ..................................................................................................................... 36
Continued use .................................................................................................................. 36
VIII . PREEMPTION ................................................................................................................. 37
IX. LIABILITY PROTECTION AND COMPENSATION
UNDER OTHER STATUTES ....................................................................................... 39
APPENDIX A .FACT SHEET for the Health Care Provider o r Authorized Dispenser ....40
APPENDIX B .FACT SHEET for the Recipient ................................................................... 45
APPENDIX C .
CONTACT INFORMATION for Liability and Compensation
Programs Under Other Statutes .............................................................................. 47

I
2

GUIDANCE'
Emergency Use Authorization of Medical Products

3

This guidance document represents the Food and Drug Administration's (FDA's) current
thinking on this topic. It does not create or confer any rights for or on any person and does not
operate to bind FDA or the public. You may use an alternative approach if the approach satisfies
the requirements of the applicable statutes and regulations. If you want to discuss an alternative
approach, please contact the appropriate FDA staff.
9
10
1I

I. INTRODUCTION

12
13

This guidance explains FDA's policies for authorizing the emergency use of medical products

14

under section 564 of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 360bbb-

15

3), which was amended by the Project BioShield Act of 2004 (Public Law 108-276).2 Section

16

564 permits the FDA Commissioner to authorize the use of an unapproved medical product or an

I7

unapproved use of an approved medical product during a declared emergency involving a

I8

heightened risk of attack on the public or U.S. military forces, or a significant potential to affect

19

national security.

This guidance was prepared by the Emergency Use Authorization (EUA) Principals Group and the EUA Working
Group. The EUA Working Group (WG) is composed of members with expertise in public health, medical,
regulatory, legal, ethical, and risk communication areas. The WG, on an ongoing basis, examines issues related to
issuance and implementation of an EUA. This group provides expert advice to both the Commissioner of the Food
and Drug Administration (FDA Commissioner) and the Secretary of Health and Human Services (the Secretary).
2
Section 903 of the FD&C Act and existing delegations of authority, found in the FDA Staff Manual Guide
1410.10, permit the authority of the Secretary to issue an EUA under section 564 of the FD&C Act to be delegated
to the FDA Commissioner. The Secretary has delegated his authority to issue an EUA under section 564 to the FDA
Commissioner. Thus, in this document the FDA Commissioner is identified rather than the Secretary except where
the Secretary retains the authority.

The Emergency Use Authorization (EUA) authority recently granted by Congress allows the
FDA Commissioner to strengthen the public health protections against biological, chemical,
radiological, and nuclear agents that may be used to attack the American people or the U.S.
armed forces. Under section 564, the FDA Commissioner may allow medical countermeasures
to be used in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or
conditions caused by such agents, when there are no adequate, approved, and available
alternatives.

The document is intended to inform industry, government agencies, and FDA staff of the
Agency's general recommendations and procedures for issuance of E U A S . ~FDA expects that
requests for consideration for an EUA would be submitted by government agencies (e.g., the
Department of Health and Human Services or the Department of Defense (DoD)) or private
entities. FDA may seek additional data and information on a case-by-case basis to ensure that
the statutory criteria for issuance of an EUA are met.

Additionally, the Secretary of Health and Human Services (the Secretary) will establish a
permanent Emergency Use Authorization Working Group (EUA WG), headed by the Assistant
Secretary for Preparedness and Response (ASPR), with representatives from FDA, the Centers
for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), the
Department of Defense (DoD), the Department of Homeland Security (DHS), the Department of
Veterans Affairs and, as appropriate, participants from other Federal agencies, to identify and
FDA Centers (i.e., the Center for Biologics Evaluation and Research (CBER), the Center for Drug Evaluation and
Research (CDER), and the Center for Devices and Radiological Health (CDRH)) may issue subsequent guidance
providing greater detail on these recommendations and procedures.

provide expert consultation on potential EUA candidates prior to and during declared
emergencies.

FDA's guidance documents, including this guidance, do not establish legally enforceable
responsibilities. Instead, guidances describe the Agency's current thinking on a topic and should
be viewed only as recommendations, unless specific regulatory or statutory requirements are
cited. The use of the word should in Agency guidances means that something is suggested or
recommended, but not required.

11. DECLARATION OF EMERGENCY

Section 564(b)(1) of the FD&C Act provides that, before an EUA may be issued, the Secretary
must declare an emergency based on one of the following grounds:
(1) a determination by the Secretary of Homeland Security that there is a domestic
emergency, or a significant potential for a domestic emergency, involving a heightened risk of
attack with a specified biological, chemical, radiological, or nuclear agent or agents;
(2) a determination by the Secretary of Defense that there is a military emergency, or a
significant potential for a military emergency, involving a heightened risk to United States
military forces of attack with a specified biological, chemical, radiological, or nuclear agent or
agents; or
(3) a determination by the Secretary of a public health emergency under section 3 19 of

the Public Health Service Act (PHs Act) that affects, or has the significant potential to affect,
national security, and that involves a specified biological, chemical, radiological, or nuclear

agent or agents, or a specified disease or condition that may be attributable to such agent or
agents.

Once the Secretary has declared an emergency justifying an authorization under section 564 to
use an unapproved medical product or an approved product for an unapproved use, the ASPR
may convene the EUA Working Group to provide expert consultation to the F D A . ~Based on his
review of the information and data submitted to the Agency and input from the EUA WG (if
convened) and after consulting with the Director of hTIH and the Director of CDC (to the extent
feasible and appropriate given the circumstances of the emergency), the FDA Commissioner
may authorize the emergency use of a particular product, assuming other statutory criteria and
conditions are met.5

Section 564(b)(2) states that a declaration of emergency will terminate one year after issuance or
earlier if the Secretary determines, in consultation (as appropriate) with the Secretary of
Homeland Security or the Secretary of Defense, that the circumstances that precipitated the
declaration have ceased. Before a declaration terminates, the Secretary must provide, under
section 564(b)(3), advance notice that is sufficient to allow for disposition of unapproved product
or any labeling or other information provided related to an unapproved use of an approved
product. Section 564(b)(2)(B) also authorizes the Secretary to renew a declaration.
4

The FDA Commissioner may issue one or more EUAs on the basis of a single declaration of emergency, under
section 564(b)(l), provided that the EUAs are intended for use in the same emergency involving the same
biological, chemical, radiological, or nuclear agent or agents.
5
For purposes of this document, an "unapproved" product refers to a product that is not approved, licensed, or
cleared for commercial distribution under sections 505, 5 10(k), or 5 15 of the FD&C Act or section 35 1 of the Public
Health Service Act (PHs Act); an "unapproved use of an approved product" refers to a product that is approved,
licensed, or cleared under such provisions but which use is not an approved, licensed, or cleared use of the product
(21 U.S.C. 360bbb-3).

Publication: The Secretary will promptly publish in the Federal Register notice of each
determination of actual or potential emergency, the Secretary's declaration of emergency,
advance notice of termination, and renewal of a declaration issued under section 564(b).6 The
FDA Commissioner will promptly publish in the Federal Register a notice of each authorization,
including an explanation of the reasons for issuance, a description of the intended use of the
EUA product, and its indications and contraindications. The FDA Commissioner also will
promptly publish in the Federal Register each termination or revocation of an authorization and
an explanation of the reasons for the decision.' In addition, FDA plans to provide notice of an
emergency use authorization on the Agency's website, at www.fda.gov, and through
announcements disseminated to the media.'

111. ELIGIBILITY FOR AN EUA

Section 564 permits the FDA Commissioner to authorize the introduction into interstate
commerce of a drug, device, or biological product intended for use in an actual or potential
emergency during the effective period of a declaration. EUA candidates include products and
uses that are not approved, cleared, or licensed under sections 505,5 10(k), and 5 15 of the FD&C
Act or section 35 1 of the PHs Act. The FDA Commissioner may issue an EUA only if, after
6

To the maximum extent feasible given the circumstances, Federal Register publication of the notice will occur
prior to the action that is the subject of the notice.
See supra note 6.
8
In publicly releasing information on an EUA, FDA will take necessary steps to protect classified information and
information otherwise protected by law, as appropriate.

consultation with the Director of NIH and the Director of CDC (to the extent feasible and
appropriate given the circumstances of the emergency), the FDA Commissioner concludes1) that the agent specified in the declaration of emergency can cause a serious or lifethreatening disease or condition;

2) that, based on the totality of scientific evidence available, including data from
adequate and well-controlled clinical trials, if available, it is reasonable to believe that the
product may be effective in diagnosing, treating, or preventing--(a) the serious or lifethreatening disease or condition referred to in paragraph (1); or (b) a serious or lifethreatening disease or condition caused by a product authorized under section 564, or
approved, cleared, or licensed under the FD&C Act or PHS Act, for diagnosing, treating,
or preventing the disease or condition referred to in paragraph (1) and caused by the
agent specified in the declaration of emergency;

3) that the known and potential benefits outweigh the known and potential risks of the
product when used to diagnose, prevent, or treat the serious or life-threatening disease or
condition that is the subject of the declaration; and
4) that there is no adequate, approved, and available alternative to the product for
diagnosing, preventing, or treating such serious or life-threatening disease or condition.

Categories of Products: The range of potential EUA products includes drugs, biological
products (e.g., vaccine, blood products, and biological therapeutics), and devices (e.g., in vitro
diagnostics). (Throughout this document, the term "drugs" includes biological products.)
Candidate products include those products that have not been approved or cleared under the
FD&C Act or the PHS Act ("unapproved products"), as well as unapproved uses of approved

drugs and approved or cleared devices ("unapproved uses of approved products"). Examples of
"unapproved uses of approved products" may include: 1) use of an approved antibiotic as
prophylaxis for exposure to, or treatment of disease caused by a bacterium that is not included on
the approved labeling for the antibiotic; and 2) distribution of a prescription drug by a nonlicensed provider (e.g., delivery of oral antibiotics by U.S. postal carriers). Section 564 does not
require that an investigational new drug application (DID) or investigational device exemption
(IDE) be filed for EUA candidate products, although FDA anticipates that many of the
unapproved products already will have been under evaluation through such mechanisms.

Effectiveness: Products and uses that are eligible for authorization are those that "may

be effective" to prevent, diagnose, or treat in humans serious or life-threatening diseases or
conditions that can be caused by the specified biological, chemical, radiological, or nuclear
agent(s) that led to or caused the declared emergency. Eligible products and uses also include
those that may be effective to mitigate a disease or condition caused by an FDA-regulated
product (including an EUA product, or an approved, cleared, or licensed product) used to
diagnose, treat, or prevent a disease or condition caused by such agent. The "may be effective"
standard for EUAs provides for a lower level of evidence than the "effectiveness" standard that
FDA uses for product approvals.9

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The terminology "may be effective" also appears in 21 CFR 3 12.34(b)(3)(A), where it states that a request for a
Treatment IND (tIND) for a drug intended to treat an immediately life-threatening disease may be denied due to a
lack of evidence that the drug "may be effective for its intended use in its intended population." Nevertheless, the
Agency's decisions on requests for EUAs and tINDs involve product-specific and circumstance-dependent
determinations of risks and benefits.

FDA intends to assess the potential effectiveness of an EUA product on a case-by-case
basis. The Agency has significant experience assessing effectiveness where clinical information
is limited, including experience with treatment INDs and IDEs and humanitarian device
exemptions. However, the amount, kind, and quality of evidence available to support an EUA
may not always be the same as that required for treatment INDs, IDEs, and humanitarian device
exemptions under the FD&C Act and Agency regulations. If, based on the totality of the
scientific evidence available, including adequate and well-controlled clinical trials, if they are
available, it is reasonable to believe that the product may be effective for the specified use, the
FDA Commissioner may authorize its emergency use--provided that other statutory criteria (e.g.,
relating to the risk-benefit analysis and alternatives) also are met.

Risk-Benefit Analysis: Products are eligible for emergency use authorization if FDA
determines that the known and potential benefits of the product, when used to diagnose, prevent,
or treat the identified disease or condition, outweigh the known and potential risks of the
product. In determining whether the known and potential benefits of the product outweigh the
known and potential risks, FDA intends to assess the quality and quantity of the evidence, given
the current state of scientific knowledge, of risks and benefits. The Agency intends to use this
information to make an overall risk-benefit determination. To accomplish this, FDA plans to
look at the totality of the scientific evidence, which could arise from a variety of sources. The
Agency intends to review and consider all evidence, including results of domestic and foreign
clinical trials, animal data, and in vitro data, available for Agency consideration. FDA
anticipates that, for some candidate products, data from controlled clinical trials will be
available. For others, the Agency expects to consider clinical experience from other than a

controlled trial if the circumstances warrant. For yet others, in vivo efficacy data may only be
available from animal models. The FDA Commissioner will consult with the Director of NIH
and the Director of CDC (to the extent feasible and appropriate given the circumstances of the
emergency) and will evaluate all the evidence in light of the specific circumstances of the
emergency, including potential risks of not receiving treatment with the candidate product, in
determining whether to issue an EUA.l o If the risk-benefit analysis does not support issuance of
an EUA or if the product does not otherwise meet the statutory criteria for issuance, patient
access to the investigational product may be available under other regulatory mechanisms (e.g.,
IND or IDE).

Alternatives to the Product: The FDA Commissioner may issue an EUA if he

determines that there is no adequate, approved, and available alternative to the candidate product.
A potential alternative product may be considered "unavailable" if there are insufficient supplies
to meet fully the emergency need. A potential alternative product may be considered
"inadequate" if there are contraindicating data for special circumstances or populations (e.g.,
immunocompromised individuals or individuals with a drug allergy) or if the agent is or may be
resistant to approved and available alternative products.

IV. REQUEST FOR CONSIDERATION FOR AN EUA

Although an EUA may not be issued until after an emergency has been declared by the
Secretary, FDA recognizes that during such exigent circumstances, the time available for the
'O

Such evidence includes the possible consequences of not taking or using the candidate product (e.g., possible

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submission and review of an EUA request may be severely limited. Therefore, the Agency
strongly encourages an entity with a possible candidate product, particularly one at an advanced
stage of development, to contact the FDA Center responsible for the candidate product even
before a determination of actual or potential emergency. This guidance offers recommendations
for both "pre-emergency" activities to be conducted prior to the determination of actual or
potential emergency and "emergency" activities to be performed once the determination has been .
issued. In addition, this section of the guidance sets out the types of information FDA believes
are important to allow an assessment of safety and effectiveness and to make an adequate riskbenefit determination to support issuance of an EUA.

Pre-Emergency Activities: Such activities may include discussions with FDA about a

prospective EUA product and the appropriate vehicle to use, such as an IND, IDE, or Master
File, when submitting data on the product prior to a determination of actual or potential
emergency." The Agency strongly recommends that an entity submitting data during a "preemergency" period follow the recommendations for data submission contained in "Submission of
a Request for Consideration," below. If, prior to the declaration of an emergency, FDA believes
that a candidate product may meet the criteria for an EUA, the Agency may share appropriate
information on such product with the Secretary's EUA W G . ' ~

health effects and the need for quarantine).
1I
FDA anticipates that the appropriate mechanism to use for submitting data on a candidate product during the preemergency period will vary depending on the circumstances.
I2
Disclosures of information by FDA to the Secretary's EUA WG will be consistent with applicable laws and
regulations protecting trade secrets and confidential commercial or financial information,

Emergency Activities: Once a determination of actual or potential emergency has been
made under section 564(b)(1), the Secretary may declare an emergency justifying the
authorization to use an unapproved medical product or an approved medical product for an
unapproved use. The Secretary will consult with the EUA WG; other technical experts from
FDA, NIH, and CDC; and other agencies and private entities, where appropriate, to identify
products that may be eligible for an EUA in light of the circumstances of the emergency and to
facilitate timely submission of the EUA request by an appropriate entity.

Submission of a Request for Consideration: Section 564(c) requires that the data to
support authorization demonstrate that, based on the totality of scientific evidence available to
the FDA Commissioner (including data from adequate and well-controlled clinical trials, if
available), it is reasonable to believe that the product may be effective in diagnosing, treating, or
preventing the serious or life-threatening disease or condition. The exact type and amount of
data needed to support an EUA may vary depending on the nature of the declared emergency and
the nature of the candidate product. To facilitate FDA review of such data, the Agency
recommends that a request for consideration for an EUA include a well-organized summary .of
the available scientific evidence that evaluates the product's safety and effectiveness, including
the adverse event profile when used for diagnosis, treatment, or prevention of the serious or lifethreatening disease or condition, as well as data and other information on safety, effectiveness,
risks and benefits, and (to the extent available) alternatives.

The chart below summarizes the types of data that FDA recommends be submitted to
support a request for consideration for an EUA.

Summary of Recommended Data to Support a Request for Consideration:
For FDA to evaluate a request for consideration for an EUA, the Agency recommends that the
following information be submitted:
1. a description of the product and its intended use (e.g., identification of the serious or
life-threatening disease or condition for which the product may be effective);
2. identification and an explanation of what unrnet need(s) would be addressed by
issuance of the EUA;

3. a description of the product's approval or clearance status, if any, under the FD&C Act
or licensure status under the PHs Act, and whether the product is under an
investigational application (e.g., whether the product is unapproved or whether it is
approved but the EUA is for an unapproved use; whether an IND or IDE is in effect or
has been submitted); whether the product is licensed for either the proposed or another
use in a foreign country; information on the use of the medical product by either a
foreign country or an international mutual defense organization such as NATO;
4. a list of each site where the product, if authorized, would be (or was) manufactured
and the Good Manufacturing Practices (GMP) status of the manufacturer;

5. identification of any approved alternative products, including their availability and
adequacy for the proposed use (if known);
6. available safety and effectiveness information for the product;

7. a discussion of risks and benefits;

8. a description of the information for health care providers or authorized dispensers and
recipients of the product, (e.g., two separate "Fact Sheets"), and the feasibility of
providing such information to health care providers or authorized dispensers and
recipients in emergency situations;
9. information on chemistry, manufacturing, and controls;
10. instructions for use of the EUA product (e.g., if follow-up treatment is required); and
1 1. proposed labeling (if applicable).
12. right of reference (if applicable).

Recommended Safety Data

In general: The amount and type(s) of safety data that FDA recommends be submitted as

part of a request for consideration for an EUA will differ depending upon a number of factors,
including whether the product is approved for another indication and, in the case of an
unapproved product, the product's stage of development. FDA expects to interpret safety
information in light of the seriousness of the clinical condition, alternative therapies (if any), and
the specific circumstances of the emergency. FDA strongly encourages any person or entity with
a candidate product to discuss with the Agency at the earliest possible time (even before a
determination of actual or potential emergency) the nature and type of safety data that might be
appropriate to submit to FDA.

Previously approvedproducts: If the new indication uses a similar dose, duration, route

of administration, andlor mechanism of action (as appropriate given the nature of the product),
and the intended patient population is similar to that for which the product is approved, FDA
recommends that the request for consideration for an EUA reference the approved application if
the requester submitted the approved application or has a right of reference. If the new use poses
a different risk to the patient population (e.g., suggesting the possibility of increased toxicity),
the Agency recommends that information from relevant in vitro studies, animal toxicology
studies, and (if available) human clinical data and experience be provided to support such a use.

Products under development: The range of available data for such products will differ
widely. FDA recommends that any request for consideration for an EUA include available
preclinical testing data, such as in vitro and animal toxicology data. The Agency also strongly
encourages that safety information in humans from clinical trials and individual patient
experience be provided, if available. FDA further recommends that data submitted in the request
attempt to link the likely patient exposure to any relevant existing preclinical data. Similarly,
where animal data are used, sufficient information should be provided to link the results of these
data to expected exposures related to the proposed use in humans. Any information on safety
associated with use in humans of this or related compounds or devices of a similar design also
should be submitted.

Recommended Effectiveness Data

In general: FDA recognizes that comprehensive effectiveness data are unlikely to be
available for every EUA candidate product, and the information necessary to authorize
emergency use of a product will depend on the circumstances of the declared emergency, as well
as available knowledge about the product's safety profile. FDA plans to assess the sufficiency of
the effectiveness data and the risk-benefit profile of each candidate product on a case-by-case
basis.

FDA recommends that requests for consideration for EUAs include (or, for products that
are developed under IND or IDE or have Drug or Device Master Files, refer to the appropriate
document containing) any available relevant scientific evidence regarding the following:

330

(a) mechanism(s) of the product's action to diagnose, treat, or prevent the disease

33 1

or condition underlying the request;

332

(b) preclinical testing data, such as in vitro evidence of effect of the product in

333

preventing or reducing the toxicity of the specified agent;

334

(c) for drugs, demonstration of effectiveness in diagnosing, treating, or preventing

335

the subject disease or condition in at least one animal species expected to react

336

with a response predictive for humans, where the animal study endpoint is clearly

337

related to the desired benefit in humans (e.g., enhancement of survival or

338

prevention of major morbidity);13

339

(d) evidence of effect in humans (e.g., in published case reports, uncontrolled

340

trials, controlled trials, if available, and any other relevant human use experience);

341

(e) for drugs, data to support the proposed dosage (including pharmacokinetics

342

and pharmacodynarnics data, and for vaccines or antibody therapies,

343

immunogenicity andlor achievement of protective levels of relevant parameters of

344

immunity) for the intended use; and

345

( f ) for devices, clinical testing data to support the proposed intended use, as

346

necessary and appropriate.

347
348

Other Data Considerations

349
350
351

In general: FDA recommends that the request for consideration include the following

types of data, as appropriate and to the extent feasible given the exigencies of the circumstances:

(a) Well-organized study reports that provide a complete assessment and analysis
of available safety and effectiveness data and an interpretation of the findings. If
final study reports are not yet available, any available interim study reports should
be provided and clearly identified as such;
(b) Any relevant statistical analyses; and
(c) Source data for clinical studies, nonclinical laboratory studies, and any animal
studies demonstrating activity or effectiveness of the product in the treatment of
the underlying disease or condition or a closely related disease or condition, such
as case report tabulations for key studies; case report forms for all patients who
died during the clinical studies and for all persons who did not complete the study
due to an adverse event, regardless of causality; relevant reports in the published
literature; and translations of source materials in a language other than English.

Data quality: The Agency recommends that requests for consideration for EUAs include

statements on whether the nonclinical laboratory studies were conducted in compliance with
applicable Good Laboratory Practice requirements in 21 CFR part 58 and whether the clinical
studies were conducted in compliance with applicable Good Clinical Practice standards.

Data updates: FDA recommends that any data from any ongoing testing (e.g., longer

term stability data) or other data or information that may change the Agency's evaluation of the
product's safety or effectiveness that become available during the period of review or the term of
13

See, e.g., Food and Drugs; Applications for FDA Approval to Market a New Drug; Approval Based on Evidence

the EUA (to the extent that such data are not required to be submitted under a condition of
authorization) be submitted to the Agency when such data become available.

Discussion of Risks and Benefits: FDA recommends that a request for consideration for

an EUA include a discussion of the candidate product's known and potential risks and benefits,
which includes a synthesis of the data and information requested above, including:
(a) Measures taken to mitigate risk or optimize benefit;
(b) Limitations, uncertainty, and data gaps; and
(c) A description of circumstances, if any, under which the product should not be
used (e.g., contraindications).

Format of Submissions: Submissions may be provided in paper or electronic format.

Specific information for electronic format may be obtained by reviewing guidance from the
appropriate FDA Center (CBER--www.fda.gov/cber/esub/esubguid.ht;
CDER-www.fda.gov/cder/regulatory/ersr; and CDRH--www.fda.gov/cdrh~elecsub.html).
Where a paper

submission is filed, FDA recommends that a minimum of three copies be provided.

The Agency recommends that each submission begin with a section that describes the
contents and organization of the included materials. The submitter of the original application or
anyone with a right of reference may refer to data or other information previously submitted to
the Agency in a marketing application, investigational application, or Master File.

of Effectiveness from Studies in Animals, 2 1 CFR 3 14.610(a)(2) and (3).

FDA expects material to be provided in a reviewable form and sufficiently complete to
permit substantive review. Nevertheless, the Agency recognizes that, in rapidly developing or
unexpected emergency circumstances, or when previously unanticipated or unavailable medical
countermeasures are being considered, it may not be possible for an entity to provide all of the
requested data or to provide it in the format suggested in a timely manner. In such
circumstances, the Agency will accept and evaluate the request for consideration for an EUA
based on data in the form an entity is able to submit. However, a request for consideration that is
missing data or that is otherwise incomplete or poorly documented will make determination of
whether the product's benefits outweigh its risks more difficult and may, for that reason, be more
likely to result in a request for additional information, the need for a longer time period for
review, or a decision not to authorize emergency use of the candidate product.

The addresses for submission of a request for consideration for an EUA are as follows:

For the Center for Biologics Evaluation and Research:
Food and Drug Administration
Center for Biologics Evaluation and Research
Document Control Center, HFM-99, Suite 200N
1401 Rockville Pike
Rockville, MD 20852-1448
ATTN: EUA

For the Center for Devices and Radiological Health:
Document Mail Center (HFZ-401)
Center for Device and Radiological Health
Food and Drug Administration
9200 Corporate Boulevard
Rockville, MD 20850

ATTN: EUA
For the Center for Drug Evaluation and Research:
Food and Drug Administration
Center for Drug Evaluation and Research
Central Document Room
590 1-B Amrnendale Road
Beltsville, MD 20705- 1266
ATTN: EUA

V. PROCESSING OF AN EUA

This section discusses FDA's role in pre-emergency activities for candidate EUA products, as
well as the procedures the Agency will follow in processing a request for consideration for an
EUA once the Secretary has issued a declaration of emergency.

Prioritization of Pre-Emergency Activities: The Agency intends to establish priorities
for the activities it undertakes, prior to a determination of actual or potential emergency, on
candidate products. Such prioritization may be based on the circumstances, such as:
(a) the seriousness of the clinical condition;
(b) the incidence of the clinical condition;

(c) the effect use of the product may have in ensuring national security;
(d) whether the product is included in government (Federal, State, or local)
stockpiles or whether there is a significant likelihood that the product will be
included in government stockpiles if an EUA is granted;

(e) whether the product could be used by a large population or is limited to
subpopulation(s);
(f) request of another government agency;

(g) the extent to which the product would serve a significant unmet medical need
in a special population (e.g., pregnant women, infants and children, and
immunocompromised persons);
(h) the availability and, where known, safety and effectiveness of other
countermeasures;
(i) the urgency of the treatment need (i.e., the window of opportunity for
treatment can vary between different medical conditions);
Cj) the available information concerning the likelihood that the product may be

safe and effective in treating the condition;
(k) the adequacy of the supporting nonclinical and clinical information; and
(1) the quantity of product available.

FDA intends to establish priorities for its pre-emergency activities at,the Division level or
higher and, as appropriate and feasible, will consult with the Secretary's EUA WG and may
consult other agencies on its priority setting.

Review of Pre-Emergency Submissions: To allow FDA review to begin before a

determination of actual or potential emergency, the Agency recommends that a pre-emergency
submission be filed using existing processes (e.g., IND or IDE), to the extent feasible and
appropriate. The extent of, and timelines for, review of such submission will be determined on a

case-by-case basis and will depend on the nature of the submission (e.g., whether an IND or IDE
for the product already is on file) and the workload of the reviewing Center. Subject to those
considerations and other exigent circumstances beyond Agency control, FDA anticipates that
pre-emergency submissions for high priority activities may be reviewed in a matter of weeks to
months.

Prioritization of Requests for Consideration for an EUA During a Declared
Emergency: Once the Secretary has declared an emergency justifying the authorization to use
an unapproved product or an unapproved use of an approved product, the Agency intends to
prioritize its review of requests for consideration for an EUA based on factors such as:
(a) the seriousness of the clinical condition;
(b) the incidence of the clinical condition;
(c) the likelihood that the product may be effective in treating the condition;
(d) the effect use of the product may have in ensuring national security;
(e) whether the product is included in government (Federal, State, or local)
strategic stockpiles;

(f) whether the product could be used by a large population or is limited to
subpopulation(s) (unless such use may be critical in managing a public health
threat or in protecting a subpopulation with no other suitable measures available);
(g) request of another government agency;
(h) the extent to which the product would serve a significant unrnet medical need
in a special population (e.g., pregnant women, infants and children, and
immunocompromised persons);

(i) the availability and, where known, safety and effectiveness of other
countermeasures;
(j) the urgency of the treatment need (i.e., the window of opportunity for

treatment can vary between different medical conditions);
(k) the adequacy of the supporting nonclinical and clinical information; and
(1) the quantity of product available.

FDA intends to establish priorities for its review of requests for consideration at the
Division level or higher and, as appropriate and feasible, will consult with the EUA WG and may
consult with other agencies on its priority setting.

Review Process for a Request for Consideration for an EUA: The relevant FDA

Center will be responsible for the overall coordination of the Agency's disposition of the request
and will interact directly with the entity submitting the request for consideration. The Office of
the Commissioner will arrange for the consultations with the Director of NIH and the Director of
CDC to occur, to the extent that such consultations are feasible and appropriate given the
circumstances of the emergency.I4 The Commissioner's Office also will work with the ASPR to
coordinate interactions with the EUA Working Group, if convened, although technical input
from the EUA WG will be communicated directly to the appropriate FDA review division. The
review division also may consult with other countermeasures working groups and expert
technical groups within the Agency and, depending on the complexity of the issues presented
l4 The authority of the Commissioner of Food and Drugs to perform consultations under section 564 of the Act has
been delegated to the Assistant Commissioner of Counterterrorism Policy, the CBER Director, the CDER Director,
and the CDRH Director (FDA Staff Manual Guide 1410.21).

and the nature of the declared emergency, may seek additional scientific and technical input from
outside experts or advisory committees.

FDA recognizes that the exact type and amount of data needed to support an EUA may
vary depending on the nature of the declared emergency and the nature of the candidate product.
The Agency intends to evaluate each request in light of the circumstances and the statutory
criteria for issuance.

FDA expects that the responsible FDA Center, in coordination with internal and external
technical experts (as appropriate and feasible), will perform its review of the information and
data included in the request for consideration and make recommendations to the Commissioner.
FDA anticipates that the letter authorizing, or not authorizing, a specific emergency use or uses
of the candidate product will be issued by the Office of the Commissioner. The letter
authorizing emergency use of a product will include a description of the intended use, as well as
the indications and contraindications of the product. FDA anticipates that when an EUA is
issued, the relevant Center will work with the Office of the Commissioner in drafting the Federal
Register notice of the EUA for publication by the Office of the Commissioner. In addition, FDA
plans to post information about the EUA on the Agency website (~ww.fda.gov).

Timelines for Review: The timelines for FDA review and action on a request for
consideration for an EUA will depend on the product profile; the existence, if any, of pending
applications for the product; the nature of the emergency; and other relevant factors. Although
the length of time required for FDA action will vary, the Agency recognizes that it is likely that,

in an emergency situation that is occurring or believed imminent, a request for consideration for
an EUA will be acted upon within a matter of hours or days.

VI. CONDITIONS OF AUTHORIZATION

Under section 564, the FDA Commissioner may establish conditions on an EUA. Section 564(e)
requires the FDA Commissioner (to the extent practicable given the circumstances of the
emergency) to establish certain conditions on an EUA authorization that the Commissioner finds
necessary or appropriate to protect the public health, and permits the Commissioner to establish
other conditions that he finds necessary or appropriate to protect the public health. Conditions
authorized by section 564(e) include, for example: requirements for information dissemination
to health care providers or authorized dispensers and product recipients; adverse event
monitoring and reporting; data collection and analysis; recordkeeping and records access;
restrictions on product advertising, distribution, and administration; and limitations on GMP
requirements. Some conditions, the statute specifies, are mandatory to the extent practicable for
authorizations of unapproved products and discretionary for authorizations of unapproved uses
of approved products. Moreover, some conditions may apply to manufacturers of an EUA
product, while other conditions may apply to any person who carries out any activity for which
the authorization is issued. Section 564 also gives the FDA Commissioner authority to establish
other conditions on an authorization that he finds to be necessary or appropriate to protect the
public health.

Conditions of Authorization for Emergency Use of an Unapproved Product: Section

564(e)(1) describes certain requirements with respect to the emergency use of an unapproved
product. For example, requirements to disseminate certain information to health care providers
or authorized dispensers and recipients and to perform adverse event monitoring and reporting
are mandatory under section 564(e)(l)(A) on any person who carries out any activity for which
an authorization for an unapproved product is issued, unless the FDA Commissioner determines
that such conditions are not practicable given the circumstances of the emergency. Section
564(e)(l)(A) further provides that the FDA Commissioner shall establish appropriate conditions
with respect to manufacturers' recordkeeping, reporting, and records access, to the extent that
such conditions are practicable. The FDA Commissioner also may, under section 564(e)(l)(B),
impose comparable records conditions on any person (other than a manufacturer) who carries out
any activity for which an authorization is issued. In addition, the Commissioner may impose,
under section 564(e)(l)(B), the following requirements on any person (including a manufacturer)
who carries out any activity for which the authorization of an unapproved product is issued:
restrictions on distribution of the EUA product and on who may administer it, as well as
requirements to collect and analyze safety and effectiveness data on the product. Additionally,
section 564(e)(3) authorizes the FDA Commissioner to waive or limit (as appropriate) existing

GMP requirements, and section 564(e)(4) permits the Commissioner to establish conditions for
advertising and other promotional descriptive printed matter relating to the unapproved product.
Each of the conditions described in section 564(e) is summarized below.

Conditions of Authorization for Emergency Use of an Approved Product for an
Unapproved Use: Section 564(e)(2) describes certain requirements with respect to the

emergency use of an unapproved use of an approved product. For example, the requirements of
section 564(e)(l)(A)(i) and (ii) -- to impose conditions with respect to the dissemination of
information to health care providers or authorized dispensers and recipients - are mandatory
under section 564(e)(2)(A), to the extent practicable given the circumstances of the emergency,
if a manufacturer of an approved product authorized for an unapproved use carries out any
activity for which an EUA is authorized. The FDA Commissioner also may, if he chooses under
section 564(e)(2)(A), impose on such manufacturers requirements for adverse event monitoring
and reporting as well as recordkeeping, reporting, and records access.
Under section 564(e)(2)(B), with respect to an EUA that authorizes a change in labeling
of an approved product, but for which the manufacturer chooses not to make such labeling
change, the EUA may not authorize the product's distributor or any other person to alter or
obscure the manufacturer's labeling. However, under such conditions, the FDA Commissioner
must authorize, to the extent practicable given the circumstances of the emergency, any person
(other than the manufacturer) acting pursuant to such EUA to provide appropriate information, in
addition to the manufacturer's labeling, with respect to the product.15

In addition, section 564(e)(2)(C) allows the FDA Commissioner to establish, with respect
to the distribution and administration of the product, conditions that are no more restrictive than
those established with respect to the distribution and administration of the product for the
approved use.

15

Additional information required under section 564(e)(2)(B)(ii) as a condition of authorization is not considered
"labeling" for purposes of section 502 of the FD&C Act while the EUA for the product is effective.

Additional Conditions o f Authorization: Section 564 also permits the FDA
Commissioner to establish other conditions on an EUA. For example, section 564(e)(3)
authorizes the FDA Commissioner to waive or limit, as appropriate, existing GMP requirements,
and section 564(e)(4) permits the Commissioner to establish conditions for advertising and other
promotional descriptive printed matter relating to the unapproved use. These and other
conditions are described below.

Information for Health Care Providers or Authorized Dispensers: Under section
564(e)(l)(A)(i) (for an unapproved product) and section 564(e)(2)(A) (for a manufacturer
carrying out any activity concerning an unapproved use of an approved product), the FDA
Commissioner must establish conditions on an authorization (to the extent practicable given the
circumstances of the emergency) to ensure that health care providers or authorized dispensers
who administer the EUA product are informed that the FDA Commissioner has authorized the
emergency use of the product, of its significant known and potential benefits and risks and the
extent to which such benefits and risks are unknown, as well as the available alternatives and
their benefits and risks. FDA recommends that the request for consideration for an EUA include
a "Fact Sheet" for the health care provider or authorized dispenser that would include essential
information about the product. FDA plans to review submitted Fact Sheets for accuracy and
completeness. A sample "Fact Sheet for the Health Care Provider or Authorized Dispenser"
template is provided at the end of the guidance as Appendix A. FDA recommends that the Fact
Sheet include, at a minimum, the information listed on the first page of the sample template.
FDA further recommends that the Fact Sheet target the health care provider or authorized
dispenser who has the most basic level of training, recognizing that such individuals may have

different levels of training (nurse, doctor, other), could come from a variety of backgrounds
(state, local, military, civilian), and may have different types of experience. FDA recommends
that the Fact Sheet accompany the EUA product when the product is distributed, and be in a form
that is readily accessible to the health care provider or authorized dispenser. To the extent
consistent with other conditions of authorization, information on the EUA product also may be
disseminated to providers through media, videos/DVDs, the Internet, and direct communication
from public health agencies.

Information for Recipients: Although informed consent under part 50 of FDA
regulations (21 CFR part 50) is not required for administration of an EUA product and the
information dissemination requirements of section 564 are mandatory only to the extent
conditions establishing such requirements are practicable, FDA recommends that recipients be
given as much appropriate information as possible given the nature of the emergency and the
conditions of the authorization. Under section 564(e)(l)(A)(ii)(III) (for an unapproved product)
and section 564(e)(2)(A) (for a manufacturer carrying out any activity concerning an unapproved
use of an approved product), recipients must be informed that the FDA Commissioner has
authorized emergency use of the product, of the significant known and potential benefits and
risks of the EUA product, and of the extent to which such benefits and risks are unknown.
Recipients must have an opportunity to accept or refuse the EUA product and must be informed
of any consequences of refusing administration of the product.'6 Recipients also must be
informed of available alternatives to the product and of their risks and benefits under section
16

However, Congress authorized the President to waive, under certain circumstances, the option for members of the
armed forces to accept or refuse administration of an EUA product (10 U.S.C. 1107a).

564(e)(l)(A)(ii)(III) (for an unapproved product) and section 564(e)(2)(A) (for a manufacturer
carrying out any activity concerning an approved product for an unapproved use).

Ordinarily, FDA expects that some form of written information will be given to
recipients, similar to the Fact Sheet for health care providers or authorized dispensers. To assure
that individuals of all educational levels comprehend the information provided, FDA
recommends that it be written in the simplest language possible and using other techniques to
improve health literacy.17 The Agency recommends that the written information include the
significant known and potential risks and benefits of the product and the extent to which the
potential risks and benefits are unknown, specific instructions for home use (if necessary), and
adverse event information, including contact information should adverse events occur. A sample
"Fact Sheet for Recipients" template is provided at the end of the guidance as Appendix B. FDA
recommends that the Fact Sheet include the information in the template and be submitted to the
Agency as part of the request for consideration for an EUA. Furthermore, the Agency
recommends that the Fact Sheet or other written information for recipients be tested (e.g., by
focus groups) for clarity, particularly regarding messages on uncertainty and relative risks. FDA
acknowledges, however, that exigent circumstances may dictate the use of other, more
appropriate, dissemination methods. Therefore, FDA expects that recipient information would be
disseminated in the most effective and expeditious way possible to reach the intended audience.
Methods of dissemination may include media (e.g., public service announcements),
videos/DVDs, the internet, and direct communication from health care providers and public
health agencies. Section 564(e)(l)(A)(ii) (for an unapproved product) and section 564(e)(2)(A)

(for a manufacturer carrying out any activity concerning an unapproved use of an approved
product) contemplates that the Fact Sheet or other recipient information will be provided to
recipients before administration of an EUA product. If, however, taking the time needed to
provide such information would diminish or negate the effectiveness of the product for the
recipient, the FDA Commissioner may include as part of the condition that the information be
provided to the recipient as soon as practicable afterward.

Monitoring and Reporting of Adverse Events: Section 564(e)(l)(A)(iii) (for an
unapproved product) and section 564(e)(2)(A) (for a manufacturer carrying out any activity
concerning an unapproved use of an approved product) provide for adverse event monitoring and
reporting for EUA products. FDA expects that the primary focus of such conditions will be on
capturing serious adverse events and identifying the appropriate mechanism(s) to be used for the
collection of follow-up clinical information, the size of the safety database, and the types of data
needed. Predefined mechanisms to capture adverse event data are preferred, where feasible (e.g.,
MEDWATCH and VAERS). In certain circumstances, other mechanisms also may be
considered, such as using postage-paid postcards or stickers added to the product, labeling, and
any other information that refers the health care provider or authorized dispenser and recipient to
a toll-free number and Internet site to report adverse events (such information could be included
as part of a Fact Sheet, as described above).

Records: Section 564(e)(l)(A)(iv) requires (to the extent practicable given the
circumstances of the emergency) that manufacturers of an unapproved product be required to
17

See, e.g., http://www.health.gov/communicationlliteracy/quickguideihealthinfo.htm.

maintain records and to grant to the Agency access to records concerning the EUA product. The
FDA Commissioner may impose comparable records requirements on any person other than a
manufacturer who carries out any activity for an unapproved product under section
564(e)(l)(B)(iv) and on the manufacturer of an approved product for an unapproved use under
section 564(e)(2)(A). The Agency anticipates that such records requirements may, for
manufacturers, relate to the number of doses, devices, etc. (including lot number identification)
that have been shipped or sold under an EUA; the name and addresses of the facilities where the
EUA product was shipped; and may, for persons other than manufacturers, relate to the
monitoring of patients who have been administered a product under an EUA. The FDA
Commissioner also may impose conditions regarding other matters the Agency determines are
appropriate and practicable given the circumstances of the emergency.

Additional Conditionsfor Unapproved Products: To the extent feasible given the
circumstances of the emergency, the FDA Commissioner may establish additional conditions for
unapproved products, such as the following:
Restricted distribution under the EUA--conditions may be placed on which
entities may distribute the product and how distribution is to be performed.'8
Personnel--conditions may be placed on who may administer the product, and on
the categories of individuals to whom, and the circumstances under which, the
product may be administered.
Information-conditions may be placed on the collection and analysis of
information on the safety and effectiveness of the EUA product.

The FDA Commissioner will establish these conditions on a case-by-case basis.

Additional Conditionsfor an Unapproved Use of an Approved Product: Under section
564(e)(2)(B), with respect to an EUA that authorizes a change in labeling of an approved
product, but for which the manufacturer chooses not to make such labeling change, the EUA
may not authorize a product distributor or any other person to alter or obscure the manufacturer's
labeling. However, under such conditions, the FDA Commissioner must authorize, to the extent
practicable under the circumstances of the emergency, any person (other than the manufacturer)
acting pursuant to such EUA to provide appropriate information, in addition to the
manufacturer's labeling, with respect to the product.'9

The FDA Commissioner may, under section 564(e)(2)(C), establish conditions for
distribution and administration of an approved product for an unapproved use that are no more
restrictive than those established by the Agency for the distribution and administration of the
product for an approved use. Any such additional conditions will be established by the
Commissioner on a case-by-case basis, depending on the circumstances of the emergency and
the nature of the approved product authorized for an unapproved use.

Compliance with GMPs or Alternative Approaches: The Agency expects that EUA
products will be produced in compliance with GMP; however, limits or waivers may be granted
18

FDA anticipates that distribution of EUA products will be performed according to existing response plans, as
practicable and appropriate.
l9 See supra note 13.

under section 564(e)(3), on a case-by-case basis, after consideration of the circumstances and of
any alternative proposed approach.

Advertising: Section 564(e)(4) allows the FDA Commissioner to establish conditions on

advertisements and other promotional descriptive printed matter relating to the use of an EUA
product, such as, for drugs (including biologics), requirements applicable to prescription drugs
under section 502(n) of the FD&C Act and, for devices, requirements applicable to restricted
devices under section 502(r) of the FD&C Act.

Summary of Conditions Described in Section 564(e): The following chart sets out
conditions described in section 564(e) that may be imposed on an EUA for unapproved products
and for unapproved uses of approved products, respectively. A condition is identified as
"mandatory" in the chart below if section 564(e) requires the FDA Commissioner, to the extent
practicable given the circumstances of the emergency, to establish such condition when it is
necessary or appropriate to protect the public health. A condition identified as "discretionary" in
the chart below is one that the FDA Commissioner may, under section 564(e), impose as he finds
necessary or appropriate to protect the public health. In addition to the conditions described as
"mandatory" and "discretionary" in the chart below, section 564 allows the FDA Commissioner
to establish other conditions on an authorization that he finds to be necessary or appropriate to
protect the public health.

CONDITION OF
AUTHORIZATION
Information for Health Care
Providers and Authorized
Dispensers

UNAPPROVED PRODUCT

Information for Recipients

Mandatory for manufacturers
and others*

Mandatory for manufacturers2]

Adverse Event
MonitoringIReporting

Mandatory for manufacturers
and others*

Discretionary for
manufacturers

Recordkeeping/Access

Mandatory for manufacturers;
discretionary for others*

Discretionary for
manufacturers

1 Compliance with GMPs

Discretionary for
manufacturers and others*

Discretionary for
manufacturers and others*

Advertising

Discretionary for
manufacturers and others*

Discretionary for
manufacturers and others*

Restricted Distribution

Discretionary for
manufacturers and others*

Discretionary for
manufacturers and others*

Restricted Administration

Discretionary for
manufacturers and others*

Discretionary for
manufacturers and others*

Collection/Analysis

Discretionary for
manufacturers and others*

I

Mandatory for manufacturers
and others*

I

* Others may include, for example, the U.S. government.

20

UNAPPROVED USE OF AN
APPROVED PRODUCT
Mandatory for manufacturers2'

I

Under section 564(e)(2)(B), with respect to an EUA that authorizes a change in labeling of an approved product,
but for which the manufacturer chooses not to make such labeling change, the EUA may not authorize a product
distributor or any other person to alter or obscure the manufacturer's labeling. However, under such conditions, the
FDA Commissioner must authorize, to the extent practicable under the circumstances of the emergency, any person
(other than the manufacturer) acting pursuant to such EUA to provide appropriate information, in addition t o the
manufacturer's labeling, with respect to the product.
See supra note 17.

I

Option To Carry Out Authorized Activities: Section 564(1) requires the manufacturer
of a sole-source unapproved product authorized for emergency use to inform the FDA
Commissioner, within a reasonable time after authorization, that the manufacturer does not
intend to carry out any activity under the EUA. Although the Commissioner does not have the
authority under section 564 to require a person to carry out any activity for which an EUA is
issued, section 564(1) does not limit the Commissioner's authority to impose conditions on
persons who choose to carry out any activity pursuant to an EUA.

Rules of Statutory Construction: Section 5646) provides that nothing in section 564
impairs the authority of the President as Commander in Chief of the Armed Forces under the
Constitution. In addition, section 5646) indicates that nothing in section 564 impairs the
authority of the Secretary of Defense with respect to the Department of Defense (including the
armed forces), under other provisions of Federal law. Section 564(i) also provides that nothing
in section 564, including any action by a manufacturer with respect to an unapproved use of an
approved product, impairs the authority of the United States to use or manage quantities of a
product that are owned or controlled by the United States (including products maintained in the
stockpile managed under section 3 19F-2 of the PHs Act).

VII. REVOCATION OR TERMINATION OF AN EUA

Section 564(f) provides that an EUA will be in effect for the duration of the declaration under
which it was issued (see Section 11, "Declaration of Emergency," above), unless the EUA is
revoked because the criteria of issuance (see Section 111, "Eligibility for an Emergency Use

Authorization," above) are no longer met or revocation is appropriate to protect public health or
safety.

Revocation: The FDA Commissioner will periodically review the circumstances and
appropriateness of an EUA, including circumstances that might warrant revocation of the EUA.
Such circumstances may include significant adverse inspectional findings (e.g., where an
inspection of the manufacturing site and processes have raised significant questions regarding the
purity, potency, or safety of the EUA product that materially affect the riskbenefit assessment
upon which the EUA was based); reports of adverse events (number or severity) linked to, or
suspected of being caused by, the EUA product; product failure; product ineffectiveness (such as
newly emerging data that undermine the Agency's conclusion that the product "may be effective"
against a particular agent); and availability of a preferred product.

Termination: Upon termination of the declaration, unapproved product or labeling and
product information for an unapproved use must be disposed of pursuant to section 564(b)(2)(C)
and (b)(3). A manufacturer may choose to have unapproved product returned after termination.
Notwithstanding any such termination, under section 564(f)(2) an authorization shall continue to
be effective to provide for continued use in any patient who began treatment before termination
(to the extent found necessary by the patient's attending physician).

Continued Use: Any use of an EUA product beyond the term of a declaration is subject
to investigational product regulations (e.g., IND regulations), except for use by patients who

began treatment when the declaration was in effect, to the extent found necessary by such
patient's attending physician.

VIII. PREEMPTION

FDA anticipates that preemption issues may arise when an EUA is issued to the extent that states
have existing requirements governing the dispensing, administration, or labeling of unapproved
medical products or approved medical products for unapproved uses. The Supremacy Clause
can operate to nullify both state legislative requirements and state common-law duties.
Medtronic v. Lohr, 5 18 U.S. 470,503 (1996) (Breyer, J., concurring in part and concurring in the
judgment); id. at 5 10 (OIConnor, J., joined by Rehnquist, C.J., Scalia, J., and Thomas, J.,
concurring in part and dissenting in part); Cipollone v. Liggett Group, Inc., 505 U.S. 504, 521
(1 992) (plurality opinion); id. at 548-49 (Scalia, J., joined by Thomas, J., concurring in judgment
in part and dissenting in part). Under the principles of implied conflict preemption, courts have
found state law preempted where it is impossible to comply with both federal and state law or
where the state law "stands as an obstacle to the accomplishment and execution of the full
purposes and objectives of Congress." See English v. General Electric Co., 496 U.S. 72,79
(1 990); Florida Lime & Avocado Growers, Inc., 373 U.S. 132, 142-43 (1963); Hines v.
Davidowitz, 312 U.S. 52,67 (1941). Consistent with this case law, section 4(a) of Executive
Order 13 132 states that "[algencies shall construe . . . a Federal statute to preempt State law only
where the statute contains an express preemption provision or there is some other clear evidence
that the Congress intended preemption of State law, or where the exercise of State authority
conflicts with the exercise of Federal authority under the Federal statute."

826
827

FDA believes that the terms and conditions of an EUA issued under section 564 preempt state

828

law--legislative requirements and common-law duties--imposing different or additional

829

requirements on the medical product for which the EUA was issued in the context of the

830

emergency declared under section 564. To the extent state law may impose requirements
different from or in addition to those imposed by the EUA for a particular medical product
within the scope of the declared emergency, e.g., requirements on prescribing, dispensing,
administering, or labeling of the medical product, such state law "stands as an obstacle to the
accomplishment and execution of the full purposes and objectives of Congress," See Hines, 3 12
U.S. at 67, and "conflicts with the exercise of Federal authority under [§ 5641." Executive Order
13132. Affected state laws may include, but are not limited to, laws governing the
administration of investigational medical products, such as informed consent laws and laws
requiring Institutional Review Board approval, and laws governing the prescribing or dispensing
of medical products, such as laws limiting who may prescribe or dispense medical products and
under what circumstances. FDA anticipates consulting state officials when the terms and
conditions of an EUA may preempt state law.

In an emergency, it is critical that the conditions that are part of the EUA--those that the
Commissioner has determined to be necessary or appropriate to protect the public health--be
strictly followed, and that no additional conditions be imposed. To the extent there may be
circumstances in which FDA would like people carrying out activities under an EUA also to
847

comply with requirements contained in preempted state law, FDA anticipates that the

848

Commissioner will incorporate such requirements into the terms and conditions of the EUA.

IX. LIABILITY PROTECTION AND COMPENSATION UNDER OTHER STATUTES

Apart from any applicable preemption principles, section 564 of the FD&C Act does not
establish a liability protection scheme for manufacturers or others who carry out any activity for
which an EUA is issued. However, certain persons or certain products may be eligible for
compensation or liability protection under other statutes and programs, such as the Federal
Employees' Compensation Act (5 U.S.C. 8101 et seq.); the Federal Tort Claims Act (28 U.S.C.
1346(b)); the Smallpox Vaccine Injury Compensation Program and the liability protections of
section 304 of the Homeland Security Act , as amended by Smallpox Emergency Personnel
Protection Act of 2003 (42 U.S.C. 233(p)); the National Vaccine Injury Compensation Program
(42 U.S.C. 300aa-10 et seq.); the Support Anti-terrorism by Fostering Effective Technologies
Act of 2002 (SAFETY Act); and the Public Readiness and Emergency Preparedness Act of 2005
(Pub. L. 109-148). Contact information for these statutes and programs is provided in Appendix
C.

APPENDIX A
FACT SHEET for the Health Care Provider or Authorized Dispenser

[PRODUCT for INTENDED USE]

I.

An emergency has been declared by the Secretary of Health and Human Services.

2.

[INCLUDE A BRIEF DESCRIPTION (1-2 sentences) OF THE EMERGENCY]

3.

The FDA Commissioner has authorized the emergency use of [PRODUCT] for a use

[IDENTIFY THE INTENDED USE] that has not yet obtained FDA approval by usual FDA
processes. This authorization will terminate on [DATE 1 YEAR FROM THE DATE OF
DECLARATION], or when the emergency has ceased to exist, whichever is earlier.

4.

The information in this Fact Sheet is the minimum necessary to inform you of the

significant known and potential risks and benefits of emergency use of [PRODUCT].

5.

The significant known and potential risks and benefits of emergency use of [PRODUCT]

are: [LIST]. The extent to which such risks and benefits are unknown is [EXPLAIN].

6.

The available alternatives to [PRODUCT] are: [LIST]. The risks and benefits of

[ALTERNATIVES] are: [LIS'I~].[If there is no alternative, provide an explanation of outcomes

of exposure or of any special public health measures (e.g., quarantine or monitoring) that an
individual who does not receive the EUA product may face.]

7.

[INCLUDE NAME, ADDRESS, AND TELEPHONE NUMBER FOR

MANUFACTURER.]

As the health care provider or authorized dispenser administering [PRODUCT], please
communicate the significant known and potential risks and benefits, and the extent to which such
risks and benefits are unknown, to the recipient of [PRODUCT].

Please inform the recipient that he or she has the option to accept or refuse administration of
[PRODUCT], and of the consequences of refusing administration. Please inform the recipient of
any available alternatives to [PRODUCT], and of their risks and benefits. Please provide the
"Fact Sheet for Recipients" to the recipient of [PRODUCT].

If providing this information before administration would delay the administration [PRODUCT]
to a degree that would endanger the lives of exposed or affected individuals, the information
must be provided to the recipient as soon as practicable after [PRODUCT] is administered.

If you follow these instructions when administering or using [PRODUCT], you do not need to
comply with state laws imposing different or additional requirements on use of the product in
this emergency situation.

FDA also recommends that EUA applicants include the following additional information in the
Fact Sheet for Health Care Providers or Authorized Dispensers, if it is available:

Instructions for use.

How to administer the product (including dose, route of intake or infusion, how long to
use the product, how to take care of the infusion site), how to store the product, how it is
suppliedlforms that it comes in, how to constitute;

If it is an in vitro diagnostic (IVD): what type of specimens should be collected for
testing with the product, how to store the specimens, how the laboratory should use the
product (procedure), how to interpret the results; and

Instructions for use for special populations (e.g., pregnant women, infants and children,
and immunocompromised individuals), including special dosing instructions (e-g.,
weight-based dosing), special precautions.

Known major interactions with other products or substances, including drug interactions,

cross reactivity for IVDs.

Known efficacy information or performance characteristics (for IVDs)

Adverse events. Significant known adverse event information (e.g., what are the significant

known side effects? Under what conditions should the recipient stop taking product?),

instructions for follow up in case of an adverse event, how to report an adverse event, what
to do in case of an adverse event (stop using the product? seek treatment?), whom to contact
for professional advice if an adverse event occurs or if the product does not work. Health
care providers or authorized dispensers also may report adverse events to MEDWATCH at
www.fda.gov/medwatch/report/hcp.htmor 1-800-FDA-1088, or to VAERS (for vaccines) at

www.vaers.org or 1-800-822-7967.

Alternatives. If other agents (approved/licensed/cleared products or EUA products) may
treat or prevent the same or closely related condition for [INTENDED USE], this
information should be stated. If available, the relative or expected safety and effectiveness of
the alternative should be provided, particularly for use in different populations or settings.
Such information may include:

P When an alternative product may be more appropriate, e.g., in the treatment of the
pregnant women, infants and children, and irnrnunocompromised individuals, or other
special populations.

P For preventive treatments, the time needed for [PRODUCT] to be administered in
advance of the exposure to be effective, and alternatives that may be more effective if
that time is exceeded.

Significant known and potential risks and benefits may include relevant information about
the manufacturer (e.g., a waiver of Good Manufacturing Practices compliance), if known.

Consequences of not takinglusing [PRODUCT], including possible health effects and

quarantine, and of stopping the use of [PRODUCT] against the recommendation of the
health care provider.

New findings. A statement about the fact that any significant new findings observed during

or after the course of widespread use will be made available.

Approved products. For approved products being used for unapproved indications, the Fact

Sheet also may include critical elements from the package insert.

Contacts. Whom to contact if you have any questions or concerns (other than an adverse

event report) about the product.

APPENDIX B

967

FACT SHEET for the Recipient

[PRODUCT for INTENDED USE]

1.

An emergency has been declared by the Secretary of Health and Human Services.

2.

[INCLUDE A BRIEF DESCRIPTION (1 -2 sentences) OF THE EMERGENCY].

3.

The FDA Commissioner has authorized the emergency use of [PRODUCT] for

[IDENTIFY THE INTENDED USE]. This authorization will terminate on [DATE 1 YEAR
FROM THE DATE OF DECLARATION], or when the emergency has ceased to exist,
whichever is earlier.

4.

The information in this Fact Sheet is the minimum necessary to inform you of the

significant known and potential risks and benefits of emergency use of [PRODUCT].

5.

The significant known and potential risks and benefits of emergency use of [PRODUCT]

are: [LIST]. The extent to which such risks and benefits are unknown is [EXPLAIN].

6.

The available alternatives to [PRODUCT] are: [LIST]. The risks and benefits of

[ALTERNATIVES] are: [LIST]. [If there is no alternative, provide an explanation of outcomes

of exposure or of any special public health measures (e.g., quarantine or monitoring) that an
individual who does not receive the EUA product may face.]

7.

[INCLUDE NAME, ADDRESS, AND TELEPHONE NUMBER FOR

MANUFACTURER.]

You have the option to accept or refuse administration of [PRODUCT]. The consequences of
refusing administration of [PRODUCI'] are [LIST].

Available alternatives to [PRODUCT] are: [LIST]. The risks and benefits of these alternatives
are: [LIST].

Potential adverse events for [PRODUCT] include [LIST]. Should you experience an adverse
event, [INCLUDE INSTRUCTIONS].

Any significant new findings observed during the course of emergency use of [PRODUCT] will
be made available [STATE HOW FINDINGS WILL BE MADE AVAILABLE].

APPENDIX C
LIABILITY AND COMPENSATION PROGRAMS
CONTACT INFORMATION

Federal Employees' Compensation Act

U.S. Department of Labor
Office of Workers' Compensation Programs
200 Constitution Avenue, NW
Washington, DC 202 10
(202) 693-003 1
www. dol.~ov/esa/owcpom.htm

Federal Tort Claims Act (DHHS Program)

Department of Health & Human Services
Public Health Service
FTCA
5600 Fishers Lane, Room 5C-10
Rockville, Maryland 20857
FTCA Help Line: 1-866-FTCA-HELP (382-2435
http://hphc.hrsa.gov/risk/default.htm

Smallpox Vaccine Iniurv Compensation Propram

Health Resources and Services Administration
Smallpox Vaccine Injury Compensation Program Office
5600 Fishers Lane, Room 16C-17
Rockville, MD 20857
(888) 496-0338
www.hrsa.gov/small~oxinjury

National Vaccine Iniury Compensation Program
Health Resources and Services Administration
National Vaccine Injury Compensation Program Office
5600 Fishers Lane, Room 11C-26
Rockville, Maryland 20857
(800) 338-2382
www. hrsa.gov/vaccinecompensation

SAFETY ACT:
Department of Home1and Security
ATTN: SAFETY ACT
245 Murray Lane, Bldg. 410
Washington, DC 20528
(866) 788-93 18

www.safetyact.gov

1054

PREP Act

I 05s

Department of Health and Human Services

1056

Office of Public Health Emergency Preparedness

1057

200 Independence Ave., SW, Room 638-G

1058

Washington, DC 20201

1059

(202) 205-2882

1060

www. hhs.n.ov/ophep

1061