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Public Health Law Webinar Series
“Recent Developments in FDA’s Emergency Authority for Medical Countermeasures”
Public Health Law Webinar Series
“Recent Developments in FDA’s Emergency Authority for Medical Countermeasures”
March 15, 2012
Questions and Answers
The following questions were submitted to the Food and Drug Administration (FDA) by participants during the
March 15, 2012, Public Health Law Webinar Series presentation, “Recent Developments in FDA’s Emergency
Authority for Medical Countermeasures.” Due to time constraints, it was not possible to address these questions
during the webinar. An archived version of the webinar can be accessed at the following Network for Public
Health Law website: http://www.networkforphl.org/network_resources/webinar_series/.
1.
Why is the doxycycline Emergency Use Authorization (EUA) only for anthrax when doxycycline
can be used for plague and tularemia, also Category A agents?
Certain statutory requirements under section 564 of the Federal Food, Drug, and Cosmetic (FD&C) Act
must be met before FDA can issue an EUA for a medical product (i.e., a drug, biologic, or medical
device). To date, those requirements have been satisfied to support issuance of the EUA for mass
dispensing of oral formulations of doxycycline, but not for plague or tularemia, as further explained
below.
On July 21, 2011, FDA issued an EUA for efforts related to mass dispensing of oral formulations of
doxycycline products. This EUA was issued at the Centers for Disease Control and Prevention’s (CDC)
request to facilitate local, state, and federal preparedness and response activities related to doxycycline
for post-exposure prophylaxis (PEP) for inhalational anthrax. Even though doxycycline is FDAapproved for PEP for inhalational anthrax, this EUA is needed to authorize certain emergency response
activities that might otherwise violate FD&C Act provisions.
As noted, certain statutory requirements must be met before FDA can issue an EUA for a medical
product. First, one of three possible emergency determinations must be made by either the Secretary of
the Department of Homeland Security (DHS), Department of Defense (DOD), or Department of Health
and Human Services (HHS). Second, based on that emergency determination, the HHS Secretary must
declare an emergency justifying the authorization of emergency use of the product. Only after the
requisite emergency determination and declaration are made can the FDA Commissioner issue an EUA
for the product. The July 2011 doxycycline mass dispensing EUA could be issued in advance of an
actual anthrax emergency because the requisite emergency determination for an anthrax emergency had
already been made by the DHS Secretary1 and because the HHS Secretary renewed and amended the
existing declaration of emergency justifying the authorization of emergency use of doxycycline to apply
to all oral formulations of doxycycline in July 2011 (76 Fed. Reg. 44926).
In addition to its anthrax indication, doxycycline is indicated for the treatment of plague due to Yersinia
pestis (other such drugs include streptomycin, tetracycline, and other antibacterial drugs in the
1
On September 23, 2008, the DHS Secretary 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, B. anthracis.
Memorandum from Michael Chertoff to Michael O. Leavitt, Determination Pursuant to § 564 of the Federal Food, Drug, and
Cosmetic Act. September 23, 2008.
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tetracycline group).2 Doxycycline is also indicated for the treatment of tularemia due to Francisella
tularensis. For specific information about the doxycycline indications for anthrax, plague, and tularemia,
please refer to the FDA-approved package labeling for doxycycline.
However, the doxycycline mass dispensing EUA is limited to anthrax preparedness and response efforts
because the underlying DHS emergency determination is for an anthrax emergency, the underlying HHS
emergency declaration justifying the EUA is based on the DHS anthrax emergency determination, and
CDC’s EUA request focused on anthrax activities. None of these items addressed plague or tularemia.
Currently, the requisite emergency determinations and declarations related to plague and tularemia have
not been issued in order for EUAs to be issued for the emergency use of doxycycline related to these
conditions.
If it were determined at the time of a plague or a tularemia emergency that an EUA would be needed for
the emergency use of doxycycline during the response (e.g., due to providing information that is not part
of doxycycline’s approved labeling, such as fact sheets for recipients on the emergency use of the
product), it is important to remember that separate EUAs would be needed for each disease/condition
because an EUA reflects FDA’s determination—given the circumstances of the emergency—that the
known and potential benefits of a product outweigh its known and potential risks; that there is no
adequate, approved, and available alternative to the product; etc.
2.
Has FDA considered how to convince the general public about the safety of a product distributed
under an EUA?
An EUA can be issued for (1) unapproved uses of products that have already been approved by the FDA
and (2) products that have not yet been approved for any indication by the FDA. However, an EUA
cannot be issued until certain statutory criteria under section 564 of the FD&C Act are met. One of these
is that FDA must find that, based on the totality of scientific evidence available, it is reasonable to
believe that the known and potential benefits of the product outweigh the known and potential risks of
the product, and that there is no adequate, approved, and available alternative to the product. [If these
criteria cannot be met, then alternative mechanisms (e.g., Investigational New Drug Application [IND]),
which might require additional patient protections (e.g., written informed consent), would be
considered].
Section 564 of the FD&C Act makes provisions for an EUA to include appropriate conditions to ensure
that health care professionals (or authorized dispensers who administer the EUA product) and recipients
are informed about the significant known and potential benefits and risks of the product and the extent to
which such benefits and risks are unknown, as well as any available alternatives and their benefits and
risks, among other things. Also, recipients must have an opportunity to accept or refuse the EUA
product and be informed of any consequences of refusing administration of the product. FDA has
recommended the use of written fact sheets when practicable to convey this type of information, taking
into account factors such as varied levels of training, backgrounds, and experience.
2
For example, Levaquin (levofloxacin) was recently approved to treat patients with plague and to reduce the risk of getting plague
after exposure to Yersinia pestis. U.S. Department of Health and Human Services, Food and Drug Administration. FDA approves new
antibacterial treatment for plague. April 27, 2012.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm302220.htm.
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In the case of unapproved uses of FDA-approved medical products authorized for use under an EUA,
FDA may authorize use of the product for a new indication, for a different patient population, or
possibly only for very modest deviations from the product’s approved conditions of use (e.g., the
product will be accompanied by fact sheets for recipients about the emergency use of the product that
were not part of its approved labeling). As indicated, the conditions of authorization included in each
EUA address the specific uses, as well as benefits and risks, of the product during the emergency. They
also include the type of information about the product and its use that must be communicated to
recipients/patients who receive the product and to health care professionals who dispense or administer
the product. For an example of this, refer to the Doxycycline EUA Fact Sheet for Recipients3 that was
issued with the July 2011 doxycycline mass dispensing EUA.
In cases where an unapproved product is used under an EUA, such as peramivir during the 2009 H1N1
pandemic response, the EUA would also include specific conditions to ensure the proper and safe use of
the product. For example, the peramivir EUA:

specified that peramivir was “authorized only for [certain] patients who are admitted to a hospital
and under the care or consultation of a licensed clinician…”;

required as a condition of authorization that “Health Care Providers prescribing and/or
administering authorized peramivir will ensure that the authorized Fact Sheet for Patients and
Parents/Caregivers, as well as any authorized amendments thereto, have been made available to
patients and/or parents/caregivers”; and

included a number of additional conditions for CDC, health care professionals, and the
manufacturer to ensure that adverse events were promptly reported to FDA, certain information
was communicated to patients and caregivers, and proper records were maintained (74 Fed. Reg.
56644).
In the event of a public health emergency for which an EUA or other mechanism to allow for the
emergency use of medical products is issued, FDA would also work closely with its federal partners,
including CDC and the HHS Office of the Assistant Secretary for Preparedness and Response (ASPR),
on appropriate public messaging. The type of information that would be provided would depend on the
product(s) authorized for use under an EUA(s) (or other appropriate mechanism) and on the specific
circumstances of the emergency. EUAs are also posted on FDA’s website and published in the Federal
Register for public access.
3.
The CDC Laboratory Response Network distributes some diagnostic assays that are not
cleared/approved by FDA. Is FDA exercising enforcement discretion in allowing CDC to
distribute these assays to clinical laboratories?
FDA enforces the FD&C Act and certain related statutes, such as provisions of the Public Health
Service (PHS) Act relating to approval of biologic products. FDA also enforces its regulations, which
are based on those statutes. In some cases, as with all law enforcement agencies, FDA recognizes that
3
U.S. Department of Health and Human Services, Food and Drug Administration. Exhibit 2. Doxycycline EUA Fact Sheet for
Recipients. July 21, 2011. http://www.fda.gov/downloads/EmergencyPreparedness/Counterterrorism/UCM265824.pdf.
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there are violations of its statutes and regulations for which enforcement may not be immediately
feasible. In such cases, FDA might decide to exercise its enforcement discretion.
FDA recognizes the need to have certain in vitro diagnostics (IVDs) pre-positioned to be used for
detection purposes in advance or at the outset of a chemical, biological, radiological, or nuclear (CBRN)
emergency. To the extent these tests were intended for a diagnostic use, FDA has historically exercised
its enforcement discretion. However, FDA is working closely with CDC and DOD to bring such devices
into regulatory compliance, in part to address safety concerns to protect the public health due to
significant changes in the development and use of such tests over time.
4.
What are the circumstances where an IND would be a more appropriate mechanism than an EUA
for distribution of medical countermeasures (MCMs)? Is it a realistic scenario or should local
health departments presume an EUA will be the vehicle that authorizes
dispensing/administration? What is the status of an EUA for anthrax vaccine for PEP?
Health departments should not presume that an EUA or other legal or regulatory mechanism will be the
vehicle that authorizes dispensing or administration of all MCMs.
The goal is to have approved MCMs available and ready for use during emergencies without the need to
use unapproved MCMs. If the only available MCM for an emergency response is unapproved, then FDA
could make such products available using several mechanisms. The type of mechanism that might be
used to allow for the emergency use of medical products during CBRN emergencies would depend on
the specific scope and circumstances of an emergency and the products that might be needed (and how
such products might be used) for the emergency response.
Before FDA can issue an EUA, certain statutory criteria must be met. For example, no adequate,
approved, and available alternative to the product must exist, and the known and potential benefits of the
product must outweigh its known and potential risks. These criteria cannot always be met, even during
emergency circumstances. In some cases, therefore, an IND might be the more appropriate mechanism
to allow for the use of certain products during emergencies. The IND approach includes specific patient
protections, including informed consent and institutional review board (IRB) approval.
As an example, anthrax vaccine adsorbed (AVA) is a licensed vaccine to prevent against anthrax for
adults 18-65 years of age who are at high risk for exposure to B. anthracis. Safety and efficacy have
been established for that population, but not for other populations (e.g., pediatric populations or pregnant
women). In addition, AVA is not approved for the indication of PEP of inhalational anthrax for any
population. The current thinking is that an EUA would be used for the PEP indication for adults in
response to an anthrax emergency because there exists significant data to support the risk-benefit
determination that FDA needs to make in order to issue an EUA. However, the current thinking is also
that an IND would be used for AVA use in the pediatric population. This is because there is no safety or
efficacy data for that population on which FDA can make a determination that the known and potential
benefits of AVA outweigh its known and potential risks in order to issue an EUA. Because it is
recognized that the typical IND informed consent and IRB processes may not be feasible in wide-area
anthrax emergency scenarios, more streamlined approaches are being explored for this specific type of
emergency.
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5.
How confident is the FDA that the terms of EUAs will preempt state law? Are there any subject
areas where FDA is cautious in claiming EUA preemption over state law (e.g., licensing, scope of
practice)? In follow up, the EUA guidance states: "FDA anticipates consulting state officials when
the terms and conditions of an EUA may preempt state law?” Is this happening? In an event in
which MCMs have been pushed out, such as through the SNS for PODs, does federal authority
concerning labeling and dispensing of those MCMs during the event supplant state law
requirements concerning labeling and dispensing of medical products?
As indicated in FDA’s EUA Guidance,4 FDA believes that the terms and conditions of an EUA issued
under section 564 of the FD&C Act preempt state law—legislative requirements and common law
duties—imposing different or additional requirements on the medical product for which the EUA was
issued in the context of the emergency declared under section 564.
Although section 564 of the FD&C Act does not include express preemption language, the Public
Readiness and Emergency Preparedness (PREP) Act, which provides limited immunity from tort
liability associated with certain medical countermeasure activities, includes express preemption
language regarding the FD&C Act [42 U.S.C. § 247d-6d(b)(8)]. This includes actions taken to meet the
terms of an EUA, investigational application, or any FDA-approved MCM. To date, all EUA products
have been covered by PREP Act declarations. (For additional details about the PREP Act, see Question
6 below.)
FDA is interested in learning from states about specific examples of legal concerns associated with
preemption that extend beyond tort liability, as well as specific terms or conditions that have prompted
the question regarding FDA consultation with states about preemption.
6.
Please discuss your thoughts on application of PREP Act liability protections in the event that the
U.S. donates MCMs to foreign nations (and please ignore the staggering difficulty inherent in
actually making such a donation).
The PREP Act authorizes the HHS Secretary to issue a PREP Act declaration that provides immunity
from tort liability (except for willful misconduct) for claims of loss caused by, arising out of, relating to,
or resulting from the administration or use of a countermeasure to a disease, threat, or condition
determined by the HHS Secretary to constitute a present or credible risk of a future public health
emergency to entities and individuals involved in the development, manufacture, testing, distribution,
administration, and use of the countermeasure. A PREP Act declaration is specifically for the purpose of
providing immunity from tort liability, and is different from, and not dependent on, other emergency
declarations.
Countermeasures covered under a PREP Act declaration can include products that are approved, cleared,
or licensed under the FD&C Act or the PHS Act, authorized for investigational use under the FD&C
Act, or authorized under an EUA. For example, if a person is given a countermeasure that is authorized
for emergency use under an EUA and a PREP Act declaration covering the countermeasure has been
made by the HHS Secretary, then that person may be eligible under the PREP Act for compensation
4
U.S. Department of Health and Human Services, Food and Drug Administration. Guidance—Emergency Use Authorization of
Medical Products. July 2007. http://www.fda.gov/RegulatoryInformation/Guidances/ucm125127.htm.
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through the Countermeasures Injury Compensation Program (CICP) if serious physical injury or death
results from use of the countermeasure.
According to the HHS Public Readiness and Emergency Preparedness Act Questions and Answers,5
immunity from liability is not available under the PREP Act for claims filed under foreign law in courts
outside the United States. Immunity may be available for claims filed under United States law in United
States courts, even when based on events that took place outside the United States. In addition, the CICP
has promulgated regulations that extend the compensation program to some foreign administration and
use (75 Fed. Reg. 63656, 63660). Immunity from liability is not available under the PREP Act for
lawsuits other than tort claims.
For additional information about the PREP Act, please refer to the HHS Public Readiness and Emergency
Preparedness Act Questions and Answers.
5
U.S. Department of Health and Human Services, Office of the Assistant Secretary for Preparedness and Response. Public Readiness
and Emergency Preparedness Act Questions and Answers. http://www.phe.gov/Preparedness/legal/prepact/Pages/prepqa.aspx.
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