Investigational New Drug (IND) Application, Emergency Use Authorization (EUA), and
Emergency Use Instructions (EUI): General Information Regarding Regulatory Mechanisms for Emergency Use of Stockpiled Medical Countermeasures
During a public health emergency such as an influenza pandemic or a bioterrorism event, the Centers for Disease Control and Prevention (CDC) may deploy medical countermeasures (e.g., drugs, biologics, and devices), from the Strategic National Stockpile (SNS) to help prevent, treat, and diagnose diseases or adverse effects caused by the medical countermeasures (MCMs) themselves. The deployed MCMs are subject to regulation by the U.S. Food and Drug Administration (FDA).
1. What regulatory mechanisms apply to MCMs deployed from the SNS?
The MCMs deployed from the SNS will include medical products that are:
· approved, licensed, or cleared by FDA;
or
· covered under an Investigational New Drug (IND) application or Investigational Device Exemption (IDE); or
· covered under an Emergency Use Authorization (EUA) or Emergency Use Instructions (EUI).
Additionally, certain emergency preparedness and response activities involving MCMs such as pre-positioning, deployment, distribution, and clinical use will proceed under the appropriate regulatory status (i.e., FDA-approved; IND or IDE; or EUA or EUI). The regulatory route will depend on the MCM’s FDA-approved status and intended emergency use. MCM activities (e.g., distribution, dispensing, usage, data collection) that proceed under an appropriate regulatory mechanism are eligible for liability protections under the Public Readiness and Emergency Preparedness (PREP) Act (See Question #7).
2. What is an Investigational New Drug (IND) application? An IND is a regulatory mechanism through which FDA permits access to an investigational medical product (i.e., unapproved product or unapproved use of an approved product) for clinical use or clinical study, also known as experimental or off-label use. Use of an MCM from SNS will likely proceed under a specific type of IND, called Expanded Access (also known as “compassionate” use) referring to use outside of a clinical trial. Under an IND, informed consent must be obtained from recipients, who must be informed of the investigational nature of the product; its intended use, risks and benefits; and other available treatments. Recipients should be given an opportunity to ask questions and receive information. Healthcare providers and public health officials involved in activities under the IND (e.g., informed consent, dispensing, monitoring) are considered as investigators per the FDA IND regulations; therefore, they will be required to comply with applicable IND regulations. IND requirements include monitoring safety, collecting and reporting data, receiving institutional review board (IRB) approval, and obtaining informed consent. For additional information, please see FDA’s Expanded Access IND webpage.
3. What is an Emergency Use Authorization (EUA)? An EUA is issued by the FDA commissioner to permit the emergency use of an unapproved medical product or unapproved use of an approved medical product to diagnose, treat, or prevent serious or life-threatening diseases or conditions for which no adequate, FDA-approved alternative is available. An EUA is predicated on the determination and declaration of emergency. First, determination must be made by the secretary of the Department of Homeland Security (DHS), the Department of Defense (DoD), or the Department of Health and Human Services (HHS), or a material threat determination by the DHS that there is an actual or potential domestic, military, or public health emergency involving a chemical, biological, radiological, or nuclear (CBRN) threat. Once the determination has been made, then the HHS Secretary declares a public health emergency justifying EUA.
MCM information will be provided in the form of the EUA Fact Sheet for Healthcare Providers and EUA Fact Sheet for Recipients/Patients in accordance with applicable mandatory or discretionary conditions of authorized use as issued by FDA. IRB approval and informed consent are not required under EUA. For additional information, please see FDA’s EUA webpage.
MCM use under an EUA is only authorized after FDA has issued the EUA. “Pre-EUA” is an administrative mechanism that allows for formal correspondence with FDA to obtain its review regarding the proposed emergency use of an MCM in the event of a potential public health emergency. This process is to facilitate the timely review of an EUA request during an actual or emerging public health emergency.
4. What are Emergency Use Instructions (EUI)?EUI are issued by CDC to permit stakeholders (including a federal, State, local, or tribal government entity, or a person acting on behalf of such a government entity) to disseminate emergency use instructions of a given MCM for a specific threat/disease. EUI apply only to approved, licensed, or cleared MCMs. EUI inform healthcare providers and recipients during an emergency about the MCM's approved, licensed, or cleared condition(s) of use that may deviate from the MCM’s approved labeling, standard clinical practice, and/or standard medical modality (individual prescription within the patient-clinician relationship). CDC’s issuance of EUI is predicated on a determination being made by the Secretary of DHS, DoD, or HHS that an actual or potential domestic, military, or public health emergency involving a CBRN threat exists. EUI are similar in purpose to the EUA Fact Sheet for Healthcare Providers and Fact Sheet for Recipients/Patients. MCMs covered under EUI are eligible for liability protection under the PREP Act (See Question #7).
EUI for doxycycline and ciprofloxacin were issued by CDC on March 28, 2016. Mass dispensing orders for doxycycline and ciprofloxacin were issued by FDA on April 13, 2016. Together they allow for preparedness among stakeholders in advance of an actual anthrax event. The doxycycline and ciprofloxacin EUI Fact Sheets for Healthcare Providers and Recipients can be disseminated at the time of dispensing of these antimicrobials during an event.The doxycycline mass dispensing order, current good manufacturing practices (cGMP) waiver, and EUI replace the previous FDA-issued Emergency Use Authorization.
5. Which specific FDA-regulated mechanism will be used for the release of MCMs from the SNS?The deployment of MCMs from the SNS will proceed under an appropriate regulatory status (FDA-approved; IND or IDE; or EUA or EUI) depending on the MCM’s intended emergency use. Each regulatory status or mechanism will cover a specific MCM for a specific threat or disease (e.g., separate EUA for gentamicin for treatment of tularemia and gentamicin for treatment of plague). In addition, use of a given MCM for the same threat or disease may potentially proceed under different regulatory mechanisms depending on the circumstances of the emergency, available data to support its use, and the provisions needed to safeguard the use in different populations (e.g., Neupogen under its approved use and under EUI for a modified dosing regimen).
6. For which MCMs would CDC issue EUI or hold an EUA or IND?
CDC will create and issue EUI and/or hold an EUA or IND only for MCMs that are stockpiled in the SNS or otherwise provided by CDC. CDC-issued EUI and/or a CDC-held EUA or IND for an MCM are also anticipated to extend regulatory coverage to similar MCMs that are lawfully marketed (e.g., FDA-approved and commercially available MCMs, states’ caches) provided that the MCM’s deployment, storage, and clinical use are in accordance with the terms of EUA, EUI, and/or IND.
7. What is the Public Readiness and Emergency Preparedness Act (PREP Act)?
The PREP Act authorizes the Secretary of HHS to issue a declaration that provides immunity from liability for claims of loss caused by MCMs to entities and individuals involved in certain activities regarding such MCMs. The PREP Act also authorizes an emergency fund in the U.S. Treasury to provide compensation for injuries directly caused by administration or use of the MCM covered by the Secretary’s declaration. For MCMs to be covered by immunity from liability afforded by the PREP Act during a public health emergency, they must be approved, cleared, or licensed or used under an IND/IDE or EUA/EUI. For more information, please see the Assistant Secretary for Preparedness and Response’s PREP Act webpage.
8. What are the expected responsibilities for State, Local, Tribal and Territorial (SLTT) and healthcare providers when dispensing and utilizing MCMs?
It is expected that SLTT and healthcare providers who are dispensing and utilizing an MCM will do so in accordance with the terms and conditions of the applicable regulatory mechanism. Responsibilities may include, but are not limited to:
· Communicating pertinent information to the patient/recipient including:
o description of the intended use of the MCM and instructions for use/administration
o significant known/potential risks and benefits of the MCM and the extent to which potential risks and benefits are unknown
o option to refuse the MCM and potential consequences of refusing
o availability of any alternative MCMs
· Monitoring and reporting adverse events
· Complying with any EUA conditions that may be imposed by FDA or IND requirements per FDA regulations
SLTT and healthcare providers should also be cognizant of the relevant PREP Act declarations and distribute MCMs accordingly in order to be covered under the Act's liability protections.
9. Where/how would MCMs be dispensed in the event of an emergency?
MCMs distributed from SNS would be delivered to the affected state(s). Each state and local entity would receive and further distribute/dispense MCMs according to the plans set forth by state and local preparedness directors. MCMs may be provided directly to a hospital setting, as appropriate, depending on the level of medical care required and type of MCM utilized (e.g., hospitalized patients, intravenous administration). Information on MCM availability in local communities is anticipated to be provided through multiple communication outlets.
10. How will Fact Sheets for either a CDC-issued EUI or an FDA-issued EUA be provided?
It is expected that FDA-issued EUA Fact Sheets and CDC-issued EUI will be made available and disseminated through various methods of communication (e.g., internet posting, hard copies, posters, or video messaging). Electronic versions of FDA-issued EUA Fact Sheets and/or CDC-issued EUI will be available on each agency’s respective websites and will be disseminated via email and social media as appropriate.
11. Can states distribute their own state-developed Fact Sheets for MCMs deployed from the SNS under EUA or EUI, or modify the existing Fact Sheets?
For FDA-issued EUA Fact Sheets, it is anticipated that FDA will outline the core information elements that must be contained in the EUA Fact Sheets and provide example versions authorized for dissemination. States will be allowed to create their own versions of EUA Fact Sheets provided that the contents are consistent with the FDA-issued EUA Fact Sheets and any EUA conditions specified by FDA. CDC-issued EUI Fact Sheets will be provided to aid states with information on the appropriate use of the MCM during the emergency with the option to include state-specific contact information.
12. Who can I contact for additional information regarding the regulatory mechanisms for MCMs deployed from the SNS?
For additional information concerning the regulatory mechanisms for MCMs deployed from the SNS (i.e., FDA-approved; IND or IDE; or EUA or EUI) contact CDC Regulatory Affairs at: .
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