Q's and A's on Public Health Preparedness Meeting
Questions and Answers on FDA Federal State, and Local Public Health Preparedness Meeting
Legal and Regulatory Perspectives
December 14-15, 2010
The statutory authority discussed in these questions and answers has been amended by PAHPRA, which was enacted in March 2013
This responds to specific questions that were raised by public health emergency preparedness officials and other invited participants during FDA’s December 14-15, 2010, meeting, Federal, State, and Local Public Health Preparedness Meeting: Legal and Regulatory Perspectives
. Additional information, including guidance, on FDA’s Emergency Use Authorization (EUA) authority can be found on FDA’s EUA website
Emergency Use Authorization (EUA) Requests
1. Can a local jurisdiction initiate an EUA? What agency should a State contact to initiate an EUA?
Although the Food and Drug Administration (FDA) has issued a number of EUAs at the request of manufacturers and laboratories [i.e., in vitro diagnostic (IVD) EUAs during the H1N1 response], it most typically works with federal government partners to develop EUAs. FDA cannot manage simultaneous requests by multiple jurisdictions for the same uses of the same products during an emergency. This is why the Centers for Disease Control and Prevention (CDC) is the most appropriate requester for products stockpiled by State and local jurisdictions. Therefore, States wanting to request an EUA should work through their CDC partners, and local jurisdictions should work through their State and/or CDC partners, as appropriate.
2. If doxycycline and ciprofloxacin are both approved by the FDA for treatment and post-exposure prophylaxis (PEP) of inhalational anthrax, why is it necessary to issue an EUA for these products?
Doxycycline is FDA-approved for the treatment of inhalational anthrax; ciprofloxacin is not. Both doxycycline and ciprofloxacin are FDA-approved for post-exposure prophylaxis (PEP) against inhalational anthrax. The duration of therapy for PEP against inhalational anthrax in the FDA-approved labeling for these medical countermeasures (MCMs) is 60 days. Therefore, plans that call for dispensing as part of a mass distribution strategy in a manner that is not consistent with their approved applications would render the drugs unapproved under federal law. Examples of these types of distribution include, but are not limited to:
(1) Dispensing of a prescription drug without a prescription;
(2) Distribution with information that is not consistent with the FDA-approved labeling for the product (e.g., information about a 10-day dosing regimen or home preparation instructions for doxycycline);
(3) Storage or holding that is not in compliance with storage requirements [i.e., not in compliance with current good manufacturing practice (CGMP) requirements];
(4) Distribution that does not include information on the bottle labels that is required by FDA law and regulations; and
(5) Distribution and relabeling of products that are part of the Shelf-Life Extension Program (SLEP).
Irrespective of dispensing modality, if doxycycline and ciprofloxacin are distributed or dispensed in a manner that is not consistent with their product approval and FDA laws and regulations, FDA may exercise enforcement discretion for these types of violations. However, not having an EUA in place may jeopardize Public Readiness and Emergency Preparedness (PREP) Act liability protection. This is because the PREP Act protection for these products requires the use to be licensed, approved, or cleared; covered under an investigational application; or authorized under an EUA. Therefore, FDA issues EUAs to ensure there is no gap in PREP Act coverage.
3. Can FDA/CDC provide a list of circumstances for when an EUA will be issued, for which medications, and for when an EUA will not be needed?
Because the decision to issue an EUA is event-specific, there is no comprehensive list of all possibilities for when an EUA will be issued. Typically, the federal government [e.g., CDC; Department of Health and Human Services (HHS)] or manufacturers will request an EUA in the event issuance is necessary. However, FDA recognizes the importance of delivering the right medical product to the right person during a public health emergency to prevent or treat illness resulting from the emergency (i.e., FDA may exercise enforcement discretion with regard to certain violations of FDA laws and regulations). In addition, FDA is always working with its federal partners to develop pre-EUAs (for unapproved products or for approved products to be used in ways that may be inconsistent with the limitations of the approval) for the purpose of minimizing delays in EUA issuance at the time of an emergency.
4. Is there any large scale event involving bioterrorism or another public health threat when medical intervention is needed but an EUA is not required?
If a medical product is used as approved (see Question 2), there would be no need for an EUA. While it did not involve bioterrorism, an example of this scenario is the 2009 H1N1 vaccine. The H1N1 vaccines were manufactured using the same approved processes, licensed under the same regulatory mechanism, and dispensed via the same administration mechanisms (in accord with State practice laws) as those used to produce, license, and dispense the seasonal influenza vaccines. However, during such a scenario, it would be important that any messaging, such as fact sheets with instructions handed out to recipients of the product, concerning the required dose be consistent with the approved labeling.
5. Can an EUA be “pre-authorized” and shared with the States for planning purposes (i.e., in advance of emergencies)?
FDA cannot issue an EUA without statutory prerequisites. That is, the Secretary of HHS must issue a declaration of an emergency justifying the EUA based on one of three determinations involving specified biological, chemical, radiological, or nuclear agents by the: (1) Secretary of Homeland Security of an actual or significant potential for a domestic emergency; (2) Secretary of Defense of an actual or significant potential for a military emergency; or (3) Secretary of HHS of a public health emergency under section 319 of the Public Health Service Act that affects, or has the significant potential to affect, national security.
However, FDA will facilitate the development of pre-EUA submissions to FDA for preparedness purposes. These pre-EUAs allow FDA to review and evaluate product data and information prior to the submission of an EUA request during an emergency. For example, a pre-EUA for antimicrobials for PEP against inhalational anthrax was developed for the 2009 Presidential Inauguration. FDA recognizes State and local concerns about the timing of EUA issuance and related logistics (e.g., mass printing of fact sheets at the time of an emergency). To help facilitate pre-event planning, preparedness, and post-event implementation, FDA and its federal partners worked on the development of a new EUA for oral formulations of doxycycline for PEP against inhalational anthrax based on the 2009 pre-EUAs. This EUA was issued in July 2011.
Currently, there is a determination by the Secretary of Homeland Security that there exists a significant potential for a domestic emergency involving a heightened risk of attack with anthrax. In addition, there exists a declaration by the HHS Secretary that the Department of Homeland Security (DHS) determination justified authorization of emergency use of doxycycline tablet emergency kits for eligible United States Postal Service (USPS) workers who volunteer to participate and their household members as part of the Cities Readiness Initiative (CRI) (originally issued in 2008, but subsequently renewed; see 75 FR 61489
). Based on this declaration, FDA has issued an EUA (73 FR 62507
; amended in 2010
) to support the CRI USPS pilot initiatives. The DHS determination could support additional declarations by the HHS Secretary, such as the declaration for doxycycline that supported the issuance of the new EUA for mass dispensing of oral formulations of doxycycline for PEP against inhalational anthrax described above.
6. Must a fact sheet be given to the recipient of an EUA product even when the product is already approved for the intended use (e.g., doxycycline, which is both FDA-approved for treatment and PEP of inhalational anthrax)? Can an EUA be verbally communicated to the affected population or posted or published in the newspaper to meet the requirement for notification of the affected population? Can fact sheets be translated?
FDA's EUA Guidance
states that, ordinarily, FDA expects that some form of written information will be given to MCM recipients, similar to the fact sheet for health care providers or authorized dispensers. The guidance further states that although FDA contemplates that the fact sheet or other recipient information will be provided to recipients before
administration of an EUA product, if "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 of authorization that the information be provided to the recipient as soon as practicable afterward."
For example, in the case of doxycycline the question becomes whether, for patients who may not have the fact sheets available to them (but who may get the essential message some other way), doxycycline may be used effectively and the benefits of use of the doxycycline outweigh the risks. It is FDA's belief that there is a better likelihood that doxycycline will be used as directed if the fact sheet is provided at the time of dispensing. Therefore, State and local mass dispensing plans should provide for distribution of the recipient fact sheet to accompany the product.
Notification of information can be communicated via any variety of modalities, as long as the information delivered is consistent with the authorized information. Methods of communication that supplement and are consistent with the fact sheets required by a particular EUA would be permissible. For example, a condition of authorization for the H1N1 EUAs was to allow public health authorities to provide “additional information consistent with” the authorized fact sheets. “Additional information” could include direct translations of the fact sheets into other languages, a poster display, and DVD or television announcements that relay the information contained in the fact sheets.
Another condition of the H1N1 EUAs provided that State and/or local health authorities make available “through appropriate means” fact sheets developed for recipients and for health care providers for this emergency use. Making these fact sheets available “through appropriate means” can include handing that information to the recipient with the product or otherwise making it available for reference at the location where medications are being dispensed, depending on the circumstances of the emergency. If there were a need to provide updated information to recipients during an emergency response, and recognizing that it may be impossible at that point to mass produce revised versions of information sheets, alternative approaches (e.g., public service announcements) to disseminate the updated information would be acceptable. Planners also need to consider how populations that do not have access to electronic media can obtain the information.
7. Will FDA issue home preparation instructions for ciprofloxacin?
FDA has developed home preparation instructions for doxycycline that are available on FDA’s website (In an Emergency: How to Prepare Doxycycline for Children and Adults Who Cannot Swallow Pills
) in the event that sufficient quantities of oral suspension are unavailable. FDA recognizes and shares State and local concerns about developing ciprofloxacin home preparation instructions and wants to make sure that children are adequately protected during public health emergencies. Due to the drug’s unpalatable nature, FDA is working with others in HHS to determine appropriate foodstuffs that will yield palatable, home prepared ciprofloxacin and help ensure adequate adherence to this important medical countermeasure. Until that work is successful, FDA does not have sufficient information to consider issuing optimal home preparation instructions for ciprofloxacin in the interim.
Stockpile Storage and Shelf Life Extension at the State and Local Levels
8. In any and all distribution methods for countermeasures, who is responsible at the State and local levels for storage of unused Strategic National Stockpile (SNS) countermeasures, before, during, and after the event? Will the costs for storage be compensated? Will the States’ pharmacy laws for conditions of storage, monitoring, and accounting for pharmaceuticals apply to stored countermeasures?
State and local public health authorities are responsible for these stockpiles. FDA requires that all MCMs, including those received from the SNS, be stored according to CGMPs and labeled storage conditions. In certain circumstances, the H1N1 EUAs provided waivers of these requirements—based on FDA’s knowledge about product stability—for specified durations of time (e.g., 2 weeks) to facilitate movement of product. States will need to address their applicable pharmacy law questions on a state-by-state basis due to variation in state law. It is FDA’s position that state restrictions that directly conflict with what is permitted in the EUA would be preempted by federal law. CDC (not FDA) will need to address antiviral subsidy program questions regarding compensation of storage costs.
9. Will FDA consider State stockpiles eligible to participate in the federal Shelf-Life Extension Program?
SLEP is a federal, fee-for-service program, overseen by the Department of Defense, through which the labeled shelf life of certain federally-stockpiled medical materiel can be extended after selected products undergo periodic, comprehensive testing by FDA. The purpose of the SLEP session during this meeting was to introduce health authorities from the States and directly-funded cities to a tool they can utilize to generate detailed cost projections for assessing the value of participation in a SLEP-type program. In collaboration with the Association of State and Territorial Health Officials (ASTHO), all 62 jurisdictions that were eligible to participate in the federal antiviral procurement program (i.e., the 50 states; the District of Columbia; the territories and freely associated states in the Pacific and Caribbean; and Los Angeles, Chicago, and New York City) were invited to participate in the assessment. Analysis of the data that have been submitted is currently underway by the Biomedical Advanced Research and Development Authority (BARDA) within the HHS Office of the Assistant Secretary for Preparedness and Response (ASPR). The findings will ultimately help to inform HHS whether there is continued state interest when states have a better understanding of the costs involved, and whether SLEP is a truly viable option for state and local stockpiles.
10. How should State and local health and emergency management authorities handle expired or soon-to-expire State and local/regional (i.e., non-SNS) MCM stockpiles?
FDA’s June 22, 2010, letter, Tamiflu and Relenza Emergency Use Authorization Disposition Letters and Question and Answer Attachments
, provides information about the disposition by lot number of stockpiled antivirals at or nearing expiration (since the emergency use of certain expired lots of Tamiflu and Relenza were no longer authorized after June 23, 2010). Only through issuance of an EUA can FDA authorize the retention of expired drug products (e.g., doxycycline and ciprofloxacin); however, FDA can exercise its enforcement discretion in certain situations. In the June 2010 letter, FDA stated that it does not intend to take an enforcement action with regard to certain specified lots of antivirals that could be retained for potential use in future emergencies, provided that the products are stored under the labeled storage conditions. For further information about the current shelf life extension analysis, please refer to Question 9 above.
Relabeling and CGMP
11. During tight financial times, is it necessary to relabel medications (e.g., Tamiflu) in non-SNS stockpiles? In lieu of relabeling, can jurisdictions simply supply a letter of explanation indicating that a particular product/lot number has an extended shelf life?
As discussed in Question 10 above, FDA provided disposition information on its website on June 22, 2010, regarding the specified lots of Tamiflu and Relenza that had been authorized for use beyond their labeled expiration date during the H1N1 response. FDA stated that it did not intend to take an enforcement action with regard to the lots posted that were retained for potential use in future emergencies, provided that the products were stored under the labeled storage conditions. To minimize confusion on the part of healthcare professionals and patients, FDA recommended that, prior to dispensing, the identified lots be relabeled/repackaged by an FDA-registered firm in accordance with applicable CGMP requirements. During a declared emergency, FDA can issue an EUA authorizing a fact sheet indicating that certain product and lot numbers are authorized for use even though their labeled shelf life has expired, as occurred during the H1N1 response.
12. Is it possible for States to become certified relabelers? Is it possible for States to self-certify that they meet CGMP requirements?
Some States have inquired about whether it is possible for them to become relabelers for cost saving purposes when their MCM stockpiles require relabeling. Ordinarily, medical product relabelers must, among other things, be registered with FDA and comply with all CGMP requirements that apply to their operations (i.e., methods by which manufacturers, holders, and transporters of drugs, biologics, or devices assure that every product they make, hold, or transport is—and continues to be until it is used—safe and effective). FDA also inspects establishments engaged in relabeling or other manufacturing or processing activities to ensure compliance with applicable CGMP requirements. The feasibility of any alternative mechanisms for ensuring State relabeling efforts comply with applicable CGMP requirements needs to be evaluated and may depend on a variety of factors, such as the nature of the products or operations involved. In any event, States would need to assess their ability to comply with the applicable CGMP requirements, including whether it is cost-effective for them to do so. A good starting point for any organization beginning the drug registration and listing process is: www.fda.gov/edrls.
Dispensing from Non-Federal Stockpiles
13. If medications are distributed from a State or local stockpile before an EUA is issued, would the declaration of the EUA cover such distribution and dispensing? Can an EUA be retroactive?
Any distribution of a medical countermeasure (e.g., doxycycline; ciprofloxacin) as part of a mass dispensing strategy in a manner that is not consistent with its approved New Drug Application (NDA) or Abbreviated New Drug Application (ANDA) renders the drug unapproved under the law. It is anticipated that when these drugs are dispensed during an emergency, they would be accompanied by unapproved emergency use instructions or labeling and they would otherwise be dispensed for certain unapproved uses. For example, the drugs might be accompanied by unapproved instructions about tablet home preparation or an unapproved dosing regimen, or might be repackaged outside the scope of the approved drug application. Under the law, these types of changes from the approved labeling and uses would render the products unapproved and misbranded drugs.
While an EUA cannot be retroactive to a date prior to the declaration of the Secretary of HHS authorizing the EUA, during an emergency and before any EUA declaration has been issued it is possible that State, local, and other emergency planners might distribute drugs from their own (i.e., non-SNS) stockpiles to the affected population. As previously mentioned, FDA can consider in various situations whether to exercise its enforcement discretion. Should FDA exercise its enforcement discretion, it is possible that PREP Act protections may not apply with respect to those products. However, EUAs can be issued in such a way as to permit the use of the products that may have been transported or pre-positioned in technical violation of the federal Food, Drug, and Cosmetic Act (FDCA). This was the case with the H1N1 EUAs [e.g., for the personal protective equipment (PPE) EUA: “The above products, as deployed from the…SNS…before or after the signing of this letter of authorization, are authorized to be made available…”].
14. Will EUAs be issued for events in which medications from CDC or the federal government are not provided (i.e., non-SNS MCMs)? Will EUAs cover private entities, such as occupational health providers that do not have distributors’ licenses, outpatient clinics in occupational settings, and retail pharmacies? Does the PREP Act cover those facilities and private industries that dispense medications as part of a closed point of dispensing (POD)?
First, it is important to note that if a product is distributed, dispensed, and prescribed squarely within the product’s approval and in accordance with CGMP requirements and with State and local laws, an EUA is not necessary. Each EUA will state the limits of its coverage. FDA’s current thinking is that EUAs would, in most cases, apply to the authorization of a use of a product under specified conditions, regardless of the entity or the program (similar to what was done with the H1N1 Tamiflu and Relenza EUAs). The EUAs would impose conditions, such as authorizing products to be “distributed to recipients in accordance with applicable State and local laws and/or in accordance with the public health and medical emergency response of the Authority Having Jurisdiction to prescribe, administer, deliver, distribute, or dispense the covered” medical countermeasure. Note that this language uses terminology consistent with PREP Act declarations. If private entities are acting in accordance with State and local laws and/or in accordance with the public health response of the Authority Having Jurisdiction, then they would be within the scope of these EUAs and PREP Act coverage. However, if the EUA follows this model, private entities that do not distribute product in accordance with the public health response of the Authority Having Jurisdiction would not be within the scope of the EUA—or PREP Act protection—if uses are outside the limitations of products’ approval.
Non-Licensed Healthcare Practitioner and Volunteer Dispensing
15. Would an EUA be required if a medical countermeasure is distributed in a POD by non-licensed practitioners and/or volunteers if State law permits non-licensed practitioners and/or volunteers to dispense the prescription product during a declared emergency? (For example, could paramedics or pharmacists with just-in-time training vaccinate the target group? Does the use of volunteers require an EUA, even if State law authorizes volunteers to dispense MCMs during an emergency?)
States regulate the practice of medicine, pharmacy, and other health professions. To the extent that States seek to provide more options for medical countermeasure distribution and dispensing in the event of an emergency (e.g., by authorizing paramedics or pharmacists to administer pandemic influenza vaccine to the public), State laws can potentially allow for this flexibility. For example, States (e.g., Massachusetts, Maryland, Ohio) may have laws or regulations that specifically authorize temporary expansions of practitioner scopes of practice for activities such as mass vaccination under certain emergency circumstances. State and local mass dispensing and other emergency plans and laws also vary in their use and authorization of volunteers to dispense MCMs during public health emergencies (e.g., many States may authorize non-healthcare practitioner volunteers to dispense doxycycline and ciprofloxacin to the public at PODs following an anthrax attack).
Regardless of whom a State or local jurisdiction authorizes to dispense or administer a medical countermeasure during an emergency, if the MCM is distributed, dispensed, or administered outside of its FDA-approved use or in violation of the FDCA (e.g., without the labeling normally required for a prescription drug upon dispensing), an EUA would be required to ensure PREP Act coverage is not jeopardized. (FDA may exercise its enforcement discretion with regard to such uses of approved MCMs, but the issuance of an EUA would be necessary to assure PREP Act coverage.) With respect to the emergency use of an unapproved product, the Secretary may establish such EUA conditions as the Secretary finds necessary or appropriate to protect the public health, including conditions on who may administer the product.
USPS Biohazard Detection System (BDS) and CHEMPACK
16. Would an EUA be issued for small-scale events such as a USPS BDS response? Does the PREP Act provide coverage for such events?
The necessary federal determinations and declarations need to be issued for EUA issuance and PREP Act coverage. To the extent that plans are being developed to address a response to a small-scale event based on a BDS alarm, jurisdictions with BDS responsibilities should consider developing plans that are within the product’s approval and in accordance with federal and State laws. If they are not (e.g., if the labeling for the antibiotics supplied by USPS for its workers in the event of a BDS Alert-Positive Test is not in accordance with federal law), then an EUA would be required. In certain situations, FDA can consider whether to exercise its enforcement discretion. However, if FDA exercises its enforcement discretion, then it is possible that PREP Act protections may not apply with respect to the USPS BDS drugs if a declaration is issued that covers these products.
17. Is there currently PREP Act protection for local responders who might need to administer treatment from a CHEMPACK (i.e., nerve agent antidote)?
Products pre-deployed through the CHEMPACK program include auto-injectors, bulk symptomatic treatment supplies, and other products intended to treat and care for individuals exposed to nerve agents. At present, there is no PREP Act declaration explicitly drafted to cover products intended for treatment of nerve agents. PREP Act coverage for CHEMPACK would be available if: 1) the countermeasures are used for a disease or condition covered by a current PREP Act declaration; and 2) the countermeasures are used consistent with FDA requirements under one of the available mechanisms [licensing, approval, clearance, investigational new drug (IND), investigational device exemption (IDE), EUA]; and 3) the countermeasures relate to a federal contract or are used following an emergency declaration by the authority having jurisdiction to respond. CHEMPACK products relate to a federal contract, so the third criterion is already met. Additional steps would be needed to provide PREP Act coverage: (1) because diseases or conditions related to nerve agents are not currently covered by a PREP Act declaration; and (2) if these products are not used during a response as approved, cleared, licensed, or authorized for use by FDA under an IND, IDE, or EUA.
18. What was the purpose of the EUA for N95 respirators?
FDA issued an EUA for certain disposable respirators known as N95 respirators to permit the deployment of these products—accompanied by fact sheets with information for use during the 2009 H1N1 influenza pandemic—from the SNS for use by the general public to help reduce wearer exposure to airborne germs during this emergency. An EUA was necessary for those respirators that had not been previously cleared by FDA for this use. The term "general public" in this EUA was broad and included people performing work-related duties. However, if the respirator use was within the scope of employment, then the EUA did not affect Occupational Safety and Health Administration (OSHA) regulations. In other words, the EUA did not negate OSHA regulations for fit-testing of N95 respirators in the workplace, meaning that fit testing was still required in the workplace.
19. Have HHS and the FDA considered waiving the “legend drug status” of pharmaceutical countermeasures during a declared public health emergency to allow more options for distribution, particularly by eliminating the requirement for a written or oral prescription? EUAs may waive certain statutory label requirements, but many State laws will "mirror" federal law—does the EUA preempt State law? How does an EUA affect State laws?
The requirement for dispensing a drug pursuant to a prescription could be waived as part of an EUA. As stated in the FDA’s EUA Guidance, FDA believes that the terms and conditions of an EUA issued under section 564 of the FDCA preempt State law (i.e., 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. Questions about whether specific State laws would be preempted by an EUA would need to be addressed on a case-by-case basis.
20. Does the PREP Act cover foreign federal properties, such as embassies?
Geographic application of the liability protections under the PREP Act is discussed in Public Readiness and Emergency Preparedness Act Questions and Answers
(refer to the response to Question 4 in paragraph 4), which states that “[i]mmunity from liability also 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.” Territorial application of the PREP Act Countermeasures Injury Compensation Program (CICP) provisions is explained in the interim final rule at 75 FR 63656
(October 15, 2010; see 75 FR 63660). According to the interim final rule, the HHS Secretary “has determined that, solely for the purpose of administering the CICP,
otherwise eligible individuals at American embassies, military installations abroad (such as military bases, ships, and camps) or at North Atlantic Treaty Organization (NATO) installations (subject to the NATO Status of Forces Agreement) where American servicemen and servicewomen are stationed may be considered for CICP benefits.