The Centers for Disease Control and Prevention’s Strategic National Stockpile is a national repository of potentially life-saving medical countermeasures including pharmaceuticals and medical supplies for use in a public health emergency severe enough to cause local, regional, and state supplies to run out.

Several planning considerations can assist state, local, tribal, and territorial jurisdictions in preparing to receive, distribute, dispense, and administer medical countermeasures from the Strategic National Stockpile. These considerations include, but are not limited to, issues surrounding regulatory requirements, controlled substances, cold chain management, and ancillary supply needs.

Multiple aspects to consider for each of these functions are discussed here to assist partners in their planning efforts.

The Strategic National Stockpile (SNS) of the Centers for Disease Control and Prevention (CDC) is a national repository of medical countermeasures (MCMs) that includes pharmaceuticals (antimicrobials, biologics, vaccines, and antitoxins) and nonpharmaceuticals (medical supplies, personal protective equipment, and durable medical equipment) that could be used to support state, local, tribal, and territorial (SLTT) jurisdictions during large-scale biological, chemical, radiological, or nuclear incidents; natural disasters; or public health emergencies related to emerging infectious diseases.1

SNS medical countermeasures are intended to supplement SLTT jurisdictions when their pharmaceutical or medical supplies are diminished as a result of a large-scale public health incident or when the countermeasures needed for the incident require SNS-specific products that may not be locally available or are not available readily in the commercial market. SNS medical countermeasures can be used to protect individuals from or treat illnesses caused by a specific threat or disease.

The CDC’s guidance includes recommendations for safe and effective use of MCMs for all affected populations (e.g., children, pregnant and postpartum women, elderly individuals, and immunocompromised individuals) to the extent supportive data are available.2 The SNS can deploy MCMs to SLTT partners in support of an isolated or a large-scale incident. In some cases, MCMs may already be pre-positioned in jurisdictions so that they are accessible for immediate use and administration. For example, through the Strategic National Stockpile CHEMPACK program, antidotes to specific agents are placed in various jurisdictions to ensure their accessibility in case of a chemical nerve agent attack or organophosphate poisoning.3

The process of identifying and incorporating MCMs into the SNS is coordinated through a federal interagency governing body known as the Public Health Emergency Medical Countermeasure Enterprise,4 established in 2006 by Congress to coordinate federal efforts to enhance preparedness from an MCM perspective. This governing body sets SNS medical countermeasure type and quantity requirements based on material threat determinations generated by the Department of Homeland Security, with subsequent health consequence modeling performed by the Department of Health and Human Services. Partners in this interagency effort use this information, in addition to other factors such as funding and market availability, to prioritize MCMs for procurement during annual reviews of the SNS medical countermeasure formulary.

SNS medical countermeasures may be released to support a public health emergency after a formal state request and federal approval to deploy. SNS medical countermeasure needs will be specific to the incident and the jurisdictional request, with the goal of protecting and saving lives. The time frame for receiving these MCMs is dependent on the situation in question: delivery to an affected locale may occur almost immediately for products pre-positioned nearby, up to 24 hours or more after the federal decision to deploy SNS assets, or over time depending on SLTT needs and incident durations. In the case of certain threats such as anthrax that require rapid dispensing to the public, SNS assets may arrive in 12 hours or less, especially in high-risk and heavily populated areas (e.g., large metropolitan areas).

SLTT planning efforts must be considered prior to any incident occurring to ensure timely and effective MCM deployment, distribution, dispensing, and administration. Response planning will be tailored to and conducted by each jurisdiction; however, in preparation for initial SNS medical countermeasure delivery and receipt, all jurisdictional response plans should incorporate considerations including but not limited to regulatory requirements, controlled substances, cold chain management, and ancillary supply needs.

Distribution and clinical use of medical products such as drugs, biologics, and medical devices are subject to US Food and Drug Administration (FDA) regulations, including stockpiled MCMs deployed from the SNS. Regulatory mechanisms are important because they facilitate MCM activities such as storage, distribution, dispensing, clinical use, and data collection. As well, liability protection available under the Public Readiness and Emergency Preparedness Act applies to MCMs used under appropriate regulatory mechanisms.5 This legislation authorizes the Department of Health and Human Services Secretary to issue a declaration providing immunity (except in cases of willful misconduct) for claims related to administration or use of MCMs against diseases or threats determined via the Secretary’s declaration.

Different regulatory mechanisms may apply depending on the approval status of SNS medical countermeasures, available scientific information about these countermeasures, their intended use, and the circumstances of the event. State and local health officials receiving MCMs from the SNS should be aware of the type of regulatory mechanism an MCM falls under and requirements associated with that mechanism. SNS medical countermeasures may include medical products used under one or more of the following regulatory mechanism categories: FDA approved, licensed, or cleared; investigational new drug application (IND); emergency use authorization (EUA); or CDC Emergency Use Instructions (EUI) authority (with or without the FDA’s other emergency use authorities).

Investigational New Drug Applications

An IND is a regulatory mechanism by which the FDA permits use of an MCM that has not been approved by the FDA (i.e., an “investigational” or unapproved product) or unapproved use of an FDA-approved MCM (also referred to as off-label use). INDs can be used for clinical trials or expanded access (i.e., “compassionate use”). IND requirements include obtaining informed consent, monitoring safety, collecting and reporting data, and obtaining institutional review board approval.

CDC institutional review board approval is in place for SNS medical countermeasures that are required to be used under an IND. Therefore, each state or local health jurisdiction can rely on or cede to the CDC’s institutional review board as the central institutional review board, which can help reduce the administrative burden on local jurisdictions. Informed consent involves discussions with recipients or legal guardians, obtaining their signatures, and recordkeeping. Health care providers and public health officials involved in activities under the IND mechanism (e.g., informed consent, product accountability and recordkeeping, adverse event monitoring and reporting) are considered investigators per the FDA investigational new drug regulations and must comply with applicable regulations.

An example of an MCM expected to be used via an expanded access IND mechanism during a public health emergency response is anthrax vaccine adsorbed (AVA) for children younger than 18 years.6 Although the FDA has approved AVA for postexposure prophylaxis among adults aged 18 to 65 years, it has not been approved for children.7 Because currently no pediatric AVA data are available, AVA administration among children must be under an expanded access IND mechanism if an anthrax event occurs that involves use of AVA postexposure prophylaxis for children. Given the public health responsibility to evaluate AVA if the vaccine is used to protect a pediatric population during an anthrax event, a separate study protocol would be implemented to assess immunogenicity and reactogenicity among a subset of children who have voluntarily been vaccinated with AVA under an expanded access IND.

Emergency Use Authorization

An EUA is a statutory authority of the FDA commissioner to authorize the use of unapproved products or unapproved uses of approved products for the diagnosis, treatment, or prevention of serious or life-threatening diseases for which no adequate, approved, or available alternatives exist. FDA issuance of an EUA is predicated by determination of an emergency by the Department of Homeland Security Secretary, Department of Defense Secretary, or Department of Health and Human Services Secretary and an emergency declaration by the Department of Health and Human Services Secretary.8 Unlike with an IND, institutional review board approval and informed consent are not required for MCM use under an EUA.

Each EUA includes conditions of authorization that are specific to the MCM and the emergency response. For example, information about emergency use of the authorized MCM will be provided via EUA fact sheets for health care providers and recipients. State and local health officials should expect to distribute EUA fact sheets in accordance with the EUA conditions. Fact sheets may be provided in a number of ways during an incident (e.g., via hardcopy, the Internet, mailings, posters, radio or TV, public service announcements, newspapers). EUA fact sheets issued for SNS-held MCMs will be available in multiple languages. Adverse event monitoring and reporting, as well as recordkeeping and reporting, are requirements under an EUA. The FDA commissioner may establish additional conditions on MCM uses, including but not limited to product distribution and administration and data collection and analysis. An example of a currently issued EUA is authorization of the atropine auto-injector for nerve agent or insecticide poisoning.3

Emergency Use Instructions

Depending on the circumstances of an emergency, use of an FDA-approved MCM regarding its FDA-approved indication may need to be modified. EUI authority, delegated to the CDC, facilitates such modified emergency uses (e.g., dosing regimens, durations differing from approved labeling). EUI provide essential information regarding emergency use of the MCM, including clear instructions on product use, potential risks and benefits of the MCM, and event-specific emergency instructions or modifications from approved labeling or use, such as a change in dosing or duration. Similar to EUAs, EUI also include fact sheets for health care providers and recipients. EUI fact sheets will be available in multiple languages, and, as noted, state and local health officials can distribute fact sheets in a number of ways during an incident.

Other FDA emergency use authorities (e.g., emergency dispensing orders, expiry extensions, waivers of current good manufacturing practices, and the Risk Evaluation and Mitigation Strategies requirement) may be issued in concert with EUI. For example, the FDA issued emergency dispensing orders for doxycycline and ciprofloxacin concurrent to the CDC-issued EUI for use of these MCMs for anthrax postexposure prophylaxis.9,10

MCMs can be used via multiple regulatory mechanisms for different populations during a response, so it is essential that state and local health officials stay informed of communications from the CDC and FDA regarding SNS-deployed MCMs. As SNS assets are deployed throughout a response, the CDC, in coordination with the FDA, will communicate regulatory mechanisms by which MCMs will be used so that health officials are able to prepare accordingly. Irrespective of the regulatory mechanisms required for SNS medical countermeasures, distribution and patient tracking may be required given that the data gathered would provide access to information that can be used, if necessary, to facilitate a recall of the MCM being used, investigate safety issues with the MCM, or document patient administration (see the box on this page).

BOX 1
Summary Comparison of Investigational New Drug Applications, Emergency Use Authorizations, and Other Emergency Use Authorities
Table
Table
Investigational New Drug ApplicationsEmergency Use AuthorizationsOther Emergency Use Authoritiesa
Nonemergency or emergencyEmergency or pre-event preparednessEmergency or pre-event preparedness
No emergency declaration requiredEmergency/potential emergency determination and declaration requiredEmergency/potential emergency determination required
MCM use for isolated incidents or mass eventsMCM use for mass eventsMCM use for mass events
Unapproved MCM or unapproved use of approved MCMUnapproved MCM or unapproved use of approved MCMApproved MCM regarding approved conditions of use
IRB review/approval requiredNo IRB review/approval requiredNo IRB review/approval required
Informed consent requiredIncludes fact sheets for health care providers and recipientsIncludes EUI (fact sheets for health care providers and recipients)
Authorized by FDAAuthorized by FDAEUI issued by CDC with or without FDA’s other emergency use authorities
Data collection and reporting (e.g., recordkeeping, adverse events, clinical outcomes)Conditions per FDA (e.g., recordkeeping, adverse events)Voluntary adverse event reporting
Liability protection under PREP appliesLiability protection under PREP appliesLiability protection under PREP applies
Example: anthrax vaccine adsorbed for anthrax postexposure prophylaxis among childrenExample: atropine auto-injector for nerve agent or insecticide poisoningExample: ciprofloxacin and doxycycline for anthrax postexposure prophylaxis

Note. CDC = Centers for Disease Control and Prevention; EUI = Emergency Use Instructions; FDA = US Food and Drug Administration; IRB = institutional review board; MCM = medical countermeasure; PREP = Public Readiness and Emergency Preparedness Act.

aThe CDC’s EUI with or without the FDA’s other emergency use authorities.

The transfer of SNS assets must also comply with regulations set forth by the Drug Enforcement Administration (DEA).11 The DEA is the lead agency responsible for enforcing controlled substance laws and regulations in the United States as well as the provisions of the Controlled Substances Act as they pertain to the distribution and dispensing of legal controlled substances.12 The Controlled Substances Act categorizes all substances into one of five schedules according to their medical use, potential for abuse, and safety or dependence liability.13 The SNS currently contains drugs classified as Schedule II and Schedule IV controlled substances that could be used during a public health emergency.14

SNS controlled substances will be deployed in accordance with DEA federal regulations, including product delivery in secured and approved DEA containers. To receive controlled substances from SNS, a jurisdiction must identify an authorized DEA registrant or an authorized designated assignee to sign appropriate custody and transfer forms, including DEA’s Form 222 (an order and receipt form available to and signed by authorized DEA registrants for recording chain of custody). Once received, the transfer and storage of the controlled substances should include appropriate security measures, cold chain management, and product tracking, in accordance with Title 21 Code of Federal Regulations (21 CFR), chapter II.15

SLTT partners receiving controlled substances from the SNS must abide by all local, state, and federal regulations pertaining to the distribution, dispensing, and tracking of these products down to the patient level, similar to those processes already in place to support area health care facilities on a daily basis. In some instances, the controlled substance laws of the jurisdiction may be more stringent than 21 CFR. Planners should consult with their local DEA office and their jurisdiction’s public health legal advisors to review and ensure compliance with federal and state laws.

Transfer of certain controlled substances, vaccines, and biologics from the SNS requires adherence to cold chain management, which involves a system for transporting, storing, and distributing products at refrigerated (2°–8°C [35°–46°F]) or freezing (at or below 0°C [32°F]) temperatures to maintain their potency per current good manufacturing practices described in 21 CFR, part 211.16 Although the SNS may deploy frozen or refrigerated products, SLTTs would be expected to maintain products at refrigerated temperatures for immediate use. Temperature documentation and validation are also necessary under current good manufacturing practices to ensure that the safety, efficacy, and quality of MCMs are not compromised during distribution and dispensing activities.

The SNS will deliver temperature-sensitive products in validated temperature-controlled trucks or validated insulated shipping containers designed to maintain the required temperature during the packing and transport process to SLTTs. The SNS uses several types of insulated shipping containers, some of which can maintain specified temperatures for up to several days without electricity. Once sealed, these shipping containers have digital temperature monitoring systems that record and verify cold chain compliance and deviations. SNS insulated shipping containers are designed to temporarily maintain proper cold chain temperatures during product shipping. SLTT partners should not rely on or use these shipping containers for primary storage of SNS-received products given that the containers may not be able to maintain the product temperatures required throughout the dispensing process and temperature control cannot be guaranteed once the seal is broken.

SLTT partners are responsible for maintaining, monitoring, tracking, and documenting cold chain management after receipt of products from the SNS and for returning durable insulated shipping containers, batteries, and power cords to the CDC after use. Proper temperatures must be maintained at all receiving facilities and during additional transport within the jurisdiction. Jurisdictions should have processes in place for tracking and documenting storage temperatures from product receipt to product dispensing; should have necessary supplies such as ice, dry ice, and gel packs, temperature monitoring devices, insulated packing containers, and refrigerated trucks in place to transport cold chain management products; and should have appropriate refrigerated storage available at all receiving sites. The CDC’s Web page on vaccine storage and handling offers additional cold chain management information, and the product package insert or accompanying fact sheet, if available, will provide information on temperature and storage requirements for MCM dispensing.17

In addition to supplies needed to assist with cold chain management, SLTT planners should account for ancillary supplies needed for use of SNS-provided pharmaceuticals, vaccines, biologics, antitoxins, and equipment. Ancillary supplies are supplies used in conjunction with a primary item to create a complete system. Examples of ancillary supply needs for SNS medical countermeasures include administration sets for intravenous drug administration, measuring tools for suspension reconstitution, syringes and needles for vaccine administration, and closed circuit system parts for ventilators.

Although the SNS has ancillary supplies to assist with product administration and equipment use, SNS inventory levels for ancillary supplies may be lower than actual needs as a result of prioritization of other MCMs, product attrition and expiration, funding, or market availability. In some cases, the SNS shipment may not include ancillary supplies to support a product or these supplies may not support proprietary systems in place for a given facility (e.g., SNS intravenous administration sets may not be compatible with the intravenous infusion pumps used at all local hospitals). The CDC’s Division of Strategic National Stockpile is collaborating with manufacturers and distributors to determine alternate solutions for product distribution during a mass public health incident, but in the interim SLTT partners should consider local ancillary supply options.

Planning considerations are an integral component of response efforts. The planning considerations discussed here represent examples rather than an exhaustive list for SLTTs to consider while developing their response plans. The Division of Strategic National Stockpile continues to work with industry partners toward identifying measures designed to ensure that public health emergency and response activities are efficient and effective and to ensure the best use of SNS medical countermeasures. Such measures include collaborating with manufacturers and distributors to explore ways that private industry and government can work together to facilitate rapid and successful distribution of MCMs during a public health emergency. In addition, the CDC continues to solicit feedback from SLTT partners to assist with developing planning tools that would be useful during public health responses. Working and planning together at all levels before an incident will ensure the most successful response possible.

References

1. Centers for Disease Control and Prevention. Strategic National Stockpile. Available at: https://www.cdc.gov/phpr/stockpile/index.htm. Accessed May 1, 2018. Google Scholar
2. Centers for Disease Control and Prevention. Emergency preparedness and response. Available at: https://emergency.cdc.gov/groups.asp. Accessed May 1, 2018. Google Scholar
3. Centers for Disease Control and Prevention. Strategic National Stockpile CHEMPACK. Available at: https://www.cdc.gov/phpr/stockpile/chempack.htm. Accessed May 1, 2018. Google Scholar
4. US Department of Health and Human Services. Public Health Emergency Medical Countermeasures Enterprise. Available at: https://www.phe.gov/Preparedness/mcm/phemce/Pages/default.aspx. Accessed May 1, 2018. Google Scholar
5. US Department of Health and Human Services. Public Readiness and Emergency Preparedness Act. Available at: http://www.phe.gov/Preparedness/legal/prepact/Pages/default.aspx. Accessed May 1, 2018. Google Scholar
6. Bradley JS, Peacock G, Krug SE, et al. Pediatric anthrax clinical management. Pediatrics. 2014;133(5):e1411e1436. Crossref, MedlineGoogle Scholar
7. Emergent BioSolutions. BioThrax (anthrax vaccine adsorbed) package insert. Available at: https://www.fda.gov/downloads/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/UCM074923.pdf. Accessed May 1, 2018. Google Scholar
8. US Food and Drug Administration. Medical devices: emergency use authorizations. Available at: https://www.fda.gov/MedicalDevices/Safety/EmergencySituations/ucm161496.htm. Accessed May 1, 2018. Google Scholar
9. Centers for Disease Control and Prevention. Emergency use instructions for doxycycline and ciprofloxacin for postexposure prophylaxis of anthrax. Available at: https://www.cdc.gov/anthrax/medical-care/emergency-use-doxycycline-ciprofloxacin.html. Accessed May 1, 2018. Google Scholar
10. US Food and Drug Administration. Emergency dispensing orders. Available at: https://www.fda.gov/EmergencyPreparedness/Counterterrorism/MedicalCountermeasures/MCMLegalRegulatoryandPolicyFramework/ucm495126.htm. Accessed May 1, 2018. Google Scholar
11. US Drug Enforcement Administration. Mission statement. Available at: https://www.dea.gov/about/mission.shtml. Accessed May 1, 2018. Google Scholar
12. US Drug Enforcement Administration, Diversion Control Division. Controlled Substances Act. Available at: https://www.deadiversion.usdoj.gov/21cfr/21usc/index.html. Accessed May 1, 2018. Google Scholar
13. US Drug Enforcement Administration. Controlled Substances Act schedules. Available at: https://www.dea.gov/druginfo/csa.shtml. Accessed May 1, 2018. Google Scholar
14. US Drug Enforcement Administration. Drugs of abuse: a DEA resource guide. Available at: https://www.dea.gov/pr/multimedia-library/publications/drug_of_abuse.pdf#page=8. Accessed May 1, 2018. Google Scholar
15. US Department of Justice. Title 21 Code of Federal Regulations, part 1300 to end. Available at: https://www.deadiversion.usdoj.gov/21cfr/cfr. Accessed May 1, 2018. Google Scholar
16. US Food and Drug Administration. Code of Federal Regulations Title 21. Available at: https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=211. Accessed May 1, 2018. Google Scholar
17. Centers for Disease Control and Prevention. Vaccine storage and handling: recommendations and guidelines. Available at: https://www.cdc.gov/vaccines/hcp/admin/storage/index.html. Accessed May 1, 2018. Google Scholar

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Tina R. Bhavsar, PharmD, Deborah L. Esbitt, RN, MS, Patricia A. Yu, MPH, Yon Yu, PharmD, and Susan E. Gorman, PharmD, MSTina R. Bhavsar, Deborah L. Esbitt, and Susan E. Gorman are with the Division of Strategic National Stockpile, Office of Public Health Preparedness and Response, Centers for Disease Control and Prevention (CDC), Atlanta, GA. Patricia A. Yu and Yon Yu are with the Office of the Director, National Center for Emerging and Zoonotic Infectious Diseases, CDC. “Planning Considerations for State, Local, Tribal, and Territorial Partners to Receive Medical Countermeasures From CDC’s Strategic National Stockpile During a Public Health Emergency”, American Journal of Public Health 108, no. S3 (September 1, 2018): pp. S183-S187.

https://doi.org/10.2105/AJPH.2018.304472

PMID: 30192668