Embed Size (px)
Citation preview
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile
Planning Considerations for State, Local, Tribal, and Territorial Partners
Centers for Disease Control and Prevention Office of Public Health Preparedness and Response
Division of State and Local Readiness Division of Strategic National Stockpile
June 2017
Note: This document contains sensitive information and should not be distributed widely.
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile i
Table of Contents
Overview ..................................................................................................................................... 1
Purpose ........................................................................................................................................ 2
Preparedness Considerations...................................................................................................... 2
Countermeasures .................................................................................................................... 3
Post-exposure Prophylaxis (PEP) ............................................................................................. 3
Treatment .................................................................................................................................... 3
Federal Response Guidance ........................................................................................................ 4
Receiving PEP Countermeasures from the SNS .......................................................................... 5
Oral Antimicrobial Drugs: Ciprofloxacin and Doxycycline (Tablets) ........................................ 5
Oral Antimicrobials: Amoxicillin (Capsules) ............................................................................. 7
Oral Antimicrobials: Amoxicillin, Ciprofloxacin, and Doxycycline (Oral Suspension) ............. 8
Anthrax Vaccine Adsorbed (AVA) .......................................................................................... 10
Receiving Treatment Countermeasures from the SNS ............................................................. 12
IV Antimicrobial Drugs ........................................................................................................... 13
Anthrax Antitoxins: Anthrax Immune Globulin and Raxibacumab ....................................... 13
Ventilators ............................................................................................................................. 14
Requesting a Subject Matter Expert (SME) ............................................................................... 15
SNS Asset Recovery Following an Anthrax Incident .................................................................. 15
Authorities ................................................................................................................................. 16
References ................................................................................................................................. 16
Current clinical recommendations for adults ........................................................................ 16
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile ii
Current clinical recommendations for pediatrics .................................................................. 16
Appendix 1 – 60-Day Anthrax Response Timeline .................................................................... 18
Appendix 2 – Anthrax MCMs with Ancillary Supplies ............................................................... 19
Appendix 3 – MCMs Regulatory Status ..................................................................................... 20
Anthrax MCMs Status and Requirements ............................................................................. 21
FDA Resources ....................................................................................................................... 22
EUA Conditions ...................................................................................................................... 22
Appendix 4 – Definitions and Common Acronyms ................................................................... 23
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 1
Overview
Anthrax is a deadly infectious disease caused by Bacillus anthracis (B. anthracis) bacteria. According to the U.S. Department of Homeland Security (DHS) and public health experts, anthrax is the most likely agent to be used in a biological attack because of its potential to devastate a city or a region, causing massive disease outbreak and death.
It only takes a small amount of B. anthracis spores to infect a large number of people. An aerosolized release of B. anthracis spores is likely to cause an extreme public health emergency where the number of casualties could be in the hundreds to thousands. Inhalational anthrax is expected to account for the most serious morbidity and most mortality following aerosolized release of B. anthracis spores.1 Post-exposure prophylaxis (PEP) is required to protect potentially exposed populations, and early diagnosis of anthrax and initiation of appropriate treatment are necessary for those who become symptomatic.
Experts emphasize that the use of PEP countermeasures in the first 48 hours following an anthrax incident is crucial to saving lives. Current clinical recommendations for effective anthrax PEP include 60 days of oral antimicrobial drugs in conjunction with a three-dose course of anthrax vaccine for all potentially exposed individuals.2 Anthrax vaccine is currently in limited supply, so prioritization strategies may be necessary in the event of a large multijurisdictional anthrax incident.3 The federal government, through the Centers for Disease Control and Prevention's (CDC) Strategic National Stockpile (SNS), will deploy antimicrobial drugs, antitoxins, vaccine, and other medical countermeasures (MCMs) in response to an anthrax incident to save lives. The MCMs are dispensed as oral PEP, vaccines, and other treatments.
Based on clinical recommendations, CDC will execute a multipronged response plan. Initially, CDC will deploy a 10-day supply of oral antimicrobial drugs to affected jurisdictions. This will be followed by a 50-day supply of oral antimicrobial drugs and anthrax vaccine to complete the 60-day oral and vaccine courses. In consultation with jurisdictional officials, CDC may continue distributing MCMs for an extended period of time.
1 Inglesby TV, O'Toole T, Henderson DA, et al. Anthrax as a biological weapon, 2002: updated recommendations for management. JAMA 2002;287:2236–52. 2 Wright JG, Quinn CP, Shadomy S, Messonnier N. Use of anthrax vaccine in the United States: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. MMWR Recomm Rep. 2010;59(RR-6):1–30 3 CDC's Considerations for Anthrax Vaccine Adsorbed (AVA) Post-Exposure Prioritization Final, January 2013
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 2
A combination of 10-day unit-of-use (u/u) bottles and 50-day u/u bottles will complete the required medication for 60 days for one person of any age. Anthrax vaccine will be distributed as multidose vials under cold-chain management (CCM) to affected jurisdictions according to approved plans. In addition to PEP countermeasures, CDC maintains anthrax treatment countermeasures that are primarily intended for symptomatic patients in hospital settings. CDC may deploy the treatment MCMs as part of the 50-day follow-up response.
Purpose
State, local, tribal, and territorial (SLTT) governments are responsible for detecting and responding to an anthrax incident and implementing measures to mitigate the adverse health, social, and economic consequences. CDC and other federal partners provide support to help affected jurisdictions prepare for, respond to, and recover from exposures to biological agents. Focused on inhalational anthrax, these planning considerations provide information about the SNS MCM distribution operations that may help public health and healthcare planners coordinate efforts to allow for receipt, distribution, and dispensing of MCMs to exposed populations during an anthrax response.
Preparedness Considerations
Preparedness involves many pre-incident actions to ensure that jurisdictions are ready for an anthrax response. Determining the appropriate MCMs, developing response plans, training personnel, evaluating operational readiness, and maintaining situational awareness, in coordination with subject matter experts (SMEs), are key actions to perform in advance of an emergency.
CDC's Division of State and Local Readiness (DSLR) and Division of Strategic National Stockpile (DSNS) work closely with public health partners across the nation to coordinate their anthrax readiness and response plans. This planning partnership supports developing plans that promote the seamless transfer of SNS assets from states to local jurisdictions and, ultimately, to the people who need them.
CDC will deliver MCMs to designated receipt, stage, and store (RSS) facilities managed by state, local, or territorial partners.4 All designated RSS facilities must have a completed RSS facility site
4 SLTT requests for anthrax MCMs should be made according to existing guidance found in CDC's Receiving, Distributing, and Dispensing Strategic National Stockpile Assets: A Guide for Preparedness, Version 11, Chapter 4: Requesting Strategic National Stockpile Assets.
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 3
survey filed with CDC and either possess or have available the required cold temperature storage capacity.5
Countermeasures
The Public Health Emergency Medical Countermeasure Enterprise (PHEMCE) coordinates MCM-related efforts within the U.S. Department of Health and Human Services (HHS) and works in cooperation with PHEMCE interagency partners to determine the appropriate type and quantity of MCMs for the SNS formulary. The current SNS inventory of anthrax countermeasures for PEP and treatment, determined through the PHEMCE process, is listed below. However, these MCMs are subject to change through the annual PHEMCE SNS review process.
• Oral antimicrobial drugs (tablets/capsules): amoxicillin, ciprofloxacin, doxycycline
• Oral antimicrobial drugs (suspension): amoxicillin, ciprofloxacin, doxycycline
• Intravenous (IV) antimicrobial drugs: ciprofloxacin, clindamycin, doxycycline, levofloxacin, penicillin G, rifampin, vancomycin
• Vaccine: anthrax vaccine adsorbed (AVA)
• IV antitoxins: anthrax immune globulin (AIG), raxibacumab
• Ventilators
Post-exposure Prophylaxis (PEP)
Providing PEP countermeasures to a population potentially exposed to B. anthracis requires rapid decision making, distribution, dispensing, and administration of appropriate medications to decrease the infection rate of persons exposed.6 Experts emphasize that the use of oral PEP countermeasures in the first 48 hours following an anthrax incident is crucial to saving lives. For PEP, CDC recommends a 60-day course of oral antimicrobial drugs given in conjunction with three doses of anthrax vaccine for all potentially exposed individuals.
Treatment In addition to PEP for the potentially exposed population, CDC will deploy MCMs to support anthrax treatment protocols in appropriate healthcare settings following state protocols.
5 CDC's Receiving, Distributing, and Dispensing Strategic National Stockpile Assets: A Guide for Preparedness, Version 11, Chapter 5: Receiving, Staging, and Storing Medical Countermeasures and Appendix E: Cold Chain Management 6 CDC will use metropolitan statistical area (MSA) population data until SMEs can provide better estimates of the potentially exposed population. As public health officials gather better epidemiologic data, the population requiring prophylaxis will be refined.
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 4
Anthrax treatment consists of a multidrug course, starting with IV antimicrobial drugs. Depending on the severity of the illness, the patient may require antitoxins in addition to antimicrobial drugs. After a patient has successfully completed a prescribed course of IV antimicrobial drugs, treatment should change to oral antimicrobial drugs to complete a 60-day course.7
Federal Response Guidance
An anthrax incident may be recognized through several means: environmental monitoring (e.g., BioWatch8), credible intelligence, or confirmation of anthrax in humans through traditional disease reporting. Following consultation with jurisdictional officials, a confirmed anthrax incident will trigger the following federal response operations.
1. Homeland security: DHS will work with the Federal Bureau of Investigation (FBI) regarding criminal investigation and intelligence activities.
2. Public health and medical: HHS will conduct the following activities:
o Activate Emergency Support Function (ESF) #8 – Public Health and Medical Services response assets
o Declare a public health emergency9
o Direct CDC to
Begin epidemiological and surveillance tasks,
Deploy MCM, and
Maintain situational awareness.
The HHS Secretary may direct deployment of MCMs upon receipt of credible intelligence that an anthrax incident occurred or is imminent. Since anthrax MCM effectiveness is directly related to early administration, once a federal decision to deploy is made, jurisdictions should be prepared to rapidly receive, distribute, dispense, and administer these SNS assets.
7 Hendricks KA, Wright ME, Shadomy SV, Bradley JS, Morrow MG, Pavia AT, et al. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis [Internet]. 2014 Feb 8 https://www.dhs.gov/biowatch-program 9 Declarations and determinations applicable to an emergency by the Secretary of the Department of Health and Human Services may include those under Section 319 of the Public Health Service (PHS) Act and Section 564 of the Federal Food, Drug, and Cosmetic (FD&C) Act.
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 5
With the exception of antitoxins, CDC will deliver MCMs to the designated RSS facility in the affected jurisdictions. After receipt of the MCMs, the jurisdictions will distribute assets from the RSS facility to their affected localities based on established distribution plans. Each state, territory, or directly funded locality is responsible for determining the best distribution model for its unique circumstances and resources, which includes transfer of MCMs and integration of plans between the various jurisdictions.
Receiving PEP Countermeasures from the SNS
MCMs are deployed from the SNS using a two-phased strategy. The initial PEP MCM deployment consists of 10-day u/u oral antimicrobial drugs. The initial round is followed by a second deployment of 50-day u/u oral antimicrobial drugs and vaccine (a three-dose course administered at 0, 2, and 4 weeks) to complete the 60-day PEP course.
CDC will deliver these MCMs in the ratio in which they are available in the SNS inventory at the time of the response. The following is a description of the types of MCMs that CDC can deploy in response to an anthrax incident by type of medication and SNS response phase.
Oral Antimicrobial Drugs: Ciprofloxacin and Doxycycline (Tablets)
Ciprofloxacin and doxycycline are approved by the Food and Drug Administration (FDA) for PEP and are the preferred oral antimicrobial drugs recommended to protect against inhalational anthrax infection. Affected jurisdictions will receive u/u bottles of ciprofloxacin and doxycycline tablets in multiple deliveries:
• Initial Response: 10-day supply
• Follow-up Response: 50-day supply
Initial Response: 10-day Supply
Immediately following a federal decision to deploy, CDC will begin delivery of 10-day u/u oral ciprofloxacin and doxycycline to initiate PEP for the potentially exposed population. Cases of oral antimicrobial drugs may ship in air cargo containers, on pallets, or a combination of both and are delivered directly to the RSS facilities in the affected jurisdictions.
Follow-up Response: 50-day Supply
The deployment process for the 50-day supply begins immediately following shipment of the initial 10-day supply. Affected jurisdictions should receive their 50-day u/u oral
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 6
antimicrobial supply at their RSS facilities no more than eight days after the federal decision to deploy. The follow-up shipments will contain enough PEP for the potentially exposed population.
• The number of 50-day u/u bottles deployed will be sufficient to cover the same population used for the 10-day u/u calculation unless epidemiological data or state or local investigations provide a refined exposed population requiring PEP.
Special Considerations for Ciprofloxacin and Doxycycline
Oral ciprofloxacin and doxycycline are FDA approved for use as PEP. However, use of both MCMs will be through the Emergency Use Instructions (EUI)10 regulatory mechanism in combination with relevant FDA actions (e.g., emergency dispensing order, current good manufacturing practice [cGMP] waiver, etc.). This is due to bottle packaging, labeling, and participation in FDA's Shelf Life Extension Program (SLEP). The CDC-issued EUI for ciprofloxacin and doxycycline for PEP of anthrax, including doxycycline crushing instructions (pamphlet, one-pager, and video) have been posted on CDC's password protected Online Technical Resource and Assistance Center (On-TRAC), as well as provided to jurisdictions for planning purposes. In addition, these materials will be posted to CDC's external website during an anthrax event.
During an emergency, public health officials in affected jurisdictions should disseminate the EUI materials to the public through various communication channels, including print and electronic media. In addition, information on the EUI fact sheets may be disseminated to healthcare providers or other authorized dispensers through mass media including print; broadcast, radio, satellite, Internet, or other electronic means; videos/DVDs; or direct communication from public health agencies.
Affected jurisdictions and healthcare providers should be aware of the relevant Public Readiness and Emergency Preparedness (PREP) Act declarations and distribute MCMs accordingly to ensure coverage under the PREP Act's liability protections. Lastly, suspected adverse reactions should be reported to either FDA MedWatch or the manufacturer.11
10 http://www.fda.gov/EmergencyPreparedness/Counterterrorism/MedicalCountermeasures/MCMLegalRegulatoryandPolicyFramework/ucm495126.htm 11 https://www.phe.gov/Preparedness/legal/prepact/Pages/default.aspx
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 7
Oral Antimicrobials: Amoxicillin (Capsules)
Amoxicillin is not FDA approved for anthrax PEP; however, it may be used via an Emergency Use Authorization (EUA). Due to possible side effects of long-term use of ciprofloxacin and doxycycline in children younger than 18 years of age, amoxicillin is the preferred antimicrobial drug for these age groups. While quantities of amoxicillin are limited in the SNS, CDC will likely recommend that these age groups take amoxicillin if it is shown to be effective against the anthrax strain. Per CDC's Special Considerations for Prophylaxis and Treatment of Anthrax in Pregnant and Postpartum Women (2014)12, pregnant women should only be switched to amoxicillin if there are medical contraindications to other antibiotics (i.e., doxycycline and ciprofloxacin) or the general population (non-pregnant) has been advised to switch to amoxicillin. Affected jurisdictions should take these issues into consideration and address this scenario in their response plans.
Initial Response: 10-day Supply
Amoxicillin is not included in the initial 10 day u/u deployment.
Follow-up Response: 50-day Supply
Affected jurisdictions will receive amoxicillin (50-day u/u) at their RSS facilities. Amoxicillin capsules may be packaged such that multiple u/u bottles will be needed to complete the remaining 50 days of PEP. Due to possible side effects of long-term use of ciprofloxacin and doxycycline in children younger than 18 years of age, amoxicillin is the preferred antimicrobial drug for this age group. Because quantities of amoxicillin are limited in the SNS, CDC will likely recommend that children 8 years of age and younger receive priority taking amoxicillin.
Special Considerations for Amoxicillin
• Amoxicillin is the preferred antimicrobial drug for pediatrics.
• Amoxicillin requires an EUA for use as PEP.
• Quantities of amoxicillin are limited in the SNS.
Affected jurisdictions should be aware that EUAs can come with conditions that must be followed at the time of an event; the FDA will list these conditions as part of the EUA. As with EUI materials, during an emergency, public health officials in affected jurisdictions
12 Meaney-Delman D, Zotti ME, Creanga AA, et al. Special Considerations for Prophylaxis for and Treatment of Anthrax in Pregnant and Postpartum Women. Emerg Infect Dis. 2014 Feb; 20(2): e130611.
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 8
should disseminate informational materials on products used under an EUA to the public and healthcare providers through various communication channels, including print and electronic media.
Affected jurisdictions and healthcare providers should be aware of the relevant PREP Act declarations and distribute MCMs accordingly to ensure coverage under the PREP Act's liability protections. Lastly, suspected adverse reactions should be reported to either FDA MedWatch or the manufacturer.13
Oral Antimicrobials: Amoxicillin, Ciprofloxacin, and Doxycycline (Oral Suspension)
The quantities of pediatric antimicrobial suspension on hand in hospitals or pharmacies may not be sufficient in a large anthrax incident. Therefore, CDC simultaneously deploys pediatric antimicrobial suspensions with the initial shipment of MCMs to RSS facilities in the affected jurisdictions. Pediatric antimicrobial (amoxicillin, ciprofloxacin, and doxycycline) suspension is reserved for children younger than 1 year of age.
The 10-day and 50-day shipments include a sufficient amount of oral dosing syringes. Suspension is shipped from the SNS in powder form and must be reconstituted prior to patient administration. CDC does not supply the distilled water for reconstitution of amoxicillin and doxycycline suspension. Ciprofloxacin comes packaged with its own diluent. There are no special transportation requirements for suspension.
Initial Response: 10-day Supply
Affected jurisdictions will receive 10-day supplies of pediatric antimicrobial (ciprofloxacin, doxycycline) suspension in the first shipments following the federal decision to deploy. CDC deploys pediatric antimicrobial suspension simultaneously with the 10-day u/u tablets to the RSS.14
Follow-up Response: 50-day Supply
Immediately following the initial response, CDC will deploy the 50-day suspension supply. Affected jurisdictions can expect to receive the second shipment of 50-day pediatric antimicrobial (first shipment of amoxicillin and second shipments of ciprofloxacin and doxycycline) suspension within eight days of the federal decision to deploy. Not all three
13 https://www.phe.gov/Preparedness/legal/prepact/Pages/default.aspx 14 If a state, territory, or directly funded city receives its initial oral antimicrobial supply from a 12-hour Push Package, SNS simultaneously deploys pediatric antimicrobials from MI to RSS site.
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 9
types of suspensions may be recommended during an event; only those recommended by SMEs will be shipped. Due to possible side effects of long-term use of ciprofloxacin and doxycycline in children younger than 18 years of age, amoxicillin is the preferred antimicrobial drug for this age group, thus children less than 1 year of age may be switched from ciprofloxacin or doxycycline suspension to amoxicillin suspension.
Special Considerations for Pediatric Antimicrobial Oral Suspension
• Ciprofloxacin and doxycycline suspension are approved by the FDA for use as anthrax PEP. However, both antimicrobials require EUIs15 in combination with relevant FDA actions (e.g., emergency dispensing order, cGMP waiver, etc.) due to bottle packaging, labeling, and participation in FDA's SLEP. Affected jurisdictions should be familiar with the specific emergency dispensing order/cGMP waiver for pertinent information. In this situation, FDA would grant a mass dispensing waiver to avoid the need for individual prescriptions or specific labeling information and to allow temperature excursions for these two products. These documents are part of a regulatory package that will allow the use of these two medications without an EUA and associated EUA conditions.
• Amoxicillin suspension is not FDA approved for anthrax PEP. Amoxicillin suspension requires an EUA for use as anthrax PEP.
• Due to limited quantities available in the SNS, suspension is recommended for use in children younger than 1 year of age. Depending on the scale of the response, there may not be enough suspension for all children less than 1 year of age. In that case, crushing tablets may be advised. Crushing instructions are available on CDC's On-TRAC.
• CDC supplies oral dosing syringes but does not supply the distilled water for reconstitution of pediatric suspension MCMs.
• Affected jurisdictions and healthcare providers should be aware of the relevant PREP Act declarations and distribute MCMs accordingly to ensure coverage under the PREP Act's liability protections. Lastly, suspected adverse reactions should be reported to either FDA MedWatch or the manufacturer.16
15 http://www.fda.gov/EmergencyPreparedness/Counterterrorism/MedicalCountermeasures/MCMLegalRegulatoryandPolicyFramework/ucm495126.htm 16 https://www.phe.gov/Preparedness/legal/prepact/Pages/default.aspx
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 10
Anthrax Vaccine Adsorbed (AVA)
AVA17 is the only licensed human anthrax vaccine in the United States. AVA is FDA approved for prophylaxis before and after anthrax exposure in adults ages 18 years to 65 years. AVA must be used under an Investigational New Drug (IND) application for PEP in children younger than 18 years of age. IND use requires individual written informed consent for children younger than 18 years of age who receive the anthrax vaccine.
AVA as part of PEP therapy is administered in a three-dose course at 0, 2, and 4 weeks following anthrax exposure along with 60 days of oral antimicrobial drugs. The first dose of anthrax vaccine should be administered within the first 10 days of exposure. Epidemiological data that better defines this affected population should be available before the second vaccine dose is due to prevent unnecessary vaccinations.
The SNS has limited quantities of AVA, which may be insufficient to immunize the entire affected population in a large anthrax incident. Health and emergency management officials in the affected jurisdictions will make final decisions on the administration of the anthrax vaccine. CDC's recommendation for AVA use during an anthrax incident is for vaccinating the entire affected population. However, since AVA is a limited resource, CDC developed the following three-tier system for consideration in prioritizing assets following anthrax exposure.18
17 Because there is no data on AVA use in children, vaccine will be offered to children 0-17 years under an IND protocol. 18 https://www.cdc.gov/anthrax/pdf/ava-post-event-prioritization-guidance.pdf
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 11
Refer to CDC's Considerations for Anthrax Vaccine Adsorbed (AVA) Post-Exposure Prioritization Final, January 2013 for operational planning and prioritization of AVA following a large anthrax incident. In the event of a vaccine shortage, CDC may provide additional prioritization guidance at the time of an anthrax incident.
Initial Response: 10-day Supply
CDC does not include AVA in the initial 10-day deployment.
Follow-up Response: 50-day Supply
Affected jurisdictions will receive the first AVA doses concurrently with 50-day u/u bottles of oral antimicrobial drugs deployed to their RSS facilities or other predesignated locations. RSS CCM19 should be in place as verified in the RSS facility site survey. The first shipment of AVA is the initial vaccine dose allocation (week 0) for a metropolitan statistical area (MSA) population or initially identified exposed population.
CDC deploys the second and third AVA doses to the RSS facilities or designated locations (weeks 2 and 4) according to the recommended vaccine schedule. The AVA quantity for the second and third doses will be the same as the first dose, unless epidemiologists provide refined exposed population data.
Special Considerations for AVA
• The use of AVA as PEP requires an IND for children younger than 18 years of age. Although not strictly contraindicated, AVA should not be co-administered with routine childhood vaccinations during an anthrax event. The co-administration of routine vaccines to children in addition to the recommended three doses of AVA within six weeks of the final AVA immunization could contribute to increased adverse reactions, resulting in a reduction in adherence to full vaccine schedules for both routine vaccines and AVA.
• AVA requires CCM and must be stored at 2°C - 8°C (36°F - 46°F).
• Anthrax vaccination record cards used to track dosage, dates, and other vaccination details are shipped with AVA. Each person receiving the anthrax vaccine will receive one vaccination card.
19 RSS CCM capacity is part of the MCM Operational Readiness Review. RSS facilities are required to have cold chain storage capabilities.
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 12
o Anthrax vaccination record cards are wallet-sized reminders for anthrax vaccine recipients to know when to return to a vaccination clinic for their subsequent anthrax vaccine dose(s).
o The anthrax vaccination record cards include blank spaces for the vaccination clinic to fill out recipient's name, date of each vaccination, and date to return for next vaccination, as well as contact information for recipients to report adverse events.
o Anthrax vaccination record cards can assist vaccination clinics with verifying recipient dose schedules and needs.
o Jurisdictions may also consider entering the vaccination data in their immunization information systems.
• As previously stated, the SNS has limited quantities of anthrax vaccine; prioritization strategies may be necessary.
• The SNS is working to increase its limited quantities of ancillary supplies such as needles and syringes to administer AVA. Therefore, affected jurisdictions should consider how to acquire and provide necessary ancillary supplies for vaccine administration. These ancillary supplies should include sterile syringe and needle (size as appropriately identified by state or local immunization services), and sterile alcohol pads.
• Affected jurisdictions and healthcare providers should be aware of the relevant PREP Act declarations and distribute MCMs accordingly to ensure coverage under the PREP Act's liability protections. Lastly, suspected adverse reactions to AVA should be reported to the Vaccine Adverse Event Reporting System (VAERS) and/or the manufacturer.20
Receiving Treatment Countermeasures from the SNS
Treatment countermeasures held in the SNS for an anthrax response include IV antimicrobial drugs and IV antitoxins. IV antimicrobial drugs will be delivered to RSS sites, while IV antitoxins can be delivered to an RSS site, a coordinating hospital, or an individual hospital.21
20 https://www.phe.gov/Preparedness/legal/prepact/Pages/default.aspx
21 More information on the role hospitals and treatment centers play in an anthrax response is available on CDC's Receiving, Distributing, and Dispensing Strategic National Stockpile Assets: A Guide for Preparedness, Version 11, Chapter 12: Hospital and Treatment Center Coordination
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 13
IV Antimicrobial Drugs
The SNS inventory contains the following IV antimicrobial drugs used to treat anthrax.
• Ciprofloxacin
• Clindamycin
• Doxycycline*
• Levofloxacin
• Penicillin G*
• Rifampin
• Vancomycin
Special Considerations for IV Antimicrobial Drugs
Quantities of IV antimicrobial drugs are deployed based on patient counts, hospital needs, jurisdictional requests, SME guidance, and product availability. There are no special transportation requirements for IV antimicrobial drugs.
Affected jurisdictions and healthcare providers should be aware of the relevant PREP Act declarations and distribute MCMs accordingly to ensure coverage under the PREP Act's liability protections. Lastly, suspected adverse reactions should be reported to either FDA MedWatch or the manufacturer.22
Anthrax Antitoxins: Anthrax Immune Globulin and Raxibacumab
An anthrax antitoxin should be added as a combination to antimicrobial drug treatment for any patient for whom there is a high level of clinical suspicion for systemic anthrax. Individuals who contract inhalational anthrax may require antitoxins in addition to IV antimicrobial drugs. There are currently two available anthrax antitoxins in the SNS: anthrax immune globulin and raxibacumab. Both are FDA approved to treat inhalational anthrax, require CCM, and are available in limited quantities.
According to CDC recommendations,23 allocation of anthrax antitoxins will be prioritized, as clinically appropriate, to persons determined to have laboratory-confirmed anthrax. In a mass casualty situation, allocation of anthrax antitoxins will be prioritized to persons whose illness is clinically compatible with anthrax, have a risk of exposure, and who have systemic involvement. Persons with simple, uncomplicated infections would not be eligible for anthrax immune globulin or raxibacumab. 22 https://www.phe.gov/Preparedness/legal/prepact/Pages/default.aspx 23 Bower WA, Hendricks D, Pillai S, et al., Clinical Framework and Medical Countermeasure Use During an Anthrax Mass-Casualty Incident: CDC Recommendations. MMWR Recomm Rep 2015;64(No. RR-4):1-22.
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 14
CDC can send anthrax immune globulin and raxibacumab from the SNS to a hospital or another location designated by the affected jurisdiction. This hospital can be established to act as the recipient of these time-sensitive MCM resources and serve as the coordinating hub for other hospitals and redistribute MCMs as required. This model allows CDC to ship directly to a single location that is prepared to handle and manage these critical resources without having to ship to every hospital.
Special Considerations for Anthrax Antitoxins
• Anthrax immune globulin and raxibacumab are both FDA approved to treat inhalation anthrax. However, they will be used with EUI describing information related to use during an anthrax emergency. This information will be provided as fact sheets for both the public and healthcare providers.
• Anthrax immune globulin requires CCM and must be stored at ≤ -15°C. (≤ 4°F).
• Raxibacumab requires CCM and must be stored at 2°C-8°C (36°F - 46°F).
• Anthrax immune globulin and raxibacumab require special approval. CDC will approve release of antitoxins for individuals on a case-by-case basis, if the incident allows for it. Information about requesting these MCMs from CDC will be made available at time of incident.
• Affected jurisdictions and healthcare providers should be aware of the relevant PREP Act declarations and distribute MCMs accordingly to ensure coverage under the PREP Act's liability protections. Lastly, suspected adverse reactions should be reported to either FDA MedWatch or the manufacturer.24
Ventilators
Ventilators are intended to supplement those at medical treatment facilities in affected jurisdictions during public health emergencies severe enough to exhaust local supplies. Mechanical ventilators are a critical lifesaving MCM that may be needed for persons with severe respiratory illness associated with B. anthracis exposure.
Ventilators are an extremely limited resource and likely will be in high demand following an anthrax incident. There are three different models in SNS managed inventory:
• LTV 1200 (20 per air cargo container)
24 https://www.phe.gov/Preparedness/legal/prepact/Pages/default.aspx
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 15
• Impact 754 (28 per air cargo container)
• LP10 (10 per air cargo container)
To provide an initial allocation of ventilators, CDC may deploy approximately 20 to 60 ventilators to the RSS facilities in affected jurisdictions as early as day 3 but no later than day 10. After the initial deployment, affected jurisdictions may request additional units as needed. Ventilators are deployed with the necessary ancillary supplies needed to use the ventilator for both adult and pediatric patients, and all three models come with an operations manual on DVD. Hands-on training and instructions manuals are available on all SNS ventilator models.25
Special Considerations for Ventilators
• Ventilators are a recoverable asset.
• Jurisdictions that receive ventilators are required to track them to facilitate CDC recovery of these assets following the incident.
• The tracking requirement is outlined on the property custody form and requires signature by the receiving jurisdictional authority at the RSS facility upon receipt.
• Prior to returning the ventilators to CDC, the hospital must clean the ventilators according to infection control guidelines.
Requesting a Subject Matter Expert (SME)
Upon request by jurisdictional officials, CDC may deploy SMEs to assist in a jurisdiction's response operations.
SNS Asset Recovery Following an Anthrax Incident
Countermeasures that are sent to a jurisdiction during a response become the property of jurisdictional authority and cannot be returned to CDC. Exceptions to this include any unused assets maintained under federal control or durable medical products (e.g., ventilators, aspirators, air cargo containers, other moveable containers), which are expected to be returned to the SNS inventory. Jurisdictions can return these assets at any time during or following the response.
25 Strategic National Stockpile Ventilator Training Program
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 16
Authorities
1. Executive Order 13527, Establishing Federal Capability for the Timely Provision of Medical Countermeasures Following a Biological Attack, December 30, 2009 https://obamawhitehouse.archives.gov/the-press-office/executive-order-medical-countermeasures-following-a-biological-attack
2. HSPD-21, Public Health and Medical Preparedness, October 18, 2008 http://www.fas.org/irp/offdocs/nspd/hspd-21.htm
References
Current clinical recommendations for adults
3. Hendricks KA, Wright ME, Shadomy SV, Bradley JS, Morrow MG, Pavia AT, et al. Centers for Disease Control and Prevention expert panel meetings on prevention and treatment of anthrax in adults. Emerg Infect Dis [Internet]. 2014 Feb
4. Bower WA, Hendricks D, Pillai S, et al., Clinical Framework and Medical Countermeasure Use During an Anthrax Mass-Casualty Incident: CDC Recommendations. MMWR Recomm Rep 2015;64(No. RR-4):1-22.
5. Meaney-Delman D, Zotti ME, Creanga AA, et al. Special Considerations for Prophylaxis for and Treatment of Anthrax in Pregnant and Postpartum Women. Emerg Infect Dis. 2014 Feb; 20(2): e130611.
Current clinical recommendations for pediatrics
6. Bradley JS, Peacock G, Krug SE, Bower WA, et al., Clinical Report: Pediatric Anthrax Clinical Management. Pediatrics 2014;133:e1411–e1436
7. CDC's Considerations for Anthrax Vaccine Adsorbed (AVA) Post-Exposure Prioritization Final, January 2013 https://www.cdc.gov/anthrax/pdf/ava-post-event-prioritization-guidance.pdf
8. National Strategy for Countering Biological Threats, National Security Council, November 2009 https://obamawhitehouse.archives.gov/sites/default/files/National_Strategy_for_Countering_BioThreats.pdf
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 17
9. Biological Incident Annex, NRF, August 2008 http://www.fema.gov/pdf/emergency/nrf/nrf_BiologicalIncidentAnnex.pdf
10. FEMA Concept of Operations (CONOPS) and Requirements for a Federal Medical Countermeasures (MCM) Rapid Response (draft), March 12, 2010
11. CDC All-Hazards Preparedness Guide, March 2013 https://www.cdc.gov/phpr/documents/ahpg_final_march_2013.pdf
12. CDC Anthrax website https://www.cdc.gov/anthrax/
13. CDC. Use of Anthrax Vaccine in the United States. MMWR 2010;59 (No. RR-6):1-23.
14. Receiving, Distributing, and Dispensing Strategic National Stockpile Assets: A Guide for Preparedness, Version 11, February 2014
15. Clinical and Epidemiologic Principles of Anthrax, Theodore J. Cieslak and Edward M. Eitzen, Jr., U.S. Army Medical Research Institute of Infectious Diseases, Ft. Detrick, Maryland https://wwwnc.cdc.gov/eid/article/5/4/99-0418_article
16. Conference report on public health and clinical guidelines for anthrax. Stern EJ, Uhde KB, Shadomy SV, Messonnier N. Emerg Infect Dis. 2008 Apr [26Feb2010]. https://wwwnc.cdc.gov/eid/article/14/4/07-0969_article
17. How to Crush Doxycycline for Children & Adults Who Cannot Swallow Pills https://www.youtube.com/watch?v=Wecask69YXw
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 18
Appendix 1 – 60-Day Anthrax Response Timeline
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 19
Appendix 2 – Anthrax MCMs with Ancillary Supplies
Table 1. Anthrax MCMs with Ancillary Supplies
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 20
Appendix 3 – MCMs Regulatory Status
The table below lists the regulatory status or regulatory mechanism needed to use specific drug products in the SNS for the treatment or prevention of anthrax as of June 2017.
Table 2. Anthrax MCM Regulatory Status/Mechanisms Needed for Product Use
*EUA supports IV antimicrobial drugs used as part of a multidrug approach to treat anthrax.
**EUI regulatory mechanism will be used for certain FDA-approved MCMs in combination with relevant FDA actions (e.g., issuing an emergency dispensing order to authorize dispensing
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 21
without individual prescriptions, partial doses, without all required labeling, by non-healthcare professionals, etc.).
Under section 564A(e) of the Food, Drug & Cosmetic (FD&C) Act, CDC may create and issue, and government stakeholders may disseminate, an EUI26 (also referred to as fact sheets for recipients of an MCM and for healthcare professionals) about the FDA-approved conditions of use for such MCMs before or during a chemical, biological, radiological, or nuclear (CBRN) event. When feasible, FDA and CDC will coordinate issuance of an emergency dispensing order and EUI for an MCM. To facilitate creation of EUI, FDA and CDC entered into a memorandum of understanding. The HHS Secretary delegated the EUI authority to the CDC Director in 2013.
Anthrax MCMs Status and Requirements
• Oral doxycycline and ciprofloxacin – While FDA approved, u/u and suspension bottles require an EUI in combination with relevant FDA actions (e.g., emergency dispensing order, cGMP waiver, etc.) due to product packaging, SLEP, etc.
• Oral amoxicillin – Requires EUA.
• Anthrax vaccine – FDA approved for adults 18 years to 65 years of age. IND needed for children 0 years to 17 years of age.
• IV doxycycline and penicillin G – FDA approved for the treatment and PEP of anthrax. Use of these MCMs during an emergency will be through CDC-issued EUI describing information related to use during an anthrax emergency, provided as fact sheets in combination with other emergency use authorities by FDA as applicable.
• IV ciprofloxacin and levofloxacin – FDA-approved for PEP of anthrax. Use of these MCMs during an emergency will be through CDC-issued EUI describing information related to use during an anthrax emergency, provided as fact sheets in combination with other emergency use authorities by FDA as applicable.
• IV clindamycin, rifampin and vancomycin – require an EUA and used as part of a multi-drug treatment approach.
• Anthrax Immune Globulin and raxibacumab – FDA approved for treatment of inhalational anthrax. However, EUI will be used in combination with relevant FDA actions (e.g., emergency dispensing order, cGMP waiver, etc.) describing information related to use during an anthrax emergency.
• Raxibacumab –FDA approved for inhalational anthrax PEP. However, EUI will be used in 26 https://www.fda.gov/EmergencyPreparedness/Counterterrorism/MedicalCountermeasures/MCMLegalRegulatoryandPolicyFramework/ucm411432.htm
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 22
combination with relevant FDA actions. FDA Resources
FDA has available informational resources on EUI, EUA, and IND, including fact sheets that can be disseminated through a variety of methods to healthcare providers and recipients. EUI fact sheets are available for planning purposes on CDC's On-TRAC.
EUA Conditions
Affected jurisdictions should be aware that EUAs27 can come with conditions that must be followed at the time of an event. The FDA will list these conditions as part of the EUA. As with EUI materials, during an emergency, public health officials in affected jurisdictions should disseminate informational materials on products used under an EUA to the public and healthcare providers through various communication channels, including print and electronic media.
Affected jurisdictions and healthcare providers should be aware of the relevant PREP Act declarations and distribute MCMs accordingly to ensure coverage under the PREP Act's liability protections. Lastly, suspected adverse reactions should be reported to either FDA MedWatch, VAERS, or the manufacturer.28
27 https://www.fda.gov/EmergencyPreparedness/Counterterrorism/MedicalCountermeasures/MCMLegalRegulatoryandPolicyFramework/ucm411432.htm 28 https://www.phe.gov/Preparedness/legal/prepact/Pages/default.aspx
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 23
Appendix 4 – Definitions and Common Acronyms
1. Anthrax – A serious, deadly infectious disease caused by gram-positive, rod-shaped bacteria known as Bacillus anthracis (also B. anthracis).
2. Anthrax Incident – In this plan, the term "anthrax incident" will refer to any large release of B. anthracis in a populated area that is likely to cause extensive illness, widespread panic, and disruption of civil services. While there are several methods to deploy anthrax, aerosolized anthrax is the most likely and most dangerous means for a large incident.
3. Antimicrobial Drug - A drug used to treat a microbial infection. "Antimicrobial drug" is a general term that refers to a group of drugs that includes antibiotics, antifungals, antiprotozoals, and antivirals.
4. Directly Funded Locality – One of four localities in the United States that directly receives funding from CDC's Public Health Emergency Preparedness cooperative agreement. They include Chicago, Los Angeles County, New York City, and Washington, D.C.
5. Emergency Use Authorization (EUA) - Allows the U.S. Food and Drug Administration (FDA) Commissioner to permit the use of unapproved medical products or unapproved uses of approved medical products in an emergency. An EUA authorizes the wide-scale emergency use of unapproved, uncleared, or unlicensed MCMs in an emergency to diagnose, treat, or prevent serious or life-threatening diseases or conditions when there are no adequate, approved, and available alternatives.
6. Emergency Use Instructions (EUI) – The Pandemic and All Hazards Preparedness Reauthorization Act (PAHPRA) allows a designated HHS official or unit to create and issue special emergency use instructions about the conditions of use for such MCMs both (a) before a chemical, biological, radiologic or nuclear incident occurs and (b) during a response. These instructions can be used by anyone during a response and can be disseminated by government entities (or persons acting on behalf of those entities) in preparation for an emergency response. EUI are intended to be similar to the fact sheets for healthcare professionals and fact sheets for patients/recipients and parents/caregivers that have been authorized in past EUAs. The authority to issue EUI has been delegated by the HHS Secretary to CDC.
7. Investigational New Drug (IND) Application – A regulatory mechanism in which FDA permits use of a medical product that is not FDA approved or unapproved use of an FDA-approved product. Product use under the IND must comply with FDA regulations including but not limited to informed consent, disclosure of investigational status,
Receiving 60-day Anthrax Medical Countermeasures from CDC's Strategic National Stockpile 24
purpose and risk-benefit to the recipients, and product usage in accordance with the IND protocol and Institutional Review Board approval.
8. Oral Suspension Antimicrobial Drugs – A liquid preparation mixture of antimicrobial drugs.
9. Public Health Emergency Preparedness (PHEP) cooperative agreement – Managed by CDC's Division of State and Local Readiness, PHEP is a critical source of funding for state, local, and territorial public health departments. Through the PHEP cooperative agreement, CDC helps public health departments strengthen their abilities to respond to all types of public health emergencies and build more resilient communities.
10. Receipt, Stage, and Store (RSS) Sites – Facilities that accept, store, and prepare for further distribution of MCMs. These functions are largely carried out at the state level but, depending on jurisdictional plans, this responsibility may also be carried out in major metropolitan cities or regionally. The RSS facility will act as the hub of the distribution system for the state or other jurisdiction to which SNS assets are deployed.
11. RSS Survey – CDC developed the RSS facility site survey to assist planners in determining the suitability of RSS facilities. The RSS site survey helps identify, verify, and reverify facilities as RSS sites for federal MCM assets. CDC will use the data collected from the facility site survey to determine a facility's use as an RSS site from an all-hazards approach. The RSS site survey defines the elements needed for an optimal RSS site. CDC recognizes that some of the features described in the RSS site survey may not be on the site but plans are in place to provide such equipment at the time of a response.
12. Shelf Life Extension Program (SLEP) – A program sponsored by FDA and Department of Defense that defers costs for stockpiling and replacement of federally maintained, perishable pharmaceuticals by extending their useful life following testing.
13. Strategic National Stockpile (SNS) – A national repository of antimicrobial drugs, chemical antidotes, antitoxins, life-support medications, intravenous (IV) administration, airway maintenance supplies, and medical/surgical items. Managed by CDC's Division of Strategic National Stockpile (DSNS), the SNS is designed to supplement and resupply state, local, and territorial public health agencies in a national emergency anywhere and at any time within the United States or its territories.
14. Unit of Use (UoU) or u/u – Package of medication that contains a quantity designed and intended to be dispensed directly to a patient for a specific use without modification.
