International COVID19 Vaccine Handling Guide

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International COVID!19 Vaccine Handling Guide

COVID!19 Vaccine Information continues to evolve. Please scan the QR code to visit the website for the latest information. International COVID!19 Vaccine Handling Guide

Background

Regulators around the world have authorized the use of several COVID!19 vaccines to help mitigate the devastating impact of the COVID!19 pandemic on global communities and economies. As vaccination campaigns are underway in many countries, concerns have emerged with potential COVID!19 vaccine wastage at each stage of the supply chain.1 In February 2021, USP convened a group of experts to develop and publish the USP COVID!19 Vaccine Handling Toolkit, which includes general strategies, as well as COVID!19 vaccine product-speci"ic information for vaccines available in the United States to help address operational ef"iciency gaps across U.S. states and territories.2 USP’s COVID!19 Vaccine Handling Toolkit and related guides (e.g., factsheets, videos, etc.) were designed to help accelerate the pace of vaccination, expand the available supply of vaccines by preventing waste, and build healthcare practitioner con"idence as COVID!19 vaccine providers.

Disclaimer: This document is for informational purposes only and is intended to address operational considerations for COVID!19 vaccine preparation during the COVID!19 pandemic. Where a particular COVID!19 vaccine is mentioned, this identi"ication is furnished solely for informational purposes as a matter of convenience, without implication of approval, authorization, endorsement, or certi"ication. This document does not re"lect the USP Healthcare Safety and Quality Expert Committee’s opinions on future revisions to of"icial text of the USP!NF. Parties relying on the information in this document bear independent responsibility for awareness of, and compliance with, any applicable laws and regulations of the applicable regulatory jurisdiction and regulatory status of any COVID!19 treatment. All product names, logos, and brands are property of their respective owners.

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International COVID!19 Vaccine Handling Guide Development

This International COVID!19 Vaccine Handling Guide has vaccine trade name listed in Table 1: COVID!19 Vaccines been developed based on the core concepts described in Described in the International COVID!19 Vaccine Handling the USP COVID!19 Vaccine Handling Toolkit and provides Guide. Since the Janssen and Moderna COVID!19 vaccines information related to several available COVID!19 vaccines do not yet have a vaccine trade name, these vaccines will be currently used internationally. The selection of the vaccines referred to as the Janssen COVID!19 vaccine and Moderna in this international guide is based on those which have COVID!19 vaccine, respectively. received regulatory authorization, have been distributed and COVID!19 vaccine information varies worldwide. Resources utilized in multiple countries, and based on the availability used to compile this information include publicly available of published resources on the vaccines. The focus of this information from the vaccine manufacturers, the WHO, and guide is on vaccines that have been granted Emergency other regulatory bodies. Use Listing (EUL) by the World Health Organization (WHO) The USP Healthcare Safety and Quality Expert Committee for worldwide distribution through COVAX, and COVID!19 (HSQ EC), with experts from the Package and Distribution (PD vaccines available in Brazil and India, where USP has of"ices EC), Nomenclature and Labeling (NL EC), Health Information and where COVID!19 variants bring a sense of urgency. This and Technology (HIT EC), Complex Biologics and Vaccines international guide is not intended to be an exhaustive guide (BIO3 EC), and Compounding (CMP EC) Expert Committees of all the COVID!19 vaccines that are utilized internationally. developed this International COVID!19 Vaccine Handling USP is actively monitoring the evolving situation and will Guide based on stakeholder input, and in anticipation of continue to update this international guide as more vaccines challenges that may arise during the preparation of several become authorized and additional information becomes available COVID!19 vaccines. See Appendix I: Independent available. The inclusion of a COVID!19 vaccine in this guide Expert Volunteers and Other Contributors to the International does not imply approval, authorization, endorsement, or COVID"19 Vaccine Handling Guide. certi"ication by USP or the Expert Committee. Considering the public health emergency posed by During the COVID!19 pandemic, manufacturers are COVID!19, this document was developed without a public partnering with other manufacturers to ensure supply of comment period. This document is not a USP compendial vaccines. For example, the COVID!19 vaccine developed by standard; rather, it re"lects considerations developed by AstraZeneca and University of Oxford [Vaxzevria] has the the USP HSQ EC and other EC members, based on their same formulation as the COVID!19 vaccine manufactured scienti"ic and professional expertise, as well as input by the Serum Institute of India [Covishield]. For consistency from stakeholders. in this document, the vaccine will be referred to by the

Table1: COVID!19 Vaccines Described in the International COVID!19 Vaccine Handling Guide

Manufacturer Vaccine Trade Name Alternative Name

AstraZeneca and University of Oxford Vaxzevria AZD1222

Beijing Bio-Institute of Biological Products (BBIBP) Sinopharm BBIBP!CorV

Bharat-Biotech and Indian Council of Medical Research Covaxin BBV152

Gamelaya Institute Sputnik V Gam-COVID!Vac

Janssen Biotech (Johnson & Johnson) Ad26.COV2.S

Moderna mRNA!1273

P"izer-BioNTech Comirnaty BNT162b2

Serum Institute of India Covishield

Sinovac CoronaVac

Modi"ied and adapted from https://covid19.trackvaccines.org/vaccines/

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1 Preparation

Operational Considerations for COVID!19 Vaccine Preparation

Background • Items that are not necessary for vaccine preparation should be removed from the vaccine preparation area Preparing a conventionally manufactured COVID!19 vaccine (e.g., food, drinks, and other materials). should be performed in accordance with the directions in the • Whenever possible, there should be a sink, water, and manufacturer’s authorized labeling, the laws and regulations soap for hand hygiene in the proximity of the area for of the applicable regulatory jurisdiction and the WHO. This vaccine preparation. If not possible, alcohol-based section focuses on considerations for the preparation of hand sanitizer (see USP Hand Sanitizer Toolkit3, WHO COVID!19 vaccines for administration and can be used to guidance4) should be available. For alcohol-based hand supplement a manufacturer’s authorized labeling, but not sanitizers, the Centers for Disease Control & Prevention replace them. In addition, this information should not replace (CDC) recommends a concentration of 60% to 95% a facility’s existing policies and procedures. ethanol or isopropanol (i.e., isopropyl)5 alcohol.6 • Equipment available in the dedicated area or room may Environmental Considerations include sharps containers, alcohol swabs, sink and/or hand for Vaccine Preparation sanitizer, and materials for personnel hygiene and garbing. • When manufacturer labeling permits, COVID!19 vaccines Achieving and maintaining sterility and can be prepared in ambient air without using a Primary overall freedom from contamination of the vaccines is Engineering Control (PEC) device (e.g., prepared outside dependent on the environmental conditions under which of an International Organization for Standardization (ISO) the preparation process is performed. The following Class 5 air environment). considerations should be made when selecting an environment for preparation of vaccines: • A PEC is de"ined as a device or zone that provides an ISO Class 5 air environment which minimizes the risk of • A dedicated area or room should be utilized for vaccine microbial contamination. preparation. • ISO Class 5 describes the concentration of total • The dedicated area or room should be a clean, particulates per unit volume in the air.7 (See USP uncluttered, functionally separate workspace. General Chapter <1116> Microbiological control and • Whenever possible, the dedicated area or room monitoring of aseptic processing environments). should be away from windows, doors, air vents, etc., to • Understanding that the vaccine preparation will take minimize air"low disruptions. place across a variety of practice settings, it is important • Whenever possible, the area dedicated for vaccine to adhere to aseptic technique to ensure the quality and preparation should not be in an area or close to an safety of the preparation of these vaccine products. area where environmental control challenges could • Clean and disinfect the surface where the vaccine negatively affect the air quality (e.g., restrooms, preparation will take place using a solution of at least warehouses, or food preparation areas). 70% isopropyl alcohol or utilize clean preparation mats per your facility’s policy and procedures. 4 International COVID!19 Vaccine Handling Guide

Personnel Hygiene and Garbing • Inspect vials for cracks or leaks prior to proceeding further. • Disinfect entry points on the diluent and vaccine vials (e.g., Healthcare workers who supervise the preparation vial stoppers) by wiping the vials with single-use alcohol of the vaccines should ensure that personnel are swabs. Allow the alcohol to dry before piercing stoppers adequately skilled, educated, and trained to correctly with sterile needles. perform preparation of COVID!19 vaccines. Before beginning preparation of COVID!19 vaccines, personnel should consider • During preparation of the vaccine, personnel should avoid the following aspects of hygiene and garbing: touching critical parts of the components being used for preparation of the vaccines (e.g., needles, disinfected vial • Personnel should remove hand, wrist, and other exposed stoppers) to minimize microbial contamination. jewelry that could interfere with the effectiveness of • Place all used syringes, needles, vials into puncture-proof garbing or otherwise increase the risk of contamination of containers (e.g., sharps container) and dispose of the the vaccines. containers according to regulatory requirements. • Fingernails should be clean and neatly trimmed to minimize • The disposal of COVID!19 vaccine vials should be particle shedding and avoid glove punctures. secured in a way that mitigates potential tampering. • Personnel should perform hand hygiene by washing hands with soap and water for at least 30 seconds or use hand sanitizer rubbed between hands and "ingers and then Withdrawing Doses allowed to dry. • Personnel should don powder-free gloves before preparing Manufacturer-supplied information on the steps for vaccines for administration. Powder-free gloves should be preparation of the available COVID!19 vaccines is inspected regularly for holes, punctures, or tears and must provided on the manufacturer’s COVID!19 resource webpages be replaced immediately if such defects are detected. per country. For speci"ic COVID!19 vaccine considerations, see Appendix II: Considerations for Handling Speci#ic • Personnel should don and replace garb (e.g., masks, COVID"19 Vaccine Products. Additional considerations, freshly laundered lab coat, powder-free gloves, clean applicable to all vaccines, on how to help ensure complete scrubs) immediately if it becomes visibly soiled or if its doses are withdrawn and safe practices include the following: integrity is compromised. • If applicable, ensure needle and syringe are tightly luer- locked together. Basic Aseptic Considerations • Consider using the smallest syringe appropriate for the for Vaccine Preparation dose to improve dose accuracy. For example, a 0.3 mL or 0.5 mL dose should be drawn up using a 1 mL syringe or 3 Aseptic technique is a set of processes used to mL syringe, respectively, based on syringe availability. keep objects and areas free of microorganisms and thereby • The same needle should be used for withdrawal and minimize infection risk to patients. Aseptic technique should administration. This eliminates the need to change needles be utilized to prepare vaccines for administration to prevent and therefore reduces the risk of touch contamination to the vaccines from being contaminated with microorganisms the vaccine and potential loss of volume. More information from the environment or from the persons preparing them. is provided in the FAQ for Optimizing COVID!19 Vaccine Manufacturer-supplied information on the steps for thawing, Preparation and Safety accessible on page 14.8 storage temperatures, and preparation of the available COVID!19 vaccines is provided on the manufacturer’s • Use the appropriate needle gauge and length for the COVID!19 resource webpages per country. Aseptic technique recipient. considerations for vaccine preparation should include • For example, see the U.S. Centers for Disease Control the following: and Prevention (CDC) Vaccine Administration: Needle Gauge and Length Guide which bases the selection • Follow facility and regulatory requirements related of needle gauge and length on patient age, gender, to competency, training, or certi"ication of vaccine and weight.9 preparation and administration, as appropriate. • Exercise care to avoid contaminating or bending the • Combining vaccine in one syringe from more than one needle if it is being used for both withdrawal and vial to obtain a complete dose is not supported, due to administration. microbial contamination risks and the frequent absence of preservatives.

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• Refrain from using transfer devices (e.g., mini spikes, Beyond-Use Dating dispensing pins) or using one needle to prepare multiple syringes, due to potential loss of vaccine in dead space, or Considerations for damage to the stopper and loss of integrity of the vial. Pre-drawn Syringes • Use a new needle, preferably a smaller needle (e.g., 25 gauge), for each vial puncture to preserve vial septum Opened Vials integrity. Once a vial is punctured, it is considered an opened vial. • Utilize safe practices when recapping the needle after Beyond-use dates and available information for healthcare withdrawing and before administration. practitioners for opened vaccine vials vary across regions. • While small air bubbles can be ignored, large air bubbles See Appendix III: Temperature and Maximum Allowable can lead to underdosing and should be addressed (see Storage Times for Unopened and Opened COVID"19 Vaccine example image of small versus large bubble in Figure 1 of Vials based on information from WHO, Brazil, and India. the FAQ for Optimizing COVID!19 Vaccine Preparation and Open vial policies set by applicable health authorities Safety accessible on page 14.)8 should be followed. For example, in India, open vial policies • If diluent is required, slowly inject the diluent, aiming factor the presence of a vaccine vial monitor (VVM) for the towards the wall of the vial to prevent excess foaming determination of beyond-use dates, and if a VVM is not used, 11 or bubbling. opened vials need to be discarded four hours after opening. VVMs are chemical-indicator labels that adhere to vaccine • Minimize tapping or "licking of the syringe due to the vials or ampules. They show the cumulative heat exposure theoretical risk of inactivating the vaccine or degrading an individual container of vaccine has received through a its quality. gradual and irreversible color change.12 • Slowly withdraw the vaccine to prevent excess foaming or bubbling. Pre-drawn Syringes • Rotate the insertion point of the needle across various Pre-drawing syringes is when a practice setting prepares locations of the vial septum for each withdrawal to reduce and pre-draws the vaccine into syringes in one area and leakage of vaccine. transports them to another area for administration. If pre-drawn syringes are used, one must comply with laws • Independent double check is preferred when resources are and regulations of the applicable regulatory jurisdiction. available. This is best practice to incorporate a process for WHO guidance and several health authorities, including checking that the correct dose and vaccine is prepared, those of India and Brazil, do not recommend pre-drawing particularly in a multi-vaccine environment (i.e., sites where syringes.11,13,14 Physical stability, chemical stability, and more than one vaccine type is administered). According to microbial contamination studies are critical to support this the Institute for Safe Medication Practices (ISMP), further practice and some manufacturers have conducted them. mix-ups have been reported between COVID!19 vaccines Manufacturer-released supporting studies for beyond- and COVID!19 speci"ic monoclonal antibodies, which use dates for Comirnaty, Janssen, and Moderna COVID!19 further highlights the importance of checking the correct vaccines are provided in Appendix IV: Beyond-Use Dating for dose and medicine.10 Pre-Drawn Syringes.

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Labeling Considerations References 1. https://theconversation.com/covid-vaccine-some-waste-is- If vaccines are pre-drawn and not administered normal-but-heres-how-it-is-being-kept-to-a-minimum-152772 immediately, the best practice is to adhere a 2. https://www.usp.org/covid-19/vaccine-handling-toolkit label to the syringe or container(s) (e.g., a light protected, 3. https://www.usp.org/covid-19/hand-sanitizer-information self-sealing bag in which the syringes are stored and 4. https://www.who.int/gpsc/5may/Guide_to_Local_Production.pdf transported). Syringes prepared for administration must be labeled with legible identifying information to prevent errors 5. https://www.cdc.gov/niosh/npg/npgd0359.html during storage, dispensing, transport, and use. 6. https://www.cdc.gov/coronavirus/2019-ncov/hcp/hand-hygiene. html Personnel should consider adding the following labeling 7. https://www.iso.org/standard/53394.html components to the containers in which the vaccine syringes 8. https://www.ashp.org/-/media/assets/pharmacy-practice/ are stored, as well as the vaccine syringe(s). resource-centers/Coronavirus/docs/FAQ-optimizing-covid- vaccine-prep-safety.ashx Container labeling components: 9. https://www.cdc.gov/vaccines/hcp/admin/downloads/vaccine- • Facility name and phone number administration-needle-length.pdf • Quantity of syringes 10. https://www.ismp.org/resources/learning-errors-new-covid-19- • Name and amount of vaccine vaccines 11. https://www.mohfw.gov.in/pdf/COVID19VaccineOG111Chapter16. • The exact beyond-use date and time pdf • Lot number 12. https://www.who.int/immunization_standards/vaccine_quality/ • Initials of preparer(s) What%20is%20VVM%20and%20how%20does%20it%20work.pdf 13. https://www.who.int/publications/m/item/why-are-there-extra- Example of syringe storage container labels doses-of-vaccine-in-the-vaccine-vial 14. http://bvsms.saude.gov.br/bvs/publicacoes/manual_ COVID-19 Vaccine product name procedimentos_vacinacao.pdf Facility name and phone number Quantity and syringes Date & Time to discard (X hours after vial is opened) Lot number Initials of preparer(s)

Syringe labeling components: • Name and amount of vaccine • Route of administration • The exact beyond-use date and time • Lot number • Initials of preparer(s)

Examples of pre-drawn syringe labels

COVID-19 Vaccine product name Route of administration Date & Time to discard (X hours after vial is opened) Lot number Initials of preparer(s)

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Storage and 2 Transportation

Operational Considerations for Storing, Handling and Transporting COVID!19 Vaccines

Background storage and handling SOPs (including those that address Proper storage, handling, and transportation of COVID!19 inclement weather, natural disasters, and traf"ic disruptions). vaccines are critical activities in their integrated supply Sample SOPs, for example purposes only, are available chain. Failure to store and handle vaccines properly can online.1,2 The QMS, along with related SOPs, helps ensure potentially reduce their potency, leading to inadequate proper procedures are followed and problems (e.g., immune response in patients and poor protection against damaged packages or vials) are identi"ied, reported, and COVID!19. Proper storage, handling, and transportation of corrected. SOPs should also provide direction for handling the COVID!19 vaccines begins with an effective cold chain emergencies, such as equipment malfunctions or power process, which is temperature-controlled, using related failures. All staff members who come in contact with the equipment and procedures. It begins with cold storage at vaccines, or who administer the vaccines, should be trained the manufacturing facility and extends to the proper on all relevant practices and procedures. The objective of the receiving, storage, and handling of the vaccine at the training should be to reduce the gap between existing staff provider facility, and in some situations, transportation off- competencies and those required to perform the job (see site or to satellite facilities. USP General Chapter <1079> Risks and Mitigation Strategies for the Storage and Transportation of Finished Drug Products). Manufacturer-supplied information for storing and handling COVID!19 vaccines is provided on the manufacturer’s COVID!19 resource webpages per country. This document Receiving Vaccine focuses on considerations for storing, handling, and transporting vaccines and can be used to supplement, but not When vaccines arrive at the facility, they should be replace a manufacturer’s labeling. In addition, this document transferred as quickly as possible to a designated should not replace a facility’s existing policies and procedures. storage area and stored at the recommended temperature. Receiving areas should protect the product from inclement weather during unloading. Access to the Quality Management System receiving area should also be limited to authorized persons (QMS) only. Deliveries should be examined at receipt to check that shipping containers are not damaged, and that the shipment Developing and maintaining clearly written, corresponds to the order. Check the temperature monitoring detailed, and up-to-date receiving, storage, handling, and device, if applicable, for any indication of temperature transporting standard operating procedures (SOPs) are excursion(s) during transit. Each organization should have a essential. This occurs within the framework of a robust receiving procedure that determines the appropriate checks QMS, which is a set of policies, processes, and procedures for this operation. A checklist can be used as a reminder of required to execute core activities. Due to the risk associated what to inspect and what to record (see USP General Chapter with vaccine transport caused by improper packing or <1079> Risks and Mitigation Strategies for the Storage and storage unit failure, it is necessary to include detailed Transportation of Finished Drug Products). packing and transport protocols in the organization’s

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Vaccine Storage If your facility provides frozen vaccine, a separate freezer unit is necessary.”3 Under no circumstance should a vaccine Storage units are required to maintain the be stored in a small combination refrigerator with a freezer product temperature between the limits de"ined located within the refrigerator compartment. Food and drinks on the product label (see USP General Chapter <695> and/or biological specimens should not be stored in the Packaging and Storage Requirements). Detailed information same unit as the vaccine. on vaccine storage and temperature monitoring equipment is included in section 3 of the CDC Vaccine and Storage Standard operating procedures (SOPs) should be in place Handling Toolkit.3 Manufacturer-supplied information for to ensure power supply or alternative options when power storing the authorized COVID!19 vaccines is provided on the outage occurs. Routine maintenance should be conducted to manufacturer’s COVID!19 resource webpages per country. ensure proper function of the refrigeration unit. Depending on the time of year (e.g., summer, winter), thermostats may The WHO recommends use of temperature monitoring need to be reset, depending on room temperature. devices, based on the speci"ic cold chain equipment application and intended purpose for temperature Typically, a refrigeration unit speci"ication would be set to monitoring. For more information on the various types 5°C (41°F) with an allowable range of ± 3°C (2°C to 8°C or of devices and how they should be used, see the WHO 38°F to 44°F) to store products labeled 2°C to 8°C (36°F to Guidance: How to Monitor Temperature in the Vaccine 46°F). Freezer temperatures may vary and typically range Supply Chain.4 In addition, the WHO sets standards on from -25°C to -10°C (-13°F to 14°F). Most standard freezer minimum, technical, and stability standards, and has a list of units do not meet ultra-cold freezer requirements for storing prequali"ied devices and equipment on their website.5 vaccines between -60°C and -80°C (-76°F and -112°F). According to the CDC Vaccine Storage and Handling Toolkit, If ultra-low freezer temperatures are required and the COVID!19 Vaccine Addendum section, it is essential to utilize manufacturer provides or speci"ies the use of dry ice continuous temperature monitoring systems to ensure that (e.g., Comirnaty COVID!19 vaccine), additional handling the vaccines are stored within the correct temperature precautions should be taken, such as the following: range. Use of a speci"ic device, a digital data logger (DDL) 1. Store thermal shippers containing dry ice, as well as dry with an external display, is preferred.3 A DDL is an electronic ice replenishment containers, in a well-ventilated area. device that records data digitally over time or in relation Because frozen carbon dioxide changes phase (i.e., melts) to location, either with a built-in or external instrument or into a gaseous state, elevated levels of carbon dioxide sensor. Although automated systems monitor temperature can be dangerous to personnel operating within a poorly continuously, manual checks must be performed as ventilated area, which may lead to asphyxiation. appropriate to ensure functionality as well as when the 2. Because of the thermal expansion of dry ice as it changes vaccine is removed from storage. Temperature monitoring phases from a frozen to gaseous state, it should never be devices should be calibrated (in the United States - NIST stored in a tightly sealed device. traceable)3 against nationally accepted standards to ensure 3. Wear impermeable loose-"itting gloves (e.g., leather, accuracy of readings (see USP General Chapter <1118> lined oven mitts, etc.) to protect from contact freezing Monitoring Devices—Time, Temperature, and Humidity). (similar to a burn). Gloves must be insulated to protect Calibration testing should be done every one to two years, or from general freezing temperatures (dry ice is -78.5°C or according to the manufacturer’s suggested timeline. Alarm -109.3°F). systems may be part of the temperature monitoring system. 4. Wear goggles or a face shield to protect your eyes. Pharmaceutical-grade refrigerators and freezers are preferred because they are designed speci"ically for storing For maintaining temperatures at outdoor venues, keep biopharmaceuticals, including vaccines. Per CDC guidance, opened vials or pre-drawn syringes at temperatures “household-grade units can be an acceptable alternative at or below 25°C (77°F) within the beyond-use date for refrigeration in some situations. However, the freezer timeframe until the time of administration to the patient. compartment of household-grade units is not recommended For further information, see the USP Transporting COVID!19 to store vaccines and there may be other areas of the Vaccines Off-Site Guide accessible on page 14. refrigerated compartment that should be avoided as well.

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Temperature Excursions Vaccine Transport Inclement weather, natural disasters, and traf"ic (Off-site or Satellite Facilities) disruption can cause receiving delays and potential Vaccine transport off-site or to satellite temperature excursions. A temperature excursion is any facilities involves the process of transporting vaccines temperature reading outside of the recommended range for over short distances and time frames in accordance with vaccine storage as de"ined in the manufacturer’s package practice setting SOPs. The total time for transport should insert. Temperature excursions or inappropriate storage be minimized to reduce potential risk for a temperature conditions require immediate action. Each excursion excursion due to a storage unit or thermal packaging should be documented, including the magnitude of the system failure. Suf"icient transport supplies (e.g., materials temperature excursion, and the total amount of time that and equipment) are needed. These can include portable temperatures were out of range. For refrigerated vaccines, refrigerator/freezer units, quali"ied containers, coolant Mean Kinetic Temperature may be calculated (see USP materials, insulating materials, and the required temperature General Chapter <1079.2> Mean Kinetic Temperature in the monitoring devices. Evaluation of Temperature Excursions During Storage and Transportation of Drug Products). To determine the impact When vaccine transport is necessary, consider these storage of an excursion, and whether the vaccines are still viable, recommendations: contact the manufacturer for guidance on whether the • The manufacturer-supplied packaging can be used in affected vaccines should be discarded or can be utilized. accordance with the directions in the manufacturer’s While this determination is being made, the vaccines labeling. should be maintained at the appropriate temperature with • Transport the vaccines using a portable refrigerator and/or temperature monitoring and clearly labeled “DO NOT USE freezer unit with a temperature monitoring device. pending guidance by the manufacturer.” Place them in a separate container apart from other vaccines and do not • Appropriate measures should be taken to ensure the discard these vaccines. The ability of the manufacturer vaccine is cushioned and protected from agitation to determine the excursion impact will depend on the during transport. information provided. Detailed information regarding • If a portable refrigerator and/or freezer unit is not available, the excursion will enable the manufacturer to better quali"ied containers and packouts with a temperature provide assistance. Each excursion event is unique and a monitoring device can be used. A container or packout manufacturer’s recommendation for a speci"ic excursion is ‘quali"ied’ through laboratory testing under controlled event should not be applied to future events that appear conditions to ensure they achieve and maintain desired to be similar. temperatures for a set amount of time. They are available via packaging suppliers. Temperature excursion labeling

DO NOT USE pending guidance by the manufacturer.

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• For example, to prepare a packout for transportation of • Secure temperature monitoring device near COVID!19 vaccine pre-drawn syringes or vials: container with pre-drawn syringes or vials for most • The following materials are needed: accurate temperature monitoring. • Temperature monitoring device, with continuous • Place the expanded polystyrene foam container in monitoring being preferred. the hard-plastic container to protect the vaccine during transport. • Bubble wrap or corrugated cardboard cushioning material (at least 1” thick) to provide barrier between • Close the hard-surface or hard-plastic container. cooling agent and pre-drawn syringes. When transporting the vaccine, the temperature should be • Light-protected zip-lock bag or similar container for validated whenever the storage container is opened. pre-drawn COVID!19 vaccine syringes or vials. Vaccines must be secured from theft and tampering • Ice pack or other cooling agent. when not under supervision of healthcare personnel, • Expanded polystyrene foam container to maintain as with other medications. Strategies to ensure secure temperature. transport can include the use of ‘tamper proof’ or ‘tamper • Hard-surface or hard-plastic container to protect evident’ measures (e.g., locks, tape) on these containers as from damage during transport. appropriate, per the healthcare professional’s judgment. For additional information on tampering/damage, see the • The following steps should be taken to prepare a Falsi"ied COVID Vaccine Visual Inspection Guide accessible packout for transportation: on page 14. • Insulate the expanded polystyrene foam container The redistribution of vaccine supply to other in-network with bubble wrap or corrugated cardboard settings for preparation and administration also requires the cushioning. redistribution of adequate ancillary supplies for preparation • Add ice pack or other cooling agent. and administration. • Add bubble wrap or corrugated cardboard cushioning. • Add light-protected container with pre-drawn syringes or vials to top of cushioning material and References secure container. 1. https://www.healthvermont.gov/sites/default/"iles/documents/ pdf/ID_IZ_INFOHCP_S&H_VaccineManagementPlan.pdf 2. https://www.mass.gov/doc/sample-standard-operating- procedure-sop-0/download 3. https://www.cdc.gov/vaccines/hcp/admin/storage/toolkit/ index.html 4. https://apps.who.int/iris/handle/10665/183583 5. https://apps.who.int/immunization_standards/vaccine_quality/ pqs_catalogue/index.aspx

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Waste Minimization and Ancillary 3 Supply Disposal

Operational Considerations for Waste Minimization and Ancillary Supply Disposal for COVID!19 Vaccines

Background • Ensure cold chain is properly maintained with proper storage conditions and continuous temperature monitoring The variety of COVID!19 vaccines in the manufacturing to prevent the need to discard any product due to pipeline will continue to pose challenges for the safe and temperature excursions. This includes implementing proper minimization of waste of unused vaccines and effective procedures for preventative maintenance and safe disposal of ancillary supplies (e.g., dry ice, syringes, repair of cold chain equipment and developing and needles). Disposal of unused vaccines or ancillary supply rehearsing contingency plans in case of emergency waste from a COVID!19 vaccine that has been authorized by situations. local regulators should be performed in accordance with • Ensure vaccine preparers are properly trained and the directions in the manufacturer’s labeling. This document demonstrate competency for proper aseptic technique to focuses on considerations for disposal of unused or ancillary minimize the risk of contaminating the product. supply waste of COVID!19 vaccines and can be used to supplement but not replace a manufacturer’s labeling. • Maximize doses withdrawn from vials by utilizing low dead- In addition, this document should not replace a facility’s volume syringes/needles, whenever possible. A low dead- existing policies and procedures. volume (LDV) syringe is designed to limit dead space that exists between the syringe hub and needle. COVID!19 Vaccine Waste • If pre-drawing is permitted, use pre-drawn syringes with Minimization the earliest discard time "irst to avoid waste. • Carefully consider the number of pre-drawn syringes to Given the critical shortage of COVID!19 vaccines prepare to avoid drawing up unnecessary doses. worldwide, sites should accordingly plan and build standard operating procedures (SOPs) to minimize loss of doses • Carefully insert and withdraw needle from vial septum to while following local regulatory guidance. The following not bend the needle, which could lead to wastage. considerations should be made to minimize or control • Ensure safe practices when recapping the needle and vaccine waste: appropriate closure of safety shield to reduce need to • A site should have plans in place to minimize waste discard product due to microbiological risks. of usable vaccine (e.g., a waiting list for vaccines, plans to distribute vaccines if individuals do not keep appointments, agreements with pharmacies and other local centers for vaccine transport, etc.).

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According to the WHO, “A variety of disposal methods can Considerations for the be chosen, depending on the amount of waste, the location Disposal of Vaccines and (rural or urban) and the availability of local disposal facilities. Ancillary Supplies The method should be safe, respect the environment, and comply with national laws and codes on health and During this pandemic, a large volume of waste could be safety. Open-air incineration is not recommended due to 1 potentially generated due to the large amount of vaccine environmental risks.” use, usage of personal protective equipment (PPE) and other ancillary supplies. The safe disposal of waste is essential to Items to be discarded immediately after use or a eliminate the potential risks to healthcare workers and the recommended double check, or when the vaccine public, and to protect the environment. Disposal of medical exceeds its beyond-use-date and time, may include: waste is managed through national or local laws per country. • Empty vials For information on how to assess, design, and implement • Vials with unused vaccine appropriate waste management mechanisms, see this • Vials with unused diluent WHO interim guidance, COVID!19 Vaccination: Supply and Logistics Guidance.1 • Pre-drawn syringes and needles Medical waste is healthcare waste that may be contaminated • Used syringes and needles (e.g., post patient injection, by blood, body "luids, or other potentially infectious materials.2 used in dilution process, etc.) Medical waste disposal requirements are set by regulatory Facilities should have policies and procedures for security agencies. Follow regulatory or facility policies for appropriate and storage for the COVID!19 vaccines. In addition, the disposal, including for vaccines which contain genetically disposal of COVID!19 vaccine vials should be secured in a modi"ied organisms (Covishield/Vazevria). Empty vaccine vials way to mitigate potential tampering. are usually not considered hazardous or medical waste and do 3 not require disposal in a biomedical waste container. References Needles must be discarded in biohazard containers that are closable, puncture-resistant, leakproof on sides and bottom, 1. https://www.who.int/publications/i/item/who-2019-ncov- vaccine-deployment-logistics-2021!1 labeled, and color-coded (e.g., a sharps container). This is important to help prevent an accidental needlestick, which 2. https://www.epa.gov/rcra/medical-waste can lead to transmission of infection. Dispose of biohazard 3. https://www.cdc.gov/vaccines/hcp/admin/storage/toolkit/ containers according to facility and regulatory requirements. index.html

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Supplemental content is also available Handouts and related content intended to highlight key information and visually represent techniques discussed in this toolkit are also available by clicking on the links below. These handouts include:

Maximizing Doses of P"izer- Maximizing Doses of Moderna Beyond use date in vial or syringe for BioNTech COVID!19 Vaccine COVID!19 Vaccine Max 15 dose vial COVID!19 Vaccines Download the guide Download the guide Download the factsheet View the Video

Transporting COVID!19 ASHP| ISMP | USP FAQs Falsi"ied COVID Vaccine Vaccines Off-Site for Optimizing COVID!19 Vaccine Visual Inspection Guide Download the guide Preparation and Safety Download the guide Download the FAQ

Your feedback helps us improve the content that we offer. Please submit any questions or comments, including if this toolkit has been helpful to you, to [email protected].

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Appendix I: Independent Expert Volunteers and Other Contributors to the International COVID!19 Vaccine Handling Guide The Guide’s development was led by USP’s Healthcare Safety & Quality Expert Committee (HSQ), with input from other USP Expert Committees, government liaisons, observers, and USP staff. Participants as of June 2021:

Healthcare Safety & Quality Expert Committee Nomenclature and Labeling Expert Committee Melody Ryan, PharmD, MPH, (Chair) Professor and Associate Provost Sasha Beselman, PharmD, Investigational Drug Pharmacist, for Global Health Initiatives, University of Kentucky Johns Hopkins Danial Baker, PharmD, (Vice-Chair) Professor and Director of Drug Michael Cohen, MS, RPh, President, Institute for Safe Medication Information Center, Washington State University Practices Timothy Albertson, PhD, MD, MPH, Professor and Chair, Internal Ginette Pepper, PhD, RN, Professor Emeritus, University of Utah Medicine, University of California, Davis College of Nursing Bernard Appiah, DrPH, BS Pharm, Assistant Professor, Department of Public Health, Syracuse University Packaging and Distribution Expert Committee Nisha Bhide, PharmD, Senior Clinical Operations Manager, Capital Rx Chris Anderson, MA, Director, Quality Systems, Cardinal Health Lakesha Butler, PharmD, Professor, Southern Illinois University, Glaucia Braga, PhD, Auditor of the Public-Private Partnership – Edwardsville Senior Quality Assurance Analyst, FURP Mark Decerbo, PharmD, Associate Professor of Pharmacy, Roseman University of Health Sciences Government Liaison (HSQ) Lauren Hoffman, PharmD, MPH, Senior Consultant, Linda Kim-Jung, PharmD, FDA Center for Veterinary Medicines (CVM) Express Scripts, Inc. Jo Wyeth, Surveillance Program Lead, FDA CDER, Division of Raymond Love, PharmD, Professor and Director of Mental Health Medication Error Prevention and Analysis (DMEPA) Program, University of Maryland, Baltimore Joseph Lubega, MD, MPH, Assistant Professor, Baylor College Government Liaison (Observers) of Medicine Anita Patel, PharmD, Senior Advisor, Pandemic Medical Care and Linda Pugh, PhD, Retired nurse professor Countermeasures Lead, In"luenza Coordination unit, National Center Michelle Then, PharmD, MBA, Pharmacy Manager-Medication Safety, for Chronic Disease Prevention and Health Promotion, CDC Quality, Compliance, Denver Health Medical Center JoEllen Wolicki, BSN, Nurse Educator, National Center for Chronic Dennis West, PhD, BS Pharm, Professor Emeritus of Dermatology and Disease Prevention and Health Promotion, CDC Pediatrics, Northwestern University Sara Gagneten, PhD, Associate Division Director, Division of Shonna Yin, MD, MS, Associate Professor of Pediatrics and Population Viral Products, OVRR, CBER, FDA Health, NYU School of Medicine Other Observers Complex Biologics and Vaccines Expert Committee Michael Ganio, PharmD, Director Pharmacy Practice and Quality, Mark van Ooij, PhD, Scienti"ic Director, Janssen Vaccines (J&J), American Society of Hospital Pharmacists Netherlands Ganesh Barhate, PhD, Senior Technical Manager, MS&T, Novartis USP Staff Technical Operations, Austria Farah Tow"ic, PharmD, MBA, Director, CEO Operations Paul Stickings, PhD, Principal Scientist, National Institute for Biological Nurisha Wade, Vice President, Healthcare Quality & Safety Center Standards and Control, United Kingdom for Excellence Nakia Eldridge, PharmD, MBA, Senior Manager, Healthcare, Compounding Expert Committee Patient Safety & Information Lisa Ashworth, BS Pharm, Compounding Specialist and Clinical Brian Serumaga, PhD, RPh, MPH, Senior Manager, Personalized Pharmacist, Children’s Health System of Texas Medicines, Compounding Expert Committee Phil Ayers, PharmD, Chief, Clinical Pharmacy Services, Mississippi Desmond Hunt, PhD, Principal Scienti"ic Liaison, Packaging & Baptist Medical Center Distribution Expert Committee Kevin Hansen, PharmD, MS, Assistant Director of Pharmacy, Diana Kwan, PharmD, Scienti"ic Liaison, Healthcare Safety & Quality Cone Health Expert Committee Connie Sullivan, BS Pharm, President and CEO, National Home Donna Bohannon, B.S. Pharm, MS, Senior Scienti"ic Liaison, Healthcare Infusion Association Information and Technology Expert Committee Misti Spann, PharmD, Scienti"ic Liaison, Nomenclature and labeling Health Information & Technology Expert Committee Expert Committee Roy Guharoy, PharmD, MBA, Vice President, Chief Pharmacy Lindsey Clawson, MBA, Lead, COVID!19 Vaccine Strategy Of"icer, Baptist Health Marissa Brykman, JD, United States Regulatory Affairs Policy Director Shreya Parekh, PharmD, Clinical Informatics Specialist, Jeanne Sun, PharmD, JD, Counsel Jefferson Health Abigail Ammerman, Expert Committee Manager James Austgen, PhD, Expert Committee Manager

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Appendix II: Considerations for Handling Speci"ic COVID!19 Vaccine Products The selection of the vaccines in this international guide is based on those which have received regulatory authorization, distributed and utilized in multiple countries, and availability of published resources. The focus of this guide is vaccines granted WHO Emergency Use Listing (EUL) for worldwide distribution through COVAX and COVID"19 vaccines available in Brazil and India, where USP has local of#ices, and which are areas where COVID"19 variants of concern bring a sense of urgency. The inclusion of a COVID"19 vaccine in this guide does not imply approval, authorization, endorsement, or certi#ication.

Comirnaty COVID!19 Step 2: Dilute the vaccine Vaccine Considerations • Visually inspect vial for cracks and leaks. • Wipe diluent vial stopper using sterile 70% isopropyl Preparation alcohol swab and allow to dry. • Maximize doses withdrawn from vials (at least 6 doses) • If applicable, ensure needle and syringe are tightly luer- by utilizing low dead-volume (LDV) syringes/needles, locked together. whenever possible. A low dead-volume syringe is designed • Withdraw 1.8 mL 0.9% sodium chloride, preservative to limit dead space that exists between the syringe hub free, diluent into syringe. Discard vial after diluent and needle. withdrawal. • Practice settings that may not have adequate quantities • To prevent excess foaming or bubbling, slowly inject of LDV syringes can maximize doses by utilizing a 1.8 mL of 0.9% sodium chloride, preservative free, combination of LDV and non-LDV syringes (e.g., 3 LDV diluent onto the wall of the vaccine vial. syringes and 3 non-LDV syringes). The ratio of LDV to non- LDV syringes should be dependent on the type of syringe • Before removing the needle from the vaccine vial, and needle used. move the needle tip to the air headspace of the vial and draw out 2.1 mL of air to optimize vial pressure. • Regardless of diluent vial size, only a single needle entry can be used to withdraw a single 1.8 mL volume of • Gently invert the diluted vial 10 times to mix. Do not shake. preservative-free 0.9% sodium chloride diluent to prepare • Record dilution date and time on vaccine vial and one vial of the Comirnaty COVID!19 vaccine. Any excess store diluted vaccine for up to 6 hours at 2°C to 25°C diluent must be discarded. (35°F to 77°F). • Preservative-free 0.9% sodium chloride diluent should not be drawn up in advance as it is preservative-free. Step 3: Draw up each dose of the vaccine • The manufacturer states that for dose preparation, a • Wipe vaccine vial stopper using sterile 70% isopropyl 21-gauge or narrower needle helps prevent leaking from alcohol swab and allow to dry. the stopper when doses are withdrawn. • If applicable, ensure needle and syringe are tightly luer- locked together. Withdrawal • Inject 0.2 mL of air into the vial of reconstituted vaccine to The following are steps for withdrawing doses, including optimize vial pressure. optimizing vial pressure to ensure that the number of doses • Slowly withdraw 0.3 mL of vaccine into the administration is maximized for each Comirnaty COVID!19 Vaccine vial. syringe. Follow aseptic technique throughout vaccine preparation. • While small air bubbles can be ignored, large air bubbles Step 1: Prepare for dilution can lead to underdosing and should be addressed. Minimize tapping of the syringe due to theoretical risk of • A Comirnaty COVID!19 vaccine vial must reach room inactivating the vaccine or degrading quality. temperature before dilution and be diluted within 2 hours of removal from frozen or refrigerated storage. • Utilize safe practices when recapping the needle after withdrawing and before administrating. • Inspect liquid to ensure it is a white to off-white suspension which may contain white to off-white opaque amorphous • Rotate the insertion point of the needle across various particles. locations of the vial septum for each withdrawal to reduce leakage of vaccine. • Invert vaccine vial gently 10 times. Do not shake.

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Moderna COVID!19 Vaccine Considerations

Preparation • Maximize doses withdrawn from vials by utilizing low-dead volume (LDV) syringes/needles whenever possible to minimize drug loss in syringe/needles. • Practice settings with adequate quantities of LDV syringes, utilizing only LDV syringes, should consistently withdraw the maximum number of extractable doses (11 or 15). • Practice settings that may not have adequate quantities of LDV syringes can consistently achieve 14 doses from the Moderna COVID!19 vaccine Max 15 doses vial by utilizing a combination of LDV and non-LDV syringes (e.g., 7 LDV syringes and 7 non-LDV conventional or luer-locked. needles/syringes). The ratio of LDV to non-LDV syringes should be dependent on the type of syringe and needle used.

Withdrawal The following are steps for withdrawing doses, including optimizing vial pressure to help maximize doses for the Moderna COVID!19 vaccine multiple-dose vial with • Slowly withdraw 0.5 mL of vaccine into the Max 15 doses. administration syringe. Follow aseptic technique throughout vaccine preparation: • While small air bubbles can be ignored, large air bubbles can lead to underdosing and should be addressed. Step 1: Prepare Moderna Max 15 dose vial Minimize tapping of the syringe due to theoretical risk of • Thaw each vial before use. Vials may be thawed: inactivating the vaccine or degrading quality. • In the refrigerator at 2°C to 8°C (36°F to 46°F) • Rotating the insertion point of the needle across various for 3 hours. locations of the vial septum for each withdrawal to reduce leakage of vaccine. • At room temperature at 15°C to 25°C (59°F to 77°F) for 1 hour and 30 minutes. • Gently swirl and tilt the vial to withdraw the "inal dose to maximize the volume of vaccine withdrawn. Be careful Step 2: Draw up each dose of the vaccinea not to bend the needle. • Visually inspect vial for cracks and leaks. • Utilize safe practices when recapping the needle after withdrawing and before administering. • Swirl vial gently after thawing and between each withdrawal. Do not shake. • Wipe vaccine vial stopper using sterile 70% isopropyl alcohol swab. Allow to air dry before inserting needle. • If applicable, ensure needle and syringe are tightly luer-locked together. • Inject 0.2 mL of air into the vial of vaccine to optimize vial pressure.

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Janssen COVID!19 Vaccine Considerations

• Visually inspect vial for cracks and leaks. • Wipe vaccine vial stopper using sterile 70% isopropyl alcohol swab. Allow to air dry before inserting a needle. • Before withdrawing each dose of vaccine, carefully mix the contents of the multi-dose vial by swirling gently in an upright position for 10 seconds. • Do not shake the vial. • The same needle should be used for withdrawal and administration. This eliminates the need to change needles and therefore reduces the risk of touch contamination to the vaccine and potential loss of volume. • Rotate the insertion point of the needle across various locations of the vial septum for each withdrawal to reduce leakage of vaccine. • The product should be protected from light and ultraviolet light. PHOTO: U.S. Army National Guard, Sgt. Sebastian Rothwyn

Covishield/Vaxzevria COVID!19 Vaccine CoronaVac COVID!19 Vaccine Considerations Considerations

• Visually inspect vial for cracks and leaks. • Visually inspect vial for cracks and leaks. • Inspect the vial to make sure the liquid is clear to slightly • Do not use vaccine vial if it is cracked, has a badly printed opaque, and colorless to slightly brown. or unlit label, or if there is a foreign body in the vaccine • Inspect the vial for the presence of any particulate matter vial. or other coloration prior to administration. Discard • Wipe vaccine vial stopper using sterile 70% isopropyl if particulate matter or differences in the described alcohol swab. Allow to air dry before inserting a needle. appearance are observed. • Shake well before administration. Unlike some of the other • Wipe vaccine vial stopper using sterile 70% isopropyl COIVD!19 vaccines which should not be shaken, this alcohol swab. Allow to air dry before inserting a needle. vaccine must be shaken. • Do not shake the vial. • If precipitation is observed, disperse it by shaking. • The same needle should be used for withdrawal and • The same needle should be used for withdrawal and administration. This eliminates the need to change needles administration. This eliminates the need to change needles and therefore reduces the risk of touch contamination to and therefore reduces the risk of touch contamination to the vaccine and potential loss of volume. the vaccine and potential loss of volume. • Rotate the insertion point of the needle across various • Rotate the insertion point of the needle across various locations of the vial septum for each withdrawal to reduce locations of the vial septum for each withdrawal to reduce leakage of vaccine. leakage of vaccine. • The product should be protected from light and • The product should be protected from light and ultraviolet light. ultraviolet light.

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Sinopharm COVID!19 Vaccine Considerations

• Visually inspect vial or pre-"illed syringe for cracks and leaks. • Inspect the vial or pre-"illed syringe to make sure that the liquid is an opalescent suspension, milky-white in color. • If precipitation is observed, disperse it by shaking. Unlike some of the COVID!19 vaccines which should not be shaken, this vaccine should be shaken. • For manufacturer pre-"illed syringes of Sinopharm: • If applicable, ensure needle and syringe are tightly luer-locked together. • For single-dose vials of Sinopharm: • Wipe vaccine vial stopper using sterile 70% isopropyl alcohol swab. Allow to air dry before inserting a needle. • The same needle should be used for withdrawal and administration. This eliminates the need to change needles and therefore reduces the risk of touch Covaxin COVID!19 Vaccine contamination to the vaccine and potential loss Considerations of volume. • The product should be protected from light and • Visually inspect vial for cracks and leaks. ultraviolet light. • Inspect the vial for the presence of any particulate matter or other coloration prior to administration and discard if particulate matter or differences in the described Sputnik V COVID!19 Vaccine appearance are observed. Considerations

• Wipe vaccine vial stopper using sterile 70% isopropyl • Visually inspect vial for cracks and leaks. alcohol swab. Allow to air dry before inserting a needle. • Wipe vaccine vial stopper using sterile 70% isopropyl • Shake vaccine vial to obtain a uniform, whitish translucent alcohol swab. Allow to air dry before inserting a needle. suspension before administration. Unlike some of the • Carefully mix the contents of the vial by swirling gently. other COVID!19 vaccines which should not be shaken, this Do not shake. vaccine must be shaken. • The same needle should be used for withdrawal and • The same needle should be used for withdrawal and administration. This eliminates the need to change needles administration. This eliminates the need to change needles and therefore reduces the risk of touch contamination to and therefore reduces the risk of touch contamination to the vaccine and potential loss of volume. the vaccine and potential loss of volume. • Rotate the insertion point of the needle across various • Rotate the insertion point of the needle across various locations of the vial septum for each withdrawal to locations of the vial septum for each withdrawal to reduce reduce leakage of vaccine. leakage of vaccine. • The product should be protected from light and • The product should be protected from light and ultraviolet light. ultraviolet light.

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Appendix III: Temperature and Maximum Allowable Storage Times of COVID!19 Vaccines for Unopened and Opened Vials Based on Information from WHO, Brazil, and India

The selection of the vaccines in this international guide is based on those which have received regulatory authorization, distributed and utilized in multiple countries, and availability of published resources. The focus of this guide is vaccines granted WHO Emergency Use Listing (EUL) for worldwide distribution through COVAX and COVID"19 vaccines available in Brazil and India, where USP has local of#ices, and which are areas where COVID"19 variants of concern bring a sense of urgency. The inclusion of a COVID"19 vaccine in this guide does not imply approval, authorization, endorsement, or certi#ication.

WHO (Last updated June 29, 2021)

Route/ # of Maximum allowable storage time at different Maximum allowable storage time at Presentation Dose doses temperatures for UNOPENED vials different temperatures for OPENED vials

Comirnaty1 Intramuscular Multi-dose 0.3 mL Frozen solid vaccine vials For diluted vaccine injection/ 2 vials (single dose) • At ultra-low freezer temperature of At refrigerator to ambient room doses -80°C to -60°C (-112°F to -76°F), the shelf life is temperature of 2°C to 30°C (35°F to 86°F), 6 months after time of manufacturing. the maximum allowable storage time • At thermal shipper container temperature of is 6 hours after dilution or at the end of -90°C to -60°C (-130°F to -76°F),can be used the immunization session, whichever up to 30 days, if following manufacturer re- comes "irst. icing instructions (should be re-iced every 5 days if opened up to 2 times a day, less than 3 minutes at a time). • At frozen temperature of -25°C to -15°C (-13°F to 5°F), the maximum allowable storage time is a total of 2 weeks. For unopened thawed vaccine • At refrigerator temperature of 2°C to 8°C (36°F to 46°F), can be used up to 120 hours (5 days) prior to dilution. • At ambient room temperatures up to +30°C (86°F), can be used up to 2 hours.

CoronaVac2 Intramuscular Single-dose 0.5 mL At refrigerator temperatures of 2°C to 8°C (35°F For single dose presentation injection/ 2 and multi- (single dose) to 46°F), the shelf life is 12 months, the expiry Should be used immediately after doses dose vials date as indicated on label and packaging. opening. and pre-"illed syringes

Covishield/ Intramuscular Multi-dose 0.5 mL At refrigerator temperatures of At refrigerator temperatures of 2°C to 8°C Vaxzevria3 injection/ 2 vials (single dose) 2°C to 8°C (35°F to 46°F), the expiry date is (35°F to 46°F), the maximum allowable doses indicated on label and packaging. The expiry storage time is 6 hours after vial puncture date refers to the last day of that month. or at the end of the immunization session, whichever comes "irst.

Janssen4 Intramuscular Multi-dose 0.5 mL Frozen solid vaccine vials At refrigerator temperatures of 2°C injection/ 2 vial (single dose) • At frozen temperature of -25°C to -15°C (-13°F to 8°C (35°F to 46°F), the maximum doses to 5°F), the shelf-life is 24 months, the expiry allowable storage time is 6 hours after date is indicated on label and packaging. vial puncture, or at the end of the For unopened thawed vaccine immunization session, whichever comes • At refrigerator temperature of 2°C to 8°C (36°F "irst. to 46°F), the maximum allowable storage time for a single period of up to 3 months once removed from freezer.

Moderna5 Intramuscular Multi-dose 0.3 mL Frozen solid vaccine vials At refrigerator to ambient room injection/ 2 vials (single dose) • At frozen temperature of -25°C to -15°C (-13°F temperature of 2°C to 25°C (35°F to 77°F), doses to 5°F), the unopened vials can be stored until the maximum allowable storage time is expiry date. 6 hours after vial puncture or at the end For unopened thawed vaccine of the immunization session, whichever • At refrigerator temperature of 2°C to 8°C (36°F comes "irst. to 46°F), the maximum allowable storage time is up to 30 days. • At ambient room temperatures 8°C to 25°C (46°F to 77°F), the maximum allowable storage time is 12 hours.

Sinopharm6 Intramuscular Single-dose 0.5 mL At refrigerator temperature of 2°C to 8°C (36°F For single-dose presentation injection/ 2 vial and (single dose) to 46°F), the shelf life is 24 months from time of Should be used immediately after doses pre-"illed manufacturing, the expiry date is indicated on opening. syringes label and packaging.

1. https://www.who.int/publications/m/item/comirnaty-covid-19-mrna-vaccine 2. https://www.who.int/news/item/01!06!2021-who-validates-sinovac-covid-19-vaccine-for-emergency-use-and-issues-interim-policy-recommendations 3. https://www.who.int/publications/m/item/chadox1-s-recombinant-covid-19-vaccine 4. https://www.who.int/publications/m/item/janssen-ad26-cov2-s-recombinant-covid-19-vaccine 5. https://www.who.int/publications/m/item/moderna-covid-19-vaccine-(mrna-1273) 6. https://www.who.int/publications/m/item/sinopharm-vero-cell---inactivated-covid-19-vaccine

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Brazil (Last updated June 29, 2021)

Route/ # of Maximum allowable storage time at different Maximum allowable storage time at Presentation Dose doses temperatures for UNOPENED vials different temperatures for OPENED vials

Comirnaty1 Intramuscular Multi-dose 0.3 mL Frozen solid vaccine vials For diluted vaccine injection/ vial (single dose) • At ultra-low freezer temperature of -90°C to At refrigerator to ambient room 2 doses -60°C (-130°F to -76°F), the shelf life is temperature of 2°C to 30°C (35°F to 86°F), 6 months from time of manufacturing. the maximum allowable storage time is • At frozen temperature of -25°C to -15°C (-13°F 6 hours after dilution. to 5°F), the closed vials can be transported for a single period of up to 2 weeks and can be returned to -90°C to -60°C (-130°F to -76°F). For unopened thawed vaccine • At refrigerator temperature of -2°C to 8°C (35°F to 46°F), the maximum allowable storage time is 31 days.2 • At ambient room temperatures up to +30°C (86°F), can be used up to 2 hours.

CoronaVac3 Intramuscular Single-dose 0.5 mL At refrigerator temperatures of 2°C to 8°C For single-dose presentation: injection/ and multi- (single dose) (35°F to 46°F), the shelf life is 12 months from Should be used immediately after 2 doses dose vials time of manufacturing, the expiry date is opening. indicated on label and packaging. For multi-dose presentation: At refrigerator to ambient room temperature of 2°C to 30°C (35°F to 86°F), the maximum allowable storage time is up to 8 hours.

Covishield4 Intramuscular Multi-dose 0.5 mL At refrigerator temperatures of 2°C to 8°C At refrigerator temperature of 2°C to 8°C injection/ vial (single dose) (35°F to 46°F), the shelf life is 6 months from (35°F to 46°F), the maximum allowable 2 doses time of manufacturing, the expiry date is storage time is 48 hours after opening. indicated on label and packaging. At ambient room temperatures of up to +30°C (86°F), the maximum allowable storage time is 6 hours after opening.

Covaxin5 Intramuscular Single-dose 0.5 mL Approved in June 2021 for import by ANVISA, Brazil’s National Health Surveillance Agency. injection/ and multi- (single dose) Information not available at time of publication. 2 doses dose vials

Janssen6 Intramuscular Multi-dose 0.5 mL Store at refrigerator temperatures of 2°C to 8°C At refrigerator temperatures of 2°C injection/ vial (single dose) (35°F to 46°F). Check expiry date by: to 8°C (35°F to 46°F), the maximum 1 dose allowable storage time is 6 hours after • Scanning the QR code on the back of the box opening. using a mobile device camera; • On the internet: www.vaxcheck.jnj; or At ambient room temperatures up to the maximum allowable • By phone: calling SAC Janssen Brasil: 25°C (77°F), storage time is 2 hours after opening. 0800 701 1851.

Sputnik V5 Intramuscular Single-dose 0.5 mL Approved in June 2021 for import by ANVISA, Brazil’s National Health Surveillance Agency. injection/ and multi- (single dose) Information not available at time of publication. 2 doses dose vials

1. https://www.p"izer.com.br/bulas/comirnaty 2. https://www.gov.br/anvisa/pt-br/assuntos/noticias-anvisa/2021/agencia-autoriza-novas-condicoes-de-conservacao-para-vacina-da-p"izer 3. https://vacinacovid.butantan.gov.br/bulas 4. https://www.gov.br/anvisa/pt-br/assuntos/paf/coronavirus/vacinas-covid/registros 5. https://en.mercopress.com/2021/06/05/anvisa-allows-for-limited-imports-of-sputnik-v-and-covaxin-into-brazil 6. https://www.janssen.com/brasil/sites/www_janssen_com_brazil/"iles/prod_"iles/live/vacina_covid-19_recombinante_pub_vps.pdf

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India (Last updated June 29, 2021)

Route/ # of Maximum allowable storage time at different Maximum allowable storage time at Presentation Dose doses temperatures for UNOPENED vials different temperatures for OPENED vials

Covishield1 Intramuscular Single-dose 0.5 mL At refrigerator temperatures of At refrigerator to ambient room injection/ 2 and multi- (single dose) 2°C to 8°C (35°F to 46°F), the expiry date is temperature of 2°C to 25°C (35°F to 77°F), doses dose vials indicated on label and packaging. the maximum allowable storage time is 6 hours after vial puncture or at the end of the immunization session, whichever comes "irst.

Covaxin2 Intramuscular Single-dose 0.5 mL At refrigerator temperatures of 2°C to 8°C At refrigerator temperature of 2ºC to 8ºC injection/ 2 and multi- (single dose) (35°F to 46°F), the expiry date is indicated (35°F to 46°F), the maximum allowable doses dose vials on label and packaging. storage time is 6 hours after opening.

Sputnik3 Intramuscular Single-dose 0.5 mL India granted Emergency Use Authorization in April 2021. Information not available injection/ 2 and multi- (single dose) at time of publication. doses dose vials

1. https://www.seruminstitute.com/pdf/covishield_ChAdOx1_nCoV19_corona_virus_vaccine_insert.pdf 2. https://cdsco.gov.in/opencms/export/sites/CDSCO_WEB/en/COVAXIN!SMPC_-BBIL.pdf 3. https://timeso"india.indiatimes.com/india/covid-19-india-approves-russian-vaccine-sputnik-v-for-emergency-use/articleshow/82030439.cms

22 International COVID!19 Vaccine Handling Guide

Appendix IV: Beyond-Use Dating for Pre-Drawn Syringes

If pre-drawing is permitted, consider the following Janssen COVID!19 Vaccine manufacturer-released information supporting stability of the • According to Janssen Biotech, Inc., based on data on "ile, vaccine pre-drawn into syringes for Comirnaty, Janssen, and pre-drawn syringes can be stored: Moderna COVID!19 vaccines provided below. • In the refrigerator at 2°C to 8°C (36° to 46°F) provided Comirnaty COVID!19 Vaccine they are administered within 6 hours of the "irst time the source vial is punctured. • P"izer has conducted physical and chemical stability • In ambient room temperature up to 25°C (77°F) studies which have shown that the vaccine maintains all its provided they are administered within 2 hours of the measured quality attributes when diluted vaccine is stored "irst time the source vial is punctured. in polycarbonate and polypropylene syringes with stainless steel needles for 6 hours at 2°C to 25°C (35°F to 77°F) after • Per Janssen Biotech, Inc., common disposable syringes the source vial is diluted. made of polypropylene or polycarbonate are suitable for use. • Microbiological risk was assessed through a microbiological challenge study which showed that Moderna COVID!19 Vaccine microbiological growth has a greater potential to occur • According to the Chemistry, Manufacturing and Control after 6 hours. The hold time of 6 hours, from the time (CMC) department at Moderna, pre-drawn syringes can be the source vial is diluted, is not speci"ically tied to a stored in the refrigerator to ambient room temperature at preparation environment and can be applied to doses 2°C to 25°C (35° to 77°F) provided they are administered prepared outside of ISO Class 5 environment (PEC). within 12 hours of the "irst time the source vial is punctured. • Per Moderna, common disposable syringes made of polypropylene or polycarbonate are suitable for use.

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