Immunizing agents are biologic materials that are subject to gradual loss of potency from deterioration and denaturation. Loss of potency can be accelerated under certain conditions of transport, storage and handling and may result in failure to stimulate an adequate immunologic response, leading to lower levels of protection against disease. Conditions that result in loss of potency vary among products.
Maintaining the potency of vaccines is important for several reasons:
A detailed discussion of storage and handling recommendations for immunizing agents is beyond the scope of the Canadian Immunization Guide. Detailed information for vaccine providers regarding vaccine storage and handling is available in the Public Health Agency of Canada’s (PHAC) National Vaccine Storage and Handling Guidelines for Immunization Providers (2007). Recommendations for vaccine storage and handling procedures may vary across jurisdictions.
Vaccines are biological products which may become less effective, or even be destroyed, if exposed to light or temperatures outside the recommended range.
Vaccine “Cold Chain”
“Cold chain” refers to the process used to maintain optimal conditions, particularly temperature, during the transport, storage and handling of vaccines, beginning at the manufacturer and ending with administration of the vaccine to the vaccine recipient. Monitoring of vaccines’ cold chain is required to ensure that these products have been stored and transported at recommended temperatures. Exposure of a vaccine to environmental conditions outside those recommended for the product is called a cold chain break, breach or failure, or temperature excursion. Refer to the list of steps in handling vaccines exposed to inappropriate vaccine storage conditions for product specific storage recommendations.
There are several negative consequences of breaks in the cold chain. Vaccines exposed to temperatures above the recommended temperature range may experience some loss of potency with each episode of exposure. Repetitive exposure to increased temperature can result in protein denaturation and a cumulative loss of potency that is not reversible. Some vaccines, such as those containing an aluminum adjuvant, experience a permanent loss of potency due to adjuvant clustering when subjected to freezing and thawing. Freezing of a vaccine or diluent may cause cracks in the container which may lead to contamination of the contents.
It can be difficult to assess the potency of a mishandled vaccine because there is little information about vaccine degradation; multipoint stability studies on vaccines are challenging to perform and information from manufacturers is not always available. Data are available to indicate that some products remain stable at temperatures outside of the recommended range for specified periods of time, but mechanisms rarely exist for monitoring the effect of cumulative exposures. Products that have been exposed to adverse environmental conditions should be managed in accordance with specific instructions from public health officials or the vaccine supplier.
Ongoing cold chain monitoring is an integral part of immunization practices. PHAC’s National Vaccine Storage and Handling Guidelines for Immunization Providers (2007) provides detailed information on establishing standards for cold chain monitoring (i.e., temperature monitors in packages or on vaccine vials, freeze indicators) and evaluating awareness, equipment, practices and potential administrative errors during vaccine transportation and storage.
Single-dose vaccines should be reconstituted or drawn up immediately before administration. They should be discarded if the vaccine has been drawn up or reconstituted and subsequently not used within the time frame specified by the manufacturer or jurisdictional guidelines. If the protective cap on a single-dose vial is removed, or if a manufacturer’s pre-filled syringe is opened (e.g., syringe cap removed), the vaccine should be used on that clinic day or discarded.
Once punctured, multi-dose vials should be marked with the date of initial entry into the vial and, if reconstituted, marked with the date and time of reconstitution. Some vaccines provided in multi-dose vials must be used within a specified time after initial puncturing of the vial or after reconstitution. This date will be different than the expiration date printed on the vial by the manufacturer. The new “use by” date should be written on the vial once it has been punctured.
Multi-dose vials must be maintained under appropriate storage conditions (+2°C to +8°C in a secure site to prevent tampering) and removed from the refrigerator (or cooler in community immunization clinics) only to withdraw the required dose from the vial. Vaccine providers should observe strict aseptic technique when using multi-dose vials.
In immunization clinic sessions in which only a single vaccine is being administered, the contents of more than one multi-dose vial may be combined to prevent wastage if the vials have the same lot number.
Manufacturer’s recommendations or jurisdictional guidelines for use of multi-dose vials should be followed. Available information from the product monographs has been summarized in Annex 1.
Reconstitution of lyophilized vaccines
For optimal potency, lyophilized (freeze-dried) vaccines (refer to Appendix 1) should be reconstituted immediately before use with the diluent provided by the manufacturer for that purpose. Refer to the product leaflet, product monograph, or jurisdictional guidelines for vaccine-specific recommendations regarding storage requirements for lyophilized vaccines and diluents, and the time frame for use following reconstitution. If not otherwise instructed by the manufacturer or jurisdictional guidelines, diluents that do not contain vaccine components and that are packaged separately from the vaccine may be stored at room temperature to conserve refrigerator space. The vaccine for which the diluent should be used must be marked clearly to avoid using the wrong diluent.
Reconstituted vaccines should be discarded if not used within the time frame specified for use by the manufacturer or jurisdictional guidelines.
Pre-loading vaccines in syringes
Many vaccines are now provided by manufacturers in pre-loaded syringes. If a vaccine is not provided in a pre-loaded syringe, it should ideally be drawn into the syringe immediately before use. If pre-loading vaccines in syringes is undertaken in an office setting, vaccine providers should prepare only the number of vaccine doses that are expected to be administered during the consultation. If pre-loading vaccines in syringes is undertaken in an immunization clinic setting, vaccine providers should prepare only the number of doses required to keep the clinic running efficiently and doses should be used as soon as possible. If syringes are pre-loaded by a hospital pharmacy, labels should indicate the time by which the vaccine should be used. Vaccine administrators need to consider: the length of time the vaccine will be stored in the pre-loaded syringe; the type of vaccine (i.e., live vs. inactivated vaccine); the potential of exposure to light; the potential for interaction between the vaccine and the material used in the syringe; and the manufacturers’ specifications for vaccine storage. Refer to Vaccine Administration Practices in Part 1 for additional information.
Vaccine-specific storage and handling information
Appendix 1 provides vaccine-specific storage and handling information. For additional storage and handling information consult the product leaflet or information contained within the product monograph available through Health Canada’s Drug Product Database.
Store vaccines in their original packaging; the packaging provides protection from light and physical damage.
The storage temperature for refrigerated vaccines is between +2°C and +8°C.
Store frozen vaccines at a temperature between -15°C to -50°C or as specified by the product monograph. It should be noted that the use of dry ice may subject vaccines to temperatures colder than -50°C. In general vaccines that have thawed should not be refrozen.
Exposure to freezing
Vaccines that should be stored at +2°C to +8°C should not be used if they have been frozen. Diluent that has been frozen should not be used. Before use, vaccines should be inspected and not used if the usual appearance is altered or a temperature recording device shows that the vaccine was exposed to temperatures below 0ºC. If a vaccine has been exposed to freezing, refer to The list of steps in handling vaccines exposed to inappropriate vaccine storage conditions. and Appendix 1 and consult public health officials for advice. Additional information regarding stability of vaccines is available from the World Health Organization.
Exposure to heat
Refer to the section on cold chain break management below.
Exposure to light
Vaccines should be stored in their original packaging and protected from light, as exposure to light may cause loss of potency in some vaccines. Some vaccines (such as measles-mumps-rubella (MMR), varicella, and Bacille Calmette-Guérin [BCG] vaccines) should be protected from light exposure at all times. Exposure to light should be limited when pre-loading syringes.
All vaccines and diluents have expiration dates beyond which the product must not be used. Expiration dates are labelled on product containers (e.g., vials, syringes) and package boxes. When the expiration date is marked with only a month and year, the vaccine or diluent may be used up to and including the last day of the month indicated on the vial. If vaccine has been inappropriately exposed to excessive heat, cold, or light, its potency may be reduced before the expiration date is reached. If an expired vaccine has been inadvertently administered, it should not be counted as a valid dose and should be repeated, respecting the appropriate interval between live parenteral vaccines.
Vaccines that cannot be used because of expiry or breach of the cold chain should either be returned to the supplier for disposal or appropriately disposed of according to jurisdictional standards. Live vaccines and their containers must be disposed of according to standards for biologic products.
Any refrigerator or freezer used for vaccine storage must:
Central vaccine depots should be equipped with auxiliary generators for refrigerators in case of power failures.
Refer to Section 3 of PHAC’s National Vaccine Storage and Handling Guidelines for Immunization Providers (2007) for detailed information on vaccine storage equipment, including guidelines for purchase of vaccine refrigerators.
The temperature in frost-free refrigerators may vary widely; temperature should be monitored to ensure that temperature cycling is within the acceptable range of +2ºC to +8ºC. Maximum/minimum thermometers are commercially available and are useful for refrigerators used to store vaccines in offices. Constant chart-recording thermometers with alarms are appropriate for larger vaccine storage depots.
Current, maximum and minimum refrigerator temperatures should be recorded twice daily and local public health officials or the vaccine supplier should be contacted if vaccines are exposed to temperatures outside the recommended range. Refer to Cold chain break management for additional information.
Domestic refrigerators are not designed to meet the requirements for vaccine storage; therefore, precautions and modifications are needed if vaccines are stored in such refrigerators. Refrigerators older than 10 years are more likely to malfunction and to have breaks in the seal around the door, leading to temperature instability. The use of such refrigerators for vaccine storage is a leading cause of cold chain breaks.
Purpose-built vaccine refrigerators
A purpose-built vaccine refrigerator (pharmacy, lab-style or laboratory grade refrigerator) is the standard for storing large inventories of vaccines. Under-counter purpose-built vaccine refrigerators are acceptable for vaccine storage.
Refer to PHAC’s National Vaccine Storage and Handling Guidelines for Immunization Providers (2007) for detailed information on vaccine inventory management and storage practices. The following procedures are recommended to ensure that storage of vaccines in vaccine provider offices is optimized.
An adequate supply of vaccines should be maintained to meet the monthly needs of the served population. Do not over order vaccines since this increases the risk of wastage (e.g. cold chain break as a result of power failure, or expiry of unused vaccines). To ensure good management of inventory:
Cold chain break management
If vaccines are exposed to temperatures outside the recommended range (refer to Appendix 1) or other inappropriate storage conditions, immediate action should be taken in order to avoid product loss (refer to The list of steps in handling vaccines exposed to inappropriate vaccine storage conditions). It should not be assumed that vaccine inappropriately exposed to light or to temperatures outside the recommended range cannot be salvaged.
In general, live attenuated vaccines, even in their lyophilised form, are more sensitive to heat exposure than inactivated vaccines. High ambient temperatures (up to +37°C) may not cause an immediate loss of potency but can shorten the shelf life of a vaccine. Evidence on the thermostability of vaccines suggests that an increase in temperature to above +8°C for a short period of time is unlikely to affect the potency of most vaccines significantly, particularly if the vaccines are used relatively quickly.
When a cold chain break is identified after an affected vaccine has been administered, consult local public health officials or the vaccine supplier for advice. The type of vaccine, as well as the duration and temperature of the exposure, need to be taken into account when assessing the situation. Serological testing or revaccination may be suggested.
Refer to Section 6 of PHAC’s National Vaccine Storage and Handling Guidelines for Immunization Providers (2007) for detailed information on handling vaccines that have been exposed to inappropriate storage conditions.
|Vaccine form||Vaccine presentation||Storage temperatureFootnote 1 (°C)
(* = +2° to +8°C)
(* = +2° to +8°C)
y = yes
|Time frame for use||Additional recommendations and information|
|L = Lyophilized powder
LS = Liquid or solution
S = Suspension
NI = no information
|Reconstituted vaccineFootnote 2||Multi-dose vial after entryFootnote 3||Protect from light||Do not freeze||NI = no information|
|V = vial
S = pre-filled syringe
|Y = with preservative
N = no preservative
Table developed from information contained in manufacturer’s product monographs accessed April 2013 at Health Canada’s Drug Product Database. Product monographs are continually updated; it is a best practice to consult the current product monographs available at Health Canada’s Drug Product Database. Additional information regarding stability of vaccines is available from the World Health Organization.
hr = hours
|Act-HIB®||L||V||*||*||Use immediately||Y||Use immediately after reconstitution||Diluent: sterile saline in a vial|
|ADACEL®||S||V||*||Y||NI||Stable at above +8° and up to +25° for maximum of 72 hr, before openingFootnote 4|
|ADACEL® -POLIO||S||V or S||*||Y||NI||Stable at above +8° and up to +25° for maximum of 72 hr, before openingFootnote 4|
|AGRIFLU®||S||S||*||Y||Y||NI||Can be used after 2 hr exposure at +8° to +25° before openingFootnote 4|
|BCG vaccine (live)||L||N||*||*||*||*||Y||Y||Discard if not used within 8 hr after first puncture||
|BOOSTRIX®||S||S||*||Y||Y||NI||Stable at 21° for 8 hr, before openingFootnote 4|
|BOOSTRIX® -POLIO||S||V or S||*||Y||Y||NI|
|CERVARIX®||S||V or S||*||Y||Y||NI|
|DUKORAL®||S||V||*||Room temp (up to 25°)||Room temp||Y||2 hr after opening||
|ENGERIX®-B (multi-dose)||S||Y||*||*||Y||Y||24 hr after first puncture|
|ENGERIX®-B (single-dose)||S||V||*||Y||Y||Use immediately after withdrawl|
|FLUAD®||S||S||*||Y||Y||NI||Can be used after 2 hr exposure at temperatures between +8° to +25°, before openingFootnote 4|
|Flulaval™ Tetra||S||Y||*||*||Y||Y||28 days after first puncture|
|FLUMIST® (live)||Intranasal spray||Nasal sprayer||*||Y||NI|
|FlulavalTM Tetra||S||Y||*||*||Y||Y||28 days after first puncture|
|FLUVIRAL® (multi-dose)||S||Y||*||*||Y||28 days after first puncture|
|FLUZONE® (multi-dose)||S||Y||*||*||Y||Y||28 days after first puncture|
|FLUZONE® (single-dose)||S||V or S||*||Y||Y||NI|
|FLUZONE® Quadrivalent (single-dose)||S||V or S||*||Y||Y||NI|
|GARDASIL®||S||V or S||*||Y||Y||NI|
|HAVRIX®||S||V or S||*||
||Use immediately||Y||Use immediately after reconstitution||Diluent: sterile water in syringe|
||Use immediately||Y||Y||Use immediately after reconstitution||
|IMOVAX® Rabies||L||V||*||*||Use immediately||Y||Use immediately after reconstitution||Diluent: sterile water in syringe|
|INFANRIX hexa®||L & S||V & S||*||*||
|INFANRIX®-IPV/Hib||L & S||V & S||*||*||
|Menjugate®||L||V||*||*||Use immediately||Y||Y||Use immediately after reconstitution||
|MENOMUNE® (multi-dose)||L||Y||*||*||*||*||Y||35 days after first puncture||Diluent: sterile saline with lactose and thimerosal in vial|
|MENOMUNE® (single-dose)||L||V||*||*||*||Y||24 hr after reconstitution||Diluent: sterile saline with lactose in vial|
|Menveo™||L & LS||V||*||*||
|M-M-R® II Live||L||V||* or frozen at temperature above –50°||
|NeisVac-C®||S||S||*||Y||NI||Alternatively, can be stored for a single period not exceeding 9 months at room temperature (up to +25°), if unopened|
|NIMENRIXTM||L||V||*||Room temp (up to 25°)||Y||Y|
|PNEUMOVAX® 23 (multi-dose)||LS||Y||*||*||48 hr after first puncture|
|PNEUMOVAX® 23 (single-dose)||LS||V||*||NI|
|Prevnar® 13||S||S||*||Y||NI||Prevnar 13 has been shown to be stable at temperatures of up to 25°C for 4 days. Cumulative multiple temperature excursions between 8°C and 25°C are permitted, as long as the total time does not exceed 4 days (96 hours). These data are not recommendations for shipping or storage, but may guide decisions for use in case of temporary temperature excursionsFootnote 4|
|PRIORIX® (live)||L||V||*||Room temp (up to 25°)||*||Y||
||Diluent: sterile water in ampoule|
||Diluent: sterile water in pre-filled syringe or ampoule|
|PROQUADTM||L||V||*||* or room termperature (up to 25°)||Room termperature (up to 25°)||Y||
|RabAvert®||L||V||*||*||Use immediately||Y||Use immediately after reconstitution||
|RECOMBIVAX HB® (single-dose)||S||V||*||Y||NI|
|ROTARIX™ (live)||LS||Oral applicator||*||Y||Y||NI|
|RotaTeq® (live)||LS||Oral applicator||*||Y||Y||
|Smallpox Vaccine (live)||L||N||Frozen at -15°C to -25°C||Do not freeze+15° to+30°||* Do not freeze||* Do not freeze||Preferably use at once Stable for 6-8 hr at 20-25°C and 30 days at +2° to +8°C after reconstitutions||Supplied with bifurcated needles for percutaneous scarification
Diluent: glycerol in McIlvaine buffer with 0.2% v/v phenol
||Can be administered when vaccine has been at +8°C to +25°C for up to 72 hours before opening. These data are not recommendations for storage.|
|SYNFLORIX® (single-dose)||S||V or S||*||Y||Y||NI|
|Td POLIO ADSORBED||S||V||*||Y||NI|
|TWINRIX®||S||V or S||*||Y||Y||NI|
|TYPHIM Vi® (multi-dose)||Y||*||* Do not freeze||Y||6h after first puncture|
|TYPHIM Vi® (single-dose)||LS||S||*||Y||NI|
|VARILRIX® (live)||L||V||*||* or +8° to +25°||*||Up to 8 hr at +2° to +8°C
Up to 90 min at +25°C after reconstitution
|VARIVAX® III (live)||L||V||*or Frozen at above -50°||
||Do not freeze||Y||Up to 90 min at +20° to +25°C after reconstitution||
|VAXIGRIP® (multi-dose)||S||Y||*||*||Y||Y||7 days after first puncture|
|VAXIGRIP® (single-dose)||S||Ampoule or S||*||Y||Y||NI|
|ViVAXIM®||S & LS||S||*||Use immediately after mixing||Y||Use immediately after mixing||
|Vivotif® (live)||L||Oral capsule||*||Y||Y||NI||
|YF-VAX® (live, multi-dose)||L||N||*||* Do not freeze||*||*||Y||60 min after reconstitution||Diluent: sterile saline in vial|
|YF-VAX® (live, single-dose)||L||V||*||* Do not freeze||*||Y||60 min after reconstitution||Diluent: sterile saline in vial|
|ZOSTAVAX® (live)||L||V||Frozen at -15° to -50°||
||Y||30 min after reconstitution||Diluent: sterile water in vial|