Page 9: Canadian Immunization Guide: Part 1 - Key Immunization Information

Storage and Handling of Immunizing Agents

General Considerations

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 immunizing agents is important for several reasons:

  • There is a need to ensure that an effective product is being used. Administration of a compromising immunizing agent may result in the occurrence and possible transmission of a vaccine preventable disease.
  • Losses of immunizing agents are expensive and may exacerbate existing supply problems. Loss of immunizing agents may result in the cancellation of immunization clinics, resulting in lost opportunities to immunize, as well as increased costs to the program.
  • The recommendation for revaccination of people who have received a potentially ineffective immunizing agent may cause a loss of public confidence in vaccines and the health care system, as well as inconvenience for the vaccine recipient and the provider.

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 (2015). Recommendations for vaccine storage and handling procedures may vary across jurisdictions, and if additional information is required, it is advised to consult your jurisdictional/local public health office or immunization program.

Handling of Vaccines

Immunizing agents 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 and in correct conditions. 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 (2015) 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 vials

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 local/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.

Multi-dose vials

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, between +2°C to +8°C (+35°F and +46°F), in a secure site to prevent tampering. They should be 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.

Manufacturer's recommendations or jurisdictional guidelines for use of multi-dose vials should be followed.

Reconstitution of lyophilized vaccines

For optimal potency, lyophilized (freeze-dried) vaccines 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

For vaccine specific storage and handling information consult the product leaflet or information contained within the product monograph available through Health Canada's Drug Product Database.

Storage of Vaccines

Packaging

Store vaccines in their original packaging; the packaging provides protection from light and physical damage.

Refrigerated immunizing agents 

The storage temperature for refrigerated vaccines and passive immunizing agents is between +2°C and +8°C (+35°F and +46°F).

Frozen vaccines

Store frozen vaccines at an optimum temperature of  -15°C (+5°F ) or colder 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 (+35°F and +46°F) 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 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 ultraviolet (UV) light exposure at all times. Exposure to light should be limited when pre-loading syringes.

Expiration Dates

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.

Vaccine Disposal

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.

Refrigerators and Freezers for Vaccine Storage

General requirements

Any refrigerator or freezer used for vaccine storage must:

  • maintain required vaccine storage temperatures; under-counter bar or dormitory refrigerators should not be used because they do not reliably maintain temperature.
  • hold sufficient inventory, including vaccine for the influenza season, and should not be an under-counter bar or dormitory type refrigerator
  • have a calibrated temperature-monitoring device inside each storage compartment
  • be dedicated to the storage of vaccines only
  • be placed in a secure location away from unauthorized and public access

Central vaccine depots should be equipped with auxiliary generators for refrigerators in case of power failures.

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. A purpose-built vaccine refrigerator (pharmacy, lab-style or laboratory grade refrigerator) is the standard for storing large inventories of vaccines.

Refer to Section 3 of PHAC's National Vaccine Storage and Handling Guidelines for Immunization Providers (2015) for detailed information on vaccine storage equipment, including guidelines for purchase of vaccine refrigerators.

Temperature monitoring

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. Thermometer calibration should be accurate within ±0.5°C (±1°F). 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.

Recommended Office Procedures

Refer to PHAC's National Vaccine Storage and Handling Guidelines for Immunization Providers (2015) 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.

Inventory management

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:

  • Designate and train one staff member to be responsible for managing vaccines and another staff member as a backup.
  • Limit access to the vaccine supply to authorized personnel only. This will help to protect the vaccine supply by avoiding inappropriate removal of vaccine or inappropriate handling of vaccine and vaccine storage units by untrained personnel. All staff handling vaccines should be familiar with policies and procedures for vaccine storage and handling.
  • Place vaccines into the designated refrigerator immediately upon delivery to the office.
  • Rotate stock so that vaccines with the earliest expiration date are at the front of the shelf.
  • Check inventory and expiry dates monthly.
  • Store vaccine products that have similar packaging in different locations that are clearly marked in order to avoid confusion and administration errors.
  • Place expired vaccine into a marked box and remove from the refrigerator for appropriate disposal.
  • Establish at least one alternate storage facility where vaccine can be appropriately stored and monitored in case of failure of the designated refrigerator.

Refrigerator

  • Post storage and handling guidelines on the refrigerator.
  • Place full, plastic water bottles in the lower compartment and door shelves of the refrigerator and ice packs in the freezer compartment to help stabilize temperatures, especially in the event of a power failure.
  • Store vaccines in the middle of the refrigerator to avoid the coldest and warmest parts of the refrigerator; do not store vaccines on the door shelves or in the vegetable and fruit bins i.e. crispers of domestic refrigerators.
  • Ideally, store frozen vaccines in a separate, designated, frost-free freezer unit at -15° C (+5°F ) or colder. Place a maximum/minimum thermometer on the middle shelf of the fridge and another in the freezer compartment.
  • Read, record and re-set the thermometer inside each compartment of the vaccine storage unit at least twice during each work day - once at the beginning of the day and once at the end of the day just before the door is closed for the last time.
  • Check the thermometer function every six months to a year (refer to section 3.7 of PHAC's National Vaccine Storage and Handling Guidelines for Immunization Providers (2015) for instructions).
  • Secure the electrical cord from the fridge to the wall outlet to prevent the plug from being removed from the electrical socket. Place a warning near the outlet stating that the plug must not be disconnected.
  • Ensure that the refrigerator door does not inadvertently open by installing a fail-safe closing mechanism (e.g., hook and ladder fastener). Keyed door locks to the room storing the refrigerator contribute to vaccine inventory security.
  • Do not store food or biologic specimens in the same refrigerator as vaccines.
  • If refrigerator malfunction is suspected on the basis of temperature readings, obtain servicing immediately, move the vaccine to an alternative refrigerator and refer to the section on cold chain break management below.
  • In the event of a power failure, move the vaccine to an alternative refrigerator and refer to the section on cold chain break management below.
  • Avoid unnecessarily opening the refrigerator door.
  • Remove the vaccine from the refrigerator only immediately prior to administration.

Vaccine transportation

  • Use insulated storage containers with ice packs for transport of vaccines out of the office (e.g., to vaccinate people in their homes or in off-site clinics); to avoid freezing, do not place vaccine packages in direct contact with ice packs.
  • Maintain vaccine between +2°C and +8°C (+35°F to +46°F) during off-site clinics; store in an insulated container with ice packs. Keep the container closed as much as possible. Keep a thermometer in the container with the vaccines, and check and record temperatures periodically to ensure that the cold chain is maintained.
  • When transporting vaccines, keep a log of pre- and post-transport vaccine temperatures and the vaccine lots transported.

Cold chain break management

If vaccines are exposed to temperatures outside the recommended range or other inappropriate storage conditions, immediate action should be taken in order to avoid product loss. It should not be assumed that vaccine inappropriately exposed to light or to temperatures outside the recommended range cannot be salvaged.

List of steps in handling vaccines exposed to inappropriate vaccine storage conditions

  1. Separate the affected vaccine from other vaccine supplies and label it as "DO NOT USE" to ensure that the vaccine is not administered. Store the affected vaccine under appropriate cold chain conditions until its integrity is determined.
  2. Record the following information:
    1. Vaccine name, lot number, expiry date
    2. Date and time of incident
    3. The issue (e.g., exposure to inappropriate temperature or exposure to light)
    4. Length of time the vaccine may have been exposed to inappropriate conditions
    5. Whether any of the affected vaccines had been administered
    6. The room temperature where the vaccine storage unit is located
    7. Current temperature inside the vaccine storage unit (and freezer)
    8. Minimum and maximum temperature readings inside the vaccine storage unit (and freezer)
    9. Presence of water bottles in the refrigerator
    10. Presence of frozen packs in the freezer
  3. Contact local public health officials or the vaccine supplier to seek advice regarding use of the vaccine. Provide the information outlined in step 2.
  4. Follow directions provided by local public health officials or the vaccine supplier regarding use or disposal of affected vaccines. Record actions that have been taken to remedy the situation.

Adapted from PHAC's National Vaccine Storage and Handling Guidelines for Immunization Providers (2015).

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 additional 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 (2015) for detailed information on handling vaccines that have been exposed to inappropriate storage conditions.

Selected References

  • Centers for Disease Control and Prevention. The Vaccine Storage and Handling Toolkit. June 2016. Accessed July 2016 at:
    http://www.cdc.gov/vaccines/hcp/admin/storage/toolkit/storage-handling-toolkit.pdf
  • Health Canada. Guidelines for temperature control of drug products during storage and transportation. 2011. Accessed July 2016 at:
    http://www.hc-sc.gc.ca/dhp-mps/compli-conform/gmp-bpf/docs/gui-0069-eng.php
  • Milhomme P. Cold chain study: danger of freezing vaccines. Can Commun Dis Rep 1993;19(5):33-8.
  • Public Health Agency of Canada. National Vaccine Storage and Handling Guidelines for Immunization Providers (2015). Accessed July 2016 at:
    http://healthycanadians.gc.ca/publications/healthy-living-vie-saine/vaccine-storage-entreposage-vaccins/index-eng.php
  • United Kingdom, Department of Health. Immunisation Against Infectious Disease. The Green Book. 2013. Accessed July 2016 at:
    http://immunisation.dh.gov.uk/category/the-green-book/.
  • WHO Vaccine Management Handbook: Module VMH-E2-01.1. How to monitor temperatures in the vaccine supply chain. Accessed October 2016 at:
    http://www.who.int/immunization/documents/financing/who_ivb_15.04/en/
 
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