All vaccines supplied by MSF are pre-qualified by the WHO. If pre-qualified vaccines are unavailable, MSF may procure vaccines that are not WHO-pre-qualified but are licenced by stringent regulatory authorities. Before ordering vaccines, verify any specific requirements related to national vaccine policy (e.g. strains, VVM type, ...) and regulatory bodies.

THERMOSENSITIVE PRODUCTS AND COLD CHAIN

(Cf Introduction: Thermosensitive products and Cold chain)

Vaccines, along with most medicines and rapid diagnostic tests, are highly sensitive to light and temperature. Exposure to heat and/or freezing conditions can negatively affect their quality, safety, and efficacy.

Thermosensitive codes define the required storage and transport temperature conditions. These codes correspond to the typical (or targeted) storage and transport facilities used in the field (freezers, refrigerators, pharmacies, medical warehouses, or transport vehicles) and the temperature ranges they are designed to maintain.

In medical catalogues and ordering tools, all thermosensitive products are assigned a thermosensitive code, as listed in the table below.

All thermosensitive vaccines with the code 0208 must be stored in a refrigerator and transported in cold chain. The cold chain refers to the means used to store and transport thermosensitive products at temperature between +2ºC and +8ºC.

HOW TO ENSURE THE EFFECTIVENESS OF THERMOSENSITIVE PRODUCTS

In general

• Pay close attention to storage and transport conditions at all times.
• Some vaccines, medicines and rapid diagnostic tests transported in cold chain can be severely damaged by freezing:
• Use only icepacks filled with cold water for transport. Place them in the refrigerator for at least 12 hours before use. Icepacks pre-filled with eutectic liquid (coloured gel) are not suitable because their freezing point may be below 0ºC.
• Allow frozen icepacks to warm to 0ºC before placing them in the cold box. Leave them at room temperature for at least 30 minutes until they begin to "sweat" and liquid appears on the surface.

Vaccines

In accordance with WHO recommendations:

• Some vaccines are labelled with a WHO CTC (Controlled Temperature Chain) pre-qualification. This means:
• The vaccine is stable and can be stored up to 3 days at ambient temperature not exceeding 40°C, immediately before administration, provided the VVM has not reached its limit and the expiry date is still valid.
• Any unused vaccines after a CTC excursion must be discarded.
• For CTC use, refer to CARD indicator for overrun +40°C (Temptime) irreversible (PCOLMONICTB)
• CTC Implementation requires proper planning and staff training.
• Currently, three vaccine are WHO-pre-qualified for CTC use:
• oral cholera vaccine Shanchol (DVACVCHO1V-) (40°C/14 days)
• meningococcal A conjugate vaccine (MenAfriVac) 1-29 years, 10mcg (DVACVMENA1VD) (40°C/4 days)
• 4-valent HPV vaccine (Gardasil)(DVACVHPV4V-) (42°C/3 days): contact your medical department for guidance
• Freezing of vaccines:
• WHO no longer recommends freezing vaccines, except oral polio vaccine, and only at national or regional levels.
• BCG, measles, yellow fever, meningitis, and Hib vaccines must be stored between +2ºC and +8ºC and must be not frozen. Freezing does not damage these vaccines but is unnecessary and should be avoided (except in exceptional situations).
• Diluents:
• Diluents must be kept at the same temperature as the vaccines (between 2ºC and 8ºC) at the moment of reconstitution. They do not need to be stored in a refrigerator permanently; however, the required quantity should be placed in a refrigerator or cool box 24 hours before use. Diluents must never be frozen.

THE VACCINE VIAL MONITOR (VVM)

Heat exposure of a vaccine is cumulative.

The VVM is a thermosensitive label placed on vaccine vials to indicate whether the vaccine has been exposed to excessive temperatures over time. The combined effects of time and temperature cause a gradual, irreversible colour change in the VVM.

VVMs are designed according to the stability profile of each vaccine, with an additional safety margin. Four VVM types exist, each with a specific heat-response level based on the vaccine's heat stability (see table 1):

The VVM clearly indicates if a vaccine can be used or not (see figure 2).

Not all vaccine vials have a VVM. Whenever possible, vaccines with a VVM should be used.

Caution: the VVM does not replace other temperature indicators. A vaccine with a correct VVM but expired cannot be used.

COLD CHAIN MANAGEMENT

MSF supplies only equipment that has been pre-qualified by WHO (PQS). Before ordering cold chan equipment, consult your technical department. Incorrect selection can lead to significant losses of vaccines, medicines, or rapid diagnostic tests, delays in programme activities, or worse, the use of ineffective products.

Proper maintenance is essential for all cold chain equipment and must be performed regularly to ensure the equipment remains fully functional. Maintenance tasks ae described in the relevant technical documentation and guidelines.

Cold chain equipment is divided into two main categories:

Active cold chain: Equipment in this category requires energy to produce and maintain cold. It is mainly used for storage or for icepack production. It includes:

• ice-lined refrigerators
• freezers (for icepack production or storage of F-20 products)
• cold rooms

Passive cold chain: Equipment in this category requires pre-conditioned ice-packs to maintain cold. It includes:

• isothermal/cold boxes
• vaccine carriers
• icepacks

The selection of cold chain equipment (PCOL) depends on several factors, including required vaccine storage capacity, cold life, weight and volume of the box (based on the transport mode), and the number of ice-packs needed. Refer to the PCOL catalogue for manufacturer specification and item details.

Practical recommendations

It is essential to qualify refrigerators before using them to store medicines. You can seek support from your cold chain referent and your MSF procurement centre for assistance with the qualification process.

Designate and train a person responsible for the cold chain, as well as a backup, to manage the following:

Temperature monitoring

Thermosensitive items must be continuously monitored throughout their lifecycle using standard tools from the PCOL catalogue, such as:

• alcohol thermometers
• freezing indicators (FreezeTag^®)
• historical data loggers (LogTag^®)
• remote monitoring and alerts (BluLog^®)

For detailed instruction on use and configuration, refer to your OC-specific guidelines and protocols.

Stock management

• Prepare a contingency plan in case of a cold chain break, including:
• isothermal containers for temporarily storing the most sensitive products
• sufficient frozen icepacks and a system for their regular renewal (based on the number and type of cold boxes)
• a list of products categorised by thermosensitivity to quickly determine the appropriate action
• Carefully document any breakdown (duration, temperatures reached, and exposed products) and consult the pharmacist in the medical department for guidance on appropriate actions.
• Store thermosensitive products according to expiry date (first expired, first out).
• Do not store food or beverages in medical refrigerators or freezers.

Transport

• During distribution, protect products that should not be frozen, as the risk of accidental freezing is particularly high at this stage.
• Develop clear procedures for the transport of thermosensitive products and for the preparation of cold boxes.
• Place cardboard between products and icepacks to prevent direct contact.

Assessment of the existing cold chain

• Is the quality of the cold chain satisfactory?
• Have the refrigerators been qualified, and is the qualification report available?
• Have the procedures for cold chain management been defined and are they available?
• Is the equipment suitable for your needs in terms of storage volume and performance?
• Is all equipment in good working order?
• How reliable is the power supply?
• Is the equipment permanently accessible?
• Are the refrigerators and freezers located in cool, clean, and well-ventilated rooms?
• Is there sufficient capacity to store all thermosensitive products and to freeze the required number of icepacks?
• Is the temperature-monitoring equipment for each refrigerator / freezer complete and functional?
• Are procedures in place for monitoring thermosensitive products upon arrival and departure?
• Are the temperature charts correctly filled in twice a day?

Needs assessment

• What is the nature of your activities (routine immunisation, immunisation campaign, laboratory, etc.)?
• How much storage capacity do you need?

The volume of vaccines varies depending on presentation and manufacturer.

For injectable vaccines in 10-dose vials, you need 2 to 3 cm³ per dose.

To store 1,000 doses, you need:

• 2 litres if 2 cm³ per dose
• 3 litres if 3 cm³ per dose
• 2.5 litres if 2.5 cm³ per dose

Caution

Newly introduced vaccines (rotavirus, cholera...) are often more voluminous. Always check volume requirements when ordering.

To determine the volume of medicines and diagnostic tests, contact your supply centre.

• How much freezing capacity do you need for icepacks?
• How many cold boxes, vaccine carriers and icepacks do you need?
• Which monitoring tools do you need to order (thermometers, freezing indicators, etc.)?

WHO RECOMMENDATIONS ON OPEN VIALS OF VACCINE

The term "open vial" refers to a vaccine vial from which one or more doses have been used during a vaccination session.

WHO Policy statement: Multi-dose Vial P (MDVP), Revision 2014
https://apps.who.int/iris/handle/10665/135972

These WHO recommendations apply only to vaccines that meet WHO specifications for efficacy and thermostability and that contain an adequate amount of preservative. The vaccines provided by MSF meet these requirements.

• The location of the VVM provides a first indication of the application of the multi-dose vial policy:
• VVM on the vaccine label: the opened vial may be kept for up to 28 days for subsequent vaccination sessions, regardless of formulation (liquid or freeze-dried)
• VVM placed other than on the label: the opened vial must be discarded at the end of the vaccination session or within 6 hours of opening, whichever comes first, regardless of formulation.
• Always check the vaccine leaflet to confirm whether the specific product may be used up to 28 days after opening.
• To apply the multi-dose vial policy, good injection practices must be strictly followed:
• Use a new sterile syringe and needle for each injection.
• Never leave a needle inserted into a vial.
• Ensure the vial septum is not contaminated and has not been in contact with water.
• Do not use any vial with visible contamination of the contents, without a label, or with an illegible label.

Caution

Always check the national protocol for the use of open vials.

VACCINE ORDERS

Orders must always be placed in number of doses, not in number of vials!

Formula for a first order

Number of doses needed = target population x coverage objective x number of doses per person (according to the vaccination schedule) x loss multiplying factor + reserve stock (e.g. 25%)

Formula for subsequent orders

Number of doses needed – number of doses in stock

Loss multiplying factor

The loss multiplying factor is used to calculate the real number of doses to order in order to vaccinate the target population, taking into account the expected wastage depending on:

• the vaccination strategy (routine immunisation activities or mass campaign),
• the type of vaccine (freeze-dried or liquid)
• the presentation (multi-dose or mono-dose).

For routine immunisation activities:

• BCG : x 2 (50% loss)
• Other vaccines : x 1.05 to 1.66 (5 to 40% loss), use specific wastage data if available for your activities

For vaccination campaigns or in-country (national programme):

• x 1.17 (15% loss)

The loss multiplying factor is a standard factor based on experience to calculate the first order. For a long-term programme, it should be adjusted according to real observed losses or specific vaccine data, in consultation with the medical department.

Example:

• Initial order of DTP-Hib-HepB for vaccination of children aged 0-11 months:
• Total population = 50,000 inhabitants
• Target population (4%) = 2,000 persons
• Coverage 100% (x 1) = 2,000 persons
• Number of doses (x 3) = 6,000 doses
• Number of doses + loss (x 1.17) = 7020 doses
• Number of doses + loss (x 1.17) + reserve (x 1.25) = 8,775 doses/year

=> Need for three months => 2,194 doses

• Order for the next three months:
• Estimated needs for three months = 2,194 doses
• Number of doses in stock = 220 doses

=> To be ordered: 2,194 - 220 = 1,974 doses

• Calculation of the storage volume
• for example: 1 dose = 3 cm³
• 2,194 x 3 cm³ = 6,582 cm³
• 6,582 cm³ / 1,000 = 6.6 litres (1 litre = 1,000 cm³)