All vaccines supplied by MSF are pre-qualified by the WHO. If pre-qualified vaccines are unavailable, , MSF will procure vaccines without pre-qualification label but are licenced by stringent regulatory authorities. Before ordering vaccines, verify any specific requirements related to national vaccine policy (strains, VVM, ...) 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 are defined only for storage and transport temperature requirements. They are aligned with the typical (or targeted) storage facilities in the field (freezers, refrigerators, pharmacies, medical warehouses, or transport vehicles) and their target temperature ranges.

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

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

HOW TO ENSURE THE EFFECTIVENESS OF THERMOSENSITIVE PRODUCTS

In general

• Pay particular attention to storage and transport conditions.
• Some vaccines, medicines and rapid diagnostic tests transported in cold chain may be severely damaged by freezing:
• Use only icepacks filled with cold water for transport. Place them in the refrigerator for at least 12 hours. 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. Let them at room temperature for at least 30 minutes until they "sweat" and liquid appears in the ice-packs.

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 for 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: see the related article CARD indicator for overrun +40°C (Temptime) irreversible (PCOLMONICTB)
• CTC Implementation should only be done after proper planning and training.
• Currently, three vaccine are pre-qualified with a CTC label:
• oral cholera vaccine Shanchol (DVACVCHO1V-) (40°C/14 days)
• meningococcal A conjugate vaccine 1-29 years; MenAfriVac 10mcg (DVACVMENA1VD) (40°C/4 days)
• 4-valent HPV vaccine (DVACVHPV4V- Gardasil) (42°C/3 days): contact your medical department
• Freezing of vaccines:
• WHO no longer recommends freezing vaccines, except for the oral polio vaccine at national and regional levels.
• BCG, measles, yellow fever, meningitis and Hib vaccines should be stored between +2ºC and +8ºC but should not be frozen. Freezing does not affect these vaccines but is unnecessary (except in some exceptional situations).
• Diluents:
• Diluents should be kept at the same temperature as the vaccines (between 2ºC and 8ºC) during reconstitution. While not required to be stored in a refrigerator, the necessary quantity of diluent should be placed in a refrigerator or cool box 24 hours before use. Diluents should 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 based on the stability curve of each vaccine, with an additional safety margin. The heat response levels are specific to the four models of VVM, depending on their 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. Preferably use vaccines with a VVM.

Caution, the VVM does not replace other temperature indicators. Clearly, a vaccine with a correct VVM but an expiry date passed cannot be used.

COLD CHAIN MANAGEMENT

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

Proper maintenance is essential for all cold chain equipment and should be performed regularly to ensure equipment remains in good condition. Details of these tasks can be found in the relevant technical documentation and guidelines.

Cold chain equipment is divided into two main categories:

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

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

Passive cold chain: This category includes equipment that 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 factors such as the required vaccine storage capacity, cold life, weight, and volume of the box (depending on the transport mode), and the number of ice-packs needed. Refer to the PCOL catalogue for manufacturer's specification and item details.

Practical recommendations

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

Designate and train a person responsible for the cold chain, along with a backup, to manage:

Temperature monitoring

Thermosensitive items must be continuously monitored for temperature 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 more details on their use and configuration, refer to the specific guidelines and protocols provided by your OC.

Stock management

• Prepare a contingency plan in case of a cold chain break, including:
• isothermal containers for storing the most sensitive products
• sufficient frozen icepacks and their 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 to decide on the appropriate actions.
• Store thermosensitive products based on their 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 is particularly high at this stage.
• Develop procedures for the transport of thermosensitive products and for the preparation of cold boxes.
• Place cardboard between the 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 volume and performance?
• Is the 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 rooms?
• Is there sufficient capacity to store all thermosensitive products and to freeze icepacks?
• Is the monitoring equipment in each refrigerator / freezer complete and functional?
• Are procedures in place for monitoring thermosensitive products on arrival and departure?
• Are the temperature charts filled in correctly twice a day?

Needs assessment

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

The volume of vaccines varies according to the presentation and the manufacturer.

For 1 dose in a 10-dose vial of injectable vaccines you need 2 to 3 cm³.

To store 1,000 doses, you need:

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

Caution

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

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

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

WHO RECOMMENDATIONS ON OPEN VIALS OF VACCINE

The term "open vial" refers to a vaccine vial of 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

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

• The location of the VVM gives a first indication of the application of the multi-dose vial policy:
• If the VVM is on the vaccine label: the vaccine vial, once opened, can be stored for subsequent vaccination sessions for up to 28 days, regardless of the product formulation (liquid or freeze-dried)
• If the VVM is attached in a different place from the label: the vaccine vial should be discarded at the end of the vaccination session or within 6 hrs of opening, whichever comes first, regardless of product formulation.
• Check the vaccine leaflet to ensure that the use of a specific product is permitted up to 28 days after opening.
• In order to implement the multi-dose vial policy, good injection practices should be followed at all times. For example, a new sterile syringe and needle must be used for each injection, and the needle must never be left inside the vial. In addition, the septum should not be contaminated or have been immersed in water, and there must be no visible contamination of the contents of the vial. Any vaccine vial without a label or with an illegible label should never be used.

Caution

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

VACCINE ORDERS

Orders are always done in number of doses and 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 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 be ordered to vaccinate the target population, taking into account the estimated loss according to the vaccination strategy (routine immunisation activities or mass campaign), the type of vaccine (freeze-dried or liquid) and its 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) or specific data available for your activities

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

=> x 1.17 (15% loss)

The multiplying factor is a standard factor based on experience to calculate the first order. For a long-term programme, it should be adapted according to real losses or specific data available on the vaccine (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)

REFERENCE DOCUMENTS

• Temperature sensitivity of vaccines (WHO/IVB/06.10)
• Essential drugs, MSF - L014DRUM01E-P
• Clinical guidelines, MSF - L002CLIM01E-P
• Management of a measles epidemic, MSF - L003MEAM01E-P
• Cold Chain Management guideline - 1st edition 2022 - L049COLM08E-P
• Logistics catalogue (cold chain family), MSF - L045CATM07EFP