In recognition that an increasing number of vaccines are able to tolerate temperatures well above those officially stated on their labels, the World Health Organization (WHO) has been supporting efforts to assess and take advantage of the true heat stability of vaccines. Upstream work in this regard includes dialogue with vaccine manufacturers to ensure that new vaccines, where possible, reflect a maximum heat stability compatible with WHO’s definition of a Controlled Temperature Chain (CTC) and that existing vaccines are assessed to generate a clearer picture of their actual heat stability and the potential for re-licensure and pre-qualification for use in a CTC. WHO’s Programmatic Suitability for Prequalification (PSPQ) document and the Vaccine Presentation and Packaging Advisory Group’s (VPPAG) Generic Preferred Product Profile for vaccines have both been recently updated accordingly, presently containing strong recommendations for vaccines to be tested and licensed per CTC conditions, where feasible.
In parallel, WHO is also conducting significant work to facilitate regulatory pathways, including the development of guidelines for the licensure of products for use in a CTC (expected in 2015). Downstream work on CTC involves supporting country uptake (see Guidelines on the Use of MenAfriVac in a CTC during campaigns) and documenting best-practices, while also generating additional data on the risks and benefits associated with CTC implementation. Three publications documenting field experience and the benefits of CTC are:
(1) Simona Zipursky et al. Benefits of using vaccines out of the cold chain: Delivering Meningitis A vaccine in a controlled temperature chain during the mass immunization campaign in Benin
(2) Patrick Lydon et al. Economic benefits of keeping vaccines at ambient temperature during mass vaccination: the case of meningitis A vaccine in Chad
(3) Aitana Juan-Giner et al. A cluster randomized non-inferiority field trial on the immunogenicity and safety of tetanus toxoid vaccine kept in controlled temperature chain compared to cold chain
WHO defines a[color=#00bbbb] Controlled Temperature Chain (CTC)[/color]
as a set of conditions under which a vaccine (preferably single-antigen) with the relevant licensure and labelling may be kept and administered at ambient temperatures of up to 40°C for a limited period of time, as appropriate to the stability of the antigen and per the instructions specified on the product label. Among the conditions enabling a CTC are:
– A campaign or special strategy context (CTC is not currently recommended for routine immunization) where ambient temperatures do not typically exceed 40°C;
– A single “temperature excursion” for a limited period of time (length of time will vary by antigen and setting, though a minimum of 3 days is preferred by WHO) immediately preceding administration;
– The use of dedicated equipment and procedures to control and monitor storage temperature, including a VVM and a peak threshold temperature indicator; and
– Proper use of the traditional +2 to +8°C cold chain up until the CTC excursion.
WHO recommends that a CTC only be adopted when there are sufficient resources and time available for proper planning, training, supervision and monitoring. CTC should only be considered for districts demonstrating a pronounced need for the flexibility offered by this innovation. Examples of the latter would include clear cold chain constraints and challenging outreach conditions.
While the benefits of dropping the cold chain may seem apparent, a CTC approach nevertheless involves some trade-offs, as listed below.
[color=#008888]GAINS/BENEFITS vs COSTS/RISKS: [/color]
(1) INFRASTRUCTURE / PLANNING
+ Starting from the location in the supply chain where the CTC starts, there is no need to provide additional space in the cold chain for the vaccine.
+ No additional freezer capacity is needed for ice packs.
- As CTC is a new practice, there is an increased risk of confusion, especially with subsequent campaigns involving non-CTC eligible vaccines.
- One peak threshold indicator per vaccine carrier or equivalent will be necessary. These are a low-cost paper card with a temperature-sensitive sticker costing under US$ 1 each, depending on the quantities needed.
+ Unopened vaccines are frequently discarded when the label becomes detached or unreadable after a day in a humid vaccine carrier. A CTC eliminates this problem because the air inside the vaccine carrier will be dry.
- Higher levels of closed-vaccine wastage may be seen in a CTC context if the vaccine needs to be discarded because the temperature has exceeded 40°C, or the 4-day time limit has been passed.
+ Savings of staff time —specifically around planning and managing extra cold-chain issues and ice-pack logistics. The time used for planning cold-chain space, freezing ice packs and managing the cold-chain equipment needed for transportation can be reallocated to other supervisory and field activities.
+ Increased ease of vaccine transportation and reduced volume and weight burden for health-care workers to transport.
+ Reduced number of trips by health workers to the district level to pick up vaccines and/or ice packs
- Additional time and resources may be required to familiarize vaccinators and supervisors with this new approach.
The value of identifying more vaccines that are compatible with a CTC and seeking their licensure and WHO pre-qualification has been endorsed by major global health stakeholders and is part of the Global Vaccine Action Plan’s (GVAP) framework for 2011 – 2020. Currently there are almost a dozen vaccines from eight manufacturers being examined for CTC approval. We are expecting that this number will continue to increase in the near future.