Beyond the standard cold chain

The “controlled temperature chain" (CTC) is a specific short-term approach to vaccine management that allows vaccines to be kept at temperatures above the long-term +2° to +8° C storage condition for a limited period of time under monitored and controlled conditions appropriate to the stability of the antigen. Current WHO programme conditions for CTC include a single exposure just prior to administration, tolerating ambient temperatures of at least 40°C for a limited duration of at least three days, with these temperature and time conditions included in the approved label.

The World Health Organization has established the following programmatic criteria for a vaccine to be labelled for and used in a CTC:

• The vaccine should be used alone or in combination only with other vaccines, which are also licensed for use in a CTC.
• The vaccine must be able to tolerate ambient temperatures of at least +40°C for a minimum of three days and should be accompanied by:
• a vaccine vial monitor (VVM) on each vial, and
• a peak threshold indicator in each vaccine carrier.
• The vaccine must be licensed for use in a CTC by the relevant regulatory authorities, with a label that specifies the conditions.

The following pages provide a list of useful publications and resources relating to CTC.

The CTC Working Group, co-led by WHO and PATH between 2016 and 2020 as a temporary sub-group to WHO’s Immunization Practices Advisory Committee (IPAC),  developed a Strategic Roadmap for CTC Priority Vaccines, which addresses supply and programmatic issues, aiming for CTC priority vaccines to become licensed for CTC use and facilitating uptake of the CTC vaccine delivery approach.

This roadmap focuses primarily on four vaccine types selected by the CTC-WG and endorsed in February 2017:

• Human papillomavirus (HPV);
• Oral cholera vaccine (OCV);
• Tetanus toxoid vaccine (including TT [tetanus toxoid] vaccine, Td [tetanus diphtheria low dose] vaccine, or other TT-CVs [tetanus-toxoid-containing vaccines]) and;
• Hepatitis B vaccine birth dose (HepB-BD).

These four vaccine types were the leading priorities of the CTC programme of work between 2017 and 2020.

In 2020, the Strategic Roadmap for CTC Priority Vaccines was reviewed by the CTC Working Group. Typhoid Conjugate Vaccine (TCV) was added as an additional priority vaccine and the CTC-WG confirmed that the commitments outlined in the Roadmap are still relevant and valid for an extended time period through 2024, in view of the many targets still not being met.

For more information on CTC, please contact vaccines@who.int. 

Other immunization partners are playing a key role in advancing the use of vaccines in a CTC.  The Vaccine Innovation Prioritisation Strategy (VIPS) is a collaboration between the Gavi Secretariat, World Health Organization (WHO), Bill & Melinda Gates Foundation, UNICEF and PATH to develop a single integrated framework to evaluate, prioritise and drive forward vaccine product innovations.  CTC is one of three innovations prioritized by VIPS in 2020 and is now benefiting from a dedicated VIPS Action Plan to:

• Contribute to the generation of evidence on the impact of CTC-qualified vaccines through robust research studies that address key barriers to CTC; and
• In parallel, accelerate the most promising opportunities to facilitate the availability and uptake of CTC for priority vaccines in lower-income countries.

For more information please visit:  https://www.gavi.org/our-alliance/market-shaping/vaccine-innovation-prioritisation-strategy