Controlled Temperature Chain (CTC)
Vaccines have to be kept under recommended storage conditions that guarantee the maintenance of their quality during production, storage, handling, transportation and use. As a result, extensive measures are put in place to avoid exposure of the product to inappropriate temperatures. Almost all vaccines used in immunization programs today are licensed for storage and distribution within a temperature-controlled supply chain of between 2°C and 8°C. However, keeping vaccines within this range is extremely difficult in countries with limited cold chain and ice pack production capacity.
As a result, the increasing cost and/or logistical constraints of vaccine delivery due to these cold chain requirements, significantly hamper vaccine access. Immunization programs therefore would benefit greatly from novel approaches to vaccine stability assessment and management that would permit the use of product at ambient temperatures, in a controlled temperature chain (CTC) for defined periods of time, as appropriate to the stability profile of the antigen.
Progress is presently being made in developing a regulatory framework for the stability evaluation of vaccines under a CTC which will take advantage of the true heat stability of vaccines. It is now known that several vaccines have the potential to be stored safely at temperature ranges higher than the approved 2-8C as appropriate to a vaccine’s heat stability profile for at least short periods of time. This would be product specific. Two consultations (Ottawa, Canada, December 2012 and Langen, Germany, 2013) have set the scene for moving forward on this issue and where it was agreed that there was a need for WHO guidance on stability evaluation of vaccines for CTC use. Clear labelling would be critical. WHO is continuing to develop consensus guidelines for submission to the WHO Expert Committee on Biological Standardization either in 2014 or 2015 using its usual international public consultation process.
One vaccine, the Meningitis A conjugate vaccine developed by the Serum Institute of India through the WHO/PATH Meningitis Vaccine Project has already been licensed in India and Pre-qualified by WHO for use in a CTC system. The label draws attention to “on label” use through appropriate label variation - “Stable up to 40°C for 4 days prior to reconstitution. Use within 6 hours of reconstitution”.
Guidelines on the stability evaluation of vaccines for use under extended controlled temperature conditions, Technical Report Series No. 999, Annex 5
WHO/Paul-Ehrlich-Institut Informal Consultation on Scientific and Regulatory Considerations on the Stability Evaluation of Vaccines under Controlled Temperature Chain (CTC), Langen, Germany, 4-6 June 2013
WHO/Health Canada Drafting Group Meeting on Scientific and Regulatory Considerations on the Stability Evaluation of Vaccines under Controlled Temperature Chain, Ottawa, Canada, 4-6 December 2012