Labeling vaccines to reflect their true heat stability

by Simona Zipursky, PATH; Christoph Conrad, WHO/Quality, Safety & Standards; Tony Richardson, CDC/Vaccine Supply & Assurance Branch They call it the Decade of Vaccines for a reason. More new vaccines will become available between 2010 and 2020 than all previous decades combined. Not only that, these vaccines will reach new target groups at different stages of life and in more remote geographic areas. While still among the most cost-effective of all public health interventions, these newer vaccines are more expensive and better suited to single-dose presentations, both to avoid waste and minimize the need to reformulate with preservatives. The requirement to store these vaccines between 2°C to 8°C means that low-resource countries, which stand to benefit enormously from increased access to lifesaving vaccines, must stretch limited financial, human, and capital resources to safely manage the distribution of these vaccines—including dealing with tropical temperatures, impassable roads, long foot trails, and unreliable electricity. Historically, it has been prudent to maintain a single global policy regarding temperature management of vaccines. Until very recently, every country in the world has been instructed to keep all vaccines between 2°C and 8°C at all stages of the supply chain past the central level. But maintaining such a narrow temperature range is difficult. Vaccines are often damaged through accidental freezing, requiring health workers to discard vaccines that are exposed to temperatures below 0°C. In reality, however, many vaccines are or could be highly stable at temperatures up to 37°C, and laboratory tests have shown that some remain stable at this temperature for as long as six months without a significant impact on potency. Supporting countries to safely transport specific, heat-stable vaccines at higher temperatures for limited excursions will not only prevent accidental damage by freezing, but enable health workers to reach the most remote communities, even when electricity or ice packs are not available. Several countries have demonstrated the feasibility of such an approach. Indonesia, for example, has demonstrated how to reach infants with a birth dose of hepatitis B vaccine by allowing midwives to carry vaccines the last few miles of the last few days of the supply chain without ice packs. Studies like these are promising but are still just that—small-scale studies and pilot projects. Global policy change will not occur unless manufacturers are willing to work collaboratively with the public sector to label vaccines to reflect their true heat and freeze stability. Developing countries are not alone in their need for more flexible vaccine temperature requirements for heat-stable vaccines. Despite comparatively less extreme environmental conditions, industrialized countries are also interested in a controlled-temperature supply chain. The US Centers for Disease Control and Prevention (CDC) has formed an international vaccine stability working group to discuss the possibility of expanding temperature control guidelines with manufacturers. At the request of the provincial health authorities, vaccine manufacturers have submitted to Health Canada changes to product inserts for some vaccines so that labels include information regarding higher-temperature storage. This review has led to changes in the labels of certain vaccines, such as Vaqta®, a vaccine that protects against hepatitis A, manufactured by Merck Frosst. While Vaqta®’s label in most countries, such as the United States, stipulates that it must always be stored between 2° to 8°C, it reads differently in Canada: Store vaccine at 2° to 8°C (36° to 46°F). DO NOT FREEZE since freezing destroys potency. Stability studies with VAQTA® show that the potency of unopened vaccine is not significantly affected after exposure at 37°C for up to 6 months. This is not, however, a storage recommendation. WHO’s quality, safety and standards team, which is responsible for reviewing and prequalifying all vaccines procured through the United Nations system, is currently also reviewing the data available on the true stability of the vaccines in its system that have revised labels in Canada. This review aims to see how the true stability of vaccines and guidance on cold chain excursions can best be supported in developing countries, building on the learning and work of Health Canada. These changes to the product inserts are a step in the right direction but as of yet do not endorse what developing countries are hoping for—the ability to store vaccines out of the cold chain for limited periods of time. Last year, the CDC’s International Vaccine Stability Workgroup created a subgroup on stability data and temperature control guidelines to discuss the issue with manufacturers. Representatives from Health Canada, the CDC, the US Food and Drug Administration, PATH, and the World Health Organization had a preliminary discussion in October 2010. A second meeting has been scheduled for November 2011 to share more about the risks and opportunities of new labeling standards. As part of this work, we are seeking input from countries and partners on their experiences of using vaccines in a controlled temperature chain. We are also interested in thoughts and experiences with the controlled temperature chain approach including how and where it can be used for maximum impact. To comment, click reply.