Developing technologies to prevent damage from heat and cold

The weather forecast calls for sunshine and temperatures nearing 95°F (35°C). This is decent weather for a bumpy motorcycle ride to a rural village in Ghana—unless you are transporting vaccine.

One of the biggest challenges to proper vaccine use is temperature regulation. Overexposure to extreme heat or cold can ruin desperately needed vaccines.

In many parts of the world, the need to keep vaccines cold during storage and transport requires using the vaccine cold chain: a global distribution network of equipment and procedures for maintaining vaccine quality (potency) during transport and storage in both developed and developing countries. Despite these efforts, a growing body of evidence indicates that temperature excursions—when vaccine is exposed to extreme heat or cold—occur with high frequency. They happen even in the developed world.

Under the best circumstances, health workers who discover temperature excursions will discard the damaged vaccines as a precaution. In other instances, health staff may not discover exposures to extreme heat or cold until after vaccination, when temperature records are reviewed—necessitating revaccination if and when immunization programs can afford it. Sometimes, the vaccine damage goes undetected, increasing the chance that recipients will get vaccines with reduced potency, which can put them at considerable health risk.

To increase the reach of immunization programs, PATH is advancing technologies that help ensure vaccine performance and effectiveness under the toughest temperature conditions. Using advanced vaccine formulation designs and stabilization technologies, we are researching methods to improve the thermostability of both new and existing vaccines. Such methods include:

• Freeze drying, foam drying, and spray drying of vaccines.
• Formulation methods to protect vaccines containing aluminum adjuvant from freeze damage.
• Formulation methods to protect vaccines from heat damage.

PATH is also investigating the potential for manufacturing stable vaccine formulations and the regulatory pathways needed to bring these to fruition. And we’re evaluating the economic benefits the improved formulations will offer when adopted and used at large scale.

Value-added technologies

Spray drying is a process previously used in the food industry to create instant drink mixes and powdered milk. PATH is adapting this process for use with vaccines that can be reconstituted for injection, oral administration, or inhalation. We have established an in-house spray-drying laboratory to conduct feasibility studies with various vaccines. We have made substantial progress using this method with meningococcal A vaccine and are now testing the viability of spray drying oral vaccines for bacterial diarrheal diseases.

Freeze stabilization is a method developed by PATH that uses common ingredients to guard vaccines against extreme cold. PATH has successfully applied this technique to protect hepatitis B, diphtheria, pertussis, and tetanus vaccines against freezing temperatures. Read our overview of protecting aluminum-adjuvanted vaccines from freeze damage and our answers to frequently asked questions.

PATH is also advancing liquid vaccine formulations that maximize heat stability. One of PATH’s partners, for example, has developed a method that uses stabilizing and buffering ingredients to protect vaccines from heat damage. PATH has already applied this approach effectively with hepatitis B vaccine.

Moving from research to adoption

To move these stabilization methods from the laboratory to use in immunization programs, PATH is collaborating with manufacturers and technical partners to apply these technologies to new and existing vaccines. We have already placed the freeze-protection technology in the public domain for free use by manufacturers.

PATH’s work is helping to give vaccine producers access to a broad range of stabilization technologies. Ultimately, this work will help ensure that children even in the most remote areas of the world are fully protected against common childhood diseases.

Photo: Umit Kartoglu.