Developing a vaccine that is stable at room temperature for 8 weeks

Jan 01, 2010

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There is a pressing need to improve the storage stability of currently available vaccines, and achieving this could facilitate mass vaccination campaigns and increase vaccination coverage on a global scale — particularly to underserved and remote regions of the world. With the cost of coldchain maintenance high and its quality control difficult to ensure in developing countries, it is imperative that the stability of vaccines be improved. As such, we sought to develop a measles vaccine formulation that could be stored for a reasonable length of time at ambient temperature (25–50 °C), and be transported and administered both safely and conveniently.

Following our research efforts, in collaboration with the international non-profit organization PATH, we formulated and developed an improved measles vaccine that is stable for at least 8 weeks at 37 °C.1

Developing a stable formulation

The growing need for auto-injectors
Through formulation development and spray drying, we vastly improved the storage stability of the measles vaccine.

Delivering drugs through mucus
Spray drying the measles vaccine under mild conditions (i.e., low atomization pressure and drying temperature) was the key to maintaining the titre of the vaccine during processing. We utilized a nozzle that atomized the liquid vaccine into fine droplets at a relatively low pressure (compared with commercially available two-fluid nozzles) and the drying temperature was optimized accordingly; the choice of drying temperature is a fine balance between drying efficiently (i.e., at higher temperatures) and minimizing vaccine deactivation (i.e., at lower temperatures).

The stable formulations, which comprised all excipients that are approved for human use, consisted of a mixture of sugars (trehalose and sucrose) in potassium phosphate buffer as base excipients. We then incorporated our patented plasticisation technology to further enhance the storage stability of the measles vaccine. Other components that we found to stabilize the vaccine included Larginine, human serum albumin and a mixture of divalent cations.

Process challenges

The challenges we faced with the measles vaccine were the same as those encountered with other virus and bacteriabased vaccines, which we have worked on previously: to minimize the process loss; and to maintain the vaccine titre during storage.

The measles vaccine comprises live attenuated measles virus and, as such, we could not employ traditional spray drying conditions (i.e., high atomization pressure, high drying temperature, etc.); we observed process loss resulting in > 1 Log10 in vaccine titre under traditional spray drying conditions. With optimization in atomization pressure, drying temperature and solution feed rate, we minimized the process loss to < 0.2 Log10. The formulation components do have an impact on process recovery; with certain formulation mixtures, we were able to see no process loss from spray drying.