Stability of vaccines
Unlike chemical drugs, many biological preparations are unstable during storage and this instability can reduce the safety and efficacy of the biological medicinal product. Proteins and other macromolecules may be sensitive to heat, light, radiation, changes in the environment, or they may interact with the container materials or other components of the vaccine mixture. Determining these relationships and optimizing stability from production to administration to the patient is therefore an important part of vaccine development. Even with optimal conditions, reduction in potency may occur gradually as a function of the time elapsed since production.
Significant changes in the stability profile may occur following exposure to temperature stresses exerted through fluctuations in handling or storage conditions. Because of this, the stability characteristics of each vaccine must be determined empirically through testing, and the storage and handling conditions be defined to ensure that, over the stated shelf-life of the vaccine, minimum standards of potency, identity, and purity continue to be met. The temperature sensitivity of vaccines has led to the development of cold chain requirements for all vaccines.
More recently, technical adjuncts such as temperature sensors and vaccine vial monitors (VVMs) have evolved where the thermal stresses to which vaccine shipments have been exposed to can be estimated. The stability of multi-dose vials following opening has also to be considered. In the 1980s and the beginning of the 1990s, the major focus was on thermostability testing as measured by potency assays as part of lot release. More recently, guidance has been developed to address the importance of studies performed under storage conditions reflecting relevant environmental factors. In addition, the WHO guidelines for nonclinical and clinical evaluation of vaccines stress a need for stability data to support clinical trial approvals.
WHO guidance on the stability evaluation of vaccines, the design of stability studies and stability considerations for combined vaccines were adopted by the Expert Committee for Biological Standardization (ECBS) in 2006.