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Guidelines on stability evaluation of vaccines
2016.06.16

The stability of vaccines has a major impact on the success of immunization programmes worldwide. As part of its efforts to assure vaccine quality, WHO has acknowledged the importance of clearly defining the stability characteristics of a vaccine and emphasizes the role of national regulatory authorities in overall vaccine evaluation.

The aim of this document is to provide the scientific basis and guiding principles for evaluation of vaccine stability for the purpose of clinical trial approval, licensing, and post-licensure monitoring. The temperature sensitivity of vaccine characteristics, particularly potency, led to the development of storage and cold chain requirements for all vaccines. In the 1980s and at the beginning of the 1990s, a major WHO focus was on thermostability testing, as measured by potency assays, as part of lot release.More recently, guidance has addressed the importance of studies performed under real storage conditions, in real time, and with other relevant environmental factors. In addition, the WHO guidelines for nonclinical and clinical evaluation of vaccines, stress a need for stability data to support approval of a clinical trial(1, 2). However, until now there has been no comprehensive guidance document available which deals with the evaluation of the stability of vaccines at different stages of their development, production, licensing, lot release and post-licensing. At its fifty-first meeting, the Expert Committee on Biological Standardization recommended that WHO set up a working group on stability evaluation of vaccines to examine this issue. The first meeting of the working group was held at the Paul Ehrlich Institute, in Langen, Germany, in February 2002, when key issues to be included in guidelines were identified. At its second meeting, held at WHO, Geneva, in 2004, the working group suggested further additions and improvements to the proposed guidelines including guidance on the design of stability studies. Reviews of stability studies undertaken on different types of vaccines were carried out in 2004 and 2005. These revealed problems in the conduct, analysis and the interpretation of data. In particular, difficulties were identified with the application of the pharmaceutical accelerated stability testing programme to vaccines and with the mathematical models used in data analysis. Additionally, differences in current practice with regard to the selection of parameters measured and the frequency of testing were identified. Two extremes were noted. In some cases numerous parameters were evaluated while in others only potency was examined. Similarly, the frequency and the rationale for defining appropriate intervals of testing varied considerably. Furthermore, the assignment of shelf-life to intermediates, as well as their cumulative age, was identified as a problem for both vaccine manufacturers and national regulatory authorities. The stability assessment of combined vaccines is an additional issue. A survey of current approaches to the stability testing of vaccines targeting both manufacturers and regulatory practices was conducted in 2006. The outcomes of all these activities were used to define the scope and to provide the guiding principles set out in this document...

For more information, please refer to: http://www.who.int/biologicals/vaccines/Annex_3_WHO_TRS_962-3.pdf