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Guidelines on stability evaluation of vaccines

The stability of vaccines has a major impact on the success of immunizationprogrammes worldwide. As part of its efforts to assure vaccine quality, WHOhas acknowledged the importance of clearly defining the stability characteristicsof a vaccine and emphasizes the role of national regulatory authorities in overallvaccine evaluation.

The aim of this document is to provide the scientific basis and guidingprinciples for evaluation of vaccine stability for the purpose of clinical trialapproval, licensing, and post-licensure monitoring.The temperature sensitivity of vaccine characteristics, particularlypotency, led to the development of storage and cold chain requirements for allvaccines. In the 1980s and at the beginning of the 1990s, a major WHO focus wason thermostability testing, as measured by potency assays, as part of lot release.More recently, guidance has addressed the importance of studies performedunder real storage conditions, in real time, and with other relevant environmentalfactors. In addition, the WHO guidelines for nonclinical and clinical evaluationof 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 documentavailable which deals with the evaluation of the stability of vaccines at differentstages of their development, production, licensing, lot release and post-licensing.At its fifty-first meeting, the Expert Committee on BiologicalStandardization recommended that WHO set up a working group on stabilityevaluation of vaccines to examine this issue. The first meeting of the workinggroup was held at the Paul Ehrlich Institute, in Langen, Germany, in February2002, when key issues to be included in guidelines were identified. At its secondmeeting, held at WHO, Geneva, in 2004, the working group suggested furtheradditions and improvements to the proposed guidelines including guidance onthe design of stability studies. Reviews of stability studies undertaken on differenttypes of vaccines were carried out in 2004 and 2005. These revealed problemsin the conduct, analysis and the interpretation of data. In particular, difficultieswere identified with the application of the pharmaceutical accelerated stabilitytesting programme to vaccines and with the mathematical models used in dataanalysis. Additionally, differences in current practice with regard to the selectionof parameters measured and the frequency of testing were identified. Twoextremes were noted. In some cases numerous parameters were evaluated whilein others only potency was examined. Similarly, the frequency and the rationalefor defining appropriate intervals of testing varied considerably.Furthermore, the assignment of shelf-life to intermediates, as well as theircumulative age, was identified as a problem for both vaccine manufacturers andnational regulatory authorities. The stability assessment of combined vaccinesis an additional issue. A survey of current approaches to the stability testing of vaccines targeting both manufacturers and regulatory practices was conductedin 2006. The outcomes of all these activities were used to define the scope and toprovide 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