2. WHO approach and key issues
2.1 Stability evaluation of vaccines: WHO approach
Dr. Knezevic outlined general WHO strategies to support introducing safe and
efficacious vaccines, one of which is to assist regulators and manufacturers for a common
understanding in assessing and evaluating the stability profile of vaccines by organizing a
series of explanatory and interactive workshops. These series of workshops will help to
strengthen regulatory capacity and build a network of regulators and manufacturers for a
common understanding of the guidelines.
Activities which assure the quality of existing and new vaccines have served as a basis
for vaccine use and have contributed to the WHO’s immunization goals. Accordingly,
quality assurance of vaccines has been achieved through a program of Biological
Standardization which includes setting international written standards such as new
guidelines for novel vaccines and revised recommendations (formerly, requirements) for
existing vaccines or other guidelines on general matters of regulatory concerns.
Stability is a key facet of vaccine quality. Stability is a cross-cutting quality issue.
Stability evaluation must be based on sound scientific principles, standardized test
methods and analysis. Further, monitoring in use as well as during the whole life span of
the vaccine product forms an essential part of stability evaluation.
Stability-indicating parameters may include all batch-release specifications, but they
mainly focus on safety and potency. New vaccines should be characterized to understand
the key parameters that determine stability, including the relationship of an effective
potency at the end of shelf-life and a safe potency at releasing the product. The
cumulative age of the antigens in the vaccine may be important and at least the age of
specific antigens in a batch should be well documented.
https://www.who.int/docs/default-source/biologicals/vaccine-...

The Vaccine Stability Study Technology
The methods for determining product shelf life. One is compliance method, that is, a certain index is tested at different time points within a period of time, and the measured value is constantly changing with the passage of time. When the measured value exceeds the specified standard, the maximum shelf life is taken at that time point. Another method is statistical method, that is, a certain index is tested at different time points in a period of time, and finally the results are statistically analyzed, the average value is calculated and the data is analyzed.

The methods for reducing stability variability. One is repeated testing. According to statistics, the variability of repeated 2 tests of a certain method can be 44, and the variability of repeated 6 tests can be reduced to 16. Another method is to use the standard substances in testing. Besides, collecting samples and keeping them under proper temperature while testing, can also reduce stability variability. https://www.creative-biolabs.com/vaccine/the-stability-tests...
https://www.sciencedirect.com/science/article/pii/S093964111...

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Note added at 3 óra (2022-04-15 12:46:22 GMT)
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As shown in WHO, TRS 993, 2015: Guidelines on procedures and data requirements
for changes to approved vaccines, the number of batches and data required are
dependent on the type and condition of variations. This Guideline should be considered
and applied as appropriate for supporting each variation/change. The smaller scale and
bracketing stability study may be acceptable, when justified.
Reference:
1) WHO TRS. No. 962, 2011. Annex 3: Guidelines on stability evaluation of
vaccines
2) WHO TRS. No. 993, 2015. Annex 4: Guidelines on procedures and data
requirements for changes to approved vaccines.
https://www.fda.gov.ph/wp-content/uploads/2021/03/QA-on-the-...