Abstract
Potency is a critical quality attribute of a vaccine and those attributes that impact potency are essential to assuring vaccine quality. Over its entire shelf life, a vaccine must exceed a minimal potency value and, when defined, cannot exceed a maximal potency.
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Notes
- 1.
Although maximal potency values are set for the majority of vaccines, certain vaccines have no defined upper potency limit.
- 2.
The World Health Organization, in its Guidelines on Stability Evaluation of Vaccines, has noted that “In many countries, expiry periods of vaccine products are calculated by testing a predefined number of Lots, at pre-defined intervals, and designating the expiry period as the first time at which a stability measurement falls below an acceptable threshold”. The WHO Guideline also notes that “This approach has the advantage of simplicity, but may yield spurious results due to assay variability”.
- 3.
ICH Q1E notes that, “for an attribute known to decrease with time, the lower one-sided 95 % confidence limit should be compared to the acceptance criterion. For an attribute known to increase with time, the upper one-sided 95 % confidence limit should be compared to the acceptance criterion. For an attribute that can either increase or decrease, or whose direction of change is not known, two-sided 95 % confidence limits should be calculated and compared to the upper and lower acceptance criteria”. In the examples of the time dependence of potency presented in this chapter, a loss in potency with time is considered.
- 4.
Analysis of covariance (ANCOVA) can be employed, where time is considered the covariate, to test the differences in slopes and intercepts of the regression lines among batches. Each of these tests should be conducted using a significance level of 0.25 to compensate for the expected low power of the design due to the relatively limited sample size in a typical formal stability study.
- 5.
Although other confidence limits might be chosen, 95 % is a generally agreed-to default value.
- 6.
The relationship between reaction rates and temperature was developed by the Swedish physical chemist, Svante August Arrhenius (1859–1927).
- 7.
The half-life for a reaction is the time taken for one-half of a reactant to be consumed; for a first-order reaction, the half-life, τ ½, is equal to ln (2)/k.
- 8.
Although potency tests are designed to indicate the expected effects in the intended recipient population, they are, in reality, often imperfect predictors.
- 9.
In the above example, activation energies, E a, of 94.28 and 92.67 kJ/mole (with a pre-exponential factor of 10−9 ) were chosen to mimic the kinetics at 5 °C and to subsequently calculate the rates at 25 °C.
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Appendix
Appendix
See Table 14.4.
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Egan, W., Schofield, T. (2015). Establishing a Shelf Life and Setting Lot-Release Specifications. In: Nunnally, B., Turula, V., Sitrin, R. (eds) Vaccine Analysis: Strategies, Principles, and Control. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45024-6_14
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DOI: https://doi.org/10.1007/978-3-662-45024-6_14
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