Uncertainty of measurement and error in stability studies.

It is required that shelf life be determined based on the lower limit of the confidence interval of the estimate from the stability tests. Simulations indicate that a 1-year prediction of shelf life will have approximately 1 month of error. However, this is product specific and is related to the uncertainty of measurement and experimental design. Factors associated with product and experimental design, such as degradation rate, number of time points, implementing a full versus a reduced design, etc., can significantly affect the error of shelf life. Uncertainty in measurement is positively correlated to the amount of error through the manufacturing lot-to-lot variability, precision of the analytical method and calibrator. Experimental design can control random variability and actually can reduce error by increasing number of lots and replicates in stability tests. The decision on the number of lots and replicates will be a balancing act between the uncertainty of the measurement, design and other practical considerations.