The uncertainty budget in pharmaceutical industry

Measurements in a pharmaceutical industry are usually carried out to ascertain the quality of a product or the control of a process; in either case the measurement result serves to demonstrate that the value of the measurand is within specified limits. No method is without bias, and no result is without uncertainty; the result of a measurement is therefore only an estimate of the value of the measurand. Traditionally it is assumed that specifications duly reflect both bias and measurement uncertainty in such a way that conformity requires only that the measurement result falls within specified limits. In our age of globalization this assumption can no longer be upheld, and external specifications have to be taken as real, rational expressions of limits not to be exceeded [1]. Demonstration of conformity therefore requires results to be corrected for bias and accompanied by a statement of their uncertainty, exactly as described in GUM [2]. Pharmaceutical industry has therefore over the last 5 years shown increasing interest in accreditation according to ISO 17025 [3], and today uncertainty budgets are being developed for all so-called critical measurements. The uncertainty of results obtained by methods under development or with limited practical experience has to be estimated by a bottom-up procedure, while results obtained by routine methods or standardized methods from the Pharmacopoeia can apply the top-down approach, using already existing statistical information. It is important to remember that the uncertainty of a particular result is independent of the method used for its estimation. Several examples of uncertainty budgets for critical parameters based on the bottom-up procedure will be discussed, and it will be shown how the top-down method is used as a means of verifying uncertainty budgets, based on Type B experience [4].