The design space for a process is defined as the set of control factors settings that have been demonstrated to assure product quality. The concept of Quality by Design treats analytical methods as a process. The product of an analytical method is the measurement result. These measurement results are used to make development and commercial decisions. Thus, the design space for a method is the region of operation where the assay will provide results which are fit for purpose, or which facilitate risk based decisions.This may be accomplished by demonstrating that the analytical methods operates within pre-defined acceptance limits for one or more analytical methods characteristics which are linked to decision making risks. A key challenge is to derive acceptance limits or specifications that are relevant with respect to the objectives and use of results. The methodologies presented in this talk will address several dimensions. First, modeling and simulation will be used to develop and justify acceptance limits on assay characteristics (aTPP) which are based on practical settings and aims. Second, a Bayesian approach will be used to predict that results will be within acceptance limits (CQA). A methodology will be proposed to develop analytical methods that will remain reliable and robust over time. These concepts will be illustrated for an HPLC and an ELISA method using a calibration curve to measure drug product for release to market. The precision and the accuracy profiles derived from the different potential calibration strategies will be used as a basis for deriving assay characteristics (CQA) which are directly linked to release decisions. DOE will be used in conjunction with Bayesian analysis to define the design space (DS) for the analytical methods.Finally, the Bayesian predictive distribution or the tolerance interval will be used to define the future quality control limits to ensure the analytical method is maintained within a �state of control�.

Quality by design for analytical methods: Connecting the dots from development to routine

247th National Meeting (2014)

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