Rapid Method Development and Quality Regulatory Submissions: Combining UPLC, Quality-by-Design (QbD)

Method development and validation are essential parts of the pharmaceutical drug approval process. As process modifications are made and approval criteria become increasingly stringent, changes to the validated method are sometimes necessary. A Quality by Design (QbD) approach to method development uses statistical design of experiments (DoE) to generate a robust method ‘design space’. The design space defines a region in which changes to method parameters will not significantly affect the results, incorporating risk-based assessment of the final method. Rather than developing and validating a single method and proceeding through re-validation as modifications are made, a design space incorporates allowable flexibility into the method.
 

A QbD approach is demonstrated here in the development of a stability-indicating method, using UPLC for fast, sensitive separations, and software-driven validation. The flexibility of transferring methods between UPLC and HPLC will also be demonstrated. This streamlined approach to method development affords considerable cost savings as well as a significantly more robust and quality submission to regulatory authorities for faster drug approval.