Quality by Design (QbD) is well established in the pharmaceutical industry for manufacturing processes, including active pharmaceutical ingredients and drug products. The knowledge obtained during development can establish the design space and determine suitable process controls. The novelty of the multivariate approach over the more traditional one-factor-at-a-time (OFAT) type of study is the ability to evaluate both the individual factor effects and the factor-factor interactions that can also be significant.
These same QbD principles have been applied to the development of analytical methods. In this case study, a QbD approach was used to solve a high-performance liquid chromatography (HPLC) analytical method problem where impurity peaks had shifting retention times making identification and quantitation problematic. For one critical pair of impurity peaks, the variability was large enough that an unpredictable reversal of elution order occurred that appeared to be column lot specific (same column, different lot).