Robust method optimization strategy - A useful tool for method transfer: The case of SFC

The concept of Quality by Design (QbD) is now well established in pharmaceutical industry and should be applied to the development of any analytical methods. In this context, the key concept of Design Space (DS) was introduced in the field of analytical method optimization. In chromatographic words, the DS is the space of chromatographic conditions that will ensure the quality of peaks separation, thus DS is a zone of robustness. In the present study, the interest of robust method optimization strategy was investigated in the context of direct method transfer from sending to receiving laboratory. The benefit of this approach is to speed up the method life cycle by performing only one quantitative validation step in the final environment of method use. A Supercritical Fluid Chromatography (SFC) method previously developed was used as a case study in this work. Moreover, the interest of geometric transfer was investigated simultaneously in order to stress a little bit more the transfer exercise and, by the way, emphasize the additional benefit of DS strategy in this particular context. Three successful transfers were performed on two column geometries. In order to compare original and transferred methods, the observed relative retention times (RT) were modelled as a function of the predicted relative RT and of the method type (original or transferred). The observed relative RT of the original and transferred methods are not statistically different and thus the method transfer is successfully achieved thanks to the robust optimization strategy. Furthermore, the analytical method was improved considering analysis time (reduced five times) and peak capacity (increased three times). To conclude, the advantage of using a DS strategy implemented for the optimization and transfer of SFC method was successfully demonstrated in this work. (C) 2013 Elsevier B.V. All rights reserved.