Design Spaces for Analytical Methods

Since the adoption of the ICH Q8 document concerning the development of pharmaceutical processes following a Quality by Design (QbD) approach, there have been many discussions on the opportunity for analytical method developments to follow a similar approach. A key component of the QbD paradigm is the definition of the Design Space of analytical methods where assurance of quality is provided. Several Design Spaces for analytical methods have been published, stressing the importance of this concept. This paper aims at explaining what is an analytical method Design Space, why it is useful for the robust development and optimization of analytical methods and how to build such a Design Space. A strong emphasis is made by distinguishing the usual mean response surface approach, overlapping mean response surfaces and the desirability function one to other probabilistic approaches as only these last ones correctly define a Design Space. In addition, recent publications assessing the Design Space of analytical methods are reviewed and discussed