The lifecycle of analytical methods has three stages: Design, Qualification, and Continued Verification. Ideally, a design space is defined during the early stages of the method development. Methods design is a range of parameters within which the method performs as intended and within which the method is fit for use. ICH Q8(R2) states that “working within the design space is not considered as a change.” In addition, ICH Q12 (draft) introduces a post-approval management plan to be initiated at submission (Post-Approval Change Management Protocol or PACMP). It integrates flexibility and lowers the need for new validation when changes are made to the method in Stage 3 (i.e., continued verification).
When one runs into problems with a method in Stage 3, it may be necessary to return to design and development (Stage 1) to resolve the problems. This task can be an arduous one, especially when production is ongoing. Indeed, one department typically handles both Stage 1 method development and design, while the Stage 3 routine method use is handled by a different department, with tight timelines for production of results.
DryLab4 software from Molnár Institute can help with this challenge because it can optimize the performance of an existing method in three simple steps: input runs, peak tracking and create the model, which helps find the most robust separation within the existing design space. The input runs bracket the existing method conditions about the allowed variations for the multiple variables of the method. Peak tracking is the identification of peaks in the input runs. DryLab then creates the model.
Using just a few experimental runs, DryLab visualizes the chromatographic process interactively, running hundreds of simulations in a few moments to find the best separation conditions, highest critical resolution, shortest run time and the highest robustness. Furthermore, evaluating method robustness during method development, while defining the analytical target profile (ATP), ensures a working design space for post-approval management and flexibility in dealing with out of specification (OoS) results in routine work. DryLab can be used at all stages, as shown in Figure 1/Slide 6.
Figure 1. Lifecycle Management of Analytical Methods, showing DryLab should be used in all phases to enhance a better chromatographic method understanding.