Analytical Quality by Design is a concept for (rapid, consistent and) systematic development of robust analytical methods that are designed to meet predefined criteria. The method is designed with the knowledge of what the method needs to do (Analytical Target Profile), followed by technique selection, systematic method development to achieve initial conditions, risk assessment(s)to identify and rank method ruggedness/robustness aspects and design of experiments to understand the actual impact. A resultant understanding of the method conditions that meet the preset criteria are identified.
During development of the AQbD workflow, capability gaps were identified around the informatics and data handling components. Significant time was spent on informatics activities (e.g., sample/method set creation, data processing/MS peak tracking, DOE design, DOE sample/method set creation, DoE output/report generation) rather than experimentation, so software was developed to minimize resources associated with these aspects. Several process step deficiencies identified above were enhanced:
1. A “software wrapper sample submission user interface (UI)” to seamlessly control both the Waters MassLynx and Waters Empower based LC/MS screening system within Empower
2. Method (set) creation, sample submission, auto generation of injection sequences, and sample queuing
3. Peak tracking (rather than peak counting) using MS and UV spectra using Chemometric Data Preprocessing with Component Data Analysis (CODA) and facile manual assignments
4. Ability to write individual peak identification into custom fields for each Empower result injection
5. Simple UI to create DoEs (or import DoE designs)
6. Report generation to support modeling.
The presentation discusses AQbD concepts, hurdles that encumber AQbD methods development, rationales behind, benefits and examples of the Accela software package to rapidly progress development of robust methods using LC/MS.