In the pharmaceutical industry there’s a shift and it’s changing the way we think about and develop analytical methods. Change can be uncomfortable, but when the driving forces are to ensure data quality, make better decisions and improve patient outcomes, how can we resist?
Traditional chromatographic method development begins with an understanding of the physicochemical properties of the compounds to be separated and the goal of obtaining well-resolved analyte peaks in a reasonable timeframe. Under a new paradigm, one which applies quality by design principles to analytical procedures (AQbD), methods are held to a different standard. Analyte understanding remains important, but method understanding is paramount.
Method Lifecycle Management (MLCM), of which AQbD is an integral part, states that the new standard is not just a robust method, but a method that is fit for its intended purpose and achieves predetermined performance goals that are linked to the Critical Quality Attributes (CQA) of the drug product. The new measure of method success is the output, or reportable result. To achieve a trustworthy result, the method should be well-understood, undergo an upfront risk assessment and its performance criteria should be specified in terms of accuracy and precision in an Analytical Target Profile (ATP). The method should also embody a control strategy designed to mitigate the identified risks and method performance trending should take place throughout the method’s life.
For more detail on method lifecycle concepts, refer to the stimuli article Proposed New USP General Chapter: The Analytical Procedure Lifecycle <1220>. With a method lifecycle approach the downstream gains can be significant.
Help is on the way…
In addition to MLCM and AQbD risk-based strategies, modern tools and technologies are taking hold and leading to fit for purpose methods, greater efficiencies, controlled risks, and reportable results that lead to better decision-making. Recent software advances such as fully automated Design of Experiments (DOE) and MS peak tracking have led to increased adoption of software-assisted AQbD method development. Both software-assisted AQbD and risk-based systematic method development using modern LC technologies are gaining greater acceptance as tools to improve efficiency and manage risk within a method lifecycle framework.
To explore these strategies further:
- See Applying a Software-Assisted Analytical Quality by Design Approach for the Analysis of Formoterol, Budenoside and Related compounds by UPLC-MS and Automated Peak Tracking Using Mass Detection and Fusion QbD Software to uncover how mass detection and other technologies improve efficiency and control risk in method development
- Refer to A Complete Solution to Perform a Systematic Screening Protocol for LC Method Development for a contemporary systematic approach that serves as an alternative to software-assisted method development.
For more information on companies who have successfully implemented MLCM and AQbD approaches, see:
- Analytical Procedure (Method) Lifecycle Management Drives Method Development at Innovative CDMO
- The Method Detectives: Building a New Business Model with Analytical Procedure (Method) Lifecycle Management
Stay tuned for our next blog where we will post a scientist interview that probes these concepts in just a bit more detail. See you then!