Isabelle VuTrieu, Pharmaceutical Market Development Manager, Waters Corp.
Genotoxic Impurities. Dr. Phil Borman, Director of Product Quality at GSK, provided this response when asked where he applies the lifecycle management approach. As Phil explained in the first episode of the MLCM podcast series1, complex methods that require a tight control of the critical quality attributes are opportunities to leverage the lifecycle management approach. Taking a risk-based approach, Phil’s team identifies methods designed to detect genotoxic impurities as ones with potential control issues, which require stringent controls. They are absolutely critical for the patients.” He continues “[We] focus our efforts on critical parts of our product control strategy to make sure those methods are of a high standard so the patient is confident that these are not present, or exist at very low limits of a process”
In recent years, the increased number of method transfer failures has led to greater transfer scrutiny by industry and regulators. And for good reason. Simple paper transfers between sending and receiving units and provision of ambiguous information are widely regarded as insufficient. These outdated practices are now being superseded by more proactive approaches to support successful method transfer, including the provision of method transfer packages and improved lab-to-lab communication1. Indeed, it was a decade ago that Nethercote, et al2 described the benefits of Quality-by-Design based method development with the goal of creating more robust analytical procedures. Despite these advances, however, there are still situations where methods that come into the receiving lab are poorly understood, or insufficient information is available. Even with the implementation of pharmacopoeial methods, or well-understood robust methods, predicting problems can be challenging, and many only show up over time.
Dr. Fadi Alkhateeb of Waters Corporation discusses his recent method development work.
What does it mean to develop a good LC method?
With Method Lifecycle Management (MLCM) we focus not only on the quality of the analytical method but also on the quality of the reportable result. The goal is to generate quality data across the life of a method. To achieve this, method development begins with an Analytical Target Profile (ATP) in which performance objectives are defined in terms of accuracy and precision, independent of the analytical technology chosen. The ATP is linked to the Critical Quality Attributes (CQA) of the drug product and the Critical Process Parameters (CPP) of the manufacturing process. The traditional method development goals of resolution and peak shape are critical method parameters, but what defines a good method under MLCM principles is one that achieves the accuracy and precision goals specified in the ATP. This leads to a quality reportable result throughout the method’s life.
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?
Sample handling and preparation can have a substantial effect on an analytical method’s variability and data quality. It is important to consider and address the risks associated with sample preparation as part of the method development process. This requires carefully designed and executed experiments and clear documentation in the method to give the analyst an effective analytical control strategy. Through proper technique, the choice of reproducible consumables and method lifecycle approaches, including an Analytical Target Profile (ATP), risk assessment (RA) and analytical control strategy (ACS), an analyst can effectively mitigate risk and improve the robustness of their analytical methods.