In preparation for Stage 1, define an analytical target profile (ATP), show how your method’s performance characteristics meet required criteria, and consider overall measurement uncertainties. Getting in-depth knowledge of what affects your method’s performance using Quality by Design (QbD) concepts helps you ensure your method’s robustness from the start.
The Stages of Method Lifecycle Management
Methods with greater agility, robustness, and capacity for change can help reduce regulatory burden, failure risk, and costs. Discover the stages, concepts, and terms that define lifecycle management, then explore them in depth below.
Design & Development in Depth
The presence of impurities, even at trace levels, may affect the quality, safety and efficacy of drug products. Impurities in a drug substance or drug product can arise from chemical synthesis, degradation, manufacturing, storage conditions, packaging, excipients or contamination. Analytical method development for impurity detection and quantitation is a necessary and often challenging task for pharmaceutical manufacturers. Risk-based approaches such as Analytical Quality by Design (AQbD) and Method Lifecycle Management (MLCM) can be implemented to develop fit-for-purpose and robust methods that improve the control of impurities.
Reducing sources of variability is key to the MLCM process. Empower scoring reports allow users to choose the best conditions for their methods, relying on metrics instead of individual judgement. The scoring report allows the user to quickly identify the conditions that met the pre-established criteria (ATP) — removing analyst variability and bias in the method development process. This technology brief demonstrates the capabilities of Empower 3 Software for scoring chromatographic separations using custom calculations and custom reports.
Pfizer's Dr. Pankaj Aggarwal discusses the use of data-driven modeling to build quality and robustness into analytical methods.
Applying Quality-by-Design approaches to analytical method development has many benefits. It emphasizes the identification of the sources of variability and their impact on method performance.
Analytical methods are required to be developed at different stages of the pharmaceutical product life cycle. Two of the most widely used strategies for method development are: one-factor-at-a-time (OFAT) and analytical quality-by-design approach (AQbD).
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.
Tracking peaks across different chromatograms in the method development process can be challenging. This is because sample components could shift, switch retention times, or even coeleute under different separation conditions. Many method development protocols rely on ultra violet (UV) spectral data only to track peaks. Despite the potential benefits of such protocols they can still have some limitations.
The goal of a method development process is to find a well-working and robust method that consistently delivers the expected performance throughout its lifecycle. This process can be very complex and time-consuming, especially if multiple chromatographic parameters need to be explored.
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?
Paula Hong of Waters illustrates how the ACQUITY QDa mass detector can be used as an orthogonal detection approach to UV in methods development.
The ACQUITY QDa mass detector aids in efficient and robust method development, minimizing the need for standards to confirm peak identity by retention time. In this video, we demonstrate the use of qualitative mass spectral data in method development, using an ACQUITY QDa mass detector to confirm the identity of ziprasidone HCl and related compounds.
This white paper describes a synergistic, systematic, and streamlined approach to method development that takes advantage of UPLC instrumentation, sub-2-μm column chemistries, and Empower 3 Software.
In the following study, a careful evaluation of the USP assay for atorvastatin was performed. To minimize the impact of environmental conditions, both sample preparation and mobile phase composition were controlled using approaches allowed within USP chapter 621. These studies enabled scientists to devise a strategy to minimize any variation in the method transfer of the USP method across multiple labs on different continents.
This application describes a case study where a Quality by Design (QbD) approach was used to develop an analytical stability-indicating method for monitoring degradation of amoxicillin powder for oral suspension. It illustrates how QbD leveraged the software assistance of Fusion QbD to select factor value combinations, create acquisition methods, and evaluate modeled responses.