How do you use risk assessment tools to prioritize method development activities and resources?

1 QbD and risk assessment

QbD is a scientific and risk-based approach to analytical method development that aims to ensure the quality and reliability of the method throughout its lifecycle. QbD involves defining the analytical target profile (ATP), identifying the potential sources of variability, and designing experiments to control and optimize the method parameters. Risk assessment is a key step in QbD that helps you evaluate the impact and likelihood of each source of variability on the method performance and select the most critical ones for further investigation.

2 Risk assessment tools

Risk assessment for analytical method development can be aided by various tools and techniques, the most common of which are Failure Mode and Effects Analysis (FMEA), Fishbone Diagrams, Pareto Charts, and Risk Matrices. FMEA is a systematic method to identify and rank potential failure modes and their causes and effects on the method performance. Fishbone Diagrams are graphical tools to visualize the main factors and their sub-factors that can affect method performance and quality. Pareto Charts are bar charts that show the frequency or magnitude of each factor or cause in descending order, helping you identify the most significant ones. Risk Matrices are tables that show the combination of impact and likelihood for each factor or cause, aiding in classifying them into low, medium, or high risk categories.

3 How to use risk assessment tools

To use risk assessment tools effectively, you must define the scope and objectives of your risk assessment, as well as criteria for evaluating the impact and likelihood of each factor or cause. Gather relevant information about your method, its intended use, and potential sources of variability. Choose the appropriate tool or technique for your risk assessment and apply it, such as FMEA to list failure modes and assign a Risk Priority Number (RPN), or a fishbone diagram to organize factors into categories. Use a Pareto chart or risk matrix to rank and prioritize factors based on their frequency or magnitude and their impact and likelihood. Analyze the results to identify critical factors that need to be controlled or optimized, then plan and execute DOE to study the effects of these factors on method performance and quality. Evaluate the results of DOE and determine optimal settings and ranges for method parameters, using statistical tools such as ANOVA, regression analysis, contour plots, or Pareto charts.

4 Benefits of risk assessment and DOE

Using risk assessment and DOE for analytical method development can offer several advantages, such as saving time and resources, improving method performance and quality, enhancing robustness and reliability, increasing knowledge and understanding, and facilitating method transfer, scale-up, or change. These benefits are achieved by reducing the number of experiments, optimizing and controlling parameters to minimize variability and uncertainty, establishing the MODR and MVAC, identifying sources and effects of variability and their interactions, as well as providing a scientific rationale and documentation for the method design and validation.

5 Challenges and limitations of risk assessment and DOE

When conducting risk assessment and DOE, it is important to be aware of the challenges and limitations. This includes selecting the right tool or technique, considering the advantages and disadvantages of each, as well as selecting relevant factors or causes for your DOE. Additionally, designing and conducting your DOE in a reliable and reproducible way is important, as is analyzing and interpreting your results in a valid and meaningful way. To do this, you need to follow good laboratory practices (GLP), ensure accuracy and precision of measurements, control or randomize sources of variation, use appropriate statistical methods and tools, check assumptions and conditions of analysis, and account for uncertainty and variability of results.