Analytical method development in pharmaceutical industry is a risk-based approaches for the assessment of the quality of drug substances and drug products based on product QTPP and CQAs. It’s determine what to measure and when to measure.
The goal of method development is to obtain an analytical method fit for its intended purpose: to measure an attribute or attributes of the drug substance or drug product with the needed specificity/selectivity, accuracy and/or precision over the reportable range.
Analytical method development should include the following elements as minimal approach:
- Identifying which attributes of the drug substance or drug product need to be tested.
- Selecting an appropriate analytical method and related instruments or suitable apparatus.
- Conducting appropriate development studies to evaluate analytical method performance characteristics such as specificity, accuracy and precision over the reportable range (including the calibration model, limits at lower and/or higher range ends) and robustness.
- Defining an appropriate analytical method description including the control strategy (e.g., parameter settings and system suitability).
Major Steps for Analytical Method Development
- Analyte information collection
- Literature search for method development
- Selection of analytical technique and instruments
- Risk assessment of analytical method
- Design of experiment and evaluation of method
- Control strategy
The enhanced approach offers a systematic way of developing and refining knowledge of an analytical method. An enhanced approach should include one or more of the following elements in addition to those already described for the minimal approach:
- An evaluation of the sample properties and the expected variability of the sample based on manufacturing process understanding.
- Defining the analytical target profile (ATP).
- Conducting risk assessment and evaluating prior knowledge to identify the analytical method parameters that can impact performance of the procedure.
- Conducting uni- or multi-variate experiments to explore ranges and interactions between identified analytical procedure parameters.
- Defining an analytical method control strategy based on enhanced procedure understanding including appropriate set-points and/or ranges for relevant analytical method parameters ensuring adherence to performance criteria.
- Defining a lifecycle change management plan with clear definitions and reporting categories of established conditions (ECs), proven acceptable ranges (PARs) or method operational design regions (MODRs) as appropriate.
Analytical Method Development Guidelines
Analytical procedure development and change management approaches are described in ICH Q14 whereas analytical procedure validation is described in ICH Q2.