Dr Joachim Ermer, Ermer Quality Consulting, Germany
Besides regulatory expectations, this Live Online Training provides practical recommendations and orientation for demonstration of the on-going suitability of analytical procedures. A rational and efficient validation approach is ultimately based on the respective routine application, which should be reflected in the validation design. This includes the identification of the relevant performance parameters, the selection of appropriate tests and calculations and, in particular, the establishment of acceptance criteria for the Evaluation.
This Training focusses on the parameters Accuracy, Specificity, Linearity and Quantitation Limit.
According to EU GMP Guide Part 1, Chapter 6, Quality Control (6.15) and US 21 CFR 211.194, analytical procedures must be suitable for their intended purpose. The regulatory requirements to validation of analytical procedures utilised for release and stability studies of drug substances and drug products are described in the ICH guideline Q2(R1). However, its degree of detail is rather low, and the discussion is mainly focused on chromatographic methods. The latter is one of the reasons for the started revision of the guideline, as well as inclusion of lifecycle and risk management aspects, which gained increasing attention in the last years.
This Training is aimed at executives and employees from Quality Control, Quality Assurance, and regulatory who want to gain a better understanding of the GMP requirements as well as current trends and are interested in practical recommendations for an efficient design, execution, and evaluation of a successful analytical validation.
For our Live Online Training Courses and Webinars, we use Cisco WebEx, one of the leading suppliers of online meetings.
At http://www.webex.com/test-meeting.html you can check if your system meets the necessary requirements for the participation at a WebEx meeting and at the same time install the necessary plug-in. Please just enter your name and email address for the test. If the installation is not possible because of your rights for the computer system, please contact your IT department. WebEx is a standard nowadays and the necessary installation is fast and easy.
Lifecycle Concept and Precision:
Regulatory Requirements and the Lifecycle Concept for Analytical Procedures
- ICH Q2-Guideline – requirements and gaps
- ICH Q2-Revision and Q14 Development of Analytical Procedures (intended changes and content)
- USP <1220> Draft: The Analytical Procedure Lifecycle
- Requirements to the analytical performance (Analytical Target Profile)
- Verification of compendial procedures
Performance Attributes of Analytical Procedures
- Validation characteristics and error types
- Distribution of analytical data
- Evaluation of performance parameters (simple, statistical)
- Efficient validation
- Precision levels (system precision, repeatability, intermediate precision, reproducibility)
- Acceptance limits for assay
- Derivation from probability, measurement uncertainty, tolerance factors
- Concentration dependency of precision (Horwitz function)
- Acceptance limits for impurities
- Design of precision studies and calculations
- Uncertainty of precisions: point estimators and confidence intervals
- Optimisation of precision by averaging (replication strategy)
- Precision of the reportable value (small molecules, bioassay)
- Assay for small molecules, bioassay
Workshop: Multiple Choice Questions (from Publications)
- How to avoid mistakes in validation
Accuracy, Specificity, Linearity and Quantitation Limit
- Comparison and recovery
- Statistical significance and equivalence tests
- Variability and expected difference between means
- Acceptance criteria for assay and impurity determinations
- Separate and combined evaluation of accuracy and precision
- Comparison and (chromatographic) separation
- Samples for investigation of specificity
- Peak purity investigations
- Gaps in the ICH Q2-Guideline
- Requirements to calibration models
- linear single-point and multiple-point calibration,
- non-linear calibration
- standard addition
- Statistical calculations (regression, suitable parameters)
- Acceptance criteria for calibration function
- residual and sensitivity plot
- ordinate intercept
Detection and Quantitation Limit
- Determination of the quantitation limit (blank procedures, from linearity, from precision)
- Is less more?
- Capability and requirement based quantitation limits
- Consideration of practical relevance (samples, concentration range for linearity approaches)
Workshop: Multiple Choice-Questions (from Publications)
- How to avoid mistakes in validation