Method Validation: What Are Its Key Parameters?
What is Validation? •
Methods validation is the process of demonstrating that analytical procedures are suitable for their intended use‐Guidance for Industry
•
Validation is a process‐risk will determine the effort
High Risk
Moderate risk
Low risk
• Total validation
• Testing, documentation
• Testing the change
Validation Parameters for Different Methods Analytical Tsk
Identification
Impurity Quantitative
Impurity Qualitative
Assay
Accuracy
No
Yes
No
Yes
Precision
No
Yes
No
Yes
Specificity
Yes
Yes
Yes
Yes
Limit of Detection
No
No
Yes
No
Limit of Quantitation
No
Yes
No
No
Linearity
No
Yes
No
Yes
Range
No
Yes
No
Yes
Robustness
Expected to be done during method development
Accuracy ICH defines accuracy of an analytical procedure as the closeness of agreement between the conventional true value or an accepted reference value and the value found. % Accuracy = Experimental‐ True Value * 100 True Value
Precision Precision of analytical procedure is defined as closeness of agreement in values between a series of measurements. As per ICH, precision is considered at three different levels: • Repeatability or intra—assay precision: precision data are obtained by repeatedly analyzing, in one lab on one day, aliquots of a homogeneous sample. • Intermediate precision: precision obtained when the assay is performed by multiple analysts, multiple instruments, and multiple days in one lab. • Reproducibility: precision between laboratories.
Specificity • Specificity is the ability of the method to accurately measure the analyte response in the presence of all potential sample components. • It is very important in the analysis of complex mixtures by GC, HPLC, AA, ICP, etc.
Limit of Detection (LOD) • Limit of Detection (LOD) is the lowest amount of analyte in a sample which can be reliably detected but not necessarily accurately or precisely measured. • Signal/Noise = 2 to 3
Limit of Quantitation (LOQ) • Limit of Quantitation (LOQ) is the lowest amount of an analyte that can be quantitatively determined with suitable precision and accuracy. • Signal/Noise = 10 to 20
Linearity and Range • Linearity of an analytical procedure is its ability (within a given range) to obtain test results which are directly proportional to the concentration (amount) of analyte in the sample. • Range: Interval from the upper to the lower concentration (amounts) of analyte in the sample (including these concentrations) for which it has been demonstrated that the analytical procedure has a suitable level of precision, accuracy and linearity – Must cover 80‐120% of product claims – Usually evaluated from the same data set as linearity, precision, accuracy
Want to learn more about analytical method validation, FDA requirements and best practices to comply with them? ComplianceOnline webinars and seminars are a great training resource. Check out the following links: • ICH, FDA and USP Requirements for Method Validation • How to Validate Analytical Methods and Procedures • Validation of Analytical Methods and Procedures • Eliminate the Confusion ‐ Analytical Method Qualification and Validation • Lifecycle Approach to Analytical Methods with QbD Elements • Analytical Instrument Qualification and System Validation • Lifecycle Approach to Analytical Methods for Drug Products