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:Total validation
Moderate Risk:Testing,Documentation
Low Risk:Testing the change
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
For details vis
2. 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
• Total validation
Moderate
risk
• Testing, documentation
Low risk
• Testing the change
3. 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
4. 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.
5. 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
6. 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
7. 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
