This document discusses analytical method validation which is the process of confirming that an analytical method is suitable for its intended purpose. Key aspects of method validation discussed include accuracy, precision, specificity, linearity, range, detection limit, quantitation limit, repeatability and intermediate precision. The document outlines validation parameters for different types of analytical methods and provides examples of acceptance criteria. It also discusses guidance from regulatory agencies on analytical method validation.
Analytical method validation as per ich and usp shreyas B R
Analytical method validation is a process of documenting/ proving that an analytical method provides analytical data acceptable for the intended use.After the development of an analytical procedure, it is must important to assure that the procedure will consistently produce the intended a precise result with high degree of accuracy. The method should give a specific result that may not be affected by external matters. This creates a requirement to validate the analytical procedures. The validation procedures consists of some characteristics parameters that makes the method acceptable with addition of statistical tools.
Analytical method validation as per ich and usp shreyas B R
Analytical method validation is a process of documenting/ proving that an analytical method provides analytical data acceptable for the intended use.After the development of an analytical procedure, it is must important to assure that the procedure will consistently produce the intended a precise result with high degree of accuracy. The method should give a specific result that may not be affected by external matters. This creates a requirement to validate the analytical procedures. The validation procedures consists of some characteristics parameters that makes the method acceptable with addition of statistical tools.
In this slide contains Introduction, levels of cleaning, mechanism, sampling method of cleaning validation.
Presented by: P. VENKATESH (Department of pharmaceutical analysis).RIPER, anantapur
The objective of any chemical analytical measurement is to get consistent, reliable and accurate data.
Proper functioning and performance of analytical instruments and computer systems plays a major role in achieving this goal.
Therefore, analytical instrument qualification (AIQ) and calibration should be part of any good analytical practice.
Analytical method validation, ICH Q2 guidelineAbhishek Soni
Analytical Method Validation, ICH Q2 Guideline.
General principles related to the analytical method validation.
Validation of analytical method as per International Council for Harmonisation(ICH) guidelines and the United States Pharmacopeia(USP).
Glossary.
Useful in understanding the terms :
Specificity
Linearity
Range
Accuracy
Precision
Detection limit
Quantitation limit
Robustness
Ruggedness
System suitability testing
It is process of “Establishing documentary evidence that provide a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes”.
In the pharmaceutical industry, it is very important that in addition to final testing and compliance of products, it is also assured that the process will consistently produce the expected results.
Validation is action of proving in accordance with the principles of good manufacturing practices, that any procedure, process, equipment, material, activity or system actually leads to expected results.
Cleaning validation is documented evidence with a high degree assurance that one can consistently clean a system or a piece of equipment to predetermined and acceptable limits.
The primary regulatory concern driving the need for cleaning validation is cross contamination of the desired drug substance either by other API from previous batch runs or by residues from the cleaning agents used.
The prime purpose of validating a cleaning process is to ensure compliance with federal and other standard regulations
1. Cross contamination with active ingredients
Contamination of one batch of product with significant levels of residual active ingredients from previous batch cannot be tolerated.
In addition to the obvious problems posed by subjecting consumers or patients to unintended contaminants, potential clinically significant synergistic interactions between pharmacologically active chemicals are a real concern.
2. Contamination with unintended materials or compounds
While inert ingredients used in drug products are generally recognized as safe for human consumption, the routine use, maintenance and cleaning of equipment's provide the potential contamination with such items as equipment parts, lubricants and chemical cleaning agents3. Microbiological contamination
Maintenance , cleaning and storage conditions may provide adventitious microorganisms with the opportunity to proliferate within the processing equipment.
QUALIFICATION OF UV-VISIBLE SPECTROPHOTOMETER, FTIR, DSC, HPLCAnupriyaNR
Analytical method qualification consists of a simplified evaluation of a subset of validation characteristics with a goal to demonstrate that an analytical method is scientifically sound and suitable for its intended use. In contrast to validation, analytical method qualification is performed without predefined acceptability criteria. Qualification may be performed as a prerequisite to method validation, or when an assay for product knowledge has not yet been established as a test for a critical product quality attribute. Qualification of equipment is pre-requisite for validation of the process in which the equipment is being used. Many types of equipment have measuring devices on them. Calibration of measuring devices is a part of qualification. Calibration of measuring devices is important, as the data is often collected through them. If the data collected is not from measuring devices that have been calibrated, the data cannot be relied upon. Thus the whole validation exercise can be questioned.
Introduction, Regulatory requirements for validation, Role of FDA, Code of Federal regulation, Validation life cycle, Significance of validation, Types of validation, Process valiadation, Phases of process validation, Process capability design, Process Qualification, Validation maintainance phase
Types of Process validation, Examples
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
In this slide contains Introduction, levels of cleaning, mechanism, sampling method of cleaning validation.
Presented by: P. VENKATESH (Department of pharmaceutical analysis).RIPER, anantapur
The objective of any chemical analytical measurement is to get consistent, reliable and accurate data.
Proper functioning and performance of analytical instruments and computer systems plays a major role in achieving this goal.
Therefore, analytical instrument qualification (AIQ) and calibration should be part of any good analytical practice.
Analytical method validation, ICH Q2 guidelineAbhishek Soni
Analytical Method Validation, ICH Q2 Guideline.
General principles related to the analytical method validation.
Validation of analytical method as per International Council for Harmonisation(ICH) guidelines and the United States Pharmacopeia(USP).
Glossary.
Useful in understanding the terms :
Specificity
Linearity
Range
Accuracy
Precision
Detection limit
Quantitation limit
Robustness
Ruggedness
System suitability testing
It is process of “Establishing documentary evidence that provide a high degree of assurance that a specific process will consistently produce a product meeting its predetermined specifications and quality attributes”.
In the pharmaceutical industry, it is very important that in addition to final testing and compliance of products, it is also assured that the process will consistently produce the expected results.
Validation is action of proving in accordance with the principles of good manufacturing practices, that any procedure, process, equipment, material, activity or system actually leads to expected results.
Cleaning validation is documented evidence with a high degree assurance that one can consistently clean a system or a piece of equipment to predetermined and acceptable limits.
The primary regulatory concern driving the need for cleaning validation is cross contamination of the desired drug substance either by other API from previous batch runs or by residues from the cleaning agents used.
The prime purpose of validating a cleaning process is to ensure compliance with federal and other standard regulations
1. Cross contamination with active ingredients
Contamination of one batch of product with significant levels of residual active ingredients from previous batch cannot be tolerated.
In addition to the obvious problems posed by subjecting consumers or patients to unintended contaminants, potential clinically significant synergistic interactions between pharmacologically active chemicals are a real concern.
2. Contamination with unintended materials or compounds
While inert ingredients used in drug products are generally recognized as safe for human consumption, the routine use, maintenance and cleaning of equipment's provide the potential contamination with such items as equipment parts, lubricants and chemical cleaning agents3. Microbiological contamination
Maintenance , cleaning and storage conditions may provide adventitious microorganisms with the opportunity to proliferate within the processing equipment.
QUALIFICATION OF UV-VISIBLE SPECTROPHOTOMETER, FTIR, DSC, HPLCAnupriyaNR
Analytical method qualification consists of a simplified evaluation of a subset of validation characteristics with a goal to demonstrate that an analytical method is scientifically sound and suitable for its intended use. In contrast to validation, analytical method qualification is performed without predefined acceptability criteria. Qualification may be performed as a prerequisite to method validation, or when an assay for product knowledge has not yet been established as a test for a critical product quality attribute. Qualification of equipment is pre-requisite for validation of the process in which the equipment is being used. Many types of equipment have measuring devices on them. Calibration of measuring devices is a part of qualification. Calibration of measuring devices is important, as the data is often collected through them. If the data collected is not from measuring devices that have been calibrated, the data cannot be relied upon. Thus the whole validation exercise can be questioned.
Introduction, Regulatory requirements for validation, Role of FDA, Code of Federal regulation, Validation life cycle, Significance of validation, Types of validation, Process valiadation, Phases of process validation, Process capability design, Process Qualification, Validation maintainance phase
Types of Process validation, Examples
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
Analytical method development and validation are one of the very imp aspects in Drug testing and approval process.Here I tried to explain the same with my experience.
Understanding of Analytical Method Validation Approach in Pharmaceutical Industry. Analytical method validation Verification is a wide chapter and a huge scope of applicability. In different types of methods, instrument, measurement approach all can effect the validation effort. However the basic fundamental will remains same, the parameters, acceptance criteria, functionality may vary depending upon the type of method, instrument etc.
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References
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Reaction, End point & Indicators
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2. Analytical methods are used to test and ensure the
Quality of Drug substances / Drug products
Analytical methods are followed from Official
Pharmacopeia or developed by users.Pharmacopeia or developed by users.
How can assure the analytical methods are suitable
for it purpose.
Hence Analytical Method has to be validated or
confirm its suitability?
3. Method validation is the process of planned
and systematic study to confirm that it is
suitable for its intended use.
Method is reliable, accurate & reproducible
Pharmaceutical Industries governed by rules &
regulations.
Method validation is mandatory as per
regulatory agencies.
4. Guidance for Method Validation
CDER : “Analytical Procedures and Method
Validation” Draft guidance August 2000
ICH: Validation Of Analytical Procedures:
Text And Methodology Q2(R1) 2005.Text And Methodology Q2(R1) 2005.
USP 41: General Chapter <1225> Validation
of Compendial Methods
5. Four most common types of analytical
procedures:
◦ Identification tests - Eg FTIR spectrum
◦ Quantitative tests for impurities: Eg. 10ppm to 2%◦ Quantitative tests for impurities: Eg. 10ppm to 2%
◦ Limit tests for the control of impurities: Eg < 100ppm
◦ Quantitative tests of the active substance - Assay /
purity : Eg 99-101%
7. Analytical procedure
Characteristics
Identification
Tests for impurities
Assay
Quantitative Limit test
Accuracy No Yes No Yes
Precision- Repeatability No Yes No Yes
Intermediate precision No Yes No YesIntermediate precision No No
Specificity Yes Yes Yes Yes
Limit of Detection No Yes Yes No
Limit of Quantitation No Yes No No
Linearity No Yes No Yes
Range No Yes No Yes
Robustness * No Yes No Yes
8. Specificity
Ability of an analytical method to measure the analyte free
from interference from components.
Example:
• HPLC/ GC: well separation of all peaks. Drug from Impurities
Analytical Method Validation
• HPLC/ GC: well separation of all peaks. Drug from Impurities
• Peak purity- No overlapping of peaks / co elution
9. Analytical Method Validation
Accuracy:
The accuracy of an analytical procedure expresses the
closeness of agreement between the value which is
accepted either as a conventional true value or an
accepted reference value and the value found.accepted reference value and the value found.
The accuracy is closeness
between the experimental
value and true value.
10. Assay:
Test the assay at 80%, 100% & and 120%
Acceptance criteria:
Recovery : 99.0-101.0%
% RSD should be less than 2.0.
Analytical Method Validation
Impurities -Related substances:
Test impurities at 50% - 150% to the limit value.
Acceptance criteria:
Recovery 90.0% to 110.0%
% RSD should be less than 10.0%.
11. Linearity
The 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.
Linearity :should be proportional
response to analyte concentration.
Experiment: Detection level to 150% to limit
Acceptance criteria:
Plot Linear Regression (y = mx +c)
Linear regression r2 > 0.98
12. Range:
The range of an analytical procedure is the interval between the
upper and 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.accuracy and linearity.
◦ For Drug Substance & Drug product Assay
80 to 120% of test Concentration
◦ For Impurities:
LOQ Level to 120% of Limit
13. Limit of Detection
Lowest amount of analyte
in a sample that can be
detected
Limit of Quantitation:
Lowest amount of analyte in a
sample that can be quantified
Analytical Method ValidationAnalytical Method Validation
detected
• Estimated by Signal to Noise
Ratio of 3:1 or
• 3.3 x Standard Deviation /
Slope
with suitable accuracy and
precision.
• Estimated by Signal to Noise Ratio
of 10:1. or
• 10 x Standard Deviation / Slope
15. Analytical Method ValidationAnalytical Method Validation
LOD and LOQLOD and LOQ
3.3X Standard Deviation / Slope
Ybl
LOD LOQ
Statistical estimate of LOD & LOQ
LOD = 3.3 Sbl / b LOQ = 10 Sbl / b
Y = b X + a
16. Precision:
Closeness of agreement (degree of scatter) between
a series of measurements obtained from multiple
testing under the prescribed conditions.
Precision to be established :
Repeatability, Intermediate precision and
Reproducibility.
The precision of an analytical procedure is
usually expressed as the variance, standard
deviation or coefficient of variation
17. Repeatability
Repeatability expresses the precision under the same operating
conditions over a short interval of time.
Intermediate precision
Intermediate precision expresses within-laboratories variations: Intermediate precision expresses within-laboratories variations:
different days, different analysts, different equipment, etc.
Reproducibility
Reproducibility expresses the precision between laboratories
19. Robustness:
Analytical procedure is capable to remain unaffected by small, but
deliberate variations in method parameters and provides an
indication of its reliability during normal usage.
Examples of typical variations in LC
pH of mobile phase ( 5.0±0.2)
Mobile phase composition (±10 % of solvent)
Different columns (different lots and/or suppliers)
Temperature ( 30±° 2C)
Flow rate (1.5 ml ±0.1ml)
Comparison results under differing conditions with under normal