Validation is defined as establishing documented evidence that a process will consistently produce results meeting pre-determined specifications. Key aspects of analytical method validation include accuracy, precision, specificity, limit of detection/quantitation, linearity, range, robustness, and system suitability. Validation demonstrates a method is suitable for its intended use and ensures consistent, reliable results are obtained in compliance with regulations.
Impurity profiling and degradent characterization {presented by shameer m.pha...ShameerAbid
these slides discuss
Impurity profiling
Degradation characterization
Stability testing & Accelerated stability testing (ICH)
Evaluation of the test (shelf life)
analytical method development
ICH vs USP definition
methods for identification
method for the isolation of the impurity
factors affecting the degradation of formulation
What is degradation characterization
general protocol of degradation conditions used for drug substance and drug product
Degradation conditions
Stress testing
Container closure system
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.
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.
Impurity profiling and degradent characterization {presented by shameer m.pha...ShameerAbid
these slides discuss
Impurity profiling
Degradation characterization
Stability testing & Accelerated stability testing (ICH)
Evaluation of the test (shelf life)
analytical method development
ICH vs USP definition
methods for identification
method for the isolation of the impurity
factors affecting the degradation of formulation
What is degradation characterization
general protocol of degradation conditions used for drug substance and drug product
Degradation conditions
Stress testing
Container closure system
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.
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.
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with qualifications of HPLC which is the " High Performance Liquid Chromatography".
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
Validation of Analytical and Bioanalytical methodssarikakkadam
Guidelines for Validation of Analytical and Bioanalytical methods as per ICH (Q2R1) and USFDA respectively with an example of Bioanalytical method validation.
In this slide contains Introduction, levels of cleaning, mechanism, sampling method of cleaning validation.
Presented by: P. VENKATESH (Department of pharmaceutical analysis).RIPER, anantapur
Notes* for the subject 'Advanced Pharmaceutical Analysis'Sanathoiba Singha
As per the syllabus prescribed by Rajiv Gandhi University of Health Sciences, Karnataka, for M. Pharm (Pharmaceutical Analysis) 1st semester.
*not all topics have been included in this collection of notes.
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with qualifications of HPLC which is the " High Performance Liquid Chromatography".
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
Validation of Analytical and Bioanalytical methodssarikakkadam
Guidelines for Validation of Analytical and Bioanalytical methods as per ICH (Q2R1) and USFDA respectively with an example of Bioanalytical method validation.
In this slide contains Introduction, levels of cleaning, mechanism, sampling method of cleaning validation.
Presented by: P. VENKATESH (Department of pharmaceutical analysis).RIPER, anantapur
Notes* for the subject 'Advanced Pharmaceutical Analysis'Sanathoiba Singha
As per the syllabus prescribed by Rajiv Gandhi University of Health Sciences, Karnataka, for M. Pharm (Pharmaceutical Analysis) 1st semester.
*not all topics have been included in this collection of notes.
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.
Analytical Method Validation is a process that is used to demonstrate the suitability of an analytical method for an intended purpose.Regulations and quality standards that have an impact on analytical laboratories require analytical methods to be validated.
Method Validation - ICH /USP Validation, Linearity and Repeatability labgo
Prepared by : Santram Rajput (Technical Manager)
Validation of analytical procedures reinforce the reliability and suitability of a methodology for providing accurate and precise results. This slide show elaborates in detail about the need for method validation with examples, along with that it also covers the factors to be evaluated prior to validation. This slide show further touches upon the characteristics which are of significance in context of the validation procedure.
This presentation was made to solely for students to make them aware/ understand basics of “Analytical Method Validation”. These slides are part of lectures delivered in M. Pharmacy Curriculum & taken up from various books and websites
Method validation for drug substances and drug product _remodified_2014Ramalingam Badmanaban
Method validation is the process of proving that an analytical method is acceptable for its intended purposes.
METHOD VALIDATION = ERROR ASSESSMENT
Method validation is the process of demonstrating that analytical procedures are suitable for their intended use and that they support the identity, strength, quality, purity and potency of the drug substances and drug products
Validation: Prior ConsiderationsSuitability of Instrument Status of Qualification and Calibration Suitability of Materials Status of Reference Standards, Reagents, Placebo Lots Suitability of Analyst Status of Training and Qualification Records Suitability of Documentation Written and approved standard test procedure and proper approved protocol with pre-established acceptance criteria
Compendial vs. Non-compendial Methods
Compendial methods-Verification
Regulatory analytical procedure in USP/NF
Non- compendial methods-Validation
Alternative analytical procedure proposed by the applicant for use instead of the regulatory analytical procedure
Chromatographic Methods
Demonstrate Resolution
Impurities/Degradants Available
Spike with impurities/degradants
Show resolution and a lack of interference
Impurities/Degradants Not Available
Stress SamplesFor assay, Stressed and Unstressed Samples should be compared.
Ability of an analytical method to measure the analyte free from interference due to other components.
Selectivity describes the ability of an analytical method to differentiate various substances in a sample
Original term used in USP
Also Preferred by IUPAC and AOAC
Also used to characterize chromatographic columns
Degree of Bias (Used in USP)
The difference in assay results between the two groups
the sample containing added impurities, degradation products, related chemical compounds, placebo ingredients
Selectivity: For impurity test, impurity profiles should be compared.
Temperature (50-60℃)
Humidity (70-80%)
Acid Hydrolysis (0.1 N HCl)
Base Hydrolysis (0.1 N NaOH)
Oxidation (3-30%)
Light (UV/Vis/Fl)
Intent is to create 10 to 30 % Degradation
Change in the analytical procedure, drug substance, drug product, the changes, may necessitate revalidation of the analytical procedures.
“The degree of revalidation depends on the nature of the change.”
“FDA intends to provide guidance in the future on post-approval changes in analytical procedures.”
By Visual Inspection of plot of signals vs. analyte concentration
By Appropriate statistical methods
Linear Regression (y = mx + b)
Correlation Coefficient, y-intercept (b), slope (m)
Acceptance criteria: Linear regression r2 > 0.999
Requires a minimum of 6 concentration levels
Normally derived from Linearity studies.
Established by confirming that the method provides acceptable degree of linearity, accuracy, and precision.
Specific range dependent upon intended application of the procedure.
Macroeconomics- Movie Location
This will be used as part of your Personal Professional Portfolio once graded.
Objective:
Prepare a presentation or a paper using research, basic comparative analysis, data organization and application of economic information. You will make an informed assessment of an economic climate outside of the United States to accomplish an entertainment industry objective.
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
Welcome to TechSoup New Member Orientation and Q&A (May 2024).pdfTechSoup
In this webinar you will learn how your organization can access TechSoup's wide variety of product discount and donation programs. From hardware to software, we'll give you a tour of the tools available to help your nonprofit with productivity, collaboration, financial management, donor tracking, security, and more.
Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
June 3, 2024 Anti-Semitism Letter Sent to MIT President Kornbluth and MIT Cor...Levi Shapiro
Letter from the Congress of the United States regarding Anti-Semitism sent June 3rd to MIT President Sally Kornbluth, MIT Corp Chair, Mark Gorenberg
Dear Dr. Kornbluth and Mr. Gorenberg,
The US House of Representatives is deeply concerned by ongoing and pervasive acts of antisemitic
harassment and intimidation at the Massachusetts Institute of Technology (MIT). Failing to act decisively to ensure a safe learning environment for all students would be a grave dereliction of your responsibilities as President of MIT and Chair of the MIT Corporation.
This Congress will not stand idly by and allow an environment hostile to Jewish students to persist. The House believes that your institution is in violation of Title VI of the Civil Rights Act, and the inability or
unwillingness to rectify this violation through action requires accountability.
Postsecondary education is a unique opportunity for students to learn and have their ideas and beliefs challenged. However, universities receiving hundreds of millions of federal funds annually have denied
students that opportunity and have been hijacked to become venues for the promotion of terrorism, antisemitic harassment and intimidation, unlawful encampments, and in some cases, assaults and riots.
The House of Representatives will not countenance the use of federal funds to indoctrinate students into hateful, antisemitic, anti-American supporters of terrorism. Investigations into campus antisemitism by the Committee on Education and the Workforce and the Committee on Ways and Means have been expanded into a Congress-wide probe across all relevant jurisdictions to address this national crisis. The undersigned Committees will conduct oversight into the use of federal funds at MIT and its learning environment under authorities granted to each Committee.
• The Committee on Education and the Workforce has been investigating your institution since December 7, 2023. The Committee has broad jurisdiction over postsecondary education, including its compliance with Title VI of the Civil Rights Act, campus safety concerns over disruptions to the learning environment, and the awarding of federal student aid under the Higher Education Act.
• The Committee on Oversight and Accountability is investigating the sources of funding and other support flowing to groups espousing pro-Hamas propaganda and engaged in antisemitic harassment and intimidation of students. The Committee on Oversight and Accountability is the principal oversight committee of the US House of Representatives and has broad authority to investigate “any matter” at “any time” under House Rule X.
• The Committee on Ways and Means has been investigating several universities since November 15, 2023, when the Committee held a hearing entitled From Ivory Towers to Dark Corners: Investigating the Nexus Between Antisemitism, Tax-Exempt Universities, and Terror Financing. The Committee followed the hearing with letters to those institutions on January 10, 202
"Protectable subject matters, Protection in biotechnology, Protection of othe...
Analytical Method Validation
1.
2. What is Validation?
• Validation is defined as establishing documented evidence
which provides a high degree of assurance that a specific process
will consistently produce a product meeting its pre-determined
specifications and quality attributes.
Identification
Determination of impurities
Assay
8 January 2016 Analytical Method Validation 2
3. Why Validation?
• The objective of any analytical measurement is to obtain
consistent, reliable and accurate data. Validated analytical
methods play a major role in achieving this goal.
• Validation of analytical methods is also required by most
regulations.l.
8 January 2016 Analytical Method Validation 3
4. Typical Analytical Procedures To
Be Validated
• Four most common types of analytical procedures to be
validated:
• Identification tests
• Quantitative tests for impurities content
• Limit tests for the control of impurities
• Quantitative tests of the active moiety
8 January 2016 Analytical Method Validation 4
5. Revalidation
• Revalidation may be necessary in the following circumstances:
• Changes in the synthesis of the drug substance
• Changes in the composition of the finished product
• Changes in the analytical procedure
8 January 2016 Analytical Method Validation 5
6. Parameters
1. Linearity and Range
2. Specificity
3. Precision
4. Accuracy
5. Limit of Detection
6. Limit of Quantitation
7. Robustness
8. System Suitability
8 January 2016 Analytical Method Validation 6
7. Characteristic Identification Impurities Testing Assay
Quantitative Limit
Accuracy _ + _ +
Precision
a. Repeatability _ + _ +
b. Intermediate precision _ + _ +
Specificity + + + +
LOD _ _ + _
LOQ _ + _ _
Linearity _ + _ +
Range _ + _ +
8 January 2016 Analytical Method Validation 7
-signifies that this characteristic is not normally evaluated
+ signifies that this characteristic is normally evaluated
8. 1. Linearity and Range
LINEARITY
• Ability to obtain test results that are directly (or by a well-defined
mathematical transformation) proportional to the concentration
of analyte in samples within a given range. (y = mx + c)
• The following parameters should be determined:
correlation coefficient
y-intercept(c)
slope of the regression line(m)
8 January 2016 Analytical Method Validation 8
9. Determination of Linearity
• For establishment of linearity, minimum 5 concentrations are
recommended.
• Linearity results should be established by appropriate statistical
methods.
8 January 2016 Analytical Method Validation 9
y = 0.0868x + 0.019
R² = 0.9988
0
0.2
0.4
0.6
0.8
1
0 2 4 6 8 10 12
10. • Transformations are also acceptable and may include log, square
root, or reciprocal (other transformations are acceptable)
8 January 2016 Analytical Method Validation 10
Conc.
(µg/ml)
Response
1 0.0625
2 0.25
3 0.562
4 0.922
5 1.562
y = 0.3671x - 0.4296
R² = 0.9515
-0.2
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
0 2 4 6
11. • If linearity is not attainable, a nonlinear model may be used. The
goal is to have a model (whether linear or nonlinear) that
describes closely the concentration-response relationship.
• Acceptance criteria: Linear regression r2 > 0.95
8 January 2016 Analytical Method Validation 11
Conc.
(µg/ml)
√Response
1 0.25
2 0.5
3 0.75
4 0.96
5 1.25
y = 0.246x + 0.004
R² = 0.9982
0
0.2
0.4
0.6
0.8
1
1.2
1.4
0 2 4 6
12. RANGE
8 January 2016 Analytical Method Validation 12
• The range of an analytical procedure is the interval between the
upper and lower levels of analyte(including these levels) that
have been demonstrated with a suitable level of precision,
accuracy, and linearity.
• For assay tests, ICH requires the minimum specified range to be
80 to 120 percent of the test concentration. It also requires the
range for the determination of an impurity to extend from the
limit of quantitation or from 50 percent of the specification of
each impurity, whichever is greater, to 120 percent of the
specification
13. 8 January 2016 Analytical Method Validation 13
• Acceptable range having linearity, accuracy, precision.
• For Drug Substance & Drug product Assay
– 80 to 120% of test Concentration
• For Content Uniformity Assay
– 70 to 130% of test Concentration
• For Dissolution Test Method
– +/- 20% over entire Specification Range
• For Impurity Assays
– From Reporting Level to 120% of Impurity Specification for
Impurity Assays
– From Reporting Level to 120% of Assay Specification for
Impurity/Assay Methods
14. 2. Precision
• The precision of an analytical procedure expresses the closeness
of agreement (degree of scatter) between a series of
measurements obtained from multiple sampling of the same
homogeneous sample under the prescribed conditions.
• Sample prepared in six replicates on the same day and analysed
as per the method.
• The precision is reported in terms of %RSD
8 January 2016 Analytical Method Validation 14
16. • Precision may be considered at three levels:
8 January 2016 Analytical Method Validation 16
Precision
Repeatability
Intermediate
Precision
Reproducibility
17. 1. Repeatability
• Repeatability expresses the precision under the same
operating conditions over a short interval of time.
• Repeatability should be assessed using a minimum of
9 determinations covering the specified range.
2. Intermediate Precision
• Intermediate precision expresses variations within
laboratories, such as different days, different analysts,
different equipment, and so forth
3. Reproducibility
• Reproducibility expresses the precision between
laboratories. It is assessed by means of an inter-
laboratory trial. (Defined as ruggedness in USP, ISO
17025)
8 January 2016 Analytical Method Validation 17
18. • Following parameters should be reported:
a. Standard deviation
b. Relative standard deviation (coefficient of variation)
8 January 2016 Analytical Method Validation 18
Concentration
µg/ml
Absorbance SD & % RSD
8
0.337 0.00041,
1.223%
0.348
0.341
12
0.575 0.0106,
1.815%
0.583
0.596
20
0.967
0.0091,
0.933%
0.985
0.978
0
0.2
0.4
0.6
0.8
1
1.2
4 8 12 16 20 24
8
8
8
12
12
12
20
20
20
19. 3. Accuracy
• Closeness of agreement between the conventional true value /
an accepted reference value and the value found.
High Accuracy Less Accuracy
(Less Precision) (High Precision)
8 January 2016 Analytical Method Validation 19
20. Determination of Accuracy
Drug Substance
a)application of analytical
procedure to a reference
material
b) to compare the results
c) accuracy may be inferred
once precision, linearity
and specificity have been
established.
Drug Product
a)application of the analytical
procedure to synthetic
mixtures to which known
quantities of the drug
substance have been added
b) to compare the results
c) accuracy may be inferred
once precision, linearity and
specificity have been
established.
8 January 2016 Analytical Method Validation 20
1. Assay
21. 2. Impurities (Quantitation)
Assessed on samples (drug substance/drug product) spiked with
known amounts of impurities.
Accuracy should be assessed using a minimum of 9 determinations
over a minimum of 3 concentration levels covering the specified
range (e.g., 3 concentrations/3 replicates each of the total
analytical procedure).
Accuracy should be reported as percent recovery by the assay of
known added amount of analyte in the sample or as the difference
between the mean and the accepted true value.
8 January 2016 Analytical Method Validation 21
22. 4. Limit of Detection & Limit of
Quantitation
LOD
Lowest amount of analyte in a
sample that can be detected
but not necessarily
quantitated.
Estimated by Signal to Noise
Ratio of 3:1.
LOQ
Lowest amount of analyte
in a sample that can be
quantified with suitable
accuracy and precision.
Estimated by Signal to
Noise Ratio of 10:1.
8 January 2016 Analytical Method Validation 22
23. 4. Limit of Detection & Limit of
Quantitation
• Limit of Detection:
• It is the lowest amount of analyte in a sample which can be
detected but not necessarily quantitated.
• Limit of Quantitation:
• It is the lowest amount of analyte in a sample which can be
quantitatively determined with suitable precision and accuracy.
8 January 2016 Analytical Method Validation 23
24. Determination of LOD & LOQ
Limit of Detection
Method
Based on visual evaluation
Based on standard deviation
of response and slope
LOD = 3.3 σ / Slope
Signal to noise ratio 2:1 or 3:1
Limit of Quantitation
Method
Based on visual evaluation
Based on standard deviation
of response and slope
LOD = 10 σ / Slope
Signal to noise ratio 10:1
8 January 2016 Analytical Method Validation 24
26. 6. Specificity
• The ability to detect the analyte of interest in the presence of
interfering substances (typically impurities, degradants, matrix).
1. Identification
• Suitable identification tests should be able to discriminate
between compounds of closely related structures which are
likely to be present.
• The discrimination of a procedure may be confirmed by
obtaining positive results from samples containing the analyte,
coupled with negative results from samples which do not
contain the analyte.
• The identification test may be applied to materials structurally
similar to or closely related to the analyte to confirm that a
positive response is not obtained.
8 January 2016 Analytical Method Validation 26
27. 2. Assay and impurity test:
a. Impurities are available
• For the assay , this should involve demonstration of the
discrimination of the analyte in the presence of impurities
and/or excipients.
• This can be done by spiking pure substances with
appropriate levels of impurities and/or excipients and
demonstrating that the assay result is unaffected by the
presence of these materials.
• For the impurity test, the discrimination may be established
by spiking drug substance or drug product with appropriate
levels of impurities and demonstrating the separation of
these impurities individually and/or from other components
in the sample matrix.
8 January 2016 Analytical Method Validation 27
28. b. Impurities are not available
• If impurity or degradation product standards are unavailable,
specificity may be demonstrated by comparing the test results
of samples containing impurities or degradation products to a
second well-characterized procedure e.g. pharmacopoeial
method or other validated analytical procedure.
• As appropriate, this should include samples stored under
relevant stress conditions: light, heat, humidity, acid/base
hydrolysis and oxidation.
8 January 2016 Analytical Method Validation 28
29. 7. Robustness
• The robustness of an analytical procedure is a measure of its
capacity to remain unaffected by small, but deliberate variations
in method parameters and provides an indication of its reliability
during normal usage.
• If measurements are susceptible to variations in analytical
conditions, the analytical conditions should be suitably
controlled or a precautionary statement should be included in
the procedure, such as:
• Use solution within 24 hours
• Maintain temperature below 25 degrees
8 January 2016 Analytical Method Validation 29
30. • In the case of liquid chromatography, examples of typical
variations are:
influence of variations of pH in a mobile phase
influence of variations in mobile phase composition
different columns (different lots and/or suppliers)
temperature
flow rate
• In the case of gas-chromatography, examples of typical variations
are:
different columns (different lots and/or suppliers)
temperature
flow rate
8 January 2016 Analytical Method Validation 30
31. 8. System Suitability
• System suitability testing is an integral part of many analytical
procedures. The tests are based on the concept that the
equipment, electronics, analytical operations and samples to be
analyzed constitute an integral system that can be evaluated as
such.
• Determination: repeatability, tailing factor (T), capacity factor
(k’), resolution (R), and theoretical Plates (N)
8 January 2016 Analytical Method Validation 31
32. System Suitability Requirements
Parameters Recommendations
K’ In general k’ ≥ 2.0
R
R >2, between the peak of interest and
the closest potential interferent (degradant,
internal STD, impurity, excipient, etc…)
T T ≤ 2
N In general N > 2000
Repeatability RSD ≤ 2.0% (n ≥ 5)
8 January 2016 Analytical Method Validation 32
33. Conclusion
• When the method is properly validated consistent, reliable
and accurate results are obtained. Also, Validation of
analytical methods is also required by regulations. Hence it
is very important to validate any analytical method that has
been developed.
8 January 2016 Analytical Method Validation 33