Analytical method validation it is helpful for you all

ANALYTICAL
METHOD
VALIDATION
PRESENTED BY-
ASHA DHAKAL
M. PHARM (QUALITY ASSURANCE)
2ND SEMESTER
PHARMACEUTICAL VALIDATION
(202T)
PRESENTED TO-
DR. SAURABH DAHIYA SIR
DELHI INSTITUTE OF PHARMACEUTICAL SCIENCES AND RESEARCH

CONTENT
• Introduction
• General Principle
• Types of analytical method validation
• ICH and USP parameters for analytical method validation
• ICH Q2(R2) guideline on analytical method validation
• Analytical procedure validation study
ASHA DHAKAL DIPSAR

INTRODUCTION
• Validation: it is an act of demonstrating and documented evidence that any procedure,
process, and activity will consistently lead to the expected results
• Analytical method: method used to determine a chemical or physical property of a chemical
substance or mixture.There is a wide variety of techniques used for analysis, from simple
weighing to advanced techniques using highly specialized instrumentation. (titrimetric,
instrumental and chromatographic analysis etc.)
• Analytical method validation: it is a procedure of performing numerous assessments
designed to verify that an analytical test system is suitable for its intended reason & capable
of producing beneficial and legitimate analytical data.
ASHA DHAKAL DIPSAR

GENERAL PRINCIPLE OF ANALYTICAL METHOD VALIDATION
OBJECTIVE
❑ The objective of validation of an analytical procedure is to demonstrate that it is suitable for its
intended purpose.
❑ Analytical methods must be validated or revalidated- before their introduction into routine use.
❑ Furthermore 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
❑ The document indicates the data that should be presented in a regulatory submission
ANALYTICAL PROCEDURE
• The analytical procedure refers to the way of performing the analysis.
• The analytical procedure should describe in sufficient detail the steps necessary to perform each
analytical test
ASHA DHAKAL DIPSAR

TYPES ANALYTICAL METHOD VALIDATION
❑ Identification tests
❑ Quantitative tests for impurities' content
❑ Limit tests for the control of impurities
❑ Quantitative tests of the active moiety in samples of drug substance or drug product or other selected
component(s) in the drug product (Assay test)
• Identification tests are intended to ensure the identity of an analyte in a sample. This is normally achieved by
comparing a property of the sample (e.g., spectrum, chromatographic behaviour, chemical reactivity, etc.) to that of a
reference standard
• Testing for impurities can be either a quantitative test or a limit test for the impurity in a sample. Either test is
intended to reflect the purity characteristics of the sample accurately.
• Assay procedures are intended to measure the analyte present in a given sample. The assay quantitatively measures
the drug substance’s major component(s).
ASHA DHAKAL DIPSAR

ICH/USP PARAMETERS OF ANALYTICAL METHOD
VALIDATION
❑Accuracy
❑Precision
• Repeatability
• Intermediate Precision
❑Specificity
❑Detection Limit
❑Quantitation Limit
❑Linearity
❑Range
❑Robustness
Andra Pradesh State gives
Qualified Driving Licenses to
Range Rover car owners
ASHA DHAKAL DIPSAR

ACCURACY: The accuracy of an analytical procedure expresses the closeness of agreement between the value
accepted as a conventional true value or an accepted reference value and the value found.
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. Precision may be considered at three levels: repeatability, intermediate precision and
reproducibility. The precision of an analytical procedure is usually expressed as the variance, standard deviation or
coefficient of variation of a series of measurements.
1. REPEATABILITY: Repeatability expresses the precision under the same operating conditions over a short interval
of time. Repeatability is also termed intra-assay precision
2. INTERMEDIATE PRECISION: Intermediate precision expresses within-laboratories variations: different days,
different analysts, different equipment, etc.
3. REPRODUCIBILITY: Reproducibility expresses the precision between laboratories (collaborative studies, usually
applied to standardization of methodology).
SPECIFICITY: Specificity is the ability to assess unequivocally the analyte in the presence of components that may be
expected to be present. Typically these might include impurities, degradants, matrix, etc
ASHA DHAKAL DIPSAR

DETECTION LIMIT: The detection limit of an individual analytical procedure is the lowest amount of analyte in
a sample which can be detected but not necessarily quantitated as an exact value
QUANTITATION LIMIT: The quantitation limit of an individual analytical procedure is the lowest amount of
analyte in a sample which can be quantitatively determined with suitable precision and accuracy. The
quantitation limit is a parameter of quantitative assays for low levels of compounds in sample matrices and is
used particularly for the determination of impurities and/or degradation products.
LINEARITY: The linearity of an analytical procedure is its ability (within a given range) to obtain test results
that are directly proportional to the concentration (amount) of analyte in the sample.
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.
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.
ASHA DHAKAL DIPSAR

ICH Q2(R2) GUIDELINE ON ANALYTICAL
METHOD VALIDATION

ICH Q2(R2) GUIDELINE ON ANALYTICAL METHOD VALIDATION
OBJECTIVE
• This guideline presents elements for consideration during the validation of analytical procedures included as part
of registration applications
• Analytical procedure validation forms a part of the analytical procedure lifecycle, as described within ICH Q14
Analytical Procedure Development. ICH Q2(R2) guides the selection and evaluation of the various validation tests
for analytical procedures.
• This guideline includes a collection of terms and their definitions, which are meant to bridge the differences
between various compendia and documents of the ICH member regulatory authorities.
• The objective of validation of an analytical procedure is to demonstrate that the analytical procedure is fit for the
intended purpose. Further general guidance is provided on validation studies for analytical methods.
ASHA DHAKAL DIPSAR
VALIDATION OF ANALYTICAL PROCEDURE Q2(R2)
FINAL VERSION ADOPTED ON 1 NOVEMBER 2023

SCOPE
• This guideline applies to analytical procedures used for release and stability testing of commercial drug substances
and products, hereafter referred to as ‘products’.
• The guideline can also be applied to other analytical procedures used as part of the control strategy (ICH Q10
Pharmaceutical Quality System) following a risk-based approach.
• The scientific principles described in this guideline can be applied phase-appropriate to analytical procedures used
during clinical development.
• The guideline is directed to common uses of analytical procedures, such as assay, potency, purity, impurity
(quantitative or limit test), identity or other quantitative or qualitative measurements.
ASHA DHAKAL DIPSAR

GENERAL CONSIDERATION
• This guideline indicates the data that should be presented in a regulatory submission.
• Suitable data derived from development studies (see ICH Q14) can be used as part of validation data.
• When an established platform analytical procedure is used for a new purpose, validation testing can be
abbreviated, if scientifically justified. (EG. USING TABLET ASSAY METHOD FOR BLEND ASSAY)
• Approaches other than those outlined in this guideline may be applicable and acceptable with appropriate
science-based justification.
• The applicant is responsible for designing the validation studies and protocol most suitable for their
product.
• The protocol should contain information about the intended purpose of the analytical procedure, the
performance characteristics to be validated and the associated criteria.
ASHA DHAKAL DIPSAR

GENERAL CONSIDERATION
• The experimental design of the validation study should reflect the number of replicates used in routine analysis to
generate a reportable result.
• If justified, it may be acceptable to perform some validation tests using a different number of replicates or to adjust
the number of replicates in the analytical procedure based on data generated during validation
• Reference materials, or other suitably characterized materials, with documented identity, purity, or any other
characteristics as necessary, should be used in the validation study.
• As described in ICH Q14, the system suitability test (SST) is an integral part of analytical procedures and is generally
established during development as a regular performance check.
• Robustness is typically evaluated as part of development before executing the analytical procedure validation study
(ICH Q14).
ASHA DHAKAL DIPSAR

ASHA DHAKAL DIPSAR
Analytical Procedure Validation Study

- signifies that this test is not normally conducted
+ signifies that this test is normally conducted
† in some complex cases DL may also be evaluated
QL, DL: quantitation limit, detection limit
(1) other quantitative measurements can follow the scheme for impurity if the range limit is close to the
DL/QL; other quantitative measurements can follow the scheme for assay (content or potency) if the
range limit is not close to the DL/QL
(2) some performance characteristics can be substituted with technology-inherent justification in the
case of certain analytical procedures for physicochemical properties
(3) lack of specificity of one analytical procedure should be compensated by one or more other
supporting analytical procedures unless appropriately justified (assay by potentiometry 99% and RS by
HPLC result in 1%)
(4) alternatively, a combined approach can be used to evaluate accuracy and precision. {single test eg.
Precision triplicate preparation at 3 concentration (9) and Accuracy triplicate preparation at 3 conc. (9)}
(5) where reproducibility has been performed and intermediate precision can be derived from the
reproducibility data set, an independent study for intermediate precision is not required.
ASHA DHAKAL DIPSAR

Analytical method validation it is helpful for you all

More Related Content

Similar to Analytical method validation it is helpful for you all (20)

Recently uploaded (20)

Analytical method validation it is helpful for you all