The document outlines the validation parameters for analytical methods as per FDA and ICH guidelines, highlighting specificity, linearity, accuracy, precision, limit of detection, and robustness. It distinguishes between validation concepts in ICH and USP, emphasizing the necessity of methods being suitable for intended use. Key terms and definitions related to these parameters are provided, along with specific criteria for assay accuracy and precision in various tests.

1. ICH/USFDA
VALIDATION PARAMETERS
OF
ANALYTICAL METHOD
Kushal Shah,
M.Pharm (Pharmaceutical Analysis)

2.  FDA-guidelines:
◦ Validation is 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
 “Methods validation is the process of
demonstrating that analytical procedures are
suitable for their intended use”
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3.  USP
 Specificity
 Linearity and Range
 Accuracy
 Precision
 Limit of Detection
 Limit of Quantitation
 Ruggedness
 Robustness
 ICH
 Specificity
 Linearity
 Range
 Accuracy
 Precision
◦ Repeatability
◦ Intermediate Precision
◦ Reproducibility
 Limit of Detection
 Limit of Quantitation
 ICH takes system suitability as a
part of the method validation,
whereas the USP deals it in a
sepárate chapter.
 Robustness for the ICH is part of
precision.
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4.  Ability of an analytical method to measure the analyte free from interference
due to other components.
 Specificity
 Ability to assess unequivocally the analyte in the presence of of components which
may be expected to be present (impurities,degradants, matrix)
 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
- the sample without added substances
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5.  Ability of an assay to
elicit a direct and
proportional
response to changes
in analyte
concentration.
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6.  Closeness of the test
results obtained by
the method to the
true value.
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7.  The closeness of
agreement (degree of
scatter) between a
series of
measurements
obtained from multiple
samplings of the same
homogeneous sample.
 Should be investigated
using homogeneous,
authentic samples.
◦ Precision…
Considered at 3 Levels
◦ Repeatability
◦ Intermediate Precision
◦ Reproducibility
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8.  Precision under the same operating conditions
over a short interval of time.
 Method
- 9 determinations covering the specified
range
- or: 6 determinations at 100% of the test
concentration
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9.  Definition: Ability reproduce data within the
predefined precision
 Determination: SD, RSD interval
◦ Repeatability test at two different labs.
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10.  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.
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11.  Definition: Capacity to remain unaffected by
small but deliberate variations in method
parameters
 Determination: Comparison results under
differing conditions with precision under normal
conditions
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12.  Degree of reproducibility of test results under a
variety of conditions
 Different Laboratories
 Different Analysts
 Different Instruments
 Different Reagents
 Different Days
 Etc.
 Expressed as %RSD
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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
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14. Definition
◦ Set of parameters and criteria there off to ensure
the system is working properly.
 Aspects
- Dependent on type of test
- For chromatographic methods: tailing factor, rel.
retention times, resolution factor, rel. st.
deviation, number of theoretical plates
- To be checked before start of run and to be
verified afterwards
- Described in Pharmacopoeias
System Suitability Test
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15.  THANK YOU
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