How analytical method validation differs between ICH and USP. Includes basis definition and difference.

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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