ICH/USFDA

VALIDATION PARAMETERSOF

ANALYTICAL METHOD

Kushal Shah, M.Pharm (Pharmaceutical Analysis)

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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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 apart of the method validation,whereas the USP deals it in asepárate chapter.

Robustness for the ICH is part ofprecision.

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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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Ability of an assay toelicit a direct andproportionalresponse to changesin analyteconcentration.

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Closeness of the test results obtained by the method to the true value.

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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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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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Definition: Ability reproduce data within the

predefined precision

Determination: SD, RSD interval

◦ Repeatability test at two different labs.

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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. 5/14/2017 10

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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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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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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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 beverified afterwards

- Described in Pharmacopoeias

System Suitability Test

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THANK YOU

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