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Q2B Validation of Analytical Procedures: Methodology

FinalCenter for Drug Evaluation and Research Center for Biologics Evaluation and Research05/19/1997
Validation of Analytical ProceduresSystem Suitability TestingRobustnessSpecificityLinearityAccuracyPrecisionRepeatabilityIntermediate PrecisionReproducibility

Description

This document is complementary to the ICH guidance entitled Text on Validation of Analytical Procedures (ICH Q2A), which presents a discussion of the characteristics that should be considered during the validation of analytical procedures. Its purpose is to provide some guidance and recommendations on how to consider the various validation characteristics for each analytical procedure. In some cases (for example, demonstration of specificity), the overall capabilities of a number of analytical procedures in combination may be investigated in order to ensure the quality of the drug substance or drug product. In addition, the document provides an indication of the data that should be presented in a new drug application.

Key Topics

Terms and concepts identified from this document

Scope & Applicability

Product Classes

2
Biological products

development program for drug and biological products

Biotechnological products

analytical procedures for biological and biotechnological products

Stakeholders

1
Applicant

Entity submitting development data and knowledge; Entity performing the work process for change

Regulatory Context

Regulatory Activities

1
New Drug Application

Rule does not apply to products marketed under an NDA

Document Types

3
Protocol

Defines the standard of veterinary practice and limits for anesthetic regimens

Chromatogram

Visual representation of impurity profiles in batches.

Marketing authorization dossier

reproducibility data are not part of this dossier

Attributes

9
Specificity

Ability to detect intended mechanism of action without interference; Performance characteristic to be validated

Linearity

Performance characteristic to be validated

Range

validation characteristic to provide a sound, overall knowledge of the capabilities

Accuracy

Performance characteristic assessed via linearity experiment

Precision

Closeness of agreement between a series of measurements from multiple samplings.; Performance characteristic measured by intermediate precision; Performance characteristic to be validated

Detection Limit

Analytical procedure validation characteristic

Quantitation Limit

Must be not more than the reporting threshold.

Robustness

Evaluation of robustness and parameter ranges of analytical procedures; Development of a robust multivariate analytical procedure includes scientifically justified sample selection; Capacity of an analytical procedure to meet performance criteria during normal use.; Assessed using retention time models; Performance characteristic to be validated

Signal-to-Noise Ratio

Used for estimating detection and quantitation limits

Technical Details

Substances

6
Drug substance

quantitative measurement of the major component(s) in the drug substance; changes in the synthesis of the drug substance

Analyte

Stability of the analyte in the studied matrix; Specific chemical moiety being measured in a biological matrix.

Drug product

assaying for the active or other selected component(s)

Reference materials

Suitably characterized materials used in validation studies

Excipients

Differences in excipients may affect product stability

Impurities

Components which may be expected to be present alongside the analyte.

Testing Methods

10
Statistical methods

sponsors should propose statistical methods that properly account for missing data

Gas-Chromatography

In the case of gas-chromatography, examples of typical variations are different columns and flow rate.

Liquid Chromatography

In the case of liquid chromatography, examples of typical variations are pH and mobile phase composition.

Visual Evaluation

Visual evaluation may be used for non-instrumental methods.

Signal-to-Noise Ratio

Image quality metric assessment

Calibration Curve

The slope S may be estimated from the calibration curve of the analyte.

Identification tests

intended to ensure the identity of an analyte in a sample

Assay

Part of stability testing parameters

Impurity Test

investigation of specificity should be conducted during the determination of impurities; discrimination established by spiking drug substance or drug product

Chromatographic procedures

For chromatographic procedures, which make up the majority of procedures used in tobacco chemistry

Processes

1
System Suitability Testing

integral part of many analytical procedures

Standards & References

External Standards

2
Pharmacopoeias

See Pharmacopoeias for additional information on system suitability test parameters.

Pharmacopoeial method

comparing test results to a second well-characterized procedure

Specifications

3
Detection Limit

Typical validation characteristics which should be considered; lowest amount of analyte in a sample which can be detected but not necessarily quantitated

Resolution Test

system suitability parameters (e.g., resolution test) is established

Quantitation Limit

Typical validation characteristics which should be considered; lowest amount of analyte in a sample which can be quantitatively determined

ICH References (4)

ICH Q2B

Validation of Analytical Procedures: Methodology

ICH Q2A

Text on Validation of Analytical Procedures

ICH Q3A

impurities in new drug substances; Referenced regarding impurities and polymorphism.

ICH Q3B

impurities in new drug products; Impurities in new drug products; Recommendations for genotoxicity studies and toxicological qualification; Impurities in New Drug Products; Qualification study(ies) as described in ICH Q3B

Related MFDS Guidelines

Korean regulatory guidelines covering similar topics

See Also (8)

Q2B Validation of Analytical Procedures: Methodology | Guideline Explorer | BioRegHub