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ICH

This document provides guidance on evaluating stability data to propose a retest period or shelf life for drug substances and products. [1] It describes how stability data from studies conducted according to ICH Q1AR2 should be presented and evaluated. [2] A decision tree in Appendix A outlines an approach for using stability data to determine an appropriate retest period or shelf life through evaluation of data from accelerated, intermediate, and long-term studies, including the potential for extrapolation beyond the periods covered by long-term data. [3] Appendix B provides examples of statistical analysis that can be used to evaluate certain quantitative attributes from stability studies.

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146 views4 pages

ICH

This document provides guidance on evaluating stability data to propose a retest period or shelf life for drug substances and products. [1] It describes how stability data from studies conducted according to ICH Q1AR2 should be presented and evaluated. [2] A decision tree in Appendix A outlines an approach for using stability data to determine an appropriate retest period or shelf life through evaluation of data from accelerated, intermediate, and long-term studies, including the potential for extrapolation beyond the periods covered by long-term data. [3] Appendix B provides examples of statistical analysis that can be used to evaluate certain quantitative attributes from stability studies.

Uploaded by

Faiza Dinda
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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1.

ICH Q1E Guideline

Evaluation of Stability Data

Step 4 in the ICH process

Comments for its application

ICH QIE C 55
1. Introduction

1.1 Objectives of the Guideline

The guideline provides recommendation on how to use stability data generated


according Q1AR2
It is described:
• How to propose a retest period for drug substances and a shelf life for drug
products in the registration application,
• When and how a extrapolation beyond available data can be considered.

2. Guidelines

2.1 General Principals

• A systematic approach should be adopted in the presentation and evaluation of


the stability information.
• The stability information should include as appropriate the results from the
physical, chemical, biological and microbiological tests.
Mass balance should be considered.
• The basic concepts of stability evaluation are the same for single-versus multi-
factor designs and for full versus reduced design studies.
• Data from formal stability studies and supporting data should be evaluated to
determine the critical quality attributes.
• Each attribute should be assessed separately and an overall assessment should
be evaluated to propose a retest period or a shelf life.
• In the appendix A a decision tree outlines a stepwise approach to stability data
evaluation and when and how much extrapolation can be considered for a
proposed retest period or shelf life.
• Appendix B provides information on
- How to analyze long-term data for appropriate quantitative test attributes from
a study with a multi-factor, full or reduced design
- How to use regression analysis
- Examples of statistical procedure to determine poolability of data from different
batches
• Certain quantitative chemical attributes (assay, degradation products,
preservative content) can follow zero order kinetics, therefore evaluation
according appendix B
• Qualitative attributes are not amenable to statistical analysis.
• Statistical analysis is not intended to imply when it can be justified to be
unnecessary.

2.2 Data presentation

Data of all attributes should be presented in an appropriate format:


• tabular
• graphical

ICH QIE C 56
• narrative
If a statistical analysis is performed, the procedure and the assumption underlying the
model should be stated and justified.

2.3 Extrapolation

Extrapolation is the practice of using dataset to infer information about future data.
• Extrapolation to extend retest period or shelf life beyond period covered by long-
term data an be proposed in the application
- Particularly if no significant change is observed at the accelerated condition.
• An extrapolation assumes that the same change pattern will continue to apply
beyond the period covered by long-term data.
• A retest period or shelf life granted on the basis of extrapolation should always be
verified by additional long term stability data as soon as these data become
available.

2.4 Data Evaluation for Retest Period of Shelf Life Estimation for Drug
Substances or Products intended for Room Temperature Storage.

• Stability data for each attribute should be assessed sequentially


• Assessment starts with
- With any significant change at accelerated condition or
- or intermediate condition and
- and progress through the trends and variability of the long term data.
• See decision tree in appendix A

Data of Stability Testing Requirement Extrapolation


Accelerated Intermediate Long-term Beyond covered
by long term
data
Drug substances and products intended for room temperature storage
Little or no change, - Little or no change, No statistical ≤ 12 months
little or no variability little or no variability analysis required
Change over time Change over time • Long-term • ≤ 12 months
and or variability and or variability data amenable
to statistical
analysis,
relevant suppor-
ting data
• Not ame- • ≤ 6 months
nable to statisti-
cal analysis but
relevant suppor-
tive data
Significant change No significant Change over time • Long-term • ≤ 6 months
within 6 months change and or variability data amenable
to statistical
analysis,
relevant suppor-
ting data

ICH QIE C 57
• Not ame- • ≤ 3 months
nable to statisti-
cal analysis
but relevant
supportive data
Significant change Significant No extrapolation
within 6 months change
Drug substances and drug products intended for storage below room temperature
No significant Little or no change, ≤ 6 months
change at 25°C little or no variability
No significant Change over time • Long-term • ≤ 6 months
change at 25°C and or variability data amenable
to statistical
analysis,
relevant suppor-
ting data
• Not ame- • ≤ 3 months
nable to statisti-
cal analysis
but relevant
supportive data
Significant change No extrapolation
within 6 months
Significant change No extrapolation
within 3 months Address short time
excursion of label
storage
Drug substances or products intended for storage in a freezer
No extrapolation
Address short time
excursion by
storing at 5°C

Appendix B: Examples of Statistical Approaches to Stability Data Analysis

• Linear regression analysis


• Poolability tests
• Statistical modeling

These procedures an be used in the analysis of stability data that are amenable to
statistical analysis for a quantitative attribute for which there is a proposed criterion.
Significant change
within 6 months

ICH QIE C 58

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