guideline on stability testing-emea

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The European Agency for the Evaluation of Medicinal Products

Evaluation of Medicines for Human Use

London, 17 December 2003

CPMP/QWP/122/02, rev 1

COMMITTEE FOR PROPRIETARY MEDICINAL PRODUCTS

(CPMP)

GUIDELINE ON STABILITY TESTING:

STABILITY TESTING OF EXISTING ACTIVE SUBSTANCES

AND RELATED FINISHED PRODUCTS

DISCUSSION IN THE QUALITY WORKING PARTY (QWP) TRANSMISSION TO THE CPMP

ADOPTION OF THE REVISION BY THE CPMP

DATE FOR COMING INTO OPERATION October 2003 December 2003 December 2003 March 2004

This guideline supersedes it’s earlier version CPMP/QWP/122/02 corr. and CPMP/QWP/122/02, which came into operation in June 2003. CPMP/QWP/122/02 has replaced CPMP/QWP/556/96.

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The guideline CPMP/QWP/122/02, corr. was revised to be brought in line with the requirements of the Note for Guidance on Evaluation of Stability Data (CPMP/ICH/420/02) and the Note for Guidance on Stability Testing of New Drug Substances and Products (CPMP/ICH/2736/99 corr). These changes are:

1. The possibilities to extend the retest period/shelf-life beyond the period of time

covered by real-time data by extrapolation are described in more in Annex II with reference to the respective note for guidance

2. 30° C ± 2° C/35 % RH ± 5% RH has been added as a suitable alternative long-term

storage condition to 25° C ± 2° C/40 % RH ± 5% RH in section 2.2.7.3 Finished products packaged in semi-permeable containers.

3. The statement on implementation of the change in intermediate storage conditions in

the Introductory Note to the Revision of December 2002 has been clarified.

The guideline CPMP/QWP/122/02 was corrected in the paragraph 2.1.7 to give consistent guidance on the duration of long-term stability testing.

The guideline CPMP/QWP/556/96 was given a new number CPMP/QWP/122/02 and revised to be brought in line with the requirements of the Note for Guidance on Stability Data Package for Registration in Climatic Zones III and IV (CPMP/ICH/421/02), the Note for Guidance on Stability Testing of New Drug Substances and Products (CPMP/ICH/2736/99 corr) and the Common Technical Document (CPMP/ICH/ 2287/99).

As a consequence, the relative humidity at storage under intermediate conditions, i.e. presently 30 °C ± 2 °C/60 % RH ± 5% RH, will be changed to 30 °C ± 2 °C/65 % RH ± 5% RH. The implementation time of this change will be defined in line with the implementation time for the Note for Guidance on Stability testing of New Drug Substances and Products (CPMP/ICH/2736/99 corr).

Within the EU, data from studies generated using the new conditions are accepted immediately. Furthermore, data from studies where the relative humidity has been changed from 60 % RH to 65 % RH during the study to meet the new requirements will also be accepted under the condition that the respective storage conditions and the date of the change are clearly documented and stated in the application file.

It is recommended that all marketing authorisation applications contain data from complete studies at the intermediate storage condition 30 °C ± 2 °C/65 % RH ± 5% RH, if applicable, by February 2006.

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STABILITY TESTING OF EXISTING ACTIVE SUBSTANCES

AND RELATED FINISHED PRODUCTS

1. INTRODUCTION

1.1 Objectives of the Guideline

The following guideline is an extension of the Note for Guidance on Stability testing of New Drug Substances and Products (CPMP/ICH/2736/99 corr) and sets out the stability testing requirements for existing active substances and related finished products. For the purposes of this guideline, an existing active substance is one that has been authorised previously through a finished product within the European Community1

This guideline is applicable to chemical active substances and related finished products, herbal drugs, herbal drug preparations and related herbal medicinal products and not to radiopharmaceuticals, biologicals and products derived by biotechnology.

The guideline seeks to exemplify the core stability data package required for such active substances and finished products, but leaves sufficient flexibility to encompass the variety of different practical situations that may be encountered due to specific scientific considerations and characteristics of the materials being evaluated. Alternative approaches can be used when there are scientifically justifiable reasons.

1.2 Scope of the Guideline

The guideline addresses the information to be submitted in registration applications for existing active substances and related finished products.

For herbal drugs, herbal drug preparations and herbal medicinal products, reference is made to the stability section of the Note for Guidance on Quality of Herbal Medicinal Products (EMEA/CPMP/2819/00).

1.3 General Principles

The purpose of stability testing is to provide evidence on how the quality of an active substance or finished product varies with time under the influence of a variety of environmental factors such as temperature, humidity, and light, and to establish a re-test period for the active substance or a shelf life for the finished product and recommended storage conditions.

The choice of test conditions defined in this guideline refers to the Note for Guidance on Stability testing of New Drug Substances and Products (CPMP/ICH/2736/99 corr).

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