Stability testing of active pharmaceutical ingredients and finished pharmaceutical products

Introduction and background:

The guidance on Stability testing of active pharmaceutical ingredients and finished pharmaceutical products was published as Annex 2 in the World Health Organization (WHO) Technical Report Series, No. 953, 2009 (1).

The aim of these regulatory guidelines is to outline the core stability data package required for registration of active pharmaceutical ingredients (APIs) and finished pharmaceutical products (FPPs), replacing the previous WHO guidelines in this area. The guidelines cross-refer to the series of related documents published by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) (2) and other WHO guidelines.

It was recommended that at the time of their publication these guidelines should also be applied to products that are already being marketed, making allowance for an appropriate transition period, for example, they could become applicable upon re-registration or upon re-evaluation.

The 2009 guidance not only followed the usual consultation process, but it was also the result of numerous discussions with the various regulatory forums, including ICH. As a result, the ICH parties withdrew one of their guidance texts (Q1F) and published the following text on their website:

“Explanatory Note on the Withdrawal of ICH Q1F for the ICH Website:

ICH Q1 F Stability Data Package for Registration Applications in Climatic Zones III and IV defined storage conditions for stability testing in countries located in Climatic Zones III (hot and dry) and IV (hot and humid), i.e. countries not located in the ICH regions and not covered by ICH Q1 A (R2) Stability Testing for New Drug Substances and Drug Products. ICH Q1 F described harmonised global stability testing requirements in order to facilitate access to medicines by reducing the number of different storage conditions. In the course of the discussions which led to the development of the guideline, WHO conducted a survey amongst their member states to find consensus on 30 °C/65% [relative humidity] RH as the long term storage conditions for hot and humid regions. As no significant objections were raised in this survey, 30 °C/65% RH was defined as the long-term storage condition for Climatic Zone III/IV countries in ICH Q1F. The document was adopted by the ICH Steering Committee in February 2003 and subsequently implemented in the ICH regions.

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Table of Contents

1. Introduction

1.1 Objectives of these guidelines

1.2 Scope of these guidelines

1.3 General principles

2. Guidelines

2.1 Active pharmaceutical ingredient

2.1.1 General

2.1.2 Stress testing

2.1.3 Selection of batches

2.1.4 Container-closure system