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Stability testing of active pharmaceutical ingredients and finished pharmaceutical products
1. Introduction:
1.1 Objectives of these guidelines:
These guidelines seek to exemplify 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 (1,2). However, alternative approaches can be used when they are scientifically justified. Further guidance can be found in International Conference on Harmonisation (ICH) guidelines (3) and in the WHO guidelines on the active pharmaceutical ingredient master file procedure (4).
It is recommended that these guidelines should also be applied to products that are already being marketed, with allowance for an appropriate transition period, e.g. upon re-registration or upon re evaluation.
1.2 Scope of these guidelines:
These guidelines apply to new and existing APIs and address information to be submitted in original and subsequent applications for marketing authorization of their related FPP for human use. These guidelines are not applicable to stability testing for biologicals (for details on vaccines please see WHO guidelines for stability evaluation of vaccines (5)).
1.3 General principles:
The purpose of stability testing is to provide evidence of how the quality of an API or FPP varies with time under the influence of a variety of environmental factors such as temperature, humidity and light. The stability programme also includes the study of product-related factors that influence its quality, for example, interaction of API with excipients, container closure systems and packaging materials. In fixed-dose combination FPPs (FDCs) the interaction between two or more APIs also has to be considered.
As a result of stability testing a re-test period for the API (in exceptional cases, e.g. for unstable APIs, a shelf-life is given) or a shelf-life for the FPP can be established and storage conditions can be recommended.
Various analyses have been done to identify suitable testing conditions for WHO Member States based
on climatic data and are published in the literature (6–9) on the basis of which each Member State can
make its decision on long-term (real-time) stability testing conditions. Those Member States that have notified WHO of the long-term stability testing conditions they require when requesting a marketing authorization are listed in Appendix 1.
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WHO TRS (Technical Report Series) 953, 2009 Annex 2:
