Appendix 1: Long-term stability testing conditions as identified by WHO member states.(WHO EXPERT COMMITTEE ON SPECIFICATIONS FOR PHARMACEUTICAL PREPARATIONS)(World Health Organization)

In order to be able to reduce the amount of stability testing required, the number of different long-term testing conditions must be reduced to a sufficient extent. This approach was proposed by Paul Schumacher in 1972 (1) and by Wolfgang Grimm in 1986 (2), and in 1998 (3) when they defined four different long-term testing conditions, which match with the climatic conditions of the target markets categorized in just four different climatic zones. This concept is described in regulatory guidelines and pharmacopoeias and has become an established standard in developing finished pharmaceutical products (FPPs).

At the fortieth meeting of the WHO Expert Committee on Specifications for Pharmaceutical Preparations held in Geneva in October 2005 (4), it was recommended to split the current Climatic Zone IV (hot and humid) into two zones: Climatic Zone IVA--for which 30 [degrees]C/65% RH will remain the standard long-term testing condition--and Climatic Zone IVB for which, if justified, 30[degrees]C/75% RH will become the long-term testing condition. The criteria and long-term testing conditions proposed are listed in Table 1.

Additional testing conditions, i.e. accelerated and--if applicable--intermediate conditions have to be used as described in these guidelines.

Selection of the conditions for stability testing is based on a risk analysis. Testing at a more severe long-term condition can be an alternative to storage testing at 25[degrees]C/60% RH or 30[degrees]C/65% RH.

The evaluation of the climatic conditions by each WHO Member State resulted in the recommended storage condition for long-term stability studies shown in Table 2 (in some of the countries listed, more extreme conditions are also accepted). The list is grouped by WHO regional offices.

References

[1.] Schumacher P. 1972, Uber eine fur die Haltbarkeit von Arzneimitteln massgebliche Klimaeinteilung [The impact of climate classification on the stability of medicines]. Die Pharmazeutische Industrie, 34:481-483.

[2.] Grimm W. 1986, Storage conditions for stability testing (Part 2). Drugs Made in Germany, 29:39-47.

[3.] Grimm W. 1998. Extension of the International Conference on Harmonisation Tripartite Guidelines for stability testing of new drug substances and products to countries of Climatic Zones III and IV. Drug Development and Industrial Pharmacy, 24:313-325.

[4.] Guidelines for stability testing of pharmaceutical products containing well established drug substances in conventional dosage forms. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-fourth report. Geneva, World Health Organization, 1996, Annex 5 (WHO Technical Report Series, No. 863).

These guidelines were revised at the thirty-seventh and fortieth meetings of the WHO Expert Committee on Specifications for Pharmaceutical Preparations. In: WHO Expert Committee on Specifications for Pharmaceutical Preparations. Thirty-seventh report. Geneva, World Health Organization, 2003 (WHO Technical Report Series, No. 908), p. 13 and WHO Expert Committee on Specifications for Pharmaceutical Preparations. Fortieth report. Geneva, World Health Organization, 2006 (WHO Technical Report Series, No. …