Regulatory · Stability

What stability data does a medicine need for hot and humid markets?

Long-term data at the condition the target region applies. WHO Technical Report Series No. 1010, Annex 10, lists 25 °C/60% RH, 30 °C/65% RH and 30 °C/75% RH, and several hot, humid zone IV countries use up to 30 °C/75% RH. Data from zone II conditions alone supports only "Do not store above 25 °C" there.

Why does the climatic zone matter to a stability dossier?

Because your shelf life and label storage statement are only as good as the conditions your stability studies were run at. Data from a temperate market does not necessarily hold for a hotter, more humid one. The World Health Organization sets out the framework in WHO Technical Report Series No. 1010, Annex 10, Stability testing of active pharmaceutical ingredients and finished pharmaceutical products, published in the Fifty-second report of the WHO Expert Committee on Specifications for Pharmaceutical Preparations (2018).¹

That guideline refers to climatic zones. Zone III is described as hot and dry and zone IV as hot and humid, and the guideline refers separately to zone IVa and zone IVb long-term conditions.¹

What happened to ICH Q1F?

It was withdrawn. The explanatory note reproduced in Annex 10 says ICH Q1F, Stability Data Package for Registration Applications in Climatic Zones III and IV, defined storage conditions for countries outside the ICH regions and not covered by ICH Q1A(R2). WHO surveyed its member states, found no significant objections to 30 °C/65% RH, and ICH Q1F set that as the long-term condition for zones III and IV. The ICH Steering Committee adopted it in February 2003.¹

The note continues that some zone IV countries later wanted a larger safety margin than ICH Q1F foresaw, and several countries and regions revised their own guidelines, defining up to 30 °C/75% RH as the long-term condition for hot and humid regions. Because of that divergence, the ICH Steering Committee withdrew ICH Q1F and left the definition of storage conditions in zones III and IV to the respective regions and WHO.¹

Which long-term conditions does WHO list?

Three. Section 2.1.7.1 of Annex 10, the general case, gives the following storage conditions and the minimum period the data should cover at submission:¹

"Long-term" is therefore not one condition, and which of the three your data covers decides which markets it supports.

Do all hot and humid countries apply the same condition?

No. WHO Technical Report Series No. 953, Annex 2, Appendix 1, Stability conditions for WHO Member States by region, update March 2021, records a long-term condition for each member state, grouped by WHO region.² Within the South-East Asia region alone, the table lists India at 30 °C/70% RH, Indonesia, Myanmar, Nepal and Thailand at 30 °C/75% RH, and Bhutan at 30 °C/65% RH.²

Read the footnotes before relying on any row. They say the information came from different routes: regional harmonisation groups and official communications from national regulatory authorities, the 13th International Conference of Drug Regulatory Authorities (ICDRA) in 2008, or the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA).² Each entry carries a footnote marker showing which route it came from. Treat it as a planning aid, not as the current requirement of the authority you file with.

What label statement does zone II data support in zone IV?

"Do not store above 25 °C". Appendix 3 of Annex 10 says label storage statements must be read in the context of both the region where the stability studies were done and the region where the product will be distributed.¹

Its example is a product approved in a zone II region and tested at accelerated and zone II long-term conditions, which may carry "Store between 15 and 30 °C" under the convention of some zone II regions. A product with that statement, received in a zone IV country, would be expected to have demonstrated stability at zone IVa or IVb long-term conditions. Where it was demonstrated only at zone II long-term conditions, WHO says the appropriate statement for distribution in zone IV would be "Do not store above 25 °C".¹

So the same product can need a different storage statement depending on where it is sold. Shelf life also drives what reaches the buyer; see remaining shelf life at shipment. For the handover points where temperature control is most at risk, see cold chain at the border.

How does this apply to products for the Republic of Yemen?

Start from the international framework above: know which long-term condition your data covers, and match the label storage statement to a hot and humid destination. What the national authority in the Republic of Yemen currently asks for on stability is confirmed case by case, for the specific product, and is worth raising before a dossier is assembled. For the wider picture of the market, see entering the Yemen market.