Climatic Zones for Stability Studies

Stability study is an important part of pharmaceutical product quality. For safety, efficacy and quality of pharmaceutical products, environmental conditions are the most significant factor that influence drug stability because product is stored, transported and used in these conditions. Environmental conditions are different and different reasons of the world. The world health organization (WHO) and ICH have classified the world into different climatic zones according to their climatic conditions.

What Are Climatic Zones?

Climatic zones are the regions of the world categorized according to their average annual temperature and humidity because temperature and humidity can significantly impact the degradation rate of active pharmaceutical ingredients and finished products. Climatic zones help to identify the testing conditions across various regions in the world.

Classification of Climatic Zones

In initial stage, WHO classified the world into four main climatic zones based on their mean kinetic temperature and relative humidity. Later further divisions are done to accommodate diverse environmental condition in some countries. Following are 5 calamitic zones suggested by WHO and ICH.

Climatic Zone	Type of Climate	Long-term Testing Conditions
Zone I	Temperate	21°C ± 2°C / 45% RH ± 5%
Zone II	Subtropical and Mediterranean	25°C ± 2°C / 60% RH ± 5%
Zone III	Hot and Dry	30°C ± 2°C / 35% RH ± 5%
Zone IVa	Hot and Humid	30°C ± 2°C / 65% RH ± 5%
Zone IVb	Hot and Very Humid	30°C ± 2°C / 75% RH ± 5%

Understanding Each Climatic Zone

Zone I – Temperate Climate

Template climatic zone has regions such as Northern Europe, Canada and northern parts of United States. These areas have mild temperatures and moderate humidity. Stability testing under Zone I conditions is applied to the products stored in cool environments.

Zone II – Subtropical and Mediterranean

Countries in Southern Europe, parts of Japan and the central United States are considered in Zone II. Products tested under these conditions should be stable at moderately warm and humid environmental conditions.

Zone III – Hot and Dry

Regions of the world like Middle East, parts of Africa and some area of India belong to this climatic category. In these environmental conditions, high temperature and low humidity can affect volatile components, coatings and packing materials of pharmaceutical products. Stability studies under Zone III ensure product robustness against heat stress.

Zone IVa – Hot and Humid

Countries like Indonesia, Thailand and southern India fall into this climatic zone. These areas have high humidity that can lead to moisture absorption by the product and resulting in microbial growth. Testing under 30 °C and 65% humidity fulfills the conditions of these areas.

Zone IVb – Hot and Very Humid

This zone is introduced later to reflect tropical regions such as Singapore Malaysia and Philippines. This zone has most challenging conditions for stability. With 75% RH studies ensure that product remains stable in extreme humidity.

Related: Significant Change in Pharmaceutical Stability Testing

Importance of Climatic Zones in Stability Studies

1. Regulatory Compliance

Different regulatory agencies require stability study based on climatic zones relevant to their intended in market. For example, if a product is intended to global distribution that must be tested under multiple climatic zones as per ICH Q1A R2 and WHO stability guidelines.

2. Product Shelf Life Determination

By stability testing, manufacturer can understand the behavior of product on the basis of temperature and humidity conditions and they can assign accurate shelf life and storage condition on the level of the product.

3. Packaging Selection

The packaging material of the product is decided on the basis of climatic conditions because climate affects product in packaging too. Stability studies help to determine whether the blister pack, bottle or foil packaging can effectively protect the drug from environmental conditions during storage and transport.

4. Ensuring Global Quality.

Pharmaceutical companies send their product in international markets in different climatic zones. Stability testing across multiple climatic zones ensures product consistency and compliance across different countries and environmental conditions.

ICH Guidelines on Stability Studies

ICH Q1 (R2) guideline provides the stability testing requirements for new drug substances and products. It specifies long term, intermediate and accelerated testing conditions based on different climatic zones.

Key Testing Conditions as per ICH Q1A (R2):

Long Term Stability Testing Conditions

Climatic Zone	Temperature	Humidity	Minimum Duration
Zone I	21ºC ± 2ºC	45% RH ± 5% RH	12 Months
Zone II	25ºC ± 2ºC	60% RH ± 5% RH	12 Months
Zone III	30ºC ± 2ºC	35% RH ± 5% RH	12 Months
Zone IVa	30ºC ± 2ºC	65% RH ± 5% RH	12 Months
Zone IVb	30ºC ± 2ºC	75% RH ± 5% RH	12 Months
Refrigerated	5ºC ± 3ºC	No Humidity	12 Months
Frozen	-15ºC ± 5ºC	No Humidity	12 Months

Accelerated and Intermediate Stability Testing Conditions

Climatic Zone	Temperature	Humidity	Minimum Duration
Accelerated Ambient	40ºC ± 2ºC	75% RH ± 5% RH	6 Months
Accelerated Refrigerated	25ºC ± 2ºC	60% RH ± 5% RH	6 Months
Accelerated Frozen	5ºC ± 3ºC	No Humidity	6 Months
Intermediate	30ºC ± 2ºC	65% RH ± 5% RH	6 Months

Related: List of Current ICH Quality Guidelines
Update: The whole world is divided into 5 groups according to their climatic conditions. Following is the list of countries of different climatic zones for stability studies.

Classification of Countries According to Climate Zones

Country	Climatic Zones	Assigned To Zone
Afghanistan	I, II	II
Algeria	II, III	II
Angola	II, IV	II
Argentina	II	II
Armenia	I, II	II
Australia	I, II, III, IVa	II
Azerbaijan	I, II	II
Bahrain	IVa	IVa
Bangladesh	IVa	IVa
Barbados	IVb	IVb
Belize	IVa	IVa
Benin	IVa	IVa
Bolivia	I, II, IVb	IVb
Botswana	III	III
Brazil	II, IVb	IVb
Bulgaria	I, II	II
Burkina Faso	IVa	IVa
Burundi	IVa	IVa
Cameroon	IVb	IVb
Canada	I	I
Canary Islands	II	II
Central African  Republic	IVb	IVb
Chad	III, IVa	III
Chile	I, II	II
China	I, II, IVa	II
Columbia	IVb	IVb
Congo	II, IVa	IVa
Costa	IVa	IVa
Cuba	IVb	IVb
Dominican Republic	IVa	IVa
Dutch Antilles	IVa	IVa
Ecuador	I, II, IVa	IVa
Egypt	II, III	II
El Salvador	IVa	IVa
Ethiopia	II, IVa	IVa
Fiji	IVa	IVa
France	I, II	II
Gabon	IVa	IVa
Gambia	IVa	IVa
Georgia	I, II	II
Germany	I	I
Ghana	IVb	IVb
Greece	II, IVa	II
Guatemala	IVa	IVa
Guyana	IVb	IVb
Guinca	IVa	IVa
Haiti	IVa	IVa
Honduras	II, IVa	IVa
Hong Kong	IVa	IVa
India	III, IVa	IVa
Indonesia	IVb	IVb
Iran	I, II, IVa	II
Iraq	II, III, IVa	III
Israel	II, III	II
Italy	I, II	II
Ivory Coast	IVa	IVa
Jamaica	IVa	IVa
Japan	I, II, IVa	II
Jordan	II, III	III
Kampuchea	IVa	IVa
Kazakstan	I, II	II
Kenya	II, IVa	IVa
Kirghizia	I, II	II
Korea	I, II	II
Kuwait	IVa	IVa
Laos	IVb	IVb
Lebannon	II	II
Liberia	IVa	IVa
Libya	II, III	II
Madagascar	II, IVa	IVa
Malawi	II, IVa	IVa
Malaysia	II, IVb	IVb
Maldive Islands	IVa	IVa
Mali	III, IVa	IVa
Marshall Islands	IVa	IVa
Mauretania	IVa	IVa
Mexico	II, IVa	II
Morocco	II, III	II
Mozambique	IVb	IVb
Myanmar (Burma)	IVb	IVb
Namibia	II	II
Nepal	II	II
New Caledonia	II, IVa	IVa
New Zealand	I, II	II
Nicaragua	IVa	IVa
Niger	III, IVa	IVa
Nigeria	IVb	IVb
Oman	IVa	IVa
Pakistan	II, III, IVa	IVa
Panama	IVb	IVb
Papua-New Guinea	IVa	IVa
Paraguay	IVa	IVa
Peru	IVb	IVb
Philippines	IVb	IVb
Portugal	I, II	II
Puerto Rico	IVa	IVa
Qatar	IVa	IVa
Remaining Southern	II	II
European Nations
Rumania	I	I
Russia	I	I
Rwanda	II	II
Samoa	IVa	IVa
Saudi Arabia	II, III, IVa	IVa
Senegal	IVa	IVa
Sierra Leone	IVb	IVb
Singapore	IVb	IVb
Society Islands	IVa	IVa
Somalia	IVa	IVa
South Africa	II	II
Spain	I, II	II
Sri Lanka	IVa	IVa
Sudan	III, IV	IV
Syria	II	II
Tadzhikistan	I, II	II
Taiwan	IV	IV
Tanzania	II, IVb	IVb
Thailand	IVb	IVb
Togo	IVb	IVb
Tonga	II, IVa	IVa
Tunisia	II	II
Turkey	I, II	II
Turkmenia	I, II	II
Uganda	IVa	IVa
United Arab  Emirates	IVa	IVa
Uruguay	II	II
United States	I, II, III, IVa	II
Uzbekistan	I, II	II
Venezuela	II, IVb	IVb
Vietnam	IVb	IVb
Yemen	II, IVa	IVa
Zaire	II, IVa	IVa
Zambia	II	II
Zimbabwe	IVb	IVb

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