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.
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.
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.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.
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 Eastern European Nations
|
I
|
I
|
Remaining Northern and Central European Nations
|
I
|
I
|
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
|
The above data given basic clarity, Thank you sir.
ReplyDeleteOn what basis shelf life of the drug and drug products are desited.
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ReplyDeleteGood information sir
ReplyDeleteTHANK YOU FOR THE INFORMATION, IT'S SO USEFUL
ReplyDeleteMinimum Zone ivb stability batches required for Malaysia registration.2 or 3
ReplyDeleteWhat is the source for the assigned climatic zone in the table? I am mostly interested of countries with several climatic zones but assigned II e.g. China and Australia. What does the "assigned" climatic zone mean and when is it used? To my understanding its up to the different authorities but both China and Australia usually want more data than for Climate zone II.
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