Stability Study of Pharmaceutical Products (Basic Knowledge)

Climatic zones 

The four zones in the world that are distinguished by their characteristic prevalent annual climatic conditions.

• Zone I - Temperate zone: 21̊C, 45%  
• Zone II - Subtropical zone: 25̊C, 60%
• Zone III - Hot-dry zone: 30̊C, 35%
• Zone IVa - Hot humid zone: 30̊C, 60%
• Zone IVb - Hot higher humid zone: 30̊C, 75%

Accelerated testing 

Studies designed to increase the rate of chemical degradation or physical change of a drug substance or drug product by using exaggerated storage conditions as part of the formal stability studies.

Stress testing

Stress testing of the drug substance can help identify the likely degradation products, which can in turn help establish the degradation pathways and the intrinsic stability of the molecule and validate the stability indicating power of the analytical procedures used.

Bracketing 

The design of a stability schedule such that only samples on the extremes of certain design factors, e.g., strength, package size, are tested at all time points as in a full design.

Matrixing 

The design of a stability schedule such that a selected subset of the total number of possible samples for all factor combinations is tested at a specified time point. At a subsequent time point, another subset of samples for all factor combinations is tested.

Re-test date 

The date after which samples of the drug substance should be examined to ensure that the material is still in compliance with the specification and thus suitable for use in the manufacture of a given drug product.

Storage condition & minimum time period covered by data at submission as per ICH guideline

• Long term*: 25°C ± 2°C/ 60% RH ± 5% RH  or  30°C ± 2°C/ 65% RH ± 5% RH (12 months) 
• Intermediate*: 30°C ± 2°C/ 65% RH ± 5% RH (6 months)
• Accelerated: 40°C ± 2°C/ 75% RH ± 5% RH (6 months) 

*If 30°C ± 2°C/65% RH ± 5% RH is the long-term condition, there is no intermediate condition. If long-term studies are conducted at 25°C ± 2°C/60% RH ± 5% RH and “significant change” occurs at any time during 6 months’ testing at the accelerated storage condition, additional testing at the intermediate storage condition should be conducted and evaluated against significant change criteria. “Significant change” for a drug substance is defined as failure to meet its specification.

Drug substances intended for storage in a refrigerator

• Long term: 5°C ± 3°C (12 months)
• Accelerated: 25°C ± 2°C/ 60% RH ± 5% RH (6 months) 

Drug substances intended for storage in a freezer

• Long term: - 20°C ± 5°C (12 months)

In-use-stability

The purpose of in-use stability testing is to establish - where applicable - a period of time during which a multidose product can be used whilst retaining quality within an accepted specification once the container is opened.

‘Significant change’ in stability study

In general, “significant change” for a finished pharmaceutical product is defined as: a 5% or more change in assay from its initial content of API(s), or failure to meet the acceptance criteria for potency when using biological or immunological procedures.