Stability Studies and ICH guidelines

Stability study is conducted to determine the life (or shelf life) of the pharmaceutical product during which it retain its safety and efficacy, under appropriate storage conditions.

The stability of the product is usually tested against the following three environment variables.

• Temperature
• Humidity
• Light

To specify the range of temperature and humidity, ICH provide a division of zones. Each zone is assigned by a unique temperature and humidity, on which the stability of the product is determined. Following is the list of different zones with their associated environmental conditions.

 ICH guidelines demand the stability of the product to be tested at the following conditions.

1. Real time / Long term testing: Conditions that are specified in different climatic zones, for the whole stated shelf life of the product (minimum 12 months at the time of submission).
2. Accelerated testing: This study is conducted at 38 - 42 degree centigrade / 70 - 80% humidity for 6 months at the time of submission.
3. Intermediate testing: At 28 - 32 degree centigrade / 60 - 70% humidity for 12 months (minimum 6 months at the time of submission). This study is conducted if there is a "Significant Change" in the product during the accelerated testing. Moreover, this study ensures stability against temporary excursions in the storage conditions during shipment etc. If the temperature for the long term testing is 28 - 32 degree centigrade, there is no need to conduct the intermediate testing.  
4. Stress conditions: This study is actually a development strategy and is conducted at 10 degree centigrade increments over Accelerated conditions. 

For products to be stored in a refrigerator
The Long term stability study for the refrigerated products is conducted at 2 - 8 degree centigrade.
Accelerated studies are conducted at 23 - 27 degree centigrade, 55 - 65% humidity.

Photostability
Photostabilty is conducted on one batch of the product. Two options are available for the light sources.
Option 1: Any light source that produce an output similar to D65/ID65 emission standard.
Option 2: Expose the product separately to both of the following light sources.

• Near UV fluorescent lamp with a spectral distribution between 320 nm - 400 nm.  
• Cool white fluorescent lamp that produce an output similar to the specified criteria of ISO 10977(1993).

Batchs for The Stability Studies
ICH guidelines has stated that the stability study must be conducted on the Pilot scale batches. Where, a Pilot scale batch is 1/10th of the Commercial Batch.
For solid dosage forms (eg. capsules and tablets), the batch must not be less than 100,000 units.

Significant Change
A 5% change in the critical quality attributes of a product is considered a significant change according to the ICH guidelines.

Testing Frequency
The analysis is conducted at every 3rd month during the 1st year of the stability studies. In the 2nd year, the tests are performed every 6th month. If the study is supposed to be conducted for more than 2 years, the tests are performed annually after 2 years.

Bracketing and Matrixing
Bracketing
If there are more then one strengths of a drug product, ICH guidelines provide a lenience for conducting their stability studies. In such case, the study is conducted on the lowest and the highest strengths. The results of this study will be valid for all the strengths of that drug product.

Matrixing
As it has been mentioned that the stability study must be conducted on three pilot scale batches, there is no need to perform analysis on all the three batches at every testing interval. One or two batches can be skipped at each testing interval.