These studies are designed to complement pre-formulation and routine ICH Q1A Registration Batch Stability Studies.

ICHQ1A states that the data from accelerated stability studies can be used to evaluate the effect of short-term excursions higher or lower than label storage conditions that may occur during the shipping of the drug product.

Thermal Cycling

The withdrawn FDA Draft Guidance for stability testing recommended thermal cycling to examine the effects of temperature variation on drug products.  Packaged drug products are cycled through the temperature conditions that simulate the changes likely to be encountered once the drug product is in distribution. The product is cycled from high to low temperature for several days and the exposure is repeated several times.

Monographs & Labels

The USP recommends that if no specific storage directions or limitations are provided in the individual monographs but the label provides storage temperature on the basis stability data, then the product storage label applies.  Articles for which storage at controlled room temperature is indicated may be alternately stored and distributed in a cool place, unless otherwise specified in the individual monograph or on the label. Products having no specific storage conditions or limitations in the monograph should be stored and distributed with protection from moisture, freezing and excessive heat.

In general, regulatory agencies expect the manufacturer of a drug product to establish the product’s stability profile. Stability programs corresponding to the actual conditions during distribution should be performed. Temperature excursions during transportation are not rare occurrences. Distribution Stability Studies should be conducted with the stability profiles indicate the need for additional data.

Proper Conduct of Temperature Excursion and Thermal Cycling Studies

Short term temperature excursion and thermal cycling studies should be conducted on the final formulation in the intended commercial package. The question that should be asked is ‘does this excursion have a critical consequence on the product’s quality’?

Ideally, these studies should be run on multiple batches. The studies should be developed to anticipate stressful environmental conditions.  These stress conditions may include temperature, humidity and in some cases, light, and in certain instances, vibration and radiation.  This approach demonstrates higher or lower temperature excursions than what is expected to occur during routine distribution of a product.

For copies of suggested Short Term Temperature Excursion and Thermal Cycling Excursion Studies please fill out a contact form on this page.