The purpose of stability testing is to provide evidence on how the quality of a drug substance or drug product varies with time under the influence of a variety of environmental factors such as temperature, humidity, and light. It is also to establish a re-test period for the drug substance or shelf life for the drug product and recommended storage conditions.

Stress testing is a technique used in stability studies. 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 the power of the analytical procedures used.

The nature of the stress testing will depend on the individual drug substance and the type of drug product involved. Under the International Council for Harmonization (ICH) guideline, there are certain protocols that pharmaceutical companies must follow when testing the stability of drug substances.

For long-term studies, the frequency of testing should be sufficient to establish the stability profile of the drug substance. For drug substances with a proposed re-test period of at least 12 months, the frequency of testing at the long-term storage condition should normally be every three months over the first year, every six months over the second year, and annually thereafter through the proposed re-test period.

At the accelerated storage condition, a minimum of three time points, including the initial and final time points (e.g., 0, 3, and 6 months), from a 6-month study is recommended. Where an expectation (based on development experience) exists that results from accelerated studies are likely to approach significant change criteria, increased testing should be conducted either by adding samples at the final time point or by including a fourth time point in the study design.

When testing at the intermediate storage condition is called for as a result of significant change at the accelerated storage condition, a minimum of four time points, including the initial and final time points (e.g., 0, 6, 9, 12 months), from a 12-month study is recommended.

In general, a drug substance should be evaluated under storage conditions (with appropriate tolerances) that test its thermal stability and, if applicable, its sensitivity to moisture. The storage conditions and the lengths of studies chosen should be sufficient to cover the storage, shipment, and subsequent uses.

The long-term testing should cover a minimum of 12 months on at least three primary batches at the time of submission and should be continued for a period of time sufficient to cover the proposed re-test period.

Additional data accumulated during the assessment period of the registration application should be submitted to the authorities if requested. Data from the accelerated storage condition and, if appropriate, from the intermediate storage condition can be used to evaluate the effect of short-term excursions outside the label storage conditions (such as might occur during shipping).

Long-term, accelerated, and, where appropriate, intermediate storage conditions for drug substances are detailed in the sections below. The general case applies if the drug substance is not specifically covered by a subsequent section. Alternative storage conditions can be used if justified.

A specified environment must be simulated in the framework of the stability test. High-quality climate chambers are used for climate simulation.

Binder’s stability chambers, developed specifically for stress tests, work independently of the presence of water supply. In addition, because of their relatively wide instead of deep chambers, they require comparatively less space. Constant climate chambers offer an ideal alternative to enable laboratories to carry out stability tests reliably and take advantage of the results.