The guidance stated in the ICH harmonised tripartite guideline Stability Testing of New Drug Substances and Products” (27 October 1993) applies in general to biotechnological/ biological products.

However, biotechnological/ biological products do have distinguishing characteristics to which consideration should be given in any well-defined testing program designed to confirm their stability during the intended storage period. 

For such products, in which the active components are typically proteins and/or polypeptides, maintenance of molecular conformation and, hence of biological activity, is dependent on noncovalent as well as covalent forces. 

The products are particularly sensitive to environmental factors such as temperature changes, oxidation, light, ionic content, and shear. 

In order to ensure maintenance of biological activity and to avoid degradation, stringent conditions for their storage are usually necessary.

The evaluation of stability may necessitate complex analytical methodologies. 

Assays for biological activity, where applicable, should be part of the pivotal stability studies. 

Appropriate physicochemical, biochemical and immunochemical methods for the analysis of the molecular entity and the quantitative detection of degradation products should also be part of the stability program whenever purity and molecular characteristics of the product permit use of these methodologies.

With the above concerns in mind, the applicant should develop the proper supporting stability data for a biotechnological/ biological product and consider many external conditions which can affect the product’s potency, purity and quality. 

Primary data to support a requested storage period for either drug substance or drug product should be based on long-term, real-time, real-condition stability studies. 

Thus, the development of a proper long-term stability program becomes critical to the successful development of a commercial product. 

The purpose of this document is to give guidance to applicants regarding the type of stability studies that should be provided in support of marketing applications. It is understood that during the review and evaluation process, continuing updates of initial stability data may occur.