European Union has issued guidelines on stability testing for application in  order to support a variation to a Marketing Authorization. The guideline provides general guidance on stability testing.

The guidelines replaces the previous rules referred to as CPMP/QWP/576/96 Rev 1 & EMEA/CVMP/373/04.

The new guidelines provide general guidance on stability testing in case of type I (A and B) variations and addresses the data requirements for widely encountered cases of type II variations. It sets out the stability testing requirements for variations to a Marketing Authorization after approval. This guideline is an extension of the CHMP and CVMP Guidelines on Stability Testing of Existing Active Substances and Related Finished Products and the ICH/VICH Guidelines for New Active Substances and Drug Products.

The guideline seeks to exemplify the stability data required for variations to active substances and finished products. It is not always necessary to follow this when there are scientifically justifiable reasons for using alternative approaches.

Further, it provides a general indication on the requirement for stability testing, but leaves sufficient flexibility to include the variety of different practical situations required for specific scientific situations and characteristics of the material being evaluated.

If a variation to a marketing authorization fulfils the conditions defined in Commission Regulation EC  1234/2008 for Type IA variations and if stability data are required, for medicinal products for human use and veterinary medicinal products, it will need to be submitted.

European Commission Regulations EC 1234/2008 defines Type II variation as major variations which have the highest potential impact on the quality, safety or efficacy of medicinal products.

The guideline is applicable to chemical active substances and related finished products, herbal drugs, herbal drug preparations along with related herbal medicinal products. However it is not for radiopharmaceuticals, biologicals and products derived from biotechnology.

Variations for active substances and finished products encompass a wide range of situations. In cases of variations which require generation of stability data on the finished product, the stability studies required, would include  commitment batches, and should be continued up to the approved shelf life. Moreover the authorities should be informed immediately if any problems with the stability appear during storage, for instance, if outside specification or potentially outside specification.

The scope and design of the stability studies for variations and changes are based on the knowledge and experience acquired on the active substances and finished products. The available information must be taken into account for  active substances with the supportive data and primary data of accelerated and long term testing.

In the case of finished products, the supportive data should include the   primary data of accelerated and long term testing.

In all cases of variations, the applicant have to investigate whether the intended change will have an impact or not on the quality characteristics of active substances and/or finished products and consequently on their stability, stated the guidelines report issued.

When stability data is required, the choice of test conditions defined in the guideline refers to the CHMP/ICH Guideline on Stability Testing of New Drug Substances and Products.