New Designs for Stability Testing Programs: Matrix or Factorial Designs. Authorities' Viewpoint on the Predictive Value of Such Studies

Abstract

Stability testing on the finished product forms an important part of the quality dossier when documentation is presented to the licensing authorities in an application for marketing authorization. In most guidelines on stability investigations, it is required that not less than three batches of a finished product is investigated. If the product exists in various strengths, and if furthermore, several types of packaging materials have to be considered, an enormous number of analyses have to be performed. Therefore, very large resources in both personnel and equipment are required to run such program. Is it possible to reduce the workload by using an appropriate design of the stability program? Various forms of factorial designs have been proposed, such as matrix design and bracketing. Such designs are constructed with the view of reducing the number of tests performed during the investigational period, ie, that not all samples are carried through all test procedures at each testing point. Reduced testing, using specially designed programs, are not mentioned in any of the official stability guidelines. Therefore, in the European Community (EC) the authorities of the individual member states may well take different views on such proposals from an applicant. The possibilities of achieving a harmonized view within the EC or even an international harmonization is discussed.