ABSTRACT
Bracketing can be applied to studies with multiple strengths of identical or closely related formulations. The parent guideline notes that the use of matrixing and bracketing can be applied, if justified, to the testing of new drug substances and products, but provides no further guidance on the subject. Matrixing designs can be applied to strengths with identical or closely related formulations. Reduced designs can be applied to the formal stability study of most types of drug products, although additional justification should be provided for certain complex drug delivery systems where there are a large number of potential drug–device interactions. The differences in the samples for the same drug product should be identified as, for example, covering different batches, different strengths, different sizes of the same container closure system, and possibly, in some cases, different container closure systems. Care should be taken to select the extremes by comparing the various characteristics of the container closure system that may affect product stability.
