The ICH Guideline for Stability Testing—What Matrixing does it Permit?

Abstract

This paper examines the allowance for matrix designs in stability testing included in the 1993 International Conference on Harmonization (ICH) international guideline for stability testing of new drug substances and products. The paper first provides some concept of different types of statistical designs for stability testing, including the general concepts of bracket and matrix designs. Secondly, it restates the guideline's definition of matrixing and the associated definition of a drug product. It then seeks to understand what the matrixing definition actually permits in a design for stability testing. Finally, the paper suggests that the ICH guideline's definition of matrixing leaves the new drug sponsor doubtful about what matrixing really is, or what might be permitted in a statistical design for stability testing under the label “matrixing.” Interaction with the Food and Drug Administration (FDA) is cited to indicate the agency's perspective on the ICH allowance for matrix designs.