Examination of selection of immediate release dissolution acceptance criteria

Abstract

Controversy and approval delays often arise between a sponsor company and regulatory agencies over the establishment of dissolution acceptance criteria.For a US submission,the dissolution specification that is established is based on the acceptance criteria in USP Dissolution General Chapter <711 >.When defining the acceptance criteria,the sponsor must propose a 'Q'value and a time point (e.g.,30 minutes or45 minutes) at which point the data will be evaluated against the appropriate criteria. In many instances,there is disag reement between the sponsor and theFDAon the appropriate valuesforthe collection time point and the valueof'Q! This paperwill illustrate the very conservative nature of the Stage 1 acceptance criteria relative to that of the other stages.This paper demonstrates that a major issue that must be addressed when approaching this topic is the large difference in the discriminatory ability of the initial and subsequent stages of the dissolution test. Another issue brought forth is the traditional establishment of the Q value only in 5 unit increments.This paper will illustrate via theory and examples the problems presented by the above two issues. Finally, this article will present an alternative data-driven approach that could be used to arrive at potential dissolution specifications.