Scientific and regulatory standards for assessing product performance using the similarity factor, f2.

Abstract

The similarity factor, f2, measures the sameness of dissolution profiles. The following commentary is an overview of discussions and presentations from a group of industry and US regulatory experts that have integrated the science and regulatory research and practice for assessing product performance, particularly for modified-release (MR) dosage forms, using f2. For a drug development sponsor or applicant with an orally complex dosage formulation, it is critical to understand dissolution methods and the similarity factor and how and/or when to apply it in their NDA, ANDA, or PMA submission. As part of any regulatory submission, it is critical to justify that the product performance has not been impacted by any change in the manufacturing process and/or the delayed and/or prolonged drug release characteristics compared to a similar conventional or another orally complex dosage form. The purposes of this document are (1) to provide a description of appropriate dissolution methods, how is the f2 calculated and how it can be used to justify product performance similarity, or not; (2) to provide an overview of alternative methods available for dissolution profile comparisons, and (3) to illustrate how applying these concepts in a focused way supports approval of submissions and regulatory dossiers and aligns them with on-going science and regulatory initiatives. A case study will be used as an example to demonstrate how dissolution testing and the f2 calculation results can impact regulatory outcomes from an NDA (505(b)(1)), NDA (505(b)(2)), ANDA (505(j)), supplemental NDAs/ANDAs, or PMA perspective.