This paper addresses statistical issues of similarity factor f2 as a criterion for assessment of similarity between two in vitro dissolution profiles as proposed in 'Guidance on Immediate Release Solid Oral Dosage Forms; Scale-up and Postapproval Changes: Chemistry, Manufacturing, and Controls; In Vitro Dissolution Testing; In Vivo Bioequivalence Documentation' (SUPAC), issued by the United States Food and Drug Administration on November 30, 1995. These issues include the invariant property of f2 with respect to the location change and the consequence of failure to take into account shape of the curve and unequal spacing between sampling time points. The similarity factor f2 is a sample statistic which cannot be used to formulate a statistical hypothesis for assessment of dissolution similarity. It is, therefore, impossible to evaluate false positive and false negative rates of decisions for approval of drug products based on f2. Implementation of f2 to assess dissolution similarity is, in fact, a one-sided problem rather than an interval criterion suggested by the SUPAC. Complexity of the form in the distribution of f2 even under a very strict assumption prevents one from finding its expected variance and hence, confidence interval for the mean. The large-sample distribution of f2 by the usual delta method fails to provide an adequate approximation to the empirical distribution obtained by simulation. In addition, simulation results also indicate that the similarity factor is too liberal in concluding similarity between dissolution profiles.
All Science Journal Classification (ASJC) codes
- Pharmacology (nursing)
- Drug guides
- Public Health, Environmental and Occupational Health
- Pharmacology (medical)