Albuterol MDI in Vivo Bioequivalence: FDA's Office of Generic Drugs' Dose-Response Studies

Abstract

Bioequivalence studies based on pharmacodynamic response must be sensitive to differences in dose of drug. Pilot dose-response studies in asthmatic subjects were conducted under agency contract to evaluate the suitability of three study designs for use in the documentation of in vivo bioequivalence of multisource albuterol inhalation aerosols (metered dose inhalers [MDI]). Differences between study designs were observed in the ability to fit individual subject dose-response curves to an E _max model, in the estimates of ED ₅₀, and in the response to two actuations relative to one actuation of albuterol MDI. One of the three study designs appeared preferable as a basis for development of an in vivo bioequivalence guidance. Subsequent to review of study data by an advisory committee, an interim guidance based upon this study design was issued by the Division of Bioequivalence in the Food and Drug Administration's (FDA) Office of Generic Drugs in January 1994.