Current Scientific and Regulatory Approaches for Development of Orally Inhaled and Nasal Drug Products: Overview of the IPAC-RS/University of Florida Orlando Inhalation Conference

Abstract

Abstract. This article summarizes discussions at the March 2014 conference organized by the University of Florida (UF) and International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS), entitled BOrlando Inhalation Conference: Approaches in International Regulation.^The special focus of the conference was on global scientific and regulatory issues associated with the testing and demonstration of equivalence for the registration of orally inhaled drug products (OIDPs) in the United States, Europe, Brazil, China, and India. The scope included all types of OIDPs throughout their lifecycle, e.g., innovator/brand-name products, generics, modifications due to lifecycle management, device changes, etc. Details were presented for the U.S. Bweight of evidence approach^for registration of generic products (which includes demonstration of in vitro and in vivo equivalence, as well as quantitative and qualitative sameness, and device similarity). The European Bstepwise^approach was elucidated, and the thinking of regulatory agencies in the major emerging markets was clarified. The conference also highlighted a number of areas that would benefit from further research and discussion, especially around patient/device interface and human factor studies, statistical methods and criteria for demonstrating equivalence, the relative roles of in vivo and in vitro tests, and appropriate designs and metrics for in vivo studies of inhaled drugs.

Comparison of systemic pharmacodynamic effects of two combination pressurized metered dose inhalers that deliver salmeterol and fluticasone propionate

“…It is recognized that this pharmacodynamic study included healthy subjects rather than patients with asthma. The selection of healthy subjects rather than a patient group for a PD study has been debated in scientific/regulatory meetings and the consensus (but not uniform agreement) is that the best design to discriminate product differences when comparing equivalence is to include healthy subjects as they are the less variable pharmacokinetic population than patients with compromised lung function and are therefore the preferred study population .…”

Towards Standardized Dissolution Techniques for In Vitro Performance Testing of Dry Powder Inhalers

“…Furthermore, APSD alone might be misleading, as two formulations with similar APSD may not necessarily have a similar pharmacokinetic (PK) profile (23). More recently (2015), it was stated that there is a need to develop relevant in vitro dissolution testing methods for predicting DPIs performance (24). The dissolution behavior of OIDPs was presented as the critical quality attribute for poorly soluble drug substances (25).…”

Rethinking bioequivalence and equivalence requirements of orally inhaled drug products

“…The FDA has developed an aggregate weight-of-evidence approach which utilizes in vitro studies, PK equivalence studies, and pharmacodynamic (PD) or clinical endpoint (CE) studies (also called Therapeutic Equivalence (TE) studies), to establish BE of inhalation products [21]. Equivalence in all categories of interest is required [22]. As such, a generic formulation of a reference inhaler product needs to demonstrate that 1) its device will be judged to be equivalent in a patient's hand, 2) that its in vitro characteristics and performance in terms of emitted dose and aerodynamic particle size distribution is equivalent, 3) that its systemic PK exposure is equivalent, and finally that 4) its clinical efficacy is equivalent.…”