Statistical evaluation methods of in vitro studies for bioequivalence for orally inhaled and nasal drug products

This article systematically reviews the background and regulatory requirements of bioequivalence of orally inhaled and nasal drug products (OINDPs), as well as the basic regulatory requirements for the assessment by the guidelines and guidance issued in China, the United States, and the European Union. Detailed statistical evaluation method considerations and calculations of the US FDA population bioequivalence (PBE) method were presented for the evaluation of in vitro bioequivalence (IVBE) for OINDPs. Using the example described in the FDA Draft Guidance for budesonide inhalation suspension, the PBE analysis statistical parameters were calculated via the R programming, and the results were compared with that in the guidelines. Moreover, pseudo-code for the PBE calculation program was provided. This paper aims to provide guidance and references for the research and development of new drug, as well as pharmaceutical quality control, and development of generic medicinal products for OINDPs.