Many pharmaceutical developers of generic orally inhaled products (OIPs) are facing significant issues in passing the regulatory requirement to show pharmacokinetic (PK) bioequivalence (BE) to the originator product. The core of the issue is that no reliable in vitro-in vivo correlation (IVIVC) is available to guide their development. In this paper, several issues are identified and means to improve the data used for developing an IVIVC are discussed. The article also presents an "IVIVC-free" approach for developing a formulation matching the originator's PK performance.
Keywords: Aerodynamic particle size distribution; Between-batch PK variability; Clinically relevant test methods; Computational models; Fine particle dose; Inhalation profiles; Mouth/throat models; Orally inhaled products; Pharmacokinetic studies.
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