Establishing bioequivalence for inhaled drugs; weighing the evidence

During drug development and product life-cycle management, it may be necessary to establish bioequivalence between two pharmaceutical products. Methodologies to determine bioequivalence are well established for oral, systemically acting formulations. However, for inhaled drugs, there is currently no universally adopted methodology, and regulatory guidance in this area has been subject to debate.

This paper covers the current status of regulatory guidance on establishing the bioequivalence of topically acting, orally inhaled drugs, the value and limitations of in vitro and in vivo bioequivalence testing, and the practical issues associated with various approaches. The reader will gain an understanding of the issues pertaining to bioequivalence testing of orally inhaled drugs, and the current status of regulatory approaches to establishing bioequivalence in different regions.

Establishing bioequivalence of inhaled drug products involves a multistep process; however, methodologies for each step have yet to be fully validated. Our lack of understanding about the relationship between in vitro, in vivo and clinical data suggests that in most cases, unless there is a high degree of pharmaceutical equivalence between the test and reference products, consideration of a combination of preclinical and clinical data may be preferable to abridged approaches relying on in vitro data alone.