Considerations in establishing bioequivalence of inhaled compounds

ABSTRACT

Introduction: Generic inhalers are often perceived as inferior to their branded counterparts; however, they are safe and effective if they can meet the regulatory requirements. The approach to assess bioequivalence (BE) in oral dosage form products is not sufficient to address the complexities of inhalational products (e.g., patient-device interface); hence, more considerations are needed and caution should be applied in determining BE of inhaled compounds.

Areas covered: This review outlines the evaluation process for generic inhalers, explores the regulatory approaches in BE assessment, and highlights the considerations and challenges in the current in vitro and in vivo approaches (lung deposition, pharmacokinetic, pharmacodynamic/clinical studies, and patient-device interface) for establishing BE of inhaled compounds.

Expert opinion: The ultimate goals in this field are to establish uniformity in the regulatory approaches to speed the drug submission process in different regions, clear physicians’ misconception of generic inhalers, and have meaningful clinical endpoints such as improvement in patient quality of life when compared to placebo and brand name drugs. As inhalational drugs become more common for other indications such as antibiotics, the technologies developed for inhaled compounds in the treatment of chronic pulmonary diseases may be extrapolated to these other agents.

KEYWORDS:

• Bioequivalence
• inhaled compounds
• generic inhalers
• chronic obstructive pulmonary diseases
• asthma

Declaration of interest

I Mayers has received an honorarium from Boeringher Ingelheim for CME related to generic inhalers. Medical writing assistance was used in the development of this paper and was carried out by Jane Cheung (SAGE Medica Inc.). The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Article highlights

• Generic inhalers are not inferior to branded inhalational products in terms of effectiveness, safety, and quality; they are safe and effective if they can meet the regulatory requirements.

• Regulatory approaches for the BE assessment of oral dosage form products are not sufficient for inhalational products, and caution should be applied in determining BE of inhaled compounds.

• In the evaluation approaches, aerosol behaviour should be studied, and lung deposition studies are suggested in the current approach to assess BE of inhaled compounds.

• Clinical trials should be of adequate duration (e.g., long-term studies), which include evaluations of both safety and effectiveness for each compound.

• There are still challenges in establishing BE of inhaled compounds (e.g., no uniform regulatory approaches).

This box summarizes key points contained in the article.

Additional information

Funding

This paper was not funded.