An overview of regulations for bioequivalence assessment of locally acting orally inhaled drug products for the United States, Europe, Canada, and India

ABSTRACT

Introduction

Bioequivalence is established by comparing the bioequivalence study results of generic drugs with the reference listed drug. Several global regulatory agencies have published the guidance for locally acting orally inhaled drug products (OIDPs) for bioequivalence approaches.

Areas covered

The prime intent of the present article is to compare the regulatory guidance for bioequivalence assessment of locally acting OIDPs published by global regulatory authorities. Regulatory recommendations on bioequivalence were based on assessment for different parameters such as inhaler device, formulation, reference product selection, in-vitro, and in-vivo studies. The United States Food and Drug Administration and Health Canada suggest an aggregated weight of evidence approach and the European Medicines Agency promotes a stepwise approach, whereas though the Indian authorities have not published guidance specifically on OIDPs but provided guidelines for bioavailability and bioequivalence studies.

Expert opinion

For OIDPs, currently, there is no universally adopted methodology, and regulatory guidance has not been globally harmonized. By understanding and comparing bioequivalence recommendations for different regions, we can create more sensitive, and economic evaluation methods for OIDPs. This could open more alternatives of safe, effective generic OIDPs to the public.

KEYWORDS:

• Regulatory Guidance
• Bioequivalence
• Orally inhaled drug products
• Pharmacokinetics
• Pharmacodynamics

Funding

This paper was not funded.

Article highlights

• No universally adopted methodology or globally harmonized regulations for OIDPs.

• Comparison of regulatory guidance for bioequivalence assessment of OIDPs.

• Aggregated weight of evidence and stepwise approach in establishing bioequivalence.

• Providing a robust model for in-vitro equivalence for development of generic OIDPs.

• Providing choices of safe, effective, bioequivalent, less expensive generic OIDPs.

• Scope for future global harmonization of bioequivalence recommendations for OIDPs.

This box summarizes key points contained in the article.

Declaration of interest

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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.