A review of bridging clinical studies between different presentations of biological products approved by the United States Food and Drug Administration (US FDA)

ABSTRACT

Introduction

There is growing interest in the development of multiple presentations for biological products for subcutaneous (SC) injection for life cycle management and product differentiation. Bridging clinical studies are required to extrapolate the existing data package to new presentations.

Areas covered

This review compiles information of bridging clinical studies conducted for biological products administered by the SC route and approved in more than one presentation by the United States Food and Drug Administration’s Center for Drug Evaluation and Research up until 31 December 2021. Information regarding indication(s), presentation(s), approval pathways, approval timelines, and various aspects of bridging clinical studies was collected from published documents.

Expert opinion

The type of bridging clinical study can depend on the extent of differences between presentations, existing data packages, and the stage of the product development. Design of a bridging clinical study should be based on the characteristics of a biological product and should be aimed at detecting the relevant differences between presentations. Single-dose comparative pharmacokinetics in normal healthy volunteers is the most common bridging clinical study design. Covariates like body weight and injection site should be considered during the design of these studies. The impact of the different user interfaces of presentations should also be considered.

KEYWORDS:

• Bioequivalence
• biological product
• bridging
• clinical
• pharmacokinetic
• presentation

Article highlights

• Bridging clinical studies are required to extrapolate existing data packages from one to another presentation.

• Establishing the bridge in terms of systemic exposure across presentations is the most common approach.

• Design of a bridging clinical study should take into account the characteristics of a biological product.

• The impact of covariates such as body weight and injection site should be considered during the design of bridging clinical studies.

• Need for additional studies should be considered based on the nature and extent of differences between presentations, stage of development, and the existing data package for each presentation.

This box summarizes key points contained in the article.

Declaration of interest

R Patel, P Ghadge, PA Nair, M Kumar and L Adhikary are employees of Intas Pharmaceuticals Limited. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

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

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14712598.2022.2113053

Additional information

Funding

This paper was not funded.