Need for a risk-based control strategy for managing glycosylation profile for biosimilar products

ABSTRACT

Introduction

Monoclonal antibodies, though a popular class of therapeutics, are complex molecules that are manufactured using complex processes, making it nontrivial to maintain high level of batch-to-batch consistency in product quality. Glycosylation is a posttranslation modification that is widely considered a critical quality attribute (CQA) as its variations are known to impact the Fc effector functions of mAbs. With continuing rise of biosimilars, comparability of these products to the reference product with respect to glycosylation is a topic of immense interest.

Areas covered

In this article, we focus on the various aspects related to this topic including criticality of the various glycosylated forms, as well as comparability of biosimilars with respect to glycosylation.

Expert opinion

We propose that manufacturers should focus on those glycoforms that are present in larger amounts and are known to be critical with respect to the biotherapeutic’s safety and efficacy. Such risk-based evaluation of glycoforms and their control would offer an optimal route to biosimilar manufacturers for a cost-effective approach toward product development without compromising on the safety and efficacy characteristics of the therapeutic. For mAbs lacking Fc effector function, devising stringent glycosylation control strategies can be bypassed, thereby simplifying process and product development.

KEYWORDS:

• mABs
• Biosimilars
• Comparability
• Glycosylation
• Criticality
• Variability

Acknowledgments

The authors would like to thank Dr. Shyamapada Mandal (IIT Delhi) for his inputs in analysis of literature data.

Article Highlights

• Glycosylation composition amongst biosimilars of the different mAbs have been reviewed.

• Aspects of criticality, variability, and abundance for common glycoforms have been discussed.

• Recommendations for biosimilar industry has been proposed as per observations from the literature.

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 relationships or otherwise to disclose.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was funded by the Department of Biotechnology, Ministry of Science and Technology (BT/COE/34/SP15097/2015).