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

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.