How Similar Is Biosimilar? A Comparison of Infliximab Therapeutics in Regard to Charge Variant Profile and Antigen Binding Affinity

Abstract

Biosimilars are increasing in economic importance. Just how similar a biosimilar needs to be to gain market approval is currently still decided on a per case basis. The authors try to shed light on one often cited critical quality attribute of monoclonal antibodies, namely charge heterogeneity. Using high resolution electrophoretic and chromatographic methods, the authors are able to separate and quantify the charge variant content of infliximab originator and three biosimilars. Additionally the authors quantified and compared the antigen binding affinity in an SPR based binding assay and analyzed the glycosylation pattern of all four of these infliximab biosimilar products. Even though the analytical methods did not show full similarity between originator and some biosimilars, all of the biosimilars have gained approval based on their clinical comparability. The authors would therefore argue, that analytical comparison is not always a good predictor for clinical interchangeability. Any future regulatory framework for the approval of biosimilars should reflect that the parameters chosen for analytical comparability have to be chosen carefully.

A novel method for continuous chromatographic separation of monoclonal antibody charge variants by combining displacement mode chromatography and step elution

“…Although complete displacement of acidic species may be desirable for some applications such as product characterization, it is not suitable for commercial processing. For biosimilar manufacturers, the primary objective is to match the charge variant profile to the innovator product 31 . Hence, in this study, our aim is to use the displacement mode along with a salt‐based step gradient elution to obtain the desired charge variant composition in the final product.…”

“…For biosimilar manufacturers, the primary objective is to match the charge variant profile to the innovator product. 31 Hence, in this study, our aim is to use the displacement mode along with a saltbased step gradient elution to obtain the desired charge variant composition in the final product. To achieve this, we first performed process development and optimization studies in the batch mode, followed by process integration to arrive at the final continuous platform.…”

Biosimilar-to-Biosimilar Switching: What is the Rationale and Current Experience?

“…Licensure or approval of a biosimilar is based on totality-of-the-evidence and is granted on a case-by-case basis, exclusively with respect to the reference product [ 29 , 98 , 103 ]. Distinct from the approval process for a reference biological product, the regulatory pathway adopted for biosimilars relies more heavily upon comparative analytical data, with less emphasis placed upon multiple, lengthy, large-scale, comparative clinical trials [ 30 , 104 ].…”