A novel approach to evaluate the pharmacokinetic biocomparability of a monoclonal antibody derived from two different cell lines using simultaneous crossover design.

A parallel study design with a large number of subjects has been a typical path for pharmacokinetic (PK) biocomparability assessment of biotherapeutics with long half-lives and immunogenic propensity, for example, monoclonal antibodies (mAb). A recently published innovative bioanalytical method that can quantify mAb produced from two different cell lines in the same sample opened an avenue to exploring a simultaneous crossover study design for PK biocomparability assessment of biotherapeutics. Siltuximab, a chimeric IgG1 mAb-targeting interleukin-6, was studied as an example.

Characterization of critical reagents in ligand-binding assays: enabling robust bioanalytical methods and lifecycle management.

The effective management of validated ligand-binding assays used for PK, PD and immunogenicity assessments of biotherapeutics is vital to ensuring robust and consistent assay performance throughout the lifetime of the method. The structural integrity and functional quality of critical reagents is often linked to ligand-binding assay performance; therefore, physicochemical and biophysical characterization coupled with assessment of assay performance can enable the highest degree of reagent quality. The implementation of a systematic characterization process for monitoring critical reagent attributes, utilizing detailed analytical techniques such as LC-MS, can expedite assay troubleshooting and identify deleterious trends.

A novel approach for the simultaneous quantification of a therapeutic monoclonal antibody in serum produced from two distinct host cell lines.

Therapeutic monoclonal antibodies (mAbs) possess a high degree of heterogeneity associated with the cell expression system employed in manufacturing, most notably glycosylation. Traditional immunoassay formats used to quantify therapeutic mAbs are unable to discriminate between different glycosylation patterns that may exist on the same protein amino acid sequence. Mass spectrometry provides a technique to distinguish specific glycosylation patterns of the therapeutic antibody within the same sample, thereby allowing for simultaneous quantification of the same mAb with different glycosylation patterns.