Analytical characterization of coformulated antibodies as combination therapy.

MAbs
Jun KimXiangyang Wang

Abstract

When two therapeutic agents are combined in a single formulation, i.e., coformulated, the quality and safety of the individual agents must be preserved. Here we describe an approach to evaluate the quality attributes of two individual monoclonal antibodies (mAbs), designated mAb-A and mAb-B, in coformulation. The mAbs were fractionated from heat-stressed coformulated drug product (DP) by hydrophobic interaction chromatography. Each purified mAb fraction was then compared with mAb-A and mAb-B in their individual formulations from the same drug substance sources used to make the coformulated DP lot, which was subjected to the same stress conditions. Product variants were evaluated and compared by using several analytical tests, including high-performance size exclusion chromatography (HPSEC), reducing and nonreducing gel electrophoresis, ion-exchange chromatography, capillary isoelectric focusing, and peptide mapping with mass spectrometry. Intermolecular interactions in coformulated and photostressed DPs were studied by evaluating aggregates fractionated from coformulated DP by HPSEC. Aggregate fractions of coformulated DP contained dimers, but not coaggregates, of mAb-A or mAb-B. Moreover, extensive assays for higher-order stru...Continue Reading

References

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Citations

Dec 5, 2020·Scientific Reports·Hongyu Zhang, Paul A Dalby
Jul 21, 2020·Molecular Pharmaceutics·Dennis KriegHristo L Svilenov

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Methods Mentioned

BETA
deamidation
size
ion-exchange chromatography
electrophoresis
IEC
surface plasmon resonance
chip
circular dichroism
isothermal
dynamic light scattering

Software Mentioned

Combo
SEDFIT
Empower

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