Stability liabilities of biotherapeutic proteins: Early assessment as mitigation strategy

January 5, 2021

Lobo, S., Baczyk, P., Wyss, B., et al.

Journal of Pharmaceutical and Biomedical Analysis 2021, vol: 192 doi: 10.1016/j.jpba.2020.113650

Abstract

Identification of molecular liabilities and implementation of mitigation strategies are key aspects that need to be considered by pharmaceutical companies developing therapeutic proteins.

In the field of monoclonal antibodies, an efficient and streamlined process known as developability assessment is used for the selection of the “fittest” candidate. Other protein modalities, have in most cases only a limited number of possible candidates, requiring a paradigm change to a concept of candidate enabling. The assessment of liabilities at early project phases with the possibility to re-engineer candidates becomes essential for the success of these projects.

Each protein possesses a unique stability profile resulting from the interplay of conformational, colloidal, chemical and physical stability attributes. All of these attributes strongly depend on external factors. Conformational and colloidal stability profiles of three non-immunoglobulin domain based proteins, namely Carbonic anhydrase, Ovalbumin and Thyroglobulin, and of two monoclonal antibodies were assessed in dependence of solution pH, ionic strength and varying buffering agents. The impact of screened external factors on proteins’ stability attributes varied significantly, indicating presence of molecule specific liabilities. Screening of such a broad space of conditions at early project phases is only feasible using low-material consuming, high-throughput analytical methods as exemplified in this study.

View Publication

Topics: Prometheus, nanoDSF, Biologics, Publications

Previous Video
Multi-parameter formulation development for an HIV-vaccine protein with direct validation of epitope binding
Multi-parameter formulation development for an HIV-vaccine protein with direct validation of epitope binding

Join Thomas Schubert, CEO of 2bind, as he walks through experiments done on the Prometheus Panta to determi...

Up next
Your guide to efficiently develop antibody-based therapeutics
Your guide to efficiently develop antibody-based therapeutics

How to measure stability, why it's important, and where it belongs in the workflow

Want to see more
biologics content?

Explore resources