Methods for addressing host cell protein impurities in biopharmaceutical product development

Biotechnol J. 2023 Mar;18(3):e2200115. doi: 10.1002/biot.202200115. Epub 2022 Dec 13.

Abstract

The high demand for monoclonal antibody (mAb) therapeutics in recent years has resulted in significant efforts to improve their costly manufacturing process. The high cost of manufacturing mAbs derives mainly from the purification process, which contributes to 50%-80% of the total manufacturing cost. One of the main challenges facing industry at the purification stage is the clearance of host cell proteins (HCPs) that are produced and often co-purified with the desired mAb product. One of the issues HCPs can cause is the degradation of the final mAb protein product. In this review, techniques are considered that can be used at different stages (upstream and downstream) of mAb manufacture to improve HCP clearance. In addition to established techniques, many new approaches for HCP removal are discussed that have the potential to replace current methods for improving HCP reduction and thereby the quality and stability of the final mAb product.

Keywords: biopharmaceutical manufacturing; cell line engineering; formulation; host cell protein(s); purification.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal* / metabolism
  • Biological Products*
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Kinetics

Substances

  • Antibodies, Monoclonal
  • Biological Products