From cell factories to patients: Stability challenges in biopharmaceuticals manufacturing and administration with mitigation strategies

Abstract

Active ingredients of biopharmaceuticals consist of a wide array of biomolecular structures, including those of enzymes, monoclonal antibodies, nucleic acids, and recombinant proteins. Recently, these molecules have dominated the pharmaceutical industry owing to their safety and efficacy. However, their manufacturing is hindered by high cost, inadequate batch-to-batch equivalence, inherent instability, and other quality issues. This article is an up-to-date review of the challenges encountered during different stages of biopharmaceutical production and mitigation of problems arising during their development, formulation, manufacturing, and administration. It is a broad overview discussion of stability issues encountered during product life cycle i.e., upstream processing (aggregation, solubility, host cell proteins, color change), downstream bioprocessing (aggregation, fragmentation), formulation, manufacturing, and delivery to patients.

Keywords: Biopharmaceuticals; Enzymes; Gene therapy; Insulin; Monoclonal antibodies; Nanotechnology; Protein aggregation; Recombinant proteins; Stability; Vaccines.