Abstract

Infectious diseases, along with cancers, are among the main causes of death among humans worldwide. The production of therapeutic proteins for treating diseases at large scale for millions of individuals is one of the essential needs of mankind. Recent progress in the area of recombinant DNA technologies has paved the way to producing recombinant proteins that can be used as therapeutics, vaccines, and diagnostic reagents. Recombinant proteins for these applications are mainly produced using prokaryotic and eukaryotic expression host systems such as mammalian cells, bacteria, yeast, insect cells, and transgenic plants at laboratory scale as well as in large-scale settings. The development of efficient bioprocessing strategies is crucial for industrial production of recombinant proteins of therapeutic and prophylactic importance. Recently, advances have been made in the various areas of bioprocessing and are being utilized to develop effective processes for producing recombinant proteins. These include the use of high-throughput devices for effective bioprocess optimization and of disposable systems, continuous upstream processing, continuous chromatography, integrated continuous bioprocessing, Quality by Design, and process analytical technologies to achieve quality product with higher yield. This review summarizes recent developments in the bioprocessing of recombinant proteins, including in various expression systems, bioprocess development, and the upstream and downstream processing of recombinant proteins.

Highlights

  • Biopharmaceuticals are the main drugs developed in the pharma sector

  • This study found that cell lysis could be delayed and that recombinant protein yields could be increased by using cell lines constitutively expressing vankyrin or vankyrin-encoding baculovirus vectors (Steele et al, 2017)

  • This study demonstrated the use of CRISPR-Cas9 for editing an endogenous insect cell gene and altering protein glycosylation in the baculovirus-insect cell system

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Summary

INTRODUCTION

Biopharmaceuticals are the main drugs developed in the pharma sector. Market demand has instigated the development of various protein expression hosts and bioprocessing technologies. The products approved from 2014 to mid-2018 include 68 monoclonal antibodies (mAbs), 23 hormones, 16 clotting factors, nine enzymes, and seven vaccines (Walsh, 2018). Advancements in the area of recombinant protein production have changed the previous trend, making the yield much higher and the cost much lower, allowing the production of such proteins on an industrial scale and opening the door for the treatment of multiple diseases and disorders

Trends in Bioprocessing of Recombinant Biopharmaceuticals
Manufacturer Host cell
EXPRESSION HOSTS FOR RECOMBINANT PROTEIN PRODUCTION
Escherichia coli
Mammalian Cells
Transgenic Animals
Transgenic Plants
Insect Cells
UPSTREAM PROCESS DEVELOPMENT
Expression system
Insect cells
Transgenic animals
RECENT DEVELOPMENTS IN UPSTREAM PROCESSING
System details
Applikon GE Sartorius
Design of Experiments Approach
Process Modeling
Perfusion Culture Process
DOWNSTREAM PROCESS DEVELOPMENT
Chromatography Processes
RECENT PROGRESS IN DOWNSTREAM
Thermo Fisher
Downstream Processing
Modeling Approach
Continuous Downstream Processing
Continuous Precipitation
Continuous Chromatography
Protein A
Continuous Viral Inactivation and Clearance
Continuous Refolding
Continuous Formulation
Findings
INTEGRATED CONTINUOUS
Full Text
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