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Recent developments in chromatographic purification of biopharmaceuticals

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Abstract

Over the last several decades, researchers have time and again proposed use of non-chromatographic methods for processing of biotherapeutic products. However, chromatography continues to be the backbone of downstream processing, particularly at process scale. There are many reasons for this, critical ones being the unparalleled scalability, robustness, and selectivity that process chromatography offers over its peers. It is no surprise then that process chromatography has been a topic of major developments in resin matrix, ligand chemistry, modalities, high throughput process development, process modelling, and approaches for control. In this review, we attempt to summarize major developments in the above-mentioned areas. Greater significance has been given to advancements in the last 5 years (2013–2017).

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Fig. 1

Adapted from Orr et al. (2013)

Fig. 2

Adapted from Rathore et al. (2017)

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Abbreviations

AEX:

Anion exchange

ATPS:

Aqueous two phase separation

CEX:

Cation-exchange

CIP:

Cleaning-in-place

CAC:

Continuous annular chromatography

CCC:

Countercurrent chromatography

CCT:

Countercurrent Tangential

cGMP:

Current good manufacturing practices

DoE:

Design of experiments

FDA:

Food and drug administration

HPLC:

High performance liquid chromatography

HTPD:

High throughput process development

HTS:

High throughput screening

HCP:

Host cell proteins

HCIC:

Hydrophobic charge induction chromatography

HIC:

Hydrophobic interaction chromatography

MPC:

Model predictive control

mAb:

Monoclonal antibodies

MCSGP:

Multicolumn countercurrent solvent gradient purification chromatography

MM:

Multimodal or mixed mode

PAROC:

Parametric optimization and control

PDAE:

Partial differential and algebraic equations

PCC:

Periodic countercurrent chromatography

PEG:

Polyethylene gycol

PAT:

Process analytical technology

PID:

Proportional-integrator-derivative

QbD:

Quality by design

SMB:

Simulated moving bed

SEC:

Size exclusion chromatography

TRPA:

Thermal responsive protein A

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Acknowledgements

This work was funded by the Center of Excellence for Biopharmaceutical Technology Grant from Department of Biotechnology, Government of India (Number BT/COE/34/SP15097/2015).

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Authors and Affiliations

  1. Department of Chemical Engineering, DBT Center of Excellence for Biopharmaceutical Technology, Indian Institute of Technology, Delhi, Hauz Khas, New Delhi, 110016, India

    Anurag S. Rathore, Devashish Kumar & Nikhil Kateja

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  1. Anurag S. Rathore
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  2. Devashish Kumar
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  3. Nikhil Kateja
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Correspondence to Anurag S. Rathore.

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Rathore, A.S., Kumar, D. & Kateja, N. Recent developments in chromatographic purification of biopharmaceuticals. Biotechnol Lett 40, 895–905 (2018). https://doi.org/10.1007/s10529-018-2552-1

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