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Biopharma 4.0 for Biologics Manufacturing Under Pandemic Constraints

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Biopharmaceutical Manufacturing

Part of the book series: Cell Engineering ((CEEN,volume 11))

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Abstract

Biologics are the fastest growing molecular group in pharmaceutical therapies as supplying large most human-body like molecules with high efficacy at low doses and less side effects. Biopharma 4.0 relates to the fourth industrial revolution based on digitalization. Digitalization has reached biopharmaceutical industry along the whole development and value chain. Biologics manufacturing of such complex three-dimensional molecules in correct folding and glycosylation pattern for best bioavailability is still a challenge for world scale amount supply. As the variety of new entities vary recently quite broad from peptides, virus like particles, pDNA and mRNA to cell therapies new process design and development methods are needed to speed up robust product supply for patients. A sound theoretical basis is needed to utilize process modeling tools as digital twins for autonomous operation of manufacturing processes. Qualified operators are the rare resource bottleneck to guarantee product quality. Therefore, continuous biomanufacturing as well as the consequent application of the quality by design approachare key-enablers towards biopharma 4.0.

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Abbreviations

APC:

advanced process control

AMWHV:

Arzneimittel- und Wirkstoffherstellungsverordnung

CBM:

continuous biomanufacturing

cGMP:

current Good-Manufacturing-Practice

CHO:

chinese hamster ovary

COG:

cost of goods

CQA:

critical quality attributes

DARPA:

Defense Advanced Research Projects Agency

DoE:

Desing-of-Experiments

FDA:

Food and Drug Administration

FMEA :

failure-mode-error-analysis

GMP :

Good-Manufacturing-Practice

GWP:

global warming potential

HIV:

human immunodeficiency viruses

ICH :

International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use

LNP:

lipid nano particle

mAbs :

monoclonal antibodies

mRNA :

messenger RNA

NN:

neural network

OLS:

ordinary least squares

PAT:

Process-Analytical-Technology

pDNA :

plasmid DNA

PLS:

partial least squares

QbD:

Quality-by-Design

QTPP :

quality-target-product-profile

RTRT:

Real-time-release-testing

scFv :

single chain variable fragment

SU:

single use

VLP:

Virus-like particle

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Acknowledgments

The authors would like to thank the whole institutes team like Heribert Helgers for cell line development and upstream processing, Florian Vetter and Dr.-Ing. Steffen Zobel-Roos for continuous chromatography and Alex Juckers for lyophilization; Mourad Mouellef and Thomas Knebel for their endless automation efforts; the mechanical and electrical workshop with Nils Hoffmann and Volker Strohmeyer is thanked for their fast-track assembly of IVT and LNP units – under budgeting supervision of Claudia Lacheta; laboratory-head Frank Steinhäuser for his full-time trouble-shooting and total support. Prof. Dr. Martin Tegtmeier as qualified person for his regulatory guidance and supervision.

Conflicts of Interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Institute for Separation and Process Technology, Clausthal University of Technology, Clausthal-Zellerfeld, Germany

    Axel Schmidt, Alina Hengelbrock & Jochen Strube

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  1. Axel Schmidt
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Correspondence to Jochen Strube .

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  1. Institute of Bioprocess and Biosystems Engineering, Hamburg University of Technology, Hamburg, Germany

    Ralf Pörtner

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Schmidt, A., Hengelbrock, A., Strube, J. (2023). Biopharma 4.0 for Biologics Manufacturing Under Pandemic Constraints. In: Pörtner, R. (eds) Biopharmaceutical Manufacturing. Cell Engineering, vol 11. Springer, Cham. https://doi.org/10.1007/978-3-031-45669-5_10

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