Bioprocessing 4.0 in biomanufacturing: paving the way for sustainable bioeconomy

Kamini Pandey1, Muskan Pandey1, Vinay Kumar2(), Upasana Aggarwal3, Barkha Singhal1,e()

Systems Microbiology and Biomanufacturing ›› 2023, Vol. 4 ›› Issue (2) : 407-424. DOI: 10.1007/s43393-023-00206-y
Review

Bioprocessing 4.0 in biomanufacturing: paving the way for sustainable bioeconomy

  • Kamini Pandey1, Muskan Pandey1, Vinay Kumar2(), Upasana Aggarwal3, Barkha Singhal1,e()
Author information +
History +

Abstract

The past decade has been envisaged as a period of unprecedented growth and development in the bioprocessing industry due to the increasing prominence of manufacturing bioproducts encompassing day-to-day life. Bioprocesses are the heart of biotechnology and represent the most dynamic constituent for conceptualizing the bioeconomy as it has the potential to tackle the most burgeoning problems such as climatic adversity, global population growth, reduced ecosystem resilience. The promising amalgamation of digitalization, biologicalization, and biomanufacturing paved the way for an emerging concept of “bio-intelligent value addition” or more prominently Bioprocessing 4.0 that enables the transformation in the landscape of biomanufacturing. Despite its positive credentials, the technology is facing technical, organizational, economical, and likely some unforeseen challenges that must be resolved for its successful implementation for hailing the sustainability development goals (SDGs) of bioeconomy. Though the road of bioeconomy is quite arduous, the continuous demand for bioproducts and their timely delivery at a faster rate necessitates the culture of sharing knowledge, digitalization, automation, and development of flexible modular and podular facility footprints to accelerate biomanufacturing. Therefore, it is worth summarizing the major portfolios of Bioprocessing 4.0 such as conception of biofoundry, bioprocess intensification strategies, process and data analytics, software and automation, and its synergistic correlation with bioeconomy. Thus, the present article advocates about the technological glance of Bioprocessing 4.0 along with technical challenges and future research priorities for sparking the glory of this industrial landscape for enshrining the bioeconomy.

Keywords

Industry 4.0 / Biofoundry / Upstream processing / Downstream processing / Bioeconomy / Process intensification

Cite this article

Download citation ▾
Kamini Pandey, Muskan Pandey, Vinay Kumar, Upasana Aggarwal, Barkha Singhal. Bioprocessing 4.0 in biomanufacturing: paving the way for sustainable bioeconomy. Systems Microbiology and Biomanufacturing, 2023, 4(2): 407‒424 https://doi.org/10.1007/s43393-023-00206-y

References

1.
Rader RA, Langer ES. Biopharmaceutical manufacturing: historical and future trends in titers, yields and efficiency in commercial-scale bioprocessing. Bioprocess J, 2015, 13: 47-52
2.
Udugama IA, ?ner M, Lopez PC, Beenfeldt C, Bayer C, Huusom JK, Gernaey KV, Sin G. Towards digitalization in bio-manufacturing operations: a survey on application of big data and digital twin concepts in Denmark. Front Chem Eng, 2021, 3: 727152
3.
Gargalo CL, de Las Heras SC, Jones MN, Udugama I, Mansouri SS, Krühne U, Gernaey KV. Towards the development of digital twins for the bio-manufacturing industry. Adv Biochem Eng Biotechnol, 2021,
4.
Singh N, Singhania RR, Nigam PS, Di Dong C, Patel AK, Puri M. Global status of lignocellulosic biorefinery: challenges and perspectives. Bioresour Technol, 2022, 344: 126415,
5.
Velvizhi G, Balakumar K, Shetti NP, Ahmad E, Kishore Pant K, Aminabhavi TM. Integrated biorefinery processes for conversion of lignocellulosic biomass to value added materials: paving a path towards circular economy. Bioresour Technol, 2022, 343: 126151,
6.
Krüger A, Sch?fers C, Busch P, Antranikian G. Digitalization in microbiology—paving the path to sustainable circular bioeconomy. New Biotechnol, 2020, 59: 88-96
7.
Kardung M, Cingiz K, Costenoble O, Delahaye R, Heijman W, Lovri? M, van Leeuwen M, M’barek R, van Meijl H, Piotrowski S, Ronzon T, Sauer J, Verhoog D, Verkerk PJ, Vrachioli M, Wesseler JHH, Zhu BX. Development of the circular bioeconomy: drivers and indicators. Sustainability, 2021, 13: 413
8.
Zobel-Roos S, Schmidt A, Uhlenbrock L, Ditz R, K?ster D, Strube J. Digital twins in biomanufacturing. Adv Biochem Eng Biotechnol, 2021,
9.
Walsh I, Myint M, Nguyen-Khuong T, Ho YS, Ng SK, Lakshmanan M. Harnessing the potential of machine learning for advancing “Quality by Design” in biomanufacturing. MAbs, 2022, 14: 2013593, pmcid: 8744891
10.
Holowko MB, Frow EK, Reid JC, Rourke M, Vickers CE. Building a biofoundry. Synth Biol, 2021, 6: ysaa026
11.
Farzaneh T, Freemont PS. Biofoundries are a nucleating hub for industrial translation. Synth Biol, 2021, 6: ysab013
12.
Lawson CE, Martí JM, Radivojevic T, Jonnalagadda SVR, Gentz R, Hillson NJ, Peisert S, Kim J, Simmons BA, Petzold CJ, Singer SW, Mukhopadhyay A, Tanjore D, Dunn JG, Garcia Martin H. Machine learning for metabolic engineering: a review. Metab Eng, 2021, 63: 34-60,
13.
Sa?ek K, Euston SR, Janek T. Phase behaviour, functionality, and physicochemical characteristics of glycolipid surfactants of microbial origin. Front Bioeng Biotechnol, 2022, pmcid: 8830654
14.
Karim AS, Dudley QM, Juminaga A, Yuan Y, Crowe SA, Heggestad JT, Garg S, Abdalla T, Grubbe WS, Rasor BJ. In vitro prototyping and rapid optimization of biosynthetic enzymes for cell design. Nat Chem Biol, 2020, 16: 912-919,
15.
Faulon J-L, Faure L. In silico, in vitro, and in vivo machine learning in synthetic biology and metabolic engineering. Curr Opin Chem Biol, 2021, 65: 85-92,
16.
Koch M, Duigou T, Faulon JL. Reinforcement learning for bioretrosynthesis. ACS Synth Biol, 2020, 9: 157-168,
17.
Kharissova OV, Kharisov BI, González CMO, Méndez YP, López I. Greener synthesis of chemical compounds and materials. R Soc Open Sci, 2019, 6: 191378, pmcid: 6894553
18.
Rahman SA, Cuesta SM, Furnham N, Holliday GL, Thornton JM. EC-BLAST: a tool to automatically search and compare enzyme reactions. Nat Methods, 2014, 11: 171-174, pmcid: 4122987
19.
Carbonell P, Le Feuvre R, Takano E, Scrutton NS. In silico design and automated learning to boost next-generation smart biomanufacturing. Synth Biol, 2020, 5: ysaa020
20.
Noll P, Henkel M. History and evolution of modeling in biotechnology: modeling & simulation, application and hardware performance. Comput Struct Biotechnol J, 2020, 18: 3309-3323, pmcid: 7670204
21.
Coppens MO. Nature-inspired chemical engineering for process intensification. Annu Rev Chem Biomol Eng, 2021, 12: 187-215,
22.
Gupta P, McLaughlin K. A strategic approach to selecting the optimal process intensification scenario. BioProcess Int, 2021, 19(10): 2-4
23.
Tripathi NK, Shrivastava A. Recent developments in bioprocessing of recombinant proteins: expression hosts and process development. Front Bioeng Biotechnol, 2019, 7: 420, pmcid: 6932962
24.
Chen C, Wong HE, Goudar CT. Upstream process intensification and continuous manufacturing. Curr Opin Chem Eng, 2018, 22: 191-198
25.
Xu J, Xu X, Huang C, Angelo J, Oliveira CL, Xu M, Xu X, Temel D, Ding J, Ghose S, Borys MC, Li ZJ. Biomanufacturing evolution from conventional to intensified processes for productivity improvement: a case study. MAbs, 2020, 12: 1770669, pmcid: 7531520
26.
Malla R, Shah D, Gajendragadkar C, Vamanan V, Singh D, Gupta S, Vengovan D, Trivedi R, Weichert H, Carpio M, Chandran K. Seed train process intensification strategy offers potential for rapid, cost-effective scale-up of biosimilars manufacturing. Bioprocess J, 2021,
27.
Bausch M, Brandl M, Horry H. Seed train intensification using high cell density cryopreservation and specially-designed expansion medium. White Pap. 2020.
28.
Yang WC, Lu J, Kwiatkowski C, Yuan H, Kshirsagar R, Ryll T, Huang YM. Perfusion seed cultures improve biopharmaceutical fed-batch production capacity and product quality. Biotechnol Prog, 2014, 30: 616-625,
29.
Mirasol F. Jumping seed train intensification hurdles to maximize yield. Biopharm Int, 2021, 34: 20
30.
Hancu G, Orlandini S, Papp LA, Modroiu A, Gotti R, Furlanetto S. Application of experimental design methodologies in the enantioseparation of pharmaceuticals by capillary electrophoresis: a review. Molecules, 2021, 26: 4681, pmcid: 8348688
31.
Wu Y, Bissinger T, Genzel Y, Liu X, Reichl U, Tan WS. High cell density perfusion process for high yield of influenza A virus production using MDCK suspension cells. Appl Microbiol Biotechnol, 2021, 105: 1421-1434, pmcid: 7847233
32.
Eibl R, Eibl D. Single-use technology in biopharmaceutical manufacture. Single-Use Technol Biopharm Manuf, 2019,
33.
Samaras JJ, Micheletti M, Ding W. Transformation of biopharmaceutical manufacturing through single-use technologies: current state, remaining challenges, and future development. Annu Rev Chem Biomol Eng, 2022, 13: 73-97,
34.
Kaiser SC, Decaria PN, Seidel S, Eibl D. Scaling-up of an insect cell-based virus production process in a novel single-use bioreactor with flexible agitation. Chem Ing Tech, 2022, 94: 1950-1956
35.
Ton C, Stabile V, Carey E, Maraikar A, Whitmer T, Marrone S, Afanador NL, Zabrodin I, Manomohan G, Whiteman M, Hofmann C. Development and scale-up of rVSV-SARS-CoV-2 vaccine process using single use bioreactor. Biotechnol Rep, 2023, 37: e00782
36.
Nadar S, Shooter G, Somasundaram B, Shave E, Baker K, Lua LHL. Intensified downstream processing of monoclonal antibodies using membrane technology. Biotechnol J, 2021, 16: 2000309
37.
Matte A. Recent advances and future directions in downstream processing of therapeutic antibodies. Int J Mol Sci, 2022, 23: 8663, pmcid: 9369434
38.
Patrascu I, Bildea CS, Kis A. Eco efficient downstream processing of biobutanol by enhanced process intensification and integration. Sustain Chem Eng, 2022, 6: 5452-5461
39.
Ding C, Ierapetritou M. A novel framework of surrogate-based feasibility analysis for establishing design space of twin-column continuous chromatography. Int J Pharm, 2021, 609: 121161,
40.
Sun YN, Shi C, Zhong XZ, Chen XJ, Chen R, Zhang QL, Yao SJ, Jungbauer A, Lin DQ. Model-based evaluation and model-free strategy for process development of three-column periodic counter-current chromatography. J Chromatogr A, 2022, 1677: 463311,
41.
Warikoo V, Brower K, Jain S, Cummings D, Simons E, Johnson T, Walther J, Marcella Y, Yu M, Wright B, McLarty J. Integrated continuous production of recombinant therapeutic proteins. Biotechnol Bioeng, 2012, 58: 350-362
42.
Komuczki D, Lingg N, Jungbauer A, Satzer P. In-situ gradient formation by direct solid addition of buffer components. J Chromatogr A, 2020, 1634: 461663,
43.
Tsai A, Carredano E, Busson K. Deploying automated buffer production for cGMP use: points to consider. Bioprocess J, 2019,
44.
Grangeia HB, Silva C, Sim?es SP, Reis MS. Quality by design in pharmaceutical manufacturing: a systematic review of current status, challenges and future perspectives. Eur J Pharm Biopharm, 2020, 147: 19-37,
45.
Gerzon G, Sheng Y, Kirkitadze M. Process analytical technologies—advances in bioprocess integration and future perspectives. J Pharm Biomed Anal, 2022, 207: 114379,
46.
Romann P, Kolar J, Tobler D, Herwig C, Bielser JM, Villiger TK. Advancing Raman model calibration for perfusion bioprocesses using spiked harvest libraries. Biotechnol J, 2022, 11: e2200184
47.
Hubli GB, Bannerjee S, Rathore AS. Near-infrared spectroscopy-based monitoring of all 20 amino acids in mammalian cell culture broth. Talanta, 2023, 254: 124187,
48.
Tiwari A, Bansode V, Rathore AS. Application of advanced machine learning algorithms for anomaly detection and quantitative prediction in protein A chromatography. J Chromatogr A, 2022, 1682: 463486,
49.
Ye K, Sambanis A. Advanced biomanufacturing: a radical manufacturing paradigm shift from conventional, centralized, off-the-shelf production to on-demand, decentralized, plug-and-play production of cell- and tissue-based products. ACS Biomater Sci Eng, 2017, 3: 1460-1461,
50.
Dyball LE, Smales CM. Exosomes: biogenesis, targeting, characterization and their potential as “Plug & Play” vaccine platforms. Biotechnol J, 2022, 17: 2100646
51.
Cummings M, Peters AD, Whitehead GFS, Menon BRK, Micklefield J, Webb SJ, Takano E. Assembling a plug-and-play production line for combinatorial biosynthesis of aromatic polyketides in Escherichia coli. PLoS Biol, 2019, 17: e3000347, pmcid: 6638757
52.
Adiga R, Al-adhami M, Andar A, Borhani S, Brown S, Burgenson D, Cooper MA, Deldari S, Frey DD, Ge X, Guo H, Gurramkonda C, Jensen P, Kostov Y, LaCourse W, Liu Y, Moreira A, Mupparapu KS, Pe?alber-Johnstone C, Pilli M, Punshon-Smith B, Rao A, Rao G, Rauniyar P, Snovida S, Taurani K, Tilahun D, Tolosa L, Tolosa M, Tran K, Vattem K, Veeraraghavan S, Wagner B, Wilhide J, Wood DW, Zuber A. Point-of-care production of therapeutic proteins of good-manufacturing-practice quality. Nat Biomed Eng, 2018, 2: 675-686,
53.
Crowell LE, Lu AE, Love KR, Stockdale A, Timmick SM, Wu D, Wang YA, Doherty W, Bonnyman A, Vecchiarello N, Goodwine C, Bradbury L, Brady JR, Clark JJ, Colant NA, Cvetkovic A, Dalvie NC, Liu D, Liu Y, Mascarenhas CA, Matthews CB, Mozdzierz NJ, Shah KA, Wu SL, Hancock WS, Braatz RD, Cramer SM, Love JC. On-demand manufacturing of clinical-quality biopharmaceuticals. Nat Biotechnol, 2018, 36: 988-995
54.
Yuan SF, Brooks SM, Nguyen AW, Lin WL, Johnston TG, Maynard JA, Nelson A, Alper HS. Bioproduced proteins on demand (Bio-POD) in hydrogels using Pichia pastoris. Bioact Mater, 2021, 6: 2390-2399, pmcid: 7846901
55.
Sullivan CJ, Pendleton ED, Sasmor HH, Hicks WL, Farnum JB, Muto M, Amendt EM, Schoborg JA, Martin RW, Clark LG, Anderson MJ, Choudhury A, Fior R, Lo YH, Griffey RH, Chappell SA, Jewett MC, Mauro VP, Dresios J. A cell-free expression and purification process for rapid production of protein biologics. Biotechnol J, 2016, 11: 238-248,
56.
Murphy TW, Sheng J, Naler LB, Feng X, Lu C. On-chip manufacturing of synthetic proteins for point-of-care therapeutics. Microsyst Nanoeng, 2019, 5: 13, pmcid: 6431678
57.
Hart J, Pomponi F. A circular economy: where will it take us?. Circ Econ Sustain, 2021, 1: 127-141, pmcid: 7941867
58.
Sherwood J. The significance of biomass in a circular economy. Bioresour Technol, 2020, 300: 122755,
59.
Issa I, Delbrück S, Hamm U. Bioeconomy from experts’ perspectives—results of a global expert survey. PLoS ONE, 2019, 14: e0215917, pmcid: 6494193
60.
Rasheed A, San O, Kvamsdal T. Digital twin: Values, challenges and enablers from a modeling perspective. IEEE Access, 2020, 8: 21980-22012
61.
Valverde JM, Avilés-Palacios C. Circular economy as a catalyst for progress towards the sustainable development goals: a positive relationship between two self-sufficient variables. Sustainability, 2021, 13: 12652
62.
Rathore AS, Mishra S, Nikita S, Priyanka P. Bioprocess control: current progress and future perspectives. Life, 2021, 11: 557, pmcid: 8231968
63.
Witcher M. integrating development tools into the process validation lifecycle to achieve six sigma pharmaceutical quality. Bioprocess J5, 2018,

Accesses

Citations

Detail

Sections
Recommended

/