Biopharmaceutical benchmarks 2018
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Between 2014 and 2018, 84% of newly approved antibody therapeutics were produced in CHO cells.
“between 2014 and 2018 the vast majority (84%) of newly approved antibody therapeutics were produced in CHO cells [5].”
From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [5]
Atezolizumab is a clinically approved (2016-US, 2017-EU) glycoengineered anti-PD-L1 mAb whose Fc has been engineered to lack glycosylation.
“Coming back to Ig-based biotherapeutics, atezolizumab, an oncolytic anti-PD-L1 mAb, is another clinically approved (2016-US, 2017-EU) glycoengineered product, except the Fc has been engineered to lack glycosylation [5].”
From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [5]
CHO cells have become dominant in biotherapeutic production because they produce non-immunogenic and near human-like glycosylation.
“CHO cells have become dominant in biotherapeutic production because they produce non-immunogenic and near human-like glycosylation [5].”
From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [5]
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High-Resolution Native Mass Spectrometry
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“%) were from mammalian cells, one from a transgenic system, five from E. coli, and four from S. cerevisiae (Walsh, 2018).”
BackgroundInfluentialBiopharmaceutical benchmarks 2022
Walsh, G., & Walsh, E. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01582-x · Cited by 575 · see citing works
Self-citationRecent advancements in the genetic engineering of microalgae
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“They represent six of the top ten selling drugs (7) with annual sales exceeding $120 billion in 2017 (8) and are expected to reach $130–200 billion by 2022 (9).”
BackgroundCritical Analysis of the Commercial Potential of Plants for the Production of Recombinant Proteins
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“Biotherapeutics account for approximately 47% of the drugs approved in the United States between 2014–2018, thus there are significant incentives for establishing of PAT‐based analytics for biologics (Walsh, 2018).”
BackgroundSingle B cell technologies for monoclonal antibody discovery
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“are gaining importance as leading therapeutic biologic drugs [4,5].”
BackgroundA single molecular descriptor to predict solution behavior of therapeutic antibodies
Kingsbury, J. S., Saini, A., Auclair, S. M., Fu, L., Lantz, M. M., Halloran, K. T., Calero‐Rubio, C., Schwenger, W. J., Airiau, C. Y., Zhang, J., et al. (2020) · Science Advances · doi:10.1126/sciadv.abb0372 · Cited by 158 · see citing works
“INTRODUCTION Monoclonal antibodies (mAbs) have emerged as a major therapeutic class with more than 60 approved products for treating a wide spectrum of disease, from arthritis to cancer (1) and even infectious diseases (2).”
BackgroundBiotechnology and Bioengineering: Volume 117, Number 10, October 2020
Rombouts, J. L., Kranendonk, E. M. M., Regueira, A., Weissbrodt, D., Kleerebezem, R., & van Loosdrecht, M. (2020) · Biotechnology and Bioengineering · doi:10.1002/bit.27043 · Cited by 141
“The biopharmaceutical industry is following other industries in moving from discrete batch operation to integrated continuous manufacturing, especially for high demand products, such as monoclonal antibodies (MAbs; Shukla, Wolfe, Mostafa, & Norman, 2017; Walsh, 2018).”
Industrial Production of Proteins with Pichia pastoris—Komagataella phaffii
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“, Chinese hamster ovary, CHO), and this outpouring in the biotherapeutics sector can be explained by the increasing monoclonal antibodies’ dominance, requiring humanized post-translational modifications [70].”
BackgroundThe role of Raman spectroscopy in biopharmaceuticals from development to manufacturing
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“Today, there are over 300 approved biopharmaceutical products on the market, consisting mostly of monoclonal antibodies (mAb) produced by mammalian cells [6].”
BackgroundAnimal immunization, in vitro display technologies, and machine learning for antibody discovery
Laustsen, A. H., Greiff, V., Karatt-Vellatt, A., Muyldermans, S., & Jenkins, T. P. (2021) · Trends in Biotechnology · doi:10.1016/j.tibtech.2021.03.003 · Cited by 157 · see citing works
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“The PSIM (Supplementary Data 2) contains the necessary information to construct a protein-speci fi c secretory model from the template reactions in our reconstruction.”
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“Similarly, a variety of protein drugs have been successfully marketed, including monoclonal antibodies (mAbs), recombinant vaccines, and hormones, demonstrating that RPs already play a significant role in the biopharmaceutical field [4].”
BackgroundNanocarriers surface engineered with cell membranes for cancer targeted chemotherapy
Lei, W., Yang, C., Wu, Y. Y., Ru, G., He, X., Tong, X., & Wang, S. (2022) · Journal of Nanobiotechnology · doi:10.1186/s12951-022-01251-w · Cited by 138 · see citing works
“In this connection, efforts to reduce immunogenicity and improve biopharmaceutical stability through modification of biopharmaceuticals have increased [11].”
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Assessing developability early in the discovery process for novel biologics
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“Transient human expression systems are often preferred early on due to the ease and speed of production of workable product quantities,(227) while stable CHO cell lines are preferred for commercial production.(9) This change can cause profound differences in the product yield and quality MABS 9”
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PEGylated liposomes enhance the effect of cytotoxic drug: A review
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Genetic glycoengineering in mammalian cells
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The Role of 89Zr-Immuno-PET in Navigating and Derisking the Development of Biopharmaceuticals
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“Food and Drug Administration (FDA)–approved drugs was about 25% from 2010 to 2013 and 47% from 2014 to 2018 (3).”
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“Over the last few years, several therapeutic proteins have been approved for clinical usage, and others are in the process of development (Leader et al., 2008; Walsh, 2018).”
BackgroundEnzyme capacity-based genome scale modelling of CHO cells
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Nanosuspension Innovations: Expanding Horizons in Drug Delivery Techniques
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“This expression system has been used to produce 84% of the antibodies approved during 2015–2018, accounting for more than half of all approved antibodies during this period (Walsh, 2018).”
MethodKastberg, L. L. B., Ard, R., Jensen, M. K., & Workman, C. T. (2022) · Frontiers in Fungal Biology · doi:10.3389/ffunb.2022.827704 · Cited by 92 · see citing works
“Although several valuable pharmaceutical proteins are expressed from mammalian cell platforms, including therapeutic monoclonal antibodies (Kunert and Reinhart, 2016; Walsh, 2018), these cells grow slower than microbial cell factories and are much more expensive to cultivate (Karbalaei et al.”
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Critical challenges and advances in recombinant adeno‐associated virus (rAAV) biomanufacturing
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“Proteome has been widely utilized in studying monoclonal antibody (mAb) producing CHO cell lines (Strasser, Farrell, et al., 2021; Walsh, 2018), which currently has been engineered and optimized for higher productivity based on earlier proteome investigations.”
BackgroundMethodEnzyme capacity-based genome scale modelling of CHO cells
Yeo, H. C., Hong, J., Lakshmanan, M., & Lee, D.-Y. (2019) · bioRxiv · doi:10.1101/2019.12.19.883652 · Cited by 71
Metabolic Profiling of CHO Cells during the Production of Biotherapeutics
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“Sixty-eight new mAbs were approved between 2014 and 2018, thus representing more than 50% of all new biopharmaceutical products on the market, and mAbs represented the most lucrative product class, with a revenue of $123 billion registered in 2017 [2].”
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Aspergillus: A Powerful Protein Production Platform
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“In fact, almost 84% of the biopharmaceutical proteins are currently produced by Chinese Hamster Ovarian (CHO) cell lines [5].”
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“There is a tremendously strong market demand for recombinant proteins such as industrial enzymes and biopharmaceutical proteins (Walsh, 2018).”
BackgroundScope and limitations on aerosol drug delivery for the treatment of infectious respiratory diseases
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“Currently several biopharmaceutical products (most of them protein-based) are approved in the United States and Europe for the treatment of various diseases [46, 47].”
BackgroundMS/MS-Based Molecular Networking: An Efficient Approach for Natural Products Dereplication
Qin, G.-F., Zhang, X., Zhu, F., Huo, Z.-Q., Yao, Q., Feng, Q., Liu, Z., Zhang, G.-M., Yao, J., & Liang, H.-B. (2022) · Molecules · doi:10.3390/molecules28010157 · Cited by 65
“The reasons given were the rapid advances of biopharmaceuticals [10], kinase-based drugs [11], antibody-drug conjugates (ADC) [12], proteolysis-targeting chimeras (PROTAC) [13], and other methodologies [14,15].”
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“2015; Kaplon and Reichert 2019; Walsh 2018).”
Hybrid modeling for biopharmaceutical processes: advantages, opportunities, and implementation
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“Despite the increasing market sizes and approvals (Walsh, 2018; Walsh and Walsh, 2022), the development of such biologics is typically a slow and resource-intensive process taking up to 10–12 years and an investment of at least 2 billion USD (Narayanan et al.”
BackgroundEmploying active learning in the optimization of culture medium for mammalian cells
Hashizume, T., Ozawa, Y., & Ying, B.-W. (2022) · bioRxiv · doi:10.1101/2022.12.24.521878 · Cited by 63
1Progress, applications, challenges and prospects of protein purification technology
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“Produce drugs (Walsh, 2018), prepare monoclonal antibodies, produce important recombinant glycoproteins such as immunoglobulin G (IgG), growth factor, clotting factor VII, erythropoietin, and α-1 anti-trypsin (Nishida et al., 2017; Goh and Ng, 2018) Insect baculovirus expression vector system It is…”
BackgroundTherapeutic proteins: developments, progress, challenges, and future perspectives
Kumar, V., Barwal, A., Sharma, N., Mir, D. S., Kumar, P., & Kumar, V. (2024) · 3 Biotech · doi:10.1007/s13205-024-03958-z · Cited by 62 · see citing works
“%) of the approved biopharmaceutical products on the market today are produced in CHO cell-based systems (57 products), with the remaining antibodies being expressed in NS0 cells (9 products) or Sp2/0 cells (2 products) (Walsh 2018).”
InfluentialGlycosylation Shapes the Efficacy and Safety of Diverse Protein, Gene and Cell Therapies
Rocamora, F., Peralta, A. G., Shin, S., Sorrentino, J., Wu, M. Y. M., Toth, E. A., Fuerst, T. R., & Lewis, N. E. (2023) · Biotechnology Advances · doi:10.1016/j.biotechadv.2023.108206 · Cited by 63 · see citing works
“Galactosylated rituximab had higher CDC than degalactosylated glycoforms due to its higher affinity to C1q receptors; when Campath-1H was deglycosylated, CDC activity was reduced by 50%(Peschke et al., 2017, Hodoniczky et al., 2005, Boyd et al., 1995).”
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Continuous biomanufacturing with microbes — upstream progresses and challenges
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Microbial protein cell factories fight back?
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Studying protein structure and function by native separation–mass spectrometry
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“Aβ(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage.”
BackgroundMaximizing the Production of Recombinant Proteins in Plants: From Transcription to Protein Stability
Feng, Z., Li, X.-F., Fan, B., Zhu, C.-H., & Chen, Z.-X. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113516 · Cited by 55
“By 2018, 374 protein-based pharmaceutical products had gained a license in the United States and European Union, which accounts for about a third of all pharmaceuticals in development [1].”
BackgroundProtein Engineering Strategies for Improved Pharmacokinetics
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Applications of capillary electrophoresis for biopharmaceutical product characterization
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“…production, specific demands for human post-translational modifications for certain r-proteins have made HEK293 successful alternatives to the conventional CHO cells and in 2018 five approved protein therapeutics were produced in HEK293 cell lines (Dumont et al., 2016; Walsh, 2018).”
BackgroundNanotechnology‐Assisted RNA Delivery: From Nucleic Acid Therapeutics to COVID‐19 Vaccines
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“Moss-based biopharmaceuticals As high-value pharmaceutical products, recombinant pharmaceutical proteins display an increasing sector within the pharmaceutical market [31].”
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“combinant molecules, but particularly mAbs (Walsh, 2018).”
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Sánchez-Trasviña, C., Flores-Gatica, M., Enriquez-Ochoa, D., Rito-Palomares, M., & Mayolo-Deloisa, K. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.717326 · Cited by 49 · see citing works
“9:717326. doi: 10.3389/fbioe.2021.717326 Frontiers in Bioengineering and Biotechnology | www.frontiersin.org August 2021 | Volume 9 | Article 7173261 REVIEW published: 20 August 2021 doi: 10.3389/fbioe.2021.717326 hormones, 16 clotting factors, and nine enzymes were approved in the United States and the European Union…”
BackgroundInfluentialShin, S., Kim, S. H., Shin, S., Grav, L. M., Pedersen, L. E., Lee, J. S., & Lee, G. (2020) · ACS Synthetic Biology · doi:10.1021/acssynbio.0c00097 · Cited by 49
Perspectives for Glyco-Engineering of Recombinant Biopharmaceuticals from Microalgae
Barolo, L., Abbriano, R. M., Commault, A. S., George, J., Kahlke, T., Fabris, M., Padula, M. P., Lopez, A., Ralph, P. J., & Pernice, M. (2020) · Cells · doi:10.3390/cells9030633 · Cited by 65 · see citing works
“Few recombinant biopharmaceuticals produced in alternative host systems have successfully passed clinical trials and reached commercialization status [2,78].”
BackgroundAn optimized genome-wide, virus-free CRISPR screen for mammalian cells
Xiong, K., Karottki, K. J. L. C., Hefzi, H., Li, S., Grav, L. M., Li, S., Spahn, P. N., Lee, J. S., Ventiņa, I., Lee, G. M., et al. (2021) · Cell Reports Methods · doi:10.1016/j.crmeth.2021.100062 · Cited by 38 · see citing works
“In this study, we present a new VF CRISPR screening platform and demonstrate it in CHO cells, the model of choice for producing pharmaceutical proteins (Walsh, 2018).”
Hilliard, W., MacDonald, M. L., & Lee, K. H. (2020) · Biotechnology and Bioengineering · doi:10.1002/bit.27432 · Cited by 48 · see citing works
“CHO cells have several advantageous characteristics, including robust growth in suspension culture and the ability to generate proteins with human‐ like glycosylation patterns, that have led to their long history of use as a workhorse organism to produce many recombinant proteins, and monoclonal antibodies (mAbs) in p…”
BackgroundAttenuating apoptosis in Chinese hamster ovary cells for improved biopharmaceutical production
Henry, M. N., MacDonald, M. A., Orellana, C. A., Gray, P. P., Gillard, M., Baker, K. N., Nielsen, L. K., Marcellin, E., Mahler, S. M., & Martínez, V. S. (2020) · Biotechnology and Bioengineering · doi:10.1002/bit.27269 · Cited by 51 · see citing works
“Introduction The global biotherapeutics market was valuated at $188 billion USD in 2017 (Walsh, 2018) and continues to grow.”
Screening Strategies for High-Yield Chinese Hamster Ovary Cell Clones
Yang, W., Zhang, J., Xiao, Y., Li, W., & Wang, T. (2022) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2022.858478 · Cited by 43 · see citing works
“Among the top 10 drugs in global sales in 2019, eight are biopharmaceuticals, and seven are monoclonal antibodies produced in CHO cells (Walsh, 2018; Bhutani et al., 2021), mainly due to its ability to express various recombinant proteins with a post translational modification pattern similar to…”
BackgroundDomján, J., Pantea, E., Gyürkés, M., Madarász, L., Kozák, D., Farkas, A., Horváth, B., Benkő, Z., Nagy, Z. K., Marosi, G., et al. (2022) · Biotechnology Journal · doi:10.1002/biot.202100395 · Cited by 49 · see citing works
“Chinese hamster ovary (CHO) cells are themost commonly usedmammalian host organism for the production of high-value therapeutic monoclonal antibodies (mAbs).[1,2] The process performance of CHO cell cultures strongly depends on the cultivation conditions prevailing”
BackgroundProgress of cationic gene delivery reagents for non-viral vector
Ma, K., Mi, C.-L., Cao, X.-X., & Wang, T.-Y. (2021) · Applied Microbiology and Biotechnology · doi:10.1007/s00253-020-11028-6 · Cited by 46 · see citing works
“Mammalian cells e expression systems have some advantages compared with other expression system, such as Escherichia coli, yeast, and insect cells (Walsh 2018).”
BackgroundKoenig, S., Bee, C., Borovika, A., Briddell, C., Colberg, J., Humphrey, G., Kopach, M., Martínez, I., Nambiar, S., Plummer, S., et al. (2019) · ACS Sustainable Chemistry and Engineering · doi:10.1021/acssuschemeng.9b02842 · Cited by 46 · see citing works
Rong, Y., Jensen, S. I., Lindorff-Larsen, K., & Nielsen, A. (2022) · Biotechnology Advances · doi:10.1016/j.biotechadv.2022.108079 · Cited by 45 · see citing works
Refolding in the modern biopharmaceutical industry
Buscajoni, L., Martinetz, M. C., Berkemeyer, M., & Brocard, C. (2022) · Biotechnology Advances · doi:10.1016/j.biotechadv.2022.108050 · Cited by 48 · see citing works
Rashid, M. H. (2022) · mAbs · doi:10.1080/19420862.2022.2111748 · Cited by 47 · see citing works
“It remains a popular host as evidenced by its use in the production of more than 85 approved drugs, and many more protein therapeutics in clinical and preclinical development.(3,4) This popularity stems from its fast growth, low cost of production, easy handling, versatile genetic manipulation, high productivity, and…”
BackgroundThe cell density effect in animal cell-based bioprocessing: Questions, insights and perspectives
Lavado‐García, J., Pérez‐Rubio, P., Cervera, L., & Gòdia, F. (2022) · Biotechnology Advances · doi:10.1016/j.biotechadv.2022.108017 · Cited by 47 · see citing works
β-Glucans from Yeast—Immunomodulators from Novel Waste Resources
Thomas, S., Rezoagli, E., Abidin, I. Z., Major, I., Murray, P., & Murphy, E. J. (2022) · Applied Sciences · doi:10.3390/app12105208 · Cited by 51 · see citing works
Yeasts as Biopharmaceutical Production Platforms
Kulagina, N., Besseau, S., Godon, C., Goldman, G., Papon, N., & Courdavault, V. (2021) · Frontiers in Fungal Biology · doi:10.3389/ffunb.2021.733492 · Cited by 45
“Following the first murine mAb approved and commercialized in 1986 to prevent kidney transplant rejection, more than 100 mAbs were developed (Walsh, 2018).”
BackgroundInfluentialValdez‐Cruz, N. A., García‐Hernández, E., Espitia, C., Cobos-Marín, L., Altamirano, C., Bando-Campos, C. G., Cofas‐Vargas, L. F., Coronado-Aceves, E. W., González-Hernández, R. A., Hernández‐Peralta, P., et al. (2021) · Microbial Cell Factories · doi:10.1186/s12934-021-01576-5 · Cited by 49 · see citing works
Sergeeva, D., Lee, G. M., Nielsen, L. K., & Grav, L. M. (2020) · ACS Synthetic Biology · doi:10.1021/acssynbio.0c00322 · Cited by 58 · see citing works
Protein materials as sustainable non- and minimally invasive strategies for biomedical applications.
Stie, M. B., Kalouta, K., Vetri, V., & Foderà, V. (2022) · Journal of Controlled Release · doi:10.1016/j.jconrel.2022.02.016 · Cited by 44 · see citing works
Temperature-responsive chromatography for bioseparations: A review
Nagase, K., & Kanazawa, H. (2020) · Analytica Chimica Acta · doi:10.1016/j.aca.2020.07.075 · Cited by 52 · see citing works
Roesch, A., Zölls, S., Stadler, D., Helbig, C., Wuchner, K., Kersten, G. F. A., Hawe, A., Jiskoot, W., & Menzen, T. (2021) · Journal of Pharmaceutical Sciences · doi:10.1016/j.xphs.2021.12.011 · Cited by 44 · see citing works
Torres, M., Akhtar, S., McKenzie, E. A., & Dickson, A. J. (2020) · Biotechnology Journal · doi:10.1002/biot.202000081 · Cited by 49 · see citing works
Farsang, E., Guillarme, D., Veuthey, J., Beck, A., Lauber, M. A., Schmudlach, A., & Fekete, S. (2020) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2020.113207 · Cited by 55 · see citing works
Towards a new avenue for producing therapeutic proteins: Microalgae as a tempting green biofactory
Dehghani, J., Adibkia, K., Movafeghi, A., Maleki, H., Saeedi, N., & Omidi, Y. (2019) · Biotechnology Advances · doi:10.1016/j.biotechadv.2019.107499 · Cited by 51 · see citing works
The Rocky Road From Fed-Batch to Continuous Processing With E. coli
Kopp, J., Slouka, C., Spadiut, O., & Herwig, C. (2019) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2019.00328 · Cited by 42 · see citing works
“Even though biopharmaceutical production is generally still carried out batch-wise, new technology has emerged (Walsh, 2014, 2018), and many drugs can currently be sold at the cheapest prices ever (Berlec and Strukelj, 2013; Jungbauer, 2013; Walsh, 2018).”
BackgroundAmasawa, E., Kuroda, H., Okamura, K., Badr, S., & Sugiyama, H. (2021) · ACS Sustainable Chemistry and Engineering · doi:10.1021/acssuschemeng.1c01435 · Cited by 41 · see citing works
Recent applications of ion mobility spectrometry in natural product research
Masike, K., Stander, M. A., & de Villiers, A. J. (2020) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2020.113846 · Cited by 50 · see citing works
- Authors
- Walsh, G.
- Affiliations
- University of Limerick (IE)
- Corresponding author
- Walsh, Gary
- ORCID
- Walsh, Gary
- Venue
- Nature Biotechnology
- Published
- 2018-12
- Volume
- 36
- Issue
- 12
- Pages
- 1136-1145
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- OpenAlex
- W2917928050
- Cited by
- 978
- References
- 15
- Citations by year
- 2026: 68 · 2025: 68 · 2024: 88 · 2023: 141 · 2022: 173 · 2021: 197 · 2020: 173 · 2019: 65
- FWCI
- 165.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Pharmaceutical Economics and Policy
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Keywords
- biopharmaceutical market, monoclonal antibodies, cell therapy, gene therapy, biosimilars, biologics, market growth
- MeSH terms
- Animals, Antibodies, Monoclonal, Biological Products, Biotechnology, Drug Industry, European Union, Humans, Nucleic Acids, Recombinant Proteins, United States, United States Food and Drug Administration, Drug Approval, Benchmarking, Biosimilar Pharmaceuticals
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