Current and future issues in the manufacturing and development of monoclonal antibodies
Abstract
Despite a slow beginning, monoclonal antibodies have had many successes over the past decade. It is important that these successes continue, bringing more products for more indications to market. Although manufacturing is not the most common cause of product failure, product quality issues can delay antibody development. Manufacturing has depended on the triad of process validation, process control and product testing. Applying product knowledge proactively to manufacturing (quality by design) may allow greater flexibility and maintain or improve product quality. An integrated approach to biological characterization is an important aspect of product knowledge. Greater product knowledge also facilitates development in other disciplines. Independent of manufacturing strategy, there are a number of regulatory hurdles in initial and ongoing antibody development. These are described to help prevent unnecessary delays.
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Current best practice relies on three pillars: selection of appropriate starting and raw materials with a low risk of adventitious virus; testing of cell banks and in-process materials to ensure they are free from detectable viruses; and incorporation of steps to remove and inactivate potential undetected adventitious and endogenous viral contaminants during purification.
“The lessons of the past have led to the current best practice, which relies on three pillars: the selection of appropriate starting and raw materials with a low risk of containing adventitious virus; testing of cell banks and in process materials to ensure they are free from detectable viruses; and finally, the incorporation of steps to remove and inactivate potential undetected adventitious and”
From Viral contamination in biologic manufacture and implications for emerging therapies (2020) · cites this paper as [14]
Virus-risk mitigation for biopharmaceutical manufacturing uses three complementary approaches: preventing virus entry by selecting low-risk starting and raw materials and utilizing manufacturing controls; testing of in-process materials to ensure they are free of virus and enable lot rejection; and clearance of virus by inactivation and/or removal from the product.
“As noted above, virus-risk mitigation for biopharmaceutical manufacturing uses three complementary approaches: 1) preventing virus entry by selecting low risk starting and raw materials and utilizing manufacturing controls, 2) testing of in process materials to ensure they are free of virus and enable lot rejection and 3) clearance of virus (inactivation and/or removal) from the product 9,14 .”
From Viral contamination in biologic manufacture and implications for emerging therapies (2020) · cites this paper as [14]
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Can LC-MS/MS and ligand-binding assays live in harmony for large-molecule bioanalysis?
Papadimitriou, A., Bansal, S., Heinrich, J., & Staack, R. (2014) · Bioanalysis · doi:10.4155/bio.14.144 · Cited by 12
Development of Monoclonal Antibodies in China: Overview and Prospects
Zhang, M., Lu, J., Wang, L., Gao, Z.-C., Hu, H., Ung, C. O. L., & Wang, Y. (2015) · BioMed Research International · doi:10.1155/2015/168935 · Cited by 10 · see citing works
“The success of R&D in this area relies heavily on government policies encouraging ethical achievement of gene cloning, humanized construction [37], high expression, mAbs purification [38], and platform construction of phage antibody library technology [39, 40].”
BackgroundMiletich, J., Eich, G., Grampp, G., & Mounho, B. (2011) · mAbs · doi:10.4161/mabs.3.3.15599 · Cited by 11
High-Throughput Process Development for Biopharmaceuticals.
Shukla, A., Rameez, S., Wolfe, L., & Oien, N. P. (2018) · Advances in Biochemical Engineering/Biotechnology · doi:10.1007/10_2017_20 · Cited by 11 · see citing works
Analytical characterization of ch14.18
Soman, G., Kallarakal, A. T., Michiel, D. F., Yang, X., Saptharish, N., Jiang, H., Giardina, S. L., Gilly, J. A., & Mitra, G. (2012) · mAbs · doi:10.4161/mabs.4.1.18566 · Cited by 11 · see citing works
“The ability to sufficiently compare product attributes is dependent on a variety of methods needed to characterize different attributes or the orthogonal methods used to characterize the same attribute.(5,6) Second, a thorough understanding of product attributes can also facilitate a “quality by design” (QbD) approach…”
History of monoclonal antibodies and lessons for the development of stem cell therapeutics
Vertès, A. A., & Dowden, N. J. (2015) · doi:10.1002/9781118846193.ch33 · Cited by 8 · see citing works
Geist, B. J., Davis, D. L., McIntosh, T., Yang, T.-Y., Goldberg, K. M., Han, C., Pendley, C., & Davis, H. (2013) · mAbs · doi:10.4161/mabs.22773 · Cited by 9
“With the development of soft ionization techniques such as electrospray ionization (ESI) or matrix-assisted laser desorption/ionization (MALDI), MS has become a fundamental methodology for comparative structural analysis of therapeutic antibodies from different production systems or formulations Due to their PTMs, rec…”
MethodBioanalytical considerations in the comparability assessment of biotherapeutics.
Lee, J. W., Wang, Y.-M. C., Moxness, M., & Desilva, B. S. (2011) · Bioanalysis · doi:10.4155/bio.11.25 · Cited by 9
- Authors
- Kozlowski, S., & Swann, P.
- Affiliations
- United States Food and Drug Administration (US)
- Corresponding author
- Kozlowski, Steven
- ORCID
- Kozlowski, Steven
- Venue
- Advanced Drug Delivery Reviews
- Publisher
- Elsevier BV
- Published
- 2006-08
- Volume
- 58
- Issue
- 5-6
- Pages
- 707-722
- ISSN
- 0169-409X (ISSN-L)
- OpenAlex
- W2084180910
- Cited by
- 170
- References
- 0
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 4 · 2023: 3 · 2022: 7 · 2021: 5 · 2020: 11 · 2019: 7 · 2018: 6 · 2017: 11 · 2016: 8 · 2015: 10 · 2014: 6 · 2013: 14 · 2012: 16
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Advanced Drug Delivery Reviews (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Keywords
- monoclonal antibodies, biopharmaceutical manufacturing, process validation, process control, quality by design, biological characterization, regulatory challenges, product quality, antibody development
- MeSH terms
- Animals, Antibodies, Monoclonal, Drug Compounding, Drug Industry, Humans, Quality Control, Drug Design
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