The DOI matches its Crossref record; 53 of the 54 references it cites were found in a registry or an index.
Determination of critical quality attributes for monoclonal antibodies using quality by design principles
Abstract
Quality by design (QbD) is a global regulatory initiative with the goal of enhancing pharmaceutical development through the proactive design of pharmaceutical manufacturing process and controls to consistently deliver the intended performance of the product. The principles of pharmaceutical development relevant to QbD are described in the ICH guidance documents (ICHQ8-11). An integrated set of risk assessments and their related elements developed at Roche/Genentech were designed to provide an overview of product and process knowledge for the production of a recombinant monoclonal antibody. This chapter describes the identification of critical quality attributes (CQAs) as an important first step for QbD development of biopharmaceuticals. A systematic scientific based risk ranking and filtering approach allows a thorough understanding of quality attributes and an assignment of criticality for their impact on drug safety and efficacy. To illustrate the application of the approach and tools, a few examples from monoclonal antibodies are shown. The identification of CQAs is a continuous process and will further drive the structure and function characterization of therapeutic proteins.
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“Regulatory agencies such the US Food and Drug Administration and European Medicines Agency emphasize that the impact of a CQA on safety and efficacy should be evaluated using a risk assessment and expressed relative to a change in clinical potency compared the reference standard.78”
From Impact of process parameters on IgG glycosylation in CHO systems: a comprehensive quantitative analysis (2026) · cites this paper as [78]
In the citing paper
“In the case of biopharmaceuticals, such as rAAV, attributes of the drug substance (e.g., identity) and knowledge of impurities—either product related (e.g., inactive product variants and aggregates) or process related (e.g., host cell proteins or DNA)—help identify CQAs early in development.11,13”
From Analytical methods for process and product characterization of recombinant adeno-associated virus-based gene therapies (2021) · cites this paper as [13]
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Mistranslation-Induced Protein Misfolding as a Dominant Constraint on Coding-Sequence Evolution
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THE COVALENT STRUCTURE OF AN ENTIRE γG IMMUNOGLOBULIN MOLECULE
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Harris, R. J., Kabakoff, B., Macchi, F. D., Shen, F. J., Kwong, M. Y., Andya, J. D., Shire, S. J., Bjork, N., Tótpál, K., & Chen, A. B. (2001) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(00)00548-x · Cited by 501
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1 of the 54 references couldn’t be matched to a known paper.
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- International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, 2009
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The making of bispecific antibodies
Brinkmann, U., & Kontermann, R. E. (2017) · mAbs · doi:10.1080/19420862.2016.1268307 · Cited by 961
Pharmacokinetics of monoclonal antibodies and Fc-fusion proteins
Liming, L. (2017) · Protein & Cell · doi:10.1007/s13238-017-0408-4 · Cited by 407
Forced degradation of recombinant monoclonal antibodies: A practical guide
Nowak, C., Cheung, J. K., Dellatore, S. M., Katiyar, A., Bhat, R., Sun, J., Ponniah, G., Neill, A., Mason, B. D., Beck, A., et al. (2017) · mAbs · doi:10.1080/19420862.2017.1368602 · Cited by 262
Predicting antibody developability profiles through early stage discovery screening
Bailly, M., Mieczkowski, C., Juan, V., Metwally, E., Tomazela, D., Baker, J., Uchida, M., Kofman, E., Raoufi, F., Motlagh, S., et al. (2020) · mAbs · doi:10.1080/19420862.2020.1743053 · Cited by 228
Gimpel, A. L., Katsikis, G., Sha, S., Maloney, A. J., Hong, M. S., Nguyen, T. N. T., Wolfrum, J., Springs, S. L., Sinskey, A. J., Manalis, S. R., et al. (2021) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2021.02.010 · Cited by 185
Metadata
- Authors
- Alt, N., Zhang, T. Y., Motchnik, P., Taticek, R., Quarmby, V., Schlothauer, T., Beck, H., Emrich, T., & Harris, R. J.
- Affiliations
- Genentech (US)
- F. Hoffmann-La Roche AG (CH)
- Corresponding author
- Alt, Nadja
- Venue
- Biologicals
- Publisher
- Elsevier BV
- Published
- 2016-09
- Volume
- 44
- Issue
- 5
- Pages
- 291-305
- ISSN
- 1045-1056 (ISSN-L)
- OpenAlex
- W2498896723
- Cited by
- 294
- References
- 54
- Citations by year
- 2026: 27 · 2025: 31 · 2024: 39 · 2023: 31 · 2022: 39 · 2021: 29 · 2020: 35 · 2019: 18 · 2018: 18 · 2017: 19 · 2016: 7
- FWCI
- 1.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biologicals (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Life Sciences › Immunology and Microbiology › Immunology › Monoclonal and Polyclonal Antibodies Research
- Keywords
- critical quality attributes, quality by design, monoclonal antibodies, biopharmaceuticals, risk assessment, risk prioritization, recombinant protein expression, drug safety and efficacy, process knowledge
- MeSH terms
- Animals, Antibodies, Monoclonal, Humans, Quality Control, Recombinant Proteins
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