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 as 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 to the reference standard.
“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 biopharmaceuticals such as rAAV, attributes of the drug substance and knowledge of impurities, either product related or process related, help identify critical quality attributes early in development.
“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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- 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
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › 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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