Batch-to-batch N-glycosylation study of infliximab, trastuzumab and bevacizumab, and stability study of bevacizumab
Open accessAbstract
OBJECTIVES: Infliximab, trastuzumab and bevacizumab are among the most frequently prescribed therapeutic proteins, and like most other therapeutic proteins, are glycosylated. As differences in glycosylation may significantly change the safety and efficacy of therapeutic glycoproteins, it is extremely important to control N-glycosylation consistency. In the first part of this study, the batch-to-batch consistency of the N-glycosylation of infliximab, trastuzumab and bevacizumab was analysed. In the second part, the consistency of the N-glycosylation of bevacizumab stored in polycarbonate syringes (for off-label drug use) for 3 months was examined. METHODS: N-glycans were (i) enzymatically released using peptide-N-glycosidase F, (ii) reduced, and (iii) analysed using hydrophilic interaction liquid chromatography coupled with high-resolution mass spectrometry. Mass spectrometry data were interpreted using principal component analysis combined with two-way analysis of variance and Tukey post hoc tests. The biological activity of infliximab and trastuzumab was examined using enzyme-linked immunosorbent assays. RESULTS: The results of both studies make important contributions to the field of hospital pharmacy. All batches of the studied therapeutic glycoproteins (infliximab, trastuzumab and bevacizumab) varied considerably (especially in galactosylation), while the N-glycosylation of bevacizumab remained unchanged during 3-month storage. CONCLUSIONS: Threshold values for batch-to-batch N-glycosylation variations should be established and batch-to-batch glycosylation consistency should be regularly tested. In our study, samples with significantly different N-glycosylation profiles showed no significant variations in biological activity, suggesting that the differences are probably not therapeutically significant.
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The non-templated biosynthesis of glycans produces heterogeneous glycomic profiles due to enzymatic competition for a common substrate, substrate availability and enzyme-substrate specificity.
“the non-templated biosynthesis of glycans is a major hurdle that produces heterogeneous glycomic profiles as a result of enzymatic competition for a common substrate, substrate availability and enzyme-substrate specificity [6,7].”
From Glycoengineering Chinese hamster ovary cells: a short history (2021) · cites this paper as [7]
The Introduction (page not supplied) describes consistent N-glycosylation profiles as difficult to obtain. The discussion (section labeled “Some,” page not supplied) attributes differing glycosylation patterns in the studied therapeutic proteins to the involvement of hundreds of enzymes. It does not state that glycan biosynthesis is non-templated or identify competition for a common substrate, substrate availability, or enzyme–substrate specificity as the causes. (LLM, conf=0.87)
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- Authors
- Planinc, A., Dejaegher, B., Vander Heyden, Y., Viaene, J., Van Praet, S., Rappez, F., Van Antwerpen, P., & Delporte, C.
- Affiliations
- Université Libre de Bruxelles (BE)
- Centre Hospitalier Universitaire de Saint-Pierre (BE)
- Corresponding author
- Planinc, Ana
- ORCID
- Delporte, Cédric
- Venue
- European Journal of Hospital Pharmacy
- Publisher
- BMJ
- Published
- 2016-09-15
- Volume
- 24
- Issue
- 5
- Pages
- 286-292
- ISSN
- 2047-9956 (ISSN-L)
- 2047-9964
- PMC
- PMC6451607
- OpenAlex
- W2520070907
- Cited by
- 41
- References
- 23
- Citations by year
- 2026: 6 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 9 · 2020: 3 · 2019: 4 · 2018: 2 · 2017: 1
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Hospital Pharmacy (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Fonds De La Recherche Scientifique - FNRS (34553.08)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
- Keywords
- N-glycosylation, infliximab, trastuzumab, bevacizumab, batch-to-batch variation, N-glycan profiling, galactosylation, drug stability, off-label drug use, therapeutic glycoproteins, biological activity, hospital pharmacy
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