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Cited by 158Protein purification and stabilityBiosimilars and Bioanalytical MethodsAnalytical Methods in Pharmaceuticals

Effects of Syringe Material and Silicone Oil Lubrication on the Stability of Pharmaceutical Proteins

Open access
Krayukhina, Elena, Tsumoto, Kouhei, Uchiyama, Susumu, Fukui, Kiichi·2015·Journal of Pharmaceutical Sciences
DOI 10.1002/jps.24184PMC PMC4359023
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Abstract

Currently, polymer-based prefillable syringes are being promoted to the pharmaceutical market because they provide an increased break resistance relative to traditionally used glass syringes. Despite this significant advantage, the possibility that barrel material can affect the oligomeric state of the protein drug exists. The present study was designed to compare the effect of different syringe materials and silicone oil lubrication on the protein aggregation. The stability of a recombinant fusion protein, abatacept (Orencia), and a fully human recombinant immunoglobulin G1, adalimumab (Humira), was assessed in silicone oil-free (SOF) and silicone oil-lubricated 1-mL glass syringes and polymer-based syringes in accelerated stress study. Samples were subjected to agitation stress, and soluble aggregate levels were evaluated by size-exclusion chromatography and verified with analytical ultracentrifugation. In accordance with current regulatory expectations, the amounts of subvisible particles resulting from agitation stress were estimated using resonant mass measurement and dynamic flow-imaging analyses. The amount of aggregated protein and particle counts were similar between unlubricated polymer-based and glass syringes. The most significant protein loss was observed for lubricated glass syringes. These results suggest that newly developed SOF polymer-based syringes are capable of providing biopharmaceuticals with enhanced physical stability upon shipping and handling.

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Crossref · 10.1002/jps.24184

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  • Protein aggregates can form prior to intravitreal injection and can be further induced by SO release from syringes.

    “Protein aggregates can form under a variety of circumstances prior to intravitreal injection of the drug and they can be further induced by SO release from syringes [57–59].”

    From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [57]

    The Introduction describes aggregation during shipping and handling, and the Results report more insoluble aggregates in silicone oil-lubricated than silicone oil-free syringes. The Quantification of Protein Particles section finds a correlation between silicone oil droplets and particle formation, but does not establish that oil released from syringes caused the aggregates. The study used abatacept and adalimumab under agitation stress; it did not examine drugs prior to intravitreal injection. Page numbers are unavailable in our copy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Many processes involved in shipping, handling and storage of anti-VEGF medications and syringes can contribute to SO release and protein aggregation.

    “Many processes involved in the shipping, handling and storage of anti-VEGF medications and syringes can contribute to SO release and protein aggregation [55, 57–59].”

    From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [57]

    The Introduction describes shipping- and handling-related agitation as a cause of protein aggregation, and Results and Discussion (Quantification of Protein Particles) reports silicone oil droplets and increased particle counts in lubricated syringes. The study tested abatacept and adalimumab, not anti-VEGF medications, and it does not establish effects of storage. No page numbers are available in our copy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Various factors can contribute to SO release from the inner cylinder wall, protein denaturing, or both.

    “Various factors can contribute to SO release from the inner cylinder wall, protein denaturing, or both [55, 57–59].”

    From Mechanisms of sterile inflammation after intravitreal injection of antiangiogenic drugs: a narrative review (2021) · cites this paper as [57]

    The Results and Discussion (Quantification of Protein Particles; page not provided) reports silicone-oil droplets in syringe samples and examines how syringe material and lubrication relate to protein particle formation. It also says the reason for higher droplet counts in glass syringes is unclear. The paper supports the broad point that several factors affect protein stability, but it does not establish which factors cause silicone oil to be released from the inner wall or demonstrate protein denaturation specifically. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

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Cites

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Research works printed but not linked: 1

  1. [15]Kirshner S Regulatory expectations for analysis of aggregates and particles Talk at workshop on protein aggregation and immunogenicity 2012 Breckenridge, Colorado 12 July

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Authors
Krayukhina, E., Tsumoto, K., Uchiyama, S., & Fukui, K.
Affiliations
  • Shijonawate Gakuen Junior College (JP)
  • Institute of Medical Science, The University of Tokyo (JP)
  • The University of Osaka (JP)
Corresponding author
  • Uchiyama, Susumu
  • Fukui, Kiichi
ORCID
Venue
Journal of Pharmaceutical Sciences
Publisher
Elsevier BV
Published
2015-02
Volume
104
Issue
2
Pages
527-535
ISSN
0022-3549 (ISSN-L)
DOI
10.1002/jps.24184
PMC
PMC4359023
OpenAlex
W1973254030
Cited by
158
References
23
Citations by year
2026: 13 · 2025: 14 · 2024: 5 · 2023: 13 · 2022: 15 · 2021: 18 · 2020: 17 · 2019: 19 · 2018: 15 · 2017: 14 · 2016: 11 · 2015: 4
FWCI
3.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Pharmaceutical Sciences (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc)
  • OUKA (Osaka University Knowledge Archive) (Osaka University) (submittedVersion, cc-by-nc)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein purification and stability
  • Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
  • Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
Keywords
glass syringes, protein aggregation, protein stability, abatacept, adalimumab, recombinant fusion protein, IgG1, accelerated stress testing, subvisible particles
MeSH terms
Humans, Immunoglobulin G, Lubrication, Silicone Oils, Syringes, Protein Stability, CTLA-4 Antigen

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