Immunogenicity of therapeutic proteins. Part 2: Impact of container closures

Sharma, Basant

doi:10.1016/j.biotechadv.2007.01.006

Cited by 93 publications

(35 citation statements)

References 24 publications

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“…Furthermore, contact materials such as glass, steel, silicone, plastic, rubbers, etc. may influence aggregation 78 where histidine formulated bulk of an IgG1 including sodium chloride resulted in high aggregate levels when stored in a stainless steel tank. 79 …”

Section: Solvent and Surface Effectsmentioning

confidence: 98%

Protein aggregation: Pathways, induction factors and analysis

Mahler

Frieß

Grauschopf

et al. 2009

Journal of Pharmaceutical Sciences

764

635

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Section: Solvent and Surface Effectsmentioning

confidence: 98%

Protein aggregation: Pathways, induction factors and analysis

Mahler

Frieß

Grauschopf

et al. 2009

Journal of Pharmaceutical Sciences

764

635

View full text Add to dashboard Cite

“…There may even be losses to container closures (Sharma 2007) and residual metals (e.g. tungsten in syringes; Bee et al 2009c) are known to interact with protein products, causing aggregation.…”

Section: Figure 2 Herementioning

confidence: 99%

Effects of shear on proteins in solution

2010

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The effects of "shear" on proteins in solution are described and discussed. Research on this topic covers many decades, beginning with investigations of possible denaturation of enzymes during processing, whilst more recent concerns are how the quality of therapeutic proteins might be affected by shear or shear related effects.The paradigm that emerges from most studies is that shear in the fluid mechanical sense is unlikely by itself to damage most proteins and that interfacial phenomena are critically important. In particular, moving gas-liquid interfaces can be very deleterious. Aggregation of therapeutic proteins on nanoparticles shed from solid surfaces is a recent concern because of potential consequences on patient safety. It is clear that labeling such damage as "shear" is a mistake as this inhibits clear investigations of, and thinking about, the true causes of damage to proteins in solution during processing.

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“…[5][6][7] Interactions between proteins and foreign materials, such as rubber, metal particles, and administration devices, can also occur. [8][9][10][11][12] For injectable formulations, syringes (glass or polypropylene) and needles are used for reconstitution and administration. In these devices, silicone oil is used as a lubricant for ease of handling.…”

mentioning

confidence: 99%

Reconstitution of L-Asparaginase in Siliconized Syringes with Shaking and Headspace Air Induces Protein Aggregation

Uchino

Miyazaki

Ohkawa

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

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The aim of this study was to characterize protein aggregation during reconstitution of a highly concentrated solution of lyophilized L-asparaginase (L-ASP). The effect of the preparation method on L-ASP aggregation using siliconized or non-siliconized syringes and the effect of storage after preparation were evaluated by far-UV circular dichroism spectroscopy, Raman microscopy, flow cytometry, and flow particle image analysis. To investigate the effect of syringe type in combination with shaking and headspace air on L-ASP aggregation, four kinds of L-ASP in 5% glucose solutions were prepared (in the presence or absence of silicon oil and headspace air). Slight differences in L-ASP secondary structure were observed between the siliconized and non-siliconized syringe systems before shaking. Large numbers of sub-visible (0.1-100 µm) and submicron (0.1-1 µm) particles were formed by preparation with siliconized syringes and the combination of shaking and headspace air. The number of aggregated particles was not decreased with increased storage time. The Raman microscopy, flow cytometry and flow particle image results suggested that L-ASP interacted with silicone oil, which induced aggregation. Nevertheless, sub-visible and submicron particles were also formed with non-siliconized syringes. However, using non-siliconized syringes, the number of aggregated particles decreased with storage. No changes in particle character were observed before or after shaking with headspace air in non-siliconized syringes, indicating that soluble aggregates formed and dissolved with storage. Silicone oil in syringes, in combination with shaking and headspace air, strongly affected the aggregation of lyophilized L-ASP formulations during preparation.Key words protein aggregation; silicone oil; L-asparaginase (L-ASP); sub-visible particle; flow cytometry; Raman microscopy Various therapeutic proteins have been commercialized owing to recent advances in biotechnology and formulation. These therapeutic proteins are used for the treatment of numerous diseases including cancer, autoimmune diseases, and diabetes mellitus. However, it has been reported that protein aggregates in these products have caused side effects, immunogenicity, and allergic reactions.1-3) Substantial effort has been expended to develop stable formulations to prevent these events. These stable formulations are necessary for safe and effective pharmaceutical therapies.There has been great interest in the external stress affecting protein stability during production, filling, shipment, storage, and final administration. [4][5][6] These external stressors include temperature changes, lyophilization, rehydration, oxidation, and light exposure. [5][6][7] Interactions between proteins and foreign materials, such as rubber, metal particles, and administration devices, can also occur. [8][9][10][11][12] For injectable formulations, syringes (glass or polypropylene) and needles are used for reconstitution and administration. In these devices, silicone oil is used as a lubricant ...

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Immunogenicity of therapeutic proteins. Part 2: Impact of container closures

Cited by 93 publications

References 24 publications

Protein aggregation: Pathways, induction factors and analysis

Protein aggregation: Pathways, induction factors and analysis

Effects of shear on proteins in solution

Reconstitution of L-Asparaginase in Siliconized Syringes with Shaking and Headspace Air Induces Protein Aggregation

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