Evaluation of the Effect of Syringe Surfaces on Protein Formulations

Majumdar, Sumit; Ford, Brandi M.; Mar, Kevin D.; Sullivan, Vince; Ulrich, Robert G.; D'Souza, Ajit Joseph M.

doi:10.1002/jps.22515

Cited by 89 publications

(76 citation statements)

References 12 publications

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“…One important factor to consider is the different types of syringe that are used for bevacizumab. Reports have been published about bevacizumab being compounded into polypropylene (PP) syringes 13,14,29,30 and the effects of storage conditions 20,31 on the stability and efficacy of bevacizumab. Polycarbonate (PC) syringes have also been used, and were used in the IVAN trial.…”

Section: Introductionmentioning

confidence: 99%

Storage stability of bevacizumab in polycarbonate and polypropylene syringes

Khalili

Sharma

Froome

et al. 2015

Eye

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Section: Introductionmentioning

confidence: 99%

Storage stability of bevacizumab in polycarbonate and polypropylene syringes

Khalili

Sharma

Froome

et al. 2015

Eye

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“…Recently, several authors reported that silicone oil induced protein aggregation. [13][14][15][16] Jones et al showed that aggregation of model proteins occurred with the addition of 0.5% (w/v) silicone oil during incubation at elevated temperatures. 17) Additionally, Thirumangalathu et al reported that silicone oil induced the aggregation of a monoclonal antibody in aqueous solution, and that polysorbate 20 was a useful additive for inhibiting aggregation.…”

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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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“…Conditions of testing need to be carefully evaluated in a case‐by‐case approach. In a study by Majumdar et al, the effect of siliconized and modified syringe surfaces on the stability of different proteins (among others a protein with known sensitivity toward silicone oil) was assessed under quiescent storage at 2–8°C and 25°C, as well as agitation after storage 135. As another example, compatibility with stainless steel surfaces can be evaluated in downscaled stainless steel mini tanks, in which the protein formulation is stored at various temperature conditions for specified and relevant time frames.…”

Section: Overview Of Methods For Forced Degradation Studiesmentioning

confidence: 99%