Demonstrating the Stability of Albinterferon Alfa-2b in the Presence of Silicone Oil

Auge, Kristin B.; Blake‐Haskins, Angela W.; Devine, Sean; Rizvi, S. A.; Li, Yiming; Hesselberg, Mark; Orvisky, Eduard; Affleck, Richard P.; Spitznagel, Thomas M.; Perkins, Melissa D.

doi:10.1002/jps.22704

Cited by 28 publications

(20 citation statements)

References 29 publications

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“…These silicone oil droplets may prompt particle formation from protein adsorption to the droplets and coalescence arising from decreased colloidal stability . The silicone oil droplets themselves along with any silicone oil‐induced complexes contribute to a formulation's subvisible particle (SbVP) population . SbVPs are of potential concern because of limits on particulate matter in injectable solutions and the possibility that they may elicit an immunogenic response …”

Section: Introductionmentioning

confidence: 99%

“…It is currently not possible to generalize the effect of silicone oil on every protein; different proteins may vary in their sensitivity. For example, silicone oil has been shown to have no effect on the purity, structure, stability, or biological activity of the fusion protein albinterferon alfa‐2b . On the contrary, the fusion protein abatacept forms visible particles within 20 min of filling into siliconized syringes .…”

Section: Introductionmentioning

confidence: 99%

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Cross-Linked Silicone Coating: A Novel Prefilled Syringe Technology That Reduces Subvisible Particles and Maintains Compatibility with Biologics

DePaz¹,

Chevolleau

Jouffray

et al. 2014

Journal of Pharmaceutical Sciences

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cross-Linked Silicone Coating: A Novel Prefilled Syringe Technology That Reduces Subvisible Particles and Maintains Compatibility with Biologics

DePaz¹,

Chevolleau

Jouffray

et al. 2014

Journal of Pharmaceutical Sciences

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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.…”

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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“…Silicone oil itself was found to cause little damage to the protein during quiescent storage, but did accelerate agitation‐induced aggregation 129. However, silicone oil is not always detrimental to proteins, as was shown for a fusion protein of albumin and interferon α‐2b 132…”

Section: Overview Of Methods For Forced Degradation Studiesmentioning

confidence: 99%

Forced Degradation of Therapeutic Proteins

Hawe

Wiggenhorn²,

Weert

et al. 2012

Journal of Pharmaceutical Sciences

221

154

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Demonstrating the Stability of Albinterferon Alfa-2b in the Presence of Silicone Oil

Cited by 28 publications

References 29 publications

Cross-Linked Silicone Coating: A Novel Prefilled Syringe Technology That Reduces Subvisible Particles and Maintains Compatibility with Biologics

Cross-Linked Silicone Coating: A Novel Prefilled Syringe Technology That Reduces Subvisible Particles and Maintains Compatibility with Biologics

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

Forced Degradation of Therapeutic Proteins

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