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

DePaz, Roberto A; Chevolleau, Tzvetelina; Jouffray, Sébastien; Narwal, Roja; Dimitrova, Mariana N.

doi:10.1002/jps.23947

Cited by 37 publications

(13 citation statements)

References 24 publications

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“…This may result in aggregation formation with the protein and silicon oil droplets in the protein formula, which could also influence flow and regularity of delivery, as well as the action of the protein‐based drug 13 . There have been various attempts to confront the problem with new coating techniques for syringe housing showing promising advantages regarding protein aggregation and silicon oil droplet formation in small syringes 14,15 . Whether the newly developed systems can be used on these larger types of syringes and with short‐acting cardiovascular drugs has yet to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Flow irregularities from syringe infusion pumps caused by syringe stiction

Peduzzi

Batliner

Grass

et al. 2020

Pediatric Anesthesia

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Objective The current study aimed to evaluate the extent of the slide‐stick phenomenon in differently designed infusion syringes at various infusion rates and filling positions. Methods Fluid delivery from three 50‐mL infusion syringe brands (BD; Codan; Fresenius) was investigated using a flow sensor at flow rates of 0.5, 1.0, or 5.0 mL h−1, with the syringes filled with either 10, 30, or 50 mL of distilled water. Two identical models (A/B) of the same infusion pump model were used. The effect of flow rate variations on the plasma concentration of a continuous epinephrine infusion in a 3 kg neonate receiving a continuous infusion of 0.1 μg kg min−1 epinephrine was studied using a pharmacokinetic simulation model. Results Considerable variations in calculated plasma epinephrine concentration were detected between flow rates of 5 and 0.5 or 1 mL h−1 for all syringe types and filling volumes. The median deviation of plasma concentration for the 5 mL h−1 flow rate varied depending on assembly from 1.3% (Codan) to 1.8% (Fresenius). This was more pronounced for lower flow rates, where at 1 mL h−1 the deviation varied from 3.3% (BD) to 4.8% (Fresenius) and at 0.5 mL h−1from 4.9% (BD) to 5.4% (Fresenius). Differences between filling volumes (within syringe type and flow rate) did not appear to have relevant influence on variations in calculated plasma epinephrine concentration. Conclusion Infusion set rate rather than syringe brand or filling volume was a major predictor for syringe stiction‐related amount of variation in the calculated plasma epinephrine concentration.

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Section: Discussionmentioning

confidence: 99%

Flow irregularities from syringe infusion pumps caused by syringe stiction

Peduzzi

Batliner

Grass

et al. 2020

Pediatric Anesthesia

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“…It was shown that a baked-on silicone oil surface resulted in less particulate formation for an IgG 2 mAb compared to a standard siliconized glass syringe (see Figure 5 in Badkar, Wolf, Bohack, & Kolhe, 2011). Alternative technologies using cross-linked silicone oil to minimize sloughing from the surface have also been developed (Depaz, Chevolleau, Jouffray, Narwal, & Dimitrova, 2014). A comparison of submicron particulate counts in polysorbate 80 solutions in phosphate-buffered saline shows a reduction in counts for a baked-on silicone oil layer and a chemically cross-linked silicone oil surface compared to a standard sprayed-on process for prefilled syringes (Figure 8.2(a)) using different instruments ( Figure 8.2(b)).…”

Section: Silicone Oil Interactions With Proteins and Mabs In Prefillementioning

confidence: 97%

Development of delivery device technology to deal with the challenges of highly viscous mAb formulations at high concentration

Shire¹

2015

Monoclonal Antibodies

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“…There are numerous studies assessing the mechanisms of mAb aggregation (Li et al, 2011;Morris et al, 2009) and the effects of silicone-oil (Basu et al, 2013;Gerhardt et al, 2014;Jones et al, 2005;Weinbuch et al, 2013b) or polysorbate surfactants (Agarkhed et al, 2013;Khan et al, 2015) in influencing the aggregation process; such studies include novel methods to reduce in situ mAb aggregation in PFS (Depaz et al, 2014). However, the focus has been the larger sub-visible size range of particulates i.e.…”

Section: Common Termsmentioning

confidence: 99%

“…The limit of detection (LOD) was set at 0.01 Hz (corresponding to 0.07 µm for protein particles and 0.17 m for silicone-oil particles) and 0.03 Hz (corresponding to 0.33 µm for protein particles and 0.68 m for silicone-oil particles) for the nano and micro sensors, respectively. System set-up and cleaning procedures are described by the manufacturer and elsewhere (Depaz et al, 2014;Weinbuch et al, 2013b). …”

Section: Resonant Mass Measurement (Rmm)mentioning

confidence: 99%

Evaluation of aggregate and silicone-oil counts in pre-filled siliconized syringes: An orthogonal study characterising the entire subvisible size range

Shah

Rattray

Day³

et al. 2017

International Journal of Pharmaceutics

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Characterisation of particulates in therapeutic monoclonal antibody (mAb) formulations is routinely extended to the sub-visible size-range (0.1-, with the increased use of prefilled syringes (PFS), particle differentiation is required between proteinaceous and non-proteinaceous particles such as silicone-oil droplets. Here, three orthogonal techniques: Raster Image Correlation Spectroscopy (RICS), Resonance Mass Measurements (RMM) and Micro-Flow Imaging (MFI), were evaluated with respect to their sub-visible particle measurement and characterisation capabilities. Particle formation in mAb PFS solutions was evaluated with increasing polysorbate-20 (PS-20) concentrations. All three techniques provided complementary but distinct information on protein aggregate and silicone-oil droplet presence. PS-20 limited the generation of mAb aggregates during agitation, while increasing the number of silicone-oil droplets (PS-20 concentration dependent). MFI and RMM revealed PS-20 lead to the formation of larger micron-sized droplets, with RICS revealing an increase in smaller submicron droplets. Subtle differences in data sets complicate the apparent correlation between silicone-oil sloughing and mAb aggregates' generation. RICS (though the use of a specific dye) demonstrates an improved selectivity for mAb aggregates, a broader measurement size-range and smaller sample volume requirement. Thus, RICS is proposed to add value to the currently available particle measurement techniques and enable informed decisions during mAb formulation development. ABSTRACTCharacterisation of particulates in therapeutic monoclonal antibody (mAb) formulations is routinely extended to the sub-visible size-range (0.1-10 m). Additionally, with the increased use of pre-filled syringes (PFS), particle differentiation is required between proteinaceous and non-proteinaceous particles such as silicone-oil droplets. Here, three orthogonal techniques: Raster Image Correlation Spectroscopy (RICS), Resonance Mass Measurements (RMM) and Micro-Flow Imaging (MFI), were evaluated with respect to their sub-visible particle measurement and characterisation capabilities. Particle formation in mAb PFS solutions was evaluated with increasing polysorbate-20 (PS-20) concentrations. All three techniques provided complementary but distinct information on protein aggregate and silicone-oil droplet presence. PS-20 limited the generation of mAb aggregates during agitation, while increasing the number of silicone-oil droplets (PS-20 concentration dependant). MFI and RMM revealed PS-20 lead to the formation of larger micron-sized droplets, with RICS revealing an increase in smaller sub-micron droplets. Subtle differences in data sets complicate the apparent correlation between silicone-oil sloughing and mAb aggregates' generation. RICS (though the use of a specific dye) demonstrates an improved selectivity for mAb aggregates, a broader measurement size-range and smaller sample volume requirement. Thus, RICS is proposed to add value to the currently available pa...

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

Cited by 37 publications

References 24 publications

Flow irregularities from syringe infusion pumps caused by syringe stiction

Flow irregularities from syringe infusion pumps caused by syringe stiction

Development of delivery device technology to deal with the challenges of highly viscous mAb formulations at high concentration

Evaluation of aggregate and silicone-oil counts in pre-filled siliconized syringes: An orthogonal study characterising the entire subvisible size range

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