Protein Aggregation and Particle Formation in Prefilled Glass Syringes

Gerhardt, Alana; Mcgraw, Nicole R.; Schwartz, Daniel K.; Bee, Jared S.; Carpenter, John F.; Randolph, Theodore W.

doi:10.1002/jps.23973

Cited by 157 publications

(135 citation statements)

References 46 publications

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“…Proteins migrate to the air-water interface (11) and unfold (12) causing aggregation and particle formation (13,14); data supporting this concept can be found in the literature (8)(9)(10). Additionally, agitation may be necessary for induction (10,15,16) and can synergistically worsen aggregation (17,18). …”

Section: Discussionmentioning

confidence: 81%

“…An IA of >∼305 mm 2 was found to promote particle formation for this bioconjugate under the studied experimental conditions and time scales. It is well known that the airwater interface promotes aggregate and particle formation (8,(18)(19)(20), and agitation and/or rupture of the protein gel at the hydrophobic air-water interface leads to increased aggregation (16,17,21). In addition to the presence of an airwater interface, the air-water IA is equally important and a critical IA may promote or inhibit particle formation depending on the therapeutic molecule.…”

Section: Discussionmentioning

confidence: 97%

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Visible and Sub-visible Particle Formation for a Model Bioconjugate

et al. 2016

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The time-course and extent of visible particle (VP) and sub-visible particle (SVP) formation was monitored as a function of interfacial area (IA) for a model bioconjugate. To facilitate particle formation, the bioconjugate was agitated in a glass vial and exposed to IAs up to 478 mm. Since vials had equal fill and headspace volumes, the area of the air-water interface was varied by placing vials on angled blocks at 0°, 30°, 60°, or 90° from the horizontal. A significant increase in visible and sub-visible particle formation was observed with increasing air-water IA. Exposure to IAs below ∼305 mm resulted in the formation of very few particles, while IAs > ∼305 mm resulted in substantial particle formation. Visible and sub-visible particle morphology varied with interfacial area and time. The sub-visible particles initially increased with time but did not reach steady state; instead the initial increase was followed by complete depletion. These phenomena indicate that visible particle formation likely increased at the expense of the sub-visible particle population and demonstrate a potential link between the two particle populations for this model bioconjugate. Initiation of particle formation did not result in corresponding decreases in protein concentration or increases in soluble aggregates. However, extended agitation time resulted in a significant decrease in protein concentration.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 97%

Visible and Sub-visible Particle Formation for a Model Bioconjugate

et al. 2016

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“…This partially unfolded mAb was prone to aggregation, especially during agitation. In another study, mAb formulated without surfactant was filled into prefilled syringes where the mAb was exposed directly to silicone oil/glass surfaces, air-water interfaces, and agitation (Gerhardt et al, 2014). Flow microscopy was used to detect the presence of particles ≥ 2 μm in diameter.…”

Section: Silicone Oil Interactions With Proteins and Mabs In Prefillementioning

confidence: 99%

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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“…Lubricant (silicone oil) in pre-filled glass syringes can cause an aggregation of proteins and therefore generate particles [38]. The reconstitution of L-Asparaginase in siliconised syringes induces protein aggregation [39].…”

Section: Particles From Infusion Setsmentioning

confidence: 99%

Particulate Matter in Injectable Drugs: Evaluation of Risks to Patients

Perez

Maiguy-Foinard

Barthélémy

et al. 2016

Pharmaceutical Technology in Hospital Pharmacy

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AbstractOne of the fundamental principles guiding the pharmaceutical quality of parenteral products is to prevent injecting contaminants from microbiological, chemical or physical sources. It is just as difficult to ensure the absence of chemical and particulate contaminants in injectable products as it is to weigh up the microbiological risk. The problem of particulate matter is mainly related to the preparing and administrating of injectable drugs rather than through the contamination of marketed products. Particulate contamination also arises

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Protein Aggregation and Particle Formation in Prefilled Glass Syringes

Cited by 157 publications

References 46 publications

Visible and Sub-visible Particle Formation for a Model Bioconjugate

Visible and Sub-visible Particle Formation for a Model Bioconjugate

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

Particulate Matter in Injectable Drugs: Evaluation of Risks to Patients

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