title: Evaluation of aggregate and silicone-oil counts in pre-filled siliconized syringes: An orthogonal study characterising the entire subvisible size range.
abstract: Characterisation of particulates in therapeutic monoclonal antibody (mAb) formulations is routinely extended to the sub-visible size-range (0.1-10μm). 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 particle measurement techniques and enable informed decisions during mAb formulation development.
authors.affiliation: Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: Maryam
authors.initials: M
authors.lastname: Shah
authors.affiliation: Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Rattray
authors.affiliation: MedImmune Ltd, Formulation Sciences, Granta Park, Cambridge, UK.
authors.forename: Katie
authors.initials: K
authors.lastname: Day
authors.affiliation: MedImmune Ltd, Formulation Sciences, Granta Park, Cambridge, UK.
authors.forename: Shahid
authors.initials: S
authors.lastname: Uddin
authors.affiliation: School of Chemical Engineering and Analytical Sciences, University of Manchester, Manchester, UK.
authors.forename: Robin
authors.initials: R
authors.lastname: Curtis
authors.affiliation: MedImmune Ltd, Formulation Sciences, Granta Park, Cambridge, UK.
authors.forename: Christopher F
authors.initials: CF
authors.lastname: van der Walle
authors.affiliation: Division of Pharmacy and Optometry, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. Electronic address: Alain.Pluen@manchester.ac.uk.
authors.forename: Alain
authors.initials: A
authors.lastname: Pluen
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D012827:Silicone Oils / Q000737:chemistry*; D013594:Syringes
chemical_list: D000911:Antibodies, Monoclonal; D011136:Polysorbates; D012827:Silicone Oils
keywords: Monoclonal antibody; Particle; Primary packaging; Protein aggregation; Raster image correlation spectroscopy; Silicone-oil