title: Evaluation of the effect of syringe surfaces on protein formulations.
abstract: Packaging of drugs in prefillable syringes offers considerable advantages over conventional vials. Almost all major biotech molecules are available on the market today in prefilled syringes, and are safe and efficacious. Newer high-concentration liquid formulations, especially fusion proteins, however, can suffer from instability in prefilled syringes due to syringe components like silicone oil. To assess the effect of siliconized and modified syringe surfaces on protein formulations, the stability of the recombinant protective antigen (rPA) for anthrax, abatacept, a fusion protein formulation with known silicone oil sensitivity, and an antistaphylococcal enterotoxin B (anti-SEB) monoclonal antibody (mAb) was assessed in siliconized, uncoated, and BD-42-coated (a proprietary coating developed by BD Technologies) prefilled syringes under different conditions. Both the soluble protein content and the number of subvisible particles were followed over time. When filled in siliconized syringes, all three protein solutions showed increased number of subvisible particles relative to uncoated or BD-42-coated syringes; the abatacept formulation with known silicone sensitivity also developed visible particles. Although rPA and anti-SEB mAb formulations mainly showed individual droplets, presumably of silicone, the abatacept formulation also showed droplets entangled in a fibrous structure. Uncoated glass and BD-42-coated syringes considerably reduced the formation of both visible and subvisible particles after immediate contact and after agitation. The anti-SEB mAb also adhered as a thin layer to the siliconized surface after agitation, irrespective of storage temperature. The development of visible particles could not be correlated with the loss of soluble protein fraction at protein concentrations above 4 mg/mL. It appears that protein formulations interact differently with different surfaces. The BD-42 coating appears to be a promising solution for packaging silicone-sensitive proteins in prefillable syringes and needs to be investigated further. It is demonstrated that BD-42 provides an inert surface with adequate lubrication while limiting the formation of visible and subvisible particles. It is hypothesized that these particles are formed due to the release of silicone droplets in the solution and result in the formation of silicone-induced visible aggregates.
authors.affiliation: BD Technologies, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Sumit
authors.initials: S
authors.lastname: Majumdar
authors.forename: Brandi M
authors.initials: BM
authors.lastname: Ford
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Mar
authors.forename: Vince J
authors.initials: VJ
authors.lastname: Sullivan
authors.forename: Robert G
authors.initials: RG
authors.lastname: Ulrich
authors.forename: Ajit Joseph M
authors.initials: AJ
authors.lastname: D'souza
mesh_terms: D000069594:Abatacept; D000268:Adhesiveness; D022122:Anthrax Vaccines / Q000737:chemistry; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D004768:Enterotoxins / Q000276:immunology; D004867:Equipment Design; D018796:Immunoconjugates / Q000737:chemistry; D011489:Protein Denaturation; D055550:Protein Stability; D011994:Recombinant Proteins / Q000737:chemistry; D012827:Silicone Oils / Q000737:chemistry*; D012995:Solubility; D013499:Surface Properties; D013594:Syringes; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D013997:Time Factors
chemical_list: D022122:Anthrax Vaccines; D000911:Antibodies, Monoclonal; D004768:Enterotoxins; D018796:Immunoconjugates; D011994:Recombinant Proteins; D012827:Silicone Oils; C031818:enterotoxin B, staphylococcal; D000069594:Abatacept