ABSTRACT
Aqueous extractables/leachables from three sterilizing-grade filter membranes [polyvinylidene fluoride (PVDF), polyethersulfone (PES), and mixed cellulose ester (MCE)] were found to significantly reduce the surface tension of aqueous solutions. To evaluate the effect of these extractables/leachables from filter membranes on stability of protein formulations, model IgG2 formulations (with or without added surfactant) were spiked with different levels of filter extractables from stock solutions as a stress study. The stock solutions of extractables were created by processing the filter membranes through autoclaving and soaking steps. The IgG2 formulations were subsequently subject to agitation and temperature stress. Extractables/leachables from the filters were found to have a significant protective (PVDF, PES) and destabilizing (MCE) impact on both visible and subvisible particulates formation under agitation stress for formulations that did not contain any additional surfactant such as polysorbate 80. The impact of filter extractables/leachables on chemical stability of the antibody formulation displayed a more complicated pattern, but was generally destabilizing, causing increases in aggregation, oxidation, and acidic species. In conclusion, extractables/leachables from filter membranes may have impact on protein formulation stability and caution should be exercised during protein filtration, especially when filtering small volumes and in preformulation or high-throughput screening studies.
Subject(s)
Filtration/instrumentation , Membranes, Artificial , Proteins/chemistry , Calorimetry, Differential Scanning , Cellulose , Chromatography, Gel , Chromatography, High Pressure Liquid , Electrophoresis, Capillary , Gas Chromatography-Mass Spectrometry , Hot Temperature , Polymers , Polyvinyls , Sulfones , Surface TensionABSTRACT
Electron attachment to SOF(2), SOCl(2), SO(2)F(2), SO(2)FCl, and SO(2)Cl(2) was studied with two flowing-afterglow Langmuir-probe apparatuses over the temperature range 300-900 K. Attachment rate coefficients at 300 K are k(a) = 2.6+/-0.8x10(-10)(SOF(2)), 1.8+/-0.5x10(-8)(SOCl(2)), 4.8+/-0.7x10(-10)(SO(2)F(2)), 2.4+/-0.7x10(-9)(SO(2)Cl(2)), and 2.0+/-0.6x10(-7) cm(3) s(-1)(SO(2)FCl). Arrhenius plots of the data imply activation energies of 56+/-22 meV(SOF(2)), 92+/-40(SO(2)F(2)), 44+/-22 meV(SOCl(2)), and 29+/-15 meV(SO(2)Cl(2)). The rate coefficients for SO(2)FCl decrease slightly with temperature, commensurate with the decrease in the capture rate coefficient. Electron attachment to SOF(2) and SO(2)F(2) is nondissociative, while reaction with SOCl(2), SO(2)FCl, and SO(2)Cl(2) is dissociative. Dissociative attachment is dominated by channels arising from S-Cl bond cleavage but also includes a minor channel forming a dihalide product ion. Branching fraction data are reported for the dissociative attachment channels.
Subject(s)
Chlorine Compounds/chemistry , Electrons , Fluorine Compounds/chemistry , Oxygen Compounds/chemistry , Sulfur Compounds/chemistry , TemperatureABSTRACT
This article presents case studies involving the use of thermal desorption gas chromatography-mass spectrometry to compositionally characterize pharmaceutical packaging materials for potential extractables. Knowledge of potential extractables and leachables early in the product development program allows the project team to make informed decisions, potentially minimizing redevelopment efforts and reducing cost. Case studies include selection of a label for use on a polyethylene bottle, selection of a drug contact surface of a blister packaging system, and selection of a stopper.
