Controlled Extraction Studies Applied to Polyvinyl Chloride and Polyethylene Materials: Conclusions from the ELSIE Controlled Extraction Pilot Study.

The effective management of leachables in pharmaceutical products is a critical aspect of their development. This can be facilitated if extractables information on the materials used in a packaging or delivery system is available to assist companies in selecting materials that will be compatible with the drug product formulation and suitable for the intended use. The Extractables and Leachables Safety Information Exchange (ELSIE) materials working group developed and executed a comprehensive extraction study protocol that included a number of extraction solvents, extraction techniques, and a variety of analytical techniques. This was performed on two test materials, polyethylene (PE) and polyvinyl chloride (PVC), that were selected due to their common use in pharmaceutical packaging. The purpose of the study was to investigate if the protocol could be simplified such that (i) a reduced number or even a single extraction technique could be used and (ii) a reduced number of solvents could be used to obtain information that is useful for material selection regardless of product type. Results indicate that, at least for the PVC, such reductions are feasible. Additionally, the studies indicate that levels of extractable elemental impurities in the two test materials were low and further confirm the importance of using orthogonal analytical detection techniques to gain adequate understanding of extraction profiles.

Characterization of the initial level and migration of silicone oil lubricant in empty prefilled syringes for biologics using infrared spectroscopy.

Glass prefillable syringes are lubricated with silicone oil to ensure functionality and a consistent injection for the end user. If excessive silicone is applied, droplets could potentially result in aggregation of sensitive biopharmaceuticals or clouding of the solution. Therefore, monitoring and optimization of the applied silicone layer is critical for prefilled syringe development. The hydrophobic properties of silicone oil, the potential for assay interference, and the very small quantities applied to prefilled syringes present a challenge for the development of a suitable assay. In this work we present a rapid and simple Fourier transform infrared (FTIR) spectroscopy method for quantitation of total silicone levels applied to prefilled syringes. Level-dependent silicone oil migration occurred over time for empty prefilled syringes stored tip-up. However, migration from all prefilled syringes with between 0.25 and 0.8 mg of initial silicone oil resulted in a stable limiting minimum level of between 0.15 and 0.26 mg of silicone in the syringe reached after 1 to 4 years of empty tip-up storage. The results of the FTIR assay correlated well with non-destructive reflectometry characterization of the syringes. This assay can provide valuable data for selection of a robust initial silicone oil target and quality control of prefilled syringes intended for biopharmaceuticals. LAY ABSTRACT: Glass prefillable syringes are lubricated with silicone oil to ensure functionality and a consistent injection for the end user. If excessive silicone is applied, droplets could potentially result in aggregation of sensitive biopharmaceuticals or clouding of the solution. Therefore, monitoring and optimization of the applied silicone layer is critical for prefilled syringe development. The hydrophobic properties of silicone oil, the potential for assay interference, and the very small quantities applied to prefilled syringes present a challenge for the development of a suitable assay. In this work we present a rapid and simple Fourier transform infrared (FTIR) spectroscopy method for quantitation of total silicone levels applied to prefilled syringes. Level-dependent silicone oil migration occurred over time for empty prefilled syringes stored tip-up. However, migration from all prefilled syringes with between 0.25 and 0.8 mg of initial silicone oil resulted in a stable limiting minimum level of between 0.15 and 0.26 mg of silicone in the syringe reached after 1 to 4 years of empty tip-up storage. The results of the FTIR assay correlated well with non-destructive reflectometry characterization of the syringes. This assay can provide valuable data for selection of a robust initial silicone oil target and quality control of prefilled syringes intended for biopharmaceuticals.