Using Extractables Data of Sterile Filter Components for Scaling Calculations.

Abstract

Users of single-use (SU) components need extractables data to demonstrate material safety for regulatory bodies before incorporation in the biopharmaceutical process. In this context, the correct use of such extractables data is key to deriving realistic risk assessments for SU devices. In this paper, a standardized extractables approach was used that provides comprehensive extractables information including identity and quantity. The combination of extractables data obtained from different components of a sterile filter capsule, such as the filter cartridge and housing, and the scaling thereof is presented. A sterile filter type including polyethersulfone membrane was extracted with pure water and pure ethanol at 40°C for 24 h. The organic extractables were identified and their concentration quantified using state-of-the-art analytical methods such as gas chromatography-mass spectrometry for semivolatile compounds together with headspace sampling for volatile compounds, and liquid chromatography coupled with high-resolution mass spectrometry. The extractables detected were assigned to the materials of filter construction. The evaluation showed that the extractables quantities per device depended on the surface areas of the contact materials, such as the filter membrane, and also on the plastic parts. This paper confirms the validity of a so-called component approach and a scaling concept to calculate extractables data for SU filters of different sizes with short-term contact.LAY ABSTRACT: In the biopharmaceutical industry, a large number of SU system combinations with a variety of different sizes are used. Suppliers of such diverse SU systems and assemblies cannot perform extraction studies for all of the different configurations and sizes individually. It is acceptable in this industry to use component approaches and scaling concepts to provide extractables data for SU systems and assemblies derived from a dedicated extraction experiment. This paper shows the applicability of a so-called component approach and of a scaling concept to calculate extractables data for sterile polyethersulfone membrane filters and filter capsules of different sizes. Selected extraction conditions allow scaling calculations according to underlying physical principles. The extractions were performed under short-term contact, for example, 24 h, to ensure that the release of extractables was diffusion-controlled. The results demonstrated that extractables quantities depend on the surface area of the contact material. Membrane-related compounds were scalable with the membrane area, whereas polypropylene (PP)-related compounds were scalable with the PP contact area.