Comparative Extractables Study of Autoclavable Polyethersulfone Filter Cartridges for Sterile Filtration.

Sterile filters are ubiquitous in biopharmaceutical manufacturing processes. Because such filters are in direct contact with the process fluid, profiling of the extractables is of utmost importance. The work presented here reveals the extractables profile from filter cartridges for sterilizing-grade filtration, which were obtained from six different vendors. All filters contain a 0.2 μm polyethersulfone membrane for sterile filtration combined with a polyethersulfone pre-filter with retention rates spanning from 0.4 to 0.6 μm. These filter cartridges are designed for use in stainless steel housings which allow for in-line steam sterilization. A combination of different analytical techniques such as (headspace) gas chromatography-mass spectrometry, ultra-performance liquid chromatography-high-resolution mass spectrometry (electrospray ionization), inductively coupled plasma mass spectrometry, total organic carbon, non-volatile residue, conductivity, and pH value were applied to develop a comprehensive extractables profile on a qualitative and semi-quantitative basis. Pure ethanol and purified water were used as extraction media. The extractables profile consisted of various polyolefin-related extractables, additives such as antioxidants and degradation products thereof, hydrocarbons, and processing aids in addition to membrane-related extractables. Filter cartridges or other filter products for sterile filtration are currently most commonly made of polymeric materials such as polypropylene, and a filter membrane material such as polyethersulfone. These materials will usually release chemical substances upon extraction in the laboratory (), or upon application in biopharmaceutical processing (). Potential extractables and leachables are additives used to tailor the physicochemical properties and to protect the polymeric materials, or degradants of these substances, or they arise from substances used during the manufacturing of the filter cartridges. Multiple analytical techniques were applied here to investigate the concentration and chemical nature of extractables obtained upon application of two distinct extraction solvents. Typical extractables found were antioxidants or releasing agents in addition to compounds originating from the polyethersulfone membrane.