Comparative Extractables Study of Autoclavable Polyethersulfone Filter Cartridges for Sterile Filtration

Abstract

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.

X‐ray sterilization of biopharmaceutical manufacturing equipment—Extractables profile of a film material and copolyester Tritan™ compared to gamma irradiation

“… a Quantities estimated from UV signal using Tris(2,4‐di‐ tert ‐butylphenyl) phosphite as reference, degradants included methyl and ethyl esters for Irgafos® 168 or typical degradants after hydrolysis, oxidation, or tert ‐butyl split off for Irganox® 1010. 21 , 30 …”

“…The analytical system for analysis of the individual extractables, that is, GC‐MS and LC‐MS are qualified and used in routine extractables and leachables screening. Instrument parameters, the analytical methods, and the standard mixtures were identical to the conditions published by Menzel et al 30 Details about the instruments can be found in the Supporting Information S1 .…”

“…The compound was not present in any Quantities estimated from UV signal using Tris(2,4-di-tert-butylphenyl) phosphite as reference, degradants included methyl and ethyl esters for Irgafos ® 168 or typical degradants after hydrolysis, oxidation, or tert-butyl split off for Irganox ® 1010. 21,30 F I G U R E 4 GC-MS total ion chromatograms (TIC) of the ethanol extracts (offset) from gamma-irradiated (black) and X-ray (blue) irradiated bag samples. Intensities are normalized to the internal standard (IS) 2-fluorobiphenyl at 12.36 min of the aqueous extracts (LOQ < 0.01 μg/mL) and had identical and exceptionally low levels in both ethanol extracts.…”

Structure elucidation and toxicological evaluation of cyclic Polyethersulfone oligomers present in extracts of membrane filters

“…Menzel et al recently published a comprehensive survey of extractables of current PES membrane filters. [ 8 ] PES oligomers were detected in extracts of the investigated filters by HPLC‐UV and LC‐HRMS analysis, but mass spectra were inconclusive. This urged us to examine these compounds further by obtaining a pure representative, elucidating its structure, and performing a toxicological evaluation.…”

“…Several cyclic oligomers can be expected to be present in PES polymers. [8,9] Though isolations and structures of cyclic oligomers from the very similar polymer polysulfone (PSU) are described in the literature, [10,11] a structural characterization of PES oligomers has not been reported. We only identified one reference that described the presence of PES oligomers in food contact materials (baby bottles).…”