(147d) Purification of Biotherapeutics By High-Productivity Nonwoven Based Membrane Adsorbers

To meet the growing demand for accessible biotherapeutics and accelerate the development of new therapeutic modalities, biopharmaceutical companies are seeking to transform biomanufacturing processes to improve productivity, flexibility, and cost-effectiveness. Nonwoven based membrane adsorbers could have an important impact on current downstream processing for biotherapeutics production by providing an inexpensive single-use adsorbent with a significantly higher productivity relative to chromatographic columns. We explored various high-capacity chromatographic nonwoven membranes that were developed by UV grafting of polyglycidyl methacrylate (polyGMA) on a poly butylenes therephthalate (PBT) nonwoven fabric and subsequent functionalization with different ligands, for purification of biomolecules including monoclonal antibody (mAb), single-chain variable fragment (ScFv) and adeno-associated virus (AAV). For example, iminodiacetic acid (IDA) cation-exchange (CEX) nonwoven membranes achieved high DBC_100% for capturing polyclonal human IgG (~130 mg/mL) and scFv (~150 mg/mL) from mammalian cell culture and the DBCs were fairly constant for residence times (RTs) in the range of 0.1-2.0 min. The CEX-IDA membrane could be reused for five bind-elute cycles in capturing mAbs from cell culture harvest at 1.0 min RT with high recovery of 94.2-99.5%. The obtained purity was 87.2-87.9% as some basic impurities were co-eluted, but these values are comparable to those obtained using cation exchange resins. The achieved high mAb loading capacity of 86.4 mg per mL of membrane volume at 1.0 min RT could be highly beneficial for high-throughput production. Other types of prepared membranes also exhibited high-capacity and high-efficiency separation of AAV2 or mAbs from culture fluids. These new nonwoven chromatographic membranes offer highly viable alternatives to chromatographic resins as efficient, high-productivity separation unit in the production of high-value biotherapeutics.