High-capacity nonwoven increases productivity of mAb purification in an all-membrane process

Abstract

There is significant interest in alternative manufacturing processes for monoclonal antibodies (mAbs) to improve productivity and reduce cost. To identify a cost-effective and high-productivity alternative to the conventional Protein A-based mAb capture step, this study presents the development of a high-performance multimodal anion exchange (MMA) membrane utilizing N-Benzyl-N-methylethanolamine (BMEA) as the ligand which was covalently coupled to a polyglycidyl methacrylate (pGMA) UV-grafted polybutylene terephthalate (PBT) nonwoven. The DBC_10% of the MMA membrane for IgG ranged from 32.8-42.4 mg/mL at 0.5 to 5 min residence time. The membrane exhibited an excellent salt tolerance in protein binding near physiological conditions, high flow permeability and good reusability. The MMA membrane also showed a DBC_10% of 59.2 mg/mL for direct capture of a mAb from a CHO supernatant without the need for pH or conductivity adjustments, along with a recovery of 94.3%, a 1.0 log reduction value (LRV) of host cell proteins (HCPs), a 1.8 LRV for DNA, and a reduction of aggregates from 5.4% to 0.9%. This capture step was implemented in an all-membrane mAb purification process that included a viral inactivation step and two polishing steps using an anion exchange nonwoven (AEX-TEA) and a multimodal cation exchange nonwoven (MMC-MPCA). A side-by-side comparison with a platform mAb purification process using Protein A resin and two ion exchange resins showed that the all-membrane process exhibited similar impurity clearance, higher overall recovery (88.3% vs. 77.5%) and significantly reduced processing time (3.8 h vs. 13.1 h) with fewer steps as it eliminates the need for diafiltration for buffer exchange.