B. Bikson, N. Khadse, P. Wang
Avanpore, LLC,
United States
Keywords: continuous manufacturing, organic solvent nanofiltration, membrane separation, active pharmaceutical ingredients
Summary:
Biopharmaceutical manufacturing is undergoing a dramatic transformation, shifting from traditional batch processes to continuous manufacturing. This transition is particularly critical for advancing the synthesis of Active Pharmaceutical Ingredients (APIs), driven by the need for onshoring production, as only 4% of APIs are currently manufactured in the United States. In this evolution, separation and purification technologies play a pivotal role. Among them, Organic Solvent Nanofiltration (OSNF) has emerged as a promising technology to enable and accelerate this transition. OSNF is a membrane-based separation technology that employs nanoporous membranes to separate solutes—such as APIs, catalysts, or impurities—from organic solvent mixtures used in pharmaceutical manufacturing. Operating under moderate pressures (typically 5–40 bar), OSNF can recover valuable compounds like APIs or homogeneous catalysts, purify products without extensive heat input (unlike distillation), and recycle organic solvents and catalysts, thereby reducing waste and environmental impact. By enabling continuous and intensified processing of APIs, OSNF represents a key component of the emerging paradigm of advanced and sustainable biomanufacturing. It minimizes solvent use and energy demand, supporting green manufacturing principles. Compared with conventional separation methods such as distillation, evaporation, and chromatography, OSNF can deliver up to 90% energy savings while maintaining product quality. OSNF systems can be seamlessly integrated with digital control architectures, including real-time monitoring (PAT) and AI-based process optimization. Polymeric membranes are widely used for molecular separation in aqueous systems. However, conventional solvent-cast membranes typically exhibit limited chemical and solvent resistance, constraining their use in organic solvent environments. The broader adoption of OSNF has been hindered by the lack of solvent-stable commercial membranes. Achieving molecular-level membrane separation requires the development of new, durable membranes capable of operating in harsh organic conditions. To address this challenge, Avanpore, LLC has developed a new class of OSNF membranes through a novel method, Reticulate Rational Design (RRD), during an NSF SBIR Phase I project. This approach enables fabrication of membranes with three-dimensional architectures via Layer-by-Layer (LbL) synthesis. Using RRD, Avanpore established a membrane library spanning ultrafiltration (UF) and nanofiltration (NF) performance ranges. The membranes are based on high-performance polyether ether ketone (PEEK), a polymer renowned for its exceptional chemical resistance and thermomechanical stability. The membranes are produced in the advanced hollow fiber configuration and packaged into high surface area membrane filters. Porous hollow fibers (micro-capillaries) are produced via high-temperature melt extrusion without solvents, aligning with green manufacturing practices. These hollow fibers are then converted into composite membranes by applying a covalently bonded surface separation layer with tunable pore size and functionality, achieved through precise monomer selection in the LbL synthesis process. Scalable surface functionalization methods support commercial membrane production. The resulting OSNF membranes demonstrated nanofiltration-level performance for API separation and recovery in organic solvents, exhibiting high permeance and >99% rejection for molecules ranging from 5000 to 200 Da—meeting or exceeding commercially attractive benchmarks. Avanpore is currently scaling up manufacturing to bring these advanced membranes to market, enabling a new generation of energy-efficient, solvent-resistant separation systems that support the broader goals of advanced biomanufacturing and pharmaceutical sustainability.