Downstream process purification of proteins requires a resin with optimized bead size for ideal pressure/flow properties and decent dynamic binding capacity (DBC) that provides production efficiencies and good process economics. Our newly developed metal chelate affinity resin — Nuvia™ IMAC — provides the mechanical strength, pore structures, ligand density, and particle size distribution required for an operation run at 300 cm/hr with a DBC of > 40 mg/ml at < 2 bar column backpressure. Protein purification can efficiently be scaled…

Single-use technology (SUT) has been adopted on a global scale since its introduction 20 years ago. Its benefits are well-recognized, and it is a key enabling technology in today’s biopharm world. Thousands of single-use products are now on the market and entire processes are being run in single-use systems. Historically, end users have been encouraged to produce ‘customized’ single-use solutions for each individual application. While this can give the user exactly what they want, it can be at the expense…

The implementation of single-use technologies for pharmaceutical product development continues to gain momentum; this trend is due to the advantages of increased flexibility, speed of implementation and lower capital investment. In particular, they are seen as a means to accelerate the production of material for clinical trials. However, a primary concern regarding the use of such technologies is the impact and level of leachables in the final drug substance. Typically this concern is addressed through a risk assessment utilizing extractable…

The downstream purification process of any biologic has several objectives: purity, yield, and safety for humans or animals. A critical component of safety assurance is reducing virus to levels that meet stringent regulatory requirements. Virus reduction can be achieved through multiple complementary approaches and most processes rely on a combination of technologies that are designed primarily to achieve purification targets, but may also offer opportunities for virus reduction. The purpose of this project was to establish capabilities for producing a…

pDADMAC pretreatment of mammalian cell culture, coupled with Clarisolve® depth filters, provides for an effective pretreatment method by shifting the particle size distribution towards larger particles which can then be ‘matched’ to a graded depth filter designed for higher solids loading. Flexibility in filtration performance around pDADMAC dosing, flux rates, mixing hold times, and the variability in cell culture harvests provides for a robust clarification platform. Additionally, utilizing Clarisolve® filters for direct harvests, allows for a more compressed clarification train,…

Improvements in upstream process development often generate complex, high titer process streams, placing considerable demands on downstream processing steps. Protein aggregates in these feeds influence hydraulic performance of virus filters resulting in over-sized platforms and a significant impact on process economics. Virus filters from a broad range of manufactures provide robust viral clearance but the impact of aggregates on flux is dependent on the filter. The impact of conditioning protein solutions using prefiltration was assessed with several monoclonal antibody feed…