Year of Publication

Resin Selection to Optimize the Flexural Strength of Bioprocess Film

Abstract Single-use bioprocess technology offers several advantages for manufacturing biopharmaceuticals, such as increased transportability of fluids throughout the bioprocess workflow and a greater diversity of systems to support specific unit operations, e.g., rocking bioreactors. However, due to the flexible nature of the plastic materials used to construct the single-use containers, the flexural properties of the bioprocess film are critical for performance in such applications. This document focuses on how the resin selection and architecture of a bioprocess film can be…

A Scalable Immobilized Metal Affinity Chromatography Resin for Process Purification

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…

Comparison of the Finesse SmartGlass™ and SmartVessel™ 3L Bioreactors: Engineering Data and Cell Cultivation Results

Finesse Solutions Inc. recently introduced the single-use benchtop scale SmartVessel 3L bioreactor, which was developed based on its re-usable counterpart, the SmartGlass bioreactor. With identical main geometrical parameters, the plastic bioreactor mimics the glass vessel with minor modifications for manufacturability. The following study focuses on the engineering data of both vessels, which have been determined with special focus on animal cell culture applications. Furthermore, data from material tests on leachables and extractables as well as results from cell cultivations using…

Reducing the Complexity of Custom Single-Use Assemblies

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…

New Agarose-Based Protein A Resins Designed for Cost Effective Purification of MAbs

It is well recognized that the cost of Protein A resins is substantial. If a product makes it to marketing approval and manufacturing the high cost is amortized over a large number of purification cycles then the contribution to cost of goods is acceptable. However, a high percentage of clinical projects will fail and the Protein A resin will only be used for a small number of cycles. One way to address this issue is to use a less expensive…

Adopting a Fully Single-use Process to Improve Speed to Clinic: A Leachables Case Study

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…

Efficient Virus Clearance Across the MilliporeSigma Downstream Purification Portfolio

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…

Dosing Considerations and Impacts on the Clarification of Mammalian Cell Culture Feed Streams Using Poly-diallyldimethylammonium Chloride Flocculant in Conjunction with Clarisolve® Depth Filters

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,…

Prefiltration and Process Improvements: Enhancing Virus Filter Performance with the Use of Adsorptive Depth or Surface Modified Prefilters

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…

High Viscosity Tangential Flow Filtration (TFF) Applications

Current trends in the bioprocessing industry are driving mAb and plasma producers to formulate at higher protein concentrations. As a result, formulating using tangential flow filtration (TFF) may be limited in reaching these concentrations due to high pressures caused by highly viscous feed streams. Filtration devices used during processing have to be optimized in order to handle both high viscosity and pressures while maintaining high flux and excellent product recovery. In this study, a family of filtration devices was evaluated…