Downstream Processing

Drug Formulations Are Changing:
New Sterile Filtration Challenges in the Changing Landscape of Drug Formulations

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Read about the challenges of sterile filtration of high concentration mAbs, liposomes, and lentiviral vectors, and how to solve them in this Special Report. Development of new, complex drug formulations has given us therapeutics with properties that are markedly different from traditional drug types. High viscosity or low surface tension formulations or large viral vector molecules can mean that sterile filtration processes, which are optimized for traditional drug types, are not as efficient for the new, complex formulations. Premature filter…

November 16, 2020

Development of a Single-Use Hermetic Centrifuge System for Mammalian Harvest with Moderate to High Cell Content

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The production of increasingly higher cell densities has stressed the already limited solids-handling capabilities for traditional intermittent ejection centrifuge systems. By contrast, a single-use disc-stack centrifuge based on the solids-flow principle offers distinct advantages for cell culture harvesting. Such benefits include solids handling of high-density cell culture processes and elimination of the separation disruption and aerosol generation associated with the intermittent solids ejection. A single-use system also provides well-established benefits of disposable components — such as removal of steam- and…

October 29, 2020

A New Runway for Purification of Messenger RNA

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A high-performing capture method is a critical bedrock asset for developing industrial purification processes. This is especially true for extended families of products that share highly similar chemical composition. Therapeutic monoclonal IgG is an example. The ability of protein A affinity chromatography to achieve 95% purity in one simple step was the runway that got recombinant immunotherapy off the ground and made it available to millions. In fact, protein A did more. Beyond giving the industry a foundation manufacturing method,…

October 29, 2020

How Much Harm Can a Single Droplet Do? Considerations for a Viral Inactivation Step

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Viral clearance is a fundamental aspect of viral safety for biopharmaceutical products. Regulatory agencies around the world require biomanufacturers to segregate their operations appropriately to mitigate the risks of carryover contamination from previous process steps or product batches and of crossover contamination between product(s) made in the same facility. Guidelines are vague in defining “appropriate,” leaving biomanufacturers to interpret regulatory expectations and define their own virus reduction and segregation strategies. Given the differences among manufacturing processes and facilities housing such…

October 29, 2020

Dye-Stripping Buffer and Resin Stripped-Dye Analysis: Development and Optimization of a Novel Spectrophotometric Assay and Method for Removal of Cibacron Blue Dye

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Biopharmaceutical process-related impurities encompass all organic and inorganic materials that arise from the biomanufacturing process apart from the drug substance. According to ICH Q6B guidelines on test procedures and acceptance criteria for biotechnological products, these impurities include cell substrates such as host-cell proteins, host-cell DNA, endotoxins, and so on; inducers, antibiotics, media components, and chromatographic media used in purification processes; and solvents and buffer components (1). Impurities can cause undesired, deleterious pharmacological effects if ingested or injected by a patient,…

October 29, 2020

Streamlined Polishing and Viral Clearance Using a New Hybrid, Biomimetic, Single-Use Anion Exchanger

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Flow-through anion-exchange (AEX) chromatography is used frequently in biopharmaceutical purification processes for reduction of net–negatively charged host-cell proteins (HCPs) and viruses as part of a validated viral clearance strategy (1, 2). AEX column chromatography is the technology most often used for electrostatic viral clearance, particularly in commercial-scale biopharmaceutical manufacturing, for which columns have a long-established history of reliable and well-understood performance (3). Still, validation of HCP and viral clearance by AEX columns in biopharmaceutical processes involves complexities that contribute significantly…

October 29, 2020

Simple and Effective Method for Purification of DMT-On Oligonucleotides Using HIC Resins

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Within the biopharmaceutical industry, oligonucleotide drug pipelines have increased significantly because of the effectiveness of such drug products in treating devastating diseases. Downstream specialists need improved purification techniques for such highly valuable materials. Dimethoxytrityl (DMT) is used to synthesize oligonucleotides and temporarily mask the characteristic chemistry of the 5ʹ-hydroxy functional group. DMT can be left on an oligonucleotide following synthesis to provide stability to a molecule during subsequent processing. Herein, we describe a novel, effective, and high-recovery method for purifying…

October 29, 2020

eBook: Mixed-Mode Chromatography for Purification of Biopharmaceuticals

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Mixed-mode chromatography offers several advantages in downstream processing of biotherapeutics. Mixed-mode chromatography resins use ligands that are capable of at least two modes of interaction with solutes such as hydrophobic, ion exchange, and metal affinity. The interactions between stationary and mobile phases that result from those combinations enhance chromatographic selectivity, facilitating separation efficiencies that are not possible using other chromatography media. As this eBook illustrates, the multimodal approach can save developers time and money by enabling robust purification of biopharmaceuticals…

October 29, 2020

eBook: Viral Vector Purification — A Discussion of Current Challenges and Methods

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Adenoassociated viral (AAV) vectors have become synonymous with gene therapy delivery. However, because they are produced in such small quantities and because their upstream processes carry comparatively large amounts of host-cell DNA and other impurities, AAV purification can be challenging. Several researchers have applied different chromatographic strategies, but no universal method has been adopted in the biopharmaceutical industry. This eBook features a discussion among several industry experts that explores challenges specific to AAV purification, shedding light on whether current strategies…

September 30, 2020

The Downstream Perspective: Putting Product Knowledge to Work Using Technological Innovations

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After over a quarter century in the industry — including downstream processing (DSP) and manufacturing directorships at Boehringer Ingelheim and leadership roles in technology development, quality, and manufacturing at Novasep — European consultant Margit Holzer is a recognized expert in downstream processing of biopharmaceutical products. Holding a doctorate in biotechnology from the University of Natural Resources and Applied Life Sciences in Austria, Holzer is familiar to BPI readers as both an author and conference participant (1, 2). And in May…

June 16, 2020