Downstream Processing

Continuous Chromatography Is Now Possible for Clinical Manufacturing

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Intensified and integrated bioprocess technologies are creating a paradigm shift toward more efficient, higher flexibility facilities for biopharmaceutical manufacturing. Continuous technologies that are designed as single-use systems help to greatly facilitate process intensification, delivering further efficiencies with reduced set-up times and elimination of the need for cleaning and cleaning validation. Chromatography is often considered to be a challenging bioprocess step, which has caused great interest in a simplified, safer solution. Continuous multicolumn chromatography using a single-use flow path is an…

June 27, 2016

Development of a High-Performance, Integrated, and Disposable Clarification Solution for Continuous Bioprocessing

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Current bioprocesses combine fed-batch cell culture with batch-wise downstream processing steps. To achieve integrated upstream and downstream continuous manufacturing, the industry has been in need of a continuous cell separation and clarification solution for bioprocess fluids from bioreactors. The Cadence Acoustic Separator from Pall Life Sciences provides this solution, with continuous first-stage clarification without the need for filter media in a scalable, single-use format with no negative impact on product attributes. The Cadence Acoustic Separator delivers cost and time savings…

June 27, 2016

Optimizing Continuous Monoclonal Antibody Polishing By Using Coupled Unit Operations

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The biopharmaceutical industry is under a great deal of pressure to modernize manufacturing to meet the challenges of production at vastly different scales for niche drugs as well as for expected massive blockbusters, biosimilars, and regional manufacturing. To address these challenges, the biopharmaceutical industry is embracing process intensification through single-use and continuous processing technologies. Implementing these technologies offers increased productivity and manufacturing flexibility and reduces the footprint, capital outlay, and operating costs. Pall Life Sciences has developed several technologies designed…

June 27, 2016

Clearance of Persistent Small-Molecule Impurities: Alternative Strategies

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Small-molecule impurities that bind to and copurify with protein biopharmaceuticals traditionally have been removed using bind-and-elute (BE) chromatography. However, that approach may be undesirable for a number of reasons. For instance, it may present a facility-fit challenge or provide a lower process yield than what is acceptable. A common scenario in which BE chromatography may be undesirable is in removal of unreacted conjugation reagents. Bioconjugates represent an important and growing class of pharmaceuticals that include PEGylated proteins, vaccines, and antibody–drug…

May 11, 2016

Best Practices for Critical Sterile Filter Operation: A Case Study

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A number of regulatory guidelines recommend preuse integrity testing of critical sterilizing liquid filters for aseptic processing (1–3). Before sterilization, a preuse test will confirm that a filter is installed properly and was not damaged during shipment or handling. Performing a preuse test after sterilization detects damage that may have occurred during the sterilization cycle. Testing after sterilization limits risk, so it is a practice applied based on risk assessment. Because it is perceived to reduce business loss risk, preuse…

May 11, 2016

Accelerated, Seamless Antibody Purification: Process Intensification with Continuous Disposable Technology

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Process intensification through continuous manufacturing has been practiced in the chemical, petrochemical, and food industries for years and has gained much interest among biopharmaceutical manufacturers (1). Key drivers encouraging biomanufacturers of therapeutic molecules to convert batch processes into continuous operation include flexibility, productivity, cost effectiveness, and product consistency. Continuous upstream processing has been demonstrated for the manufacture of a broad range of molecules, including complex/labile proteins such as enzymes (2) and monoclonal antibodies (3). Recent publications have reported successful application…

May 11, 2016

Prepacked Chromatography Columns: Evaluation for Use in Pilot and Large-Scale Bioprocessing

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Time to market, resource requirements, cost, and flexibility are key considerations in designing purification processes suitable for manufacturing biopharmaceutical products. Over the past decade, many advances have been achieved in disposable processing systems that have allowed for increased processing at a lower cost. That is in part attributable to reductions in necessary resources, changeover costs, and cleaning-validation requirements. Large-scale, prepacked chromatography columns have recently become available for clinical and commercial manufacturing, and they represent a growing trend in the industry.…

April 12, 2016

Virus-Filtration Process Development Optimization: The Key to a More Efficient and Cost-Effective Step

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Size-exclusion–based parvovirus filtration is an important step toward drug product safety in biopharmaceutical production. However, once a virus filter is in place, and the required virus safety is ensured, less attention typically is paid to its optimization within the process. That might seem odd given that virus filtration can be one of the more expensive downstream processing steps ($/g protein processed). Most likely, the lack of attention can be attributed to aggressive timelines, limited process development resources, and the virus…

April 12, 2016

Factors Affecting Sterile Filtration of Sodium-Carboxymethylcellulose–Based Solutions

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Carboxymethylcellulose sodium (CMC), is widely used as an excipient in oral, topical, and parenteral pharmaceutical formulations. It increases viscosity (1–3), serves as a suspension aid (4), and stabilizes emulsions (5). More recently, applications for CMC in formulations that facilitate improved delivery of cytotoxic drugs and biologics have been evaluated (6, 7). CMC is manufactured in a broad range of viscosities, with grades typically classified as low, medium, or high viscosity. CMC grades can be divided further based on their degree…

March 11, 2016

Automated Purification of Native and Recombinant Proteins Using Multidimensional Chromatography

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In traditional sequential chromatography, columns are run as separate entities. The process requires significant hands-on time and constant manual intervention. By contrast, automated chromatography technology provides the same results more efficiently and reliably and frees researchers to focus on other tasks, thereby shortening protein purification times from days to hours. For drug discovery, purifying protein samples is required to generate enough materials for research experiments. But the process is complex and time consuming. It involves repeated single-column purifications, careful analysis,…

February 4, 2016