Downstream Processing

Continuous Chromatography Is Now Possible for Clinical Manufacturing

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…

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

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…

Optimizing Continuous Monoclonal Antibody Polishing By Using Coupled Unit Operations

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…

Clearance of Persistent Small-Molecule Impurities: Alternative Strategies

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…

Best Practices for Critical Sterile Filter Operation: A Case Study

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…

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

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…

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

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.…

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

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…

Automated Purification of Native and Recombinant Proteins Using Multidimensional Chromatography

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,…

The Secret Life of Protein A

Affinity chromatography with protein A has become the foundation for purification of nearly every therapeutic IgG in commercial production. One of the features most responsible for its success has been its compelling simplicity. IgG binds. Contaminants do not. Load, wash, and elute pure IgG. In the real world, however, protein A does not elute pure IgG. It typically contains several hundred to a few thousand parts per million (ppm) contamination by host-cell proteins (HCPs) and other contaminants. Numerous studies demonstrate…