Downstream Development

Rapid Process Development for Purification of a MAb

Time and flexibility are essential in purification process development for biopharmaceuticals. Easy translation of experimental ideas into process steps and insight into the effects of changes in chromatography parameters both help speed development and contribute toward achieving quality by design (QbD) objectives. An ability to scientifically design product and process characteristics that meet specific objectives is crucial. Opportunities to eliminate manually intensive steps all support an enhanced development process. A typical monoclonal antibody (MAb) purification process includes three chromatographic purification…

Cell Therapy Bioprocessing

          The past 15 years have seen approval and commercialization of the first cell-based therapeutics, including cartilage repair products; tissue-engineered skin; and the first personalized, cellular immunotherapy for cancer. Those successes are outnumbered, however, by all too common product failures. Notable failures can be attributed to commercial concerns such as high cost of goods (CoGs) and technical hurdles such as inadequate characterization, high process variability, and loss of product efficacy when manufacturing is scaled up (1).…

Model-Assisted Process Development for Preparative Chromatography Applications

Process modeling is a core technology in biopharmaceutical production that ensures faster, safer processing and process development. Developing a model involves quite some work, so it is important to use the model efficiently. We describe an industry example of how a mechanistic model is best used under process development and how it increases process understanding and performance.   Present State of Process Development   Biopharmaceutical process development relies heavily on experimentation and previous experience expressed as “rules of thumb” and…

Modeling Perfusion Processes in Biopharmaceutical Production

    Perfusion processes are considered more difficult to model than batch-based fermentation processes because up to a third of a perfusion-based campaign is spent outside “steady-state” production mode. Variabilities in cell density, titer, and harvest rate (HR) during ramp-up necessitate planning and explicit modeling of variabilities in these processes and their subsequent downstream operations. Longer continuous fermentation times require more rigorous attention to risk than do batch-based systems. A flexible purification platform must respond to changing fermentation conditions. Here…

Scale-Up of a Plasmid DNA Purification Process

    RecipharmCobra Biologics, Keele (previously Cobra Biomanufacturing Plc) has been producing plasmid DNA for clinical trials for more than 10 years and has an approved site under the EU clinical trials directive. During this period, the company has produced more than 40 plasmids (ranging from 500 mg to 5 g) for 25 customers in Europe and the United States. These plasmids have been used for gene therapy and vaccines as well as to produce viral vectors. RecipharmCobra has developed…

Monoliths Open the Door to Key Growth Sectors

    The enabling value of monoliths was strongly in evidence at the 4th International Monolith Symposium, held 29 May – 2 June in the Adriatic resort city of Portoroz, Slovenia. Forty-seven oral presentations and 34 posters highlighted important advances in vaccines, gene therapy, phage therapy for infectious disease, and monoclonal antibodies, as well as continuing advances in the performance of monoliths themselves. As these fields advance in parallel, it becomes increasingly apparent that monoliths offer industrial capabilities substantially beyond…

PEGylating Peptides (and Proteins)

Peptides should be promising drug candidates. But their small size makes delivery difficult and gives them an extremely short in vivo half-life. They are often cleared by the kidneys or reticuloendothelial system only minutes after being administered, and they are susceptible to degradation by proteolytic enzymes. These problems could be solved by linking them to polyethylene glycol (PEG). Repeating chains of ethylene oxide (CH2CH2O), PEG molecules can be long or short and straight or branched. PEG groups are linked to…

Industrializing Stem Cell Production

Stem cells have potential as a readily available, consistent source of many differentiated cell types. This unique property can be leveraged both for therapeutic purposes and for facilitating and improving a number of drug discovery and development processes. Large-scale, “industrialized” production of human stem cells in tightly controlled conditions will be required to deliver the quantity and quality of cells needed to support clinical trials and drug discovery development activities (Figure 1). Achieving this level of production while meeting rigorous…

Rapid and Scalable Microplate Development of a Two-Step Purification Process

    High-throughput screening and process development methods are becoming more widely used in the biopharmaceutical industry. Recent development of high-expression (high–target-titer) recombinant culture methods has enhanced the need to also develop more effective separation products, methods, and processes (1). Part of the solution would be chromatographic resins offering higher capacities and flow rates.       However, developing an optimized purification process that involves several chromatographic steps can consume significant time and samples. In addition, a purification process developed…

Improving IEX Throughput and Performance with Differentiated Chromatography Sorbents

    Optimized upstream processing and high-productivity cell culture increase not only target protein titers, but also impurity and contaminant concentrations to be removed from large volumes of feedstock. Simultaneously, biopharmaceutical drug production is increasingly driven by manufacturing cost reduction. These facts together increase the pressure on downstream processing and create an urgent need for more productive and streamlined chromatography operations. Key parameters to consider for enhanced process economics in chromatography are higher protein binding capacities at high flow rates…