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Drive efficiency in your biopharmaceutical manufacturing process.
Increasing cell densities and titers in pharmaceutical manufacturing, along with changing regulations and the desire for single-use technologies, are driving developments in the harvest and clarification of cell culture. 3M can help you address these trends in cell culture purification while driving efficiency in your biopharma manufacturing, whether you are using depth filtration or next-generation technologies like fiber chromatographic clarification.
(DESCRIPTION) A hand writes the words, Biopharmaceutical harvest and clarification on a white screen. (SPEECH) If you're responsible for process development in biopharmaceutical harvest and clarification, you may be dealing with a lot of pressure to get a good commercial fit quickly while juggling many challenging variables at the same time. (DESCRIPTION) The hand draws a person juggling. (SPEECH) New industry trends and upstream processes are introducing higher demands on the harvest and clarification process. (DESCRIPTION) They draw an arrow pointing up. (SPEECH) There are development and facility advantages for these processes to be increasingly flexible and scalable while still delivering high quality end product. (DESCRIPTION) They draw a person doing the splits, flexible. They draw a series of growing circles, scalable. (SPEECH) The flexibility and efficiency of a facility may be negatively impacted by an increased number of cell culture types and conditions required to produce an increasing portfolio of product types. (DESCRIPTION) They draw multiple folders. (SPEECH) Variable cell culture fluid creates a range of negative effects on downstream purification, including decreasing overall yield, antibody degradation, and aggregation. (DESCRIPTION) They draw a spilled beaker with a wavy arrow pointing down. (SPEECH) What makes this especially complex is that not all components of the cell culture fluid are completely removed by a single unit operation. (DESCRIPTION) They draw circles containing small particles. (SPEECH) The combination of the insoluble cells and cell debris, for example, mammalian, insect cells, bacteria, and plant. (DESCRIPTION) They draw a dog, a plant, bacteria. (SPEECH) And the cell culture soluble components-- for example, host-cell and product proteins. Host-cell DNA buffers anti-foams, and cell-culture media can cause challenges with established clarification technologies when the success metric is defined as consistent fluid quality for downstream purification. (DESCRIPTION) They draw a scientist holding a cell with a question mark over their head. (SPEECH) It is important for you to map the different interdependencies amongst the upstream and downstream unit operations so that the harvest and clarification operations can be right-sized to build and optimize process without wasted capacity and incurring additional costs. (DESCRIPTION) They draw a map. (SPEECH) Even with a clear map of your project needs, selecting the right set of unit operations to meet those needs can be difficult as many of the options being used today may come with some trade-offs. For example, extremely high removal of whole cells and cell debris with centrifugation or depth filtration may cause additional shearing of cells and an increase in host-cell protein and DNA concentration. (DESCRIPTION) They draw process flow errors, particles, examples of shear, and [DNA]strands. (SPEECH) Alternatively, low shear unit operations may result in a large equipment footprint. Currently, there aren't many harvest and clarification approaches which result in a standard conditioning of the effluent fluid across a broad array of challenge characteristics, resulting from various production scales and molecule types. (DESCRIPTION) They draw large particles, a footprint, a question mark and a chart (SPEECH) Over the last 10 years, many biopharmaceutical companies have attempted to address challenges in harvest and clarification by taking a proactive approach to map end-to-end workflows and tightly define success outcomes. Many companies generate detailed feedstock characteristics like nature of protein and volume like filter capacity targets to set goals on yield impurity removal level and processing time. (DESCRIPTION) They draw a process map and an archery target (SPEECH) But even with these clear targets, there may be technological barriers to overcome for these solutions to work. (DESCRIPTION) They draw an archer shooting an arrow which falls short of the target. (SPEECH) Let's imagine that a manufacturers aiming for 10 grams per liter product protein concentration out of the bioreactor with cell densities greater than 20 million cells per milliliter. Concurrently, cell viability at the time of clarification has generally decreased to less than 50%. (DESCRIPTION) They draw cells. (SPEECH) For this scenario, the increased cell debris and colloidal content due to lower cell viability has led to decreases in sterile microfiltration membrane life. To manage these fluid conditions, the manufacturer considered tangential flow microfiltration-- TTF-MF for short-- to increase the microfiltration membrane life. (DESCRIPTION) They draw an icon of fluid waves and arrows pointing in multiple directions. (SPEECH) However, this harvest technology displayed several shortcomings, such as reproducibility and reduction in capacity. Here, may be the reason for these shortcomings. (DESCRIPTION) They draw a combine harvesting crops. (SPEECH) Even though TTF-MF processes are often designed to minimize the rupture and fragmentation of cells in the recirculation loop, the high-cell density fluids result in increased cell shear and fragmentation. (DESCRIPTION) They draw cells bursting and shearing. (SPEECH) As a result, a secondary clarification depth filter may be required after TTF-MF to reduce the small particle load before sterile microfiltration. Although multiple linked stages are common within harvest and clarification, to achieve product clarity, each unit operation increases the potential for additional product yield loss. (DESCRIPTION) They draw a rough example of a filter with particles moving through and a chain made of links (SPEECH) So how do you overcome challenges presented by process interdependencies and limited design options? You build it on newer technologies capable of facilitating robust integration of multiple steps to simplify downstream processing. Giving yourself the flexibility of implementing newer technologies, opens up options such as single-use centrifugation, depth filtration, sonication, and flocculants-based solutions, which may maximize the reduction of the contaminants and help to generate higher yield during the harvest and clarification of high titer cultures. Technologies such as upstream chromatographic filters may enable a cleaner downstream protein A eluent. Further, new harvest and clarification solutions may enable the reduction of the size and even potentially the number of downstream unit operations, which in turn may reduce operating costs. (DESCRIPTION) They draw the scientist with a question mark over his head surrounded by tools represented by gears, a rough example of a filter and arrows. (SPEECH) 3M combines advanced materials in applied science to offer innovative harvest and clarification design architecture. (DESCRIPTION) They draw the red 3 M logo and fill it in. (SPEECH) To learn how 3M can support your harvest and clarification strategy, visit 3M.com/bioprocessing to learn more about 3M Zeta Plus and Emphaze Product Solutions.
Advancements in cell culture engineering means higher productivity and higher cell densities. This has shifted the burden to clarification and downstream processing. Learn how we can help to efficiently separate cells, cell debris and DNA from the harvest fluid with single-step chromatographic clarification.
Depth filters use porous filtration media to retain particles throughout the media, rather than just on the media surface. They are commonly used when process fluid contains a high particle load because, relative to other types of filters, they can retain a large mass of particles before becoming clogged.
High-performance filter media combined with proper media selection and sizing can provide excellent throughput performance and filtration efficiency for legacy processes. 3M™ Zeta Plus™ EXT Series Depth Filters’ dual-layer construction can enhance the filter’s contaminant holding capacity, reducing premature plugging and helping extend the service life of the media.
Industry leaders discuss next-generation bioprocess and future approaches that deliver high productivity, increased manufacturing flexibility and increased speed with reduced risk.
Cell harvesting and clarifications are both crucial steps that can have a significant impact on the design of downstream processes. By mapping the different process inter-dependencies, harvest and clarification operation can be optimized.
From Frost & Sullivan, "A Virtual Think Tank Executive Summary - A Frost & Sullivan Perspective on Next Generation Harvest Techniques" summarizes discussions from academic and industry leaders.
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