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Harvest and Clarification Solutions

Drive efficiency in your biopharmaceutical manufacturing process.

Find solutions from core methods to next-generation technologies

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.

Streamline your harvest and clarification process

  • (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 to learn more about 3M Zeta Plus and Emphaze Product Solutions.

    Challenges in biopharmaceutical harvest and clarification are  drawn on a whiteboard

    Learn how to help minimize additional costs and save capacity by watching this video from 3M and Frost & Sullivan: Right-size your harvest and clarification operations to optimize your process.

Solution being clarified by 3M fiber chromatographic capsules into a vial

Fiber Chromatographic Clarification

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.​

Benefits of fiber chromatographic clarification

  • Clean water coming out from a faucet icon
    Cleaner effluent: introduce chromatographic separation earlier to remove soluble impurities such as DNA
  • Arrows pointing upward icon
    High purity: lower HCPs and DNA post Protein-A
  • small square becomes larger square icon
    Linear scalability: from lab to commercial production

Fiber chromatographic clarification FAQ

Learn more about 3M fiber chromatography

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Depth Filtration

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.

  • How does depth filtration work?
    Depth filtration utilizes the thickness, or depth, of the filter media to trap insoluble suspended particles, separating them from the process fluid that passes through the media. Particles are captured by various mechanisms through the tortuous or complex path of the media, including direct interception, inertia impaction and electrostatic adsorption.
  • Depth filters differ from membrane filters in that they do not have a defined, or absolute, pore size. Membrane filters have holes or pores in the surface of the filter that will trap larger objects while those smaller than the pore will flow through. Therefore, membrane filters’ only mechanism of action is mechanical sieving. Depth filters, on the other hand, must rely on a combination of materials and thickness to create a maze or tortuous pathway to trap the suspended particles.
  • Depth filters are comprised typically of three components: cellulose, a filter aid, and a polymer binder resin. The material can also be functionalized to contain additional functional chemistry for enhanced performance.
  • Depending on the process, a mAb purification train will traditionally utilize a two-stage depth filter operation. The filter(s) used in the first stage have a wider nominal pore size to remove larger cells and insoluble fragments. The fluid is then fed into a filter with a narrower nominal pore size to remove finer debris. Depth filters with a certain level of positive charge may also remove some negatively charged DNA and host cell proteins.
  • Single-layer depth filters contain only a single layer of filtration media. 3M™ Zeta Plus™ EXT Series Filter Capsules and Cartridges have dual-layer configuration with two distinct layers or zones of filter media. This construction increases the holding capacity of the filter, extending its service life and providing enhanced clarification of biological fluids. In some processes, using two or more single-layer depth filters in a chain may be advantageous, as each filter could serve a specific purpose that might not be possible with a dual-layer filter.

Biopharmaceutical industry trends

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Find 3M biopharmaceutical solutions

  • Find solutions for process-related impurities leveraging membrane and chromatography technology.

  • Find solutions for more efficient bioprocessing across our portfolio.

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  • One step can transform your mAb and recombinant protein manufacturing process. At 3M, we’re helping build better, more efficient and simpler manufacturing processes by developing solutions to enhance biologic drug recovery that leads to improved process economics.​

  • Gene therapy is a fast-changing, promising field with new challenges for manufacturing and separation. Learn how we can help with our technologies and expertise.

  • Plasma fractionation has existed for decades, but additional separation methods are becoming increasingly common. We offer a range of products to help you with your process.

  • Getting the most out of your manufacturing process with speed and on budget is an increasing challenge. Our solutions may help you develop manufacturing processes for vaccines to help maximize purity, leading to overall process economics.​

  • If you need solutions for catalyst removal and recovery, color removal, particulate filtration and fill-finish, 3M offers a wide range of adsorptive depth filters and membrane products for application in the chemical pharmaceutical manufacturing.

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