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������������� ������� Upstream/Downstream � ADSL - ����������� myboat109 boatplans Challenges of the Upstream and Downstream Sector Think Oil Introduction service of experts in the field. More so, information technology plays active roles in the exploration or searching of crude oil in technology are not enough to solve the problems faced in the upstream sectorof the oil industry. Some of the challengesFile Size: KB. Dec 02, �� The Upstream Solution: Treat the Source of Your Problems, Not the Symptoms By Patrick Buggy There once was a town called Downstream, which rested on the banks of a raging river. Solution: Step 1: Calculate upstream and downstream speeds. Assume that the man�s speed in upstream be X km/h From the question, you know that his downstream speed is twice of upstream speed. Then, his downstream speed = 2X km/h You know the formula that, Man�s speed in still water = ? (Upstream speed + Downstream speed) =1/2 (X + 2X) = 3X.
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Texhnology this for a superfluous dual dowels. Middle For Upstream downstream problems with solutions technology Society Must we set up the tiny trimaran with wooden or fiberglass. It was prettier than any I ever assembled. Before we begin spending money as well as removing carried divided with wiring we could initial finalise what we what to erect.

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Separation and purification technologies are slowly catching up to upstream processing, however, and vendors are filling the gaps in their offerings. Filtration continues to advance, of course, with some options even encroaching on the adsorption mechanics of chromatography. And now even drug-product filling operations can choose single-use options. Harvest and Clarification Modern bioproduction technologies have given us expression titers measured in grams per liter of culture � whereas before the turn of the century, milligrams per liter were common.

High-density culturing is one reason, but other advancements include more complicated media and feeds, culture strategies, and optimization efforts. Some of those improvements upstream can cause trouble for harvest, clarification, and beyond. The first phase of downstream processing typically includes centrifugation or primary filtration steps followed by secondary filtration before purification involving chromatography 2. Harvesting here is just the same as in agriculture: collecting the material produced by your hard-working life forms in this case, animal cells or microbes.

Along with the expressed protein of interest come host-cell proteins that are interesting only as contaminants; nucleic acids; leftover nutrients, supplements, and byproducts; secondary metabolites; and water. Clarification follows to prepare this messy product stream for downstream chromatography and purification.

Depth filters have particular utility in clarification, which increases with the help of filter aids, flocculating agents that settle impurities out of a harvest solution, or protective prefilters. Sartorius Stedim and MilliporeSigma are well-known proponents of such approaches 2 � 4. See the next article in this featured report for more discussion.

Filters play many roles in downstream processing � beyond harvest and clarification to virus reduction, buffer exchange, volume reduction, and final sterile filtration just to name a few.

Filtration systems are highly automatable, as well see the box, below , which is increasingly needed in modern biomanufacturing. Biological production processes are inherently variable, so process engineers either use oversized filters or accept some occasional product losses to premature filter clogging. Here is where automation can help.

By putting a single-use pressure sensor in line between your bioreactor and clarification filter � and another between your clarification and sterilizing-grade devices � you can monitor pressure build-up and respond as needed. If pressure reaches a preprogrammed limit, then pump speed is reduced to maintain it below that limit while allowing the process to continue at a slower flow rate. This presents an alternative to requiring an operator to stand over the system and make manual interventions as necessary.

This ensures full product recovery regardless of feedstream quality. Centrifugation has been problematic for conversion to single use, but some suppliers Upstream Downstream Problems With Solutions Example do offer solutions. The former are based on fluidized-bed centrifuge technology originally developed by KBI Biopharma; the latter comprise more traditional technology with irradiated and disposable product-contact surfaces. The Sartorius technology can be used both for harvesting cells as product or discarding them as by-products.

Balanced centrifugal and fluid-flow forces retains particles as a concentrated fluidized bed under a continuous flow of media or buffer.

Some companies are applying it toward continuous processing. The Carr system offers continuous operation as well. Both are highly automatable, although they face limitations in scalability and process monitoring 5.

Other Options: Harvest clarification methods such as feed pretreatment involve single-use technology only in that they require tubing to move harvested material and treatments to and from a mixing system which may or may not be disposable. Acids and salts can cause solutes to precipitate out, but they also can denature proteins; cationic polymers bind contaminants together into cloudy flocs that can be filtered out, but the polymers themselves become contaminants that must be removed later.

If such methods are used, they are likely to be combined with the above technologies, whether single-use or multiuse forms thereof. Chromatography When you ask about single-use chromatography, the answer usually comes in the form of prepacked columns e.

Instead, they are washed and equilibrated for repeated use with the same product stream, then discarded along with their polymer columns once a batch is complete. In addition to the usual benefits related to cleaning and cleaning validation, however, this approach saves users the time, cost, and fussiness of column packing � giving them consistent results from expert suppliers instead.

Column volumes currently available e. And that takes time, thus adding cost. The more expensive the medium e. So too with frequent harvesting and media with long lifetimes. However, mixed-mode sorbents and sequential chromatography are improving performance while reducing costs.

Meanwhile, smaller columns are becoming more popular thanks to high-capacity, high-flow resins and smaller production batches e. A slurry of resin sequentially binds product as it flows through a series of mixers and hollow-fiber membranes, where it is also washed, eluted, and stripped in a continuous process. Alternatives to chromatography resins � in columns or otherwise � are available from membrane suppliers.

Membrane adsorbers, however, have yet to take over a significant portion of the market. The concept is not entirely new technology, but recent introductions � e. This approach may allow for some efficiencies during development, but if the two teams are not working together, it can also create problems. During downstream development, scientists are focused on a number of unit operations. For a therapeutic protein, these processes would start with a primary recovery step � where the cells and debris are removed.

Each individual step has critical process parameters CPPs that need to be monitored and controlled to ensure the critical quality attributes CQAs of the intermediates and purified protein will be achieved at the end. But the biggest factor to ensure a consistent and successful downstream process is not even one that the downstream team can control: it is the consistency of the upstream harvest material. In that sense, upstream processes have a profound impact on the reproducibility and performance of downstream processes.

Development of a robust and consistent downstream process must include the ability to understand and balance the output from the interconnected upstream process. During upstream production, we tend to overly focus on product titers, but other factors such as cell concentration, cell viability, and various product quality characteristics may be impacted to achieve those high titers.

And these upstream factors will most likely impact the subsequent recovery and purification process steps. As an example, one NS0 process developed was initially harvested at a viability of 30 percent to maximize the antibody titer. Unfortunately, this low harvest viability resulted in significant problems downstream and caused very low cumulative process yields. Through discussions with the purification team, it was decided that a new harvest viability specification of greater than 50 percent would be used for this process.

Upstream, there was a 20 percent loss in productivity, but the downstream process yields were much higher than before and the overall amount of purified protein increased. This example highlights the importance of cross-functional collaboration to ensure the entire process, and not just one discrete area, is successful.

For example, a lower cell viability at harvest typically generates a greater release of host cell protein and DNA impurities. The higher impurity load can lead to diminished product recovery, or overwhelmed chromatography processes leading to a failed batch.

Collaborating to establish upstream harvest parameters is crucial to the overall downstream success, but there is also the added challenge of accommodating unexpected and unknown variations in the upstream process.

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