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More on simulated moving bed chromatography

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Simple description of Simulated Moving Bed chromatography.
its applications for the future.

Published in: Technology

More on simulated moving bed chromatography

  1. 1. SIMULATED MOVING BEDCHROMATOGRAPHY1ExtractFeedRaffinateEluentDirection of the flowand column switchingNEXT SLIDEhttps://www.orachrom.comhttps://www.orachrom.net
  2. 2. AN OVERVIEW.2The Simulated Moving Bed (SMB) technology has been applied to both small and large molecules.Compared to single column batch chromatography, SMB separations achieve higher productivity and purity whileat the same time reducing solvent consumption and labor not to mention deriving a reproducible and reliableprocess.The challenge created by the increase in biological treatment in medicine (monoclonal antibody or vaccines) hasmade the manufacturers look for new directions other than batch mode chromatography.Very small differences in the composition of these large biomolecules as well as very low levels of impurity canhave serious heath detriment for the patient with an already compromised immune system. Thus the need for highquality processing methods that include non leaching and non contaminating process media.The downstream purification processes is also under pressure to keep up with the higher titer achieved during theupstream production.Although the interest in bio-separation processes has been rising it has yet to reach the widespread use it has inother area of continuous and automated separations.Other applications have had considerable use such as separation of proteins, sugars, ionic molecules, opticalisomers and even some monoclonal antibodies.NEXT SLIDE
  3. 3. AN OVERVIEW.3A number of API (Active Pharmaceutical Ingredients) are now manufactured using SMB technology. It isalso the case for the separation and purification of optically active chiral compounds.There are well established methods for reliable operations and scale-ups that have resulted from analyticalexperiments.In the last few years, rapid developments have been made in the areas of design, improved processschemes, optimization and robust control.The purpose of this overview is to provide the fundamentals of the SMB science and technology and somepractical issues concerning the operation of SMB units.The “triangle theory”, a design tool that is used both in the academia and industry for the design of SMBprocesses is also mentioned very briefly.NEXT SLIDE
  4. 4. AN OVERVIEW.4Traditional batch chromatography had an important role in the purification however the large amounts ofsolvent, as well as buffers makes the process prohibitive as the volume of load increases.Furthermore when it consists of large scale production the cost of labor is no longer competitive with anautomated continuous process such as SMB.In light of such given a number of equipment manufactures have indeed designed purification systems basedon SMB chromatography.A series of high-pressure and preferably high performance columns are used in series making a circulatingloop.There are two sets of ports between each column:Inlet ports for “feed” and “solvent” streams and outlet ports for “extract” and “raffinate” streams.The feed and solvent are supplied continuously while at the same time extract and raffinate arealso drawn continuously from the ports.The inlet and outlet ports are switched in a coordinated rhythm and with known intervals in the samedirection as the flow of the liquid.NEXT SLIDE
  5. 5. BASIC OPERATION.5ExtractFeedRaffinateEluentDirection of theflow and columnswitchingNEXT SLIDE
  6. 6. BASIC OPERATION.6ExtractFeedRaffinate EluentDirection of theflow and columnswitchingNEXT SLIDE
  7. 7. BASIC OPERATION.7ExtractFeed RaffinateEluentDirection of theflow and columnswitchingNEXT SLIDE
  8. 8. BASIC OPERATION.8Extract FeedRaffinateEluentDirection of theflow and columnswitchingNEXT SLIDE
  9. 9. BASIC OPERATION.9ExtractFeedRaffinateEluentDirection of theflow and columnswitchingNEXT SLIDE
  10. 10. BASIC OPERATION.10ExtractFeedRaffinate EluentDirection of theflow and columnswitchingNEXT SLIDE
  11. 11. BASIC OPERATION.11ExtractFeed RaffinateEluentDirection of theflow and columnswitchingNEXT SLIDE
  12. 12. BASIC OPERATION.12Extract FeedRaffinateEluentDirection of theflow and columnswitchingNEXT SLIDE
  13. 13. 13SIMULATED MOVING BED CHROMATOGRAPHY HAS ALSO BEEN PICTURED AS A FASTMOVING, COMPONENT (RABBIT) AND A SLOW MOVING COMPONENT, (TURTLE) ONA CONVEYOR BELT.CONSIDERING THE BELT SPEED ASTHE SPEED OF THE RABBIT ASTHE SPEED OF THE TURTLE ASBOTH IN THE OPPOSITE DIRECTION,NEXT SLIDE
  14. 14. 14NEXT SLIDETHE TURTLE WOULD THEN BE CARRIED BY THE BELT AT A SPEED OFWHEREAS THE RABBIT WOULD OUTRUN THE BELT AT A SPEED OF
  15. 15. 15NEXT SLIDEWHEN CONSIDERING THE INTERCONNECTED COLUMNS OF A SIMULATEDMOVING BED AND SIMPLIFYING IT TO A SINGLE COLUMN WE WOULD GET ASYSTEM TO WHICH “FEED” AND “SOLVENT” ARE INJECTED CONTINUOUSLYAND FROM WHICH “EXTRACT” AND “RAFFINATE” ARE WITHDRAWNCONTINUOUSLY AS WELL.FeedSOLVENTSimulatedMovement of theBed resulting fromcolumn switching RaffinateExtract
  16. 16. The Simulated Movement of the Bed through switching of the columns, creates theeffect that the “Feed”, “Raffinate”, “Eluent”, and “Extract” are moving in the samedirection as the flow of the fluid while the movement of the bed is in the oppositedirection with a very controlled speed.This apparent speed of the bed is given by the length of the column divided by theswitching intervals.The goal is to add length to “column/s” and therefore increase the resolution ofthe separation while at the same time evolving it to a continuous mode.It is clear that the final “resolution” is an increment of the sum total of the“resolution” of each column in the system.The process is well established for a binary mixture and an isocratic solvent.Attempts are made to move beyond and there should be no surprise to see ithappen.16NEXT SLIDE
  17. 17. The first step is an analytical one in order to choose the right mediawith the right resolution as well as the appropriate solvent/buffer.The analytical performances to look for are:• High resolution,• High selectivity,• Low retention time.During that process one should keep in mind that the intent of theseparation is to isolate and purify a product and avoid any addedcontamination. It is therefore important to check for:• Low column bleeding,• High column stability• Low column back pressure 17NEXT SLIDE
  18. 18. The preferred column would have high resolution, low retentiontime, no bleeding , high stability and therefore long life.t1<t2< 15 min using a 4.6 mm ID column at a linear flow rate of360 cm/hr and a length of 250 mm.18Absorbancet1 t2 Retention timeNEXT SLIDE
  19. 19. The column loadability is another parameter to be considered.That is the maximum load the column can support before reaching its saturationpoint under kinetic conditions.Any two products in this example can be considered to assess the media for itssuitability for the operation of a binary mixture.19NEXT SLIDENitrobenzeneThioureaBenzylAlcoholAnilineMethylSalicylateToluene10 8 min32 4 5 6 7mAU0502575100200125150175• The higher the load the faster the overalloperation.• The higher the capacity of the columns thefewer needed for a system.• The more stable the media the more usagein the process.• The less bleeding from the stationary phasethe higher the purity of the end product.• The lower the back pressure of the mediathe faster the run.
  20. 20. 20NEXT SLIDEThe “Triangle Theory” is a complex tool used to determine the startingconditions of the SMB.Nowadays the manufacturers of SMBsystems as well as independent softwarecompany have addressed the issue.Far less trial and error steps are neededto reach the optimal conditions for theseparation.abHB HAImpure ExtractImpure Raffinatem2m3Pure ExtractImpure RaffinateImpure ExtractPure Raffinate
  21. 21. The isolation of biotechnological products however has special criteria to be metin order to have widespread use with Simulated Moving Bed technology.As early as 1997, Gottschlich and Kasche have reported the biospecific purificationof monoclonal antibodies by SMB.Although they report a ≥ 90 % yield and a removal of more than 99 % of thecontaminating proteins and most importantly a single step process to reach thoseresults, it leaves room to achieve that golden number of 100 % uncompromisedshould the end product be used as a therapeutic in humans with poor heath.Thus far the majority of the stationary phases used were unstable reversed phasesilica based compound with minimal capacity compared to stable hard gel andporous polymeric.Affinity media has also been scarcely used and so have all other chromatographicregimen that are to pave the way for the SMB in becoming a universal process inthe isolation and purification of biopharmaceuticals including vaccines.21https://www.orachrom.comhttps://www.orachrom.net

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