Bioprocess Principles

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Biopprocess Basics/ Media/Fermentation

Text of Bioprocess Principles

  • BIOPROCESSPRINCIPLESUnit Operations inUpstream & Downstream Processing

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)DefinitionThese fundamental operations are what are called unit operations.Chemical and Bioprocess Industries consist of widely varying sequences of steps that have different combinations for different manufacturing cycles.

    What is a Unit operation?However these widely varying steps can be reduced or broken down to simple operations which are identical in fundamentals regardless of the material being processed.

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Historical DefinitionThis definition was used by A.D Little in 1915 to describe Unit Operations.Unit operations deal mainly with the transfer of energy and the transfer and change of materials primarily by physical means.What is a Unit Process?

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Different Unit OperationsDryingDistillationAdsorptionMembrane separationLeachingSedimentationMixingLiquid Liquid ExtractionAbsorptionTRANSPORT PHENOMENA Momentum TransferFluid FlowSedimenationMixingHeat TransferDryingEvaporaytion (SHMT)DistillationMass TranferAbsorptionAdsorptinDistillation

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Stages of a BioprocessA biotechnical process to produce a product can be subdivided into five successive major segments, with some overlap:

    upstream processing fermentation downstream processing product finishing treatment of waste if any

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Stages of a Traditional Bioprocess

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Stages of a Bioprocess (Details)Preparation of sterile medium.Addition (inoculation) of microbe ( pure culture) into this mediumCultivation (incubation) under controlled conditionsSterilising fermentation apparatus and preparing and sterilising feed streams to the fermentorFERMENTATIONIsolation and purification of the product from the fermented mediumPackaging of the productTreatment of the waste products if any

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Unit Operations in a Bioprocess

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Upstream ProcessingPure Upstream processing has essentially three functions: Growth of a pure culture of microorganisms in one or more steps its scale up and strain development. Sterilization of the apparatus and piping. Mixing and sterilizing the necessary raw materials and fermentation media to be supplied to the fermentation unit.

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Fermentation Stage Sometimes considered as an Upstream process while some bioprocess engineers consider it as a separate Stage in itself. Never considered as a downstream processing stage Actual fermentation is commonly a batch or fed batch process in a stirred tank fermentor. It lasts from a few hours to several days. The optimal conditions for growth of the organisms and production of the product are established. Those include temperature, pH, sterile aeration and, in fed-batch processes, continuous addition of substrate at its optimal composition.

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)SCALE UP (DEFINITION)Shake flash ExperimentsLab scale fermentor (5-10 L)Pilot scale fermentor (300-3000 L)Commercial fermentor (10,000-500,000 L)Scale up: The transfer of a process from small-scale laboratory equipment to large-scale commercial equipment

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream) lab flask (100 mL)lab-scalefermentor(110 L)pilot plantscale(300-3000 L)commercial scale(10,000-500,000 L) Scale up

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Industrial Scale up

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Industrial Fermentation Setting

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Fermentor sizes for various purposes

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Some problems in Scale up Oxygen transfer is much more difficult to obtain in large-scale Mixing and aeration more easily accomplished in small volumes Methods of temperature control must change with scale-up Sterilization protocols must change with scale-up Bioprocess Engineers required with Chemical Engineering skills: adept in gas and mass transfer, fluid dynamics, mixing, thermodynamics

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Downstream processingDownstream processing (DSP) encompasses all processes following the fermentation.

    In downstream processing, the fermentor is emptied after the fermentation is complete. The microorganisms are killed and, if necessary, removed by ultrafiltration. The liquor may be concentrated by evaporation. If necessary, the active ingredient may be isolated by a suitable separation process such as crystallization, ion-exchanging or chromatography. The subsequent product finishing is intended to transform the product into the desired marketable form, e. g., into a dry pourable granulation. That is accomplished by classical drying and granulation processes.

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Unit Operations in Down Stream ProcessingPre- treatmentSolid /liquidSeparationConcentrationPurificationFormulationCell disruptionStabilizationSterilizationPasteurization FlocculationFiltrationSedimentaionCentrifugationMembranesPrecipitationEvaporationExtractionFreeze ConcentrationPrecipitationExtractionDiafilterationAdsorptionChromatographyDryingPrillingExtrusionGranulationTabletting

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Relationship (between cost and and fermentation concentration)

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Separation Range of Downstream Unit Operations

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Product Quality Profile (during Downstream Processing Stages)

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • Differences*Unit Operation in a Bioprocess(Upstream & Downstream)

    Upstream ProcessingDownstream processingLive OrganismsNo organismsLarge VolumeProgressively Less VolumeMany ComponentsProgressively less componentsHeterogeneous mixtureHomogenous MixtureFewer OperationsMany OperationsLower Cost materialsHigher Cost materials

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Downstream ProcessingDownstream Processing begins upstreamwhy?

    A holistic approach to DSP is required and the entire process as a whole should be considered. The economic use of cheap industrial fermentation sources could cause interactions that could increase downstream processing difficulty and cost.. Hence a balance should be sought in the whole process which should be done by the Bioprocess Engineer.

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Research Areas in Upstream processingResearch areas in upstream processing being carried out todayTesting, modeling, optimization, control of novel or improved recombinant and non-recombinant cell culturesNew biochemical reactors, and new biological processes to produce useful and high value products. Basic genome and proteome based biomolecular engineering studies that lead to improved design and performance of fermentation and cell culture processes. By using on-line and real time sensing and monitoring techniques and high throughput analytical techniquesQuantitative assessment of biomolecular rate processes inside a cell toward increasing aeration and transfer rates

    Unit Operation in a Bioprocess(Upstream & Downstream)

  • *Unit Operation in a Bioprocess(Upstream & Downstream)Research Areas in Downstream processing The capability to purify bioproducts in a cost-effective manner on a commercial scale and to meet the required high purity specification for the medical grade bioproducts is an important technical goal of R & D. Research in areas as posttranslational protein processing, protein refolding, protein purification techniques, membrane technology, Various types of chromatography including bioaffinity systems, separation techniques using combined force fields, and filtration methods.

    Unit Operation in a Bioprocess(U