Post on 16-Jan-2016
description
BIOPROCESSPRINCIPLES
Unit Operations inUpstream & Downstream
Processing
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
DefinitionDefinition
These “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.
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Historical DefinitionHistorical Definition
This definition was used by A.D Little in 1915 to describe Unit Operations.
““Unit operations deal mainly with the Unit operations deal mainly with the transfer of energy and the transfer and transfer of energy and the transfer and change of materials primarily by change of materials primarily by physical means”.physical means”.
What is a Unit Process?What is a Unit Process?
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Different Unit OperationsDifferent Unit Operations
Drying Distillation Adsorption Membrane
separation Leaching Sedimentation Mixing Liquid Liquid
Extraction Absorption
TRANSPORT PHENOMENA
Momentum Transfer Fluid Flow Sedimenation Mixing
Heat Transfer Drying Evaporaytion (SHMT) Distillation
Mass Tranfer Absorption Adsorptin Distillation
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Stages of a BioprocessStages of a Bioprocess
A 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
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Stages of a Traditional Stages of a Traditional BioprocessBioprocess
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Stages of a Bioprocess Stages of a Bioprocess (Details)(Details)
Preparation of sterile medium. Addition (inoculation) of microbe ( pure culture)
into this medium Cultivation (incubation) under controlled
conditions Sterilising fermentation apparatus and preparing
and sterilising feed streams to the fermentorFERMENTATION
Isolation and purification of the product from the fermented medium
Packaging of the product Treatment of the waste products if any
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Unit Operations in a Unit Operations in a BioprocessBioprocess
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Upstream ProcessingUpstream Processing
“Pure 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.
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Fermentation StageFermentation 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.
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
SCALE UP (DEFINITION)SCALE UP (DEFINITION)
Shake flash Experiments Lab 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
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
lab flask (100 mL)
lab-scalefermentor(1–10 L)
pilot plantscale
(300-3000 L)commercial scale(10,000-500,000 L)
Scale upScale up
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Industrial Scale upIndustrial Scale up
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Industrial Fermentation SettingIndustrial Fermentation Setting
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Fermentor sizes for various purposesFermentor sizes for various purposes
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Some problems in Scale upSome 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
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Downstream processingDownstream processing
Downstream 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.
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Unit Operations in Unit Operations in Down Stream Processing Down Stream Processing
Pre- treatment
Solid /liquidSeparation
Concentration
Purification
Formulation
Cell disruptionStabilizationSterilizationPasteurization Flocculation
FiltrationSedimentaionCentrifugation
MembranesPrecipitation
EvaporationExtraction
Freeze Concentration
PrecipitationExtractionDiafilterationAdsorption
Chromatography
DryingPrillingExtrusionGranulationTabletting
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Relationship Relationship (between cost and (between cost and and fermentation concentration)and fermentation concentration)
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Separation Range of Separation Range of Downstream Unit OperationsDownstream Unit Operations
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Product Quality ProfileProduct Quality Profile (during Downstream Processing Stages)(during Downstream Processing Stages)
DifferencesDifferences
Upstream Processing
Downstream processing
Live Organisms No organisms
Large Volume Progressively Less Volume
Many Components Progressively less components
Heterogeneous mixture
Homogenous Mixture
Fewer Operations Many Operations
Lower Cost materials Higher Cost materials
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Downstream ProcessingDownstream Processing
Downstream Processing begins upstream…why?
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.
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Research Areas in Upstream Research Areas in Upstream processingprocessing Research areas in upstream processing being carried out
today Testing, modeling, optimization, control of novel or
improved recombinant and non-recombinant cell cultures
New 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 techniques
Quantitative assessment of biomolecular rate processes inside a cell toward increasing aeration and transfer rates
April 21, 2023 Unit Operation in a Bioprocess(Upstream & Downstream)
Research Areas in Research Areas in Downstream processingDownstream 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.