Biopharmaceutical Downstream Processing ... · Title: Microsoft PowerPoint -...
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Biopharmaceutical Downstream Processing and Biopharmaceutical Downstream Processing and Biopharmaceutical Downstream Processing and Integrated Bioprocess Development Integrated Bioprocess Development Integrated Bioprocess Development O Spadiut and C Herwig O. Spadiut and C. Herwig Institute of Chemical Engineering Division of Biochemical Engineering Vienna University of Technology Institute of Chemical Engineering, Division of Biochemical Engineering, Vienna University of Technology, G d f t ß 1 /166 4A 1060 Vi A ti Gumpendorferstraße 1a/166-4, A-1060, Vienna, Austria It d ti Introduction: Introduction: The bottleneck for many biopharmaceutical production processes lies in the purification of the product by chromatography, as product titers The bottleneck for many biopharmaceutical production processes lies in the purification of the product by chromatography, as product titers ill i Th f R&D ti iti dd t d b ttl k th D t P (DSP) b will increase. Therefore R&D activities are needed to debottleneck the Downstream Process (DSP) by: • understanding propagation of effects across the unit operations employing Quality by Design (QbD) principles using Design of understanding propagation of effects across the unit operations, employing Quality by Design (QbD) principles using Design of E i t (D E) Experiments (DoE) • development of alternative unit operations for purification mainly for the capture step and strategies for optimization of the use of • development of alternative unit operations for purification, mainly for the capture step and strategies for optimization of the use of multiproduct facilities multiproduct facilities Goals and activities: Goals and activities: P d t di it ti D b ttl k DSP Process understanding across unit operations Debottleneck DSP Currently our group Currently, our group works with two works with two bi tl d d recombinantly produced proteins: horseradish proteins: horseradish peroxidase (HRP) in peroxidase (HRP) in Pi hi t i d Pichia pastoris and Alkaline Phosphatase Alkaline Phosphatase Upstream Output Considerations (Titer g/L) for the (AP) in Escherichia coli Upstream Output Considerations (Titer g/L) for the next ten years in the biopharmaceutical industry (AP) in Escherichia coli. next ten years in the biopharmaceutical industry B l i QbD By employing QbD Due to the expected future high principles it is our goal Due to the expected future high tit f ti i d i principles, it is our goal titers from optimized expression to analyze and systems we aim to establish new to analyze and d t d th ff t f systems, we aim to establish new understand the effect of methods beyond chromatography changed process methods beyond chromatography h changed process such as parameters in the USP • crystallization parameters in the USP th lti • crystallization area on the resulting • precipitation product quality attributes precipitation b i t dA 2 product quality attributes • membrane assisted Aqueous 2- in the DSP area. phase systems (ATPS) in the DSP area. phase systems (ATPS) The variations of the • membrane adsorber The variations of the membrane adsorber different process St t i f ti i d lti d tf iliti different process t id Strategies for optimized multiproduct facilities parameters are carried out according to DoE It td ti & ti l i out according to DoE. Integrated time & motion analysis tools allow the analysis of the rate We thereby understand tools allow the analysis of the rate We thereby understand th ti f th limiting step for increased the propagation of the limiting step for increased d ti it i i lti d t CPP to CQA productivity in a given multiproduct CPP to CQA facility relationships across unit facility . relationships across unit ti operations. This allows the analysis This allows the analysis f th hl of the whole process: from the cryo tube to the Photos: available DSP infrastructure from the cryo-tube to the homogenizers, crossflow filtration unit, purified and frozen refolding tank, K-Prime chromatography purified and frozen ti refolding tank, K Prime chromatography system protein. system Time and Motion Analysis of Multiproduct facilities O tl k Outlook: Outlook: Bi h i l E i i i it di i li W d t l k b d th f t ti Biochemical Engineering is interdisciplinary . We need to look beyond the fermentation. The combination of all activities shown allow the determination of how to fit the process to facility or fit the facility to process The combination of all activities shown allow the determination of how to fit the process to facility or fit the facility to process. Bioprocess Technology 2010 Vienna University of Technology Bioprocess Technology 2010 Vienna University of Technology
Transcript of Biopharmaceutical Downstream Processing ... · Title: Microsoft PowerPoint -...
Biopharmaceutical Downstream Processing andBiopharmaceutical Downstream Processing andBiopharmaceutical Downstream Processing and p gIntegrated Bioprocess DevelopmentIntegrated Bioprocess DevelopmentIntegrated Bioprocess Developmentg p p
O Spadiut and C HerwigO. Spadiut and C. HerwigInstitute of Chemical Engineering Division of Biochemical Engineering Vienna University of TechnologyInstitute of Chemical Engineering, Division of Biochemical Engineering, Vienna University of Technology,
G d f t ß 1 /166 4 A 1060 Vi A t iGumpendorferstraße 1a/166-4, A-1060, Vienna, Austria
I t d tiIntroduction:Introduction:
The bottleneck for many biopharmaceutical production processes lies in the purification of the product by chromatography, as product titersThe bottleneck for many biopharmaceutical production processes lies in the purification of the product by chromatography, as product titersill i Th f R&D ti iti d d t d b ttl k th D t P (DSP) bwill increase. Therefore R&D activities are needed to debottleneck the Downstream Process (DSP) by:( ) y
• understanding propagation of effects across the unit operations employing Quality by Design (QbD) principles using Design ofunderstanding propagation of effects across the unit operations, employing Quality by Design (QbD) principles using Design ofE i t (D E)Experiments (DoE)p ( )
• development of alternative unit operations for purification mainly for the capture step and strategies for optimization of the use of• development of alternative unit operations for purification, mainly for the capture step and strategies for optimization of the use ofmultiproduct facilitiesmultiproduct facilities
Goals and activities:Goals and activities:
P d t di it ti D b ttl k DSPProcess understanding across unit operations Debottleneck DSPg p
Currently our groupCurrently, our groupworks with twoworks with two
bi tl d drecombinantly producedy pproteins: horseradishproteins: horseradishperoxidase (HRP) inperoxidase (HRP) inPi hi t i dPichia pastoris andpAlkaline PhosphataseAlkaline Phosphatase Upstream Output Considerations (Titer g/L) for the(AP) in Escherichia coli
Upstream Output Considerations (Titer g/L) for the next ten years in the biopharmaceutical industry(AP) in Escherichia coli. next ten years in the biopharmaceutical industry
B l i QbDBy employing QbD Due to the expected future highy p y gprinciples it is our goal
Due to the expected future hightit f ti i d iprinciples, it is our goal titers from optimized expression
to analyze andp p
systems we aim to establish newto analyze andd t d th ff t f
systems, we aim to establish newunderstand the effect of methods beyond chromatographychanged process
methods beyond chromatographyhchanged process such as
parameters in the USP • crystallizationparameters in the USPth lti
• crystallizationarea on the resulting • precipitationgproduct quality attributes
precipitationb i t d A 2product quality attributes • membrane assisted Aqueous 2-
in the DSP area.q
phase systems (ATPS)in the DSP area. phase systems (ATPS)
The variations of the • membrane adsorberThe variations of the membrane adsorber
different process St t i f ti i d lti d t f ilitidifferent processt i d
Strategies for optimized multiproduct facilitiesparameters are carried
g p ppout according to DoE I t t d ti & ti l iout according to DoE. Integrated time & motion analysisg y
tools allow the analysis of the rateWe thereby understand tools allow the analysis of the rateWe thereby understandth ti f th limiting step for increasedthe propagation of the limiting step for increased
d ti it i i lti d tp p g
CPP to CQA productivity in a given multiproductCPP to CQA p y g pfacilityrelationships across unit facility.relationships across unit
tioperations.p
This allows the analysisThis allows the analysisf th h lof the whole process:p
from the cryo tube to thePhotos: available DSP infrastructure
from the cryo-tube to the homogenizers, crossflow filtration unit,
purified and frozeng , ,
refolding tank, K-Prime chromatographypurified and frozent i
refolding tank, K Prime chromatographysystem
protein.system
Time and Motion Analysis of Multiproduct facilitiesp y p
O tl kOutlook:Outlook:
Bi h i l E i i i i t di i li W d t l k b d th f t tiBiochemical Engineering is interdisciplinary. We need to look beyond the fermentation.g g p y y
The combination of all activities shown allow the determination of how to fit the process to facility or fit the facility to processThe combination of all activities shown allow the determination of how to fit the process to facility or fit the facility to process.
Bioprocess Technology 2010 Vienna University of TechnologyBioprocess Technology 2010 Vienna University of Technology
