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