vienna bpi 2010 handout
TRANSCRIPT
![Page 1: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/1.jpg)
“10 Hot Topics in Biomanufacturing”
Vienna, May 20th
2010
Dr. Uwe Gottschalk, VP Purification Technologies, Sartorius Stedim
Biotech
![Page 2: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/2.jpg)
Hot Topic 1: Product
Mix, Growth Rates in Business Modells in Biopharma
![Page 3: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/3.jpg)
Hot Topic 1: Product
Mix, Growth Rates in Business Modells in Biopharma
![Page 4: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/4.jpg)
Hot Topic 1: Product
Mix, Growth Rates in Business Modells in Biopharma
![Page 5: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/5.jpg)
Hot Topic 2: High-Titer
Processes
in Mammalian
Cell
Culture
Data adapted from: F. Wurm
Production of recombinant Protein Therapeuticsin Cultivated Mammalian Cells. Nature Biotechnology 22, 1-6 (2004)
![Page 6: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/6.jpg)
Hot Topic 2: High-Titer
Processes
in Mammalian
Cell
Culture
![Page 7: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/7.jpg)
Hot Topic 3: Downstream
Processing
is
Mass-
not
Volume
Driven
6th Annual Survey of Biopharmaceutical Manufacturing. Eric S. Langer, BioPlan
Associates Inc.
![Page 8: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/8.jpg)
Jim Davis, Lonza
Economics of Monoclonal Antibody Production: The relationship between upstream titer and downstream costs; IBC San Diego March 2008
Hot Topic 3: Downstream
Processing
is
Mass-
not
Volume
Driven
![Page 9: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/9.jpg)
Hot Topic 4: Facility Fit
Dr. Christian Eckermann, Boehringer Ingelheim 2007
![Page 10: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/10.jpg)
Technical challenge
Sensitive and technically demanding products require processes with inherent
complexity and expensive infrastructure
Need for robust & scalable processes for the entire DSP
Increasing regulatory scrutiny (Comparability!)
Financial challenge
Processes are fixed-cost driven (Investment vs
Consumables)
Manufacturing costs 15 -
25% of sales price
Costs for DSP up to 75% of manufacturing costs
Cost Balance Benefit for innovative treatments
Biosimilars
Hot Topic 5: COGs
and Price –
Margin
pressure
from
both
sides
![Page 11: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/11.jpg)
MAb
manufacturing: 6 x 2,000L tanks, 2g/L, 90% utilisation; 211 #/a; 527 kg/yr; invest 172 Mio Euro;
142 $/g; Sinclair 2006
Category
Biomanufacturing
is
fixed
cost
driven
Hot Topic 5: COGs
and Price –
Margin
pressure
from
both
sides
![Page 12: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/12.jpg)
Hot Topic 6: „Biosimilars“
and „Biobetters“
![Page 13: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/13.jpg)
Hot Topic 6: „Biosimilars“
and „Biobetters“
![Page 14: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/14.jpg)
Hot Topic 7: „Offshore
Manufacturing“
![Page 15: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/15.jpg)
Gelfiltration
CHO
Human
Hybridoma
BHK
Cell Removal/Clarification
Cell Removal/Clarification CapturingCapturing Intermediate
Purification
IntermediatePurification PolishingPolishing Virus
Clearance
Virus ClearanceFermentationFermentation
Microorg.
New process trainNew process train
X-FLow
Depthfilter
Centrifuge
CEX
Mixed-Mode
Protein A
HIC
Ceramic HA
CEX
AEX (B/E)
AEX (FT)
AEX-M
Size-Exclusion
Adsorption
Inactivation
EBA
K. KonstantinovBayer Corp, USA
CHO
Protein A
CEX
AEX-Membrane
New process train ready
CHO OrthogonalCentr./DF Protein A CEX AEX (FT)
Depthfilter
Centrifuge Inactivation
Adsorption
Size-Exclusion
Hot Topic 8: Technology Platforms
![Page 16: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/16.jpg)
Cell Removal/
Clarification
ConcentrationPolishing
Media Preparation
Final concentration / buffer exchange
Virus Removal
Fermentation
Capturing
Increasing biomass and contaminant levels
Protein A pool volumes and step cost
DNA & HCP levels post Capturing
Polishing load volumes and conductivity
Hot Topic 8: Technology Platforms–
High Titer
Implications
in DSP
![Page 17: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/17.jpg)
Hot Topic 9: Emerging
Technologies
![Page 18: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/18.jpg)
•
New generation
of lenticular filtration
media
•
No Diatomeaceous
Earth; Synthetic
•
Cell
removal, clarification
& early
on contaminant
removal
Biomass
Removal and Early
Contaminant
Clearance
Increasing biomass and contaminant levels
DNA & HCP levels post Capturing
addresses:
Hot Topic 9: Emerging
Technologies
![Page 19: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/19.jpg)
CEX
TFF
Q Membrane2 g/ml
Dilution
HCP < 1000 ng/mg
VF
Mix Mode
Fig 7b. TFF based process
Dilution
HCP < 1000 ng/mg
CEX HCP < 10ng/mg
Contaminant precipitation
Q Membrane20 g/ml
Fig 7a. precipitation based process
VF
HCP BDL
Dilution
CEX
TFF
Q Membrane2 g/ml
Dilution
HCP < 1000 ng/mg
VF
Mix Mode
Fig 7b. TFF based process
Dilution
HCP < 1000 ng/mg
CEX
TFF
Q Membrane2 g/ml
Dilution
HCP < 1000 ng/mg
VF
Mix Mode
Fig 7b. TFF based process
Dilution
HCP < 1000 ng/mg
CEX
TFF
Q Membrane2 g/ml
Dilution
HCP < 1000 ng/mg
VFVF
Mix Mode
Fig 7b. TFF based process
Dilution
HCP < 1000 ng/mg
CEX HCP < 10ng/mg
Contaminant precipitation
Q Membrane20 g/ml
Fig 7a. precipitation based process
VF
HCP BDL
Dilution
CEX HCP < 10ng/mg
Contaminant precipitation
Q Membrane20 g/ml
Fig 7a. precipitation based process
VFVF
HCP BDL
Dilution
Three Birds –
one Stone: Contaminant Precipitation at Medarex(now part of BMS)
Precipitation of Process-Derived Impurities in Non-Protein APurification Schemes for MAb; J. Wang et al. BioPharm
Intl. 10/2009, 2-9
Protein A pool volumes and step cost
DNA & HCP levels post Capturing
Polishing load volumes and conductivity
addresses:
Hot Topic 9: Emerging
Technologies
![Page 20: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/20.jpg)
Hot Topic 10: Single Use
Technologies and „Integrated
Processing“
![Page 21: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/21.jpg)
Hot Topic 10: Single Use
Technologies and „Integrated
Processing“
![Page 22: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/22.jpg)
J. Zhou
BPI Vienna 2008
Hot Topic 10: Single Use
Technologies and „Integrated
Processing“
![Page 23: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/23.jpg)
“The
real voyage
of discovery
consists
notin seeking
new
landscapes
but
in having
new
eyes.”
Marcel Proust.
Summary: Biomanufacturing
2010+
![Page 24: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/24.jpg)
Summary: Yes
we
can!
![Page 25: Vienna Bpi 2010 Handout](https://reader034.vdocuments.net/reader034/viewer/2022042510/556dc94dd8b42a78768b47c8/html5/thumbnails/25.jpg)
Uwe.Gottschalk@sartorius- stedim.com
Thank
you!