“10 Hot Topics in Biomanufacturing”

Vienna, May 20th

2010

Dr. Uwe Gottschalk, VP Purification Technologies, Sartorius Stedim

Biotech

Hot Topic 1: Product

Mix, Growth Rates in Business Modells in Biopharma

Hot Topic 1: Product

Mix, Growth Rates in Business Modells in Biopharma

Hot Topic 1: Product

Mix, Growth Rates in Business Modells in Biopharma

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)

Hot Topic 2: High-Titer

Processes

in Mammalian

Cell

Culture

Hot Topic 3: Downstream

Processing

is

Mass-

not

Volume

Driven

6th Annual Survey of Biopharmaceutical Manufacturing. Eric S. Langer, BioPlan

Associates Inc.

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

Hot Topic 4: Facility Fit

Dr. Christian Eckermann, Boehringer Ingelheim 2007

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

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

Hot Topic 6: „Biosimilars“

and „Biobetters“

Hot Topic 6: „Biosimilars“

and „Biobetters“

Hot Topic 7: „Offshore

Manufacturing“

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

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

Hot Topic 9: Emerging

Technologies

•

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

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

Hot Topic 10: Single Use

Technologies and „Integrated

Processing“

Hot Topic 10: Single Use

Technologies and „Integrated

Processing“

J. Zhou

BPI Vienna 2008

Hot Topic 10: Single Use

Technologies and „Integrated

Processing“

“The

real voyage

of discovery

consists

notin seeking

new

landscapes

but

in having

new

eyes.”

Marcel Proust. 

Summary: Biomanufacturing

2010+

Summary: Yes

we

can!

Uwe.Gottschalk@sartorius- stedim.com

Thank

you!