Trends / Drivers Impact on Manufacturing

Report
Continuous Bioprocessing
Barcelona Spain
Continuous Processing in Biotech Production:
An alternative to a modern single use, batch, facility ?
Thomas Daszkowski, Bayer Technology Services
Page 1 21.10. 2013, Thomas Daszkowski
Agenda
Function and Role of Bayer Technology Services
Biopharmaceutical Market (Trends and Drivers)
Current and new Biotech Manufacturing concepts
Continuous Manufacturing
Conclusion
Page 2 21. 10. 2013, Thomas Daszkowski
Who is Bayer Technology Services (BTS)
Bayer Technology Services initiates, implements and supports technological
innovations over the long term.
From product and process development through the planning and construction of
plants to the automation and optimization of processes.
Page 3 21. 10. 2013, Thomas Daszkowski
Trends / Drivers impacting Manufacturing
Trends / Drivers
Impact on Manufacturing
 Regional Requirements
-> local instead of centralized
 Personalized Medicine
-> reduced output per drug
 Rapid Enhancements in
-> allow for changes, decouple
- Cell Biology (Titer) and
building from equipment
- Technology (Single Use)
 More Potent Drugs
-> reduced output per drug
 More Competition
-> cost pressure on production will increase
 Need for localized, yet cost competitive production units
Page 4 21. 10. , 2013, Thomas Daszkowski
Status Quo: Recent Facility Announcements
 Bristol-Myers Squibb (Devens, MA), $750MM,
6x 20,000l bioreactors – 2011 timeframe
 Pfizer Biotech Campus (Grange Castle, Ireland),
€1.8 billion, 6x 12,5000l bioreactors , additional
€145M investment announced in Sep 2011.
 MedImmune, ( Fredricksburg ), $ 600 Mill., 2011
Facility of the Year Award in the project execution
category.
 Xcellerex announces sale of FlexFactory®Bioproduction line to R‐Pharm for new manufacturing
facility in Russia
http://www.xcellerex.com/pdf/Xcellerex_rpharm.pdf
Page 5 2013, Thomas Daszkowski
Newer Facility Concepts
 GE Healthcare KUBio™
http://www.GE.com
 nne pharmaplan (Flexplant)
http://www.nnepharmaplan.com
 Merck Millipore, DSM
http://www.merckmillipore.com
 Jacobs, CRB,…..
Page 6 2013, Thomas Daszkowski
Newer Facility Concepts: Bayer Activities
Examples of Bayer Activities
 Single-Use Systems
 Functionally Closed Processing
 Ball Room Concept
 Continuous Manufacturing
MoBiDiK
Modular, Bio production, Disposable, Konti
Page 12 2013, Thomas Daszkowski
http://biopharminternational.findpharma.com/biopharm/Quality/Challenging-theCleanroom-Paradigm-for-Biopharmace/ArticleStandard/Article/detail/733336
MoBiDiK: Project Set-Up
MoBiDiK
• Industry – Academia Consortium (9 partners)
• Partially Public Funded Project through
State of NRW (Germany)
• Project Start: 1st August 2011
• Project Duration: 3 years
funded by:
Continuous, disposable and modular technologies to develop a functionally closed
mAb process of the future
Page 8 2013, Thomas Daszkowski
MoBiDiK : Fully integrated and single
use Continuous Manufacturing
Current Facilities
MoBiDiK Concept
Newer Facilities
Concept
Buffer A
200 L
Buffer B
200 L
Buffer C
Buffer D
100 L
100 L
Tarpon ProtA
pH VI &
homogenisation
Buffer E
50 L
Tarpon –
Margie
CaptoAdh
ere & AEXMA
Waste
200 L
Buffer A
200 L
Buffer A
200 L
Buffer F
Buffer J
100 L
Buffer K
100 L
100 L
Concentration
adjustment CD adjustment pH adjustment
ATF concentration
Waste
200 L
Waste
200 L
ATF cell
retention
Virusfiltration
Waste
200 L
20L
Bayshake
Fermenter
Fermenter
control
control
•
•
•
•
Batch
Stainless steel
Rooms C & D class
e.g. 6x 20,000l
bioreactors
Page 9 2013, Thomas Daszkowski
• Batch
• Single use
• Rooms C & D class
Perf.medium
200 L
Perf.medium
200 L
Control
Product
10 L Bag
• Continuous
• Single Use
Bioburden
Reduction
UFDF (ATF) &
Bags
Control
MoBiDiK :
Why Continuous Manufacturing ?
MoBiDiK Concept
1. Further reduction in Manufacturing Footprint
and Capex
Buffer A
200 L
Buffer B
200 L
Buffer C
Buffer D
100 L
100 L
Tarpon ProtA
pH VI &
homogenisation
Buffer E
50 L
Tarpon –
Margie
CaptoAdh
ere & AEXMA
Waste
200 L
Buffer A
200 L
Buffer A
200 L
Buffer F
Buffer J
100 L
Buffer K
100 L
100 L
Concentration
adjustment CD adjustment pH adjustment
2. Process Robustness (less manual
interactions and higher degree of
automation)
ATF concentration
Waste
200 L
Waste
200 L
ATF cell
retention
Virusfiltration
Waste
200 L
20L
Bayshake
Fermenter
Fermenter
control
control
Perf.medium
200 L
Perf.medium
200 L
Control
Product
10 L Bag
3. Reduction in Inventory (days at hand)
4. No scale up during drug development
required
Page 10 2013, Thomas Daszkowski
• Continuous
• Single Use
Bioburden
Reduction
UFDF (ATF) &
Bags
Control
MoBiDiK – Project Structure
Conceptual Design
• Conceptual Design
• Model-based process
Upstream Process
•
•
•
•
SU-Perfusion
development
SU-Cell retention
Pulsed Diafiltration
RQ-Control
Demonstrator
USP
disposable,
modular &
continuous
Process
DSP
Downstream Process
• Extraction
• Chromatography/
Adsorption
• Membrane Technology
• Protein Crystallization
• Protein Precipitation
Conceptual Design
Page 11 2013, Thomas Daszkowski
MoBiDiK: Process Design
Upstream
Perfusion
Clarification
Concentration
Downstream
Viral Inactivation
Page 12 • MoBiDiK – Update • Oct 2013
Polishing
Capto adhere/ AEX
Virus Filtration
Chromatography
Prot A
Formulation
UF/ DF
MoBiDiK –
Demonstrator Laboratory
A
USP
Page 13 • SCM MoBiDiK • Sep, 2013
DSP
A
3D Layout 1st Floor – Production Level
Page 14 • BTS 4:3 Template 2010 • June 2011
Comparison to facility with traditional design
and similar production capacity
Cell culture pilot plant in Wuppertal
Biofacility of the future
Purpose
• Produce material for phase 3 clinical trials
Design
• Stainless steel equipment
• Functionally closed processing
• Fed-batch fermentation
• Operations are separated in different rooms
Building Concept
• 5 levels
• ~ 5000 m2 total area
• ~ 1400 m2 cleanroom (class D and C)
Purpose
• Production for market
Design
• 100 % S.U. process equipment
• Closed processing
• Continuous processing
• Ballroom production
Building Concept
• 2 levels
• ~ 1200 m2 total area
• ~ 360 m2 cleanroom (class D and C)
Page 15 September 25, 2013, Jørgen Magnus
MoBiDiK – Challenges
 Competing with an existing well proven technology platform
 GMP readiness of equipment
 At / Inline analytics
 More complex operation , increase in operator skill set
 Regulatory buy in
Page 16 2013, Thomas Daszkowski
Conclusions
Need for localized, yet cost competitive production
units is real
 New Single Use batch operated Biotech Facilities are a first response
(biggest advantage, technology and mindset readiness)
 Conti Manufacturing allows in addition
• Next step in Footprint and Capex Reduction
• One identical platform for Clinical Development and Product Launch
• High degree of automation and reduction in manual interaction
(biggest challenge; paradigm shift (technology and mindset)
in Development and Production)
Page 17 2013, Thomas Daszkowski
Acknowledgment:
Mobidik Team, BHC GBD, Invite, Bio NRW,..
Thanks for your attention
Page 18 2013, Thomas Daszkowski
The Biopharma Market in numbers
 Biopharmaceuticals account for 15.6% of
total market in 2011
 Global biopharmaceutical market was
valued at
$138 billion in 2011
 Expected to grow to over
$320 billion by 2020
 Growth
>10% each year
 Monoclonal antibody products are the
fastest growing segment
65% of developmental pipeline
Source: Levine, bptc consultant and IMS Health
Page 19 21. 10. 2013, Thomas Daszkowski
The Biopharma Market & BRIC countries
Page 20 21. 10. 2013, Thomas Daszkowski
Continuous Manufacturing: Data Points
Source: EPSRC,Centre of Innovative Manufacturing
Page 21 April 2, 2013, Thomas Daszkowski
ESPRC and Conti Processing
Page 22 April 2, 2013, Thomas Daszkowski
ESPRC and Conti Processing cont‘d
Page 23 April 2, 2013, Thomas Daszkowski
Continuous Manufacturing: Data Points cont‘d
(Bio)pharmaceutical
Company
Continuous (bio)manufacturing
Remark
Pfizer
Continuous Processing in Pharmaceutical Manufacturing
Matthew J. Mollan Jr.,
Ph.D. and Mayur
Lodaya, Ph.D., Pfizer
Inc.

new manufacturing technology of continuous processing
involving chemistry in a pipe and continuous extraction
(implemented at Pfitzer, Ireland 2009)
Continuous wet
process using QbD and PAT
Martin Wunderlich
„Change from
togranulation
continuous
 batch
presented in December 2012 during PDA/EMA conference
IChemE 2012 Award: fully integratedmanufacturing
and closely controlled
Cooperation with
processing in pharmaceutical
GSK
tablet production process
Siemens, GEA,

Sagentia and academia
will happen soon“ (Pfizer 2003)
Roche/Genentech
Novartis/Sandoz
Sanofi/Genzyme
Merck Serono



Page 24 April 2, 2013, Thomas Daszkowski
10-year study MIT-Novartis cooperation on small molecule,
pilot plant in headquarter started, 5-10 years forecast to
convert all Novartis production sites
Bernard Trout
Continuous manufacturing will be presented during BPI
europe in 2013
K. Konstantinov
Pilot study for conti downstream presented in BPI Europe
meeting Feb 2013
Norbert Rasenack,
Thomas Linden

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