Watch the interactive on-demand webinar here: https://bit.ly/2G8KSMu The cost to develop and manufacture monoclonal antibodies has been highlighted as a substantial hurdle towards the widespread availability of these effective therapies for patients. Facility costs, utilization and labor are key contributing factors to the overall cost of these critical medicines. A proven method to increase utilization of a facility, increase process and quality robustness and lower overall costs of manufacturing is through the automation of a manufacturing process. The transformative impact that digital technologies have had on other industries’ manufacturing operations through IT and OT can be applied to the evolution happening in biopharma today. Examples of commonly used unit operations such as bioreactor, mixing and chromatography will be presented to illustrate incremental improvements that can be achieved today, and what the future looks like with the convergence of Operational Technology (OT), Information Technology (IT) and existing processing technologies. In this webinar, you will learn: - Incremental improvements that can be achieved today using process automation - Practical examples of commonly used operations to illustrate the impact of automation - How the automated facility will look like in the future

1. Merck KGaA
Darmstadt, Germany
Joshua Hays & Steve Miller
11.July.2019
The Convergence of IT, OT and Processing Technologies
Beyond
Bioprocessing 4.0

2. The life science business of
Merck KGaA, Darmstadt, Germany
operates as MilliporeSigma
in the U.S. and Canada.

3. Topics
1 Market Trends & Business Drivers
2 Industry 4.0 → Bioprocessing 4.0
3 Technologies today and use cases
4 Summary

4. Speed
Reduce new facility build
times by 70%. Compress
production lead time by
80%.
Quality
10X robustness.
90% reduction in cost of
poor quality.
Flexibility
Reduce product change-over
time by 90%.
Cost
90% reduction in cost to
manufacture and CAPEX.
Business
Drivers
Market
Growth
Uncertainty
New Product
Classes
Cost
Pressure
Market
Trends
Market Trends, Business Drivers and Key Enablers*
to Drive Bioprocessing 4.0:
Process
Intensification
Process
Analytics
Software &
Automation
Key
Enablers
Single Use
* Source: BioPhorum (BPOG)
https://www.biophorum.com/category/resources/technology-roadmapping-resources/introduction/

5. less
footprint
Less
capital
reduction in
construction time
reduction
OPEX
Reduction in
cost of quality
90%
90%
70%
60%
90%
Paradigm Shift:
The Facility of the Future will require a
transformation in how biologics are
developed and manufactured
Process
Format
Analytics
Digital Controlled
Inline
Single Use
Intensified
Integrated
Real Time
Closed
Connected
Autonomous
Predictive
Sterile
Continuous

6. Poll question 1

7. Topics
1 Market Trends & Business Drivers
2 Industry 4.0 → Bioprocessing 4.0
3 Technologies today and use cases
4 Summary

8. But where did we begin?
Continuous Manufacturing
The Cromford Mill (the world's
first water-powered cotton
spinning mill) of 1771, designed
by Richard Arkwright, was the
first factory to use a continuous
process from raw material to
finished product in a series of
operations.
https://commons.wikimedia.org/wiki/File:Arkright%27s_Mill_-_Cromford_29-04-06.jpg

9. Continuous Manufacturing
https://www.thedrive.com/vintage/1071/after-102-years-fords-assembly-line-is-still-incredible
Ford’s well-known Model
T assembly line

10. What is Industry 4.0?
By Christoph Roser. Please credit "Christoph Roser at AllAboutLean.com". - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=47640595

11. Where does the Industrial Internet of Things (IIOT) fit?
http://emertxe.com/blog/2017/10/internet-of-things.html https://www.pcr-online.biz/resellers/iot-to-drive-investment-in-it-operations-management

12. Bonner, Mike. "What is Industry 4.0 and What Does it Mean for My Manufacturing?"
1. Interconnection: Connected machinery, sensors, and other devices to the people
tasked with monitoring your process for effectiveness and efficiency.
2. Information transparency: Interconnectivity allows collection of immense amounts
of data and information from all points in the manufacturing process, thus aiding
functionality and identifying key areas that can benefit from innovation and improvement.
3. Decentralized decisions: The ability to combine local and global information at the
same time helps to drive better decision-making and increase overall productivity.
4. Technical assistance: Assistance systems are designed to support operators that
need to make informed decisions to solve urgent problems on short notice.
Four design principles of Industry 4.0

13. Process
Format
Analytics
Digital
Intensified
Single Use
Inline
Controlled
Connected
Closed
Real Time
Integrated
Continuous
Sterile
Predictive
Autonomous
END STATE
Bioprocessing 4.0
Evolutionary Journey Across Many Disciplines

14. https://www.reply.com/en/topics/internet-of-things/the-evolution-of-the-consumer-internet-of-things
Imagine running your manufacturing operation like a ‘smart’ home

15. Poll question 2

16. Topics
1 Market Trends & Business Drivers
2 Industry 4.0 → Bioprocessing 4.0
3 Technologies today and use cases
4 Summary

17. Case Study – the evolution of the “bioreactor”
https://rockland-inc.com/images/products/MAB-062-Roller-Bottle-Figure1-4x3.jpg
https://www.concordia.ca/content/concordia/en/research/genomics/facilities-instruments/cell-culture/_jcr_content/content-main/image_1.img.jpg/1400010807836.jpg

18. Case Study – the evolution of the “bioreactor”

19. Interconnection – ATF + Sensors, etc.
https://www.instrumart.com/assets/ysi-ph100probe_200.jpg
https://www.vernier.com/images/cache/product.do-bta._hero.001.590.332.jpg
http://www.bioprocessintl.com/wp-content/uploads/2016/11/XCell-ATF-2-6-Su-300x297.jpg

20. Case Study – the evolution of chromatography
https://www.khanacademy.org/test-prep/mcat/chemical-processes/separations-purifications/a/principles-of-chromatography
https://bitesizebio.com/wp-content/uploads/2016/08/cc-fig-1.jpg

21. Case Study – the evolution of chromatography
http://www.maschinenreich.com/wp-content/uploads/2016/11/20160407_181619-1.jpg
https://i.ytimg.com/vi/RCa4nE6Z-SE/hqdefault.jpg
https://encrypted-tbn0.gstatic.com/images?q=tbn:ANd9GcRYctzLNSSHHbj-H9hSS_kgRFhhgAZLFgWwd6KlBM7BC0zRYJ_a3g

22. Case Study – the evolution of chromatography

23. 23
Now both are being adapted to IoT and Industry 4.0
Fully Tested, Qualified
and Validated✓
Enabled with
Vendor Know-How
Future Ready with new
tech embedded
Flexible
Deployments
&
Reconfiguration
Machine2Machine
Connectivity
01010101010
01011000111
Functional
Extendibility
Smart Sensors
Smart Consumables
Smart Unit Ops
Beyond Bioprocessing 4.0 | 02.April.2019

24. 24
OLD WAY NEW WAY
FIXED
FIXED UI
THICK CLIENT
EMBEDDED DESKTOP LAPTOP
TABLET PHONE
AR GLASSES VR GLASSES WEARABLES
Beyond Bioprocessing 4.0 | 02.April.2019
Now both are being adapted to IoT and Industry 4.0

25. 25
Vision of the future – connect all unit operations and adhere to all 4 design principles
OLD WAY
0101
0101
0001
0101
0101
0001
Orchestration Platform
Data Aggregation &
Normalization
NEW WAY
010101
010000
101010
101010
Recipe Download &
Automatic Execution
Other
Systems
Beyond Bioprocessing 4.0 | 02.April.2019

26. 26
Vision of the future – connect all unit operations and adhere to all 4 design principles
OLD WAY NEW WAY
HISTORIAN HISTORIAN
Beyond Bioprocessing 4.0 | 02.April.2019

27. 27
Data Processing Vision
Data Management & Advanced Analytics
People
Things
Unit Operation
Systems
Environment
Ecosystem
ReportsData LakeData Sources
“Closing the
Loop”
Projections
Data Information Knowledge Insights
Ingestion Normalization Analysis Prediction
AI, ML, DL
Beyond Bioprocessing 4.0 | 02.April.2019

28. Poll question 3

29. Topics
1 Market Trends & Business Drivers
2 Industry 4.0 → Bioprocessing 4.0
3 Technologies today and use cases
4 Summary

30. DRAFT
30 Beyond Bioprocessing 4.0 | 02.April.2019
Confluence of Evolving Process & Digital Technologies
Process Simulation
Predictive Analytics
EBR
Track & Trace
IoT Platform
Electronic Batch Record PhI
Orchestration
DOE & QbD Modules
Process Analytical Technologies
(PAT)
Harmonized
Unit Operation
Control
DigitalCapabilityFootprint
2019
2020+
>2025
Intensified
Seed Train
Perfusion
Intensified
Capture
In-Line VI &
Buffer
Flow Through
Polishing
Continuous Processing
The Facility of the Future

31. Classification: CONFIDENTIAL
CONFIDENTIAL - Classified by M173177
Leveraging the Digital Era: 2020+
Connect and Enhance your process
using an orchestration platform designed
for the biopharma industry to centralize
your unit operations in a single platform
31
Collect and analyze your process data to
enable rapid decision making and process insights to
optimize and avoid process deviations
Control your process with a next
generation control platform to improve the
user experience to effectively manage,
control and operate a given unit operation,
while being able to integrate within an
overall digital ecosystem

32. Driving towards Industry 4.0
Centralized vs. Modular Control Strategy
DEDICATED SYSTEM DESIGN MULTIPURPOSE SYSTEM DESIGN
CENTRALIZED CONTROL SYSTEM
ORCHESTRATION PLATFORM
ANALYTICS RECIPE MGMT OTHER…
CLOUD SERVICES
DEVICE MANAGEMENT

33. 33 Highly Confidential
The Future of Biopharma
Interconnected Ecosystem of Equipment, Operators and Consumables
Implement
Latest
Standards
Enable
New
Technologies
Build
Partnerships

34. Facility of the Future
Process
Format
Analytics
Digital Controlled
Inline
Single Use
Intensified
Integrated
Real Time
Closed
Connected
Autonomous
Predictive
Sterile
Continuous

35. The life science business of Merck KGaA, Darmstadt, Germany operates as MilliporeSigma in the U.S. and Canada
© 2019 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved. MilliporeSigma, the vibrant M and BioContinuum are trademarks of Merck KGaA, Darmstadt, Germany or its affiliates. All other trademarks are the property of their
respective owners. Detailed information on trademarks is available via publicly accessible resources.

36. Steven.miller@milliporesigma.comJoshua.hays@milliporesigma.com
http://www.emdmillipore.com/BioContinuum
Steve MillerJoshua Hays
BioContinuum™ Platform