Use this link to participate in the interactive on-demand webinar: http://bit.ly/Bio4COrchestrator Detailed description: In this talk, we discuss how orchestration software improves bioprocessing efficiency through the centralized configuration and management of connected unit operations for process and workflow automation across the plant floor. A browser-based software solution, Bio4C™ Orchestrator software connects to individual unit operations from a centralized orchestration layer for remote access to systems, recipes, reports, user accounts and alarms from a holistic process dashboard.

1. The life science business of Merck KGaA,
Darmstadt, Germany operates as
MilliporeSigma in the U.S. and Canada.
Aniruddha Bose
Global Product Manager
13 May 2021
Better Bioprocessing
efficiency through
Centralized Orchestration

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

3. Agenda
1
2
3
Digital Plant Maturity Model
Biomanufacturing Landscape
Gaps in Custom Automation Solutions
4 Innovations in Bio4C™ Orchestrator
5 Use Cases
Value Creation
Q&A

4. DIGITAL PLANT MATURITY
MODEL

5. 5
Industry 4.0
First Generation Automation Industry 4.0 Impact
Heavy capital investments Reverse Engineered – Based
on use cases
Value-driven/value
enhancement decisions
Longer deployment cycles Faster/Shorter deployment
cycles
Speed in Concept to Go live
Heavily dependent on System
integrators
Empower users directly Solution focussed/ problem
solving approach
Inflexible reprogramming Flexibility and agility Big focus on software
solutions - incrementally
Difficult to replicate and scale Easy to replicate and scale Shorter delivery cycles
Reference: Wikipedia web
1st 2nd 3rd 4th
Mechanization
waterpower,
steam power
Mass
production,
assembly line,
electricity
Computer and
automation
Cyber
Physical
Systems

6. Bioprocessing 4.0 & the Digital Plant Maturity Model (DPMM)
6
Biopharma Is on Evolutionary Journey to the Facility of the Future
BioContinuum™
Platform Scope
Process
Analytical
Technologies
(PAT)
Digital Technologies
& Data Management
Process
Technologies
Maturity level
and its
capabilities
Business
Drivers
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.
Market
Trends
Market
Growth
Uncertainty New Product
Classes Cost
Pressure
Pre-Digital Plant
✓ Paper-Based
✓ Manual processes
✓ Isolated Unit operations
Digital Siloes
✓ Islands of automation
✓ Recipes on systems
✓ Offline analytics
Connected Plant/
Predictive Plant
✓ Vertically integrated
systems
✓ Automated data
analytics
✓ Processing Modeling
& Monitoring
Fully Digital Adaptive
✓ Predictive analytics
✓ “Plug and Play”
Automation
✓ Continuous process
verification
Reference: BioPhorum (BPOG)

7. BioContinuum™
Platform Scope
Process
Analytical
Technologies
Digital Technologies
& Data Management
Process
Technologies
Defining
Capabilities
Maturity
level
Pre-Digital Plant
✓ Paper-Based
✓ Manual processes
✓ Isolated Unit operations
Digital Siloes
✓ Islands of automation
✓ Recipes on systems
✓ Offline analytics
Connected Plant/
Predictive Plant
✓ Vertically integrated
systems
✓ Automated data
analytics
✓ Processing Modeling
& Monitoring
Fully Digital Adaptive
✓ Predictive analytics
✓ “Plug and Play”
Automation
✓ Continuous process
verification
Flexible platform and modules expand digital capabilities
7
Bio4C™ Orchestrator Helps Biopharma Manufacturers
Bio4C Suite™
Orchestrator Essentials
Bio4C™ Orchestrator
software, part of
Bio4C Suite™
Advanced Analytics Module
EBR Module
Workflow Management Module
MES
We see this solution working for the mAb
world and are thinking about the 5-year
future with semi-continuous processes,
getting unit operations to talk together
and pushing for automation.
- Multinational Biopharma Manufacturer
The universal digital platform. The Biopharma
all-in-one! This is crossing many boundaries
in the industry today!
-European CDMO
Reference: BioPhorum (BPOG)

8. BIOMANUFACTURING
LANDSCAPE

9. - Accelerates commercial production by scaling up
easily over time
- CAPEX can be spread out over large number of years
- Real-time data coupled with manufacturing context
addresses issues before the batch moves to next
step and allows adjustments in real time
- Single use equipment – reduce CAPEX, minimize
supply chain challenges, reduce energy and water
consumption
Bio4C™ Orchestrator | 13.05.2021
9
The Biomanufacturing Landscape
Modular manufacturing
Reference: Contract Pharma “The Manufacturing Revolution In
Medicine” May 2019

10. - Allows non-stop production within same facility –
integrated production line backed by real-time
operational data
- Eliminates hold times between batches and
mitigates risks with storing critical raw materials
- Seamless process integration and utmost control
needed – operational data and automation plays a
key role here
Bio4C™ Orchestrator | 13.05.2021
10
The Biomanufacturing Landscape
Continuous manufacturing
Reference: Contract Pharma “The Manufacturing Revolution In
Medicine” May 2019

11. - Involves batches of materials specific to an
individual patient
- Manufacturers produce very small volume each
time – sub litres
- Modular manufacturing scaled down in size and
volume
- Lower production foot print
Bio4C™ Orchestrator | 13.05.2021
11
The Biomanufacturing Landscape
Personalized medicine
Reference: Contract Pharma “The Manufacturing Revolution In
Medicine” May 2019

12. Deliver
Performance
Fast and easy
to deploy
Highly
scalable
Towards automation solutions
Critical Aspects in Biomanufacturing Facility
12

13. GAPS IN CUSTOM SOLUTIONS

14. 18 months
Keeping up
with the
pace?
14
Starting from a
‘blank page’

15. Adoption
for
biopharma
Roadmap
15
Custom
validation –
activities in
series

16. INNOVATION FROM
Bio4C™ ORCHESTRATOR

17. 17
Introducing Bio4C™ Orchestrator
• Bio4C™ Orchestrator software connects to unit operations from a
centralized “orchestration layer” for complete visibility, monitoring,
and management of regulatory-compliant biomanufacturing systems
and processes.
• Browser-based, Bio4C™ Orchestrator provides easy, remote access to
systems, recipes, reports, user accounts and alarms from a holistic
process dashboard.
• Monitor and visualize your bioprocesses from anywhere –you don’t
need to be on the plant floor to check your production run.

18. 18
What Makes Bio4C™ Orchestrator Unique?
Solutions in biopharma manufacturing: reduced manual intervention,
better compliance and reliable automation.
SENSORS AND ACTUATORS/
HARDWARE
PLC/LOCAL
CONTROLS
Bio4C™ Orchestrator PLATFORM
3rd PARTY Systems
connectivity
REMOTE
SUPPORT
Workflow
Modules
Plug & Play
Inventory
Management
Electronic
Batch Records
Enterprise
Applications
Advanced
Analytics
STANDARD INDUSTRY OFFERINGS
This is in between MES & DCS, e.g., a standard
MES would have 14 modules that are for
general manufacturing, We will only develop
what is required for Biopharma.
DCS/
SUPERVISORY
CONTROLS
MES
OUR COMPANY’S OFFERINGS R1 AND BEYOND

19. Flexibility & Modularity
19
Flexible Solution Lowering Entry Barrier
Facility Automation Pyramid
SENSORS AND ACTUATORS/
HARDWARE
PLC/LOCAL
CONTROLS
DCS/
SUPER-
VISORY
CONTROLS
MES
One Bio4C™ Software Suite can adapt to different typologies of customers in a
solution-centric approach driven by a customer success strategy as opposed to
standard product offering.
Solution
software
by design
Bio4C™ ProcessPad
DCS
Bio4C™ Orchestrator
Bio4C™ ProcessPad
Bio4C™ Orchestrator
Collect
Bio4C™ ProcessPad
MES
Connect
Bio4C™ Orchestrator
DCS
Control
Flexibility
modularity
Manufacturing site
type A
Manufacturing site
type B
Manufacturing site
type C

20. USE CASES

21. Bio4C™ Orchestrator
21
Managing Passwords and Users Efficiently
6 HMIs to Login
10 Operators in the manufacturing facility
60 User creations
60*4 Roles assigns and management
Bio4C™ Orchestrator manages the workflow
• Singlehandedly
• Remotely
• Enhances monitoring experience w.r.t role allocations
• Administrator can seamlessly assign and un-assign roles to users
• Future User Catalogue / AD support
Sterile
filtration
Virus
removal
Cell culture Harvest Chromatography
Clarification
Tangential flow
filtration
Formulation &
Final Fill

22. Bio4C™ Orchestrator
22
Managing Unit Op Reports and Batch Reports Centrally
• Audit trails reports
• Run reports
• Batch reporting
• Send for Prints from individual
PCs connected to Bioprocess
equipment
• Actions * 6 SKIDs
• Same or Different locations
• Gown up/Gown down time
• US and DS end times not
precisely predictable
Bio4C™ Orchestrator manages the Reporting workflow
• Remote access for all 6 SKIDs
• No physical connection or presence needed
• Batch reporting for USP DSP process runs
• Intuitive UI
• Secure connection
• Seamless approval process
• No need to walk to HMI for Reports
Sterile
filtration
Virus
removal
Cell culture Harvest Chromatography
Clarification
Tangential flow
filtration
Formulation &
Final Fill

23. People
 Lack of subject matter experts – knowledge of both IT and bioprocess
 Skill gaps
Operational
 Not focusing on value added actions/operations – focus on repeat actions
 Change management and user adoption
 Lack of scaling plant
Financial
 Technology led, not value led
 Lack of clarity to: P&L impact & ROI
Digital Infrastructure
 Scalable architecture
 Last level of connectivity
 IT/OT convergence strategy
23
Why do digital enablement pilots get stuck?
Managing Scalability in Digital Enablement

24. Flexible platform and modules expand digital capabilities
24
Bio4C™ Orchestrator Offers Scalability in Digital Enablement
Add-On Modules in future
Bio4C™ Orchestrator Essentials
• Process dashboard
• Recipe management
• Run reports
• Data storage
• User management
• CCP® Skids Connectivity
• Regulatory Compliance

25. Bio4C™ Orchestrator | 13.05.2021
25
Seamless Tech Transfers
Process Development
Sterile
filtration
Virus
removal
Cell culture Harvest Chromatography
Clarification
Tangential
flow filtration
Formulation
& Final Fill
Pilot lab
Clinical or Commercial
manufacturing
Two sites at a Commercial
scale
Sponsor organization and a
CMO at a manufacturing scale

26. 26
Seamless Site Expansions
• CoPrime® Biochromatography Systems
• Mobius® Smart Chromatography
• Mobius® Smart TFF
• Mobius® Single-use Bioreactors
• New hardware expansion in later years
3X
2X
1X
3X
2022
4X
2021

27. 27
Bio4C™ Orchestrator DI Assessment

28. 28
Bio4C™ Orchestrator 21CFR Part 11 Compliance

29. VALUE CREATION
THROUGH PROCESS
ORCHESTRATION

30. Bio4C™ Orchestrator Live Launch – Oct 2020
Bio4C™ Orchestrator Deployment in 2021
Bio4C™ Orchestrator @ M LabTM Collaboration Centers

31. 31
Value Drivers - Bio4C™ Orchestrator
Less manual intervention, better compliance & reliable automation
Modular Automation
solutions
Solution caters to Multiple
Molecules in production
batches
Vendor agnostic enhanced
connectivity across
Biomanufacturing SKIDS
21 CFR Part 11 and
EudraLex Vol. 4 Annex 11
compliance
Process Dev. &
Facility Conceptual
Design
Planning &
development
Design
& procure
Construct &
validate
Operate and
Maintain
Upgrade /
Refurbish
DEPLOY
EMBED
OPTIMIZE
…a cost-effective
solution faster
…bioprocess specific
automation solutions
…our users’ CAPEX
today and grow as
per their needs
Our
Value
Delivery
Speed
Quality
Flexibility
Cost
User
Expectations

32. The vibrant M, 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.
© 2021 Merck KGaA, Darmstadt, Germany and/or its affiliates. All Rights Reserved.
Global Product Manager
Bangalore, India
aniruddha.bose@emdgroup.com
ANIRUDDHA BOSE

33. 33
Q&A
Data Sheet White Papers
Demo Video
Website