Technologies by themselves rarely provide a business advantage in a manufacturing setting. Manufacturing is inherently complex and therefore the use of technology typically is very complicated and risky. This is even more evident in a regulated environment where introduction of new technologies require extensive testing and robustness. That is why when evaluation new technological advances the benefits have to be evaluated based on a sound technology architecture that is rooted in the business drivers. With that in mind we can take a look at some very interesting innovations and technologies that with the right implementation can provide substantial business value. Now we have to challenge our industry to take the leap to see if we can move the productivity, quality and flexibility needle.

1. Vendor
Innovation - New
Technologies in
Practice
Gilad Langer and Jeff Odum

2. Our inherent angst of all that is new in Manufacturing
Drug Development Drug Manufacturing

3. Key Business Drivers
Fast to Market Right First Time Quality Volume Gowth Efficiency
• Fast products
introduction (date
driven approach)
• Fast ramp-up
• Flexible batch
sizes
• Flexible resource
handling
• Reduced time for
changes
• System enforces
compliance
• Readiness for
Inspection
• Less paperwork
• Reduced time for
review and release
• Less Events, NCs,
Exceptions
• Zero Recalls
• Less Complaints
• Elimination of
variability
• Narrow
specifications
• Reduced safety
stock
• Less scrap &
waste
• Less deviations
• Less maintenance
• Better demand
fulfilling (stock-
outs)
• On-time delivery
• Reduced
stock/inventory
• Reduced transport
• Reduced
distribution time
• Better capacity
utilisation
• Increased
throughput
• Increased yield
• Shorter throughput
time
• Reduced resource
consumption
• Lower cost

4. Determining the Real Business Objectives
Practical Example
4
New Product Intro Stable Production Volumes Patent Expiry
Agile Manufacturing Effective Documentation Process Capability Supply Chain Reliability Operational Excellence
Flexibility Compliance Quality Volumes Competitiveness
Time
Review by
Exception
Batch
Reporting &
Verification
Electronic Log
Books
Recipe/
Workflow
Execution
Product &
Process
Definition
Batch Control
Transport
Control
Manufacturing
Intelligence
Quality
Monitoring
Data
Collection
Laboratory
Data
Management
Maintenance
Management
Calibration
Management
Quality Test
Workflow
Execution
Enterprise
Resource
Planning
Scheduling
Unit Control
Automation&ITCapabilitiesBusinessObjectives
Recipe/
Workflow
Execution
Product &
Process
Definition

5. Automation & MIS Technology Investment with a Purpose
5

6. The facility of the future – key features
• Operational flexibility
• High throughput
• Validated system closure
• Optimized segregation strategy
• Integrated automation & control
• Appropriate material flow capabilities
for SUT implementation
• Multi-product capability
• “Hybrid” equipment capability

7. New Paradigm with Continuous Manufacturing
7
Same equipment,
located at one or more
sites, used at each stage
of the process

8. Lean Thinking/Cost Reduction/Operational Excellence
8
• High governmental pressure for cost cutting in pharma industry
• Most pharmaceutical plants are still very inefficient compared to other
industries
• Cost reduction is necessary (COGS typical 25% compared to 15% in
other industries)
• ERP used to optimize supply chain
• MES used to eliminate costly paper-based procedures
• Automation will be integrated with PAT (Process Analytical Technology)
• Automation provides data for analysis and optimization of processes
(e.g. MVDA)
• Automation will be used as real-time window to the process
Control Define
Measure
Analyze
Improve
COGS = Cost of Goods Sold, OEE = Overall Equipment Efficiency
PAT = Process Analytical Technology, CQA = Critical Quality Attributes, CPP = Critical Process Parameters

9. System Life Cycle Management
9
• Automation and Manufacturing IT systems are characterized by a
relative short life time.
• Very often the systems have to be upgraded or replaced long time
before the process equipment has reached its end of the life cycle.
• For most companies it is a challenge to manage upgrade or
replacement of systems in a running production environment.
• Often the need for upgrade or replacement is ignored until it
appears as an unpleasant surprise.
• Technology and risk assessments
• Long term migration planning
• Tools for Life Cycle Management like ART developed for NN.
Planned
mitigation
of risk
Unmitigated risk scenario
Mitigated risk scenario

10. Flexible Manufacturing/Customized Products
10
• Many pharma & biotech plants are designed without flexibility (one
product)
• Introduction of new more customized products are very costly
• Much more flexibility is needed for launch of new products, shift
between products, optimization etc.
• Standardized product and recipe specification based on recognized
standards become important (S88)
• Using single use technologies may be part of the solution
• Flexible solutions based on Modular/Podular* Design become important
• Automation & IT to be based on configurable/data driven procedures
• Smart recipe management becomes crucial
• Flexibility may be achieved by “looser” integration
• Tracking of disposable equipment and load carriers by use of RFID/MES
is a new trend
*Podular Design is e new term for design based on independent modules, e.g. a clean room with its own HVAC system

11. Paperless Manufacturing
11
• The pharmaceutical industry is still burdened with a lot of tedious
paper work
• Approximately 50% of the staff is allocated to paper work
• Paperless manufacturing solutions are emerging in leading
companies e.g. PAS-X in Novo Nordisk
• Review/approval by exception is the new trend
• MES can eliminate/decrease the amount of paperwork -> less
resources
• MES can improve the quality of records through automated data
capture and dynamic verifications
• MES can provide data for both documentation and optimization
PAS-X = ProduktionsAbwicklungsSystem (German MES product from company Werum)

12. Virtualisation and Cloud Computing
12
• It is difficult and expensive to operate and maintain a multitude of
different control systems locally.
• Automation solutions are standardised, consolidated and virtualised
to increase security and reduce operation and maintenance cost
• Virtualisation is widely used to prolong life time of outdated systems
(e.g. by VMware)
• Many control systems are now installed in central computing
facilities
• An increasing number of services are provided as cloud solutions
• Shared Computing Facilities (SCF) with Shared Services
• Cloud Computing including: Software as a Service (SaaS), Platform
as a Service (PaaS) and Infrastructure as a Service (IaaS)

13. Cyber Security
13
• Control System Infrastructure is now becoming a hacker target
• Automation Connectivity including Mobility and wireless - business
needs are driving Integration
• Control System Technology (CST), definitely no longer proprietary
• Many Mfg. sites stop dead in their tracks without control systems
on-line
• Segmentation of networks separated by firewalls
• Black/white listing of software
• Encryption of data traffic
• Intrusion Prevention/Detection
• Strong Access Control
• Strict Password Management
• Two-factor Authentication

14. Intelligent Devices & Internet of Things (IoT)
14
• As microprocessors and other electronics become increasingly
smaller, more efficient, and less expensive, we’re seeing
intelligence being embedded into more and more consumer,
commercial, and industrial devices.
• Increasingly, these devices communicate with each other via the
emerging Internet of Things (IoT)
• This brings what the industry previously referred to as machine-to-
machine (M2M) communications to a whole new level.
• IoT and M2M are essential elements of Industry 4.0

15. Smart Manufacturing / Industry 4.0
15
Industry 4.0
Movie
13,5 min
Industry 4.0
Movie
4 min

16. Summary
16
• There is a lot we can do with what we have today
• Operational Excellence
• Find more flexibility in our manufacturing
• Leverage the technology we have
• Go paperless
• Implement Cyber Security
• Innovation is not only about the drug, overcome our angst of innovation in the manufacturing space
• Look to sky and the “Cloud”
• Embrace Smart Manufacturing and relevant advanced technologies

17. Thank you
For further information please contact
Jeff Odum
Global Technology Partner
Managing Partner, Global Concept Group
ouj@nne.com
919-673-4745
Gilad Langer
Director, Automation & MIS
gidl@nne.com
415-405-6743