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Pharma 4.0Departure Into a New Dimension
Lothar Hartmann, Ph.D.
Connecting Pharmaceutical Knowledge ispe.org 2
A Story about
Algorithms and Filter Bubbles
Connecting Pharmaceutical Knowledge ispe.org
Pharma 4.0Departure into a New Dimension
1. Introduction Into the Topic
2. Pharma 4.0 – Operating Model
3. Pharma 4.0 - Enablers
4. Holistic Control Strategy
5. From Pharma 2.0 to Pharma 4.0
6. How the Future Can Look Like
Connecting Pharmaceutical Knowledge ispe.org
Pharma 4.0Departure into a New Dimension
1. Introduction Into the Topic
2. Pharma 4.0 – Operating Model
3. Pharma 4.0 - Enablers
4. Holistic Control Strategy
5. From Pharma 2.0 to Pharma 4.0
6. How the Future Can Look Like
Connecting Pharmaceutical Knowledge ispe.org 5
Source: Lawrence Yu, Ph.D. Deputy Director, Office of Pharmaceutical Quality FDA Center for Drug Evaluation and Research
Future of Pharmaceutical Quality and the Path to Get There, 3rd PQRI/FDA Conference on Advancing Product Quality, March 22-24, 2017
Connecting Pharmaceutical Knowledge ispe.org 6
6𝛔
2𝛔
„Even as it [the pharmaceutical industry] invents futuristic new drugs, itsmanufacturing techniques lag far behind those of potato-chips andlaundry-soap makers.”
‚The Wall Street Journal’, September 3, 2003
Connecting Pharmaceutical Knowledge ispe.org
What is the Challenge we are faced with?A look into history....
Connecting Pharmaceutical Knowledge ispe.org
ISPEs initiative
to provide
guidance for the
transformation
process
Connecting Pharmaceutical Knowledge ispe.org
Pharma 4.0Departure into a New Dimension
1. Introduction Into the Topic
2. Pharma 4.0 – Operating Model
3. Pharma 4.0 - Enablers
4. Holistic Control Strategy
5. From Pharma 2.0 to Pharma 4.0
6. How the Future Can Look Like
Connecting Pharmaceutical Knowledge ispe.org 10
Where we are coming from...
Connecting Pharmaceutical Knowledge ispe.org 11
ICH Q10
ICH Q10 +
Digitisation
Acatech
Ind.4.0
Pharma 4.0
The Idea Behind
Connecting Pharmaceutical Knowledge ispe.org 12
ICH Q10 plus digitisation
(developed by ISPE)
Connecting Pharmaceutical Knowledge ispe.org 13
The Operating Model
Connecting Pharmaceutical Knowledge ispe.org
The Acatech Model
Connecting Pharmaceutical Knowledge ispe.org 19
Merging the Concepts
+
Connecting Pharmaceutical Knowledge ispe.org 20
The Result
• Architecture
• Traceability
• Data Management
• Mindset
• Risk based decision
taking
• Anxiety-free
communication
• Networks
• Lifecycle approach
• Process based
• Infrastructure
• Availability
• Interface Human / Machine
Connecting Pharmaceutical Knowledge ispe.org 21
ISPE Working Groups
Connecting Pharmaceutical Knowledge ispe.org
Pharma 4.0Departure into a New Dimension
1. Introduction Into the Topic
2. Pharma 4.0 – Operating Model
3. Pharma 4.0 - Enablers
4. Holistic Control Strategy
5. From Pharma 2.0 to Pharma 4.0
6. How the Future Can Look Like
Connecting Pharmaceutical Knowledge ispe.org 23
• PQS
• QRM
• KM
• Data Integrity
• Digital Maturity
Pre-requisits for Pharma 4.0
Connecting Pharmaceutical Knowledge ispe.org 24
© Lothar Hartmann Ph.D., 2010
Process as part of a process map
Draw flow chart
Determine scope, objective, provider &
receiver
List activities performed
Describe each activity
01
02
03
05
04
Consider risks06
Communicate process09
Set up process description 07
Consider optimization
10
Agreement achieved?
08
Yes
No
Dept. X
Dept. Y
Dept. Z
Activity
Activity
Activity
ActivityDecisionyes
no
Enabler:
Pharmaceutical Quality System
Connecting Pharmaceutical Knowledge ispe.org 25
Enabler:
Pharmaceutical Quality System
The change towards a PQS entails a cultural change within a company
Ignorance
• Business as usual
• No need for
processes
Stand-alone Solutions
• Important processes are
described, but not
synchronized with one
another
PQS• Processes are the
basis for the
company
• Departments work
together independent
of functions
• Processes are
adjusted towards a
company-wide
system of objectives
Eff
icie
nc
y
Time
Cultural change
Connecting Pharmaceutical Knowledge ispe.org 26
Enabler:
Quality Risk Management
Ri s
kM
anagem
entto
ol s
Risk ReviewRisk Communication
Risk Assessment
Risk Evaluation
InitiateRisk Management Process
unacceptable
Risk Control
Output / Results of theRisk Management Process
Risk Analysis
Risk Reduction
acceptable
Risk Identification
Risk Communication
Review Events
Risk Acceptance
Risk Acceptance
Connecting Pharmaceutical Knowledge ispe.org 27
Enabler:
Quality Risk Management
Connecting Pharmaceutical Knowledge ispe.org 28
Enabler:
Knowledge Management
Facts:
Numbers, text
Relationship:
Facts within context
Guidance:
Utilisation of Information
Learning:
Application of Knowledge
Connecting Pharmaceutical Knowledge ispe.org 29
Result of pharmceutical
application to Knowledge
Management?
Enabler:
Knowledge Management
Connecting Pharmaceutical Knowledge ispe.org 30
Enabler:
Data Integrity
“The degree to which a collection
of data is complete, consistent,
and accurate.”
Connecting Pharmaceutical Knowledge ispe.org 31
Data Lifecycle ≠ Computer Lifecycle
Enabler:
Data Integrity
Connecting Pharmaceutical Knowledge ispe.org 32
Source: Acatech Study Industry 4.0 Maturity Index, April 2017
Enabler:
Digital Maturity
Connecting Pharmaceutical Knowledge ispe.org 33
<<<<<<
5
6
3
4
Information Systems
Culture
1
2
Resources
Visibility
Transparency
Predictability
Adaptability
Computerization
Connectivity
Organizational
Structure
Enabler:
Digital Maturity
Pharma 4.0 is more than a
technology revolution.
A successful transformation
requires the balance of 4
segments and 6 maturity levels
Connecting Pharmaceutical Knowledge ispe.org
Pharma 4.0Departure into a New Dimension
1. Introduction Into the Topic
2. Pharma 4.0 – Operating Model
3. Pharma 4.0 - Enablers
4. Holistic Control Strategy
5. From Pharma 2.0 to Pharma 4.0
6. How the Future Can Look Like
Connecting Pharmaceutical Knowledge ispe.org 37
Extended ICH Q10 Model
Holistic Control Strategy
PHARMA 4.0:Digital Maturity & Data Integrity by Design
Knowledge Management & Quality Risk Management
Process Performance &
Product Quality Monitoring SystemCorrective Action
Preventative Action (CAPA) System
Change Management
Management Review
PQS
Elements
Enablers
Management Responsibilities
PHARMA 4.0: Resources: Digitalization, Workforce 4.0, Available & Qualified
Information Systems: Holistic Value Network Integration & Traceability
Organization & Processes: Holistic Control Strategy, Lifecycle Management
Culture: Communication & Decision Making
New
Enablers
New PQS
Elements
Product DiscontinuationCommercial ManufacturingTechnology TransferPharmaceutical Development
Investigational Products
Connecting Pharmaceutical Knowledge ispe.org
• Control Strategy− Based on ICH Q10
− Product-related
− Established during development
• Manufacturing Control Strategy− Process-related
− Defines Master Batch Record
− Enables ongoing process verification
• Holistic Control Strategy− Systematic and controlled concept for developing and managing information
throughout entire period
− End-to-end view (lifecycle management)
Definitions
Control
Strategy
Manufacturing
Control Strategy
Holistic
Control
Strategy
Connecting Pharmaceutical Knowledge ispe.org 39
Holistic Control Strategy
Implementation Methodology
4. “Optimized” Data Flow
2. Process Data Maps
1. Process Maps
3. Critical Thinking
current
Control Strategy
Holistic
Control Strategy
Connecting Pharmaceutical Knowledge ispe.org 40
Without detailed knowledge of the processes, an
organisation of the data flow can not be made.
Connecting Pharmaceutical Knowledge ispe.org
Applying known standards,
tools and methods to determine
actual business &
manufacturing processes:
• Process Maps
• Flow Charts
• Cross-functional Maps
• RACI Matrix
• Interfaces
• KPIs
• …
41
Step 1: Process Maps
Process Maps “Optimized” Data FlowProcess Data Maps Critical Thinking
The Way Towards A Holistic Control Strategy Lifecycle Management
Determine actual data which
can be obtained from the
business & manufacturing
processes:
• What data are available?
• For which purpose are data
used?
• Who enters or changes data
and why?
• What kinds of data errors
may appear?
• How do data move through
an organisation?
• …
Re-Assess and challenge
actual processes and Data
Flows to:
• Conduct data analysis
• Identify essential data
• Identify redundant data
• Eliminate unused data
• Detect different formats of
the same data
• Question interfaces (manual
& automated)
• Detect data integrity issues
• …
Re-Design and optimize actual
processes, Data Flows and
interfaces:
• Harmonize data formats
• Reduce amount of data
• Improve data availability
• Dataflow among networks
• Implement ALCOA/ALCOA+
Principles
• enable data besed decisions
• …
Connecting Pharmaceutical Knowledge ispe.org 42
Step 2: Process Data Maps
Determine actual data which
can be obtained from the
business & manufacturing
processes:
• What data are available?
• For which purpose are data
used?
• Who enters or changes data
and why?
• What kinds of data errors
may appear?
• How do data move through
an organisation?
• …
Process Maps “Optimized” Data FlowProcess Data Maps Critical Thinking
The Way Towards A Holistic Control Strategy Lifecycle Management
Applying known standards,
tools and methods to determine
actual business &
manufacturing processes:
• Process Maps
• Flow Charts
• Cross-functional Maps
• RACI Matrix
• Interfaces
• KPIs
• …
Re-Assess and challenge
actual processes and Data
Flows to:
• Conduct data analysis
• Identify essential data
• Identify redundant data
• Eliminate unused data
• Detect different formats of
the same data
• Question interfaces (manual
& automated)
• Detect data integrity issues
• …
Re-Design and optimize actual
processes, Data Flows and
interfaces:
• Harmonize data formats
• Reduce amount of data
• Improve data availability
• Dataflow among networks
• Implement ALCOA/ALCOA+
Principles
• enable data besed decisions
• …
Connecting Pharmaceutical Knowledge ispe.org 43
Step 3: Critical Thinking
Re-Assess and challenge
actual processes and Data
Flows to:
• Conduct data analysis
• Identify essential data
• Identify redundant data
• Eliminate unused data
• Detect different formats of
the same data
• Question interfaces (manual
& automated)
• Detect data integrity issues
• …
Process Maps “Optimized” Data FlowProcess Data Maps Critical Thinking
The Way Towards A Holistic Control Strategy Lifecycle Management
Applying known standards,
tools and methods to determine
actual business &
manufacturing processes:
• Process Maps
• Flow Charts
• Cross-functional Maps
• RACI Matrix
• Interfaces
• KPIs
• …
Determine actual data which
can be obtained from the
business & manufacturing
processes:
• What data are available?
• For which purpose are data
used?
• Who enters or changes data
and why?
• What kinds of data errors
may appear?
• How do data move through
an organisation?
• …
Re-Design and optimize actual
processes, Data Flows and
interfaces:
• Harmonize data formats
• Reduce amount of data
• Improve data availability
• Dataflow among networks
• Implement ALCOA/ALCOA+
Principles
• enable data besed decisions
• …
Connecting Pharmaceutical Knowledge ispe.org 44
Step 4: "Optimized " Data Flow
Re-Design and optimize actual
processes, Data Flows and
interfaces:
• Harmonize data formats
• Reduce amount of data
• Improve data availability
• Dataflow among networks
• Implement ALCOA/ALCOA+
Principles
• enable data besed decisions
• …
Process Maps “Optimized” Data FlowProcess Data Maps Critical Thinking
The Way Towards A Holistic Control Strategy Lifecycle Management
Re-Assess and challenge
actual processes and Data
Flows to:
• Conduct data analysis
• Identify essential data
• Identify redundant data
• Eliminate unused data
• Detect different formats of
the same data
• Question interfaces (manual
& automated)
• Detect data integrity issues
• …
Determine actual data which
can be obtained from the
business & manufacturing
processes:
• What data are available?
• For which purpose are data
used?
• Who enters or changes data
and why?
• What kinds of data errors
may appear?
• How do data move through
an organisation?
• …
Applying known standards,
tools and methods to determine
actual business &
manufacturing processes:
• Process Maps
• Flow Charts
• Cross-functional Maps
• RACI Matrix
• Interfaces
• KPIs
• …
Connecting Pharmaceutical Knowledge ispe.org 45
Flow of Data
Holistic Control Strategy
Manufacturing Control Strategy
Commercial ManufacturingTechnology TransferPharmaceutical Development
Investigational ProductsProduct Discontinuation
Data
ICH Q10: Knowledge Management & Quality Risk Management
Data Integrity & Digital Maturity
Control Strategy
Connecting Pharmaceutical Knowledge ispe.org 46
Utilisation of Data
Wisdom
Knowledge
Information
Data Data Capturing / Generation
Product Process
Data Analytics
Value chain Management
Value Chain Life CycleManagement
Data Mining
Trend Reporting
Product Life Cycle Management
Commercial ManufacturingTechnology TransferPharmaceutical Development
Investigational ProductsProduct Discontinuation
Kn
ow
led
ge M
an
ag
em
en
tManufacturing Control Strategy
Enabler
Connecting Pharmaceutical Knowledge ispe.org
Pharma 4.0Departure into a New Dimension
1. Introduction Into the Topic
2. Pharma 4.0 – Operating Model
3. Pharma 4.0 - Enablers
4. Holistic Control Strategy
5. From Pharma 2.0 to Pharma 4.0
6. How the Future Can Look Like
Connecting Pharmaceutical Knowledge ispe.org 48
Pharma 2.0 – Current Situation
• Non-effective and efficient manufacturing
• Improper handling of data
• Exploding amount becomes unmanageable
• Generate data, but don’t use it
• Too much paper (paper silos)
• Manual review no longer adequate
• 2.0 does not connect systems
• Missing interfaces between systems
• No use of real time data
• No decision making by automated systems
• Too many ‘home-made’ systems
• Silo culture
• No clear definition of processes, data flow and responsibilities
• Regulated environment slows down innovation
Connecting Pharmaceutical Knowledge ispe.org 49
Pharma 4.0 – The Desired State
• Harmonised platforms (exchange of data among systems)
• Data based decisions
• Self-explaining rather than training (e.g. video SOPs)
• Vitual communities
• Collaboration with universities and authorities
• Independet of locations
• Cloud solutions and cyber security
• Knowledge Management
• Digital acceptance of decisions instead of 4 eyes principle
• Dynamic submissions (eCTD)
• Real time control and self-oprimisation
• Robust decisions
• Saving of resources
• No drug shortage
Connecting Pharmaceutical Knowledge ispe.org
Pharma 4.0Departure into a New Dimension
1. Introduction Into the Topic
2. Pharma 4.0 – Operating Model
3. Pharma 4.0 - Enablers
4. Holistic Control Strategy
5. From Pharma 2.0 to Pharma 4.0
6. How the Future Can Look Like
Connecting Pharmaceutical Knowledge ispe.org 51
A look into the crystal ball
Connecting Pharmaceutical Knowledge ispe.org
Operations
✓ Production Schedule Attainment
✓ Cycle Times
✓ Yield
✓ Right First Time
✓ Breakdown times
✓ Stock Level
✓ Raw Materials delivery
✓ Transportation Schedule Attainment
Connecting Pharmaceutical Knowledge ispe.org
These tasks can be
virtually be done from
anywhere in the world
Operations
Connecting Pharmaceutical Knowledge ispe.org
Engineering
✓ Preventive / Predictive Maintenace Program Schedule Attainment
✓ Calibration Schedule Attainment
✓ Stock Level of Critical Equipment
✓ Projects on Time
✓ Qualification / Validation Status
✓ Power Supply
✓ HVAC Status
Connecting Pharmaceutical Knowledge ispe.org
Service group of people
required to keep
production running
Engineering
Connecting Pharmaceutical Knowledge ispe.org
Regulatory Affairs
Will become
mediators between
company and
authority
Connecting Pharmaceutical Knowledge ispe.org
Quality Assurance
✓ Batch Record Review
✓ Release Time
✓ Deviations
✓ CAPAs
✓ APR / PQR
✓ Complaints
✓ Overdue Items
✓ Ensuring preventive/predictive maintenance and calibration
• Approving CMO
• Approving SOPs and MBR
• Approving Changes
• Conducting Audits
Connecting Pharmaceutical Knowledge ispe.org
Now, what will be the task of the Quality Department
in the future when we operate in a Pharma 4.0 world
Connecting Pharmaceutical Knowledge ispe.org
The Quality Department
will be the
Master of Data…
…or with other words:
Knowledge
Management
Connecting Pharmaceutical Knowledge ispe.org 60
Idea Execution
Judgement,
Coordination &
Control
Connecting Pharmaceutical Knowledge ispe.org 61
The evolution of mankind…..
Connecting Pharmaceutical Knowledge ispe.org 62
….has brought us to Industrialisation.
Connecting Pharmaceutical Knowledge ispe.org 63
Let’s take the chance that digitalisation will
bring us back into the right position.…..
Connecting Pharmaceutical Knowledge ispe.org
Thank You for Your Attention!
Phact GmbH · Christoph Merian-Ring 11 · CH-4153 Reinach BL · +41 (0)61 717 14 15 · [email protected] · www.phact.ch