OpX for a Life Sciences Process
ISPE Western Annual Conference
25 March 2009
Winnipeg, CA
John Piela – Senior Consultant
Life Sciences Industry
Introduction
• Trends in Life Sciences Industry
• Operational Excellence
• DMAIC Process
– Include Business Focus
– Include Examples of Tools
– Include some items used to justify an EBR project
• QBR’s (use cases)
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Mergers & Acquisitions ???
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Life Sciences Industry Global
Trends – 2009
• Pharma Mergers & Acquisitions continue
– Merck / Schering; Pfizer / Wyeth; & Roche / Genentech
> $150 billion sales
• Business Drivers to M&A
– Life Science & Technology Stocks are cheap
– Big Pharma seeking diversification with Generics And
Contract manufacturing
– Generics and BioTechs are booming
– Global companies cutting costs by expanding into China
and India where labor is less expensive
– govt. run health care era?
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Life Sciences Industry Global
Trends – 2009 and Beyond
• Shortage of generic capacity is imminent - by 2012
– Patent expiration: $90 billion
– Grey factor: 24% of population over 60
• FDA has embraced Innovation
– ICH Guidelines embraced - Quality by Design, Risk
based Approach,
– PAT provides online QA and batch optimization
– ASTM 2500 eliminates duplication of testing. Customers
are pushing validation on to the vendors
• Segmentation will continue: Pharmaceutical;
Biotech; Generics; Biosimilars; and CMOS
– Stem cells segment by 2012
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Operational Excellence - How to
begin ?
Benchmarking – Looking at the Trends
Focus on what can be controlled
Look at what Best-in-class are doing
What/How are Best-in-class doing to achieve
results.
Resource: Aberdeen Group does
Benchmarking
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Example Define:
Benchmarking
99.6%
97.4%
100
99.4%
96%
85-95%
90
80
90 wd
74%
60-80%
70
92%
60
50
W orld Class
50
W inning Pharma
Pharma Industry
40
30%
30
20
14
10
6 wd
1 wd
3-5
0
Stock Turn
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OTIF %
RFT %
OEE %
Data Reference: Pharmaceutical Engineering July/August 2004
Cycle Time
(w d)
How to Achieve Operational
Excellence ?
“To achieve Operational Excellence , Process
Manufacturers must be able to keep control
over cost structures while meeting customer
expectations.”
“Best-in-Class companies provide visibility into
manufacturing operations while using real time
interoperability between manufacturing systems
and business systems.”
Source: Operational Excellence in the Process Industries – Aberdeen Group September 2008
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How are Best
-in-class
Best-in-class
Manufacturers measured ?
Maturity Class Definition
Best-in-Class:
Top 20% of performance
scores
Industry Average:
Middle 50% of performance
scores
Laggard:
Bottom 30% of performance
scores
Mean Class Performance
99% Mfg Schedule Met
99% Perfect Orders
97% Overall Yield
97% OEE
94% Mfg Schedule Met
96% Perfect Orders
91% Overall Yield
85% OEE
81% Mfg Schedule Met
78% Perfect Orders
84% Overall Yield
71% OEE
Source: Operational Excellence in the Process Industries – Aberdeen Group September 2008
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How to Achieve Operational
Excellence ?
Key Differentiator
“Best-in-Class is the ability to use technology
within many aspects of manufacturing to gain
visibility into operations.
Higher Levels of interoperability between MES
and other enterprise systems such as PLM,
ERP, and SCM.
Source: Operational Excellence in the Process Industries – Aberdeen Group September 2008
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How to apply
Operational Excellence?
Focus on what can be
controlled
Look for areas of opportunity
Manage change, improve
How?
Six Sigma
Lean
Lean-Six Sigma
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How to apply
Operational Excellence?
Six Sigma
Lean
Objective:
Objective:
Reduction of defects and variation
in products and services
Elimination of waste and cycle time
reduction
Competitive Advantage:
Competitive Advantage:
Comes from stable and
predictable processes which allow
cost reduction and reliable
product performance
Comes from delivering the most value
from customer’s perspective with the
fewest resources
Examples:
• Reduce contaminations
• Improve process yields
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Examples:
• Inventory reduction
• Improve process cycle times
• Minimize unnecessary processing
Lean gives a perception of cost
reduction only!
• Key objective of OpX is to find the sweet spot
between cost and risk.
• Sub-optimizing will land the company in an
unrecoverable situation. .
• Frontier Airlines: So lean that when a snow storm
hit Philadelphia their cash flow suffered. They did
not have spare planes and pilots in other cities to
fly customers. They lost customers and still
recovering.
• Source: Tim Moore, Supply Chain VP – Genentech
at Interphex 2009, March 17, 2009
•
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DMAIC Process
• Define
– Program/Project objectives
• Measure
– Use validated data - Map your current state
• Analyze
– Assess the value and what it means to your organization
– Map your future state
• Improve
– Implementation plan (transitions)
– Change management / Project management / Training
• Control
– Celebrate successes
– Manage challenges
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Define Business Opportunities
•
•
•
•
•
•
•
•
•
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Revenue
Shareholder value
Sales
Profitability
Customer value
Employee satisfaction
Quality
ROIC
Other
ROIC Improvement Model
$#
$
(
%
&
)&&
*
+,
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!
" #
$
&&
'
Increase
profitability
by 5%
ROI
calculations
exceed
10%
Increase
RFT to
99% from
85%
Example Define:
S95 Current State
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Example Define:
Batch Record (EBR)
•
•
•
•
•
•
Batch release cycle time exceeds 115 days
A lot of paper rework
Paper tracking cumbersome processes
Inconsistency in applications
Islands of automation
Increased Inventory levels to compensate
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Measure & Collect
Relevant Data
•
•
•
•
•
•
•
•
•
•
Yield
Batch cycle time
Release cycle time
CIP/SIP or batch turnaround time
Product turnover time
Inventory
Asset availability
Customer satisfaction
Deviations
Discards & waste
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Where to get data?...and How?
•
•
•
•
•
Interviews with relevant people
Systems – ERP, LIMS, PIMS, historian, etc.
Collect data manually
Ensure that data is relevant and valid
How to ensure your data is valid
– Measurement analysis
– R & R - Repeatable & Reproducible
– Double check entries
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Measure: Value Stream Map
Processes
WORK
PROCESSES
NORMAL
VALUE
ADDED
ABNORMAL
NON-VALUE
ADDED
ESSENTIAL
FLOW
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REDUCE
UNNECESSARY
ELIMINATE
Example Measure:
Value Stream Map (VSM)
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Analyze Your Data
•
•
•
•
•
•
Where are the areas for greatest improvement?
Why are these defects happening?
Define likely causes and possible solutions.
Variability? Can a source be uncovered?
Define potential roadblocks to improvements.
Use appropriate tools.
– Value stream maps
– Business process map
– Fishbone diagrams
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Example Analyze Data:
Batch Record Review
• Batch record review & cycle time average >115 days
• Why? - Categorize into types of defects
–
–
–
–
Missing entries
Incorrect entries
Calculation errors
Deviation required
• XX hours to resolve deviations
• YY hours chasing down documents for review & approval
• Value Stream Map (VSM)
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Example Analyze:
Batch Record Review
Deviations by category
120
100
Deviations
80
Material Related
Document Related
Process Related
Operator Related
Equipment Related
60
40
20
0
Jan
Feb
Mar
Month
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Apr
May
Example Analyze:
Fishbone Diagram (Cause & Effect)
-Wording ambiguous
-Entry space not lined up
-Wording ambiguous
-Bad handwriting
-Not enough space
-Pages stuck together
-Document separated for use
-Lines run together
-Not enough space
-Explanation inadvertently missed
-Did not believe explanation was required
-Misread document
-Lines run together
-Forgot Rules
-Read numbers wrong
-Calculator broken
-Misread numbers used
= Significant Factor
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Analyze: Focus for Value
Addition
WORK
PROCESSES
NORMAL
VALUE
ADDED
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– Increase throughput
– Increase yield / Reduce
variability
ABNORMAL
REDUCE
– Reduce cycle time / WIP
• Asset Management Issues
– Reduce unplanned
downtime / equipment
failures
– Improve maintenance
processes / prioritize
efforts
NON-VALUE
ADDED
ESSENTIAL
FLOW
• Operational Issues
UNNECESSARY
ELIMINATE
• Compliance Issues
– Reduce cost of quality /
improve quality
processes
– Simplify paperwork
management / convert
to electronic tools
Example Analyze:
Savings Full Implementation
Electronic Work
Instructions /
In-Process
Material Tracking
Data
Integration
Cycle Time
Improvements
Total
$500,000
$500,000
$0
$1,000,000
Batch Cycle Time Reduction
$0
$0
$2,000,000
$2,000,000
Release Cycle Time Reduction
$0
$0
$800,000
$800,000
Extensions in Calibration Cycles
$1,000,000
$0
$0
$1,000,000
Minimize Operational Duplication
$400,000
$570,000
$0
$970,000
Reduce Maintenance Overtime
$500,000
$0
$0
$500,000
Control Monitoring
$100,000
$60,000
$0
$160,000
$0
$0
$400,000
$400,000
$250,000
$0
$0
$250,000
$0
$0
$1,200,000
$1,200,000
$2,750,000
$1,130,000
$4,400,000
$8,280,000
Annual Benefit
Batch Record Review / Release Improvement
Real Time Electricity Optimization
Eliminating Atypical Batches
Reduced Start-up and Commissioning
TOTAL
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Improve: Process Roadmap
• Current state, future state
• Journey to future state
• Types of maps
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S95 Future State
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Future State Example - Integrated
Plant Floor to Boardroom
•Enterprise Integration
•for configurable access
to all plant operations
•Compliance Suite
•Manufacturing
Operations
•for real-time,
personalized
interaction
•Integrated
•Engineering
•for unified
•recipe
development
•Compliance Suite
•for order,
resource,
•and
document
•management
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•DeltaV Batch
•to optimize
•batch
•execution
•Historical Data
•to collect and
review all
relevant data
•DeltaV
•Process
Operations
•for realtime,
personalized
interactions
•Advanced Control
•for
reduced
process
variability •Mobile Access
•PlantWeb Connectivity
•for easy, native, integration of plant floor devices
• for real-time,
• wireless
• interactions
•Asset and
Machinery
Management
•for improved
reliability
Benefits = ROI
• Calculate cost of project
• Calculate benefits
• Determine financial feasibility (and other factors)
– ROI
– IRR
– Payback
• Future State & Road map considerations
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Key Project Execution
Considerations
• Normal project tracking methods
– Schedule, cost, earned value, etc.
– Change management
– Risk management
• Training
– New or revised methods/procedures
– New or modified systems
– Refine training for existing problematic areas
• Change management/communications
– Audience analysis/job mapping
– Process Analysis/Technology Impact
• Other considerations
– Historical data (paper, electronic, etc.)
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Interfaces to other systems (ERP, Deviations, LIMS etc.)
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Examples of OpX Projects
• Define: Errors in equipment cleaning and use logs and
review time drains resources
• Measure: 8 hours review; 8 hours error resolution every
month; 16 errors found per month
• Analyze: Why; options for improving; calculate potential
savings
• Improve: Implement electronic logs; provide training for
new system
• Control: Review time reduced to 2 hours; 1 hour error
resolution per month; 1 error per month
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Case Study: Control Performance:
Batch Reactor Temperature Control
180
70
180
65
160
65
160
140
SP
PV
OUT
JACKET.OUT
55
50
120
100
45
80
40
60
35
40
30
25
0
5000
10000
15000
60
SP and PV (C)
SP and PV (C)
60
OUT (%) and JACKET.OUT (%)
70
SP
PV
OUT
JACKET.OUT
55
50
140
120
100
45
80
40
60
35
40
20
30
20
0
25
20000
Time (seconds)
35000
OUT (C) and JACKET.OUT (%)
•After Control
Performance
•As Found
0
40000
45000
50000
55000
Time (seconds)
•Results: Batch Reached Temp. Setpoint in same time but with no overshoot
• Saved approximately 50% of steam and 15% of chilled water on each batch
• Implementing changes on three reactors has saved 10% of steam consumption for
the entire building
• Project payback time < 3 months
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MES Suite – Electronic
Manufacturing
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Eli Lilly – 22 sites globally
CHALLENGE
– Global document management
SOLUTION
–
–
–
–
–
–
Implementing DCA, DA, EBR, WD, ET, SA
>10,000 active users
>80,000 controlled documents
Integrated with SAP
Paperless document management
Integrated weigh & dispense, equipment tracking,
and EBR
– Process automation systems are mix of DeltaV and
PLCs
•Pharmaceutical
Manufacturing
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RESULTS
– $3 M annual savings from reduced time and effort
managing documents
– Rollout completed in record time due to minimized
validation requirements
(configuration - not custom programming)
– Easy access to current and effective
documents
across multiple sites
Electronic Batch Record - Bill of Material
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Lonza – Visp, Switzerland
CHALLENGE : batch cycle time
SOLUTION:
– Implemented RA, DCA, MM, EBR, SA, WD, ET
– >125 active users, >500 controlled documents
– Integrated with SAP and DeltaV recipes
RESULTS
– Review by Exceptions - reduced approval time from
100hrs to 2 hrs
•Biopharmaceutical
Manufacturing
– Total cGMP material control at the container level
– Eliminated incorrect/expired material charged into
the process
– Shorter batch cycle time
– Eliminated equipment logbooks
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Electronic Work Instructions
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Electronic Batch Record - Exception
Report – The “Holy Grail”
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Bristol
-Myers Squibb
Bristol-Myers
CHALLENGE: Paper Batch
Record Execution and Review
SOLUTION
– Implemented RA, DCA, EBR, MM, SA, WD,
ET
– Integrated with SAP and DeltaV recipes
RESULTS
•Pharmaceutical
•Manufacturing
– Reduce deviations / improved right- first-time
operations
– Review by exception
– Improved release time
– 25% improvement in manufacturing cycle time
– 50% reduction in batch release time
– 25% reduction in errors
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Recipe Authoring and DCS
Integration
Recipes can initiate action
within DeltaV – such as an
equipment lockout.
DeltaV equipment graphic
can display the lockout.
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MES and ERP Integration
•A: Item Master Data
•4a: Material Availability
Confirm
•1: Process Order Release
•8: Request for Materials •6: Goods Issue
•9: Goods Receipt
•2: Transfer Order
Confirmation
•10: Manufacturing Complete
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•7: Material Adjustment
•11: Order Status
•12: Inventory
Synchronization
•2: Transfer Order
Confirmation
Other Examples of OpX Projects
• Define: Maintenance costs have grown by x%.
• Measure: Y instruments are calibrated every three months
with no adjustments z% of the time
• Analyze: Evaluate risks versus benefits of extending the
calibration time; calculate $ savings per year by extending
calibration based on manufacturer’s recommendations
• Improve: Implement new calibrations frequencies justified
by data
• Control: Continue to monitor calibrations and further refine
program based on data
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Typical OpX Project Program
A proven, data driven methodology
1. Initial Assessment:
What problem needs to be solved?
2.
Detailed Study:
What are the specifics of the problem and the
capability of the processes?
3.
Report and Recommendation:
How will modifications to business processes
and systems deliver benefit? How will
changes impact the organization
4.
Project Implementation:
Define / execute realistic plan
5.
Results Analysis:
Compare results to initial baseline
6.
On-Going Control:
What work practices can be put in place to
sustain and increase the gain?
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DMAIC Summary
• Define
– Program/Project objectives
• Measure
– Use validated data - Map your current state
• Analyze
– Assess the value and what it means to your organization
– Map your future state
• Improve
– Implementation plan (transitions)
– Change management / Project management / Training
• Control
– Celebrate successes
– Manage challenges
There are many different types of opportunities out there waiting
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for you!
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Where To Get More Information
• Benson, Roger S., McCabe, Jim D.J.,
“From Good Manufacturing Practice
to Good Manufacturing Performance:
Pharmaceutical Engineering”,
July/August 2004.
• Rath & Strong, “Rath & Strong’s Six
Sigma Pocket Guide”, 2004.
• Pzydek, Thomas, “The Six Sigma
Handbook”, New York: McGraw Hill,
2003.
• Emerson Process Management OpX
Program Materials, 2005, 2006.
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Emerson
’s Life Science
Emerson’s
Experience
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Thanks!
• John Piela
– (610) 569-4023
– John.Piela@EmersonProcess.com
• Roy Dansen
– (204) 631-0712
– Roy.Dansen@lakesidecontrols.com
• Frank Bialek
– (204) 631-0706
– Frank.Bialek@lakesidecontrols.com
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