Transcript Rockwell Automation External LTS Template

Clinical Trials Supply
Management
Kevin Walls
Rockwell Automation Life Sciences
Global Industry Consultant
Copyright © 2005 Rockwell Automation, Inc. All rights reserved.
1
What’s Keeping You Up at Night?
How can I optimize
my clinical supply
chain?
Clinical Supply
Excellence
How can I lower
Operational costs?
Would a partner help solve
my business issues faster
and better?
What will it take to
integrate all of my
data and systems?

How can I drive
global business?
Am I getting a long
term cost effective
solution?
How can we ease
compliance to
regulatory
authorities?
How can I ensure
safety down to patient
level?
Is my study data
secure?
How can I increase the
accuracy of my demand
forecast?
Copyright © 2005 Rockwell Automation, Inc. All rights reserved.
How should I interact
with my business
partners?
3
Life Sciences Industry Challenges
In the Industry’s Own Words:
“Redefining our discovery and development process to yield new products more efficiently”
“Reduce spending per by 15 to 20% in the U.S.”
“Reducing inventory by $400 million and saving $1.2 billion in procurement by 2008”
“Redesigning all of our end-to-end processes”
“Strengthened capabilities in vertical integration to secure future cost competitiveness”
“Scale in manufacturing and infrastructure in low cost regions”
“Integration of a global manufacturing network”
“Globalization, centralization and standardization of clinical trial operations and data
management”
“Creation of one Pharmaceutical Development “center of excellence” between R&D and
Manufacturing”
Source: Various life sciences manufacturing's investor relations presentations
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4
R&D Spend for New Drug Approval
• Increase of R&D costs by
400% over the last 20 years
• Decreasing output of approved
new drugs
• Spending per new drug
significant increased
• Failing studies becomes more
expensive
Increasing
R&D spending with less output
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5
New Drug Application:
Trials and Patient Numbers
• Number of clinical trial per NDA
doubled over the last 20 years
• Number of needed patients
tripled
• Clinical trials have trended
steadily higher in both cost and
complexity
• Clinical Supplies have to handle
more and more throughput
Increasing number
and complexity of Clinical Trials
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6
CTM Material Waste
Patient kit overage
Bulk dose overage
100%
50%
Average %
Average %
Best in Class %
40%
80%
Best in Class %
60%
30%
40%
20%
20%
10%
0%
0%
Phase I
Phase II
Phase III
Post
Approval
Phase I
Phase II
Phase III
Post
Approval
• Companies are producing in average 30% - 50% material overage
• Best in Class companies are able to lower overage
Source: Managing the Impact of Personalized Drugs on Clinical Trial Supply Operations, F nk Schulze, 2004
Best in Class companies
reduce material overage by 4-5 times average
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7
Working with Business Partners
% of Activity outsourced by companies
Maximum
Average
100
100
100
90
90
90
90
90
90
80
70
• Companies
are still looking for the “golden” outsourcing strategy
60
60
50
• Virtual
companies
are outsourcing almost 90% of all activities
43
40
40
30
23
33
27
22
20
12
12
Prod. of Active
Dose Forms
20
Prod. of
Placebos
30
30
41
Customs
Clearance
Distr of CTM
Shipping
Validation
Shipping Ops
Labeling Ops
Sec Pkg
Prod. of Bulk
Active
0
Primary Pkg
10
Source: Managing the Impact of Personalized Drugs on Clinical Trial Supply Ope tions, F nk Schulze, .2004
Outsourcing requires
the right information exchange platform
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8
Potential Risk in Clinical Supply
• Seeing complexity of the clinical supply chain …
–
–
–
–
–
–
Aligning the supply strategy to the short shelf life of biological IMP
Complying with regulatory rules of multiple countries
Country specific import and export regulations
Late changes of the protocol
Inconsistent patient recruitment process
Country specific labeling requirements
• … leads to higher business risk
–
–
–
–
De-blinding risk of the study
Out of stock situation at the investigator site
Inconsistencies in lacking individual patient data throughout process
Expensive supply of IMP
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10
Clinical Supply Risk Mitigation
• Manage the risk by:
– Providing transparency to the clinical supply
processes
– Balancing flexibility vs. optimization
– Taking capabilities from the API down to the
patient
– Effective material demand planning
– GMP compliant execution of Manufacturing
and Packaging
– Ensuring study blinding with Randomization
and tailored Clinical Supply labeling
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11
An Integrated Process Reduces Risk
Input for
NDA New
Report Project
Destruction of kits
• Fast input over web application
• Automatic gene tion of
study reconciliation report
Returns of kits
• Interface to IVRS, EDC
• Fast input over web application
10
Efficient project planning over all tasks /
milestones
• Automatic update over process & web
• Everyone works to the same plan using a
cent l deposit
1
Study and protocol setup
• Fast input over web request
• Interface to external systems
• Approval
9
2
Patients (kit dispense)
• Interface to IVRS, EDC
• Fast input over web application
8
3
Material
control
Approvals
IMP control on the investigator site
• Inventory Management
• Retest, Recall-Management
Chemical/ pharmaceutical
Development / API MFG
• Expand flexibility for GLP
• Restricted for GMP
• Interface (PLC, PCS)
• Process
7
Project planning
6
Shipment
• Fast input over web request
• Efficient prepe tion and status control
• Interface to external systems
4
5
Bulk MFG
• Integ ted supply chain planning from
API to KIT
Clinical Packaging
• Just in time labelling triggered over
WEB or IVRS
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12
GMP Challenges in Clinical Supply
• Ensure compliance to cGMP for investigational drug products
– Apply appropriate cGMP controls for the manufacture of investigational
drugs during development
– Providing a complete set of GMP documentation
• Coping with regional differences within Good Manufacturing
requirements
– European Guide to Good Manufacturing
• Adhere to cGMPs for placebos used in investigational studies
• Ensure complete tracking and audit till capabilities meet
regulatory requirements
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13
Key GMP Principals Addressed by a
Clinical Supply Solution
• Quality
– Integrated material testing
– Documentation of process and quality issues with Electronic Batch Recording
– Labeling for the API’s intended use
• Equipment and Facility
– Support of Equipment calibration and cleaning with integrated Dispensing and EBR
– Material handling to minimize the risk of contamination and cross-contamination
enabled by material identification and material tracking
• Production
– Documentation in batch records, providing information of use materials, equipment,
processing and scientific observations supported by MBR
• Change control
– Documentation of every change in the production and specification procedures provided
by approval workflow and audit tracking
• Documentation
– Ensure that information gained during the development is documented and available
with MBR
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14
Electronic Batch Recording for
Compliance and Efficiency
• Interactive electronic work instruction guides the operator through manufacturing and
packaging processes and eliminates documentation errors
• Automated identification with barcode and RFID process speeds up the manufacturing and
packaging processes
• Automated recording of deviation reduce the documentation effort
• Mobile solution optimize operational processes and increase efficiency
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15
EBR Document Reductions
•Documents
–
–
–
–
Pages
Entries
Creation
Number
30 - 50% reduction in pages
30 - 60% reduction in entries
25 - 40% reduction in document creation / revision time
10 - 25% reduction in number of documents
250
14000
12000
200
10000
150
Paper
EBR
100
8000
Paper
EBR
6000
4000
50
2000
0
0
Documents
Entries
Pages
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Clinical Supply and Patient Risk
• Wrong medication packed and shipped in patient kits
• Inconsistent processes for tracking and tracing from patient kit to
API and backwards
• Potential wrong information in emergency labels or emergency
letters
• Improper label context in regards to
– Direction for use
– Warning phrases
• Expired material
• Lack of drug at sites is a risk to patient health
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17
Key Patient Risks Mitigated with a
Clinical Supply Solution
• Avoid mis-packed material by controlling instances during the packaging
process
• CTM unique medication identifier provides verification that the right
medication is assembled for the individual patient kit
• CTM creates a complete material genealogy down to the individual
medication throughout the manufacturing and packaging processes
• The material genealogy is the source for any emergency labels or letters
ensuring the right information which are integrated in the CTM labeling
capabilities
• Complete approval workflows significantly lower the risk of releasing
improper information
• integration of the labeling content with the packaging execution assures the
use of the correct label text phrases
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Example: Reducing Patient Risk with
Visit Box Control
1. initialization order
step displays patient list
on mobile scanner
2. Scann visit box
(unique barcode
number)
3. Scan each component
e.g. bottles
5. Update visit box and
patient information
4. System check – bottle
matches visit box
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Alert!
If wrong bottle scanned
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Other Risks in Clinical Trials
• Inherent risks to the security of study data with clinical supply activities
– Insufficient Randomization algorithm could lead to a biased assignment of
patient/kits to treatments
– The missing quality of clinical labels, especially for re-supplies, could cause
unblinding of patient blocks or a whole study
– Uncontrolled access to data, especially Randomization data, is a threat to keep the
blinding
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20
Lowering Bias and Unblinding Risk
• Extensive Randomization capabilities reduce risk
– Proper Randomization is required to generate unbiased comparison groups in
controlled trials
– Management of several Randomization per study
– Symmetric and asymmetric Randomization
– Consecutive and non-consecutive Randomization
– Multiple patient sets
– Stratification
• Integrated Labeling tools reduce risk
– Automated tracking and allocation of printed labels for the packaging process
ensures the use of the “right” labels
– Simple re-reprint capabilities for re-supplies lowers unblinding risks
Copyright © 2005 Rockwell Automation, Inc. All rights reserved.
21
Integrated Label Creation Reduces Risk
Input:
Output:
Random
list
Internal
order for
labels.
Final
approved
CPO
Randomization
Biometrics
generation
process
Set up and
program label
text in labeling
system
Label
approval
Check labeling
system set up
Quality
control
Complete label
documentation
approved
phrases from
text library
Clinical,
Distribution site
CPO - Clinical Protocol Outline:
Drafted and approved including fixed
supplies information.
Print labels
check quality
and count
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Output:
Printed
labels
Challenges to Clinical Supply Efficiency
• Extensive operator involvement with manufacturing and
packaging processes
• Intensive quality control requirements
• Unplanned material overages
• Lengthy paper based approval processes
• Low equipment efficiency
• Manual and time consuming documentation processes
• Time intensive quality control of documentation
• Untimely data collection from diverse global environments
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24
Increase Efficiency in Dispensing
• Dispensing solution ensures the right use of material with batch
identification and eliminates loss of batches
• Guided dispensing capabilities reduce number of operators errors
• Automated tracking and electronic signature capabilities reduces number
of operators in the weighing cabins
• Automated integration of Weighing protocol into the Batch Record
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25
Typical Dispensing Operation
Before PMX Dispense
0%
25%
35%
Weighing
Data Transfer
Recording
Checking
Available
20%
20%
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26
Impact of Automated Weigh & Dispense
After PMX Dispense
25%
2%
3%
65%
5%
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Weighing
Data Transfer
Recording
Checking
Available
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Lower Operational Costs
• Quality review
– Review by exception speeds up the Batch record review process
• Workflow support
– Workflow orientated approval processes of master recipes speeds up idle time of
processes
– Reusable text libraries speeds up the label text translation
– Global web based approval workflow for clinical label layouts
• Scheduling
– Finite scheduling of resources increase the efficiency of equipment, room and
operator use
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28
Time to Market
• Accelerating a product launch by 2 years could
increase the revenue by $600 million
• An effective Clinical Trial Supply management
can help to improve the product launch date
What are delays
costing you? $1M, $2M, or more?
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30
The cost of 1 day
• Total cost of project staff and operations, internal and external:
– average $70 thousand per day
• Advance 1 day towards expiry date (risk further delay)
• Advance 1 day further through seasonality of indication (risk full year delay)
• Delayed revenue in patent life
– $500 million drug: 1 lost day costs $1.3 million+
– $1 billion drug: 1 lost day costs $2.7 million+
• Costs of delayed revenue is unrecoverable at end of patent life
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31
Streamlined Clinical Supplies Releases
Earlier Product Revenue
Improving the manufacturing,
packaging and shipping
processes by factor 3 could
accelerate revenues by $100
Million for a $1 billion drug
Speed up your Clinical Copyright
Supply
chain with your Clinical Supply solution
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32
Clinical Trial Forecasting
• Clinical Trial forecasting utilize many complex factors like:
– Varying enrollment rates
– Drop percentages
– Existing distributed inventory
– Re-test dates
– Study design (Dose escalation, Crossover, Titration,…)
– Country specific start times of studies
• Typical MRP systems are not able to handle all of these factors
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33
Demand-Planning in Clinical Supply
Solutions and ERP (MRP)
CTM
CTMS
Study Information
Countries
Recruitment rate
dropout rate
Clinical
Forecast
ERP (MRP)
PP/MM
Master data
material master data
Demand table
Estimated Demand
(Item-Quantity & Date)
Master data
Production
Planning
Purchase Orders
Execution
Planned Orders
MRP
Simulation
Investigator/Patient
screening
Distribution routes
Predictive Forecast
Lead Time
Initial/Safe Stock
reorder points
Inventory
Advice for
incoming material
Inventory
Inventory bookings
Distribution
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Project Cost
controlling
34
Integrated IT systems improve demand
forecasting
Complex Studies require IT support for successful SCM
• Inputs
– Detailed study
protocol
– Sites and countries
involved in the study
– Recruitment rate
dropout rate
– Expire/retest dates
– Packaging size
– Distribution routes
– Shipment size
– External/internal
resources
IT Systems
Kit
Structure
Study
Modelling
Study Enrollment
Plan
• Outputs
– Forecast demand for
• IMP kits (Pack
types)
• Dosage form
• Component
materials
• Drug substance
– Production schedule
– Distribution schedule
– Inventory Re order
points
Distribution
strategy
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35
Using Simulation to Improve the
Clinical Supply Chain
• Simulation of clinical supply chain
– Visualizing of the entire CTM process including all of its assumptions,
variability, interdependencies, and conflicts
– Analyzing the trial progress in advance
Titration scenarios, recruitment rate, approval times,..
and the effects on the resource levels (material, workload of the CTSU,
contractors,..) and processes using a powerful dynamic, flexible
simulation capability
– Decrease inventory, secure supply readiness and save costs by making
decisions and changes knowing in advance the most probable result
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36
Clinical Supply is a Global Business
• Lack of worldwide harmonization of
the clinical supply processes
– Each site is not able to act as back up of
each other one for full or partial process
– Resources needs to be managed in
common tools & databases
• Trend to run Clinical Trials in
Asia/Pacific area
• Limitation of being able to deliver
clinical material to Asia area, based on
incapability to print labels in Chinese,
Japanese, Indian languages, ….
Most top 10 Pharma Companies
utilize worldwide Clinical Supply units
New challenges created
by globalization and expanding trials in Asia
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37
Communication is the Key
• WEB based requests
harmonize how clinical supply
customer formulates their
needs
• One central database
provides visibility to all sites
• One central data repository
provides a common
communication platform for all
stakeholders
• Logical separation of data by
site
CRO
Cont ctors
Biometric
Statistics
Distributors
Clinical Supply
Site
Japan
Clinical Supply
Site
USA
Medical/
Monitor
cent l
database
Repository
Qualified
Person
Clinical Supply
Site
Germany
Clinic
Centers
Study
Coordinator
Affiliates
Copyright © 2005 Rockwell Automation, Inc. All rights reserved.
Investigators
38
Labeling for Global Customer
• Unicode support for all label text libraries
• Capabilities to easily print clinical supply labels in Asia/Pacific
languages
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39
Drive Tangible Benefits in a Global
Clinical Supply Chain
• One system for all clinical sites is driving common business
processes
• No timely and error prone information and data transfer
necessary using one common data repository
• Global data visibility is supporting the right business decisions
• Optimized use of GLOBAL resources
• Printing labels in native languages for all countries in the world
Consistent information
drives global business performance
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40
Outsourced Supply Chain Management
In-house
Planning
Formulations
Synthesis
Packaging
and Labeling
Shipping
Outsourcing order
Formulations
Packaging
Shipping
Packaging
and Labeling
Shipping
Outsourced
• Need to support the business object outsourcing order
• All material movements must be tracked within the outsourcing order
• Complete material genealogy incorporates outsourced activities
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41
Challenge Areas Around Outsourcing
• Outsourcing needs a high degree of coordination and
information exchange especially in the areas of:
– Process - What gets done Where
– Performance - How is the cont ct manufacturer performing
– Organization - Who is responsible
– Information Systems - Get information in time to make decisions
• Missing information linkage creates error prone, manual and
timely processes to handle contract manufactures
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42
IT Challenges with Business Partners
• Information exchange of Clinical Supply unit and Contract Manufacturers is
based on many sources, e.g.
• Descriptions on paper
• Communication via Email notifications, phone calls…
• Electronic information in various systems of varying data formats
• Different material / batch numbers
• And sometimes there is no information exchange at all,
e.g. material shipped out without any announcement …
• How to trace material?
• How to get Real Time Status Information ?
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43
Example Clinical Supply Solution IVRS Information Flow – Complex!
Clinical Supply Solution
IVRS
1
Project information
Project information
1
2
Study information
Study information
2
3
Study design
Study design
3
4
Clinical ResearchAddresses
Clinical ResearchAddresses
4
5
Warehouse/Distribution Center
Warehouse/Distribution Center
5
6
Material randomization
Material randomization
6
7
Supply request
Supply request
7
8
Material availability
Material availability
8
9
Batch data (Status/Retest)
Batch data (Status/Retest)
9
10
Shipping (Consignment) request
Shipping (Consignment) request 10
11
Shipping (Consignment) order
Shipping (Consignment) order
12
Shipping (Consignment) receipt
Shipping (Consignment) receipt 12
13
Patient dispensing
Patient dispensing
13
14
Unblinding (Patient kit)
Unblinding (Patient kit)
14
15
Destroy
Destroy
15
16
Back Shipping
Back Shipping
16
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11
44
Integrated Systems Improve Trial
Supply Operations and Reduce
Complexity
Status update triggered via IVRS arrival message
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45
Summary
• Reduce the expense and improve efficiency
• Mitigate the risk
• Shorten the timeline of clinical trials through properly managed
clinical material supply
• Do material planning
• Link systems to assure that drug supply continuously meets
demand
• Optimize supply for your clinical trials
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47
Thank You
• Rockwell Automation has the solutions to meet your Clinical Supply Chain Needs
Copyright © 2005 Rockwell Automation, Inc. All rights reserved.
48