Post on 03-Jun-2018
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The Development of an AutomationProject
Team:
K. Ha2
A. Kroetsch1
J. Mora2
A. Puri1
E. Rubin3J. Valente2
V. Vydra3
W. Ying1
1: DPST, 2: ABD, 3: LPCD
Jaquan K. Levons
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Outline
Statement of Purpose
Peer Benchmark, Lessons Learned
Process Followed for Automation Project
Mapping
Scope Value Calc.
Ability To Execute
Testing
Hardware and Workflow Summary Timeline
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Peer Benchmarkingof Aseptic Formulation Automation
Better implementation and testing to prevent 12 month + deployment
Ensure dedicated FTE with management support
Simpler workflows w/ less emphasis on integrated analytics
Integrated analytics problematic in deployment
Critical to develop appropriate testing plans (FAT & SAT) to ensureworkflow w ill operate as anticipated.
Feedback from industry peers regarding recent deployments ofsimilar automated workflows provided some guidance on lessons
learned.
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Ability to Execute Criteria
Money for CapEx andrecurring OpEx (hrdwr &sftwr maint,consumables,contractors, annualqualification)
Funding
Laboratory facilities tosupport the newworkflow and proximityto users, collaboratorsand virtually integratedequipment
Facilities
ROI that meetsorganizational needs andwhich can be measured
Value measures =Productivity, Throughput,Quality, Safety,Compliance
ValueMeasures
Impl. team in place todeliver the project
Operational execution
and support model toensure sustainablebenefits realization
Teams
Complete requirementsand testing criteria thatalign to functional area
workflows and valuemeasures
Requirements
Availability & quality oftechnology to fulfillrequirements
Technology
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Value Measures
Aseptic Technology Automation Value
Productivity
Support screening of the current
portfolio and new Projects without
the addition of FTE
Throughput 3X more samples per project with noadditional material requirement
Reduced Cycle
Time
Conduct 4 mo Of IND tox formulation
development screening in 3 mo
Quality
Variability in execution
Variability in designConsistency of experimental data
interpretations and conclusions
SafetyContainment (sample sterility)
Exposure
Definitions:
Productivity - Number of studies/ projects/
compounds executed per FTE
Throughput Number of samples/conditionsprocessed per unit time/study
Cycle Time Duration of a study or activity
from initiation to completion
(Data) Quality Accuracy, consistency of data
and data interpretation
Safety Risk of interaction with scientist due to
pharmacological activity or lab process.
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Process
1.Scoping Activities1. Define business objectives
2. Generate Current State workflow process maps to identifyopportunities/gaps
3. Draft Future State Process Maps
4. Develop Value Proposition (ROI Calculations/Business
Justification)5. Define requirements for budgetary estimate and Obtain
budgetary estimate
6. Deliver Workf low Proposal w/ROI & cost estimate forManagerial Approval
2. Procurement Activities1. Obtain spend approval
2. Engage Global Procurement to obtain vendor proposals
3. Obtain approvals to spend, CAR, PO
Project-Prosecution-TimelineActivities-24Sept2012.vsd
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Process Execution Activities
3. Execution Activit ies
1. Develop User Requirement Specifications (URS)
2. Develop/Build Automated Workflow
3. Factory Acceptance Testing (FAT)
4. Shipment/Delivery/Installation
5. Site Acceptance Testing (SAT)
6. End-User Training
7. Metrics Collection (monitor ROI)8. Establish workflow maintenance & support
9. Engage asset management &/or PDI
Project-Prosecution-TimelineActivities-24Sept2012.vsd
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Statement of Purpose
Aseptic Technologies established objectives to:
1. Meet the demand of an increasing number of biologics projects requiring formulationdevelopment in BMS
2. Increase drug product robustness by enabling QbD in formulation development
3. Expedite formulation development of incoming Pearls
4. Facilitate down stream processing with supportive data packages
5. Enable Fast to Phase I for biologics
The Aseptic Technologies group needs to manage constraints from:
1. Limited drug substance availability in early stage screening
2. Limited quality outsourcing opportunities
3. Limited headcount additions
An automated biologics formulation workflow is targeted at enabling:
1. Productivity increases in screening workflows2. Increased throughput in formulation stability screening to enable QbD
3. Develop a workflow facilitating initial process robustness data package generation
4. Reduced cycle time and miniaturized experiments during phase I formulationexploration
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Formulation Development: High-Level Overview
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Formulation Development: Future State Workflow
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Scope
Automation WorkflowsTargeted:
Asept ic TechnologyWorkflows Supported:
Early Stage: Formulationscreening Pre-FIH, platformenabling, analytics on-deck inline
Late Stage: Compounding highconcentration API, multi-excipientliquid preparations
Initial Process Robustness DataPackage: (viscosity,
concentration as a function oftemperature)
Formulation stability samplepreparation
Sample processing for analysis
Formulation physical propertycharacterization (viscosity, pH,concentration as a function of
temperature)
Enables
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Value Estimations: Productivity Calculations
Use process map to identify key activit ies and estimate time required for execution in the current state (collectingdata from peers) and future state.
Productivi ty savings measured in the amount of scientist time saved, and is the product of:
Number of scientists typically working on an activit y
Number of hours of scientist time required
Probability that thi s action will need to be executed as part of this w orkflow .
Perform macroscopic calculation to ensure numbers are consistent with actual expenditures.
Early Formulation Screening Scenario w/o
Platform
Current State Future State
# of Scientists
Activity Time
(hours)
Workflow
Percentage
Total Scientist Time
(FTE-hrs)
Total Scientist Time
(FTE-hrs)
[FTE*TIME*PERCENT]
1
Receive drug substance in native
buffer 0 0 100 0 0
2 Preparation for Buffer Exchange 1 6 100 6 2
3 Buffer Exchange 2 10 100 20 2
4 Concentration 1 4 25 1 4
5 Add/Spike Excipients 2 8 100 16 4
6 Prepare sterile area for filling 1 4 100 4 2
7 Sterile Filtration 2 2 100 4 2
8 Packaging 1 6 100 6 4
9Move samples to stresstemperature incubators 2 1 100 2 1
10 Pull samples and analytical prep 1 20 100 20 10
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Analysis, Documentation, Study
Planning 2 20 100 40 30
Total 1 Tier of Formulation Screening 119 61
49%
Percent Savings**All Values Are Examples to Illustrate Calculations Only,
and are not Representative of the Actual Scenario**
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Value Estimations: Throughput & Cycle Time
Use process map to identify key activiti es and estimate time required for execution in the current state (collectingdata from peers) and fut ure state.
Number of condit ions tested based on material constraints (e.g. 100 mg of drug substance), instrument cons traints
(e.g. > 100 L sample si ze), and st udy design in the future state. Number of tiers of screening impacts the cycle time.
Multiple tiers can be due to either a lack of throughput or need for information (e.g., optimal pH region).
Excess tiers due to lack of throughput can be minimized by a higher throughput futu re state.
Due to higher throughput, may be able to incorporate additional info rmational studies earlier and eliminatesequential tiers as well.
Perform macroscop ic calculation to ensure numbers are consistent with actual expenditures.
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Projected Return on Investment Key Metrics
FTE Savings: New workflow conducts the same work with fewer number of people
required.
Enables redeployment of FTEs to higher value added work
FTE Avoidance New workflow conducts additional work which would have required hiring
additional people instead.
Enables generation of data previously unavailable.
Financial Return Can be presented as financial value of FTEs saved/avoided minus
depreciated value of investment and recurring costs of workflow.
Often does not incorporate hard to quantify value propositions such asincreasing the value of a formulation. These can be identified separately.
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Projected Return on InvestmentVariables Future State Assumptions
Screening Projects 10 *Estimation for demonstration purposes only
Productivity w/Automation 200%
*Workflow analysis suggests ca. 50% productivity savings for screening
activities for projects where automation is applied.
FTE required to conduct manually 15
*1.5 FTE required during screening activities of each project. 1.5 FTE * 10
projects = 15 FTE.
FTE required to conduct
w/automation 10.5
*Amount of FTEs required to execute 8 projects with automation and 2
project(s) manually considering 200% productivity when automation is
leveraged with 1.5 dedicated FTE.
FTE Savings 4.5 *15-10.5=4.5
Experimental Space w/Automation 200
*8-12 compositions in each of 10 tiers screened in the current state,
compared to 32 compositions in each of 6 tiers where automation is applied
in the future state. Initial analysis done primarily on early stage screens, butis applicable broadly across screening activities.
FTE Avoidance 6.0
*Amount of FTEs required to execute the additional experimental space
(for 8 projects) manually instead of with automation. Incorporates an
engineering factor of 0.5 acknowledging that it may not take twice as
many people to conduct twice the work.
Recurring Costs $0.7 MM/yr
*Instrument cost depreciated (typically over 7 or 10 years) + maintenance
costs and consumables
FTE Savings & Avoidance $1.8 MM/yr *$175k/yr times (FTE savings + FTE avoidance)
Return/yr$1.1 MM/yr
*FTE Savings + Avoidance - Recurring Costs
**All Values Are Examples to Illustrate Calculations Only,
and are not Representative of the Actual Scenario**
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Key Aspects of Requirements
Flow of samples/materials in automated workflow
Accuracy of key quality attributes of final material (e.g., potencyaccuracy and precision, buffer pH, etc.)
Functional specifications of key unit operations
Volume transfer accuracy and precision
Dilution accuracy and precision
Manipulation of materials up to at least = 100 cp
Consider expected environmental conditions
Temperature not to exceed 25 C during processing
Enclosure capable of class 100 conditions
Consider sterility management
Stoppering/Destoppering needed
Minimize human interaction with samples
Consider expected data management
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Key Aspects of Testing (FAT/SAT)
Test an entire run of the workflow with materials that span the
properties of actual materials you w ill use. Note: one successful execution may not be indicative of
robustness
Throughput should be similar to expected production throughput.
develop test p lan that will test crit ical parameters to your workflow
liquid transfer accuracy and precision, abili ty to deliver & measure viscosi ty of concentrated protein
solutions
Throughput how will the workflow handle source reagents andconsumables during execution
Include a test of the full workflow execution. Mimic a real-life orproduction run to fully understand how the system will operate andgain understanding of constraints
Consider developing tests to gain understanding of system robustnessin an time constrained environment like FAT or SAT
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Ability To Execute
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Status
Ability To Execute
Funding Funding allocated from Strategic Initiatives Budgetover 2 years.
FacilitiesAT Automation Lab Renovation underway, available
ca. 3Q/2013. Available facilities aligned with
proposed acquisition.
Value Measures$ca. MM/yr net savings projected.
Teams
Cross-functional team evaluated solutions,
developed ROI, refined requirements, and will
support implementation.
1 dedicated FTE required for operation/execution.
Requirements
Rigorous requirements developed by cross functional
team and agreed upon with vendor. Custom
acceptance tests developed to ensure delivery of
requirements.
Availability of Technology
Solutions
Vendors biologics formulation technology deployed
at other competitors. Substantial internal experience
with vendor technology. New BMS-based workflows
to be added to the technology.
*Projected PO Approval June 30th, 2013
*2 Phase delivery, first acquisition Jan 2014
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Acknowledgements
Core Team
Andrew Kroetsch - DPST
Aastha Puri DPST
Joe Valente - ABD
Vicky Vydra LPCD
William Ying DPST
Acknowledgements
Chris Sinko
Nancy Barbour
Rajesh Gandhi
Farah Kahn
John Brunei
Ed Hensler
Krishnaswamy Raghavan
Andy Stewart
Freeslate Organizers
Dave Yamane
Carole Garner
Paul Digregorio
MVLA Strategic Initiative
Erik Rubin - LPCD
Johanna Mora ABD
Khanh Ha ABD
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Happily Ever After
*Representative image of instruments after phase 1 and 2 deployment