Ugm Presentation

8/12/2019 Ugm Presentation

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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

4


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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

Documents

Ugm Presentation