Improving Bioanalytical Communication,

Sample Handling, Data Reporting and

Decision Making with a Custom
Informatics Tool
John P. Walsh, Charles E. Taylor, Qiner Yang and Robyn A. Rourick

NON-CONFIDENTIAL October 28, 2008 1

 Overview

The Workflow Problem

Bioanalytical Manager Release 1

Bioanalytical Manager Release 2

Delivering the Product

Delivering the Business

NON-CONFIDENTIAL October 28, 2008 2

 The Workflow Problem

The “Traditional” Method

– Bioanalytical Project Representatives
– Find out about ongoing studies
– Maybe find out about planned studies
– Incomplete study information (# samples, etc.)

– Study Sponsors
– E-mail Bioanalytical group leader about samples delivered
– Hallway conversations about the intent of the study
– No awareness of other strains on resources

NON-CONFIDENTIAL October 28, 2008 3

 The Workflow Problem

Inefficient Bioanalytical sample exchanges

1) Place samples in freezer
2) Write study on whiteboard
– Coded for shelf, study, plate type, project, etc.
3) Send email to Bioanalytical Group Leader (samples in freezer)
4) Conversation about urgency, number, type of samples
[A few days later…]
5) Conversation about the timeline for analysis
[A few days later…]
6) Send out results to PK and/or project leader and/or sponsor
7) Erase whiteboard
8) Samples placed in a rack for “old” samples

NON-CONFIDENTIAL October 28, 2008 4

 The Workflow Problem

Why this was difficult to manage

– Bioanalytical resourcing was hard to capture
– Always busy, but how busy?
– What projects are putting a load on the system?
– Number of studies
– Number, type of samples

– Study histories were not organized

– Bioanalytical Group Leader had some information
– Responsible Scientist had some information
– Study Sponsor had some information
– Past study reconstruction was difficult (read: stressful)

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 Moving towards a solution…
Bioanalytical Manager Release 1

NON-CONFIDENTIAL October 28, 2008 6

 Position of Bioanalytical Research

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 Bioanalytical Manager Release 1

Facilitating Open Communication

– Primarily, a project management problem
– Scientific progress should not be altered
– Requires a more open communication standard

– Requirements of the system

– Intuitive interface aligned with other company products
– Open architecture to evolve with further enhancements
– Centralized, comprehensive display
– Everyone works from the same information
– Ability to track progress of studies RE and after bioanalytical

NON-CONFIDENTIAL October 28, 2008 8

 Bioanalytical Manager Release 1

Bioanalytical Research Group Desires

– Assignment of responsibility to team members

– Knowledge of all study relevant information

– Number, sample matrices
– Study contact for questions
– Urgency of the results
– Dose administered or levels expected

– Track the historical context of the department

– Reconstruct the competing interests on all studies at all times
– Assess bottlenecks for efficient planning

NON-CONFIDENTIAL October 28, 2008 9

 Bioanalytical Manager Release 1

Sponsor, Project and Company Desires

– Association of all bioanalytical data to a study or project

– Ability to mine data for SAR table generation

– Notification of relevant parties for significant events

– When it is being worked on, results available
– Any notes, comments or questions about the study

– Centralized location for study results

– Data was being held in multiple Excel tables in Outlook

– Notebook references for study progression

NON-CONFIDENTIAL October 28, 2008 10

 Bioanalytical Manager Release 1

Strategy
– The lifecycle of an in vivo study was broken up into several
stages

– Release 1 was a feasibility assessment

– Company-wide deployment of a Bioanalytical tool
– Refinement of the workflow tool prior to new functionality
– Will people use it???

– Business rules were applied in order to make the system work

– Adoption of the system was painless for user

– Compromise on the deployment was essential
– Compliance is high; complaints are low

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 Study Creation

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 Study Creation

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 Study Monitoring

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 Study Monitoring
Associate files with drag-and-drop
functionality

File type independent

Indexing and back-up through company

Windows directory

All study files attached!

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 Stage Breakdown
Every idea is entered regardless of feasibility

Registered compounds are associated to the study (2-way association)

Most study planning fields are entered (study name, dates, etc.)

Assessment of the studies value to the project and anticipated cost

Protocol development for the in vivo portion of the study

Approval of the relevant internal and external resources

Ordering and quarantine of test subjects

NON-CONFIDENTIAL October 28, 2008 16

 Stage Breakdown
Study is currently ongoing and being dosed or monitored

In vivo study observations and notes are entered

The expected sample drop-off time and date are input

Samples arrived in Bioanalytical Research freezers

Responsible scientist is assigned when the work is about to begin

Bioanalytical preparation and analysis of samples

A detailed bioanalytical report is issued describing the prep and results

NON-CONFIDENTIAL October 28, 2008 17

 Stage Breakdown
Interpretation of all study findings (i.e. PK, histopath, in vivo observations)

Generation of pharmacokinetic parameters, if relevant

Final study report issued with the conclusions of the study

Study Finalization
– Studies are finalized when the last report has been issued
– Studies are never deleted, only removed from viewing
– All reports are attached to the BA Manager item

NON-CONFIDENTIAL October 28, 2008 18

 The Automation Solution
Bioanalytical Manager Release 2

NON-CONFIDENTIAL October 28, 2008 19

 Bioanalytical Manager Release 2
Defining the Scope
– All bioanalytical sample processes being done manually

– Throughput requirements didn’t demand an HT solution

– ~345 samples / week (at time of assessment)
– ~5 studies / week (at time of assessment)

– Importance placed on a high quality product

– Automate routine work for PK plasma studies
– Hallway conversations about the intent of the study

– Allow scientists to be scientists

– Better methods for projects or compounds
– More information on compounds as they advance

NON-CONFIDENTIAL October 28, 2008 20

 Bioanalytical Manager Release 2
Components of the System
– Plate registration system
– Implement a standard bar-coded plate for sample submission

– Chain-of-Custody tracking of samples

– Integrate with a Freezer Management System

– Automated sample preparation on a Tecan Evo

– Including the preparation of a standard curve

– Integration with LC/MS systems

– Supply sample lists to the systems for analysis
– Associate data to each sample from the processed output

NON-CONFIDENTIAL October 28, 2008 21

 Schematic of the Design

NON-CONFIDENTIAL October 28, 2008 22

 Plate Registration System

– Excel tool for sample plate information entry

– Multi-dimensional sample information entry

NON-CONFIDENTIAL October 28, 2008 23

 Bioanalytical Manager Release 2
Tecan Sample Preparation
– Fully automated sample preparation for routine studies

– Each plate gets a customized sample preparation routine

– Based on the registered sample plate information
– Tecan GEM file created, not a worklist

– Calibration curve spiking and dilution included in the prep

– Blanks, CS0 and solvents added to the plate

NON-CONFIDENTIAL October 28, 2008 24

 Bioanalytical Manager Release 2
Tecan Sample Preparation
– Protein precipitation controlled with an internal standard

– ~42’ from thawed sample plate to LC/MS injection plate

– Simple registration of the injection plate

– Platemap is determined from sample platemap and GEM file

– Import the Tecan log file prior to injection

– Flag samples that may have had problems

NON-CONFIDENTIAL October 28, 2008 25

 Release 2 Automation Options

Centralized deployment of the

automation tasks

Created files are automatically

added to the BA Manager item

Laboratory tasks are logically laid

out in order to minimize training

NON-CONFIDENTIAL October 28, 2008 26

 Tecan Sample Prep File Generation

NON-CONFIDENTIAL October 28, 2008 27

 Analyst File Generation

NON-CONFIDENTIAL October 28, 2008 28

 Automated Preparation Results

NON-CONFIDENTIAL October 28, 2008 29

 Automated Preparation Results

NON-CONFIDENTIAL October 28, 2008 30

 Delivering the Product
Wrapping quality to the deliverable

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 Delivering the Product

– Desired product was always a quality Bioanalytical report

– Low barrier to authorship for scientists
– Use all the data collected for the study
– No more Excel tables with results only!!!

– Utilize data from multiple sources to “put it all together”

– Use all the data collected for the study

– Interface with SharePoint 2007 for storage of all final reports

– Use the XML backbone of Office 2007 applications
– Route and E-sign documents to finalize

NON-CONFIDENTIAL October 28, 2008 32

 Document Construction

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 Document Construction

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 Document Construction

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 Report Publishing

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 Delivering the Business
Intelligently using all this information

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 Delivering the Business - Conclusions

– Bioanalytical Manager has been extremely effective at

Kalypsys
– More focused discussions around bioanalytical work
– Timeline and study management simplified
– Prioritization of studies is transparent
– Weekly queue prioritization meetings are F-A-S-T

– Centralized data repository for study information

– Easily mined for IND, Due Diligence, etc.
– Full study reconstruction is possible
– Keeps the responsibility of the study de-centralized

NON-CONFIDENTIAL October 28, 2008 38

 Metrics Analysis

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 Delivering the Business - Conclusions

– Detailed metrics analysis allows the shaping of the business

– Accurate information on the output of the group
– Ensure that projects are getting stage-relevant support

– Automated sample preparation has potential in Discovery

– Allow scientists to focus on important issues
– Capture and use as much info as possible for data integrity

– Bioanalytical Research delivers a quality report with little effort

NON-CONFIDENTIAL October 28, 2008 40

 Acknowledgements

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 Thank You

NON-CONFIDENTIAL October 28, 2008 42