2008 Ala - Oral Presentation - Bioanalytical Manager

Improving Bioanalytical Communication, Sample Handling and Decision Making with a Custom Informatics Tool John P. Walsh, Charles E Taylor, Qiner Yang and Robyn Rourick Pharmaceutical Sciences, Kalypsys, Inc. LabAutomation2008 1

The Workflow Problem

Bioanalytical Manager Release 1

Bioanalytical Manager A walk through time…

The Automation Problem

Bioanalytical Manager Release 2

What Lies Ahead

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The Workflow Problem The “Traditional” Method

• Bioanalytical study planning was nonexistent – Bioanalytical Project Representatives – Find out about ongoing studies – Maybe find out about planned studies – Study information was usually incomplete (# samples, etc.) – Study Sponsors – E-mail Bioanalytical group leader about samples deliverED – Hallway conversations about the intent of the study – Couldn’t see the other strains on the resource

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The Workflow Problem The “Traditional” Method

• Bioanalytical sample exchanges were inefficient 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 – Erase whiteboard – Samples placed in a rack for “old” samples 4

The Workflow Problem The “Traditional” Method

• 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 – – – –

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

Bioanalytical Manager Release 1 Facilitating Open Information

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

• Requirements of the system – Intuitive interface consistent with the rest of the company products – Open architecture to evolve with further enhancements – Centralized, comprehensive display – Everyone works from the same information – Ability to track progress of studies BEFORE and after bioanalytical 6

Bioanalytical Manager Release 1 Bioanalytical Group Desires

• Assignment of responsibility to team members • Knowledge of all study relevant information – – – –

Number, type matrix of samples 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 better future planning

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Bioanalytical Manager Release 1 Sponsor, Project & 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 8

Bioanalytical Manager Release 1 Strategy

• The lifeline of an in vivo study was broken up into several stages

• Release 1 was a feasability 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 wasn’t painful for the users – Compromise on the deployment was essential – Compliance is high; complaints are low 9 9

Bioanalytical Manager Release 1 Study Creation – Study Information

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Bioanalytical Manager Release 1 Study Creation – Test Article Information

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Bioanalytical Manager Release 1 Study Monitoring – Homepage

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Bioanalytical Manager Release 1 Study Monitoring – Homepage

• Drag-and-Drop functionality for associating files

• File type independent • Indexing and backup through Windows directory back-end

• All study files attached!

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Bioanalytical Manager Release 1 Metrics Reporting

• SQL Queries plot metrics of the department – Routinely used to determine the best spend for the budget

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Bioanalytical Manager Release 1 Stage Breakdown

Every idea for a study is entered to the Manager: good or bad Compounds are associated to the study All expected and known field are entered with the study Assessment of feasibility and impact to the project Protocol development for the in vivo portion of the study Approval of internal and external resources Ordering and quarantine of the appropriate subjects 15

Bioanalytical Manager Release 1 Stage Breakdown

The study is currently dosing and sample collection Observations and study notes are collected Number of study samples requiring bioanalytical analysis are inputted Samples are received and appropriately logged Responsible Scientist is assigned once analysis begins Bioanalytical preparation and quantitation of all samples A detailed Bioanalytical Analysis Report is issued 16

Bioanalytical Manager Release 1 Stage Breakdown

Interpretation of all study findings Generation and analysis of any pharmacokinetic parameters, if appropriate A detailed Study Report is issued describing the conclusions of the study 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 17

The Automation Problem Defining the Scope

• All bioanalytical sample processes are being done manually • Throughput requirements don’t demand an HT solution – ~345 samples / week – ~5 studies / week

• Importance placed on a high quality product – Automate routine work for PK plasma studies

• Allow scientists to be scientists – Better methods for projects or compounds – More information on compounds as they advance 18

Bioanalytical Manager Release 2 Key Components of System

• Plate registration system – Implement a standard barcoded 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 19

Bioanalytical Manager Release 2 Key Components of System

Schematic of the Release 2

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Bioanalytical Manager Release 2 Platemap Engine – Plate Registration System

• Platemap Engine – Excel tool for sample plates – Multidimensional sample information – Registers plate

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Bioanalytical Manager Release 2 Tecan Sample Preparation

• Fully automated sample preparation for routine studies • Each plate get 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

• Protein precipitation controlled with an internal standard • ~42’ from thawed sample plate to LC/MS injection plate 22

Bioanalytical Manager Release 2 Tecan Sample Preparation

• Select a curve and a Tecan worktable layout

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Bioanalytical Manager Release 2 Tecan Sample Preparation

• Simple registration of the injection plate – User supplies the plate barcode – Platemap is determined from sample platemap and GEM file

• Import the Tecan log file prior to injection – Classifying major and minor errors – Flag samples that may have had problems

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Bioanalytical Manager Release 2 LC/MS Sample List Preparation

• Select the injection plate(s) • Determine which Cal Stds will be QC’s as well • Assign injection volume and QC spacing

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Bioanalytical Manager Release 2 Finally, some results…

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What Lies Ahead Short Term Goals

• Do several Person vs. Machine Challenges of R2 • Tweak the Tecan Error Code parser for better error handling • Upload LC/MS processed results into the database • Bioanalytical Report Generator – Provides a detailed, template report based on acquired data – Incorporation into an e-signature system

• Run NCA processing using WinNonLin – Give PK analyst a head start with the data 27

What Lies Ahead Longer Term Goals

• Integrate other pieces of equipment on the Tecan – SPE, LLE or protein precipitation plates

• Digital image capture of plate on the Tecan deck – Hemolysis or error tracking

• DMPK Report Generator • Vivarium management • Automated tissue preparation 28

Summary

• Bioanalytical Manager has been extremely effective at Kalypsys – More focused discussions around bioanalytical work – Timeline and study management simplified – Prioritization of studies is transparent

• Centralized data repository for study information – Easily mined for IND, Due Diligence, etc. – Full study reconstruction is possible

• 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 29

Acknowledgements Bioanalytical Jerry Muhammad Nahid Yazdani Steven Dorow

From Above Paul Grint Stewart Noble

DMPK Informatics & IT John McNeil Shawn Constable Chris Petersen Robert Beltran

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