Implementation of Template Driven Clinical Analyses, Plate Manager, and Clinical Protocol Manager to Replace In-House Custom Clinical Systems LabWare LIMS v6 Project Francesco DePierro Asc. Director, Research Informatics

Presentation Overview

• Vaccine Research Clinical Business Background – Clinical Work and Statistics – Robotics and Workbox Concept

• Current System Map (with LIMS v5) • New System Map (with LIMS v6) • Project Drivers and Business Case for v6 Project

– Architecture: Template Driven; Easily Scalable • Planning Process: Creating Clinical Protocols and Tracking Samples • Lab Process: Batches, Plates, Meta-Data, and Parsing Files

– Making It All Come Together in Visual Workflows • Master Data: Configuring Analyses, Analysis Groups, Plates, and

Batches • Summary & Acknowledgements

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Vaccine Research Clinical Business Background (Clinical Work and Statistics)

• Clinical sites collect samples for studies and ship samples to Vaccine Research in Pearl River NY. – Samples tested both internally and sent out to contract labs

• Depending on the vaccine study, many strains of the same “bug” may be tested.

• High volumes of samples tested on plates (diluted any number of times)

– During the process samples are transferred to various plates and the genealogy must be tracked.

– Approximately 350k samples with a total of 1m tests completed in 2012.

• Current process is highly customized – Custom programs interfaced with a “weak” LIMS v5. – Samples/Studies may be open, blinded, or double-blinded.

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Vaccine Research Clinical Business Background (Robotics and Workbox Concept)

• Samples are received at our location in random order, random aliquots, random events, etc.

• Assay testing is constantly being upgraded to make it more dependent on robotics in order to improve throughput – Aliquoting incoming samples. – Aliquoting and diluting samples into plates. – Stamping copies of plates for running assays. – Transferring well contents between various plates. – In some cases, moving plates onto/off of shakers. – Analyzing plates and generating raw results.

• The “Workbox” concept was created, to better organize samples that will be tested for similar assays.

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Current System Map (with LIMS v5)

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System map for one example assay:

Not Pictured: Archiving Application & Control Tracking/Trending Application

New System Map (with LIMS v6)

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System map for the new LIMS v6 for harmonized assays:

Not Pictured: Archiving Application & Control Tracking/Trending Application

Project Drivers and Business Case for v6 Project (Architecture: Template Driven; Easily Scalable)

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• Replace custom-built applications used for study/sample management and rudimentary plate management.

• Reduce file transfer and data transfer that is required between interfaced systems (and dependence on extensive amounts of hardware/software).

• Harmonize various parts of the business that have diverged due to custom application design.

• Create a scalable solution that allows for: flexibility in design, minimizes programming, and allows for rapid design.

• Create a foundation that will allow both greater integration of robotics into processes and improved management of data.

• Increase data security and compliance by eliminating unnecessary interfaces and open file browsing/uploading.

Result: Template Based Configuration developed around grouping of analyses to make master data creation flexible and powerful.

Planning Process: Creating Clinical Protocols and Tracking Samples

• Study/Protocol is setup according to clinical requirements. – Expected patients, groups, visits, events (sample type and

required analyses), default actions, etc are all configured in CPM. For Example: Study may have X number of patients, in groups being tested

for all strains or just a subset of strains, requiring any combo of sample types like urine and/or serum, samples pulled at all visits or just some visits, with either one or more samples drawn. When samples are collected and shipped to our site they may require testing, splitting, or storage based on requirements and order of receipt. And, furthermore, they may require aliquots to be shipped to external contract labs for analysis of all or some of the tests.

• Samples are received and managed at our internal lab as default. System has advanced AI in order to make decisions on what to do with each sample as it is received based on the configured protocol, volumes, and other parameters.

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Planning Process: Creating Clinical Protocols and Tracking Samples

Site and Subject Tracking with Clinical Protocol Manager.

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Sub Groups creation within Clinical Protocol Manager.

Planning Process: Creating Clinical Protocols and Tracking Samples

Test Group creation under Testing section within Clinical Protocol Manager.

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Configuration of Visits within Clinical Protocol Manager.

Planning Process: Creating Clinical Protocols and Tracking Samples

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Schedule and Plan Assignment with Clinical Protocol Manager.

Planning Process: Creating Clinical Protocols and Tracking Samples

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Schedule and Plan within Clinical Protocol Manager. When a sample is initially received or sent to the lab, the system does a check on this and

many other parts of both CPM tables and other tables to prompt the user with instructions.

Lab Process: Batches, Plates, Meta-Data, and Parsing Files (Making It All Come Together in Visual Workflows)

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Flexibility must exist to do each step with robotics or manually…

Lab Process: Batches, Plates, Meta-Data, and Parsing Files (Making It All Come Together in Visual Workflows)

• Samples (known as “barcodes”) are aliquoted and grouped into “workboxes” based on assay testing needs and sent to appropriate lab.

• Workboxes setup as customized Storage Locations that group samples based on assay and track (freezer/lab) chain of custody.

• Custom tables were created to allow the concept of Analysis Groups, which allow easy configuration of assays and bring together the following concepts:

– Well format for assays – 96 vs. 384 (dynamic). – Manual plate transfers allowed vs. Robotic Automation. – Sample and batch maximums for each assay. – If multiple tests are allowed – simple vs. multiplex. – Batch naming standards to be used per assay and default initial dilutions. – Where and when to create various custom robot input files. – How robots are interfaced for each assay and how to read input. – Link control, standard, and antibiotic requirements for each assay. – Specify plate mapping formats and templates – stamping 96 to 96, 96 to 384, etc – Specify Meta-data that will be collected by assay.

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Lab Process: Batches, Plates, Meta-Data, and Parsing Files (Making It All Come Together in Visual Workflows)

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Lab Manager Workflow: Creates batches, schedules plating, and assigns work. Workflow is customized to optimize batch sizes and robotic stamping based on protocol, plate

well format, volume of aliquots, and size of workboxes.

Lab Process: Batches, Plates, Meta-Data, and Parsing Files (Making It All Come Together in Visual Workflows)

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Analyst Workflow: System walks the analyst through each step

Lab Process: Batches, Plates, Meta-Data, and Parsing Files (Making It All Come Together in Visual Workflows)

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Analysts or Lab Managers will have the ability to open up their work in Plate Manager to see the linked plate genealogy and associated batch and meta-data information.

Master Data: Configuring Analyses, Analysis Groups, Plates, and Batches

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Batch Test Template and Analysis Master Data is linked up with the custom Analysis Groups that allows us to drive this process in a template fashion.

Master Data: Configuring Analyses, Analysis Groups, Plates, and Batches

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What is an Analysis Group? Collection of all the configurable and standard aspects of each assay

Master Data: Configuring Analyses, Analysis Groups, Plates, and Batches

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Master Data: Configuring Analyses, Analysis Groups, Plates, and Batches

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Master Data: Configuring Analyses, Analysis Groups, Plates, and Batches

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Screenshot shows an example (simplified) view of plate template configuration.

Summary & Acknowledgements

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• Eliminate upload/downloads between various custom systems.

• Eliminate manual file uploads for robotics and statistical application – increase compliance/productivity.

• Add efficiencies to laboratory processes and enhance AI.

• Harmonize business processes that developed in separate directions.

• Implementation of Plate Manager for tracking of plate/sample genealogy and improvement to workbox concept through storage location usage.

• Implementation of Clinical Protocol Manager for creation of study protocols, events, visits, etc.

• Reagent and inventory management from receipt of goods through prep and use on batches as Meta-Data – See presentation later today.

• Develop a process for master data configuration that is easy and scalable for future expansion of assay work (generic and dynamic).

• Build a foundation for future LIMS enhancements.