Scalable Digital Pathology in a Large, Preclinical Organization

Luc Chouinard, DVM, DACVP

Scientific Director, Pathology

OVERVIEW

• Charles River Preclinical Services• Current use of Digital Pathology in CRO• Future applications

• A leading in vivo biology company– $1.34B in net sales (FY 08)

• Unique portfolio of products and services focused on the research and development continuum for new drugs

• A multinational company with ~8,700 employees worldwide– ~70 facilities in 17 countries

Charles River Snapshot

Corporate HeadquartersWilmington, MA

4

Existing Pharma / Biotech Cluster

Emerging Market

CR Global Footprint

A global presence with proximity to our clients’ sites

Charles River Preclinical Services

PRECLINCAL/DISCOVERY Sites – Overview

• PCS– Montreal – full service, all species, some disease models– Shrewsbury – full service, all species, some disease models– Edinburgh – full service, all species, non-pharma services – Nevada – historically only primates (inc repro), now offering

rodent and dog toxicology, safety pharmacology, lab sciences

– Pennsylvania – reprotoxicity, phototoxicity, neurotoxicity– Ohio – general toxicology, carcinogenicity– China– all species (initially ≤ 3 mo), GLP and non-GLP– Sherbrooke – all species, mainly general toxicology

– PAI –Complete pathology services

• DIS– MIR – imaging, oncology/inflammation rodent models– Piedmont – oncology models– Ceribricon- CNS rodent models

Charles River Pathology Services

• More pathologists than any other company in the world

• Assessment of pathologic changes in: Drug discovery Toxicology Animal colony maintenance

Value of digital pathology services for sponsors

• Allow sharing/consultation across sponsor and CRO pathologists

• Be aware of potential adverse findings earlier• Better understanding of the toxicity profiles by

making comparisons easier• Avoid inefficient sharing of partial images or

lengthy discussion (via teleconference) to describe a finding

• Reduce costs and time delays in pathologist travel and shipping of slides

• Allow sharing with consultants

Value of digital pathology for CRO

• Further enhances client relationships • Enhance consistency• Improve training • Improve standardization• Improve productivity• Cost saving

CRO Preclinical Pathology Challenges

• Quest for faster reporting and effectiveness• Shorten turnaround time for consultations• Limiting travel for peer review on site• Avoid days or weeks for the transportation of

glass slides • Potential issues with border/custom and

international laws

PCS MTL experience

• Installation of a high capacity scanner Q1 2008

PCS MTL number

• 17 Pathologists• 1.5 M tissues processed/year• 35 000- 45 000 slides prepared/months• Average 6 peer review/week• 3 on site; 3 ship to sponsor

PCS MTL Digital Pathology Team

• 3 administrators

• Manage the Internal and Client accounts.• creating user and/or administrator accounts• assigning access levels • password administration

PCS MTL Digital Pathology Team

• Manage scan requests and all steps towards generation of the virtual images for users

• Contact material preparation group for slides access and ensure adequate slide condition prior to scanning

PCS MTL Digital Pathology Team

• Contact the pathologists and clients with access info

• Help desk/trouble shooting with clients• Responsible for deleting images/slides on servers

as per guideline

PCS MTL Digital Pathology Workflow

Metada and Laboratory information system

Local IT solution

Interfacing to laboratory information systems

SLIDE LOADER 1.0.1• No Barcoded slides!• Metadata transfer from two sources

Proventis (LIMS) and PLS form (histology lab database)

Slide loader 1.0.1

Metadata transfer - interdepartmental information –systems-applications

GUIDELINES

• PROCESS FLOW FOR SCANS • REQUEST FOR SCANS • MATERIAL PREPARATION GROUP - SLIDE

RETRIEVAL AND LOADING • MANUAL SCANS• AUTOMATIC SCANNING• TRACKING OF REQUESTS FOR SCANS • DIGITAL SLIDE CONFERENCING • DELETING IMAGES • TROUBLE SHOOTING NOTES

PCS MTL Data since installation

0

500

1000

1500

2000

2500

3000

3500

2008 2009

Total slides scanned

Internal

Client related

PCS MTL Data since installation

• More than 4000 slides scanned • 200 requests• 85 % client related• Slides scanned from 155 projects• 95% reduction of internal photomicrography

needs

Current use

• External Consultation

• Internal Training & Meeting

• QC

• Formal Complete Peer Review

• Full tissue complete GLP study evaluation

• YES

• YES

• YES

• NO

• NO

PCS MTL experience

Scanning protocols Not routine for all sponsors or projects Case by case needs for the majority Scan selection of tissues, targets or unusual

changes for discussion in the majority of the cases.

Generally limited to 10-30 slides/study. Scan of all tissues in preterminal death in a few

occasions

PCS MTL experience

Improved Pharma-CRO partnershipPre-study or pre-report meeting (TC, Web)

Review\Discuss\Share SlidesKey findings Previous studiesPotential targets Glossary Grading

Toxicity Study Dose Group Comparison

Toxicity Study Dose Group Comparison

Toxicity Study: Terminology and Grading

Challenges

• Acceptance• GLP & Implementation & Validation

STP position paper Pathology Image Data

STP position paper Pathology Image Data

Pathology images (printed, electronic, or digital) used for data generation (e.g., to make a diagnosis or for morphometric analysis) are raw data that must be authenticated and archived.

Important notes from the STP position paperDuring an informal pathology review, the opinions of any consultingpathologists are not binding on the study pathologist.

The preamble to the GLP Regulations, as amended on September4, 1987, and published in the Federal Register (Volume 52,No. 172, pages 33768-33782), states that:

“. . . . pathologists interim notes, therefore, which are subject to frequent changes as the pathologist refines the diagnosis, are not raw data because they do not contribute to study reconstruction

Accordingly, only the signed and dated final report of the pathologistcomprises raw data respecting the histopathological evaluation oftissue specimens.”

STP position paper Pathology Image DataInformal Consultation

Informal pathology consultation before the pathology report is completed is a common practice in toxicologic pathology.

Informal discussions and any associated images are not pathology raw data

Future of Digital Path in CRO

• GLP use• Enhance use of automated function and analysis

Hematology

Immunohistochemistry

Morphometry

Histology pattern recognition-CAPS

The future of Digital Pathology

Summary

• The introduction of digital pathology in a large CRO had an immediate and significant impact despite current limitations and challenges

Improved • Efficiencies• Partnership • Training• Overall Quality of Services

Summary

The future is promising!

Acceptance and new automated applications will modify the role of pathologists to further facilitate interpretation and improved translational toxicology

Thank you