Partnering for Success in Personalized Medicine

Ted E. Schutzbank, PhD, D(ABMM)

Associate Director, Genomics

Covance Central Laboratory Services

2

Companion Diagnostics (CDx)

January 15, 2001

© 2001 TIME magazine, all rights reserved.

3

Companion diagnostics are diagnostic devices or tests (IVDs) that are intended to assure that certain therapeutic drug or biological products are used in accordance with their labels to achieve approved safety and effectiveness.

Companion Diagnostics (CDx)

4

Companion Diagnostics (CDx)

5

Case Study 1

• Tx non-small cell lung cancer (NSCLC)

• Requirement for a CDx test

• Signal transduction pathway gene target

• Mutations in the target adversely affect drug efficacy

• Assay to detect specific target gene mutation

• Medical Device Partner

• IUO labeled kit

• Training

• Data to Pharma client

Pharma client for oncology protocol

Signal transduction Pathway. © 2009 QIAGEN, all rights reserved.

6

Challenges

Rapid turn-around time (TAT)

• Inclusion/exclusion

• End-stage disease population

• Heavy competition for patients

Global logistics

• Korea, India and China

• Local testing requirements (China)

• Import issues with kits & materials

• Data compatibility

• U.S. testing for all other samples

DNA extraction from multiple sample types

• FFPE tissue

• (real-time, 7 day TAT)

• Plasma

• Batched samples

7

Actions

Testing established in U.S. and Shanghai

• Standardized instrumentation and test kit lots

• Global cross correlation and QC

• Training by manufacturer at both sites

• Global SOP and method validation

FFPE Tissue samples processed and tested

Design DNA isolation procedure from plasma

• Kit designed for DNA extraction from FFPE tissue

• Lab designed and validated new plasma protocol

PLASMA samples stored frozen (-70°C), and tested at the end of the enrollment period

8

Results

FFPE tissue testing performed on time

• Met established TAT (function of logistics)

Plasma sample testing completed, data submitted to the client

All client requirements completely satisfied

9

Additional Comments

Genomic testing on Chinese patients must be done in China

• Complications often arise when dealing with Chinese regulatory agencies

• Import of instrumentation, kits and reagents

• Import of biological materials for validation purposes

Scientific expertise demonstrated through successful design and implementation for the detection of circulating tumor DNA in plasma

10

Case Study 2

Pharma company working with IVD company for the development of companion diagnostic test for melanoma drug

• Drug target is a protein in a signal transduction pathway

• Drug efficacy is affected by mutations in the gene coding for the target

• The CDx detects mutations that cause resistance to therapy

Covance was contacted by the test manufacturer to perform testing for their PMA submission to the FDA

The manufacturer provided:• Test kits• Instrumentation and equipment• Training for Genomics lab personnel• All patient samples

• Sent as tissue sections on slides• Previously tested by an outside

reference laboratory • Tested using an LDT assay

BRAF-mediated pathway. Huang, P.H., and Marais, R., "Cancer: Melanoma Troops Massed," Nature, 459:336-337 (2009).

11

Complex Handling of Samples

Histology Lab

• Samples digitally imaged in-house on Aperio scanners

Pathologist Slide Review

• Percent tumor content• Melanin• Circle areas of tumor tissue

Database

• Pathologist’s review• Total tissue area• Total tumor area• Percent tumor content

Macrodissection

• Patient slides with <80% tumor content

• Multiple slides per patient

Genomics

• DNA extraction and testing

Specimen Management

• Accessioning of all samples• Relabeling all samples• Tracking samples • Shipping unused samples,

and residual extracted DNA

12

Actions

Specimen Management

• Database construction

• All slides re-labeled with a Covance accession number prior to imaging

• LIMS system kept track of where each sample was each step along the way

• Testing

• All testing at one site (data combinability)

• Testing results entered into the manufacturers database

• Results reviewed, electronically signed off by the PI

• All entries also backed up on paper forms supplied by the manufacturer

13

Results

Successful development of in-house sample tracking system

Testing of all samples completed in advance of the manufacturer’s deadline

The data is being readied for submission to the FDA for review

14

Lessons Learned / Takeaways

Rapid TAT is critical

• Need to enroll patients quickly

• Patients are in end-stage disease, specially for melanoma

• Tremendous competition for these patients, patients are a precious resource

Scientific knowledge and expertise to develop new testing protocols

Communication

• Training by manufacturer

• What data should be captured during the slide review

• Expectations for deadlines and reporting of results

Few commonalities

• Case 1 was prospective, testing patients at enrollment

• Case 2 was retrospective, testing patients at the conclusion of the study

Learn More: www.blog.covance.com

15

As the biopharmaceutical industry increasingly turns its focus to discovering and delivering targeted, personalized medications, the companion diagnostics field is rapidly advancing. By 2015, the worldwide companion diagnostics market will be worth $3.45 billion, according to London-based market research firm Visiongain. The involvement of central laboratories in the companion diagnostics space is also growing, as they increasingly play a role as partners with, and facilitators between, biopharma and diagnostic companies.

Continue reading ---->

Partnering for Success in Personalized Medicine:Central Labs and Companion DiagnosticsPosted by Ted Schutzbank, Ph.D., Associate Director of Genomics, CovanceWednesday, October 17, 2012