Appropriateness For Ldts Companion DX Assays: Perspectives On To Be Used As

Perspectives on
Appropriateness for LDTs

to be used as
Companion Dx Assays
Presented by:
Eric Lawson
•Director, Regulatory Affairs
Voisin Consulting Life Sciences
•Chairman, AMDM Companion Dx Working Group
Association of Medical Diagnostics Manufacturers
AMDM Companion Diagnostics Working Group - - - FDA Public Meeting July 19-20 2010
LDTs and Companion Dx
Disclaimers
• The opinions expressed are those of the AMDM
Working Group on Companion Diagnostics only,
– and may not represent those of the Association of Medical
Diagnostics Manufacturers (AMDM) as a whole
• These opinions are a consensus of the Working

Group representatives — individual contributors may
and do hold additional opinions
• The term “IVD” will be used here for an
“FDA cleared/approved in vitro diagnostic test”
Overview of CDxWG Position
• The CDx Working Group recognizes the use of LDT’s
– in certain clinical diagnostic scenarios, and
– for their value as a rapidly developed, non-distributed, limited
use, adequately regulated, novel diagnostic test to address an
unmet patient need
• The Working Group is not opposed to the continued use

of LDTs in general; however,
• The Working Group does not support LDT use as a

Companion Diagnostic or “CDx”
Personalized
Medicine
Targeted Companion
Therapeutic Diagnostic
Companion Diagnostic “CDx” Definition
A CDx is a diagnostic test:

•whose information is critical to ensure the
Safety and/or Efficacy of a specific targeted
therapeutic treatment (drug) used in Personalized
Medicine
•is identified in the drug labeling to be used to
assist physicians in making treatment decisions for
their patient or a targeted patient sub-group
Companion Diagnostic Applications
• Identify patients with the disease requiring treatment
• Determine the particular drug therapy suited for which
patients, or stratified patient population
• Based on patient genotype or phenotypic expression
• Based on specific disease serotype
• Determine most effective dosage form appropriate for
patient genetic / metabolic makeup
• Reduce Adverse Events that may be caused by mis-
application of the therapeutic treatment
• Evaluate course and effectiveness of patient therapy
Companion Diagnostic Requirements
– Require close collaboration between drug company

and diagnostic manufacturer during development
– Labeling requirements for drug and IVD must be
coordinated
– CDx assays, if not analytically proven, could lead to
misuse of the drug and thereby potential harm for
patient
• The Targeted Therapeutic Drug or Biologic requires clinical data

submitted to FDA for review
– An LDT does not require independent outside review for approval
– An IVD requires analytical and clinical validation data reviewed by FDA
• The Targeted Therapeutic Drug must be approved by FDA before
widespread use
– An LDT does not
– An IVD requires FDA clearance or approval before it is available for sale
• The Targeted Therapeutic must meet strict FDA regulations for

labeling, claims, and vigilance to report adverse events to FDA
– An LDT is not currently subjected to FDA oversight
– An IVD requires FDA oversight of labeling, claims, and MDR reporting to FDA
of adverse events
• The Targeted Therapeutic Drug must meet FDA cGMP requirements
for manufacturing consistency
– An LDT is not required to meet GMP or QSR regulations
– An IVD is manufactured to the FDA Quality System Regulations, 21 CFR 820
Recent ODAC Meeting Minutes:
The FDA committee on Oncology this year commented on a drug

submission that included a Companion Diagnostic of the LDT
variety. The committee made the following statements:
•The lack of having a uniform in vitro diagnostic test creates

uncertainty
– about patient selection both in this trial and,
– more importantly, in a post-approval setting.
•Performance characteristics of an assay should be known prior to
widespread use of the assay and drug use based on this assay.
•Information for the assays … submitted to FDA’s Center for Devices
and Radiological Health (CDRH).
Limitations of LDTs
in a CDx context
– No transparency to public regarding claims
– No opportunity for FDA input or review
– FDA has not evaluated analytical or clinical data
– Lack of FDA oversight on clinical interpretation
– Lack of coordination of labeling claims for both
drug and CDx assay
– No possible coordination of CDRH and
CDER/CBER centers
– No mechanism for adverse event reporting
Recommended Review Process
for a Companion Diagnostic
CDER
Diagnostic Partner
Pharma Partner
OIVD
Recommendations for
Risk Based Labeling Approach
of Drug with CDx
• High Risk - Drug labeling requires the use of a Companion Diagnostic as
identified in its labeling to ensure Safety and Efficacy of the Drug
– The CDx test must be an FDA cleared/approved IVD assay, not an LDT
• Medium Risk - Drug labeling recommends the use of a Companion
Diagnostic as identified in its labeling to ensure Safety and Efficacy
– The CDx test must be an FDA cleared/approved IVD assay, not an LDT
• Low Risk - the Therapeutic includes For Information Only the use of a
Companion Diagnostic identified in its labeling
– The test is recommended to be an FDA regulated IVD assay, not an LDT
Conclusions
of the AMDM CDx Working Group
– While we are not strongly opposed to the use of
LDTs for certain low risk situations or unmet needs
– We do not support the long term use of LDTs for
high risk applications
– We encourage and support appropriate levels of
regulation or adequate controls for LDTs
– We feel that when a diagnostic assay will be used
to make important therapeutic decisions (a CDx),
then LDTs are not the appropriate format
– We propose that Companion Diagnostic tests must
be cleared/approved by FDA
675 Massachusetts Ave. Milton House Level 1
Cambridge, MA 02139 25 Flinders Lane
USA Melbourne, VIC 3000
eggimann@voisinconsulting.com mudge@voisinconsulting.com
3, rue des Longs Prés

92100 Boulogne 2nd floor, "Hara House"
voisin@voisinconsulting.com #1 Gutte Anjaneya Temple Street
Hosur Main Road, Wilson Garden
Bangalore 560027
Espace Performance
vcbangalore@voisinconsulting.com
Bâtiment J
Saint Grégoire Cedex
dupraz@voisinconsulting.com
PSE Building C - EPFL

CH-1015 Lausanne
Singapore
Switzerland
chan@voisinconsulting.com
alvarez@voisinconsulting.com
Please, feel free to contact me or members of
the CDx Working Group with your Questions.
Eric Lawson
lawson@voisinconsulting.com
617-386-9953
Thank you!

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Perspectives on

Appropriateness for LDTs

• These opinions are a consensus of the Working

• The Working Group is not opposed to the continued use

• The Working Group does not support LDT use as a

A CDx is a diagnostic test:

– Require close collaboration between drug company

• The Targeted Therapeutic Drug or Biologic requires clinical data

• The Targeted Therapeutic must meet strict FDA regulations for

The FDA committee on Oncology this year commented on a drug

•The lack of having a uniform in vitro diagnostic test creates

3, rue des Longs Prés

PSE Building C - EPFL

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