fda-2010-n-0274-0021.1

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 DxDisclaimers

• 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”


LDTs and Companion DxOverview 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 Therapeutic

Companion Diagnostic


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 “CDx” Definition

• 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 Applications

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


LDTs and Companion Dx

• 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


LDTs and Companion Dx

• 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


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).

Recent ODAC Meeting Minutes:


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


OIVD

CDER

Pharma Partner

Diagnostic Partner

Recommended Review Process for a Companion Diagnostic


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


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Singapore [email protected]

Please, feel free to contact me or members of the CDx Working Group with your Questions.

Eric [email protected]

617-386-9953

Thank you!AMDM Companion Diagnostics Working Group - - - FDA Public Meeting July 19-20 2010

fda-2010-n-0274-0021.1

Documents

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fda committee

fda input

fda clearance

cdx amdm companion diagnostics

amdm companion dx

companion dxdisclaimers