FDA’s Draft LDT Framework & Personalized Medicine Update Elizabeth Mansfield, PhD OIR/CDRH/FDA ACLA May 5, 2015

Proposed Framework for LDT Oversight Two draft guidance documents: Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories: Framework for Regulatory Oversight of Laboratory Developed Tests (LDTs) Draft Guidance for Industry, Food and Drug Administration Staff, and Clinical Laboratories: FDA Notification and Medical Device Reporting for Laboratory Developed Tests (LDTs)) Published October 3, 2014 Public meeting January 2015 Comment period closed March 2015

Basic Overview FDA proposed oversight of LDTs: Risk-based Phased-in Premarket review, QS for most LDTs Requirement for “notification” for all LDTs Requirement for adverse event reporting for all LDTs

“Carve-outs” Continued enforcement discretion for: Rare tests Tests for unmet need Traditional LDTs Forensic (Law Enforcement) LDTs LDTs Used in CLIA-Certified, High- Complexity Histocompatibility Laboratories for Transplantation Intent: preserve access, promote innovation

Notification All labs notify who they are and what LDTs they offer—6 months (or register and list) FDA uses notification to inform classification panels for new intended uses Highest risk LDTs identified in draft Framework

Highest Risk Regulatory Oversight Phase-in: Other high risk devices: a) LDTs with the same intended use as a cleared or approved companion diagnostic b) LDTs with the same intended use as an FDA-approved Class III medical device; and c) certain LDTs for determining the safety or efficacy of blood or blood products. Other high risk devices: a) Screening devices for serious diseases and/or conditions intended for use in asymptomatic patients with no other available confirmatory diagnostic product or procedure, such as screening device for malignant cancers (b Diagnostic devices for certain infectious diseases with high-risk intended uses c) Devices that act like companion diagnostic devices

Classification New intended uses classified through recommendation of advisory panels Several panels Draft guidance issues 24 with classifications for all tests Already classified tests use existing classification

Phase-In Schedule 9 year phase-in Highest risk first Work through risk categories until complete Categories called in by announcement in advance of requirement to submit

Comments About 300 different commenters About 1400 different comments All comments categorized and assessed Guidances to be revised to reflect FDA’s consideration of comments

Personalized Medicine Personalized Medicine Staff 5 FTEs with different types of experience Several additional FTEs may be added Projects/Guidance documents include: Companion Dx Investigation Use Device LDT NGS, etc

Precision Medicine Initiative FDA to create regulatory pathway appropriate for NGS $10M proposed Addresses data analytics, informatics, and regulatory quality databases Will be interacting with stakeholders, publishing draft guidance documents etc Stay tuned, its exciting!