1. UPCOMING CHANGES TO IN-VITRO DIAGNOSTICS (IVDs) AND LABORATORY DEVELOPED TESTS (LDTs) REGULATIONS
Moj Eram, PhD
November 5, 2015

2. IN-VITRO DIAGNOSTIC (IVD)
Overview
IVD definition
LDT definition
Comparison of LVD and LDT
EU proposed changes to IVD Regulation
US draft guidance and proposed changes to LDT regulation
Summary

3. IN-VITRO DIAGNOSTIC (IVD)
In vitro diagnostic products are those reagents, instruments, and systems intended for use in diagnosis of disease or other conditions, including a determination of the state of health, in order to cure, mitigate, treat, or prevent disease or its sequelae. Such products are intended for use in the collection, preparation, and examination of specimens taken from the human body.
Types of IVDs – Intended to be used:
In the laboratory
By health professionals at the point of care (i.e. hospitals, Laboratories)
By lay –person (self testing)
Regulatory authority
Medical devices 
Biological products
IVDs - subject to the Clinical Laboratory Improvement Amendments (CLIA '88) of 1988.

4. LABORATORY DEVELOPED TEST (LDT)
A laboratory Developed Tests (LDTs) are in vitro diagnostic tests that are developed, validated and used within a single laboratory (CLIA Certified)
Patients are treated in the facility where test is developed
It can not be used to specify a diagnosis; can state correlation of outcome of a test to a likely outcome
Does not require FDA approval or clearance
Labs not tests are regulated under CLIA

5. IVD and LDT Current Requirements and Regulations
Requirements/Regulations
IVD
LDT
Development and Manufacturing
Developed and manufactured by device manufacturer
diagnostic tests developed and manufactured by a single laboratory
Regulatory Agency
The Food and Drug Administration (FDA)
Centers for Medicare and Medicaid Services (CMS)
Regulations
Medical Device
Class I (Exempt), II (510k), & III (PMA)
CLIA Act of 1988 – CLIA Laboratories
Manufacturing under a Quality System
Yes No
Premarket Review & Approval for Tests
Establishing Clinical / Analytical Validity before using Test
What is Sold
Diagnostics
Service

6. EU – PROPOSED CHANGES TO IVD REGULATIONS
The “New Approach” is prompted by:
Rapid advances in medical device technologies and health care development
Recent finding of safety issues/concerns.
Increase focus on preventive strategies, early diagnostics, need for more self monitoring tests and cost effectiveness
Globalization – need for harmonized regulations
Public expectations
IVD market projection of $22Bn in the EU by 2018, nearly 80% of IVD devices could be subjected to notified body approval, from the currently 20%.
New regulations expected to pass in 2015 – 2016
Require manufacturers 5 years to become compliant

7. EU - UPCOMING PROPOSED CHANGES TO IVD REGULATIONS
Overview of proposed changes:
Extension of regulatory scope – to include high risk IVD manufactured and used within single health institution (LDT)
classification structure for IVD – risk based classification:
4 classes - A (low risk), B, C, D (Highest risk)
Changes in notified body unannounced audits, assessment and oversight
Increased conformity assessment
Clinical evidence - will require for all high risk devices (C & D), clinical literature will not be sufficient
Post market surveillance
Implementation of unique device identification requirements
“Qualified person” for regulatory compliance within manufacturer – assess the conformity of the product
Expanded registration database of devices

8. EU – IMPACT OF IVD REGULATION CHANGES
Anticipated impact on IVD manufacturers:
Broader applicability of regulatory requirements
More requirements for device safety and performance
Increased unannounced inspection (audits) of suppliers and more
Increased post market follow up
Competent authorities performing risk assessment – more scrutiny
Greater provisions for transparency and traceability
Increase time to market
Increased capital need

9. US - LDT REGULATIONS AND RECENT CHANGES
Currently, unlike IVDs, LDTs do not require FDA approval or clearance
FDA proposed regulatory changes due to:
Increased risk associated with LDT’s as IVDs
Inadequate controls and monitoring of tests
LDT are used more broadly outside of the manufactured laboratory
Due to increased complexity of the test
Criticality in clinical decision making in the context of personalized medicine (i.e. genetic testing)

10. US - LDT REGULATIONS AND RECENT CHANGES
Draft guidance - Framework for Regulatory Oversight of LDT - issued October 3, 2014
Risk-based regulatory framework phase over 9 years
All requirements are begin to take effect 6 months after the guidance is finalized
low risk LDT (Class I), traditional LDT, forensic, transplantation, and LDTs intended for rare diseases and unmet needs are exempt form all regulations except for:
Device registration
Device listing
Medical Device Reporting (MDR)
Highest risk LDTs will enforced first – same intended use as cleared/approved IVDs
Moderate and high risk LDTs are subject to more rigorous regulatory requirements
Premarket and post market review for all NEW LDTs

11. SUMMARY
Change is coming … Plan accordingly and get ahead and stay ahead of regulations
Have a proactive strategy to understand and prepare for changes to minimize transition time and reduce risk
For IVD regulation changes in the EU:
Begin classification of your device and plan for new certification requirements
Conduct GAP analysis to check requirements and QMR
Implement Quality Management System (QMS) updates
Understand the role of Notified bodies and plan for increased approval time (budget accordingly)
Give time for implementation/transition
For LDTs regulation changes in the US:
Understand device classification of LDT
Understand the quality and regulatory requirements (GAP Analysis)
Understand the market

12. Moj Eram, PhD Moj.eram@gmail.com
THANK YOU
Moj Eram, PhD