Transcript FDA oversight of in vitro diagnostics

FDA oversight of
in vitro diagnostics and other
medical devices
Pamela L. Bradley, Ph.D.
Personalized Medicine Staff
Office of In Vitro Diagnostics and Radiological Health
Center for Devices and Radiological Health
U.S. Food and Drug Administration
NCCS Cancer Policy Advocate Training (CPAT)
November 13, 2014
Talk Overview
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What is a medical device?
FDA’s risk-based regulation of devices
Companion diagnostics
Laboratory developed tests (LDTs)
The future of cancer diagnostics
Medical Devices
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Hospital Bed
Artificial Heart
Drug Eluting Stent
Insulin Pump
Tongue Depressor
Thermometer
Mobile Medical App
IVDs (In Vitro Diagnostic)
“an instrument, apparatus,
implement, machine,
contrivance, implant, in
vitro reagent or similar
related article…intended
for use in the diagnosis of
disease or other
conditions, or in the cure,
mitigation, treatment, or
prevention of disease, in
man or other animals”
FFDCA 201(h)
FDA Regulation of Medical Devices
• Risk-based approach
– Medical Devices are regulated to an extent that is
driven by the risk of their Intended Use
– For example: tongue depressors have a lower
regulatory bar than artificial hearts
• Components of oversight
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Registration and Listing
Premarket review
Good Manufacturing Practices
Adverse Event Reporting
Recalls
What is an IVD?
“Reagents, instruments, and systems intended for use
in the 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 in man. … for use in the collection,
preparation, and examination of specimens from the
human body.” [21 CFR 809.3]
• Can be used in clinical laboratories & other settings
(e.g., Point-of-Care/Over-the-Counter)
IVDs Used For…
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Diagnosis
Screening
Risk Assessment
Surveillance
First Response
Not Environmental Screening
Not Ancestry Information
IVDs: Risk and Intended Use
• For IVDs, intended use is what a test measures and
how to use the results
• For IVDs, the risk is based on the consequences of a
false result
For example:
– Higher risk – HIV test
– Lower risk – pregnancy test
• The same IVD could have different level of risk
depending on intended use:
– Example: Screening asymptomatic individuals for the
presence of cancer risk genes is generally higher risk than
detecting the presence of a mutation in an individual
diagnosed with cancer
Device Classification
• 3 Classification levels dictate required
regulatory controls
– Class I: common, low risk devices
– Class II: more complex, moderate risk
• Premarket review: 510(k), de novo
• “Cleared”
– Class III: most complex, high risk
• Premarket review: PMAs
• “Approved”
FDA Premarket Review
• Independent review of IVD performance
claims prior to clinical use
• Assures test performance claims are
supported by scientific evidence
• Assures claims are clinically meaningful
• Assures test limitations are described
Scientific review of IVD performance
• Analytical performance characteristics
– Reliability and accuracy of analyte measurements
• Clinical performance characteristics
– Clinical sensitivity and specificity
– Positive and negative predictive values
• Labeling
– Intended use, device design, directions for use,
warnings/limitations, result interpretation, performance
• Transparency:
http://www.fda.gov/MedicalDevices/DeviceRegulation
andGuidance/Databases/default.htm
Postmarket Surveillance and Controls
• Helps to identify and correct problems early
• Medical Device Reports (MDRs)
– Mandatory and voluntary reports submitted to MAUDE -Manufacturer and User Facility Device Experience
– Publicly available at
• http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfMAUDE/sea
rch.CFM
• Recalls
– Method to remove or correct products in violation,
– Usually voluntary
• Provides assurances of IVD performance throughout
its lifecycle
Companion Diagnostics
• Expect growing use of genetic information to
suggest, and sometimes dictate, therapy
decisions
– “only patients positive for genetic biomarker X
should receive this drug”
– “patients with genetic biomarker Y should not
receive this drug—use alternative therapy”
• Herceptin and HER-2 status first drug/dx pair
Companion Diagnostics
“The success of personalized medicine depends on having
accurate diagnostic tests that identify patients who can
benefit from targeted therapies.”
Dr. Peggy Hamburg and Dr. Francis Collins
“The Path to Personalized Medicine” New England Journal of Medicine; July
22, 2010
• Having a good test is as important as having a good
drug
• Need for a clear companion diagnostics policy for
patient safety and to support therapeutic product
approval
Companion Diagnostics: FDA Policy
• Published Guidance: In Vitro Companion Diagnostic
Devices (Draft July 2011; Final July 2014)
• Defines companion diagnostics:
– An IVD companion diagnostic device is an in vitro
diagnostic device that provides information that is
essential for the safe and effective use of a corresponding
therapeutic product.
• Describes expectations for codx contemporaneous
approval with the therapeutic product
• “How to” guidance on codevelopment coming soon
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Companion Diagnostics: Current Status
• To date: 19 different approved
drug/diagnostic combinations
– One imaging device
– Cancer leading the way – 18/19
– Many are HER-2 specific (10)
– Others: ALK, B-RAF, C-KIT, EGFR, KRAS
– Historically, one analyte—one test—one drug
– www.fda.gov/companiondiagnostics
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Laboratory Developed Tests
“test kit”
manufacturer
An LDT is a type of IVD that
is designed, manufactured
and used within a single
laboratory.
LDTs are marketed under
enforcement discretion by
FDA.
CLIA-certified
lab
FDA
“Enforcement
Discretion”
Performed in CLIAcertified lab
Performed within same lab
that developed test
Public Health Need for Greater
Oversight of LDTs
• Evolution of LDT technology, marketing, and
business models has increased risk associate
with LDTs
• Consequences
– Significant adverse health consequences
– Unnecessary healthcare costs
– Could undermine progress of personalized
medicine, which depends on tests that work
FDA’s Current Proposal for LDTs
• On Sept. 30, 2014, FDA issued draft guidance
that proposes an oversight framework for LDTs
– Informed by 2010 public meeting and public
comments
• Goal: to work with all stakeholders to
determine a framework for oversight that is in
the best interest of public health
FDA’s Current Proposal for LDTs
1. Collect basic information on all LDTs through a
notification process (a no-fee alternative to R&L)
2. Phase-in enforcement of regulatory requirements
over 9 years, based on risk
3. Use public process to obtain input on risk and
priority for enforcement
4. Continue some enforcement discretion for specific
categories determined by FDA to be in the best
interest of public health
FDA seeking comment on
Proposed LDT Framework
• Info, links, archived webinar available at:
www.fda.gov/LDTs
• 120-day comment period opened Oct 3
• Notice of Availability in Federal Register
– Points out specific issues for comment
• Questions? Email:
[email protected]
The Future of Cancer Diagnostics
• Liquid biopsies
• Cancer panels
– Combination of CoDx and novel markers
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Whole exome/Whole genome sequencing
Other omics
Big data
Centralized knowledge databases
Consideration of new regulatory approaches
Questions?
[email protected]