Transcript Historical overview of FDA regulation of digital pathology

Historical overview of FDA
regulation of digital pathology
imaging applications: the safety
and effectiveness issues
Tremel A. Faison, MS, RAC, SCT(ASCP)
FDA/CDRH/OIVD/DIHD
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Outline
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Define digital pathology
Intended Use
Reference standard-Light microscope
IVDs that utilize digital imaging
Lessons from Radiology
Safety and effectiveness issues
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Digital Pathology
• The use of computer technology to convert
analog microscopic images into digital images
• Whole slide imaging (WSI), aka digital imaging,
virtual slides, virtual microscopy
• System consisting of hardware; microscope,
camera, scanner, computer, and monitor, and
software.
• Encompasses image acquisition, processing,
archiving and retrieval
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Intended Use
• Primary diagnosis of surgical pathology
microscope slides in lieu of a microscope
• Not an adjunct
• Broad application (not organ or disease
specific)
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21 CFR 864.3600
Microscopes and accessories
• Historical reference standard for surgical
pathology diagnosis
• Optical instruments used to enlarge
images of specimens, preparations, and
cultures for medical purposes
• Class I (general controls) exempt from
premarket notification (510k) subject to
limitations in 864.9.
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21 CFR 864.9 Limitations of
exemptions from 510(k) (a few)
Exemption only to the extent that
misdiagnosis as a result of using the
device would not be associated with high
morbidity or mortality
– Different fundamental scientific technology
– IVD intended for use in diagnosis, monitoring
or screening of neoplastic diseases
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What does this mean?
SLIDE
Mechanical
scanner
Conventional
optical microscope
Light
source
Imaging
optics
Digital
image
sensor
Image
Processing
software
IMAGE
DATA FILES
Display
READER
• Microscope one component of the system
• Image acquisition, processing and display new
technology for this intended use
• Diagnostic for neoplastic disease
• WSI systems can not be considered Class I exempt
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IVD devices that utilize digital
imaging
21 CFR 864.5260
Automated cell-locating
devices
Examples
• Automated hematology
analyzers (differential cell
counters)
• Chromosome analyzers
• FISH enumeration
systems
• Urine sediment analyzers
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IVD devices that utilize digital
imaging
• Immunohistochemistry
image analysis applications
– i.e. HER2, ER
– Used as an adjunct to
quantitate amount of “brown”
stain
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IVD devices that utilize digital
imaging
• Manual Read of Digital Image
– Immunohistochemistry with no image analysis
– Pathologist performs estimation of stain
intensity and percent positivity from digital
image alone
– Limited to Breast PR and HER2 applications
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IVD devices that utilize digital
imaging
• Gynecologic Cytology
Imaging Systems
– Cytyc/Hologic ThinPrep
Imaging System
– Becton Dickinson/TriPath
FocalPoint Guided
Screening System
– Papanicolaou Stain
– Class III devices
– Detection algorithm, neural
network
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None of these examples can
be directly applied to digital
whole slide imaging
Each of these devices has a
specific and limited intended use
that is not applicable to WSI for
the breadth of surgical pathology
specimens
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Conclusion
WSI raises new questions of safety and
effectiveness that must answered through
premarket submission requirements
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What are our concerns?
• Is the WSI presented of such quality that the
same diagnosis could be made as when using
the light microscope for all surgical pathology
specimens?
• What are differences in use between the two
methods? i.e. viewing and navigating on a
computer screen vs. a light microscope
• Serious consequences to public health if
misdiagnosis is caused by poor quality image or
improper use
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What can we learn from
radiology?
• Similarities between switch from film to digital
mammography
• 21 CFR 892.2010 Medical image storage device
• 21 CFR 892.2020 Medical image communications
device
• 21 CFR 892.2030 Medical image digitizer
• 21 CFR 892.2040 Medical image hardcopy device
• 21 CFR 892.2050 Picture archiving and communications
system
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Determination of safety and
effectiveness
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21 CFR 860.7
Intended use population
Conditions of use for the device
Probable benefit to health from the use of
the device weighed against any probable
injury of illness
• Reliability of the device
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Safety
Reasonable assurance, based on valid
scientific evidence, that the probable
benefits to health from use of the device
for its intended uses and conditions of use,
when accompanied by adequate directions
and warnings against unsafe use,
outweigh any probable risks
21 CFR 860.7(d)(1)
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Effectiveness
Reasonable assurance, based on valid
scientific evidence, that in a significant
portion of the target population, the use of
the device for its intended use and
conditions of use, when accompanied by
adequate directions for use and warning
against unsafe use, will provide clinically
significant results
21 CFR 860.7(e)(1)
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How does FDA plan to ensure the
safety and effectiveness of digital
pathology devices?
• Require analytical and clinical studies to
objectively and precisely validate performance
• Knowledge of the risks, benefits and limitations
• Standardization
• Postmarket studies
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Summary
• FDA recognizes that the technological advances
associated with WSI make its use a reality
• WSI systems are not Class I exempt and are therefore,
subject to premarket requirements
• Current IVDs that utilize digital imaging for limited
applications are not applicable to the WSI paradigm
• Digital mammography may provide useful lessons but
does not address all of the concerns for WSI
• Our goal is to gain information about the technology in
order to ensure safe and effective use
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