Title: Historical overview of FDA regulation of digital pathology imaging applications: the safety and effectiveness issues
1Historical 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
2Outline
- Define digital pathology
- Intended Use
- Reference standard-Light microscope
- IVDs that utilize digital imaging
- Lessons from Radiology
- Safety and effectiveness issues
3Digital 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
4Intended Use
- Primary diagnosis of surgical pathology
microscope slides in lieu of a microscope - Not an adjunct
- Broad application (not organ or disease specific)
521 CFR 864.3600Microscopes 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- Historical reference standard for surgical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.
621 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
7What does this mean?
Conventional optical microscope
SLIDE
Image Processing software
Digital image sensor
Mechanical scanner
Light source
Imaging optics
Display
READER
IMAGE DATA FILES
- 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
8IVD 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
9IVD devices that utilize digital imaging
- Immunohistochemistry image analysis applications
- i.e. HER2, ER
- Used as an adjunct to quantitate amount of
brown stain
10IVD 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
11IVD 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
12None 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
13Conclusion
- WSI raises new questions of safety and
effectiveness that must answered through
premarket submission requirements
14What 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
15What 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
16Determination of safety and effectiveness
- 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
17Safety
- 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)
18Effectiveness
- 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)
19How 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
20Summary
- 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