(95 days)
Not Found
No
The summary describes a system for digitizing and viewing pathology slides, with performance studies focused on agreement rates and discrepancy rates compared to traditional microscopy. There is no mention of AI, ML, or any algorithms that perform automated analysis or interpretation of the images. The system is described as an "aid to the pathologist," implying the pathologist is the primary interpreter.
No
The device is described as an "automated digital slide creation and viewing system" intended "as an aid to the pathologist to review and interpret digital pathology slides." It functions for "in vitro diagnostic use" by creating and displaying digital images of scanned glass slides for primary diagnoses. This indicates it is a diagnostic tool, not a therapeutic one.
Yes
The 'Intended Use / Indications for Use' section explicitly states, "The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital pathology slides..."
No
The device description explicitly states the system is comprised of both a scanner instrument (hardware) and viewing workstation with computer and software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the system is "intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue."
- Purpose: The system is used to create and view digital images of scanned glass slides that would otherwise be examined by conventional light microscopy for diagnostic purposes.
- User: The intended user is a "qualified pathologist," who uses the system for "primary diagnoses."
- Performance Studies: The document includes a summary of performance studies that evaluate the system's accuracy and precision in the context of diagnostic interpretation.
- Predicate Device: A predicate device (Philips IntelliSite Pathology Solution) is listed, which is also an IVD digital pathology system.
All of these points strongly indicate that the Aperio AT2 DX System is an in vitro diagnostic device.
N/A
Intended Use / Indications for Use
The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens.
The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System.
Product codes
PSY
Device Description
The Aperio AT2 DX System is an automated digital slide creation and viewing system. The system is comprised of an Aperio AT2 DX scanner instrument and a Viewing Workstation with a computer and a calibrated monitor executing ImageScope DX viewer software. The system capabilities include digitizing microscope slides at diagnostic resolution, retrieving and displaying digital slides, including support for remote intra-net access over computer networks, providing tools for annotating digital slides, entering data associated with digital slides and displaying the scanned slide images for primary diagnoses by Pathologists.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Digitized microscope slides
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Pathologist
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies
The performance testing was conducted via a series of studies that included Accuracy, Intra-System, Inter-System/Site. Within-Pathologist and Between-Pathologist precision.
The accuracy was evaluated by analyzing the concordance of the diagnoses made using the Aperio AT2 DX System (also known as WSIR diagnosis) with the gold standard reference diagnoses (the original sign-out pathologic diagnosis), and the concordance of traditional light microscope slide review (MSR) diagnoses with the gold standard reference diagnoses. Accuracy was assessed by analyzing major discrepancy rates for each study modality versus the gold standard reference diagnosis and calculating the difference between the major discrepancy rates for WSIR diagnosis and MSR diagnosis. Major discrepancy was defined as a difference in diagnoses that resulted in a clinically important difference in patient management.
The acceptance criteria were as follows:
- The upper bound of the two-sided 95% CI of the difference between the overall major discrepancy rates of WSIR diagnoses and MSR diagnoses is
§ 864.3700 Whole slide imaging system.
(a)
Identification. The whole slide imaging system is an automated digital slide creation, viewing, and management system intended as an aid to the pathologist to review and interpret digital images of surgical pathology slides. The system generates digital images that would otherwise be appropriate for manual visualization by conventional light microscopy.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include the following information:
(i) The indications for use must specify the tissue specimen that is intended to be used with the whole slide imaging system and the components of the system.
(ii) A detailed description of the device and bench testing results at the component level, including for the following, as appropriate:
(A) Slide feeder;
(B) Light source;
(C) Imaging optics;
(D) Mechanical scanner movement;
(E) Digital imaging sensor;
(F) Image processing software;
(G) Image composition techniques;
(H) Image file formats;
(I) Image review manipulation software;
(J) Computer environment; and
(K) Display system.
(iii) Detailed bench testing and results at the system level, including for the following, as appropriate:
(A) Color reproducibility;
(B) Spatial resolution;
(C) Focusing test;
(D) Whole slide tissue coverage;
(E) Stitching error; and
(F) Turnaround time.
(iv) Detailed information demonstrating the performance characteristics of the device, including, as appropriate:
(A) Precision to evaluate intra-system and inter-system precision using a comprehensive set of clinical specimens with defined, clinically relevant histologic features from various organ systems and diseases. Multiple whole slide imaging systems, multiple sites, and multiple readers must be included.
(B) Reproducibility data to evaluate inter-site variability using a comprehensive set of clinical specimens with defined, clinically relevant histologic features from various organ systems and diseases. Multiple whole slide imaging systems, multiple sites, and multiple readers must be included.
(C) Data from a clinical study to demonstrate that viewing, reviewing, and diagnosing digital images of surgical pathology slides prepared from tissue slides using the whole slide imaging system is non-inferior to using an optical microscope. The study should evaluate the difference in major discordance rates between manual digital (MD) and manual optical (MO) modalities when compared to the reference (
e.g., main sign-out diagnosis).(D) A detailed human factor engineering process must be used to evaluate the whole slide imaging system user interface(s).
(2) Labeling compliant with 21 CFR 809.10(b) must include the following:
(i) The intended use statement must include the information described in paragraph (b)(1)(i) of this section, as applicable, and a statement that reads, “It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using this device.”
(ii) A description of the technical studies and the summary of results, including those that relate to paragraphs (b)(1)(ii) and (iii) of this section, as appropriate.
(iii) A description of the performance studies and the summary of results, including those that relate to paragraph (b)(1)(iv) of this section, as appropriate.
(iv) A limiting statement that specifies that pathologists should exercise professional judgment in each clinical situation and examine the glass slides by conventional microscopy if there is doubt about the ability to accurately render an interpretation using this device alone.
0
May 20, 2019
Image /page/0/Picture/1 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: a symbol on the left and the text "FDA U.S. FOOD & DRUG ADMINISTRATION" on the right. The symbol on the left is a stylized representation of the Department of Health & Human Services seal. The text on the right is in blue, with "FDA" in a larger font size than the rest of the text.
Leica Biosystems Imaging, Inc. Christine Kishi Sr. RA Specialist 1360 Park Center Dr. Vista, CA 92081
Re: K190332
Trade/Device Name: Aperio AT2 DX System Regulation Number: 21 CFR 864.3700 Regulation Name: Whole slide imaging system Regulatory Class: Class II Product Code: PSY Dated: February 13, 2019 Received: February 14, 2019
Dear Christine Kishi:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate device marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR
1
- for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Yun-Fu Hu, Ph.D. Deputy Director Division of Molecular Genetics and Pathology OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K190332
Device Name Aperio AT2 DX System
Indications for Use (Describe)
The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not use with frozen section, cytology, or non-FFPE hematopathology specimens.
The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the interpretation of images obtained using the Aperio AT2 DX System.
Type of Use (Select one or both, as applicable)X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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3
Image /page/3/Picture/0 description: The image shows the logo for Leica Biosystems. The word "Leica" is written in a stylized red font. Below the word "Leica" is the word "BIOSYSTEMS" written in a sans-serif font.
510(k) Summary Aperio AT2 DX System
I. Submitter
Leica Biosystems Imaging, Inc 1360 Park Center Dr. Vista, CA 92081
II. Contact Person
Christine Kishi Sr. Regulatory Affairs Specialist 1360 Park Center Dr. Vista, CA 92081 christine.kishi@leicabiosystems.com Phone: (760) 539-1194 Fax: (760) 539-1116
III. Device
Proprietary Name of the Device: Aperio AT2 DX System Classification Name: Whole Slide Imaging System Regulation Number: 21 CFR Part 864.3700 Regulatory Class: Class II Product code: PSY
IV. Predicate Device
Philips IntelliSite Pathology Solution (PIPS) DEN160056
4
Device Description V.
Clearance of this premarket application will enable the Aperio AT2 DX System comprised of a scanner and a viewing station for the primary diagnosis of formalin-fixed paraffin-embedded tissue.
System:
The Aperio AT2 DX System is an automated digital slide creation and viewing system. The system is comprised of an Aperio AT2 DX scanner instrument and a Viewing Workstation with a computer and a calibrated monitor executing ImageScope DX viewer software. The system capabilities include digitizing microscope slides at diagnostic resolution, retrieving and displaying digital slides, including support for remote intra-net access over computer networks, providing tools for annotating digital slides, entering data associated with digital slides and displaying the scanned slide images for primary diagnoses by Pathologists.
Image Acquisition:
The Aperio AT2 DX has a 400 glass slides capacity via an autoloader. High numeric aperture 20x objective, as found on conventional microscopes, is used to produce high-quality images. The Aperio AT2 DX digital slide scanner employs a linear-array scanning technique that generates images and accounts for merging scan stripes along the scanning axis. The result is seamless digital slide images.
The image acquisition software components include Console DX and Controller DX. The Console DX application is a user-interface for the operator. It allows users to initiate scanning and select appropriate slide areas to scan. The Controller DX application is a software subsystem that runs on the Aperio AT2 DX scanner Control PC.
Image Viewing:
The remote image viewing capabilities of the ImageScope DX software subsystem supports reading digital slides on a calibrated monitor, enabling Pathologists to make clinically relevant decisions analogous to those they make using a conventional microscope. ImageScope DX includes support for locally or intranet connected image Viewing Workstation computers, which run digital slide viewing. The software includes elements to support data confidentiality and integrity.
5
VI. Intended Use
The Aperio AT2 DX System is an automated digital slide creation and viewing system. The Aperio AT2 DX System is intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. The Aperio AT2 DX System is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens.
The Aperio AT2 DX System is composed of the Aperio AT2 DX scanner, the ImageScope DX review application and Display. The Aperio AT2 DX System is for creation and viewing of digital images of scanned glass slides that would otherwise be appropriate for manual visualization by conventional light microscopy. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using the Aperio AT2 DX System.
Comparison of technological characteristics with the predicate VII. device
| Item | Predicate Device
Philips IntelliSite Pathology Solution
(PIPS) (DEN160056) | Candidate Device
Aperio AT2 DX System |
|-----------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use/
Indications
for Use | The Philips IntelliSite Pathology
Solution (PIPS) is an automated digital
slide creation, viewing, and
management system. The PIPS is
intended for in vitro diagnostic use as
an aid to the pathologist to review and
interpret digital images of surgical
pathology slides prepared from
formalin-fixed paraffin embedded
(FFPE) tissue. The PIPS is not
intended for use with frozen section,
cytology, or non-FFPE
hematopathology specimens.
The PIPS comprises the Image
Management System (IMS), the Ultra
Fast Scanner (UFS) and Display. The
PIPS is for creation and viewing of
digital images of scanned glass slides
that would otherwise be appropriate
for manual visualization by
conventional light microscopy. It is the
responsibility of a qualified | The Aperio AT2 DX System is an
automated digital slide creation
and viewing system. The Aperio
AT2 DX System is intended for in
vitro diagnostic use as an aid to
the pathologist to review and
interpret digital images of surgical
pathology slides prepared from
formalin-fixed paraffin embedded
(FFPE) tissue. The Aperio AT2
DX System is not intended for use
with frozen section, cytology, or
non-FFPE hematopathology
specimens.
The Aperio AT2 DX System is
composed of the Aperio AT2 DX
scanner, the ImageScope DX
review application and Display.
The Aperio AT2 DX System is for |
| Item | Predicate Device
Philips IntelliSite Pathology Solution
(PIPS) (DEN160056) | Candidate Device
Aperio AT2 DX System |
| | pathologist to employ appropriate
procedures and safeguards to assure
the validity of the interpretation of
images obtained using PIPS. | creation and viewing of digital
images of scanned glass slides that
would otherwise be appropriate
for manual visualization by
conventional light microscopy. It
is the responsibility of a qualified
pathologist to employ appropriate
procedures and safeguards to
assure the validity of the
interpretation of images obtained
using the Aperio AT2 DX System. |
| Specimen
type | Surgical pathology slides prepared
from formalin-fixed, paraffin-
embedded tissue | Same |
| Principle of
operation | The technician loads the slides into the
WSI scanner. The scanner scans the
slides and generates WSI image for
each slide. The technician performs
Quality Control (QC) on scanned WSI
images and rescan the slide when QC
is failed. The acquired WSI images are
stored in an end user provided image
storage attached to the local network.
During review, the pathologist opens
WSI images acquired with the WSI
scanner from the image storage,
performs further QC and reads WSI
images of the slides to make a
diagnosis. | Same |
| Device
Components | WSI scanner (PIPS Ultra Fast
Scanner), Image Management System
and color monitor display | Same (Aperio AT2 DX scanner,
ImageScope DX application, and
color monitor display) |
6
| Differences | ||
|---|---|---|
| Item | Device | Predicate |
| Whole Slide Imaging | ||
| Scanner | Aperio AT2 DX scanner | |
| with loading capacity of | ||
| 400 slides | Ultra Fast Scanner with | |
| loading capacity of 300 | ||
| slides | ||
| Graphical User Interface | ImageScope DX | Image Management |
| System | ||
| Monitor Display | Dell MR2416 monitor | PS27QHDCR |
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VIII. Performance Data
The performance testing was conducted via a series of studies that included Accuracy, Intra-System, Inter-System/Site. Within-Pathologist and Between-Pathologist precision.
The accuracy was evaluated by analyzing the concordance of the diagnoses made using the Aperio AT2 DX System (also known as WSIR diagnosis) with the gold standard reference diagnoses (the original sign-out pathologic diagnosis), and the concordance of traditional light microscope slide review (MSR) diagnoses with the gold standard reference diagnoses. Accuracy was assessed by analyzing major discrepancy rates for each study modality versus the gold standard reference diagnosis and calculating the difference between the major discrepancy rates for WSIR diagnosis and MSR diagnosis. Major discrepancy was defined as a difference in diagnoses that resulted in a clinically important difference in patient management.
The acceptance criteria were as follows:
- The upper bound of the two-sided 95% CI of the difference between the overall major discrepancy rates of WSIR diagnoses and MSR diagnoses is Overall | 582 | 606 | 96.0% | 93.6% | 98.2% |
*A bootstrap approach was used to calculate 95% CIs.
Table 3. Within/Between -Pathologist Study: Agreement Within Pathologists
| Number of | Number of | Agreement Rate and 95% CI* | ||||
|---|---|---|---|---|---|---|
| Pathologist | Pairwise | Comparison | % Agreement | Lower | Upper | |
| Agreements | Pairs | |||||
| Pathologist 1 | 561 | ୧୦୧ | 92.6% | 89.6% | 95.7% | |
| Pathologist 2 | રેતેર | ୧୦୧ | 98.2% | 96.3% | 99.7% | |
| Pathologist 3 | 571 | ୧୦୧ | 94.2% | 91.4% | 96.9% | |
| Overall | 1727 | 1818 | 95.0% | 92.9% | 96.8% |
*A bootstrap approach was used to calculate 95% CIs.
Table 4. Within- and Between-Pathologist Study: Agreement Between Pathologists
| Pathologist
Comparison | Number of
Pairwise
Agreements | Number of
Comparison
Pairs | Agreement Rate and 95% CI* | | |
|-----------------------------------|-------------------------------------|----------------------------------|----------------------------|-------|-------|
| Pathologist 1 vs
Pathologist 2 | 572 | 606 | 94.4% | 91.6% | 96.9% |
9
| Pathologist 1 vs
| Pathologist 3 | 562 | 606 | 92.7% | 89.9% | 95.4% |
|---|---|---|---|---|---|
| Pathologist 2 vs | |||||
| Pathologist 3 | 579 | 606 | 95.5% | 93.1% | 97.7% |
| Overall | 1713 | 1818 | 94.2% | 91.7% | 96.4% |
*A bootstrap approach was used to calculate 95% CIs.
Table 5. Overall Major Discrepancy Rates for the WSIR and MSR Modalities and the Difference Between the Overall Major Discrepancy Rates
| | WSIRD Major
Discrepancy* | | | MSRD Major
Discrepancy* | | | Difference in Major
Discrepancy Rates
(WSIRD minus
MSRD) | |
|----------|-----------------------------|-------------|-----------------|----------------------------|-------------|-----------------|-------------------------------------------------------------------|-----------------|
| | Total
Reads | Rate
(%) | Model
95% CI | Total
Reads | Rate
(%) | Model
95% CI | % | Model
95% CI |
| Observed | | 3.73 | - | | 3.28 | - | 0.45 | - |
| Model | 7509 | 3.64 | (3.21,
4.12) | 7522 | 3.20 | (2.80,
3.65) | 0.44 | (-0.15%, 1.03%) |
MSRD = MSR diagnosis, WSIRD = WSIR diagnosis
IX. Conclusions
The clinical study results demonstrate that AT2 DX System is substantially equivalent to the predicate device.