(259 days)
Not Found
No
The summary describes a system for scanning, viewing, and managing digital pathology images. It mentions "Image Processing Software" but does not mention AI, ML, or any algorithms that perform automated analysis or interpretation of the images beyond basic viewing and management. The performance studies focus on the accuracy of the digital image viewing compared to traditional microscopy, not on the performance of any AI/ML-driven diagnostic aid.
No.
The device is intended for in vitro diagnostic use as an aid to pathologists to review and interpret digital images, serving as an alternative to conventional microscopy. It does not directly provide therapy or treatment to a patient.
Yes
The "Intended Use / Indications for Use" section explicitly states, "The Epredia E1000 Dx Digital Pathology Solution 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."
No
The device is described as a "Solution" consisting of multiple components, including a "Scanner (E1000 Dx Digital Pathology Scanner)" and a "Display (Barco MDPC-8127)", which are clearly hardware components. While it includes software, it is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement in Intended Use: The "Intended Use / Indications for Use" section clearly states: "The Epredia E1000 Dx Digital Pathology Solution is intended for in vitro diagnostic use..."
- Purpose of the Device: The device is designed to aid pathologists in reviewing and interpreting digital images of surgical pathology slides prepared from human tissue. This process is a key part of in vitro diagnostic procedures, where samples are examined outside the body to diagnose disease.
- Comparison to Conventional Microscopy: The description highlights that the system is an alternative to manual visualization by conventional light microscopy, which is a standard method used in diagnostic pathology.
- Clinical Performance Studies: The inclusion of a "Clinical Accuracy Study" and "Precision Study" further supports its intended use in a clinical diagnostic setting, where performance metrics are crucial for regulatory approval and clinical validity.
- Predicate Device: The mention of a predicate device (Philips IntelliSite Pathology Solution) with a K number (DEN160056) indicates that this device is being compared to a previously cleared IVD device.
All these points strongly indicate that the Epredia E1000 Dx Digital Pathology Solution is intended and functions as an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Epredia E1000 Dx Digital Pathology Solution is an automated digital slide creation, viewing, and management system. The Epredia E1000 Dx Digital Pathology Solution 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 Epredia E1000 Dx Digital Pathology Solution is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens.
The Epredia E1000 Dx Digital Pathology Solution consists of a Scanner (E1000 Dx Digital Pathology Scanner), which generates in MRXS image file format, E1000 Dx Scanner Software, Image Management System (E1000 Dx IMS), E1000 Dx Viewer Software, and Display (Barco MDPC-8127). The Epredia E1000 Dx Digital Pathology Solution 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 Epredia E1000 Dx Digital Pathology Solution.
Product codes (comma separated list FDA assigned to the subject device)
PSY
Device Description
The E1000 Dx Digital Pathology Solution is a high-capacity, automated whole slide imaging system for the creation, viewing, and management of digital images of surgical pathology slides. It allows whole slide digital images to be viewed on a display monitor that would otherwise be appropriate for manual visualization by conventional brightfield microscopy.
The E1000 Dx Digital Pathology Solution consists of the following three components:
Scanner component:
- . E1000 Dx Digital Pathology Scanner with E1000 firmware version 2.0.3
- . E1000 Dx Scanner Software version 2.0.3
Viewer component:
- E1000 Dx Image Management System (IMS) Server version 2.3.2 ●
- . E1000 Dx Viewer Software version 2.7.2
Display component:
- . Barco MDPC-8127
The E1000 Dx Digital Pathology Solution automatically creates digital whole slide images by scanning formalin-fixed, paraffin-embedded (FFPE) tissue slides, with a capacity to process up to 1,000 slides. The E1000 Dx Scanner Software (EDSS), which runs on the scanner workstation, controls the operation of the E1000 Dx Digital Pathology Scanner. The scanner workstation, provided with the E1000 Dx Digital Pathology Solution, includes a PC, monitor, kevboard, and mouse. The solution uses a proprietary MRXS format to store and transmit images between the E1000 Dx Digital Pathology Scanner and the E1000 Dx Image Management System (IMS).
The E1000 Dx IMS is a software component intended for use with the Barco MDPC-8127 display monitor and runs on a separate, customer-provided pathologist viewing workstation PC. The E1000 Dx Viewer, an application managed through the E1000 Dx IMS, allows the obtained digital whole slide images to be annotated, stored, accessed, and examined on Barco MDPC-8127 video display monitor. This functionality aids pathologists in interpreting digital images as an alternative to conventional brightfield microscopy.
Mentions image processing
Yes
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Brightfield microscopy
Anatomical Site
Surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue.
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Qualified pathologist / Not Found
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 (study type, sample size, AUC, MRMC, standalone performance, key results)
Technical Studies:
Studies were conducted to evaluate the performance of the E1000 Dx Digital Pathology Solution in accordance with the special controls listed in 21 CFR 864.3700 Whole Slide Imaging System and the FDA's guidance document titled "Technical Performance Assessment of Digital Pathology Whole Slide Imaging Devices." A detailed description of the device, along with the results of passed bench testing at the component level, including the following, were submitted as appropriate:
- a) Slide Feeder
- b) Light Source
- Imaging Optics c)
- d) Mechanical Scanner Movement
- e) Digital Imaging Sensor
- Image Processing Software f)
- g) Image Composition
- h) Image Files Format
- i) Image Review Manipulation Software
- Computer Environment j)
- k) Display
-
- Color Reproducibility
- m) Spatial Resolution
- n) Focusing Test
- o) Whole Slide Tissue Coverage
- p) Stitching Error
- q) Turnaround Time
User Interface/Human Factors Validation:
Critical tasks were identified internally by conducting a detailed uFMEA (user Failure Modes and Effects Analysis). The safety and efficacy of risk mitigation processes were validated externally in a study involving two distinct user groups: laboratory technicians and pathologists to assess software interface, hardware interface, and product labelling. Both user groups perceived that the risk mitigation steps for critical tasks were successfully implemented and that the E1000 Dx Digital Pathology Solution can be used safely and effectively by its intended users, for its intended purpose, and in its intended use environment.
Electromagnetic Compatibility (EMC) Testing:
Electrical safety testing and electromagnetic compatibility testing, conducted in accordance with the standards outlined in IEC 61010-1, IEC 61010-2-101, and IEC 61326-2-6, respectively, yielded passing results.
Clinical Testing:
a) Clinical Accuracy Study:
A multi-centered, blinded, and randomized study was conducted to demonstrate that viewing, reviewing, and diagnosing digital images of surgical pathology slides prepared from tissue slides using the E1000 Dx Digital Pathology Solution is non-inferior to an optical microscope by determining the difference in major discordance rate between manual digital (MD) and manual optical (MO) modalities when compared to the main sign-out diagnosis (SD). The observed major discordance rates were calculated using a Generalized Linear Mixed Model (GLIMMIX) logistic regression.
The major discordance rate between MD and SD was observed to be 2.54%, and the major discordance rate between MO and SD was observed to be 2.65%. The overall major discordance rates estimated by the generalized linear model were 2.51% (95% CI: 2.26%; 2.79%) for MD and 2.59% (95% CI: 2.29%; 2.82%) for MO. The estimated difference in major discordance between the MD and MO rates was calculated to be -0.15% (95% CI: -0.40%, 0.41%). The study met its acceptance criteria, as defined in the protocol.
b) Precision Study:
A study was conducted to evaluate the precision of the Epredia E1000 Dx Digital Pathology Solution. The study included intra-system, inter-system repeatability and inter-site reproducibility using a comprehensive set of clinical specimens with defined, clinically relevant histologic features from various organ systems.
1. Intra-System Repeatability Study:
The intra-system repeatability study included scanned WSIs of glass slides which were selected and enrolled according to the specified procedure. From this set, fields of view (FOVs) with one selected feature each were extracted. Additionally, "wildcard" FOVs were selected from other slides following the same procedure to minimize or avoid bias by the reading pathologist, though these wildcard FOVs were not included in the primary analysis. The study slides were divided equally and randomized across three systems at one site. Each slide set was scanned three times, with a minimum of six hours between each scan on each system. Randomly selected FOVs from the three different systems and three different iterations were read by three different reading pathologists (RPs). The pathologists recorded the presence of each observed feature on a checklist for each predetermined magnification level.
Key results: The data obtained from this evaluation for E1000 Dx Digital Pathology Solution met the acceptance criteria of a lower limit of the 95% Confidence interval (CI) greater than 85%, with an Average Positive Agreement of 96.9% (lower limit of 96.1%).
2. Inter-System Repeatability Study:
The inter-system repeatability study utilized the full set of scanned WSIs of glass slides from the intra-system study, including the same extracted FOVs, features, and wildcards. Each slide was scanned once on each system. Three reading pathologists then evaluated each enrolled FOV once on each system. The pathologists recorded the presence of each observed feature on a checklist for each magnification level.
Key results: The data obtained from this study met the acceptance criteria of a lower limit of 95% Confidence interval (CI) greater than 85%, with an Average Positive Agreement of 95.1% (lower limit of 94.1%).
3. Inter-Site Reproducibility:
For the inter-site study, the wildcards and FOVs from the intra-system and inter-system repeatability studies were used as the study FOVs. The study involved three different reading pathologists, each located at one of three different sites, each equipped with its own E1000 Dx Digital Pathology Solution. The order of FOV evaluation at each site was randomly determined. Each pathologist evaluated each FOV once and recorded the presence of each observed feature on a checklist for each magnification level.
Key results: The data obtained from this study met the acceptance criteria of a lower limit of 95% Confidence interval (CI) greater than 85%, with an Average Positive Agreement of 95.4% (lower limit of 93.6%).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Clinical Accuracy Study:
Major Discordance Rate (MD vs SD): 2.54%
Major Discordance Rate (MO vs SD): 2.65%
Estimated Difference in Major Discordance (MD - MO): -0.15% (95% CI: -0.40%, 0.41%)
Intra-System Repeatability Study:
Average Positive Agreement: 96.9% (lower limit of 96.1%)
Inter-System Repeatability Study:
Average Positive Agreement: 95.1% (lower limit of 94.1%)
Inter-Site Reproducibility:
Average Positive Agreement: 95.4% (lower limit of 93.6%)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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
Image /page/0/Picture/0 description: The image shows the logos of the Department of Health & Human Services and the Food and Drug Administration (FDA). The Department of Health & Human Services logo is on the left, and the FDA logo is on the right. The FDA logo is a blue square with the letters "FDA" in white, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.
Shandon Diagnostics Limited Naveen Kaki Regulatory Affairs Specialist Tudor Road, Manor Park, Cheshire Runcorn, WA7 1TA United Kingdom
Re: K241717
Trade/Device Name: Epredia E1000 Dx Digital Pathology Solution Regulation Number: 21 CFR 864.3700 Regulation Name: Whole slide imaging system Regulatory Class: Class II Product Code: PSY Dated: June 13, 2024 Received: June 14, 2024
Dear Naveen Kaki:
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 devices 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 (the 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 available 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.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
February 28, 2025
1
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rue"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
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/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
2
Sincerely,
Shyam Kalawar -S
Shyam Kalavar Deputy Branch Chief Division of Molecular Genetics and Pathology OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
3
Indications for Use
510(k) Number (if known) K241717
Device Name Epredia E1000 Dx Digital Pathology Solution
Indications for Use (Describe)
The Epredia E1000 Dx Digital Pathology Solution is an automated digital slide creation, viewing, and management system. The Epredia E1000 Dx Digital Pathology Solution 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 Epredia E1000 Dx Digital Pathology Solution is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens.
The Epredia E1000 Dx Digital Pathology Solution consists of a Scanner (E1000 Dx Digital Pathology Scanner), which generates in MRXS image file format, E1000 Dx Scanner Software, Image Management System (E1000 Dx IMS), E1000 Dx Viewer Software, and Display (Barco MDPC-8127). The Epredia E1000 Dx Digital Pathology Solution 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 Epredia E1000 Dx Digital Pathology Solution.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
|---|---|
| ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.#### DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
4
510(k) Summary
Epredia E1000 Dx Digital Pathology Solution
Date prepared: February 26, 2025
Submitter
Shandon Diagnostics, Ltd.. Tudor Road, Manor Park, Runcorn, Cheshire, WA7 1TA, United Kingdom.
Contact Person
| Naveen Kaki, M.Sc. | |
|---|---|
| Telephone: | (857) 263-1783. |
| Email: | Naveen.kaki@epredia.com |
Device
| Proprietary Name: | Epredia E1000 Dx Digital Pathology Solution |
|---|---|
| Classification Name: | Whole Slide Imaging System |
| Regulation Number: | 21 CFR 864.3700 |
| Regulatory Classification: | Class II |
| Product Code: | PSY |
| Review Panel: | 88 – Pathology |
| 510(k) Number: | K241717 |
Predicate Device
| Proprietary Name: | Philips IntelliSite Pathology Solution (PIPS) |
|---|---|
| Submission Number: | DEN160056 |
I. Intended Use
The Epredia E1000 Dx Digital Pathology Solution is an automated digital slide creation, viewing, and management system. The Epredia E1000 Dx Digital Pathology Solution 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 Epredia E1000 Dx Digital Pathology Solution is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens.
The Epredia E1000 Dx Digital Pathology Solution consists of a scanner (E1000 Dx Digital Pathology Scanner), which generates images in the MRXS image file format, E1000 Dx Scanner Software, Image Management System (E1000 Dx IMS), E1000 Dx Viewer Software, and Display (Barco MDPC-8127). The Epredia E1000 Dx Digital Pathology Solution 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 Epredia E1000 Dx Digital Pathology Solution.
5
II. Device Description
The E1000 Dx Digital Pathology Solution is a high-capacity, automated whole slide imaging system for the creation, viewing, and management of digital images of surgical pathology slides. It allows whole slide digital images to be viewed on a display monitor that would otherwise be appropriate for manual visualization by conventional brightfield microscopy.
The E1000 Dx Digital Pathology Solution consists of the following three components: Scanner component:
- . E1000 Dx Digital Pathology Scanner with E1000 firmware version 2.0.3
- . E1000 Dx Scanner Software version 2.0.3
Viewer component:
- E1000 Dx Image Management System (IMS) Server version 2.3.2 ●
- . E1000 Dx Viewer Software version 2.7.2
Display component:
- . Barco MDPC-8127
The E1000 Dx Digital Pathology Solution automatically creates digital whole slide images by scanning formalin-fixed, paraffin-embedded (FFPE) tissue slides, with a capacity to process up to 1,000 slides. The E1000 Dx Scanner Software (EDSS), which runs on the scanner workstation, controls the operation of the E1000 Dx Digital Pathology Scanner. The scanner workstation, provided with the E1000 Dx Digital Pathology Solution, includes a PC, monitor, kevboard, and mouse. The solution uses a proprietary MRXS format to store and transmit images between the E1000 Dx Digital Pathology Scanner and the E1000 Dx Image Management System (IMS).
The E1000 Dx IMS is a software component intended for use with the Barco MDPC-8127 display monitor and runs on a separate, customer-provided pathologist viewing workstation PC. The E1000 Dx Viewer, an application managed through the E1000 Dx IMS, allows the obtained digital whole slide images to be annotated, stored, accessed, and examined on Barco MDPC-8127 video display monitor. This functionality aids pathologists in interpreting digital images as an alternative to conventional brightfield microscopy.
III. Comparison of technological characteristics with the predicate device
| Items | K241717
Epredia E1000 Dx Digital Pathology
Solution | DEN160056
Philips IntelliSite Pathology Solution (PIPS) |
|------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Similarities | | |
| Indications
For Use | The Epredia E1000 Dx Digital Pathology
Solution is an automated digital slide
creation, viewing, and management system.
The Epredia E1000 Dx Digital Pathology
Solution 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 Epredia E1000
Dx Digital Pathology Solution is not intended
for use with frozen section, cytology, or non-
FFPE hematopathology specimens. | 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. |
6
| The Epredia E1000 Dx Digital Pathology | The PIPS comprises the Image Management | |
|---|---|---|
| Solution consists of a scanner (E1000 Dx | System (IMS), the Ultra Fast Scanner (UFS) | |
| Digital Pathology Scanner), which generates | and Display. The PIPS is for creation and | |
| images in the MRXS image file format, | viewing of digital images of scanned glass | |
| E1000 Dx Scanner Software, Image | slides that would otherwise be appropriate for | |
| Management System (E1000 Dx IMS), | manual visualization by conventional light | |
| E1000 Dx Viewer Software, and Display | microscopy. It is the responsibility of a | |
| (Barco MDPC-8127). The Epredia E1000 Dx | qualified pathologist to employ appropriate | |
| Digital Pathology Solution is for creation and | procedures and safeguards to assure the | |
| viewing of digital images of scanned glass | validity of the interpretation of images | |
| slides that would otherwise be appropriate for | obtained using PIPS. | |
| 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 Epredia E1000 Dx Digital | ||
| Pathology Solution. | ||
| Specimen type | Surgical pathology slides prepared from | |
| formalin-fixed, paraffin-embedded tissue. | Same | |
| Device components | E1000 Dx Digital Pathology Scanner, E1000 | |
| Dx IMS and a display (K203364) | Similar - PIPS Ultra Fast Scanner, Image | |
| Management System and a display. | ||
| Differences | ||
| Slide Feeder capacity | 1000 Slides | 300 Slides |
| Image File Formats | MRXS | iSyntax |
| Monitor Display | Barco MDPC-8127 | PS27QHDCR |
Despite these technological differences, the Epredia E1000 Dx Digital Pathology Solution raised no new safety or efficacy concerns. This conclusion is supported by performance studies, verification, and validation activities conducted during the controlled hardware and software development processes.
IV. PERFORMANCE DATA
1. Technical Studies
Studies were conducted to evaluate the performance of the E1000 Dx Digital Pathology Solution in accordance with the special controls listed in 21 CFR 864.3700 Whole Slide Imaging System and the FDA's guidance document titled "Technical Performance Assessment of Digital Pathology Whole Slide Imaging Devices." A detailed description of the device, along with the results of passed bench testing at the component level, including the following, were submitted as appropriate:
- a) Slide Feeder
- b) Light Source
- Imaging Optics c)
- d) Mechanical Scanner Movement
- e) Digital Imaging Sensor
- Image Processing Software f)
- g) Image Composition
7
- h) Image Files Format
- i) Image Review Manipulation Software
- Computer Environment i)
- k) Display
-
- Color Reproducibility
- m) Spatial Resolution
- n) Focusing Test
- o) Whole Slide Tissue Coverage
- p) Stitching Error
- q) Turnaround Time
2. User Interface/Human Factors Validation
Critical tasks were identified internally by conducting a detailed uFMEA (user Failure Modes and Effects Analysis). The safety and efficacy of risk mitigation processes were validated externally in a study involving two distinct user groups: laboratory technicians and pathologists to assess software interface, hardware interface, and product labelling. Both user groups perceived that the risk mitigation steps for critical tasks were successfully implemented and that the E1000 Dx Digital Pathology Solution can be used safely and effectively by its intended users, for its intended purpose, and in its intended use environment.
3. Electromagnetic Compatibility (EMC) Testing
Electrical safety testing and electromagnetic compatibility testing, conducted in accordance with the standards outlined in IEC 61010-1, IEC 61010-2-101, and IEC 61326-2-6, respectively, yielded passing results.
4. Clinical Testing
a) Clinical Accuracy Study
A multi-centered, blinded, and randomized study was conducted to demonstrate that viewing, reviewing, and diagnosing digital images of surgical pathology slides prepared from tissue slides using the E1000 Dx Digital Pathology Solution is non-inferior to an optical microscope by determining the difference in major discordance rate between manual digital (MD) and manual optical (MO) modalities when compared to the main sign-out diagnosis (SD). The observed major discordance rates were calculated using a Generalized Linear Mixed Model (GLIMMIX) logistic regression.
The major discordance rate between MD and SD was observed to be 2.54%, and the major discordance rate between MO and SD was observed to be 2.65%. The overall major discordance rates estimated by the generalized linear model were 2.51% (95% CI: 2.26%; 2.79%) for MD and 2.59% (95% CI: 2.29%; 2.82%) for MO. The estimated difference in major discordance between the MD and MO rates was calculated to be -0.15% (95% CI: -0.40%, 0.41%). The study met its acceptance criteria, as defined in the protocol.
8
| | MD: Major Discordance Rate | | | MO: Major Discordance Rate | | | Difference
MD - MO | |
|----------|----------------------------|-------|----------------|----------------------------|-------|----------------|-----------------------|-----------------|
| | N | % | 95% CI | N | % | 95% CI | % | 95% CI |
| Observed | 3897 | 2.54% | | 3881 | 2.65% | | -0.11% | |
| Modeled | 3897 | 2.51% | (2.26%, 2.79%) | 3881 | 2.59% | (2.29%, 2.82%) | -0.15% | (-0.40%, 0.41%) |
Table 1: Overall Major Discordance Rate for MD and MO
The observed difference in major discordance between MD-MO for the Epredia E1000 Dx Digital Pathology Solution is -0.11%. The data obtained from the study demonstrate that the E1000 Dx Digital Pathology Solution performs substantially equivalent to its predicate device.
b) Precision Study
A study was conducted to evaluate the precision of the Epredia E1000 Dx Digital Pathology Solution. The study included intra-system, inter-system repeatability and inter-site reproducibility using a comprehensive set of clinical specimens with defined, clinically relevant histologic features from various organ systems.
1. Intra-System Repeatability Study
The intra-system repeatability study included scanned WSIs of glass slides which were selected and enrolled according to the specified procedure. From this set, fields of view (FOVs) with one selected feature each were extracted. Additionally, "wildcard" FOVs were selected from other slides following the same procedure to minimize or avoid bias by the reading pathologist, though these wildcard FOVs were not included in the primary analysis. The study slides were divided equally and randomized across three systems at one site. Each slide set was scanned three times, with a minimum of six hours between each scan on each system. Randomly selected FOVs from the three different systems and three different iterations were read by three different reading pathologists (RPs). The pathologists recorded the presence of each observed feature on a checklist for each predetermined magnification level.
The data obtained from this evaluation for E1000 Dx Digital Pathology Solution met the acceptance criteria of a lower limit of the 95% Confidence interval (CI) greater than 85%, with an Average Positive Agreement of 96.9% (lower limit of 96.1%).
| Number of | Number of | Agreement Rate | ||
|---|---|---|---|---|
| System | Pairwise | |||
| Agreements* | Comparison | |||
| Pairs | % | 95% CI | ||
| System 1 | 820 | 837 | 98.0 | (97.3, 98.8) |
| System 2 | 803 | 837 | 95.9 | (94.4, 97.1) |
| System 3 | 810 | 837 | 96.8 | (95.7, 97.8) |
| Total | 2,433 | 2,511 | 96.9 | (96.1, 97.4) |
Table 2: Intra-system Precision Agreement Rates
*Number of agreements represents the number of a positive agreements with the original assessment
9
2. Inter-System Repeatability Study
The inter-system repeatability study utilized the full set of scanned WSIs of glass slides from the intra-system study, including the same extracted FOVs, features, and wildcards. Each slide was scanned once on each system. Three reading pathologists then evaluated each enrolled FOV once on each system. The pathologists recorded the presence of each observed feature on a checklist for each magnification level.
The data obtained from this study met the acceptance criteria of a lower limit of 95% Confidence interval (CI) greater than 85%, with an Average Positive Agreement of 95.1% (lower limit of 94.1%).
| System | Number of
Pairwise
Agreements | Number of
Comparison Pairs | Agreement Rate | |
|---------------|-------------------------------------|-------------------------------|----------------|--------------|
| | | | % | 95% CI |
| System 1 vs 2 | 788 | 837 | 94.1 | (91.2, 95.9) |
| System 1 vs 3 | 793 | 837 | 94.7 | (92.6, 96.4) |
| System 2 vs 3 | 808 | 837 | 96.5 | (94.7, 97.8) |
| Total | 2,389 | 2,511 | 95.1 | (94.0, 96.1) |
Table 3: Inter-system Precision Agreement Rates
3. Inter-Site Reproducibility:
For the inter-site study, the wildcards and FOVs from the intra-system and inter-system repeatability studies were used as the study FOVs. The study involved three different reading pathologists, each located at one of three different sites, each equipped with its own E1000 Dx Digital Pathology Solution. The order of FOV evaluation at each site was randomly determined. Each pathologist evaluated each FOV once and recorded the presence of each observed feature on a checklist for each magnification level.
The data obtained from this study met the acceptance criteria of a lower limit of 95% Confidence interval (CI) greater than 85%, with an Average Positive Agreement of 95.4% (lower limit of 93.6%).
| Number of | Agreement Rate | |||
|---|---|---|---|---|
| System | Pairwise | |||
| Agreements | Number of | |||
| Comparison Pairs | % | 95% CI | ||
| Site 1 vs 2 | 261 | 279 | 93.5 | (89.2, 96.6) |
| Site 1 vs 3 | 268 | 279 | 96.1 | (92.4, 98.3) |
| Site 2 vs 3 | 270 | 279 | 96.8 | (93.3, 98.7) |
| Total | 799 | 837 | 95.4 | (93.5, 97.0) |
| Table 4: Inter-site Reproducibility Agreement Rates | |
|---|---|
10
V. CONCLUSIONS
The study results demonstrate that E1000 Dx Digital Pathology Solution is substantially equivalent to the predicate device.