MetaLite DX Digital Pathology Software

K240303 · Jellox Biotech, Inc. · QKQ · Oct 28, 2024 · Pathology

Device Facts

• Record ID: K240303
• Device Name: MetaLite DX Digital Pathology Software
• Applicant: Jellox Biotech, Inc.
• Product Code: QKQ · Pathology
• Decision Date: Oct 28, 2024
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.3700
• Device Class: Class 2
• Attributes: Software as a Medical Device

Indications for Use

MetaLite DX Digital Pathology Software is a software only device intended for viewing and management of digital images of scanned surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue for the purposes of pathology primary diagnosis. It is an aid to the pathologist to review, interpret and manage digital images of pathology slides. MetaLite DX Digital Pathology Software is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the quality of the images obtained and, where necessary, use conventional light microscopy review when making a diagnostic decision. MetaLite DX Digital Pathology Software is intended for use with Philips Ultra Fast Scanner and the Barco MDPC-8127 display.

Device Story

MetaLite DX Digital Pathology Software is a standalone software application for viewing/managing digital pathology images. Input: iSyntax format images from Philips Ultra Fast Scanner (PIPS-UFS). Operation: Pathologist loads images into a graphical interface; software provides tools for panning, zooming, measuring lengths, and annotating. Output: Visual display of pathology slides on a Barco MDPC-8127 monitor. Context: Used in clinical settings by pathologists to aid in primary diagnosis; diagnosis is documented in external systems like LIS. Benefits: Enables digital review of pathology slides, potentially replacing or supplementing conventional light microscopy. The device operates locally without requiring internet connectivity, reducing cybersecurity risks associated with cloud/networked storage.

Clinical Evidence

No clinical data. Bench testing only. Pixel-wise comparison of 180 image-pairs (30 slides, 3 ROIs, 2 magnifications) against predicate showed 95th percentile CIEDE2000 color difference < 3 (mean 1.1). Measurement accuracy testing (1x-40x) showed < 2.4% error (acceptance < 5%). Turnaround time for opening/panning/zooming < 5 seconds (acceptance < 7s). Human factors validation confirmed safe/effective use by intended users.

Technological Characteristics

Standalone software for Windows 10+; requires Intel Core i7 11th Gen+, 16GB RAM. Compatible with Philips Ultra Fast Scanner (v1.8.4) and Barco MDPC-8127 display. Supports iSyntax file format. Implements standard image manipulation (zoom, pan, annotation, measurement). Complies with IEC 62304 (software lifecycle), IEC 62366-1 (usability), and ISO 14971 (risk management).

Indications for Use

Indicated for pathologists to view and manage digital images of FFPE surgical pathology slides for primary diagnosis. Not for use with frozen section, cytology, or non-FFPE hematopathology specimens.

Regulatory Classification

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.

Special Controls

A whole slide imaging system must comply with the following special controls: (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; (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: (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 factors 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: The intended use statement must include the information described in paragraph (i) (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 paragraph (1)(ii) and (1)(iii) of this section, as appropriate. (iii) A description of the performance studies and the summary of results, including those that relate to paragraph (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.

*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.

Predicate Devices

• Philips IntelliSite Pathology Solution (PIPS) (K203845)

Submission Summary (Full Text)

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FDA

U.S. FOOD &amp; DRUG

ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

## I Background Information:

A 510(k) Number

K240303

B Applicant

JelloX Biotech Inc.

C Proprietary and Established Names

MetaLite DX Digital Pathology Software

D Regulatory Information

| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| QKQ | Class II | 21 CFR 864.3700 - Whole Slide Imaging System | PA - Pathology |

## II Submission/Device Overview:

A Purpose for Submission:

New device

B Type of Test:

Software only device

## III Intended Use/Indications for Use:

A Intended Use(s):

See Indications for Use below.

B Indication(s) for Use:

For In Vitro Diagnostic Use

MetaLite DX Digital Pathology Software is a software only device intended for viewing and management of digital images of scanned surgical pathology slides prepared from formalin-fixed

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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paraffin embedded (FFPE) tissue for the purposes of pathology primary diagnosis. It is an aid to the pathologist to review, interpret and manage digital images of pathology slides.

MetaLite DX Digital Pathology Software is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens.

It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the quality of the images obtained and, where necessary, use conventional light microscopy review when making a diagnostic decision. MetaLite DX Digital Pathology Software is intended for use with Philips Ultra Fast Scanner and the Barco MDPC-8127 display.

## C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

## IV Device/System Characteristics:

### A Device Description:

MetaLite DX Digital Pathology Software, Model MLDXUS, version 1.2.0 is software designed for viewing digital pathology images of glass slides from the Philips IntelliSite Pathology Solution Ultra Fast Scanner (PIPS-UFS), version 1.8.4 on Barco MDPC-8127 display.

MetaLite DX Digital Pathology Software is operated as follows:

1. After the Whole Slide Images (WSIs) are successfully, acquired by using PIPS-UFS, the WSIs are stored in the Local file system. Scanned images are reviewed by scanning personnel such as histotechnicians to confirm image quality and initiate any re-scans before making it available to the pathologist per the instructions for use PIPS-UFS.
2. A qualified pathologist will upload compatible iSyntax format digital pathology images, and the software will load them to the "Main Viewer" area of the graphical interface for the pathologist to view.
3. Once properly loaded, the pathologist performs quality control procedures per the Quality Control section below. The pathologist can use the device to view and review images using the device features such as zoom-in and zoom-out functions, scale display, thumbnail view, measurement function, annotation function, and panning function.
4. After viewing all images for a patient (case), the pathologist will make a diagnosis. The diagnosis will be documented in another system, e.g., a Laboratory Information System (LIS).

The MetaLite DX Digital Pathology Software is validated for use with the components specified the tables below.

Table 1. Interoperable Components for Use with MetaLite DX Digital Pathology Software

| Component | Manufacturer | Model |
| --- | --- | --- |
| Scanner | Philips Medical Systems Nederland B.V. | Ultra Fast Scanner (UFS), version 1.8.4 |

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Display
Barco NV
MDPC-8127

Table 2. Computer Environment/System Requirements
| Environment | Component | Minimum Requirements |
| --- | --- | --- |
| Client PC | | |
| Hardware | Processor | Intel® Core (TM) I7 11th Gen or above |
| | Memory | 16GB or above |
| | Storage | USB Flash Drive 8GB or above |
| Software | Operating System | Windows 10 or above |

## B Instrument Description Information:

1. Instrument Name:
MetaLite DX Digital Pathology Software

2. Specimen Identification:
The MetaLite DX Digital Pathology Software uses WSIs obtained from the PIPS-UFS of slides prepared from FFPE tissue. The reading pathologist selects a case (patient) from a local folder for viewing with the subject device.

3. Specimen Sampling and Handling:
Specimen sampling and handling are performed upstream and independent of the use of the subject device. Specimen sampling includes biopsy or resection specimens which are processed using histology techniques. Digital images (WSIs) are then obtained from these glass slides using the PIPS-UFS.

4. Calibration:
Not applicable.

5. Quality Control:
The subject device receives WSIs from local computer storage. All WSI files are quality-controlled images acquired from the scanner according to the scanner's instructions for use. The subject device specific quality control measures are performed by viewing the pathology images. Every pathologist should perform this test on review workstation before reading pathology images using the subject device to ensure that all scanned slide images have been imported and for every case, view the thumbnails in the pathology image window to verify that each slide that should be in the case is present.

## V Substantial Equivalence Information:

A Predicate Device Name(s):
Philips IntelliSite Pathology Solution

B Predicate 510(k) Number(s):
K203845

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C Comparison with Predicate(s):

| Device & Predicate Device(s): | K240303 | K203845 |
| --- | --- | --- |
| Device Trade Name | MetaLite DX Digital Pathology Software | Philips IntelliSite Pathology Solution (PIPS) |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | For In Vitro Diagnostic Use MetaLite DX Digital Pathology Software is a software only device intended for viewing and management of digital images of scanned surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue for the purposes of pathology primary diagnosis. It is an aid to the pathologist to review, interpret and manage digital images of pathology slides. MetaLite DX Digital Pathology Software is not intended for use with frozen section, cytology, or non-FFPE hematopathology specimens. It is the responsibility of a qualified pathologist to employ appropriate procedures and safeguards to assure the quality of the images obtained and, where necessary, use conventional light microscopy review when making a diagnostic decision. MetaLite DX Digital Pathology Software is intended for use with Philips Ultra Fast Scanner and the Barco MDPC-8127 display. | 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 pathologist to employ appropriate procedures and safeguards to assure the validity of the interpretation of images obtained using PIPS. |
| Specimen Type | Digitized surgical pathology slides prepared from FFPE tissue. | Same |
| Diagnostic Image File Format | iSyntax | Same |
| Image Manipulation Functions | Panning, zooming, color manipulation function, annotations, and measurements (distance) | Panning, zooming, color manipulation function, annotations, and measurements (distance & area) |

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| General Device Characteristic Differences | | |
| --- | --- | --- |
| Type of Software Application | Stand-alone software | Internet browser-based application |
| Device Components | MetaLite DX Digital Pathology Software | Ultra Fast Scanner (UFS), Image Management System (IMS) and Display |
| Principle of Operation | After WSI images are successfully acquired using the PIPS-UFS, the pathologist performs further QC and reads WSI images of the slides to make a diagnosis. | After WSI images are successfully acquired by using PIPS-UFS, the WSI images are stored in IMS Application Server & Storage software that is not provided as part of the PIPS but may be located in a central server room separate from the workstation with the IMS viewing software and Display. During review, the pathologist opens WSI images from IMS Server & Storage, perform further QC and reads WSI images of the slides to make a diagnosis. |
| Image Storage | Images are stored in the local computer. | After WSI images are successfully acquired by using PIPS UFS, the WSI images are stored in IMS Application Server & Storage software that is not provided as part of the PIPS but may be located in a central server room separate from the workstation with the IMS viewing software and Display. During review, the pathologist opens WSI images from IMS Server & Storage, perform further QC and reads WSI images of the slides to make a diagnosis. |
| End User’s Interface | MetaLite DX Digital Pathology Software | PIPS Image Management System (IMS) |

VI Standards/Guidance Documents Referenced:

1. FDA Guidance “Technical Performance Assessment of Digital Pathology Whole Slide Imaging Devices”. April 20, 2016.
2. FDA Guidance “Applying Human Factors and Usability Engineering to Medical Devices”. February 3, 2016.
3. FDA Guidance “Content of Premarket Submissions for Device Software Functions”. June 14, 2023.
4. FDA Guidance “Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions”. September 27, 2023.

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5. AAMI TIR 45:2012 - Guidance on the use of AGILE practices in the development of medical device software.
6. IEC 62304 Edition 1.1 2015-06 CONSOLIDATED VERSION, 13-79. Medical device software – Software life cycle processes.
7. IEC 62366-1 Edition 1.1 2020-06 CONSOLIDATED VERSION, 5-129, Application of usability engineering to medical devices.
8. ISO 14971 Third Edition 2019-12, 5-125, Medical devices – Applications of risk management to medical devices.

## VII Performance Characteristics (if/when applicable):

### A Analytical Performance:

1. **Precision/Reproducibility:**
Not applicable

2. **Linearity:**
Not applicable

3. **Analytical Specificity/Interference:**
Not applicable

4. **Accuracy (Instrument):**
Not applicable

5. **Carry-Over:**
Not applicable

### B Other Supportive Instrument Performance Characteristics Data:

Technical performance testing was conducted with the subject device, MetaLite DX Digital Pathology Software as specified below.

#### 1. Bench Testing - Pixelwise comparison test

Pixel-wise comparison testing to demonstrate identical image reproduction was conducted to compare WSIs reproduced by the subject device and PIPS IMS. The subject device was compared to the predicate device’s image review manipulation software (IRMS, as defined in FDA guidance document, “Technical Performance Assessment of Digital Pathology Whole Slide Imaging Devices” dated April 20, 2016) using the quantitative pixel-wise comparison method. The basis for the comparison was the CIEDE2000 color difference equation, $\Delta E$. The devices were tested as operating with the intended components, including the scanner (PIPS UFS), image management system (PIPS IMS, MetaLite DX Digital Pathology Software) and display (Barco MDPC 8127).

The device was tested with multiple slides across multiple regions of interest (ROI) at multiple magnification levels. A total of 30 H&amp;E-stained, FFPE glass slides of normal and tumor tissues from various human anatomical organs were used in the testing. The glass slides were scanned on a PIPS UFS version 1.8.4 to obtain 30 WSIs. For each of the 30

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WSIs, 3 ROIs from different locations were selected by qualified personnel to represent various features in the tissue samples. Each ROI was captured at 2 magnification levels (20x, 40x).

The screenshots were captured from the intended display while viewing with the subject device and predicate PIPS IMS. The screenshots were cropped and registered to be pixelwise comparable. The cropped image included most of the pixels in the image except for those in the viewer-specific user interface areas.

Two sets of images were collected: PIPS IMS and MetaLite DX Digital Pathology Software. Each image set included 180 images that covered all combinations of 30 slides, 3 ROIs and 2 magnification levels. The testing data, including the overview images of the 30 glass slides with annotations of the ROIs, registration/cropping information, and captured images, were provided in the FDA specific format.

The PIPS IMS image set was used as the reference to compare the MetaLite DX Digital Pathology Software image set to determine whether all the 180 image-pairs were identical. Two images are considered identical if the 95th percentile of the pixelwise differences, computed using the International Commission on Illumination (CIE) color difference metric CIEDE2000 ($\Delta E_{00}$), is less than 3 $\Delta E_{00}$. Testing results showed that the pixelwise differences across all 180 image-pairs were less than 3 $\Delta E_{00}$. The mean 95th percentile $\Delta E_{00}$ value was 1.1 with the lowest value reported as 0 and the highest reported as 2.5. Testing results demonstrated that WSIs reproduced by MetaLite DX Digital Pathology Software are identical to images reproduced by the predicate device.

2. Turnaround Time

The turnaround times of the subject device were measured for the operations of image opening, panning, and zooming. Video recording software and calibration time software were used in the test to determine the turnaround time. The panning operation was executed by moving the image by one quarter of the screen using mouse dragging. The zooming operation was executed using the mouse wheel. Each operation was measured 10 times. The acceptance criterion was set at 7 seconds with respect to the device’s intended use. Test results show that all opening, panning, and zooming operations were completed within 5 seconds.

3. Measurement

The measurement accuracy of the subject device was tested. A calibration scale slide with length marks of 100, 300, 600, 800, and 1000 $\mu$m was used as the target with known ground truth. The scale was measured in both horizontal and vertical orientations using the subject device. The error was calculated as the ratio of the difference between the measured length and the actual length to the actual length. The acceptance criterion was set at 5% with respect to the device’s intended use. The test was conducted under magnification levels of 40X, 20X, 10X, and 1X. Test results show that the errors of all test cases were less than 2.4%.

4. Human Factor (Usability) Testing

The Human Factors (HF) validation test was conducted to demonstrate that the device can be used by the intended users without serious use errors or problems, for the intended uses and under the expected use conditions. The HF validation test was performed by representative

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users and conducted per FDA’s Guidance on Applying Human Factors and Usability Engineering to Medical Devices (2016). A systematic evaluation of task-based usability including critical tasks required for operation of the device were evaluated at multiple sites using multiple users. All tasks associated with reviewing and reporting results for cases including confirmation that all slides belonging to specific cases are reviewed before reporting results, were included in the HF validation test. Overall, the results of the human factors testing were acceptable. The MetaLite DX Digital Pathology Software device has been found to be safe and effective for intended users, users and use environments.

VIII Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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