aetherSlide

K233126 · Aetherai Co., Ltd. · QKQ · May 30, 2024 · Pathology

Device Facts

• Record ID: K233126
• Device Name: aetherSlide
• Applicant: Aetherai Co., Ltd.
• Product Code: QKQ · Pathology
• Decision Date: May 30, 2024
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.3700
• Device Class: Class 2
• Attributes: Software as a Medical Device

Indications for Use

aetherSlide is a software-only device intended for viewing and managing digital images of scanned surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. It is an aid to the pathologist to review, interpret, and manage digital images of pathology slides for primary diagnosis. aetherSlide 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. aetherSlide is intended for use with the Philips Ultra Fast Scanner (UFS) and the Philips PS27QHDCR monitor.

Device Story

aetherSlide is a web-based, software-only device for viewing/managing digital whole slide images (WSI) of FFPE tissue; inputs are iSyntax files acquired via Philips Ultra Fast Scanner (UFS) and exported from Philips IntelliSite Pathology Solution (PIPS). Operator uploads images to aetherSlide via aetherSlide Gateway; pathologist uses browser-based interface to view, zoom, pan, measure, and annotate images. Output is visual representation of WSI for pathologist review; diagnosis is documented in external Laboratory Information System (LIS). Device facilitates primary diagnosis by enabling digital review of pathology slides; intended for use in clinical environments by pathologists. Benefits include efficient digital workflow for slide interpretation; performance validated against PIPS predicate for image reproduction accuracy.

Clinical Evidence

Bench testing only. Pixel-wise comparison of 360 image-pairs (30 slides, 3 ROIs, 4 magnifications) between aetherSlide and PIPS predicate showed identical reproduction (mean 95th percentile ΔE00 = 0.16; max 0.71, threshold < 3). Measurement accuracy verified using grid micrometer (0.1 mm and 0.2 mm targets) at all magnifications. Turnaround time for loading and panning confirmed acceptable. Human factors validation conducted per FDA 2016 guidance confirmed safe/effective use by representative users for critical tasks.

Technological Characteristics

Web-based software-only device. Operates on customer-managed infrastructure (Client PC, Gateway, Server). Compatible with Philips Ultra Fast Scanner and PS27QHDCR monitor. Supports iSyntax image format. Connectivity: Networked (Ethernet). Software environment: Windows 11 (Client/Gateway), Ubuntu 22.04 LTS (Server).

Indications for Use

Indicated for pathologists to view, interpret, 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) (DEN160056)

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

K233126

B Applicant

Due to an administrative error, the applicant’s name was previously stated as “AetherAI Co., Ltd” and is now corrected.

aetherAI Co., Ltd.

C Proprietary and Established Names

aetherSlide

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.

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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B Indication(s) for Use:

For In Vitro Diagnostic Use

aetherSlide is a software-only device intended for viewing and managing digital images of scanned surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. It is an aid to the pathologist to review, interpret, and manage digital images of pathology slides for primary diagnosis. aetherSlide 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. aetherSlide is intended for use with the Philips Ultra Fast Scanner (UFS) and the Philips PS27QHDCR monitor.

C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

IV Device/System Characteristics:

A Device Description:

aetherSlide, version 101692 is a web-based, software only device that is intended to aid pathology professionals in viewing, interpretation and management of digital whole slide images (WSI) of scanned surgical pathology slides prepared from formalin-fixed paraffin-embedded (FFPE) tissue obtained from Philips Ultra Fast Scanner (UFS). It aids the pathologist in the review, interpretation, and management of pathology slide digital images used to generate a primary diagnosis.

aetherSlide is operated as follows:

1. Image acquisition is performed using the Philips UFS. The operator conducts quality control of the digital slides according to Philips UFS instructions and laboratory specifications to determine if re-scans are necessary.
2. Once the WSI is acquired using Philips UFS, it becomes available in the Philips IntelliSite Pathology Solution (PIPS) database file systems. The operator then exports the WSI in iSyntax format from PIPS Image Management System (IMS) to a designated storage path.
3. The operator can manually upload the exported WSI into aetherSlide via aetherSlide Gateway, which is a separate medical image communications software. Alternatively, the aetherSlide Gateway can automatically initiate the upload of the WSI into aetherSlide when the auto-upload function is activated on the settings page of aetherSlide Gateway. Once the WSI is uploaded, the reading pathologist uses the device to perform the following actions:

- View slide image
- Zoom and pan the image
- Measure distances in the image
- Annotate the image

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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).

aetherSlide is designed to be deployed to a customer-managed infrastructure and may be accessed on the user's workstation browser. aetherSlide operates with and is validated for use with the components specified the tables below:

Table 1. Interoperable Components for Use with aetherSlide

| Components | Manufacturer | Model |
| --- | --- | --- |
| Scanner | Philips Medical Systems Nederland B.V. | Ultra Fast Scanner |
| Display | Philips Medical Systems Nederland B.V. | PS27QHDCR Monitor |

Table 2. Computer Environment/System Requirements

| Environment | Component | Minimum Requirements |
| --- | --- | --- |
| Client PC | | |
| Hardware | Processor | Intel or AMD with 64-bit support, at least 2 GHz, at least 2 cores |
| | Memory | 4 GB RAM or higher |
| | Storage | 128 GB SSD or higher |
| | Network | 100 Mbps Ethernet or above |
| Software | Operating System | Microsoft Windows 11 |
| | Browser | Google Chrome (122 or higher) |
| Gateway Workstation | | |
| Hardware | Processor | Intel or AMD with 64-bit support, at least 2 GHz, at least 2 cores |
| | Memory | 4 GB RAM or higher |
| | Storage | 128 GB SSD or higher |
| | Network | 100 Mbps Ethernet or above |
| Software | Operating System | Microsoft Windows 11 |
| Server | | |
| Hardware | Processor | Intel or AMD with 64-bit support, at least 2 GHz, at least 8 cores |
| | Memory | 16 GB RAM or higher |
| | Storage | 512 GB SSD or higher |
| | Network | 1 Gbps or above |
| Software | Operating System | Ubuntu 22.04 LTS |

# B Instrument Description Information:

1. Instrument Name: aetherSlide
2. Specimen Identification:

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aetherSlide uses digital images of scanned surgical pathology slides of human samples prepared from formalin-fixed paraffin embedded (FFPE) tissue. The reading pathologist selects a case (patient) from a worklist whereby the subject device fetches the associated images from the image storage. The scanned images are identified based on the previously assigned specimen identifier.

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. The FFPE tissue section is H&amp;E stained. Digital images are then obtained from these glass slides using the PIPS Ultra Fast Scanner.

4. Calibration:

Not applicable

5. Quality Control:

Prior to using a whole slide image for diagnosis, the operator shall conduct quality control of the digital slides according to Philips UFS instructions and any additional laboratory specifications. This process ensures the acceptability of image quality for all scanned slide images and determines if re-scans are necessary.

V Substantial Equivalence Information:

A Predicate Device Name(s):

Philips IntelliSite Pathology Solution

B Predicate 510(k) Number(s):

DEN160056

C Comparison with Predicate(s):

| Device & Predicate Device(s): | K233126 | DEN160056 |
| --- | --- | --- |
| Device Trade Name | aetherSlide | Philips IntelliSite Pathology Solution (PIPS) |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | For In Vitro Diagnostic Use aetherSlide is a software-only device intended for viewing and managing digital images of scanned surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue. It is an aid to the pathologist to | 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 |

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| | | |
| --- | --- | --- |
| | review, interpret, and manage digital images of pathology slides for primary diagnosis. aetherSlide 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. aetherSlide is intended for use with the Philips Ultra Fast Scanner (UFS) and the Philips PS27QHDCR monitor. | 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 |
| Type of Software Application | Internet browser-based application | Same |
| Principle of Operation | After WSI images are successfully acquired by using PIPS UFS, the WSI images are stored in the image storage provided by the end user. During review, the pathologist opens WSI images from storage, 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 an end user provided image storage attached to the local network. | Images are stored in the end user provided image storage (PIPS IMS Application Server & Storage) attached to the local network. |
| Image Manipulation | Panning, zooming, color manipulation function, | Panning, zooming, color manipulation function, annotations, |

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| and Review Functions | annotations, and measurements (only for distance) | and measurements (distance & area) |
| --- | --- | --- |
| General Device Characteristic Differences | | |
| Device Components | aetherSlide imaging viewing software, aetherSlide Gateway | Ultra Fast Scanner (UFS), Image Management System (IMS), Display |
| End User's Interface | aetherSlide | PIPS IMS |

VI Standards/Guidance Documents Referenced:

1. FDA Guidance for Industry "Technical Performance Assessment of Digital Pathology Whole Slide Imaging Devices", April 20, 2016.
2. FDA Guidance for the Applying Human Factors and Usability Engineering to Medical Devices (2016)
3. FDA Guidance for the Content of Premarket Submissions for Device Software Functions (2023)
4. ISO 14971:2019, Medical devices - Application of risk management to medical devices
5. ISO/TR 24971:2020, Medical devices — Guidance on the application of ISO 14971
6. ISO 13485:2016, Medical devices — Quality management systems — Requirements for regulatory purposes
7. IEC 62304:2006/Amd:2015, medical device software — Software life cycle processes — Amendment 1
8. FDA Guidance for the Content of Premarket Submissions for Management of Cybersecurity in Medical Devices (2014)
9. ISO 14971:2019, Medical devices - Application of risk management to medical devices
10. NIST Special Publication 800-115, Technical Guide to Information Security Testing and Assessment

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

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B Other Supportive Instrument Performance Characteristics Data:

Technical performance testing was conducted with aetherSlide. The subject device was compared to the predicate device’s image review manipulation software (IRMS, as defined in FDA guidance document, “Guidance for Industry – 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, $\Delta E$.

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 devices were tested as operating with the intended components, including the scanner (PIPS UFS), image management system (PIPS IMS, aetherSlide with Google Chrome,) and display (PS27QHDCR).

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 to obtain 30 WSIs. For each of the 30 WSIs, 3 ROIs from different locations were selected by qualified personnel to represent various features in the tissue samples. Each ROI was captured at 4 magnification levels (5x, 10x, 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 aetherSlide using Google Chrome. Each image set included 360 images that covered all combinations of 30 slides, 3 ROIs and 4 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 image set was used as the reference to compare the aetherSlide image set to determine whether all the 360 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 ($\Delta$E00), is less than 3 $\Delta$E00. Testing results showed that the pixelwise differences across all 360 image-pairs were less than 3 $\Delta$E00. The mean 95th percentile $\Delta$E00 value was 0.16 with the lowest value reported as 0.00 and the highest reported as 0.71. Testing results demonstrated that WSIs reproduced by aetherSlide are identical to images reproduced by the predicate device.

2. Turnaround Time

The turnaround time for opening an image and panning were measured in the subject device when using Google Chrome over different magnifications levels and over multiple fields of view (FOVs). The test results show that:

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- When selecting a case, the average duration time until the image was fully loaded was 4.31 seconds.
- When panning the images (one quarter of the monitor), the average panning time was 1.05 seconds, 0.85 seconds, 0.99 seconds and 0.78 seconds at magnification levels of 4x, 10x, 20x, and 40x respectively.

The subject device has been found to have an acceptable turnaround time with respect to its intended use for opening and panning the image.

## 3. Measurements

Measurement accuracy testing was performed using the scanned image of a grid micrometer. The scanned image of a grid micrometer (R1L3S3P, Positive Grid Distortion Target, ThorLabs) was used as the test target to verify the length measurement accuracy of the subject device. The 100 µm grid with horizontal and vertical spacing of 0.1 mm was used in the testing. The task of the human tester was to use the subject device’s measurement tool to measure 0.1 mm (1 cell) and 0.2 mm (2 cells), both horizontally and vertically, at 5x, 10x, 20x, and 40x magnifications. Each measurement was conducted three times and the average was reported. Results showed that all measurement values obtained by the human tester using the measurement tool were also 0.1 mm or 0.2 mm for each of the specified measurements above. Test results demonstrated that the subject device performed accurate measurements with respect to its intended use.

## 4. Human Factor (Usability) testing

The aetherSlide device 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 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 aetherSlide device has been found to be safe and effective for intended users, users and use environments.

## VIII. Proposed Labeling:

The labeling supports or 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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