The VIO System is intended to acquire, store, retrieve, display and transfer in vivo images of tissue - including blood vessels, collagen, pigment, stratum corneum, hair shafts or follicles, solar elastosis, atypia, and epidermal disarray - in and through epidermis for review by physicians to assist in forming a clinical judgment. Physicians who interpret VIO System images must have dermatology medical qualifications with skin histology assessment training.

Device Description

The VIO System (REF V-1000) is a light-based in vivo microscope intended to provide images of skin tissue for review by physicians to assist in forming a clinical judgment. The device does not provide image analysis or diagnostic information. The VIO System uses a handheld reflectance confocal and multiphoton microscope that contacts the skin and optically scans at a depth where most skin conditions originate, without disrupting the tissue. The VIO System delivers low power laser light of a single wavelength (780 nm infrared, Class 1M) into the skin in brief pulses. The resulting signals are acquired while imaging the skin and each signal is assigned to one of four (4) channels: RCM (Reflectance Confocal Microscopy), SHG (Second Harmonic Generation), 2PS (2-Photon Autofluorescence Short), and 2PL (2-Photon Autofluorescence Long). For each image capture, the VIO System combines the four (4) channels to display a single, multi-color image on the VIO System, referred to as "Tetrachrome™." Three (3) view modes are accessible to the user on the VIO System: Standard View, Superficial Zoom, and Deep Zoom. Acquired images are not stored on nor analyzed by the VIO System. The images are saved on a USB flash drive, which is used to transfer images to a commercially available DICOM viewer for interpretation by a physician.

AI/ML Overview

The provided 510(k) summary for the Enspectra VIO System (K232789) outlines the device's acceptance criteria and the clinical study conducted to validate its performance.

Here's a breakdown of the requested information:

1. A table of acceptance criteria and the reported device performance

The summary states: "The effectiveness endpoint for the study was achieved as the results demonstrated overall >90% agreement between each Blinded Reader VIO image assessment and the answer key developed from the Comparative Reader validation assessment." This indicates that the acceptance criterion was >90% agreement.

Feature/Region	Acceptance Criteria	Reported Blinded Reader Accuracy (95% CI)
None/Epidermis	>90% Agreement	96.0% (93.6% to 97.7%)
Pigmented cell/Epidermis	>90% Agreement	93.5% (87.1% to 97.4%)
None/Dermis	>90% Agreement	100% (91.0% to 100%)
Collagen/Dermis	>90% Agreement	98.3% (96.7% to 99.3%)
Pigmented cell/Dermis	>90% Agreement	95.6% (89.0% to 98.8%)
Blood vessel/Dermis	>90% Agreement	87.2% (77.7% to 93.7%)
Feature
Stratum corneum	>90% Agreement	99.2% (97.1% to 99.9%)
Hair shaft or follicle	>90% Agreement	97.8% (88.2% to 99.9%)
Solar elastosis	>90% Agreement	99.1% (95.1% to 100%)
Hyperkeratosis	>90% Agreement	100% (92.1% to 100%)
Atypia	>90% Agreement	95.6% (84.9% to 99.5%)
Epidermal disarray	>90% Agreement	100% (88.4% to 100%)

Note: While the overall effectiveness endpoint states >90% agreement, the "Blood vessel/Dermis" accuracy is 87.2% (77.7% to 93.7%). This specific feature's lower bound of the CI falls below 90%, but the report concludes that the "effectiveness endpoint... was achieved as the results demonstrated overall >90% agreement." This suggests that the overall average agreement across all features met the criteria, even if individual feature performance varied.

2. Sample size used for the test set and the data provenance

Sample Size for Test Set: The study was conducted with N=65 participants. Participants were randomly assigned to either a Training Set or a Testing Set. The exact number of participants solely in the testing set is not explicitly stated as a specific number (e.g., "N=X for test set"). However, it's implied that the "Blinded Readers" were tested on images derived from this N=65 participant pool.
Data Provenance: The document does not specify the country of origin of the data. The study involved imaging skin lesions on adults (18 years and above) with Fitzpatrick Skin Type I-V, located on the head, neck, limbs, and torso. It is a prospective study as the VIO System was used to image participants during the study.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Number of Experts for Ground Truth: N=3 Comparative Readers were used to develop the answer key (ground truth) for the test set.
Qualifications of Experts: The Comparative Readers were physicians, and their role involved "validating VIO images against ground truth pathology." The text also states that "Physicians who interpret VIO System images must have dermatology medical qualifications with skin histology assessment training." It's reasonable to infer that the Comparative Readers held these qualifications.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

The ground truth was established by "N=3 Comparative Readers developed consensus training materials, then developed an answer key by validating VIO images against ground truth pathology." This implies an expert consensus method among the 3 comparative readers to establish the answer key. The specific adjudication rule (e.g., majority vote, or discussion until agreement) is not detailed, but it's clearly a consensus-based approach rather than simple averaging or individual reading.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

There is no mention of an MRMC comparative effectiveness study where human readers were compared with and without AI assistance. The study focuses purely on the performance of human readers (Blinded Readers) interpreting VIO images against a ground truth established by other human experts (Comparative Readers). The VIO System itself does not provide image analysis or diagnostic information; it generates images for physician review. Therefore, it's not an AI-assisted interpretation system in the sense of providing a computer-driven initial read or aiding diagnosis.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

No standalone algorithm performance was done/reported. The device description explicitly states: "The device does not provide image analysis or diagnostic information." The VIO System is an image acquisition device; the interpretation is performed by physicians.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The ground truth for the test set was established by expert consensus of 3 Comparative Readers, validated against pathology. Specifically: "...developed an answer key by validating VIO images against ground truth pathology." This indicates that pathology results served as the definitive reference standard, interpreted and applied to the VIO images by the expert readers.

8. The sample size for the training set

The study involved N=65 participants, randomly assigned to either a Training Set or Testing Set. The exact number of participants specifically in the training set is not explicitly stated as a specific number. However, the N=3 Comparative Readers "developed consensus training materials" which implies a portion of the N=65 dataset was used for this training.

9. How the ground truth for the training set was established

The ground truth for the training set was established by the N=3 Comparative Readers who "developed consensus training materials, then developed an answer key by validating VIO images against ground truth pathology." This suggests a similar process to the test set ground truth, involving expert consensus and correlation with pathology.

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: a symbol on the left and the text "FDA U.S. FOOD & DRUG ADMINISTRATION" on the right. The symbol on the left is a stylized image of a human figure, and the text on the right is in blue and white.

December 22, 2023

Enspectra Health, Inc. Grace Li VP, Quality and Regulatory 2495 Hospital Dr, Suite 300 Mountain View, California 94040

Re: K232789

Trade/Device Name: VIO System (V-1000) Regulation Number: 21 CFR 878.4580 Regulation Name: Surgical Lamp Regulatory Class: Class II Product Code: QZN Dated: November 30, 2023 Received: November 30, 2023

Dear Grace Li:

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"

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(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).

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 OS 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); 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-safety-reportingcombination-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.

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 mediation-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).

Sincerely.

Colin K. Chen -S

for

Tanisha Hithe Assistant Director DHT4A: Division of General Surgery Devices OHT4: Office of Surgical

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and Infection Control Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K232789

Device Name VIO System (REF V-1000)

Indications for Use (Describe)

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)

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ENSPECTRA VIO System 510(k) Summary

Per 21 CFR 807.92, the following summary of information is provided:

A. SUBMITTER

Enspectra Health, Inc.

2495 Hospital Drive, Suite 300

Mountain View, California 94040

Contact Person:

Grace Li

VP, Quality and Regulatory

Enspectra Health, Inc.

Phone: (650) 480-6022

Date Prepared:

September 11, 2023

B. DEVICE INFORMATION

Trade Name:

VIO System

Device Type/Common Name:

Multi-photon imaging

Classification Regulation:

21 CFR§878.4580 Surgical Lamp

Class:

Product Code:

QZN: Multi-photon imaging

C. PREDICATE DEVICE

VivaScope System (Caliber Imaging & Diagnostics, K180162) This predicate device has not been subject to a design related recall. No reference devices were used in this submission.

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DEVICE DESCRIPTION D.

The VIO System delivers low power laser light of a single wavelength (780 nm infrared, Class 1M) into the skin in brief pulses. The resulting signals are acquired while imaging the skin and each signal is assigned to one of four (4) channels:

Channel	Description	NominalWavelength	Created primarily by
RCM	Reflectance ConfocalMicroscopy	780 nm	Pigment and cellularmembranes
SHG	Second Harmonic Generation	390 nm	Collagen
2PS	2-Photon AutofluorescenceShort	450 nm	Cytoplasmic molecules andkeratin
2PL	2-Photon Autofluorescence Long	650 nm	Elastin and melanin

For each image capture, the VIO System combines the four (4) channels to display a single, multi-color image on the VIO System, referred to as "Tetrachrome™." Three (3) view modes are accessible to the user on the VIO System:

View Mode	Nominal Width	Nominal Depth	Description
Standard View	0.4 mm	0.3 mm	Complete area of scan
Superficial Zoom	0.13 mm	0.1 mm	Upper, center area of scan
Deep Zoom	0.13 mm	0.15 mm	Lower, center area of scan

The view modes and vertical cross-sectional orientation of each image are comparable to the view through a standard light microscope of a physical glass slide using the 20x to 40x magnification setting.

Acquired images are not stored on nor analyzed by the VIO System. The images are saved on a USB flash drive, which is used to transfer images to a commercially available DICOM viewer for interpretation by a physician. For each image capture, the following files are produced:

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DICOM Label	File Type	Color
RGB (Red Green Blue)	DICOM, PNG	Tetrachrome (color composite)
RCM	DICOM	Grayscale
SHG	DICOM	Grayscale
2PS	DICOM	Grayscale
2PL	DICOM	Grayscale

The VIO System has two (2) accessories, the VIO Imaging Cover (REF V-1100) and the VIO Targeting Sticker (REF V-1200). Both the VIO Imaging Cover and the VIO Targeting Sticker are single use accessories that are discarded after each use. Both accessories are provided nonsterile.

E. INTENDED USE/INDICATIONS FOR USE

The VIO System and the predicate device have the same intended use; both are in vivo microscopes that use reflected light to capture images of the skin. The VIO System has the following indications for use:

The VIO System is intended to acquire, store, retrieve, display and transfer in vivo images of tissue – including blood vessels, collagen, pigment, stratum corneum, hair shafts or follicles, solar elastosis, hyperkeratosis, atypia, and epidermal disarray – in and through epidermis for review by physicians to assist in forming a clinical judgment. Physicians who interpret VIO System images must have dermatology or pathology medical qualifications with skin histology assessment training.

The predicate device is intended to acquire, store, retrieve, display and transfer in vivo images of tissue, including blood, collagen and pigment, in exposed unstained epithelium and the supporting stroma. The differences in indications for use statements do not substantially modify the clinical information provided or the risk. The intended use to produce in vivo images of skin is the same between the subject and predicate devices.

F. COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE

The technological principle for both the subject and predicate devices is the use of reflected light to capture in vivo images of the skin. The subject and predicate devices use the following same technological elements:

Single-point laser scanning Reflectance Confocal Microscopy (RCM) optical technology
Illumination of unstained skin with near infrared wavelength and average power <35 mW

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Class 1M imaging laser
Presentation of digital images with cellular detail
DICOM image output

The differences in technological characteristics between the VIO System and the predicate device are:

. Optical Technology: The VIO System utilizes Multiphoton Microscopy (MPM) in addition to RCM to take in vivo pictures of skin.
. Image Presentation: The VIO System displays images in a vertical cross-sectional orientation in order to align orientation with traditional histopathology slides. The predicate device displays images in a horizontal orientation.
. Physical Design and Data Workflow: The VIO System is physically smaller and more flexible than the predicate device and has different patient contacting materials. The VIO System uses a USB flash drive to transfer data to a commercial DICOM viewer, while the predicate device is internet enabled with an embedded viewer.

PERFORMANCE DATA G.

The following performance data were provided in support of the substantial equivalence determination.

Non-Clinical Performance Data

Non-clinical design verification and validation activities were completed for the VIO System based on risk analysis assessments and product requirements. Testing included verification and validation of specifications related to safety, usability, software, and performance, including the following:

Electrical safety per ANSI AAMI ES60601-1:2005 +A1:2012 +A2:2021
EMC per IEC 60601-1-2 Ed. 4.1
Laser safety per IEC 60825-1 Ed 3.0
Biological risk assessment per ISO 10993-1:2018
Human factors assessment per IEC 62366-1:2015/Amd1:2020
. Software lifecycle management including software testing per IEC 62304 Ed 1.1
Benchtop system imaging performance

Non-clinical performance testing confirmed that the VIO System met the predetermined acceptance criteria and demonstrated that the VIO System is safe and effective for its intended use. Non-clinical performance testing demonstrated that the differences between the subject and predicate devices do not raise different questions of safety or effectiveness.

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Clinical Performance Data

A clinical study was conducted with N=65 participants to validation of tissue structures by physicians to assist in forming a clinical judgment. In the study, the VIO System was used to image adults (18 years old and above) with Fitzpatrick Skin Type I-V, on skin lesions located on the head, neck, limbs, and torso.

Participants were randomly assigned to either a Training Set or Testing Set. N=3 Comparative Readers developed consensus training materials, then developed an answer key by validating VIO images against ground truth pathology. N=3 Blinded Readers (with dermatology or pathology medical qualifications and skin histology assessment training) were trained from Comparative Reader training materials, then tested on their ability to identify labeled structures in VIO images. The Blinded Reader performance test results are summarized in Table 1.

Feature/Region	Blinded Reader Accuracy (95% CI)
None/Epidermis	96.0% (93.6% to 97.7%)
Pigmented cell/Epidermis	93.5% (87.1% to 97.4%)
None/Dermis	100% (91.0% to 100%)
Collagen/Dermis	98.3% (96.7% to 99.3%)
Pigmented cell/Dermis	95.6% (89.0% to 98.8%)
Blood vessel/Dermis	87.2% (77.7% to 93.7%)
Feature
Stratum corneum	99.2% (97.1% to 99.9%)
Hair shaft or follicle	97.8% (88.2% to 99.9%)
Solar elastosis	99.1% (95.1% to 100%)
Hyperkeratosis	100% (92.1% to 100%)
Atypia	95.6% (84.9% to 99.5%)
Epidermal disarray	100% (88.4% to 100%)

Table 1. VIO Svstem clinical performance test results

The safety endpoint for the study was assessed: no adverse events were reported during the study. The effectiveness endpoint for the study was achieved as the results demonstrated overall >90% agreement between each Blinded Reader VIO image assessment and the answer key developed from the Comparative Reader validation assessment. The secondary endpoint of >90% inter-reader agreement was also achieved.

Clinical performance testing confirmed that the VIO System met the predetermined acceptance criteria and demonstrated that the VIO System is safe and effective for its intended use. Clinical performance testing demonstrated that the differences between the subject and predicate devices do not raise different questions of safety or effectiveness.

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CONCLUSION H.

The subject device and the predicate devices are both light-based in vivo microscopes. The VIO System has the same intended use and similar indications for use compared to the predicate device. In addition to single-photon excitation similar to the predicate device, the subject device also includes two-photon excitation to produce its images. The results of performance testing confirm that the VIO System functions pursuant to its specifications and intended use and exhibits the appropriate characteristics of a light-based in vivo microscope. Performance testing demonstrated that the differences between the subject and predicate devices do not raise new types of questions regarding safety and effectiveness. Thus, the VIO System is substantially equivalent to the predicate device, the VivaScope System (Caliber Imaging & Diagnostics, K180162).

Regulation Number and Section

§ 878.4580 Surgical lamp.

(a)
Identification. A surgical lamp (including a fixture) is a device intended to be used to provide visible illumination of the surgical field or the patient.(b)
Classification. Class II (special controls). The device, when it is an operating room lamp, a surgical instrument light, a surgical floor standing light, an endoscopic surgical light, a surgical light connector, a ceiling mounted surgical light, a surgical light carrier, surgical light accessories, a surgical lamp, a remote illuminator, or an incandescent surgical lamp, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 878.9.