The Minuteful - kidney test is an in-vitro diagnostic, home-use urine analysis test system for the semi-quantitative measurement of albumin and creatinine in urine, as well as the presentation of their ratio, the albumin-creatinine ratio (ACR). The system consists of a smartphone application, proprietary Color-Board and an ACR Reagent Strip. The system is available for prescription-use only and is intended for people at risk of kidney disease. Results are used in conjunction with clinical evaluation as an aid in the assessment of kidney health.

Device Description

The Minuteful - kidney test is comprised of a kit and a smartphone application. It is intended for the semi-quantitative measurement of albumin and creatinine in urine, as well as the presentation of their ratio, the albumin-creatinine ratio (ACR). The Minuteful - kidney test is intended for prescription-use only, as a home-use device to aid in the assessment of kidney health. The results can be used together with clinical evaluation to guide patient care. The device's kit includes a urine receptacle, an ACR Reagent Strip, an absorbing (i.e. "blotting") pad, a proprietary Color-Board and a user manual. The device also consists of an easy-to-use smartphone application, image recognition algorithms, and a physician compendium. The software component of the Minuteful - kidney test consists of both an application (app) and a backend server. Both components encompass different computer vision and machine learning algorithmic components, performing the image analysis activities. The app instructs the user how to accurately administer the test. The Image Validation Transfer System (IVTS) component of the Minuteful - kidney test enables its usage across a wide range of smartphone types and operating systems, essentially making the test platform agnostic.

AI/ML Overview

The provided text describes the Minuteful-kidney test (K222921) and its substantial equivalence to a predicate device (K210069). However, it specifically states that "The rest of the analytical performance studies are still relevant for the modified version of the Minuteful - kidney test, and their summary is available in the predicate device documentation (K210069)." This means the detailed acceptance criteria and the comprehensive study demonstrating the device meets those criteria are not present in this document but are referenced as being in the predicate device's documentation.

Therefore, I can report on the studies performed for K222921 to assert its substantial equivalence, but I cannot provide a table of acceptance criteria and reported device performance from this document for the overall device functionality as those details are in K210069. Nor can I provide information regarding sample sizes for test sets, expert qualifications, adjudication methods, MRMC studies, standalone performance, or ground truth details for K222921's overall performance since those are tied to the K210069 submission.

The studies described in K222921 (the current device) are focused on demonstrating that changes made to the device in K222921 do not negatively impact performance, thus maintaining substantial equivalence to its predicate.

Here's an analysis based solely on the provided text for K222921, noting the limitations:

Acceptance Criteria and Device Performance (Limited to K222921 changes):

Since the comprehensive performance data is referenced in K210069, the "acceptance criteria" discussed here are implicitly related to demonstrating that the modifications in K222921 (e.g., multilingual support, software enhancements) do not degrade the performance previously established for K210069. The studies conducted for K222921 focused on the robustness of the Image Validation Transfer System (IVTS) and the analytical limits of detection.

Acceptance Criteria (Implied for K222921 changes)	Reported Device Performance (K222921)
Limit of Detection (LoD)	Testing was conducted in accordance with CLSI document EP17-A2. (Specific LoD values are not provided in this document but are likely in K210069).
Illumination Conditions	Performance is "not impacted" by different lighting conditions (color temperatures, intensities, light sources) representative of home use, nor by different light color saturations and intensities at the edges of device boundary conditions.
Physical Conditions	Performance is "not impacted" by different distance and angle conditions at the edges of device boundary conditions.
Multiple Shadow Conditions	Performance is "not impacted" by different shadow configurations (intensity, coverage) at the edges of device boundary conditions.
Blurriness	Performance is "not impacted" by different levels of focus and motion blur in images at the edges of device boundary conditions.
Misplaced Urine Stick	Performance is "not impacted" by different urine test strip placements at the edges of device boundary conditions.
Dirty Color-Board	Performance is "not impacted" by different dirty substances covering parts of the Color-Board at the edges of device boundary conditions.
Overall Equivalence to Predicate	The modified Minuteful-kidney test is concluded to be substantially equivalent to the predicate device (K210069), implying that the changes did not degrade its overall performance in terms of precision, interference, linearity, stability, and clinical performance, which are referenced back to the K210069 summary. The new IVTS system allows usage across a wide range of smartphone types and operating systems, making the test platform agnostic, without impacting performance in various challenging conditions.

Study Details (for K222921 specific enhancements):

Sample size used for the test set and the data provenance:
- Limit of Detection (LoD): The document does not specify the sample size for the LoD study for K222921. It mentions the study was designed and executed according to CLSI document EP17-A2.
- Illumination, Physical, Shadow, Blurriness, Misplaced Urine Stick, Dirty Color-Board Studies: The document refers to "Tested smartphones" and "different conditions," but specific numerical sample sizes (e.g., number of images, tests, or smartphones) are not provided. The data provenance is implied to be laboratory-controlled since these are experimental conditions, but no explicit country of origin or retrospective/prospective nature is stated for these new studies. The overall device is intended for home use, so these validations mimic adverse home conditions.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This information is not provided in the K222921 document. These types of analytical studies typically rely on reference methods or scientifically established standards rather than expert consensus. For the clinical performance, the document refers to the predicate device K210069, where such details would likely be found if applicable.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable/Not provided for these specific analytical studies. The assessment of whether performance was "not impacted" would likely come from statistical analysis against pre-defined thresholds.
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:
- No MRMC or comparative effectiveness study involving human readers with and without AI assistance is mentioned in the K222921 submission. This device is an in-vitro diagnostic home-use test system where the smartphone app performs the measurement, rather than assisting a human in interpreting diagnostic images. Thus, the concept of "human readers improve with AI" in a traditional MRMC sense does not directly apply to this device's function.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- The core of the described studies (LoD, Illumination, Physical, Shadow, Blurriness, Misplaced Urine Stick, Dirty Color-Board) are indeed standalone performance tests of the device's algorithmic capability to accurately read the test strip under various challenging conditions encountered in a home setting. The device is described as having "image recognition algorithms" and performing "image analysis activities."
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For the analytical studies described (LoD, Illumination, etc.), the ground truth would be based on controlled experimental conditions and potentially quantitative reference measurements (e.g., known concentrations for LoD, controlled lighting conditions). The document does not specify the exact methods for establishing this ground truth but implies scientific rigor (e.g., "in accordance with guidance provided by the Clinical and Laboratory Standards Institute (CLSI) document EP17-A2"). For the clinical performance aspects, the document refers to K210069.
The sample size for the training set:
- Not provided in the K222921 document. Training set details would typically be part of the initial K210069 submission for the machine learning algorithms.
How the ground truth for the training set was established:
- Not provided in the K222921 document. This information would be found in the K210069 submission, likely involving laboratory-controlled tests with known analyte concentrations and reference methods for accurate measurement.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there is a symbol representing the Department of Health & Human Services - USA. To the right of this symbol, there is a blue square with the letters "FDA" in white. Next to the blue square, the words "U.S. FOOD & DRUG ADMINISTRATION" are written in blue.

September 8, 2023

Healthy.io Ltd. Ron Zohar Chief Product Officer 8 Yitzhak Sadeh St. Tel Aviv, Israel 6777508

Re: K222921

Trade/Device Name: Minuteful-kidney test Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine Test System Regulatory Class: Class II Product Code: JFY, JIR, KQO Dated: June 11, 2023 Received: June 12, 2023

Dear Ron Zohar:

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 (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's

{1}------------------------------------------------

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 803) for devices or postmarketing safety reporting (21 CFR 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 (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to 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,

Paula V. Caposino -S

Paula Caposino, Ph.D. Acting Deputy Division Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K222921

Device Name Minuteful - kidney test

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)

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."

{3}------------------------------------------------

Healthy.io's Minuteful - kidney test (K222921)

Submitter:

Healthy.io Ltd. 8 Yitzhak Sadeh St. Tel Aviv, Israel 6777508

Phone: +972-54-445-4514 Facsimile: +972-77-470-4808

Contact Person: Ron Zohar

Date Prepared: September 19, 2022

Name of Device: Minuteful - kidney test

Common or Usual Name: Smartphone enabled albumin-creatinine ratio analyzer

Regulation Section and Classification Name:

Class I: Albumin Class II: Creatinine

21 CFR § 862.1645 Urinary protein or albumin (non-quantitative) test system 21 CFR § 862.1225 Creatinine test system 21 CFR § 862.2900 Automated urinalysis system

Product Code:

JIR Urinary protein or albumin (nonquantitative) test system JFY Creatinine test system KQO Automated urinalysis system

Classification Panel: Clinical Chemistry

{4}------------------------------------------------

Predicate Device:

The Minuteful - kidney test is substantially equivalent to the following predicate device:

Manufacturer	Device	510(k) Number
Healthy.io Ltd.	Minuteful - kidney test	K210069

Device Description:

The Minuteful - kidney test is intended for prescription-use only, as a home-use device to aid in the assessment of kidney health. The results can be used together with clinical evaluation to guide patient care.

The device's kit includes a urine receptacle, an ACR Reagent Strip, an absorbing (i.e. "blotting") pad, a proprietary Color-Board and a user manual. The device also consists of an easy-to-use smartphone application, image recognition algorithms, and a physician compendium.

The software component of the Minuteful - kidney test consists of both an application (app) and a backend server. Both components encompass different computer vision and machine learning algorithmic components, performing the image analysis activities. The app instructs the user how to accurately administer the test. The Image Validation Transfer System (IVTS) component of the Minuteful - kidney test enables its usage across a wide range of smartphone types and operating systems, essentially making the test platform agnostic.

Intended Use/Indications for Use:

The Minuteful - kidney test is an in-vitro diagnostic, home-use urine analysis test system for the semi-quantitative measurement of albumin and creatinine in urine, as well as the presentation of their ratio, the albumin-creatinine ratio (ACR). The system consists of a smartphone application, proprietary Color-Board and an ACR Reagent Strip. The system is available for prescription-use only and is intended for people at risk of kidney disease. Results are intended to be used in conjunction with clinical evaluation as an aid in the assessment of kidney health.

{5}------------------------------------------------

Table I Comparison between the Minuteful - kidney test (K222921) and Minuteful - kidney test (K210069) the predicate device.

Feature	Minuteful - kidney test(K210069)	Minuteful - kidney test(K222921)
Intended Use	The Minuteful – kidney test is anin-vitro diagnostic, home-useurine analysis test system for thesemi-quantitative measurement ofalbumin and creatinine in urine,as well as the presentation oftheir ratio, the albumin-creatinineratio (ACR). The system consistsof a smartphone application,proprietary Color-Board and anACR Reagent Strip. The systemis available for prescription-useonly and is intended for people atrisk of kidney disease. Resultsare intended to be used inconjunction with clinicalevaluation as an aid in theassessment of kidney health.	Same
Test Specimen	Urine	Same
DetectionMethodology	Reflectance photometry	Same
Detection Device	Photosensitive diode	Same
Strips	URiSCAN 2ACR urine strips(K141874)	Same
Analytes	albumin, creatinine	Same
Power Source	Not Applicable	Same
Data Transfer/Capabilities	Via smartphone internetconnection from the backendserver to the lay user and ahealthcare professional. Resultsare available for secure sharing	Same
Feature	Minuteful - kidney test(K210069)	Minuteful - kidney test(K222921)
	with an EMR.
Availablelanguageson screen	English	English, Spanish
MeasuringCycle/IncubationTime	75 seconds	Same
Throughput	Not Applicable	Same
Smartphones/OperatingSystems	The product supports a widevariety of currently availablesmartphones and operatingsystems. Newly introducedsmartphone-hardware and newoperating systems will bevalidated by the company on aregular basis.	Same
Dimensions	106mm (W) x 143mm (D) x30mm (H)	Same
Weight	0.105kg	Same

{6}------------------------------------------------

{7}------------------------------------------------

Summary of Performance Data:

Healthy.io conducted multiple validation studies including the Limit of Detection and the set of IVTS studies to ensure the modified device is substantially equivalent to the predicate device (Minuteful - kidney test K210069). The rest of the analytical performance studies are still relevant for the modified version of the Minuteful - kidney test, and their summary is available in the predicate device documentation (K210069).

Performance Testing:

The performance characteristics of the Minuteful - kidney test were evaluated according to the following performance tests:

Limit of Detection (LoD):

Testing of the Minuteful - kidney test detection limits was designed and executed in accordance with guidance provided by the Clinical and Laboratory Standards Institute (CLSI) document EP17-A2 - Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guidelines - Second Edition.

Illumination Conditions:

This study consisted of two separate studies; the Multiple Illuminations and Extreme Illuminations studies.

. Multiple Illuminations: Testing was conducted under different lighting conditions of different color temperatures and intensities from different light sources representative of those that may be used in the home setting. The results of the study support that the performance is not impacted by lighting conditions that are likely to be found in the home use environment.
Extreme Illuminations: Testing was conducted under different lighting conditions with . different saturation of the RGB spectrums as well as under different light intensities. Tested smartphones were evaluated at the edges of the device boundary conditions, under which the device allowed the smartphone to take an image of the urine test strip and Color-Board. The results of this testing support that the device performance is not impacted by different light color saturations.

Physical Conditions:

Testing was conducted under different distance conditions and different angle conditions. Tested smartphones were evaluated at the edges of the device boundary conditions, under which the device allowed the smartphone to take an image of the urine test strip and Color-Board. The performance of the device was not impacted within the supported conditions.

Multiple Shadow conditions:

Testing was conducted under different shadow configurations of different intensity and covering different portions of the Color-Board and urine test strip. Tested smartphones were evaluated at the edges of the device boundary conditions, under which the device allowed the smartphone to use the captured image of the urine test strip and Color-Board. The performance of the device was not impacted by the presence of shadows on the color-board and test strip within the supported conditions.

{8}------------------------------------------------

Blurriness:

Testing was conducted under different conditions of blurred images consisting of different levels of focus and motion blur. Tested smartphones were evaluated at the edges of the device boundary conditions, under which the device allowed the smartphone to take an image of the urine test strip and Color-Board. The performance of the device was not impacted by the image blur within the supported conditions.

Misplaced Urine Stick:

Testing was conducted under different urine test strip placements. Tested smartphones were evaluated at the edges of the device boundary conditions, under which the device allowed the smartphone to use the captured image of the urine test strip and Color-Board. The performance of the device was not impacted by the test strip placement within the supported conditions.

Dirty Color-Board:

Testing was conducted under different dirty substances covering different parts of the Color-Board. consisting of different levels of focus and motion blur. Tested smartphones were evaluated at the edges of the device boundary conditions, under which the device allowed the smartphone to use the captured image of the urine test strip and Color-Board. The performance of the device was not impacted by the dirty substances within the supported conditions.

Precision: See Minuteful - kidney test summary (K210069).

Interference: See Minuteful - kidney test summary (K210069).

Linearity: See Minuteful - kidney test summary (K210069).

Stability: See Minuteful - kidney test summary (K210069).

Clinical Performance Testing:

Method Comparison: See Minuteful - kidney test summary (K210069).

Conclusion:

The modified Minuteful - kidney test is substantially equivalent to the predicate device Minuteful kidney test cleared in K210069.

Regulation Number and Section

§ 862.1645 Urinary protein or albumin (nonquantitative) test system.

(a)
Identification. A urinary protein or albumin (nonquantitative) test system is a device intended to identify proteins or albumin in urine. Identification of urinary protein or albumin (nonquantitative) is used in the diagnosis and treatment of disease conditions such as renal or heart diseases or thyroid disorders, which are characterized by proteinuria or albuminuria.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.