KetoSens Blood ß-Ketone Monitoring System is intended to be used for the quantitative measurement of f-Ketone (beta-hydroxybutyrate) level in capillary whole blood samples drawn from the fingertip. The KetoSens Blood B-Ketone Monitoring Systems are for self-testing outside the body (for in vitro diagnostic use) in the home as an aid to monitor the effectiveness of diabetes control program. The system is not in the diagnosis of or screening for diabetes mellitus and is not intended for use on neonates. This system is intended to be used by a single person and should not be shared.

The KetoSens Blood ß-Ketone Test Strips work with the KetoSens Blood ß-Ketone Meter to quantitatively measure Blood ß-Ketone in capillary whole blood samples drawn from the fingertip.

KetoSens Multi Blood p-Ketone Monitoring System is intended to be used for the quantitative measurement of f-Ketone (beta-hydroxybutyrate) level in capillary whole blood from the fingertip and venous EDTA whole blood. KetoSens Multi Blood ß-Ketone Monitoring System is intended for in vitro diagnostic use and is intended for multiple-patient use in professional healthcare settings as an aid to monitor the effectiveness of diabetes control program. The system is not intended for use in the diagnosis of or screening for diabetes mellitus and is not intended for use on neonates. This system should only be used with single-use, auto-disabling lancing devices.

The KetoSens Multi Blood p-Ketone Test Strips work with Blood ß-Ketone Meter to quantitatively measure Blood B-Ketone in capillary whole blood samples drawn from the fingertip and venous whole blood drawn in professional healthcare settings.

Device Description

The KetoSens Blood ß-Ketone Monitoring System/KetoSens Multi Blood ß-Ketone Monitoring System consists of a meter, single use test strips, and control solutions with two different B-Ketone concentrations ("Control A" and "Control B" ranges).

The KetoSens Blood ß-Ketone Monitoring System/KetoSens Multi Blood ß-Ketone Monitoring System is based on an electrochemical biosensor technology (electrochemical). The System measures the Blood ß-Ketone level in whole blood samples using a small electrical current generated in the test strips.

AI/ML Overview

This document focuses on the KetoSens Blood β-Ketone Monitoring System and its validation studies. It describes various performance tests conducted to ensure the device meets specified criteria, primarily focusing on accuracy, precision, and usability.

Here's an organized breakdown of the acceptance criteria and study details based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a single table labeled "Acceptance Criteria." However, acceptance criteria are implicitly stated within the "System Accuracy Test" and "Consumer Study" results, and "Repeatability Test" and "Intermediate Precision Test" conclusions.

Test Type	Acceptance Criteria (Stated or Implied)	Reported Device Performance
Repeatability (Precision)	Pooled SD of concentrations 1, 2 should be < 0.075 mmol/L. Pooled CV % of concentrations 3, 4, 5 should be < 5.0 %.	Passed. Pooled SD (concentration 1) = 0.027 mmol/L, (concentration 2) = 0.056 mmol/L. Pooled CV % (concentration 3) = 3.7%, (concentration 4) = 3.5%, (concentration 5) = 3.6%.
Intermediate Precision	Pooled SD for concentration interval 1 < 0.075 mmol/L. Pooled CV % for interval 2, 3 < 5.0 %.	Passed. Pooled SD (concentration 1) = 0.049 mmol/L. Pooled CV % (concentration 2) = 3.8%, (concentration 3) = 4.3%.
Linearity	High linear correlation (coefficient of determination r² > 0.95).	Passed. Total r² = 0.9985 across 3 strip lots.
System Accuracy (Capillary Blood)	At ketone < 1.5 mmol/L: 95% of results within ± 0.3 mmol/L. At ketone ≥ 1.5 mmol/L: 95% of results within ± 20 %.	Passed.> At ketone < 1.5 mmol/L: 170/171 (99.4%) within ± 0.3 mmol/L.> At ketone ≥ 1.5 mmol/L: 33/33 (100%) within ± 20 %. All 204 samples (100%) fell within specified ranges.
System Accuracy (Venous Blood)	At ketone < 1.5 mmol/L: 95% of results within ± 0.3 mmol/L. At ketone ≥ 1.5 mmol/L: 95% of results within ± 20 %.	Passed.> At ketone < 1.5 mmol/L: 169/169 (100%) within ± 0.3 mmol/L.> At ketone ≥ 1.5 mmol/L: 35/35 (100%) within ± 20 %. All 204 samples (100%) fell within specified ranges.
Consumer Study (Accuracy)	Capillary blood accuracy to satisfy system accuracy requirements (as defined above).	Passed.> General user tests: 185/185 (100%) within ± 0.3 mmol/L (for ketone < 1.5 mmol/L - implicitly applies given all results fell within).> Trained user tests: 185/185 (100%) within ± 0.3 mmol/L (for ketone < 1.5 mmol/L - implicitly applies). Also, 100% of general users could use the device correctly and obtain accurate results.
Point-of-Care (POC) Test (Accuracy)	Accuracy requirements met (as defined for system accuracy).	Passed.> Capillary: 124/124 (100%) within ± 0.3 mmol/L for < 1.5 mmol/L; 12/12 (100%) within ± 20% for ≥ 1.5 mmol/L.> Venous: 121/123 (98.4%) within ± 0.3 mmol/L for < 1.5 mmol/L; 13/13 (100%) within ± 20% for ≥ 1.5 mmol/L.
Hematocrit Effect	Hematocrit biases to be within acceptable limits (specific thresholds are detailed in the results section, generally showing low bias).	Passed. Biases were within specified ranges for different ketone intervals across 20-60% hematocrit. For example, -0.09 to 0.02 mmol/L at 0.0-0.8 mmol/L ketone, and percentage biases for higher concentrations (e.g., -15.02 to 8.73% at 5.5-6.5 mmol/L ketone).
Interference Test	No significant interference from listed substances. (Implicitly, results should not show significant bias).	Passed. Differences observed are mostly small, suggesting acceptable performance in the presence of various interferents. For example, Acetaminophen showed a -5.4% to -8.3% difference in the 2.0-3.5 mmol/L range, while many others were much smaller. Specific acceptance thresholds for interference are not explicitly provided in the summary, but the conclusion implies acceptance.
Altitude Test	No significant difference from reference equipment at high altitudes (up to 10,000 feet).	Passed. No systematic response to altitudes; not significantly affected by lack of atmospheric oxygen up to 10,000 feet (3,048m).
Operating Condition Test	Meters operate normally with less than 0.03 mmol/L or 20% bias from reference results.	Passed. Confirmed normal operation at 9 combined temperature-humidity conditions (10°C, 15°C, 30°, 40%, and 90% RH), with results showing bias less than 0.03 mmol/L or 20% from reference.

2. Sample Size Used for the Test Set and Data Provenance

System Accuracy Test (Capillary Blood): 204 samples.
System Accuracy Test (Venous Blood): 204 samples.
Repeatability Test: 300 measurements (N=300 for each of 5 concentration levels). This suggests a large number of readings rather than 300 unique samples.
Intermediate Precision Test: 600 measurements (N=600 for each of 3 control levels).
Consumer Study: 185 general users.
Point-of-Care Test: 124 patients for capillary samples, 123 patients for venous samples.
Hematocrit Effect Test: 5 different hematocrit levels, 5 different ketone intervals, measured using 30 meters and 3 lots of strips.
Interference Test: 2 ketone concentrations, across 29 interferents, with 3 strip lots.
Altitude Test: Not specified in terms of distinct sample numbers, but tested.
Operating Condition Test: Not specified in terms of distinct sample numbers, but tested.

Data Provenance: The document does not explicitly state the country of origin of the data or whether the studies were retrospective or prospective. However, based on the nature of clinical evaluation, consumer studies, and POC tests involving patient samples and human participants, these are typically prospective studies. The company, i-SENS, Inc., is based in Seoul, Korea, suggesting the studies likely took place there or in a similar regulatory environment.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The document mentions "trained staff" and "Health Care Professionals" (HCPs) in the context of comparative measurements.
In the Consumer Study, results of general users are compared against "Rx Imola reference values" and "BKMS results obtained by trained staff."
In the Point-of-Care Test, "Health care professionals" (six members) performed tests, and "The study staff operates the reference equipment and modify the KetoSens Multi BKMS results are compared against the reference values."
The qualifications of these "trained staff" or "Health Care Professionals" are not explicitly defined (e.g., "radiologist with 10 years of experience"). Their role is to operate the reference equipment and/or the candidate device for comparison.

4. Adjudication Method (e.g. 2+1, 3+1, none) for the Test Set

The document does not describe an adjudication method for the test set in the context of expert review or consensus, as would be typical for image-based diagnostic AI. For a quantitative measurement device, the "ground truth" is typically established by comparative measurement to a highly accurate reference method. Discrepancies are usually managed through statistical analysis rather than an adjudication process among human readers.

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

This is not applicable as the device is a quantitative blood β-ketone monitoring system, not an AI-based diagnostic imaging tool that assists human readers. Therefore, an MRMC study and analysis of human reader improvement with AI assistance are not relevant to this device.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done

The device is a standalone quantitative measurement system. Its performance (accuracy, precision) is evaluated independently against a reference standard (Rx Imola equipment). The human user's role is to operate the device correctly, consistent with its "intended to be used for the quantitative measurement" function. The consumer study and POC test assess the usability for target users (self-testing or HCPs), but the core performance data in the system accuracy tests represent the device's measurement capabilities.

7. The Type of Ground Truth Used (Expert Consensus, Pathology, Outcomes Data, etc.)

The ground truth for the quantitative measurement of β-ketone levels was established using a reference measurement procedure/equipment. Specifically:

"The accuracy of KetoSens is evaluated with clinical evaluation using capillary and venous blood samples... and with the standard measurement."
"KetoSens BKMS did not show significant difference with respect to the Rx Imola equipment, nor with different altitudes at all ketone concentrations."
In the Consumer Study and POC test, results were compared against "Rx Imola reference values."

Therefore, the ground truth is comparative measurement to a recognized laboratory reference method/instrument (Rx Imola).

8. The Sample Size for the Training Set

The document describes performance evaluation (test set) studies but does not mention a 'training set' in the context of machine learning model development. This is because the KetoSens Blood β-Ketone Monitoring System is based on electrochemical biosensor technology, which relies on a chemical reaction to produce an electrical current proportional to the analyte, rather than an AI/ML algorithm that requires training data.

9. How the Ground Truth for the Training Set Was Established

As the device does not employ an AI/ML algorithm requiring a 'training set,' this question is not applicable. The underlying principle is electrochemical, not data-driven machine learning.

Summary

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Image /page/0/Picture/0 description: The image contains two logos. On the left is the logo for the Department of Health & Human Services - USA, featuring a stylized emblem with three figures. To the right is the logo for the U.S. Food & Drug Administration (FDA), with the FDA acronym in a blue square, followed by the words "U.S. FOOD & DRUG" stacked above the word "ADMINISTRATION", all in blue.

April 13, 2018

i-SENS, Inc. Joon Ho Jung RA Team Manager 43, Banpo-daero 28-gil, Seocho-gu Seoul, 06646 Korea

Re: K170463

Trade/Device Name: KetoSens Blood β-Ketone Monitoring System KetoSens Multi Blood ß-Ketone Monitoring System Regulation Number: 21 CFR 862.1435 Regulation Name: Ketones (nonquantitative) test system C Regulatory Class: Class I, meets limitation of exemptions 21 CFR 862.9(c)(5) Product Code: JIN Dated: April 3, 2018 Received: April 10, 2018

Dear Joon Ho Jung:

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. 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Kellie B. Kelm -S

for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K170463

Device Name KetoSens Blood ß-Ketone Monitoring System

Indications for Use (Describe)

KetoSens Blood ß-Ketone Monitoring System is intended to be used for the quantitative measurement of f-Ketone (betahydroxybutyrate) level in capillary whole blood samples drawn from the fingertip. The KetoSens Blood B-Ketone Monitoring Systems are for self-testing outside the body (for in vitro diagnostic use) in the home as an aid to monitor the effectiveness of diabetes control program. The system is not in the diagnosis of or screening for diabetes mellitus and is not intended for use on neonates. This system is intended to be used by a single person and should not be shared.

The KetoSens Blood ß-Ketone Test Strips work with the KetoSens Blood ß-Ketone Meter to quantitatively measure Blood ß-Ketone in capillary whole blood samples drawn from the fingertip.

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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CONTINUE ON A SEPARATE PAGE IF NEEDED.

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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:

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Indications for Use

510(k) Number (if known) K170463

Device Name

KetoSens Multi Blood ß-Ketone Monitoring System

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
-------------------------------------------------	--

X 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.

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."

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Image /page/4/Picture/0 description: The image shows the logo for i-sens. The logo consists of the letter "i" in blue, with a green circle above it. The word "sens" is written in blue next to the "i". The logo is simple and modern.

510(k) Summary

Introduction 1.

This summary of 510(k) information is being submitted in accordance with requirements of 21 CFR Part 807.92.

1.1	Type of 510(k):	Traditional 510(k)
1.2	Submitter Information:	i-SENS, Inc.43, Banpo-daero 28-gil, Seocho-gu, Seoul, KoreaTel.) +82-2-910-0453Fax) +82-2-942-2514e-mail: jhjung@i-sens.comContact Person: Joon Ho Jung
1.3	Prepared Date:	April 3, 2018

2. Device Name

2.1 Trade Name	KetoSens Blood β-Ketone Monitoring System
	KetoSens Multi Blood β-Ketone Monitoring System
2.2 Classification Name	JIN - Class I, 21 CFR 862.1435 Ketones (nonquantitative) test system
	Meets limitations of exemptions 21 CFR 862.9(c)(5)
2.3 510k Number	K170463

KetoSens Blood B-Ketone Monitoring System and KetoSens Multi Blood B-Ketone Monitoring System are essentially the same product in exception to the product name. The two systems include the same meter, test strips, and control solution with the only difference in the names due to the different indications for use (single vs. multiple-patient use). Due to the nature of the similarities, the candidate device's name of KetoSens Blood ß-Ketone Monitoring System will be used as a representative of the two devices in this submission.

Device Description 3.

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The following items are included in the KetoSens Blood ß-Ketone Monitoring System:

1 KetoSens Blood ß-Ketone Meter
1 Lancing device
10 Lancets
Carrying Case
1 Owner's Booklet
1 Quick Reference Guide
2 Batteries (3.0V lithium batteries)

The following items are included in the KetoSens Multi Blood ß-Ketone Monitoring System:

KetoSens Multi Blood ß-Ketone Meter
1 Owner's Booklet
2 Batteries (3.0V lithium batteries)
Carrying Case

The following items is compatible with the KetoSens Blood ß-Ketone Monitoring System and KetoSens Multi Blood ß-Ketone Monitoring System and is available separately.

KetoSens (Multi) Blood ß-Ketone Test Strips -
The KetoSens ß-Ketone Control Solution (Level A and B)

Intended Use 4.

4.1 KetoSens Blood ß-Ketone Monitoring System

KetoSens Blood ß-Ketone Monitoring System is intended to be used for the quantitative measurement of {}-Ketone (beta-hydroxybutyrate) level in capillary whole blood samples drawn from the fingertip. The KetoSens Blood ß-Ketone Monitoring Systems are for self-testing outside the body (for in vitro diagnostic use) in the home as an aid to monitor the effectiveness of diabetes control program. The system is not intended for use in the diagnosis of or screening for diabetes mellitus and is not intended for use on neonates. This system is intended to be used by a single person and should not be shared.

The KetoSens Blood ß-Ketone Test Strips work with the KetoSens Blood ß-Ketone Meter to quantitatively measure Blood ß-Ketone in capillary whole blood samples drawn from the fingertip.

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KetoSens Multi Blood ß-Ketone Monitoring System 4.2

KetoSens Multi Blood ß-Ketone Monitoring System is intended to be used for the quantitative measurement of ß-Ketone (beta-hydroxybutyrate) level in capillary whole blood from the fingertip and venous EDTA whole blood. KetoSens Multi Blood ß-Ketone Monitoring System is intended for in vitro diagnostic use and is intended for multiple-patient use in professional healthcare settings as an aid to monitor the effectiveness of diabetes control program. The system is not intended for use in the diagnosis of or screening for diabetes mellitus and is not intended for use on neonates. This system should only be used with singleuse, auto-disabling lancing devices.

The KetoSens Multi Blood ß-Ketone Test Strips work with the KetoSens Multi Blood ß-Ketone Meter to quantitatively measure Blood ß-Ketone in capillary whole blood samples drawn from the fingertip and venous whole blood drawn in professional healthcare settings.

Substantial Equivalence Information 5.

The candidate devices are comparable and substantially equivalent to the predicate device.

5.1 Predicate Device Name Nova Max Plus Blood Glucose and ß-Ketone Monitoring System Nova Max Blood Glucose and ß-Ketone Monitor -The Nova Max Plus Ketone Test Strips -
K091547 Predicate 510(k) Number 3.2

6. Comparison with Predicate Devices

Table 1. The Composition Comparison of the Candidate Devices with the Predicate device

Device Name	Nova Max Plus Blood Glucose andβ-Ketone Monitoring System( Predicate device )	KetoSens Blood β-KetoneMonitoring System( Candidate device )
Meter	Image: Nova Max Plus Blood Glucose Meter	Image: KetoSens Blood β-Ketone Monitoring System

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43, Banpo-daero 28-gil, Seocho-gu, Seoul, Korea

43, Banpo-daero 28-gil, Seocho-gu, Seoul, Korea
Tel: +82-2-916-6191 Fax: +82-2-942-2514

Device Name	Nova Max Plus Blood Glucose andβ-Ketone Monitoring System	KetoSens Blood β-KetoneMonitoring System
	(Predicate device)	(Candidate device)
Test Strips	Image: Nova Max Plus Blood Glucose and β-Ketone Monitoring System Test Strip	Image: KetoSens Blood β-Ketone Monitoring System Test Strip

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Image /page/8/Picture/0 description: The image shows the logo for i-sens. The logo is blue, except for a green dot above the "i". The text is sans-serif and bolded.

6.1 Similarities and Differences

The candidate device and the predicate device (Ketone) are classified under 21 CFR 862.1435, which states: "A ketones (nonquantitative) est system is a device intended to identify ketones in urine and other body fluids. Identification of ketones and treatment of acidosis (a condition characterized by abnormally high acidity of body fluids) or ketosis (a condition characterized by increased production of ketone bodies such as acetone) and for monitoring patients on kets and patients with diabetes." The predicate device has the capacity to measure both glucose as well as {}- ketone in blood, whereas the can'y measures }- ketone. Substantial equivalence is claimed for the ketone measurement parameter of the predicate device since the of the devices are identical in terms of measuring ketone, and the indications only differ in glucose measuring capabilities between the candidate device and the predicate device.

The intended use for Ketone, operating principle, fundamental scientific technology of the candidate device. The list of similarities and differences between the candidate device and the predicate device are shown in Table 2:

Item	Nova Max Plus Blood Glucose andβ-Ketone Monitoring System(Predicate device)	KetoSens Blood β-Ketone Monitoring System(Candidate device)
Intended use	The Nova Max Plus Blood Glucose and β-KetoneMonitoring System Monitor is intended to be used for thequantitative measurement of glucose in fresh capillarywhole blood. It is intended for use by people withdiabetes mellitus in the home and by healthcareprofessionals in clinical settings as an aid to monitor theeffectiveness of diabetes control. It is not intended for usein the diagnosis of or screening for diabetes mellitus andis not intended for use on neonates. The Nova Max BloodGlucose and β-Ketone Monitor is specifically indicatedfor the quantitative measurement of glucose in freshcapillary whole blood samples obtained from thefingertip, forearm and palm and β-hydroxybutyrate (β-ketone) in capillary whole blood from the finger only.	Single-patient useKetoSens Blood β-Ketone Monitoring System is intended to beused for the quantitative measurement of β-Ketone (beta-hydroxybutyrate) level in capillary whole blood samples drawnfrom the fingertip. The KetoSens Blood β-Ketone MonitoringSystems are for self-testing outside the body (for in vitrodiagnostic use) in the home as an aid to monitor theeffectiveness of diabetes control program. The system is notintended for use in the diagnosis of or screening for diabetesmellitus and is not intended for use on neonates. This system isintended to be used by a single person and should not be shared.The KetoSens Blood β-Ketone Test Strips work with theKetoSens Blood β-Ketone Meter to quantitatively measureBlood β-Ketone in capillary whole blood samples drawn fromthe fingertip.
	The Nova Max Plus Ketone Test Strips are intended foruse only on the Nova Max Plus Blood Glucose and β-Ketone Monitor.Nova Max Plus Ketone Control Solutions are intended foruse with Nova Max Plus Blood Glucose and β-KetoneMonitor and Nova Max β-Ketone Test Strips as a qualitycontrol check to verify the accuracy of blood ketone testresults. There are three levels of controls, (Levels 1,2 and3).	The KetoSens β-Ketone Control Solutions are intended for usewith the KetoSens Blood β-Ketone meter and KetoSens Bloodβ-Ketone test strip to check that the meter and the test strip areworking together properly and that the test is performingcorrectly.Multiple-patient useKetoSens Multi Blood β-Ketone Monitoring System is intendedto be used for the quantitative measurement of β-Ketone (beta-hydroxybutyrate) level in capillary whole blood from thefingertip and venous EDTA whole blood. KetoSens Multi Bloodβ-Ketone Monitoring System is intended for in vitro diagnosticuse and is intended for multiple-patient use in professionalhealthcare settings as an aid to monitor the effectiveness ofdiabetes control program. The system is not intended for usein the diagnosis of or screening for diabetes mellitus and is notintended for use on neonates. This system should only be usedwith single-use, auto-disabling lancing devices.
		The KetoSens Multi Blood β-Ketone Test Strips work with theKetoSens Multi Blood β-Ketone Meter to quantitativelymeasure Blood β-Ketone in capillary whole blood samplesdrawn from the fingertip and venous whole blood drawn inprofessional healthcare settings.
		The KetoSens β-Ketone Control Solutions are intended for usewith the KetoSens Multi Blood β-Ketone meter and KetoSensMulti Blood β-Ketone test strip to check that the meter and thetest strip are working together properly and that the test isperforming correctly.
Fundamental scientific technology
Operating principle	β-hydroxybutyrate (β- ketone) is converted by β-hydroxybutyrate dehydrogenase and the magnitude of	Same

Table 2. The Similarities and Differences between the Candidate Devices and the Predicate Device

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i·sens

i-SENS, Inc. 43, Banpo-daero 28-gil, Seocho-gu, Seoul, Korea Tel: +82-2-916-6191 Fax: +82-2-942-2514

Page 6 of 18

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	electrical current resulting from this enzymatic reaction
	is proportional to the amount of β-hydroxybutyrate
	present in the sample.
Assay method	Electrochemical	Same
Active reagent	β-hydroxybutyrate dehydrogenase	Same
Test measured	Blood Glucose and β-Ketone	Blood β-Ketone
Technical specifications
Sample type	Fresh capillary whole blood (fingertip)	Fresh capillary whole blood (fingertip)Venous EDTA whole blood (multi-patient use only)
Hematocrit range	25%-60%	20%-55%
OperatingTemperature Range	59°F - 86°F	50 °F ~ 104 °F
Operating RelativeHumidity	10%- 90% RH	Same
Test time (sec.)	10	8
Memory capacity	Up to 400	Up to 1,000
Power source	3 volt coin cell battery CL 2450	Two 3.0 V lithium batteries (CR2032)
Weight	2.65 oz	2.53 oz (with batteries)
Test range	0.1 - 8.0 mmol/L	Same
Controls	Nova Max Max Plus Ketone Control Solutions(Levels 1, 2, and 3)	KetoSens β-Ketone Control Solutions(Level A and B)
Coding	No User Input required for Nova Max	No coding required (Automatic code identification)

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Image /page/11/Picture/0 description: The image shows the logo for i-sens. The "i" is green and the rest of the word is blue. The logo is simple and modern.

7. Risk Analysis

We have performed a risk analysis to confirm that risks determined from Preliminary Risk Analysis and severty and to show detailed countermeasures information, warning, indication and design. Based on risk analysis results, we've conducted the performance evaluation tests to confirm the safety and effectiveness of the candidate device.

Validation Activity Summary for the Candidate Device 8.

We have conducted the following validation tests to confirm that the candidate device works properly. Table 4 is the summary of the software validation test results for the candidate device. The tests were conducted for Ketone Monitoring System software.

Test ID and name	Validation activities descriptions	Test results summary
MR16-014_3~06Performance Test (Drop,Vibration, Temperature andHumidity exposure limits tests)	Test the performance of meter bydropping, vibrating, and exposing to highor low temperature and high humidity.After the test, check the measurement andoperation performance.	Measurement and operation performance ofall meters passed the tests.
BKM-031F-R021-3Software Function Test	Test the performance of meter based on setcriteria.	100% Compliance
BKM-031F-R022-3Memory Test Report	1st Test is to confirm if the meter operatescorrectly in full occupied memorycondition.2nd Test is to confirm if the memoryrecords and recalls the measured data andcalculates average data correctly. 3rd Testis to confirm if the meter calculatesaverage value on leap year correctly.	Average calculated by meter softwareexactly matched with average calculatedmanually.
BKM-031F-R023-3	To check if the clock is runningaccurately for a period of time	It is confirmed that the time differentialbetween the meter and international

Table 3. Software Validation Summary

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Test ID and name	Validation activities descriptions	Test results summary
Time Test Report		standard time is within ±15 sec. Therefore, Time function of the meter has been verified.
BKM-031F-R024-3DAC Function Test Report	To verify that the reference voltage of the work electrode is 200 mV.	Test result shows that DAC function of the meter has been verified through 10 meters. Therefore, DAC function of the meter has been verified.
BKM-031F-R025-3Measurement Timing and ADCTest Report	To verify if the Measurement timing and ADC function works correctly corresponding to the requirement specification.	Test results confirmed that Measurment timing and ADC function of KetoSens has been verified.
BKM-031F-R026-3Code Identification Test Report	To verify the automatic code identification (no coding) function of the meter works properly.	Test result shows that code #1~15 have been correctly identified by all meters.
BKM-031F-R027-3Power Consumption Test Report	To verify the power consumption in various modes of the meter works properly.	Test result confirmed that the meter has been verified through 10 meters.
BKM-031F-R028-3Battery Lifetime Test Report	To verify capable testing times on a continuous measurement condition.	Estimation of the number of times it is capable of testing based on the electrical current consumption and it is possible test about 7320 times. The actual measurement testing was conducted with 2EA the samples. It is assured that the model is capable of testing 3000 times.

Performance Evaluation Summary of the Candidate Device 9.

9.1 Repeatability Test (Report No. BKM-031F-R001)

The purpose of repeatability test is to confirm the precision of Ketone Monitoring System through evaluating test results of blood

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samples obtained by the same user using multiple meters and strip lots.

Concentration(mmol/L)	N	Mean(mmol/L)	SD(mmol/L)	%CV
0.4	300	0.39	0.027	6.8
1.1	300	1.08	0.056	5.1
3.4	300	3.38	0.126	3.7
5.2	300	5.16	0.182	3.5
6.9	300	6.91	0.248	3.6

Summary results of repeatability test for the KetoSens Blood β-Ketone Monitoring System

Conclusion:

The pooled SD of concentration intervals 1, 2 were 0.027, 0.056mmo/L respectively that were below 0.075 mmo/L. The pooled CV % of concentration intervals 3, 4 and 5 were 3.7, 3.5 and 3.6%, respectively that were below 5.0 %.

Intermediate Precision Test (Report No. BKM-031F-R002) 9.2

The purpose of this intermediate precision test is to evaluate the test dates, other uses, and results tested with other meters in a similar environment using KetoSens Blood {}-Ketone Monitoring System (BKMS) and control solution.

Organized results for each lot and results summed up

ControlLevel	N	Mean(mmol/L)	SD(mmol/L)	%CV
Level 1	600	0.63	0.049	7.7
Level 2	600	2.23	0.085	3.8
Level 3	600	4.04	0.173	4.3

Page 10 of 18

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Conclusion:

The pooled SD for concentration interval 1 was 0.049mmol/L that is less than 0.075mmol/L, and the pooled CV for interval 2, 3 were 3.8, 4.3, respectively that are below 5.0 %.

Linearity Test (Report No. BKM-031F-R003) 9.3

The purpose of conducting linearity test is to demonstration range (from 0 mmol/L to 8.0 mmo/L) of KetoSens Blood f-Ketone Monitoring System and confirm linearity through Linearity Study.

Table 3. Summary results of Linearity test

Strip lot. ML07KEA05B : y = 1.0034x - 0.0145, r2 = 0.9987 Strip lot. ML07KEA10C : y = 1.0250x - 0.0466, r2 = 0.9982 Strip lot. ML08KEA07B : y = 1.0209x - 0.0323, r2 = 0.9982 Total 3 strip lots: y = 1.0159x -0.0303, r2 = 0.9985

Conclusion:

Linearity test was conducted by measuring the ketone level in the whole blood samples usings. These results were able to obtain the following linear equation and the coefficient of determination (x2) was able to confirm a high linear correlation above 0.95.

System Accuracy Test (Report No. BKM-031F-R004) 9.4

The purpose of conducting system accuracy of KetoSens Blood Ketone Monitoring System (BKMS) through clinical evaluation using capillary and venous blood samples. The acuracy of KetoSens is evaluated with capillary blood samples collected from a minimum of 200 sample is evaluated with each of strip lots on one meters run with the KetoSens BKMS and with the standard measurement.

Item	Result
ketoneconcentration< 1.5 mmol/L	Within ± 0.15 mmol/L	Within ± 0.225 mmol/L	Within ± 0.3 mmol/L

Summary results of system accuracy test (Capillary blood)

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	163/171(95.3%)	169/171(98.8%)	170/171(99.4%)
ketoneconcentration≥ 1.5 mmol/L	Within± 5 %	Within± 10 %	Within± 20 %
	11/33(33.3%)	23/33(69.7%)	33/33(100%)

All of 204 capillary blood samples (100 %) fell within either = 0.3 mmol/L of the reference measurement procedure at ketone concentrations < 1.5 mmol/L or within ± 20 % at ketone concentrations ≥ 1.5 mmol/L.

Item	Result
ketoneconcentration< 1.5 mmol/L	Within ± 0.15mmol/L166/169(98.2%)	Within ± 0.225mmol/L168/169(99.4%)	Within ± 0.3mmol/L169/169(100%)
ketoneconcentration≥ 1.5 mmol/L	Within± 5 %18/35(51.4%)	Within± 10 %28/35(80.0%)	Within± 15 %34/35(97.1%)
			Within± 20 %35/35(100%)

Summary results of system accuracy test (Venous blood)

All of 204 venous blood samples (100 %) fell within either ± 0.3 mmol/L of the reference measurenent procedure at ketone concentrations < 1.5 mmol/L or within ± 20 % at ketone concentrations ≥ 1.5 mmol/L.

Hematocrit effect test (Report No. BKM-031F-R005) 9.5

The purpose of this hematocri effect test is to evaluate the effect various heronoming of Ketone testing of Ketone Monitoring System (BKMS). Five different hematocrit levels (20, 30, 42, 50 and 60%) are tested to evaluate the effect of hematocrit level on measurement of ketone concentration. Each of 5 different ketone intervals (in Table 2) is prepared in Twe define concentration is measured using 30 meters and 3 lots of test strips. 10 meters are assigned to each strip lot.

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Summary results of hematocrit effect test
Range (mmol/L)	Average of 3 lots difference(Hct 20 ~ 60%)
0.0 to 0.8	-0.09~0.02
1.0 to 2.0	-7.39~7.83
2.5 to 3.5	-10.33~9.05
4.0 to 5.0	-13.49~10.72
5.5 to 6.5	-15.02~8.73

ry results of hematocrit effect test

Conclusion:

The hematocrit biases of KetoSens BKMS evaluated (-0.09 ~ 0.02) mmoVL at interval 2, (-10.33 ~ 9.05%) at interval 3, (-13.49 ~ 10.72%) at interval 4 and (-15.02 ~ 8.73%) at interval 5 of hematocrit levels 20 ~ 60%. Thus, the KetoSens BKMS is safe to use with samples containing various levels of hematocrit.

Consumer Study (Report No. BKM-031F-R007) 0.6

The purpose of conducting Consumer Study is to evaluate the reads manual, and usability of KetoSens Blood Ketone Monitoring System (BKMS) with accuracy in actual conditions of use. Target users are from various backgrounds in ages and etc. Study subjects are provided with KetoSens BKMS user manual and are allowed to read through the meter. Study subjects perform ketone testing on their own and their testing results are to be compared with the Rx Imola reference values, and also BKMS results obtained by trained staff.

General user test results
Within ± 0.15 mmol/L	Within ± 0.225 mmol/L	Within ± 0.3 mmol/L
183/185(98.9%)	185/185(100%)	185/185(100%)

Trained user test results
Within ± 0.15 mmol/L	Within ± 0.225 mmol/L	Within ± 0.3 mmol/L

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185/185(100%)	185/185(100%)	185/185(100%)
---------------	---------------	---------------

Conclusion:

Total of 185 general users participated in this study. Test subjects were able to perform ketone BKMS on their own by refering to the guidelines in the user manual. These results with Rx Inola reference results and KetoSens BKMS satisfied the system accuracy requirements. Test participants were from various in terms of age, gender, educational level and etc. Regardlessly, the comprehension level of KetoSens BKMS user manual was high. No one answered the use difficult. All of the test participants were able to use KetoSens BKMS correctly and with accurate results. In users have no problem in using KetoSens BKMS in actual conditions of use, and are able to obtain accurate ketone readings with the guidelines in the user manual. In conclusion, lay users have no problem in using. KetoSens BKMS in actual conditions of use, and are able to obtain accurate ketone readings with the help of the user manual.

Point-of-Care Test Report (BKM-031F-R008) 9.7

The purpose of conducting Point-of-care test is to evability of KetoSens Multi Blood Ketone Monitoring System by the health care professionals. The accuracy of the BKMS as well as the readability of the user's manual were assessed. This study is conducted at three different sites. The study sites chosen are hospitals for diast two Health Care Professionals perform the blood ketone tests using the KetoSens Multi BKMS at each site. Test participants (sample providers) are diabetic individuals. Health care professionals are provided with the English version of KetoSens Multi BKMS user manual and are allowed to read through the manual. perform blood ketone testing using KetoSens Multi the capillary and venous blood samples without any help from the trained study staff. The study staff operates the reference equipment and modify the KetoSens Multi BKMS results are compared against the reference values.

β-Ketone concentration <1.5 mmol/L
Within ± 0.15 mmol/L	Within ± 0.225 mmol/L	Within ± 0.3 mmol/L
115/124 (92.7%)	121/124 (97.6%)	124/124 (100%)
β-Ketone concentration ≥1.5 mmol/L
Within ±5%	Within ±10%	Within ±15%	Within ±20%
2/12 (16.7%)	8/12 (66.7%)	11/12 (91.7%)	12/12 (100%)

Venous test
ß-Ketone concentration <1.5 mmol/L
results Within ± 0.15 mmol/L/	Within ± 0.225 mmol/L	Within ± 0.3 mmol/L
113/123 (91.9%)	118/123 (95.9%)	121/123 (98.4%)

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β-Ketone concentration ≥1.5 mmol/L
Within ±5%	Within ±10%	Within ±15%	Within ±20%
7/13 (53.8%)	12/13 (92.3%)	13/13 (100%)	13/13 (100%)

Conclusion:

POC test is performed by six menbers of Health Care Professional with KetoSens multi Blood β-Ketone monitoring systems (BKMS) at three sites. They have conducted performance test on KetoSens multi a total number of 123 patients, and measured ketone level of patients based only on the manual provided. The KetoSens multi BKMS result is compared against the reference values with Randox Imola, the reference instrument. The comprehension level of KetoSens manual was high. No one answered the use of KetoSens BKMS was diffealt. All of the test HCPs were able to use KetoSens multi accurate results. In conclusion, HCPs have no problems in using the KetoSens multi BKMS in actual conditions of use, and are able to obtain accurate ketone readings with the instructions of the user manual.

7.7 Interference Test (Report No. BKM-031F-R006)

The purpose of this interference test is to evaluate the effect interfering substances have on the blood ketone measurements of KetoSens Blood p-Ketone Monitoring System (BKMS). This interference to evaluate the effect of various interfering substances in whole blood samples on ketone measurements.

Two ketone concentrations within the intervals (0.0 ~ 3.5 mmol1) were prepared in blood samples. 29 types of interferents are tested in this test. Stock solution is prepared for each interest using PBS (Phosphate Buffered Saline, pH 7.4) as a solvent. In the case of interferents that do not dissolve in PBS, 0.1M NaOH is used. To minimize change in the matrix when stock solution for each interferent is added, it is prepared by concentrating as much as possible. Each sample is divided into two portions (control and test samples) with respect to one interferent. A concentrated solution of the interferent is added to the solvent used for dissolving the interference substance

is added to the control sample.

	Difference (mmol/L or %)
Interferent	Interval 1 (0.0 ~ 0.8 mmol/L)			Interval 2 (2.0 ~ 3.5 mmol/L)
	Strip lot:	Strip lot:	Strip lot:	Strip lot:	Strip lot:	Strip lot:
	NF19KEA01A	NF25KEA01A	NF26KEA01A	NF19KEA01A	NF25KEA01A	NF26KEA01A
Acetaminophen	-0.06	-0.03	-0.02	-5.4	-8.3	-7.0
Ascorbic acid	0.06	0.06	0.03	-0.4	-0.4	1.5

Difference averages interference test

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i·sens

i-SENS, Inc. 43, Banpo-daero 28-gil, Seocho-gu, Seoul, Korea Tel: +82-2-916-6191 Fax: +82-2-942-2514

Bilirubin	0.03	0.03	0.06	-6.2	-7.4	-7.1
Cholesterol	0.00	0.01	0.01	0.3	1.0	-1.8

	Difference (mmol/L or %)
	Interval 1 (0.0 ~ 0.8 mmol/L)			Interval 2 (2.0 ~ 3.5 mmol/L)
Interferent	Strip lot:NF19KEA01A	Strip lot:NF25KEA01A	Strip lot:NF26KEA01A	Strip lot:NF19KEA01A	Strip lot:NF25KEA01A	Strip lot:NF26KEA01A
Creatinine	-0.04	-0.03	-0.06	3.0	3.0	4.3
Dopamine	0.02	-0.02	0.01	0.9	-3.6	-0.7
EDTA	-0.02	-0.08	-0.06	-2.4	-5.0	-6.2
Galactose	0.01	-0.03	-0.01	0.1	0.9	2.2
Gentisic acid	-2.04	-2.07	-2.03	4.1	-3.1	-0.9
Hemoglobin	-0.10	-0.10	-0.10	-1.8	-2.2	-3.2
Heparin	0.00	-0.04	-0.07	-2.5	-3.3	-1.8
Ibuprofen	0.04	0.03	-0.01	0.9	0.2	-0.2
L-Dopa	-0.03	-0.05	-0.02	-2.5	-0.7	-2.1
Maltose	0.07	0.04	0.07	3.4	1.0	2.0
Methyldopa	0.03	0.05	0.00	2.0	-0.8	-2.1
Salicylate	0.00	-0.01	-0.07	0.7	-1.2	-0.8
Tolazamide	-0.07	-0.01	0.01	-7.5	-4.6	-2.7
Tolbutamide	-0.03	-0.06	-0.04	4.3	2.2	3.6
Triglycerides	-0.01	-0.04	0.03	0.6	-0.2	3.9
Uric acid	-0.06	0.00	-0.02	-0.4	-2.5	-5.4
Xylose	0.01	0.02	0.00	1.6	0.9	0.2
Glutathione(Red)	-0.02	-0.01	-0.02	-1.4	0.5	-2.0
Catopril	-0.04	-0.02	0.00	-2.3	-3.1	-2.9
Tetracycline	-0.02	-0.05	-0.05	-0.7	-3.2	-3.6
Glucose	-0.03	-0.03	0.01	-1.1	-3.2	0.6
Acetone	-0.01	0.00	0.02	-3.4	1.9	0.7
Acetoacetate	-0.06	0.00	0.00	-0.1	1.0	-1.8

7.8 Altitude test report (Report No. BKM-031F-R009)

The purpose of performing altitude test is to evaluate the capability of Ketone Monitoring System (BKMS) to operate normally and to

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obtain accurate blood ketone test results at high altitudes (approximately 10,000 feet or 3048m) where the partial pressure of inspired oxygen in the blood decreases.

Conclusion:

KetoSens BKMS did not show significant difference with respect to the Rx Imola equipment, nor with different altitudes at all ketone concentrations. Hence it was confirmed that our BKMS have no systematic response to altitudes and is not significantly affected by lack of atmospheric oxygen up to 10,000 feets (3,048m) above the sea level.

7.9 Operating Condition Test (Temperature and Humidity Exposure) (Report No. BKM-031F-R016)

To evaluate the performance of Ketone Monitoring System (BKMS) in the specified operating condition (Temperature and humidity range). Operation condition test is evaluating the performance of KetoSens BKMS within the recommended temperature (10 °C) and humidity (10 % ~ 90 %) in actual conditions of use.

Conclusion:

Operating condition test was conducted at 9 combined temperature-humidity conditions of 10 °C, 15 °C, 30°, 40% and 90% RH. We have confirmed that KetoSens BKMS operates normally at the presented conditions, individual meter measurements giving less than 0.03 mmol/L or 20 % bias from Rx Imola reference results.

Sample Volume (Report No. BKM-031F-R014) 7.10

This is to verify the minimum sample volume used in KetoSens Blood (3-Ketone Monitoring System (BKMS) through testing.

Conclusion

Sample volume test was performed using wholes from 3 subjects, each divided three concentration intervals. When 0.4 uL of sample was applied to the strip, Er 4 messages appeared.

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7.11 Real lifetime test (Report No. BKM-031F-R018)

The purpose of Real-lifetime shelf-life test is to study the stability of KetoSens test and to establish expiry date before opening foil (before being put into use). Three lots of three temperatures of recommended strip storage temperatures (4 °C, 23 °C and 30 °C) at three humidity levels. The study is conducted using blood samples of three ketone concentrations. At every tessing point, strip foil are removed from the designated storage condition. The bias of meter measurement result is compared against the reference values (Rx Imola measurement results) at every ime point, and when the bias exceeds 0.225 mmo/L(for ketone concentration under 1.5 mmo/L) or 10% (for ketone concentration above 1.5 mmol/L), the stability of strip is deemed to have diminished, and the study is initially designed to be conducted for more than 18 months.

Conclusion:

Stability of KetoSens strip in foil packaging was studied for 499 days using blood samples of 3 ketone concentrations.

10. Conclusion

Based on the validation study and the performance evaluations, the candidate devices, KetoSens Monitoring System, is as safe and effective as the predicate device. The results of the KetoSens Blood 3-Ketone Monitoring System is substantially equivalent to the predicate device, Nova Max Plus Blood Glucose and ß-Ketone Monitoring System.

Regulation Number and Section

§ 862.1435 Ketones (nonquantitative) test system.

(a)
Identification. A ketones (nonquantitative) test system is a device intended to identify ketones in urine and other body fluids. Identification of ketones is used in the diagnosis and treatment of acidosis (a condition characterized by abnormally high acidity of body fluids) or ketosis (a condition characterized by increased production of ketone bodies such as acetone) and for monitoring patients on ketogenic diets and patients with diabetes.(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.