KetoSens Blood B-Ketone Monitoring System, KetoSens Multi Blood B-Ketone Monitoring System

K170463 · I-Sens, Inc. · JIN · Apr 13, 2018 · Clinical Chemistry

Device Facts

• Record ID: K170463
• Device Name: KetoSens Blood B-Ketone Monitoring System, KetoSens Multi Blood B-Ketone Monitoring System
• Applicant: I-Sens, Inc.
• Product Code: JIN · Clinical Chemistry
• Decision Date: Apr 13, 2018
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1435
• Device Class: Class 1
• Attributes: Pediatric

Indications for Use

KetoSens Blood β-Ketone Monitoring System is intended to be used for the quantitative measurement of β-Ketone (beta-hydroxybutyrate) level in capillary whole blood samples drawn from the fingertip. The KetoSens Blood β-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 β-Ketone Test Strips work with the KetoSens Blood β-Ketone Meter to quantitatively measure Blood β-Ketone in capillary whole blood samples drawn from the fingertip. KetoSens Multi Blood β-Ketone Monitoring System is intended to be used for the quantitative measurement of β-Ketone (beta-hydroxybutyrate) level in capillary whole blood from the fingertip and venous EDTA whole blood. KetoSens Multi Blood β-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 β-Ketone Test Strips work with the KetoSens Multi Blood β-Ketone Meter to quantitatively measure Blood β-Ketone in capillary whole blood samples drawn from the fingertip and venous whole blood drawn in professional healthcare settings.

Device Story

System measures β-hydroxybutyrate in capillary or venous whole blood via electrochemical biosensor technology; uses test strips with β-hydroxybutyrate dehydrogenase enzyme. Meter generates small electrical current proportional to ketone concentration. Used in home (self-test) or professional healthcare settings (Multi version). Healthcare providers/patients use output to monitor diabetes control programs. Provides quantitative ketone levels; aids in managing ketosis/acidosis. Includes meter, test strips, control solutions, lancing device. Multi version requires single-use, auto-disabling lancing devices for infection control.

Clinical Evidence

Bench testing included precision (repeatability %CV 3.5-6.8%; intermediate precision %CV 3.8-7.7%), linearity (R² > 0.998), and interference studies. POC study (n=136) and lay user study (n=185) compared device results to Randox RANBUT d-3-Hydroxybutyrate assay. POC study showed 100% of results within ±0.30 mmol/L for <1.5 mmol/L range and 100% within ±20% for ≥1.5 mmol/L range. Lay user study showed 100% within ±0.225 mmol/L for <1.5 mmol/L range. No clinical data on diagnostic sensitivity/specificity provided as device is for monitoring, not diagnosis.

Technological Characteristics

Electrochemical biosensor; β-hydroxybutyrate dehydrogenase enzyme. Measures 0.1-8.0 mmol/L. Hematocrit range 20-55%. Power: two 3.0V lithium batteries (CR2032). Automatic code identification. Connectivity: standalone meter. Sterilization: not specified. Software: embedded firmware for data processing and memory storage (up to 1,000 records).

Indications for Use

Indicated for quantitative measurement of β-hydroxybutyrate in capillary whole blood (fingertip) and venous EDTA whole blood (Multi version only) to monitor diabetes control effectiveness. Not for diagnosis/screening of diabetes mellitus. Not for use on neonates. Single-patient use (KetoSens) or multiple-patient use (KetoSens Multi) in professional settings.

Regulatory Classification

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.

Predicate Devices

• Nova Max Plus Blood Glucose and β-Ketone Monitoring System (k091547)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE

A. 510(k) Number:
k170463

B. Purpose for Submission:
New device

C. Measurand:
β-Ketone, as beta-hydroxybutyrate, in fingertip capillary whole blood and venous EDTA whole blood

D. Type of Test:
Quantitative amperometry, β-Ketone (beta-hydroxybutyrate)

E. Applicant:
i-SENS, Inc.

F. Proprietary and Established Names:
KetoSens Blood β-Ketone Monitoring System
KetoSens Multi Blood β-Ketone Monitoring System

G. Regulatory Information:
1. Regulation section:
21 CFR §862.1435, Ketones (nonquantitative) test system
2. Classification:
Class I, meets limitations of exemptions 21 CFR §862.9(c)(5)
3. Product codes:
JIN, Nitroprusside, Ketones (urinary, non-quant.)

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4. Panel:
Clinical Chemistry, 75

H. Intended Use:

1. Intended use(s):
See indication(s) for use below.

2. Indication(s) for use:

KetoSens Blood β-Ketone Monitoring System is intended to be used for the quantitative measurement of β-Ketone (beta-hydroxybutyrate) level in capillary whole blood samples drawn from the fingertip. The KetoSens Blood β-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 β-Ketone Test Strips work with the KetoSens Blood β-Ketone Meter to quantitatively measure Blood β-Ketone in capillary whole blood samples drawn from the fingertip.

KetoSens Multi Blood β-Ketone Monitoring System is intended to be used for the quantitative measurement of β-Ketone (beta-hydroxybutyrate) level in capillary whole blood from the fingertip and venous EDTA whole blood. KetoSens Multi Blood β-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 β-Ketone Test Strips work with the KetoSens Multi Blood β-Ketone Meter to quantitatively measure Blood β-Ketone in capillary whole blood samples drawn from the fingertip and venous whole blood drawn in professional healthcare settings.

3. Special conditions for use statement(s):

For the KetoSens Blood β-Ketone Monitoring System:

- The system should not be used to test neonates.
- Do not test samples other than fresh capillary whole blood obtained from the fingertip.

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- Do not use the system at altitudes above 10,000 feet (3000 meters).
- Do not use when Hematocrit is outside the acceptable hematocrit range for testing of 20% to 55%.
- Severe dehydration (excessive water loss) may cause inaccurate results. If you believe you are suffering from severe dehydration, consult your healthcare professional immediately.
- For in vitro diagnostic use only.
- Critically ill patients should not be tested with this device.
- Inaccurate results may occur in severely hypotensive individuals or patients in shock.
- Incorrect result may occur in individuals who are dehydrated.
- The meter and lancing device are for single patient use. Do not share these items with anyone, including other family members! Do not use on multiple patients!
- Do not reuse; each test strip is for single use only.
- Do not use when humidity is higher than 90% and lower than 10%, as extremes in humidity may affect results.
- For single patient use only.
- For over-the-counter use
- The system is not intended for use in the diagnosis of or screening for diabetes mellitus.

For the KetoSens Multi Blood β-Ketone Monitoring System:
- For prescription use only
- The system should not be used to test neonates.
- Do not test samples other than fresh capillary whole blood obtained from the fingertip or venous EDTA whole blood.
- Do not use at altitudes above 10,000 feet (3000 meters).
- Do not use when Hematocrit is outside the acceptable hematocrit range for testing of 20% to 55%.
- Severe dehydration (excessive water loss) may cause inaccurate results. If you believe you are suffering from severe dehydration, consult your healthcare professional immediately.
- For in vitro diagnostic use only.
- Critically ill patients should not be tested with this device.
- Inaccurate results may occur in severely hypotensive individuals or patients in shock.
- Incorrect result may occur in individuals who are dehydrated.
- Do not reuse; each test strip is for single use only.
- This system should only be used with single-use, auto-disabling lancing devices.
- Do not use when humidity is higher than 90% and lower than 10%, as extremes in humidity may affect results.
- The system is not intended for use in the diagnosis of or screening for diabetes mellitus

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4. Special instrument requirements:

KetoSens Blood β-Ketone Meter

KetoSens Multi Blood β-Ketone Meter

I. Device Description:

The KetoSens Blood β-Ketone Monitoring System consists of the KetoSens Blood β-Ketone Meter, KetoSens Blood β-Ketone Test Strips, KetoSens β-Ketone Control Solutions (Level A and B), Lancing device, Lancets, Carrying Case, Owner's Booklet, Quick Reference Guide, and two lithium batteries. The system is for self-testing. The KetoSens Blood β-Ketone Test Strips and KetoSens β-Ketone Control Solutions (Level A and B) are purchased separately.

The KetoSens Multi Blood β-Ketone Monitoring System consists of the KetoSens Multi Blood β-Ketone Meter, KetoSens Multi Blood β-Ketone Test Strips, KetoSens β-Ketone Control Solutions (Level A and B), Owner's Booklet, two lithium batteries, and Carrying Case. The system is for multiple-patient testing. The KetoSens Blood β-Ketone Test Strips and KetoSens β-Ketone Control Solutions (Level A and B) are purchased separately.

J. Substantial Equivalence Information:

1. Predicate device name(s):

Nova Max Plus Blood Glucose and β-Ketone Monitoring System

2. Predicate 510(k) number(s):

k091547

3. Comparison with predicate:

| Similarities and differences | | |
| --- | --- | --- |
| Item | Candidate device
KetoSens Blood β-Ketone
Monitoring System
k170463 | Predicate device
Nova Max Plus Blood Glucose
and β-Ketone Monitoring
System
k091547 |
| Intended use | For the quantitative measurement of β-Ketone in whole blood as an aid to monitor the effectiveness of diabetes control program. | Same |
| Use type | Single-patient patient use | For Over-the-Counter use |
| Specimen | Capillary whole blood from the fingertip, and venous EDTA whole | Capillary whole blood from fingertip |

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| Similarities and differences | | |
| --- | --- | --- |
| Item | Candidate device KetoSens Blood β-Ketone Monitoring System k170463 | Predicate device Nova Max Plus Blood Glucose and β-Ketone Monitoring System k091547 |
| | blood | |
| Method | Amperometric | Same |
| Test strip active reagent | β-hydroxybutyrate dehydrogenase | Same |
| Analytical measurement range | 0.1 - 8.0 mmol/L | Same |
| Sample volume | 0.5 μL | 0.8 μL |
| Hematocrit range | 20% - 55% | 25% - 60% |
| Operating temperature | 50°F - 100°F | Same |
| Operating humidity | 10% - 90% RH | Same |
| Test Strip Calibration Coding | Auto-coding, no user input of calibration code required | Same |
| Similarities and differences | | |
| --- | --- | --- |
| Item | Candidate device KetoSens Multi Blood β-Ketone Monitoring System k170463 | Predicate device Nova Max Plus Blood Glucose and β-Ketone Monitoring System k091547 |
| Intended use | For the quantitative measurement of β-Ketone in whole blood as an aid to monitor the effectiveness of diabetes control program. | Same |
| Use type | Multiple patient use | For Over-the-Counter use |
| Specimen | Capillary whole blood from the fingertip, and venous EDTA whole blood | Capillary whole blood from fingertip |
| Method | Amperometric | Same |
| Test strip active reagent | β-hydroxybutyrate dehydrogenase | Same |
| Analytical measurement range | 0.1 - 8.0 mmol/L | Same |
| Sample volume | 0.5 μL | 0.8 μL |

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| Similarities and differences | | |
| --- | --- | --- |
| Item | Candidate device
KetoSens Multi Blood β-Ketone Monitoring System
k170463 | Predicate device
Nova Max Plus Blood Glucose and β-Ketone Monitoring System
k091547 |
| Hematocrit range | 20% - 55% | 25% - 60% |
| Operating temperature | 50°F - 100°F | Same |
| Operating humidity | 10% - 90% RH | Same |
| Test Strip Calibration Coding | Auto-coding, no user input of calibration code required | Same |

K. Standard/Guidance Document Referenced (if applicable):

CLSI EP05-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline.

CLSI EP6-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline.

CLSI EP07-A2, Interference Testing in Clinical Chemistry; Approved Guideline.

CLSI EP25-A Evaluation of Stability of In Vitro diagnostic reagents; approved guideline.

L. Test Principle:

The test principle of the KetoSens Blood β-Ketone Monitoring System/KetoSens Multi Blood β-Ketone Monitoring System is based on the amperometric detection of beta-hydroxybutyrate (also known as 3-hydroxybutyrate) in whole blood. β-hydroxybutyrate is converted by the enzyme β-hydroxybutyrate dehydrogenase to acetoacetate. The magnitude of electrical current resulting from this enzymatic reaction is proportional to the amount of β-hydroxybutyrate present in the sample.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

The only differences between the KetoSens Blood β-Ketone Monitoring System and KetoSens Multi Blood β-Ketone Monitoring System are the trade name and intended use (single-patient home use vs. multiple-patient use); therefore, performance testing conducted on the KetoSens Blood β-Ketone Monitoring System.

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# a. Precision/Reproducibility:

# Repeatability:

Venous EDTA whole blood was spiked with five different $\beta$ -hydroxybutyrate concentrations (0.4, 1.1, 3.4, 5.2, and $6.9~\mathrm{mmol / L}$ ) and tested on ten KetoSens Blood $\beta$ -Ketone meters. Ten replicates were tested per meter per concentration with each of three lots of test strips. The results are summarized below:

| 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 |

# Intermediate Precision:

Intermediate precision was evaluated by 10 operators using three lots of test strips. Each operator was provided with three KetoSens Blood $\beta$ -Ketone meters. Each meter was assigned to a test strip lot. Each operator conducted testing of three different test strip lots a day for 20 days using three $\beta$ -Ketone control solutions. The results are summarized below:

| Control Level | 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 |

# b. Linearity/assay reportable range:

The linearity of KetoSens Blood $\beta$ -Ketone Monitoring System was evaluated using venous EDTA whole blood spiked with $\beta$ -hydroxybutyrate. Nine whole blood samples were adjusted to the following $\beta$ -hydroxybutyrate concentrations: 0.1, 0.3, 0.7, 1.2, 2.1, 3.9, 5.7, 7.7, and $9.3~\mathrm{mmol / L}$ . The concentrations were assigned using the Randox RANBUT d-3-Hydroxybutyrate assay on the RX imola analyzer. The summary of the linear regression analysis for each lot was as follow:

Lot 1: $\mathrm{y} = 1.0034\mathrm{x} - 0.0145;\mathrm{R}^2 = 0.999$

Lot 2: $\mathrm{y} = 1.0250\mathrm{x} - 0.0466;\mathrm{R}^2 = 0.998$

Lot 3: $\mathrm{y} = 1.0209\mathrm{x} - 0.0323;\mathrm{R}^2 = 0.998$

The results of the study support the sponsor's claimed $\beta$ -Ketone measurement range

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of 0.1 to 8.0 mmol/L for both systems.

Validation testing was performed demonstrating that the meter displays ‘HI’ when the measurement result is greater than 8.0 mmol/L and ‘LO’ when the measurement result is less than 0.1 mmol/L.

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

**Traceability:**

The KetoSens Blood β-Ketone Monitoring System and KetoSens Multi Blood β-Ketone Monitoring System are traceable to an in-house standard prepared from commercially available control materials. The method comparison study was performed using the Randox RANBUT d-3-Hydroxybutyrate assay on the RX imola analyzer as the comparator method (see Section M.2.a.).

**Test strip stability:**

The KetoSens Blood β-Ketone Test Strips are provided in individual foil packages. The shelf life stability of the foil packaged test strips was assessed in real-time studies. The study protocol and acceptance criteria were reviewed and found acceptable to support the sponsor’s claimed stability of 15 months when stored under the recommended storage conditions of 39°F to 86°F (4 to 30°C) and relative humidity of 20 to 80%.

Because each test strip is individually packaged, open vial stability testing is not necessary.

d. Detection limit:

The β-Ketone measuring range is 0.1 to 8.0 mmol/L. The range is validated under the linearity study. See section M.1.b.

e. Analytical specificity:

Interference testing was performed to evaluate exogenous and endogenous substances using venous EDTA whole blood spiked at two β-hydroxybutyrate concentrations of 0.6 and 2.8 mmol/L. The samples were divided into two aliquots: control (with no added interferent) and test (with added interferent at a toxic level or 10 times the known therapeutic level). Each sample was measured using 20 KetoSens Blood β-Ketone meters and three test strip lots.

The sponsor defined no significant interference according to the following:

The following table lists the concentration of each substance at which no significant interference was detected. At the β-hydroxybutyrate concentration of 0.6 mmol/L the % bias ranged from -17% to 12%. At the β-hydroxybutyrate concentration of 2.8 mmol/L the % bias ranged from -8.3% to 4.3%. The following table lists the high concentrations at which no significant interference was observed:

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| Substance | Highest concentration tested at which no significant interference is observed (mg/dL) |
| --- | --- |
| Acetaminophen | 20 |
| Ascorbic acid | 3 |
| Bilirubin, | 20 |
| Cholesterol | 500 |
| Creatinine | 30 |
| Dopamine | 13 |
| EDTA | 200 |
| Galactose | 60 |
| Gentisic acid | 50 |
| Hemoglobin | 500 |
| Heparin, U/dL | 8000 |
| Ibuprofen | 40 |
| L-Dopa | 5 |
| Maltose | 1000 |
| Methyldopa | 10 |
| Salicylate | 60 |
| Tolazamide | 100 |
| Tolbutamide | 100 |
| Triglycerides | 3000 |
| Uric acid | 20 |
| Xylose | 25 |
| Reduced Glutathione | 20 |
| Catopril | 10 |
| Tetracycline | 30 |
| Glucose | 360 |
| Acetone | 60 |
| Acetoacetate | 10 |

f. Assay cut-off:

Not applicable.

2. Comparison studies:

a. Method comparison with predicate device:

Point of Care study:

To assess the performance of the KetoSens Multi Blood $\beta$-Ketone Monitoring System in the hands of the intended operators, a point of care (POC) study was conducted by

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six health care professionals at three POC sites.

The POC study was performed on 136 patients from the intended use population using six KetoSens Multi Blood $\beta$ -Ketone meters and three lots of KetoSens Multi Blood $\beta$ -Ketone test strips. Capillary blood was collected from each patient and analyzed once using the KetoSens Multi Blood $\beta$ -Ketone Monitoring System. Venous blood was collected from the same patient using an EDTA collection tube and analyzed once using the KetoSens Multi Blood $\beta$ -Ketone Monitoring System. The $\beta$ -Ketone measurements on the fingertip capillary whole blood and venous EDTA whole blood were compared to those obtained using the Randox RANBUT d-3-Hydroxybutyrate assay on the RX imola analyzer. To test specimens with $\beta$ -Ketone concentrations at the high end of the claimed measuring range, 12 of 136 of these were altered by spiking analyte into both capillary and venous whole blood samples. The results are summarized below:

# Fingertip capillary whole blood:

$\beta$ -Ketone concentration $&lt; 1.5$ mmol/L

| Within ± 0.15 mmol/L | Within ± 0.225 mmol/L | Within ± 0.30 mmol/L |
| --- | --- | --- |
| 115/124 (92.7%) | 121/124 (97.6%) | 124/124 (100%) |

$\beta$ -Ketone concentration $\geq 1.5$ 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 EDTA whole blood:

$\beta$ -Ketone concentration $&lt; 1.5$ mmol/L

| Within ± 0.15 mmol/L | Within ± 0.225 mmol/L | Within ± 0.30 mmol/L |
| --- | --- | --- |
| 113/123 (91.9%) | 118/123 (95.9%) | 121/123 (98.4%) |

$\beta$ -Ketone concentration $\geq 1.5$ mmol/L

| Within ±5% | Within ±10% | Within ±15% | Within ±20% |
| --- | --- | --- | --- |
| 7/13 (53.8%) | 12/13 (92.3%) | 13/13 (100%) | 13/13 (100%) |

The method accuracy was further analyzed by Passing-Boblok regression analysis. The results are given below.

Fingertip capillary whole blood:

| Site | n | Range | Slope | Intercept | R2 |
| --- | --- | --- | --- | --- | --- |
| 1 | 47 | 0.1 – 7.9 | 1.076 | -0.004 | 0.998 |
| 2 | 45 | 0.1 – 7.8 | 1.107 | -0.024 | 0.989 |
| 3 | 44 | 0.1 – 7.5 | 0.947 | 0.001 | 0.998 |
| All sites combined | 136 | 0.1 – 7.9 | 1.050 | -0.006 | 0.995 |

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Venous EDTA whole blood:

| Site | n | Range | Slope | Intercept | R² |
| --- | --- | --- | --- | --- | --- |
| 1 | 47 | 0.1 – 7.7 | 1.089 | -0.004 | 0.999 |
| 2 | 45 | 0.1 – 7.0 | 1.090 | -0.026 | 0.996 |
| 3 | 44 | 0.1 – 7.9 | 1.064 | -0.005 | 0.998 |
| All sites combined | 136 | 0.1 – 7.9 | 1.087 | -0.010 | 0.998 |

The usability of the system was assessed by a questionnaire given to the operators of the system following the conclusion of the study. The sponsor's analysis of the responses to the questionnaire found the comprehension level of KetoSens Multi Blood β-Ketone Monitoring System user manual was high and no operator thought the use of the system difficult.

b. Matrix comparison:

Not applicable.

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable.

b. Clinical specificity:

Not applicable.

c. Other clinical supportive data (when a. and b. are not applicable):

**Lay user study for OTC use:**

To assess the performance of the KetoSens Blood β-Ketone Monitoring System in the hands of the intended users, a lay user study was conducted with 185 lay user participants using three KetoSens Blood β-Ketone meters and three lots of KetoSens Blood β-Ketone test strips. Each lay user participants self-tested their fingertip capillary blood β-Ketone level unassisted, and was given only the instructions and training materials routinely provided with the system.

The lay user β-Ketone measurements were compared to those obtained by trained users using the Randox RANBUT d-3-Hydroxybutyrate assay on the RX imola analyzer. The range of β-Ketone concentrations across all subjects was 0.017 to 1.054 mmol/L (based on comparator method). Each sample was measured in singlicate. The results are summarized below:

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$\beta$ -Ketone concentration $&lt; 1.5 \mathrm{mmol} / \mathrm{L}$

| Within ± 0.15 mmol/L | Within ± 0.225 mmol/L | Within ± 0.30 mmol/L |
| --- | --- | --- |
| 183/185 (98.9%) | 185/185 (100%) | 185/185 (100%) |

The method accuracy was further analyzed by Passing-Boblok regression analysis. The results are given below.

$$
y = 0.994x - 0.007, R^2 = 0.970
$$

Readability Evaluation: The readability of the home use labeling was evaluated using a Flesch-Kincaid analysis and demonstrated that the grade level scores were less than $8^{\text{th}}$ grade.

4. Clinical cut-off:

Not applicable.

5. Expected values/Reference range:

Normal levels of $\beta$ -Ketone are $&lt; 0.6 \mathrm{mmol} / \mathrm{L}$ . $\beta$ -Ketone levels of $0.6 - 1.5 \mathrm{mmol} / \mathrm{L}$ are moderately elevated, $1.5 - 3.0 \mathrm{mmol} / \mathrm{L}$ indicates risk of ketoacidosis, and $&gt;3.0 \mathrm{mmol} / \mathrm{L}$ is usually accompanied by acidosis. From A. Rewers, Current Controversies in Treatment and Prevention of Diabetic Ketoacidosis, Advances in Pediatrics 57 (2010) 247-267.

N. Instrument Name:

KetoSens Blood $\beta$ -Ketone Meter

KetoSens Multi Blood $\beta$ -Ketone Meter

O. System Descriptions:

1. Modes of Operation:

Does the applicant's device contain the ability to transmit data to a computer, webserver, or mobile device?

Yes ☐ X ☐ or No ☐

Does the applicant's device transmit data to a computer, webserver, or mobile device using wireless transmission?

Yes ☐ X ☐ or No ☐

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2. Software:

FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types:

Yes ☐ X ☐ or No ☐

3. Specimen Identification:

There is no sample identification function with this device.

4. Specimen Sampling and Handling:

The KetoSens Blood β-Ketone Monitoring System is intended to be used with capillary whole blood from the fingertip or venous whole blood. The whole blood sample is applied directly to the test strip by capillary action.

5. Calibration:

There is no calibration required for the KetoSens Blood β-Ketone Monitoring System by the user.

6. Quality Control:

Two levels of KetoSens β-Ketone Control Solution are available and must be purchased separately. The kit box label states that controls are necessary but not included and must be purchased separately.

P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:

1. Hematocrit Study:

The effect of varying hematocrit level on the measurement of β-Ketone concentration was evaluated using venous EDTA whole blood samples with hematocrit levels of 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, and 60%. Five different β-hydroxybutyrate concentrations of 0.5, 1.6, 2.9, 4.2, and 6.1 mmol/L were prepared at each of the five different hematocrit levels. The β-Ketone concentration was measured using 30 meters and three lots of test strips. The % bias at each hematocrit level relative to a plasma sample of the same concentration run on the Randox RANBUT d-3-Hydroxybutyrate assay on the RX imola analyzer was calculated. The results support the claimed acceptable hematocrit range of 20 to 55%.

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2. **Altitude study:**

An altitude/oxygen dependency study was performed to assess the effect of low oxygen levels when the system is used at elevations above sea level. For testing, three different altitudes (0, 5000, and 10000 feet) were simulated. Venous whole blood was spiked to achieve three β-hydroxybutyrate concentrations (0.6, 2.4, and 4.9 mmol/L) as measured by the Randox RANBUT d-3-Hydroxybutyrate assay on the RX imola analyzer. Each sample was tested across three lots of test strips using 15 meters. The results demonstrated acceptable bias to support the claim that altitudes up to 10,000 feet have no significant effect on β-Ketone measurement with the KetoSens Blood β-Ketone Monitoring System.

3. **Temperature and Humidity Study:**

The sponsor performed operating condition studies to evaluate the operating temperature and relative humidity (RH) ranges. Venous whole blood samples at three β-hydroxybutyrate concentrations (0.5, 2.5, and 5.0 mmol/L) were evaluated using the KetoSens Blood β-Ketone Monitoring System. Each sample was tested at the temperature and humidity conditions shown below using 30 meters and three lots of ketone test strips for a total of 30 replicates per temperature/humidity condition. The results were compared with those obtained using the Randox RANBUT d-3-Hydroxybutyrate assay on the RX imola analyzer was calculated.

50°F (10°C) and 10% RH, 40% RH, 90% RH
59°F (15°C) and 10% RH, 40% RH, 90% RH
73°F (23°C) and 10% RH, 40% RH, 90% RH
86°F (30°C) and 10% RH, 40% RH, 90% RH
104°F (40°C) and 10% RH, 40% RH, 90% RH

The results support the sponsor’s claimed operating temperature range of 50°F to 104°F and operating relative humidity range of 10 to 90%.

4. **Sample Volume Study:**

A sample volume study was conducted to verify the minimum sample volume required for the KetoSens Blood β-Ketone Monitoring System. Three venous whole blood samples were spiked to β-hydroxybutyrate concentrations of 0.7, 2.4, and 4.4 mmol/L, as measured by the Randox RANBUT d-3-Hydroxybutyrate assay on the RX imola analyzer, to evaluate the effect of different sample volumes (0.4, 0.5, 0.6, and 1.0 μL) on the accuracy performance of the device and validation of error message when sample volume is too low. Three lots of test strips and 5 meters were used. Results from the study support the claimed minimum sample volume of 0.5 μL and that the insufficient volume error message (Er4) functioned as intended.

5. **Infection Control Studies:**

The KetoSens Blood β-Ketone Monitoring System is intended for single-patient use, and the KetoSens Multi Blood β-Ketone Monitoring System is intended for multiple-patient use. Disinfection efficacy studies were performed on the materials comprising the meters by an outside commercial laboratory service to demonstrate complete inactivation of

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hepatitis B virus (HBV) with Clorox Healthcare Bleach Germicidal Wipes (EPA Reg. No. 67619-12). Robustness studies were performed by the sponsor demonstrating that there were no changes in performance or to the external materials of the meters after 10,950 cleaning and 10,950 disinfection cycles with Clorox Healthcare Bleach Germicidal Wipes. The robustness studies were designed to simulate 5 years of single-patient use and 3 years of multiple-patient use. Labeling was reviewed for adequate instructions for the validated cleaning and disinfection procedures.

6. Electromagnetic Compatibility:
The sponsor provided documentation certifying that acceptable electromagnetic testing had been performed and the KetoSens Blood β-Ketone Monitoring System was found compliant.

7. Customer service is available Monday through Saturday 9:00 am to 9:00 pm EST by calling 1-800-429-5001.

Q. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

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

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