On Call Ketone Reagent Strips for Urinalysis, Healthy Me Ketone Reagent Strips for Urinalysis

K170587 · ACON Laboratories, Inc. · JIN · Jul 6, 2017 · Clinical Chemistry

Device Facts

• Record ID: K170587
• Device Name: On Call Ketone Reagent Strips for Urinalysis, Healthy Me Ketone Reagent Strips for Urinalysis
• Applicant: ACON Laboratories, Inc.
• Product Code: JIN · Clinical Chemistry
• Decision Date: Jul 6, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1435
• Device Class: Class 1

Indications for Use

The On Call® & Healthy Me™ Ketone Reagent Strips for Urinalysis are intended for the qualitative and semi-quantitative detection of Ketoacetic acid) in urine. The identification of ketones is used in the diagnosis 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. The On Call® & Healthy Me™ Ketone Reagent strips are intended for Over the Counter use by lay people with Diabetes and/or people on low carb diets at home to check for the ketones in urine. This product is not intended for the management of diabetes.

Device Story

Device consists of plastic strip with single reagent pad containing sodium nitroprusside buffer; used for qualitative/semi-quantitative detection of urinary ketones. Operated by lay users at home via midstream or dip-and-read technique. User compares color change on reagent pad against color blocks printed on bottle label; no instrumentation required. Provides visual results ranging from beige (negative) to dark purple (positive). Assists users in identifying ketosis or acidosis; results intended for consultation with healthcare provider. Device is OTC version of previously cleared professional urinalysis strip (k061559), modified to test only for ketones.

Clinical Evidence

No clinical trials performed. Evidence consists of user performance studies (n=71 midstream; n=238 dipped; n=100 usability) comparing lay user results to professional technician results using the predicate device. Results demonstrated 99.4% to 100% agreement within one color block. Analytical interference testing confirmed no impact from common urine substances, though blood concentrations ≥1% may cause false positives.

Technological Characteristics

Plastic strip with single reagent pad; chemistry based on sodium nitroprusside and acetoacetic acid reaction. Visual read only; no energy source or connectivity. Stability and performance characteristics identical to previously cleared ACON Urinalysis Reagent Strips (k061559).

Indications for Use

Indicated for qualitative and semi-quantitative detection of acetoacetic acid in urine for lay people with diabetes or those on low-carb diets. Used for diagnosis of acidosis or ketosis and monitoring ketogenic diets. Not intended for diabetes management.

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

• Ketostix Reagent Strips for Urinalysis (k801270)

Reference Devices

• ACON Urinalysis Reagent Strips (k061559)

Submission Summary (Full Text)

{0}

1

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k170587

B. Purpose for Submission:
Modification to an existing device: change from prescription use only to over-the-counter use and change from urinalysis for ten analytes to urinalysis for one analyte only (ketone)

C. Measurand:
Ketones (urine)

D. Type of Test:
Qualitative and Semi-Quantitative

E. Applicant:
ACON Laboratories, Inc.

F. Proprietary and Established Names:
On Call Ketone Reagent Strips for Urinalysis
Healthy Me Ketone Reagent Strips for Urinalysis

G. Regulatory Information:
1. Regulation section:
21 CFR § 862.1435, Ketones (nonquantitative) test system
2. Classification:
Class I, meets the limitations of exemption per 21 CFR 862.9 (c)(9)
3. Product code:
JIN, Nitroprusside, ketones (urinary, non-quantitative)

{1}

4. Panel:
Clinical Chemistry (75)

H. Intended Use:

1. Intended use(s):
See indications for use, below.

2. Indication(s) for use:
The Healthy Me Ketone Reagent Strips for Urinalysis:
The Healthy Me Ketone Reagent Strips for Urinalysis are intended for the qualitative and semi-quantitative detection of ketone (acetoacetic acid) in urine. The identification of ketones is used in the diagnosis 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.

The Healthy Me Ketone Reagent strips are intended for over the counter use by lay people with diabetes and/or people on low carb diets at home to check for the ketones in urine. This product is not intended for the management of diabetes.

The On Call Ketone Reagent Strips for Urinalysis:
The On Call Ketone Reagent Strips for Urinalysis are intended for the qualitative and semi-quantitative detection of ketone (acetoacetic acid) in urine. The identification of ketones is used in the diagnosis 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.

The On Call Ketone Reagent strips are intended for over the counter use by lay people with diabetes and/or people on low carb diets at home to check for the ketones in urine. This product is not intended for the management of diabetes.

3. Special conditions for use statement(s):
For over-the-counter use; lay users can perform the test using the midstream technique or the dip and read technique.

4. Special instrument requirements:
These strips are visually read only.

2

{2}

3

I. Device Description:

On Call Reagent Strips for Urinalysis and Healthy Me Ketone Reagent Strips for Urinalysis are identical (and differ only by the tradename) and consist of a plastic strip to which a reagent pad is affixed. The reagent pad reacts with the urine and provides a visible color reaction.

On Call Reagent Strips for Urinalysis and Healthy Me Ketone Reagent Strips for Urinalysis are packaged along with a drying agent in a canister bottle. Each strip is ready to use upon removal from the canister. The entire reagent strip is disposable. Results are obtained by direct comparison to the test strip with color blocks printed on the bottle label. No calculations or laboratory instruments are needed.

The devices are over-the-counter versions of a previously cleared professional device for urine ketones (k061559-ACON Urinalysis Reagent Strips). The strips are identical, except that the ACON Urinalysis Reagent Strips contained test pads to evaluate 10 analytes (including ketones), and the On Call Reagent Strips for Urinalysis and Healthy Me Ketone Reagent Strips for Urinalysis strips each contain a single reagent pad (to evaluate ketones).

J. Substantial Equivalence Information:

1. Predicate device name(s):

Ketostix Reagent Strips for Urinalysis

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

k801270

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | For the detection of ketones in urine. | Same |
| Reagent | Sodium nitroprusside Buffer | Same |
| Intended specimen | Urine | Same |
| Methodology | Based on ketones reacting with nitroprusside and acetoacetic acid to produce a color change ranging from beige for negative results to a dark purple color for positive results. | Same |

{3}

| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended use population | For over the counter use | For professionals and for over the counter use |
| Time Required to Read Strips | 15 to 120 seconds | 15 seconds |

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

Clinical and Laboratory Standards Institute (CLSI) GP16-A3 “Urinalysis; Approved Guideline - Third Edition”

L. Test Principle:

The On Call Reagent Strips for Urinalysis and Healthy Me Ketone Reagent Strips for Urinalysis are for the qualitative and semi-quantitative detection of ketones (acetoacetic acid) in urine. The On Call Reagent Strips for Urinalysis and Healthy Me Ketone Reagent Strips for Urinalysis are based on ketones reacting with nitroprusside and acetoacetic acid to produce a color change ranging from beige for negative results to a dark purple color for positive results. Ketones are normally not present in urine.

M. Performance Characteristics (if/when applicable):

The ketones pad of the On Call Reagent Strips for Urinalysis and Healthy Me Ketone Reagent Strips for Urinalysis are identical to the ketones pad in the ACON Urinalysis Reagent Strips evaluated in k061559 (see device description).

1. Analytical performance:

a. Precision/Reproducibility:

The ketones pad is identical to the ketones pad in the ACON Urinalysis Reagent Strips evaluated in k061559, therefore precision/reproducibility studies were not repeated.

b. Linearity/assay reportable range:

The ketones pad is identical to the ketones pad in the ACON Urinalysis Reagent Strips evaluated in k061559, therefore linearity studies were not repeated.

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

The sponsor did not indicate any degree of traceability for their device.

The recommended storage temperature conditions and claims are unchanged and are the same stability claims described in k061559.

{4}

5

d. Detection limit:

The ketones pad is identical to the ketones pad in the ACON Urinalysis Reagent Strips evaluated in k061559, therefore sensitivity studies were not repeated.

e. Analytical specificity:

Interference study was performed according to CLSI guideline EP7-A2, “Interference Testing in Clinical Chemistry” to determine the effect of potential interfering substances commonly found in human urine on the strips. Pooled human urine was divided into three samples; a negative sample with no ketones, a sample spiked with lithium acetoacetate for a ketone concentration of 5 mg/dL, and a sample spiked with lithium acetoacetate for a ketone concentration of 160 mg/dL.

Potential interfering substances and target concentrations evaluated are shown below. Interferences were initially evaluated at concentrations listed; if interference was observed, serial dilutions of the substance were tested until no interference was observed:

| Substance | Concentration |
| --- | --- |
| Human serum albumin | 30000 mg/dL |
| Ascorbic acid | 200 mg/dL |
| D-glucose | 5000 mg/dL |
| Bilirubin conjugate | 170 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Ammonium chloride | 100 mg/dL |
| Calcium chloride | 275 mg/dL |
| Citric acid | 75 mg/dL |
| Creatinine hydrochloride | 10 mg/dL |
| Creatinine | 600 mg/dL |
| Fructose | 100 mg/dL |
| Galactose | 80 mg/dL |
| D-glucose | 5000 mg/dL |
| Glycine | 450 mg/dL |
| Lactose | 10 mg/dL |
| Lithium acetoacetate | 250 mg/dL |
| Potassium chloride | 1500 mg/dL |

{5}

| Substance | Concentration |
| --- | --- |
| Sodium chloride | 5500 mg/dL |
| Oxalic acid | 70 mg/dL |
| Riboflavin | 10 mg/dL |
| Sodium acetate | 25 mg/dL |
| Sodium bicarbonate | 1500 mg/dL |
| Sodium nitrite | 10 mg/dL |
| Sodium nitrate | 10 mg/dL |
| Sodium phosphate | 500 mg/dL |
| Theophylline | 100 mg/dL |
| Urea | 4000 mg/dL |
| Uric acid | 150 mg/dL |
| Blood | 1% |
| Leukocyte | 2500 cell/μL |
| Human Immunoglobulins | 25 mg/dL |

No interference was observed with potentially interfering substances at the concentrations listed (i.e., all results were an exact color block match to control solutions lacking interferents).

Blood at a concentration of 5% caused false positive results for the proposed device. Since blood concentration ≥ 1% may cause false positive results for the proposed device, the sponsor’s labeling states that blood in urine can lead to false positive results.

The sponsor additionally evaluated the performance of the proposed device under different light sources (incandescent, fluorescent, sunlight, mercury vapor, and sodium vapor) and determined that these sources provided adequate lighting for use since the test results (of urine samples with ketone concentrations of 5, 15, 40, 80 and 160 mg/dL) were not impacted by the different lighting conditions evaluated.

The effect of pH and specific gravity was also evaluated. Five normal fresh urine samples were pooled and split into aliquots spiked to contain ketone concentrations of 0, 5, 15, 40, 80, and 160 mg/dL. To evaluate the effect on device performance, aliquots with pH of 4, 5, 6, 7, 8, and 9, as well as aliquots with specific gravities of 1.000, 1.005, 1.010, 1.015, 1.020, 1.025, 1.030, 1.035, and 1.040 were prepared. Five replicate measurements were taken of each sample concentration at each condition. For all specific gravity and pH conditions evaluated, results were an exact color block match with the spiked sample concentrations prior to pH or specific gravity adjustment. Neither

{6}

pH nor specific gravity were observed to impact device performance across the range of pH and specific gravity evaluated.

f. Assay cut-off:

Not applicable.

2. Comparison studies:

a. Method comparison with predicate device:

User performance study (midstream collection): method comparison with predicate device:

The study evaluated the performance of the proposed device when a layperson performs the test following the product's package insert.

The study also determined if the proposed device can be used correctly by laypersons, and if results obtained by laypersons are equivalent to results obtained by trained professional operators using the predicate device.

71 volunteers at two sites performed the test on their own midstream urine with the candidate device following the product's package insert. At the same time, volunteers also collected their urine in a urine collection cup. These samples were tested by trained professional operators using the predicate device. All volunteers also answered a demographic survey and questionnaire regarding the proposed device.

Three lots of the proposed device were used in the study.

User performance study results (misdstream):

| | Results (mg/dL) of predicate by technician | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Neg | 5 mg/dL | 15 mg/dL | 40 mg/dL | 80 mg/dL | 160 mg/dL | Total |
| Results (mg/dL) using the candidate device by layperson | Neg | 42 | 0 | 0 | 0 | 0 | 0 | 42 |
| | 5 mg/dL | 0 | 21 | 0 | 0 | 0 | 0 | 21 |
| | 15 mg/dL | 0 | 0 | 6 | 0 | 0 | 0 | 6 |
| | 40 mg/dL | 0 | 0 | 0 | 2 | 0 | 0 | 2 |
| | 80 mg/dL | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| | 160 mg/dL | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| | Total | 42 | 21 | 6 | 2 | 0 | 0 | 71 |
| Same block agreement | | 100% | | | | | | |
| Agreement within ±1 block | | 100% | | | | | | |

{7}

Results show 100% exact agreement, as well as 100% agreement within one color block.

## User performance study (dipped sample): method comparison with predicate device:

238 Volunteer participants were recruited across three sites. The study evaluated the performance of the proposed device when a layperson performs the test following the product’s package insert.

The study also determined if the proposed device can be used correctly by laypersons, and if results obtained by laypersons are equivalent to results obtained by trained professional operators using the predicate device.

Each participant tested two blinded test control urine solutions (human urine spiked with ketones) with the proposed device. These solutions were also tested by trained technicians using the predicate device.

User Performance Study Results:

| | | Results (mg/dL) of predicate by technician | | | | | | Total |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Neg | 5 mg/dL | 15 mg/dL | 40 mg/dL | 80 mg/dL | 160 mg/dL | |
| Results (mg/dL) using the candidate device by layperson | Neg | 60 | | | | | | 60 |
| | 5 mg/dL | | 57 | | | | | 57 |
| | 15 mg/dL | | | 55 | | | | 55 |
| | 40 mg/dL | | | 1 | 52 | | | 53 |
| | 80 mg/dL | | | | | 60 | | 60 |
| | 160 mg/dL | | | | | 1 | 61 | 62 |
| | Total | 60 | 57 | 56 | 52 | 61 | 61 | 347 |
| Same Block Agreement | | 60/60 (100%) | 57/57 (100%) | 55/56 (98.3%) | 52/52 (100%) | 60/61 (98.6%) | 61/61 (100%) | (99.4%) |
| Agreement Within ±1 Block | | 60/60 | 57/57 | 56/56 | 52/52 | 61/61 | 61/61 | (100%) |

Results show 100% agreement within one color block.

## Additional Usability Study:

An additional usability study was conducted with 100 subjects to evaluate if the lay users can perform the test and interpret results accurately using their own urine following the product’s package insert. Users were provided a cup with which to collect their own urine sample and test with the proposed device. Collected urine was then given to a technician to evaluate with the predicate device.

{8}

9

| | Results (mg/dL) of predicate by technician | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Neg | 5 mg/dL | 15 mg/dL | 40 mg/dL | 80 mg/dL | 160 mg/dL | Total |
| Results (mg/dL) using the candidate device by layperson | Neg | 89 | 0 | 0 | 0 | 0 | 0 | 89 |
| | 5 mg/dL | 0 | 11 | 0 | 0 | 0 | 0 | 11 |
| | 15 mg/dL | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| | 40 mg/dL | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| | 80 mg/dL | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| | 160 mg/dL | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| | Total | 89 | 11 | 0 | 0 | 0 | 0 | 100 |
| Same block agreement | | 100% | | | | | | |
| Agreement within ±1 block | | 100% | | | | | | |

Results show 100% exact agreement, as well as 100% agreement within one color block.

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):
Not applicable.

4. Clinical cut-off:
Not applicable.

5. Expected values/Reference range:
The sponsor included the following information in the package insert:

{9}

Normal urine will not have any ketones present. If your results are positive, you should immediately consult your health care provider. A positive ketone level in urine is called ketonuria. This can occur in the following instances:

- When a person is on a very low carbohydrate diet
- When diabetes mellitus is out of control.
- As a result of fasting, dieting, starvation, eating disorders, high protein diets and isopropanol ingestion.
- Ketonuria may be noted in normal pregnancy.

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

Additionally, the sponsor performed a readability assessment which showed that the package insert had a Flech-Kincaid Grade Level Score of 7.9. A survey of the volunteers who participated in the lay user study indicated that over 90% of users described the overall instructions as clear and easy to understand, and no users described the instructions as difficult to follow or understand.

O. Conclusion:

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

10