Proov Test

K191462 · Mfb Fertility, Inc. · QKE · Feb 27, 2020 · Clinical Chemistry

Device Facts

• Record ID: K191462
• Device Name: Proov Test
• Applicant: Mfb Fertility, Inc.
• Product Code: QKE · Clinical Chemistry
• Decision Date: Feb 27, 2020
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1620
• Device Class: Class 1

Indications for Use

The Proov Test is intended for the detection of pregnanediol glucuronide (PdG, the major urine metabolite of progesterone) and can be used as an aid for confirmation of ovulation.

Device Story

Proov Test is a disposable, lateral flow competitive immunoassay for home use. Device detects pregnanediol glucuronide (PdG) in first morning urine samples. User dips test strip into urine; sample migrates via lateral flow across nitrocellulose membrane containing anti-PdG antibodies. Presence of PdG competes for binding sites; results visualized as red lines (one line = positive, two lines = negative). Device provides qualitative confirmation of ovulation for women. Results interpreted visually by user. No instrumentation required. Benefits include convenient, non-invasive, at-home monitoring of progesterone metabolite levels to assist in fertility tracking.

Clinical Evidence

Clinical evidence includes a method comparison study and a lay-user study. Method comparison involved 94 urine samples from healthy females, comparing Proov Test results (read by three technicians) against a validated PdG EIA procedure. Lay-user study included 101 women (ages 18-65) across three sites testing blind-labeled samples at various PdG concentrations; participants correctly interpreted results >99% of the time (121/121 samples). Surveys indicated 92% of users found instructions easy to follow.

Technological Characteristics

Lateral flow competitive immunoassay. Components: anti-PdG antibody, antigen, nitrocellulose membrane, colloidal gold conjugate pad, sample pad. Qualitative output. Analyte: PdG. Cut-off: 5 µg/mL. Storage: 4-30°C. Shelf life: 24 months.

Indications for Use

Indicated for women seeking confirmation of ovulation by detecting PdG in first morning urine during non-menstruating phases of the reproductive cycle.

Regulatory Classification

Identification

A progesterone test system is a device intended to measure progesterone (a female hormone) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of disorders of the ovaries or placenta.

Predicate Devices

• Luminescent Immunoassay Kit For The Detection Of Progesterone In Saliva (K040923)

Submission Summary (Full Text)

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Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov

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

## I Background Information:

A 510(k) Number
k191462

B Applicant
MFB Fertility, Inc.

C Proprietary and Established Names
Proov Test

D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| QKE | Class I, meets the limitation to the exemption 21 CFR 862.9(a) and 862.9(b) | 21 CFR 862.1620 - Progesterone Test System | CH - Clinical Chemistry |

## II Submission/Device Overview:

A Purpose for Submission:
New Device

B Measurand:
Pregnanediol Glucuronide (PdG)

C Type of Test:
Qualitative, lateral flow competitive immunoassay

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## III Intended Use/Indications for Use:

A Intended Use(s):
See Indications for Use below.

B Indication(s) for Use:
The Proov Test is intended for the detection of pregnanediol glucuronide (PdG, the major urine metabolite of progesterone) and can be used as an aid for confirmation of ovulation.

C Special Conditions for Use Statement(s):
OTC - Over The Counter

D Special Instrument Requirements:
Not applicable

## IV Device/System Characteristics:

A Device Description:
Each Proov test kit contains seven Proov test strips that are individually sealed. Each test strip consists of anti-PdG antibody and antigen, nitrocellulose membrane, colloidal gold conjugate pad, and a sample pad.

B Principle of Operation:
The specific analyte tested by the Proov Test is pregnanediol glucuronide (PdG), a progesterone metabolite. The Proov Test is intended for measuring PdG in first morning urine during the non-menstruating phases of the monthly female reproductive cycle. The Proov Test is a disposable lateral flow test strip, consisting of a test area and control area. The urine sample is applied to the strip by dipping. The sample moves by lateral flow into the test area, and then the control area. The test area has PdG-specific reagents impregnated on it to detect the presence of hormone metabolites in the urine. The control area has antibodies impregnated to be used as internal control for proper assay function. The test strip is intended for use outside the body (in vitro diagnostic use) and provides qualitative results with a single red line indicating a positive result for PdG and two red lines indicating a negative result for PdG in urine.

## V Substantial Equivalence Information:

A Predicate Device Name(s):
Luminescent Immunoassay Kit For The Detection Of Progesterone In Saliva

B Predicate 510(k) Number(s):
K040923

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C Comparison with Predicate(s):

| Device & Predicate Device(s): | K191462 | K040923 |
| --- | --- | --- |
| Device Trade Name | Proov Test | IBL Progesterone LIA Test |
| General Device Characteristic Similarities | | |
| Indications for Use | Intended for the confirmation of ovulation. | Same |
| General Device Characteristic Differences | | |
| Sample Type | Urine | Saliva |
| Analyte | Pregnanediol glucuronide (PdG) | Progesterone |
| Type of Test | Qualitative | Quantitative |
| Technology | Lateral Flow Immunoassay | Luminescent ELISA Immunoassay |
| Test environment | Over-the-counter home use | Prescription Use |

VI Standards/Guidance Documents Referenced:

None

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility:

Precision was evaluated using analyte-free urine specimens spiked with varying concentrations of PdG (0, 2.5, 3.75, 5, 6.25, and 7.5 µg/ml). PdG concentrations were confirmed using a validated PdG ELISA assay. Each urine sample was tested using three device lots of device, by three operators, in duplicate, across five consecutive days, for a total of 90 measurements per sample. Results are shown in the table below:

| PdG Level (µg/mL) | Percent from Cutoff | Positive | Negative | % Positive |
| --- | --- | --- | --- | --- |
| 0 | -100% | 0 | 90 | 0% |
| 2.5 | -50% | 0 | 90 | 0% |
| 3.75 | -25% | 0 | 90 | 0% |
| 5 | Cutoff | 41 | 49 | 46% |
| 6.25 | +25% | 90 | 0 | 100% |
| 7.5 | +50% | 90 | 0 | 100% |

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2. Linearity:

Not applicable since this is a qualitative device.

3. Analytical specificity/Interference:

Potential interference from exogenous interferents and potential cross-reactivity from endogenous substances was evaluated by dipping Proov Tests strips from three different lots into analyte-free urine specimens containing 6.25 µg/mL or 0 µg/mL PdG or specimens containing 6.25 µg/mL or 0 µg/mL PdG that were spiked with different interfering substances. In addition, four levels of pH and three specific gravity conditions were evaluated as potential interferences for the device. Three replicates were performed for each condition assayed. The sponsor stated that interference was non-significant if negative specimens all correctly read negative and the positive specimens all correctly read positive. Results are shown below:

| Substance | Highest Concentration Tested Without Significant Interference or Cross-Reactivity |
| --- | --- |
| Luteinizing Hormone (LH) | 600 mIU/mL |
| Human chorionic gonadotropin (hCG) | 1000 mIU/mL |
| Progesterone | 100 ng/mL |
| Pregnanediol | 60 µg/mL |
| Estrone-3-Glucuronide | 600 ng/mL |
| Acetaminophen | 20 mg/dL |
| Ascorbic Acid | 20 mg/dL |
| Caffeine | 20 mg/dL |
| Glucose | 2 mg/dL |
| Ampicillin | 20 mg/dL |
| Ketone | 1% |
| Acetylsalicylic Acid | 20 mg/dL |
| Atropine | 20 mg/dL |
| Gentisic Acid | 20 mg/dL |
| Hemoglobin | 1 mg/dL |
| Tetracycline | 20 mg/dL |
| Nitrite Positive | 1% |
| Phenothiazine | 20 mg/dL |
| Ethanol | 1% |
| Albumin | 100 mg/dL |
| pH | 4.25, 5, 8, 9 |
| Specific Gravity | 1.000, 1.015, 1.025 |

Hook Effect

The sponsor tested several high PdG concentrations (50 µg/mL, 100 µg/mL, 1 mg/mL) in their interference study to evaluate a potential Hook effect for their device. No discrepant results were observed.

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4. Assay Reportable Range:

Not applicable since this is a qualitative device.

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

Traceability

The Proov Test is traceable to a commercially available purified PdG standard.

Stability/Shelf Life:

Accelerated and real-time stability protocols were reviewed and found to be adequate to support that Proov devices are stable for 24 months when stored in the sealed foil pouch at 4-30°C (38-86°F).

6. Detection Limit:

See section VII.A.1.

7. Assay Cut-Off:

5 µg/mL. See section VII.A.1.

B Comparison Studies:

1. Method Comparison with Predicate Device:

To evaluate analytical accuracy of the Proov Test, 94 banked native female urine samples (63 negative and 31 positive) were tested using the Proov Test according to the instructions for use and read by three technicians. Frozen aliquots of each sample were evaluated externally using a validated PdG ELISA assay. Results from the Proov Test were compared to results from the ELISA assay. The results are summarized in the table below.

| | Proov Test Result | Low Negative by PdG ELISA (less than -50%) | Near Cutoff Negative by PdG ELISA (Between -50% and cutoff) | Near Cutoff Positive by PdG ELISA (Between the cutoff and +50%) | High Positive by PdG ELISA (greater than +50%) |
| --- | --- | --- | --- | --- | --- |
| Viewer A | Positive | 0 | 4 | 13 | 18 |
| | Negative | 48 | 11 | 0 | 0 |
| Viewer B | Positive | 0 | 1 | 12 | 18 |
| | Negative | 48 | 14 | 1 | 0 |
| Viewer C | Positive | 0 | 0 | 12 | 18 |
| | Negative | 48 | 15 | 1 | 0 |

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Discordant results:

| Viewer | Sample Number | PdG ELISA Result (μg/mL) | Proov Test Result |
| --- | --- | --- | --- |
| Viewer A | 12 | 4.4 | Positive |
| Viewer A | 41 | 4.6 | Positive |
| Viewer A | 66 | 4.7 | Positive |
| Viewer A | 16 | 4.8 | Positive |
| Viewer B | 16 | 4.8 | Positive |
| Viewer B | 46 | 5.2 | Negative |
| Viewer C | 46 | 5.2 | Negative |

2. Matrix Comparison:

Not applicable – urine is the only matrix.

C Clinical Studies:

1. Clinical Sensitivity:

Not applicable

2. Clinical Specificity:

Not applicable

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):

Lay User Study

A lay user study was performed with 101 women (ages 18-65) with varying educational backgrounds. Each subject tested one or two specimens (containing 1.25, 2.5, 3.75, 6.25, 7.5, or 8.75 μg/mL PdG) with a Proov Test according to the package insert. A summary of results is presented in the table below:

| PdG (μg/mL) | Negative Result | Positive Result | % correctly interpreted |
| --- | --- | --- | --- |
| 1.25 | 20 | 0 | 100 |
| 2.5 | 20 | 0 | 100 |
| 3.75 | 21 | 0 | 100 |
| 6.25 | 0 | 20 | 100 |
| 7.5 | 0 | 20 | 100 |
| 8.75 | 0 | 20 | 100 |

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Each lay person was given a questionnaire to assess the readability of the labeling. The results of the questionnaire were found to be acceptable. The readability of the labeling was found to be at the 8th grade level using a Flesch-Kincaid analysis.

## D Clinical Cut-Off:
Not applicable

## E Expected Values/Reference Range:
Not applicable

## VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.

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

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