VeriClear Digital Early Result Pregnancy Test

{0} Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT I 510(k) Number: K182328 II Applicant: True Diagnostics, Inc. III Proprietary and Established Names: VeriClear Digital Early Result Pregnancy Test IV Regulatory Information: | Product Code(s) | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | LCX | Class II | 21 CFR 862.1155 - Human Chorionic Gonadotropin (HCG) Test System | CH - Clinical Chemistry | V Submission/Device Overview: A Purpose for Submission: New Device B Measurand: Human Chorionic Gonadotropin (hCG) C Type of Test: Qualitative chromatographic immunoassay K182328 - Page 1 of 11 {1} VI Intended Use/Indications for Use: A Intended Use(s): See Indication for use below. B Indication(s) for Use: VeriClear Digital Early Result Pregnancy Test is a rapid chromatographic immunoassay for qualitative detection of human chorionic gonadotropin (hCG) in urine, as an aid in early detection of pregnancy, in some cases as early as five (5) days before the expected period, i.e., as early as six (6) days before the day of the missed period. C Special Conditions for Use Statement(s): OTC - Over The Counter VeriClear Digital Early Result Pregnancy Test is intended for over-the-counter (OTC) use. D Special Instrument Requirements: None VII Device Description: A Device Description: The VeriClear Digital hCG Early Result Pregnancy Test is a qualitative lateral flow immunoassay for the detection of hCG. Each device is provided in a sealed pouch with instructions for use and a desiccant package to control the moisture during storage. The device may be used in midstream or dip mode (with a user-supplied cup) and consists of a plastic housed test stick containing an immunochromatographic strip and electronic and optical components along with a microprocessor and specific algorithms to digitally display test results. The VeriClear Digital Early Result Pregnancy Test is powered by a battery and the test results are displayed on the device's liquid crystal display (LCD) as either "YES+" (for a positive result), "NO-" (for a negative result) or "?" (for an invalid result) on the display. B Principle of Operation: The VeriClear Digital hCG Early Result Pregnancy Test is a sandwich immunoassay employing mouse monoclonal antibodies specific for hCG, which are immobilized on the membrane as test line, and goat anti-mouse IgG immobilized on the membrane as control line. After the urine specimen is applied to the device, the hCG present in the specimen will react with a mouse anti-hCG monoclonal antibody conjugate. The conjugate complex migrates along the membrane towards the test and control zones. A digital component integral with the chromatographic strip reads and displays the result of the immunochemical reaction on an LCD (Liquid Crystal Display) screen of the device. The test result is shown on the LCD screen of the device. A "YES+" test result indicates that the pregnancy hormone (hCG) was detected, a "NO-" test result indicates that no hCG was detected, and a "?" result indicates an invalid test. K182328 - Page 2 of 11 {2} K182328 - Page 3 of 11 C Instrument Description Information: | Modes of Operation | Yes | No | | --- | --- | --- | | Does the applicant’s device contain the ability to transmit data to a computer, webserver, or mobile device? | ☐ | ☑ | | Does the applicant’s device transmit data to a computer, webserver, or mobile device using wireless transmission? | ☐ | ☑ | | Software | | | | FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types: | ☑ | ☐ | 1. Instrument Name: VeriClear Digital Early Result Pregnancy Test 2. Specimen Identification: Urine 3. Specimen Sampling and Handling: N/A 4. Calibration: N/A 5. Quality Control: N/A VIII Substantial Equivalence Information: A Predicate Device Name(s): First Response Gold Digital Pregnancy Test B Predicate 510(k) Number(s): K123567 C Comparison with Predicate: | Device & Predicate Device(s): | K182328 | K123567 | | --- | --- | --- | | General Device Characteristic Similarities | | | | Intended Use/Indications for Use | Qualitative detection of hCG as an aid in early detection of pregnancy. | Same | | Early Detection Claim | Detection of pregnancy as early as 5 days before the expected period or as early as 6 | Same | {3} | Device & Predicate Device(s): | K182328 | K123567 | | --- | --- | --- | | | days before the day of the missed period. | | | Test Principle | Lateral flow qualitative immunochromatographi c assay with digital display of the result | Same | | Sample Matrix | Urine | Same | | Traceability | WHO 4th International Standards for hCG | Same | | Limit of Detection | 10 mIU/mL | Same | | Time to Result | 3 minutes | Same | | General Device Characteristic Differences | | | | hCG Isoforms Detected | Intact hCG Hyperglycosylated hCG hCG β-subunit | Intact hCG Hyperglycosylated hCG hCG β-subunit hCG β-core fragment | | Test Result | Digital readout: result show as YES+ (pregnant), NO- (not pregnant) or ? (invalid) | Yes+ = pregnant No- = not pregnant | IX Standards/Guidance Documents Referenced: None referenced X Performance Characteristics (if/when applicable): A Analytical Performance: 1. Precision/Reproducibility: A precision study was performed using human urine samples spiked with hCG, traceable to the 4th WHO International Standard to obtain samples with hCG concentrations of 0 mIU/mL, 3 mIU/mL, 5 mIU/mL, 8.5 mIU/mL, 10 mIU/mL, 25 mIU/mL, 50 mIU/mL, and 100 mIU/mL and three lots of VeriClear Digital Early Result Pregnancy Test devices. Each sample was tested using both simulated midstream and dip methods. The tests were performed over the course of 5 consecutive days by 5 different operators. A total of 150 replicates per testing mode (2 replicates/run x 5 operators x 5 days x 3 lots) were obtained for each hCG concentration tested. K182328 - Page 4 of 11 {4} Inter-Lot Reproducibility of VeriClear Digital Early Result Pregnancy Test Device (Simulated MidStream Method): | hCG Level (mIU/mL) | Total # of Tests | VeriClear Digital Early Result Pregnancy Test Device (Simulated Midstream Mode) | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | Observed Results Lot 1 | | | Observed Results Lot 2 | | | Observed Results Lot 3 | | | | | | P (+) | N (-) | % Positive | P (+) | N (-) | % Positive | P (+) | N (-) | % Positive | | 0.0 | 150 | 0 | 50 | 0% | 0 | 50 | 0% | 0 | 50 | 0% | | 3.0 | 150 | 0 | 50 | 0% | 0 | 50 | 0% | 0 | 50 | 0% | | 5.0 | 150 | 0 | 50 | 0% | 0 | 50 | 0% | 0 | 50 | 0% | | 8.5 | 150 | 35 | 15 | 70% | 34 | 16 | 68% | 35 | 15 | 70% | | 10.0 | 150 | 50 | 0 | 100% | 50 | 0 | 100% | 50 | 0 | 100% | | 25.0 | 150 | 50 | 0 | 100% | 50 | 0 | 100% | 50 | 0 | 100% | | 50.0 | 150 | 50 | 0 | 100% | 50 | 0 | 100% | 50 | 0 | 100% | | 100.0 | 150 | 50 | 0 | 100% | 50 | 0 | 100% | 50 | 0 | 100% | Inter-Lot Reproducibility of VeriClear Digital Early Result Pregnancy Test Device (Dip Method): | hCG Standards (mIU/mL) | Total # of Test | VeriClear Digital Early Result Pregnancy Test Device (Dip Mode) | | | | | | | | | | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | | | | Observed Results Lot 1 | | | Observed Results Lot 2 | | | Observed Results Lot 3 | | | | | | P (+) | N (-) | % Positive | P (+) | N (-) | % Positive | P (+) | N (-) | % Positive | | 0.0 | 150 | 0 | 50 | 0% | 0 | 50 | 0% | 0 | 50 | 0% | | 3.0 | 150 | 0 | 50 | 0% | 0 | 50 | 0% | 0 | 50 | 0% | | 5.0 | 150 | 0 | 50 | 0% | 0 | 50 | 0% | 0 | 50 | 0% | | 8.5 | 150 | 34 | 16 | 68% | 35 | 15 | 70% | 34 | 16 | 68% | | 10.0 | 150 | 50 | 0 | 100% | 15 | 0 | 100% | 50 | 0 | 100% | | 25.0 | 150 | 50 | 0 | 100% | 15 | 0 | 100% | 50 | 0 | 100% | | 50.0 | 150 | 50 | 0 | 100% | 15 | 0 | 100% | 50 | 0 | 100% | | 100.0 | 150 | 50 | 0 | 100% | 15 | 0 | 100% | 50 | 0 | 100% | 2. Linearity: Linearity is not applicable since this is a qualitative test. 3. Analytical Specificity/Interference: Structurally non-related compounds Negative urine samples and positive urine samples (containing 10 mIU/mL hCG) were spiked with potentially interfering exogenous and endogenous substances, and then K182328 - Page 5 of 11 {5} tested using 2 lots of the candidate device. No interference effect was observed at the concentrations tested, as reported in the below table. | Substance | Concentration | | --- | --- | | Acetaminophen | 20 mg/dL | | Acetylsalicylic acid | 20 mg/dL | | Human serum Albumin | 2000 mg/dL | | Hemoglobin | 20 mg/dL | | Ampicillin | 20 mg/dL | | Ascorbic acid | 20 mg/dL | | Atropine | 20 mg/dL | | Caffeine | 20 mg/dL | | Cortisol | 200 ng/dL | | EDTA | 80 mg/dL | | Phenylpropanolamine | 20 mg/dL | | Ephedrine | 20 mg/dL | | Gentisic acid | 20 mg/dL | | Glucose | 2000 mg/dL | | Tetracycline | 20 mg/dL | | Uric acid | 10 mg/dL | | Bilirubin | 20 mg/dL | | Ethanol | 0.1 % | | Ethanol | 1 % | | Salicylic Acid | 20 mg/dL | Cross reactivity of structurally-related compounds: Negative urine samples and positive (10 mIU/mL hCG) urine samples were spiked with hLH, hFSH, and hTSH, and tested using two lots of devices. No cross reactivity was observed at the concentrations tested, as reported in the below table. | Substance | Concentration | | --- | --- | | hLH | 1000 mIU/mL | | hFSH | 1000 mIU/mL | | hTSH | 1000 μIU/mL | K182328 - Page 6 of 11 {6} Effect of urine pH and Specific Gravity: Negative urine samples and positive (10 mIU/mL hCG) urine samples were adjusted to pH values of 4.0, 5.0, 6.0, 7.0, 8.0 and 9.0 and then tested using the candidate device. The positive and negative hCG results were not affected by urine pH ranges between 4.0 and 9.0. Negative urine samples and positive (10 mIU/mL hCG) urine samples were adjusted to Specific Gravity values of 1.003, 1.005, 1.010, 1.015, 1.020 and 1.030 and then tested using the candidate device. The positive and negative hCG results were not affected by urine Specific Gravity ranges between 1.003 and 1.030. Effect of hCG β-core fragment: Negative urine samples (0 and 5 mIU/mL hCG) and positive urine samples (10, 25 and 20,000 mIU/mL hCG) were spiked with hCG β-core fragment at concentrations of 51,000 pmol/L, 102,000 pmol/L, 204,000 pmol/L and 408,000 pmol/L and tested using 2 lots of the candidate device. All samples yielded correct results with hCG β-core fragment concentrations up to 408,000 pmol/L. High dose hook effect study: Negative urine samples were spiked with hCG at concentrations up to 450,000 mIU/mL, and tested in 2 replicates per lot using two lots of devices for each format. The results demonstrated that no hook effect was observed at hCG concentrations up to 450,000 mIU/mL. 4. Assay Reportable Range: Not applicable. 5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods): The VeriClear Digital Early Result Pregnancy Test is traceable to the World Health Organization 4th International Standard for hCG. The stability testing protocol and acceptance criteria used to support the shelf life were reviewed and found to be acceptable. The sponsor claims a 24-month shelf life of the devices stored in the sealed foil pouches at 39-86 °F (4-30 °C). 6. Detection Limit: See section IX.A.1. 7. Assay Cut-Off: See section IX.A.1. K182328 - Page 7 of 11 {7} 8. Accuracy (Instrument): See section IX.B.1 9. Carry-Over: Not applicable. B Comparison Studies: 1. Method Comparison with Predicate Device: Urine samples were collected from 366 women for pregnancy testing. Of the 366 women, 215 were suspected to be pregnant. Patient samples were randomly collected at various time throughout the day. Ages of these women ranged from 19 to 41 years. All samples were masked and randomized prior to testing, and were tested by professionals using the candidate device (VeriClear Digital Early Result Pregnancy Test; in simulated midstream mode and in dip mode) and the predicate (First Response Digital Early Result Pregnancy Test; in dip mode). The results are summarized in the table below. | | Predicate Device | | | | | --- | --- | --- | --- | --- | | Candidate Device (Simulated Midstream Mode) | | Positive | Negative | Total | | | Positive | 215 | 0 | 215 | | | Negative | 0 | 151 | 151 | | | Total | 215 | 151 | 366 | | | Predicate Device | | | | | --- | --- | --- | --- | --- | | Candidate Device (Dip Mode) | | Positive | Negative | Total | | | Positive | 215 | 0 | 215 | | | Negative | 0 | 151 | 151 | | | Total | 215 | 151 | 366 | 2. Matrix Comparison: Not Applicable. The device is intended for urine samples only. C Clinical Studies: 1. Clinical Sensitivity: Not applicable. 2. Clinical Specificity: Not applicable. K182328 - Page 8 of 11 {8} 3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable): Not applicable. ## D Detection of hCG in Early Pregnancy Clinical Samples A total of 616 urine samples were collected from 56 different women (25 - 43 years old) who planned to become pregnant. The women were followed throughout their conception cycles with urine collected from day -9 to day +1 of their expected period. The VeriClear Digital Early Result Pregnancy Test device detected hCG in 69% of samples from five days before the expected menstrual period and 100% of samples from one day before the expected menstrual period. The early pregnancy detection results are summarized below: | Day in cycle relative to EMP | hCG Positive Ratio (%) | | Overall Pregnancy Detection Rate (%) | | --- | --- | --- | --- | | | Simulated Midstream Mode | Dip Mode | | | -9 days | 0% | 0% | 0% | | -8 days | 0% | 0% | 0% | | -7 days | 12% | 12% | 12% | | -6 days | 41% | 41% | 41% | | -5 days | 69% | 69% | 69% | | -4 days | 94% | 94% | 94% | | -3 days | 98% | 98% | 98% | | -2 days | 98% | 98% | 98% | | -1 days | 100% | 100% | 100% | | 0 days | 100% | 100% | 100% | | +1 days | 100% | 100% | 100% | ## E Lay User Study A lay user study was performed at an intended use site with a total of 216 women with diverse educational and professional backgrounds, ages 18 years and older. 108 lay users tested the simulated midstream method and 108 lay users tested the dip method of the device. Lay users were only provided with the package insert prior to performing the study. Lay user results compared to professional user results are listed below. | Pregnancy Result | Lay user vs. Professional user | | | --- | --- | --- | | | Simulated Midstream Mode | Dip Mode | | Pregnant | 9/9 (100%) | 7/7 (100%) | | Non-pregnant | 99/99 (100%) | 101/101 (100%) | | Total | 108/108 (100%) | 108/108 (100%) | K182328 - Page 9 of 11 {9} Besides testing their own urine samples, lay users also tested 4 spiked urine samples around the cut-off level, at concentrations of 3.0, 7.0, 8.5 and 10 mIU/mL hCG. A total of 216 samples were tested by using the VeriClear Digital Early Result Pregnancy Test at each hCG level. Among the 216 devices tested at each hCG level, 108 were tested via the simulated midstream mode, while the other 108 were tested via the dip mode. Lay user results compared to professional user results are listed below. | hCG level mIU/mL | Lay user vs. Professional user | | | | | | | --- | --- | --- | --- | --- | --- | --- | | | Simulate Midstream Mode | | | Dip Mode | | | | | Positive Results | | Percentage of Agreement | Positive Results | | Percentage of Agreement | | | Lay user | Professional user | | Lay user | Professional user | | | 3.0 | 0 | 0 | 100% | 0 | 0 | 100% | | 7.5 | 52 | 52 | 100% | 56 | 56 | 100% | | 8.5 | 77 | 77 | 100% | 73 | 73 | 100% | | 10.0 | 108 | 108 | 100% | 108 | 108 | 100% | All the lay users participated in the study were given a questionnaire to rate how well they understand the instruction in the package insert. A Flesch-Kincaid reading analysis was performed on the OTC package insert and the score demonstrated a reading Grade Level of 7.9. The result of the questionnaire reflected that the consumers found the test easy to use and that they did not have trouble understanding the labeling or interpreting results. ## F Specificity Study to Determine False-Positive Result Rate A study was performed to determine the incidence of false positive test results from VeriClear Digital Early Result Pregnancy Test among non-pregnant women in three age groups: 15–41 years of age (pre-menopausal), 42–55 years of age (peri-menopausal) and >55 year of age (post-menopausal). A total of 320 subjects provided urine samples including 100 from pre-menopausal patients, 111 from peri-menopausal patients, and 109 from post-menopausal patients. All 320 urine samples were tested with three lots of VeriClear Digital Early Result Pregnancy Test devices. No positive results were observed in any of the age groups. ## G Clinical Cut-Off: Not applicable. ## H Expected Values/Reference Range: Not applicable. ## I Other Supportive Instrument Performance Characteristics Data: Not applicable. K182328 - Page 10 of 11 {10} K182328 - Page 11 of 11 XI Proposed Labeling: The labeling supports the finding of substantial equivalence for this device. XII Conclusion: The submitted information in this premarket notification is complete and supports a substantial equivalence decision.