Pan Probe Blotech (PPB), Inc. LiveSure™ Human Chorionic Gonadotropin (LiveSure™ hCG) Rapid Urinary Pregnancy Test Strip and Test Card Immunoassay Devices are in vitro diagnostic (IVD) qualitative screening lateral flow chromatographic immunoassays that are designed for rapid detection of placental hCG related to pregnancy at an expected value cut-off level of 20 mlU of hCG/ml of human urine. These LiveSure™ IVD immunoassay devices for urinary hCG pregnancy screening are neer non to give visual, qualitative results and are intended for professional use only. The PPB LiveSure™ hCG Test Strip and Test Card Devices are not intended for quantitative results, nor over-the-counter sales, but provide only professional use preliminary screening data for use to aid in the diagnosis of pregnancy. A clinical diagnosis by a medical professional must be obtained in order to confirm any analytical result, and to rule c: I any non-pregnancy diseases that can also result in elevated hCG. Clinical considerations and professional judgment should be applied to any test result, particularly when preliminary positive results are indicated.

Device Description

The PPB LiveSure™ hCG Screen (i.e., LiveSure™ hCG) Test Strip and Test Card Devices are rapid qualitative lateral flow chromatographic IVD immunoassays and are intended for professional IVD use only. The Pan Probe Biotech LiveSure™ hCG Test Strip & Test Card Devices provide only preliminary analytical data for use to aid in the diagnosis of pregnancy. A clinical diagnosis by a medical professional must be obtained in order to confirm any analytical result. Each test device consists of a sample reaction unit, a pink colored colloidal gold conjugate unit pre-labeled with hGC-spec fic mouse-monoclonal antibody, and a chromatographic membrane was precoated with mouse-antialpha-hCG capture antibodies at the test band region and goat-antibody at the process control band region. During the test, the human urine specimen is allowed to react with hCG-specific mouse-monocloral antibodycolloid gold conjugate, which has been predried on the test component of each device. The mixture then moves chromatographically upward on the capillary action. For a pregnancy-positive specimen, gold conjugate complex binds to hCG at a level of 20 mlU/ml or greater, forming an antibody-antigen complex. This complex binds to hCG antibody as captured regents on the Test Region and produces a colored band when hCG concentration is equal to or greater than 20 mlU/ml. Absence of this colored band in the Test Region suggests a negative result Summarizing, negative urine will produce only one pink colored band in the control region, while positive urine will produce two pink colored bands, in both the control and test regions.

AI/ML Overview

Here's an analysis of the provided text to extract the requested information concerning the acceptance criteria and the study proving the device meets them:

Acceptance Criteria and Device Performance

Acceptance Criteria	Reported Device Performance
Relative sensitivity with positive pregnancy tests	100% (against clinical lab diagnoses and predicate devices, both in-house and external lab)
Relative specificity with negative pregnancy diagnoses	100% (against clinical lab diagnoses and predicate devices, both in-house and external lab)
Overall accuracy	>99% (against clinical lab diagnoses and predicate devices, both in-house and external lab)
Sensitivity of positive EIA results	100% (against quantitative Abbott's Axsym™ hCG ElA assay at external lab)
Specificity of negative EIA results	95.0% (153/161) (against quantitative Abbott's Axsym™ hCG ElA assay at external lab). The document states this was due to low EIA values below 15 mIU/ml, which were considered false negatives by EIA as patients were clinically pregnant. Therefore, from a clinical pregnancy standpoint, the device achieved 100% agreement for positive cases.
Overall statistical accuracy (vs. EIA)	96.8% (244/252) (against quantitative Abbott's Axsym™ hCG ElA assay at external lab)
Substantial equivalence	Confirmed against predicate ABI's SureStep™ and Quidel's QuickVue™ hCG test devices (both positive and negative diagnoses). Achieved 95% or better in equivalency to quantitative Axsym™ EIA assay results for negative diagnoses, and 100% for positive diagnoses.
Expected Value cut-off level	20 mU of hCG/ml of urine (device is designed for rapid detection at this level or greater)

Study Details

1. Sample sizes used for the test set and the data provenance:

External Clinical Lab: 252 urine samples with clinically confirmed diagnoses.
- Data Provenance: Retrospective (implied, as samples had "clinically confirmed diagnoses" prior to testing).
In-house Testing: 136 urine samples with clinically confirmed diagnoses.
- Data Provenance: Retrospective (implied, as samples had "clinically confirmed diagnoses" prior to testing).

2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

The document states "clinical lab data on diagnoses of pregnancy" and "clinically confirmed diagnoses." It also mentions testing performed "by several licensed technologists" at the external lab.
Number of experts: At least "several licensed technologists" were involved in running tests and presumably contributing to or validating the "clinical lab data on diagnoses of pregnancy." The exact number of specialists (e.g., physicians, pathologists) who established the initial clinical diagnoses is not specified, but it implies medical professionals.
Qualifications of experts: "Licensed technologists" for performing tests, and "medical professional" for clinical diagnosis. Specific specializations (e.g., radiologist, obstetrician) are not provided.

3. Adjudication method for the test set:

The document implies that the ground truth was established by "clinically confirmed diagnoses" or "clinical lab data on diagnoses of pregnancy." The test results from the LiveSure™ hCG devices (and predicate devices) were then compared against this established clinical truth. There is no explicit mention of an adjudication method like 2+1 or 3+1 among multiple readers for the test results themselves, rather the device's accuracy was assessed against a pre-existing clinical ground truth.

4. 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:

No, this was not a multi-reader multi-case (MRMC) comparative effectiveness study. The device is a rapid diagnostic immunoassay intended for professional use, but it does not involve human readers interpreting complex images or data assisted by AI. The comparison was device-to-device and device-to-clinical diagnosis.

5. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

The LiveSure™ hCG device itself is a "standalone" rapid test strip/card. It produces a visual result (one or two pink bands). While a "professional" interprets the result, the device's performance metrics (sensitivity, specificity, accuracy) are reported for the device purely based on its output against the ground truth. It's an "algorithm only" in the sense that the chemical and physical reactions within the strip determine the outcome, without complex human interpretation of raw data. However, it requires a human to visually read the result. Therefore, it's a "device only" performance study.

6. The type of ground truth used:

The ground truth was primarily based on expert clinical diagnoses of pregnancy.
Additionally, quantitative Abbott's Axsym™ hCG ElA assay determinations served as a comparative ground truth for analytical performance, though the document explicitly states clinical pregnancy diagnoses superseded some EIA results (e.g., when EIA gave low negative values for clinically pregnant patients).

7. The sample size for the training set:

The document does not specify a separate training set size. The described studies focus on testing the finished device against clinical samples. This type of immunoassay development typically involves extensive internal R&D, calibration, and optimization (which can be considered analogous to "training") with internal controls and characterized samples, but a distinct "training set" in the machine learning sense is not detailed in this submission summary.

8. How the ground truth for the training set was established:

As no explicit training set is described in the provided summary, the method for establishing its ground truth is also not specified. Device development and calibration would have relied on characterized hCG samples and known positive/negative clinical samples, but these are not formally presented as a "training set" in this context.

Summary

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JUL 15 2002

510k Submission for the Pan Probe Biotech, Inc. LiveSure™ Human Chorionic Gonadotropin (LiveSure™ hCG)

Rapid Urinary Pregnancy Test Immunoassay Devices

Pan Probe Biotech, Inc.

Revised July 11, 2002

SUMMARY OF SAFETY AND EFFECTIVENESS

Pan Probe Bictech, Inc., has developed, manufactured, and tested, under Good Laboratory Practices guidelines, both Test Strip and Test Card in vitro diagnostic (IVD) devices for rapid qualitative testing of urine samples for the presence of human Chorionic Gonadotrpin (hCG) related to pregnancy at an Expected Value cut-off level of 20 mU of hCG/ml of urine. The IVD medical device trade names are the Pan Probe Biotech or PPB LiveSure™ hCG Screen Test Strip and Test Card Devices, having FDA assigned name: Human Chorionic Gonadotrpin (hCG) Test Systems, and classified as Class II device per 21 CFR 862.1155, with product code: DHA.

In-house and external testing of LiveSure™ hCG Test Strip and Test Card Devices was done against currently marketed predicate hCG test devices, including: AB/s SureStep™ hCG Test and Quidel's QuickVue™ hCG Assay devices, as well as the quantitative Abbott's Axsym™ hCG ElA assay. Against clinical lab data on diagnoses of pregnancy, and against each other results, statistical agreement was obtained between LiveSure™ hCG IVD Test Strip and Test Card Devices versus the predicate ABI's SureStep™ and Quidel's QuickVue """ hCG Test IVD devices. In particular, complete agreement was obtained for 3 main statistical parameters: a) for relative sensilivity with positives pregnancy tests (100%), b) for relative specificity or agreement with negative pregnancy diagnoses (100%), and c) for over-all accuracy >99%, both at an independent clinical lab (testing 252 urine samples with clinically confirmed diagnoses and run by several licensed technologists), as well as by in-house testing of 136 urine samples (also with clinically confirmed diagnoses). Comparison of the same 252 urine assay results for both PPB LiveSure™ hCG Test Strip & Test Card Devices against quantitative hCG Axsym™ EJA Assay determinations at the external independent clinical lab resulted in: a) 100% percent agreement for relative sensitivity of positive ElA results, but relative specificity 153/161or 95.0% for ElA negatives, and an over-all statistical accuracy of 244/252 or 96.8%. The same statistice results were obtained for the AB/s SureStep™ and Quicel's QuickVue™ hCG Test devices, as well as versus the clinical lab diagnoses data of pregnancy. These results were thought to be due to 8 low ElA values out of 252 independent lab specimens and 5 low ElA negatives out of 136 in-house samples, all determined to be below 15 mlU/ml by the Axsym™ ElA method. These low Axsym™ ElA results were concluded to be False Negatives by ElA, since the same patients were independently confirmed to be clinically pregnant. Against this clinically pregnancy data, there was 100% positive agreement versus predicate ABI's SureStep™ and Quidel's QuickVue™ hGG Test devices results as well as for both PPB LiveSure™ hCG Test Strip and Test Card devices, both in-house and at the external independent clinical laboratory.

Thus, compared to independent clinically Positive diagnoses of pregnancy, these studies found that both PPB LiveSure™ hCG Test Strip and Test Card devices were substantially equivalent in performance to approved predicate ABI's SureStep™ and Quidel's QuickVue™ hCG test devices, as well as to the quantitative Axsym™ EIA assay results. Addit onally, compared to independent Negative diagnoses of pregnancy, these studies showed that both PPB LiveSure™ hCG Test Strip and Test Card devices were substantially equivalent in performance to approved predicate ABI's SureStep™ and QuickVue™ hCG test devices, and gave results that were 95% or better in equivalency to the quantitative Axsym™ EIA assay results. Substantial equivalency versus these two predicate IVD devices was thus confirmed for both PPB LiveSure™ hCG Test Strip and Test Card IVD devices.

Additional information on this submission may be obtained by contacting Alice Yu, Vice President, Pan Probe Biotech, Inc. at 1- 858-689-9936 or by fax at 1-858-689-6896.

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Image /page/1/Picture/1 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" arranged around the perimeter. Inside the circle is an abstract image of an eagle.

JUL 1 5 2002

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Pan Probe Biotech, Inc. c/o Alfredo J. Quattrone, Ph.D., D.A.B.T. Medical Device Safety Section California Department of Health Food & Drug Branch P.O. Box 942732 (MS-357) Sacramento, CA 94234-7320

1-020968 Re:

Trade/Device Name: LiveSure™ hCG Urinary Pregnancy Test Strip and Test Card Regulation Number: 21 CFR 862.1155 Regulation Name: Human chorionic gonadotropin (HCG) test system Regulatory Class: Class II Product Code: JHI Dated: June 28, 2002 Received: July 1, 2002

Dear Dr. Quattrone:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such 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 801); 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.

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This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrb/dsma/dsmamain.html".

Sincerely yours,

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory-Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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510k Submission for the Pan Probe Biotech, Inc. LiveSure™ Human Chorionic Gonadotropin (LiveSure™ hCG) Rapid Urinary Pregnancy Test Immunoassay Devices

Pan Probe Biotech, Inc.

Proprietary Information

Revision D, July 11, 2002

510(k) Number (if known): 21 CFR 862.1155; Prod. Code: DHA

DEVICE NAME: Pan Probe Biotech (PPB), Inc. LiveSure™ Human Chorionic Gonadotropin (LiveSure™ hCG) Rapid Urinary Pregnancy Test Strip and Test Card Immunoassay Devices

INDICATIONS FOR USE STATEMENT:

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Lian Cooper

Division Sign-Off Division of Clinical Laboratory Devices 510(k) Number

Prescription Use: or (Per 21 CFF 801.109)

Over-the-Counter Use: (Optional Format 1-2-96)

Regulation Number and Section

§ 862.1155 Human chorionic gonadotropin (HCG) test system.

(a)
Human chorionic gonadotropin (HCG) test system intended for the early detection of pregnancy —(1)Identification. A human chorionic gonadotropin (HCG) test system is a device intended for the early detection of pregnancy is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class II.(b)
Human chorionic gonadotropin (HCG) test system intended for any uses other than early detection of pregnancy —(1)Identification. A human chorionic goadotropin (HCG) test system is a device intended for any uses other than early detection of pregnancy (such as an aid in the diagnosis, prognosis, and management of treatment of persons with certain tumors or carcinomas) is intended to measure HCG, a placental hormone, in plasma or urine.(2)
Classification. Class III.(3)
Date PMA or notice of completion of a PDP is required. As of the enactment date of the amendments, May 28, 1976, an approval under section 515 of the act is required before the device described in paragraph (b)(1) may be commercially distributed. See § 862.3.