The Pan Probe Biotech LiveSure™ Benzodiazepines Screen Test Card and Test Strip devices are qualitative lateral flow immuno-chromatographic competitive urinary rapid in vitro diagnostic (IVD) qualitative assays for detection of Benzodiazepines drugs, and metabolites (BZD) in human urine at the NIDA (National Institute of Drug Abuse) cut-off of 300 ng BZD/ml. The cut-off for both LiveSure™ Test Card and Test Strip device methods has been set at 300 ng BZD drug/ml based upon calibration using the parent benzodiazepine/BZD drug, and using Oxazepam standards with a GC/MS method for the quantitation of all the Oxazepam standard and urine test solutions. These IVD tests are intended for visual, qualitative screening, for professional use only, and are not intended for quantitative results, nor for over the counter sales. Pan Probe Biotech LiveSure™ BZD Screen Tests for BZD provide only preliminary qualitative analytical data. A more specific quantitative alternative method must be used in order to obtain a confirmed analytical result. NIDA recommends gas chromatography/mass spectrometry (GC/MS) as the preferred confirmatory method. Clinical considerations and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are indicated.

Device Description

The Pan Probe Biotech LiveSure™ Benzodiazepines Screen Test Card and Test Strip (i.e., LiveSure™ BZD Screen Tests) devices are rapid qualitative competitive chromatographic IVD immunoassays, in which a chemically labeled drug conjugate competes with any Benzodiazepine (BZD) drugs, analogs or metabolites that may be present in test urine samples for limited specific antibody binding sites. LiveSure™ Benzodiazepines devices have a unique membrane pre-coated with a gold conjugate immunoassay indicator that is pre-labeled with specific monoclonal antibody from mouse directed against BZD drugs. The Test Strip and Test Card consists of a membrane absorbent pad having a gold-probe-conjugate pre-labeled with specific monoclonal antibody from mouse that is directed against BZD drugs, and a chromatographic membrane pre-coated with a chemically modified Benzodiazepine (Oxazepam) drug-conjugate as a capture reagent. The Test region of each device has been layered with a Benzodiazepine [Oxazepam] drug-conjugate as a 1st capture reagent, while the Process Control region has been pre-coated with a 2nd anti-mouse antibody reagent derived from goat. A pink colored anti-BZD monoconal antibody-colloidal gold conjugate pad is placed to the right of a test strip. In the absence of BZD drugs, analogs or metabolites in urine, pink colored antibody-colloidal gold conjugates move chromatographically along with the urinary samples on the membrane by capillary action. Antibody-colloidal gold conjugate binds to BZD-drug conjugate, forming an antibody-antigen complex. This antibody-BZD-drug conjugate appears as second visible pink colored band and captured reagent at the test region. Any BZD drugs, analogs or metabolites that are present in a sample urine act as antigens, competing with BZD-drug conjugate at the test band region for limited BZD-antibody binding sites on antibody-colloidal gold conjugate. When a sufficient concentration of urinary BZD drugs, analogs or metabolites are present, these analytes block the limited antibody binding sites. This blockage-binding prevents attachment of pink colored antibody-colloidal gold conjugate at the BZD-drug conjugate zone located at the test band region. To serve as a procedural control, a pink colored band in a control region will always appear, regardless of the presence of BZD in urine samples. Thus, negative urine samples produces two pink colored bands, while positive urine samples produce only one pink colored band.

AI/ML Overview

Let's break down the acceptance criteria and study details for the LiveSure™ Benzodiazepines Screen Tests based on the provided 510k submission.

Acceptance Criteria and Device Performance

The provided document describes the performance of the LiveSure™ Benzodiazepines Screen Test Card and Test Strip devices compared to a predicate device (EMIT® II Assay) and a gold standard (GC/MS). While "acceptance criteria" isn't explicitly listed in a numbered format, the submission implies acceptance based on agreement rates and accuracy compared to these benchmarks, particularly around the NIDA/SAMHSA cut-off.

Here's a table summarizing the implied acceptance criteria and reported performance:

Acceptance Criteria (Implied)	Reported Device Performance (Test Card & Test Strip)
Agreement with GC/MS (Quantitative Positive)	100% agreement with GC/MS quantitative positive results for both devices.
Agreement with GC/MS (Negative)	99.3% agreement with GC/MS negative results for both devices.
Accuracy (Overall vs. GC/MS)	385/387 (99.5%) accuracy for both devices.
False Positives at/below ±25% NIDA/SAMHSA cut-off (300 ng/ml)	No false positives (0 FP) for both devices. (EMIT® II resulted in 1 FP value below the cut-off)
Agreement with Predicate Device (EMIT® II) Positives	98.3% agreement with EMIT® II positives for both devices.
Specificity with Predicate Device (EMIT® II) Negatives	99.5% specificity (agreement) with EMIT® II negatives for both devices.

Study Details

The submission describes a clinical testing study that supports the device's performance.

Sample Size used for the Test Set and Data Provenance:
- Sample Size: 387 urine samples.
- Data Provenance: The independent clinical testing was performed at an "external reference laboratory," suggesting the data is derived from a clinical setting, presumably in the country where the external reference laboratory operates (not explicitly stated, but typically assumed to be the US for a 510k submission). The data is retrospective, as existing urine samples were tested.
Number of Experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not explicitly state the number of experts or their qualifications for establishing the ground truth. However, the ground truth was established by GC/MS (Gas Chromatography/Mass Spectrometry), which is an analytical laboratory method, not a human expert interpretation.
Adjudication method for the test set:
- Not applicable. The ground truth was established by quantitative GC/MS, an objective analytical method, not by expert consensus requiring adjudication.
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 is a rapid qualitative immunoassay for drug screening, not an AI-assisted diagnostic device that would typically involve a multi-reader, multi-case study. The device is read visually by a professional, and its performance is compared to lab-based methods.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, in a sense. The LiveSure™ devices are "standalone" in that they provide a qualitative visual result directly from the sample without further human interpretation beyond reading the positive/negative bands. Their performance was evaluated as such. The "human-in-the-loop" is the professional interpreting the visual bands.
The type of ground truth used:
- GC/MS quantitative positive results and GC/MS negative results. GC/MS is widely considered the "gold standard" for confirmatory drug testing due to its high specificity and sensitivity.
The sample size for the training set:
- The submission does not explicitly mention a separate "training set" or its size. The "in-house testing" against the EMIT® II Assay might represent an internal validation or development phase, but it's not detailed as a distinct training set for a machine learning model, which is not applicable here. The primary performance data relies on the 387 clinical samples.
How the ground truth for the training set was established:
- Not applicable, as a distinct training set (in the context of machine learning) is not described. For any internal development or optimization, the ground truth would likely also be established using GC/MS or similar validated methods, but this is not specified.

Summary

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510k Submission for

LiveSure™ BENZODIAZEPINES SCREEN TESTS

Pan Probe Biotech, Inc.

Revision E, July 16, 2001

SUMMARY STATEMENT OF SAFETY AND EFFECTIVENESS

The sponsor, Pan Probe Biotech, Inc., has developed, manufactured, and tested under Good Laboratory The openod, I an Frob diagnostic (IVD) devices for qualitative testing of urine samples for the presence of Benzodiazepines, analogs, and metabolites in an IVD screening format.

phesinde name of the devices are the Pan Probe Biotech LiveSure™ Benzodiazepines Screen Test Card The Trade Thame of the de noor and of Benzodiazepines Test Systems, and a classification as and rost billp; framig a PPR 862.3170, with product code: JXM. These IVD devices are intended for medical/forensic screening of urines for Benzodiazepines, analogs, and metabolites.

The Pan Probe Biotech LiveSure™ Benzodiazepines Screen Test Card and Test Strip (i.e., LiveSure™ The Fair - robes) devices are rapid qualitative competitive chromatographic IVD immunoassays, in which Donzoally labeled drug conjugate competes with any Benzodiazepine (BZD) drugs, analogs or metabolites that may be present in test urine samples for limited specific antibody binding sites. I liveSure™ Benzodiazepines devices have a unique membrane pre-coated with a gold conjugate immunoassay indicator that is used is pre-labeled with specific monoclonal antibody from mouse directed imministed on the strip and Test Card consists of a membrane absorbent pad having a goldarobe-conjugate pre-labeled with specific monoclonal antibody from mouse that is directed against BZD drugs, and a chromatographic membrane pre-coated with a chemically modified Benzodiazepine (Oxazepam) drug-conjugate as a capture reagent. The Test region of each device has been layered with a Benzodiazepine [Oxazepam] drug-conjugate as a 1* capture reagent, while the Process Control region has been pre-coated with a 200 anti-mouse antibody reagent derived from goat. A pink colored anti-BZD monoconal antibody-colloidal gold conjugate pad is placed to the right of a test strip. In the absence of BZD drugs, analogs or metabolites in urine, pink colored antibody-colloidal gold conjugates move chromatographically along with the urinary samples on the membrane by capillary action. Antibodycolloidal gold conjugate binds to BZD-drug conjugate, forming an antibody-antigen complex. This antibody-BZD-drug conjugate appears as second visible pink colored band and captured reagent at the test region. Any BZD drugs, analogs or metabolites that are present in a sample urine act as antigens, competing with BZD-drug conjugate at the test band region for limited BZD-antibody binding sites on antibody-colloidal gold conjugate. When a sufficient concentration of urinary BZD drugs, analogs or metabolites are present, these analytes block the limited antibody binding sites. This blockage-binding prevents attachment of pink colored antibody-colloidal gold conjugate at the BZD-drug conjugate zone located at the test band region. To serve as a procedural control, a pink colored band in a control region will always appear, regardless of the presence of BZD in urine samples. Thus, negative urine samples produces two pink colored bands, while positive urine samples produce only one pink colored band.

In-house testing of LiveSure™ Benzodiazepines Screen Test Card and Test Strip devices against EMIT® II Assay as a predicate device provided data essentially showing equivalency between these devices and the predicate EMIT® II Assay. Additionally, independent clinical testing of 387 urine samples against LiveSure™ Benzodiazepines Screen Test Card and Test Strip devices, as well as EMIT® II Assay at an external reference laboratory resulted in a 100% percent with all GC/MS quantitative positive results. Moreover, LiveSure™ Benzodiazepines Test Card or Strip gave both 99.3% agreement with GC/MS negative results. In comparing the Test Card and Test Strip positives with EMIT® II positives, both 98.3% respective agreement with EMIT® II was found. Specificity of Test Card and Test Strip negatives with EMIT® II negatives was shown to be 99.5%, respectively. In terms of overall accuracy of values at and below the ±25% range of the NIDA/SAMHSA cut-off of 300 ng/ml of Benzodiazepines, however, the LiveSure™ Benzodiazepines Screen Test Card and Strip yielded no false positives or no FP, but EMIT®Il resulted in 1 FP values for urine samples with GC/MS results below ng/ml. Finally, the LiveSure™ Benzodiazepines Test Card and the Test Strip gave overall accuracy results of 385/387(99.5%) for both, versus GC/MS data, whereas 385/387(99.5%) accuracy was obtained with EMIT®II. Thus, as judged against GC/MS results from an independent laboratory, the LiveSure™ Benzodiazepines Test Card and Test Strip were determined to be equivalent in performance to each other and somewhat superior in capability versus assays with EMIT®II.

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/0 description: The image shows the text "DEPARTMENT OF HEALTH & HUMAN SERVICES". The text is in all caps and is in a bold, sans-serif font. The text is centered in the image and is the only element present.

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Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Pan Probe Biotech, Inc. c/o James M. Barquest, Ph.D. California Department of Health Services Food and Drug Branch PO Box 942732 601 North Seventh Street (MS 357) Sacramento, CA 94234-7320

510(k) Number: K012131 Re: Trade/Device Name: Pan Probe Biotech LiveSure™ Benzodiazepines Screen Tests Regulation Number: 862.3170 Regulatory Class: II Product Code: JXM Dated: July 3, 2001 Received: July 9, 2001

JUL 2 0 2001

Dear Dr.Barquest:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent to 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). 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 (Premarket Approval), 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 895. A substantially equivalent determination assumes compliance with the Good Manufacturing Practice for Medical Devices: General (GMP) regulation (21 CFR Part 820) and that, through periodic GMP inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2

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 nothication. The I'DA intellig of succion 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 CFF Part 801 and If you desire specific advice for your astic devices), please contact the Office of Compliance at additionally 807.10 for in the claims on the promotion and advertising of your device, (301) 594-4588. Additionally, for quest at (301) 594-4639. Also, please note the regulation
complease contact the Office of Compliance at (301) 594-4639. Also, please of Co please contact the Office of Compilance (21CFR 807.97). Other general entitled, "Misoranding by reference to president to president from the Division of Small mionitation on your responsionnes and in the more (800) 638-2041 or (301) 443-6597 or at its Miandracturers "http://www.fda.gov/cdrh/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

LiveSure™ BENZODIAZEPINE SCREEN TESTS

Pan Probe Biotech, Inc.

Proprietary Information

Revision E, July 16, 2001

510(k) Number (if known): Not yet assigned

Device Name: Pan Probe Biotech LiveSure™ Benzodiazepines Screen Tests

INDICATIONS FOR USE STATEMENT:

The Pan Probe Biotech LiveSure™ Benzodiazepines Screen Test Card and Test Strip devices are The Fan Froot Diotoon ENGGIF ENGGIF - Bonabative lateral flow immuno-chromatographic competitive urinary rapid in Thro Glaghoolio (112) qualifanes drugs, and metabolites (BZD) in human urine at assays for detoon of Donestials problems (Substance Abuse and Mental Health the Nox (Hattonal mother of Brag + 300 ng BZD/ml. The cut-off for both LiveSure™ Test Card oon Test Strip device methods has been set at 300 ng BZD drug/ml based upon calibration using and root benzodiazepine/BZD drug, and using Oxazepam standards with a GC/MS method for the quantitation of all the Oxazepam standard and urine test solutions. These IVD tests are intended for visual, qualitative screening, for professional use only, and are not intended for quantitative results, nor for over the counter sales. Pan Probe Biotech LiveSure™ BZD Screen Tests for BZD provide only preliminary qualitative analytical data. A more specific quantitative alternative method must be used in order to obtain a confirmed analytical result. NIDA quartitudio anomano meeting mass spectrometry (GC/MS) as the preferred confirmatory method. Clinical considerations and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are indicated.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Jean Cooger

n Sign-Off)
Clinical Laboratory Devices
K012131

Prescription Use: or (Per 21 CFR 801.109)

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

Regulation Number and Section

§ 862.3170 Benzodiazepine test system.

(a)
Identification. A benzodiazepine test system is a device intended to measure any of the benzodiazepine compounds, sedative and hypnotic drugs, in blood, plasma, and urine. The benzodiazepine compounds include chlordiazepoxide, diazepam, oxazepam, chlorzepate, flurazepam, and nitrazepam. Measurements obtained by this device are used in the diagnosis and treatment of benzodiazepine use or overdose and in monitoring levels of benzodiazepines to ensure appropriate therapy.(b)
Classification. Class II (special controls). A benzodiazepine test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).