The Pan Probe Biotech LiveSure™ Barbiturates Screen Test Card and Test Strip devices are rapid in vitro diagnostic (IVD) qualitative lateral flow immuno-chromatographic competitive urinary assays for the detection of Barbiturates (e.g., Amobarbital, Butalbital, Pentobarbital, Secobarbital, Phenobarbital, Phenobarbital, etc.), analogs and metabolites (collectively termed: BAR) in human urine at the NIDA (National Institute on Drug Abuse) modified (Substance Abuse and Mental Health Services Administration) cut-off level of 300 ng BAR/M. The cut-off for both LiveSure™ Test Card and Test Strip device methods has been set at 300 ng BAR drug/ml based upon calibration using Secobarbital as a prototype Barbiturate/BAR drug, and ng BRK drugmit bagod upen vith a GCMS method for the quantitation of all the Secobarbital 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™ BAR Screen Tests for BAR provide only preliminary analytical data. A more specific quantitative alternative method must be used in order to obtain a confirmed analytical result. Both NIDA and SAMHSA have established gas chromatography/mass spectrometry (GC/MS) as a 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™ Barbiturates Screen Test Card and Test Strips (i.e., LiveSure™ Barbiturates) devices are rapid qualitative competitive chromatographic IVD immunoassays, in which chemically labeled drug conjugate competes with any Barbiturate (BAR) drugs, analogs or metabolites that may be present in test urinary samples for limited specific antibody binding sites. LiveSure™ Barbiturates 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 against BAR. Each 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 BAR, and a chromatographic membrane precoated with a chemically modified Barbiturate [Secobarbital] drug-conjugate as a capture reagent. The Test region of each device has been layered with a Barbiturate [Secobarbital] drug-conjugate as a 1" capture region of dail the Process Control region has been pre-coated with a 200 anti-mouse antibody reagent derived from goat. A pink colored antibody-colloidal gold conjugate pad is placed to the right of a test strip. In the absence of BAR drugs, analogs or metabolites in urine, pink colored antibodycolloidal gold conjugates move chromatographically along with a urinary sample on the membrane by capillary action. Antibody-colloidal gold conjugate binds to BAR-drug conjugate, forming an antibodyantigen complex. This antibody-BAR-drug conjugate appears as a second visible pink colored band and as a captured reagent at the test region. Any BAR drugs, analogs or metabolites that are present in a sample urine act as antigens, competing with BAR-drug conjugate at the test band region for limited BAR-antibody binding sites on antibody-colloidal gold conjugate. When a sufficient concentration of urinary BAR drugs, analogs or metabolites are present, these analytes block the limited antibody binding sites. This blockagebinding prevents attachment of pink colored antibody-colloidal gold conjugate at the BAR-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 presence of BAR in urine samples. Thus, negative urine samples produces two pink colored bands, while positive urine samples only one pink colored band.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the LiveSure™ BARBITURATES SCREEN TESTS, based on the provided 510(k) submission:

Acceptance Criteria and Device Performance Study

The primary study performed was a clinical evaluation comparing the LiveSure™ Barbiturates Screen Test Card and Test Strip devices against a predicate device (EMIT® II Assay) and a confirmatory method (GC/MS).

1. Table of Acceptance Criteria and Reported Device Performance

The submission doesn't explicitly define "acceptance criteria" as a separate, pre-specified table with target values. Instead, the study results are presented as evidence of equivalency and accuracy. Based on the "Summary Statement of Safety and Effectiveness," the implied acceptance criteria are high agreement percentages with GC/MS for both positive and negative results, and equivalency to the predicate EMIT® II Assay.

Performance Metric	Implied Acceptance Criteria (Goal)	LiveSure™ Test Card Performance	LiveSure™ Test Strip Performance	Predicate (EMIT® II) Performance against GC/MS
Agreement with GC/MS (Positive)	High agreement (e.g., >95-100%)	100%	100%	100%
Agreement with GC/MS (Negative)	High agreement (e.g., >95-100%)	100%	99.6%	99.7%
Agreement with EMIT® II (Positive)	100%	100%	100%	N/A (predicate)
Specificity vs EMIT® II (Negative)	High specificity (e.g., >95-100%)	100%	99.6%	N/A (predicate)
Overall Accuracy vs GC/MS	High accuracy (e.g., >95-100%)	335/335 (100%)	334/335 (99.7%)	334/335 (99.7%)
False Positives (at ±25% of NIDA/SAMHSA cut-off)	0 false positives	0	0	N/A (not reported for predicate)

Note: The phrasing "essentially showing equivalency" and the high agreement percentages suggest an implicit acceptance of very strong correlation and accuracy compared to the gold standard and predicate.

2. Sample Size Used for the Test Set and Data Provenance

Sample Size: 335 urine samples.
Data Provenance: The submission does not explicitly state the country of origin. It indicates "independent clinical testing...at an external reference laboratory." It is a prospective study as it involves collecting and testing samples for comparison.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

The study used GC/MS (Gas Chromatography/Mass Spectrometry) as the confirmatory method for establishing the ground truth for barbiturates presence and concentration. GC/MS is an analytical chemistry technique, not a human expert. Therefore, the concept of "experts establishing ground truth" in the traditional sense (e.g., radiologists interpreting images) does not directly apply here. Instead, it relies on the established accuracy and reliability of the GC/MS method.
The qualifications of the personnel operating the GC/MS are not specified, but it would typically be conducted by trained laboratory technicians or chemists in a certified laboratory setting.

4. Adjudication Method for the Test Set

Adjudication, as in multiple human readers resolving discrepancies, is not applicable in this context. The LiveSure™ devices provide a visual qualitative result (presence or absence of a band), and the GC/MS provides a quantitative, definitive result. Discrepancies would be resolved by the GC/MS result being the higher standard.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, an MRMC comparative effectiveness study was not done. This type of study typically applies to imaging diagnostics where multiple human readers interpret results, and the AI's impact on their performance is measured.
This submission describes a standalone performance study of an in-vitro diagnostic (IVD) device, compared to a predicate and a gold standard.

6. If a Standalone Performance Study was done

Yes, a standalone performance study was done. The results reported (e.g., "LiveSure™ Barbiturates Test Card and Test Strip gave overall accuracy results of 335/335 (100%) and 334/335 (99.7%), respectively, versus GC/MS quantitative BAR data") directly reflect the algorithm's (or device's) own performance in identifying barbiturates in urine samples without human interpretation of the device's output. The device itself produces a visual result which is then read.

7. The Type of Ground Truth Used

The primary ground truth used was GC/MS quantitative data. This is considered a highly reliable and definitive analytical method for drug identification and quantification in toxicology. The submission explicitly states, "Both NIDA and SAMHSA have established gas chromatography/mass spectrometry (GC/MS) as a preferred confirmatory method."

8. The Sample Size for the Training Set

The submission does not explicitly state a separate training set sample size. This is common for this type of IVD device where the "training" primarily involves internal development and optimization of the immunoassay components (antibodies, conjugates, cut-off levels) to achieve desired sensitivity and specificity.
The "in-house testing of LiveSure™ Barbiturates Screen Test Strip devices against EMIT® II Assay" mentioned could be interpreted as part of the development/internal validation process that predates the formal clinical study, but it's not delineated as a distinct "training set" in the context of machine learning.

9. How the Ground Truth for the Training Set Was Established

Since a distinct "training set" is not detailed, the method for establishing its ground truth is also not explicitly described. However, given the context, any internal development or optimization (analogous to 'training') would likely have used:
- Known spiked samples: Urine samples with precisely known concentrations of barbiturates (e.g., using Secobarbital as a prototype, as mentioned for calibration).
- Reference methods: Comparison against established laboratory methods, potentially including early GC/MS analyses or other validated techniques, to ensure the device's performance aligned with expected results during development. The mention of using "Secobarbital as a prototype Barbiturate/BAR drug, and with a GCMS method for the quantitation of all the Secobarbital standard and urine test solutions" points to how the calibration and development (training) would have leveraged GC/MS for accuracy.

Summary

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510k Submission for

LiveSure™ BARBITURATES SCREEN TESTS

Pan Probe Biotech, Inc.

July 16. 2001

SUMMARY STATEMENT OF SAFETY AND EFFECTIVENESS

The sponsor, Pan Probe Biotech, Inc., has developed, manufactured, and tested under Good Laboratory Practices guidelines, in vitro diagnostic (IVD) devices for qualitative testing of urine samples for the presence of Barbiturates, analogs, and metabolites in a IVD screening format.

The trade name of the devices are the Pan Probe Biotech LiveSure™ Barbiturates Screen Test Card and The Strip, having a FDA designated common name of Barbiturates Test Systems, and a classification as a rost only, naming a P D P acongreating owith product code: DIS. These IVD devices are intended for medical and forensic screening of urines for Barbiturates, analogs and metabolites.

In-house testing of LiveSure™ Barbiturates Screen Test Strip devices against EMIT® II Assay as a predicate has provided data essentially showing equivalency between these devices and the predicate EMIT® II Assay. Additionally, independent clinical testing of 335 urine samples against LiveSure™ Barbiturates Screen Test Card and Test Strip devices, as well as EMIT® II Assay at an external reference laboratory has resulted in a 100% percent agreement with all GC/MS quantitative positive results. Moreover, LiveSure™ Barbiturates Test Card or Strip gave a 100% and a 99.6% agreement with GCMS negative results. In comparing both the Test Card positives and Test Strip positives with the EMIT® II positives, a 100% agreement with EMIT® II was obtained with both Test devices. Specificity of the Test Card and Test Strip negatives with EMIT® II negatives was shown to be a 100% and a 99.6%, respectively. In terms of overall accuracy of values at and below the ±25% range of the NIDA/SAMHSA cut-off of 300 ng BAR/ml, however, the LiveSure™ Barbiturates Screen Test Card and Strip yielded no false positives or FP. Finally, versus GC/MS quantitative BAR data, the LiveSure™ Barbiturates Test Card and Test Strip gave overall accuracy results of 335/335 (100%) and 334/335 (99.7%), respectively, whereas 335/335 (100%) and 334/335 (99.7%) accuracy was obtained with EMIT®II. Thus, as judged against GC/MS results from an independent laboratory, the LiveSure™ Barbiturates Test Card and Test Strip were determined to be equivalent in performance with each other, and with EMIT®Il assays.

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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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/1/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular border with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the circumference. Inside the circle is an abstract symbol that resembles an eagle or bird in flight, composed of three curved lines.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 2 0 2001

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: K012133 Re: JT0(K) Name: Pan Probe Biotech LiveSure™ Barbiturates Screen Tests Regulation Number: 862.3150 Regulatory Class: II Product Code: DIS Dated: July 3, 2001 Received: July 9, 2001

Dear Dr.Barquest:

We have reviewed your Section 510(k) notification of intent to market the device referenced we have formewou your boouen be device is substantially equivalent to devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device mendments, or to devices that have been reclassified in accordance with the provisions of the Amendinents, or to de rios and Cosmetic Act (Act). You may, therefore, market the device, subject to I cochar I ood, Drog, and Goldine Set. The general controls provisions of the Act include the general connois pro risting 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 (1 chiaries Approval), it they of the Code of Federal Regulations, Title 21, Parts 800 to 895. allooting your as revers compliance with the Good Manufacturing A subbanianaly of a rates of the more of (GMP) regulation (21 CFR Part 820) and that, through I ractive for Meanaryons, the Food and Drug Administration (FDA) will verify such perfour offirmspocions, are south the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal audition, I Dri may puonse to your premarket notification submission does not affect Register. Thease note: This response to yours 542 of the Act for devices under the ally Contraction you might han 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 This lection. The FDA finding of substantial equivalence of your device to a legally marketed noutheation. The I Dr Financelassification 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, (201) 594-1566. Traditions 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 mionination on your roop at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Putman

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™ BARBITURATES 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™ Barbiturates Screen Tests

INDICATIONS FOR USE STATEMENT:

The Pan Probe Biotech LiveSure™ Barbiturates Screen Test Card and Test Strip devices are rapid in vitro diagnostic (IVD) qualitative lateral flow immuno-chromatographic competitive urinary assays for ഗ്രാ diagnosic (ru) qualitatio latore novembital, Phenobarbital, Phenobarbital, etc.), analogs and metabolites (collectively termed: BAR) in human urine at the NIDA (National Institute on Drug Abuse) modified (Substance Abuse and Mental Health Services Administration) cut-off level of 300 ng BAR/M. The cut-off for both LiveSure™ Test Card and Test Strip device methods has been set at 300 ng BAR drug/ml based upon calibration using Secobarbital as a prototype Barbiturate/BAR drug, and ng BRK drugmit bagod upen vith a GCMS method for the quantitation of all the Secobarbital 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™ BAR Screen Tests for BAR provide only preliminary analytical data. A more specific quantitative alternative method must be used in order to obtain a confirmed analytical result. Both NIDA and SAMHSA have established gas chromatography/mass spectrometry (GC/MS) as a 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)

Dan Cooper

(Division Sign-Off)

(Division Sign-On)
Division of Clinical Laboratory Devices
510(k) Number N02133

Prescription Use:
(Per 21 CFR 801.109)

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

Do Not Copy

Regulation Number and Section

§ 862.3150 Barbiturate test system.

(a)
Identification. A barbiturate test system is a device intended to measure barbiturates, a class of hypnotic and sedative drugs, in serum, urine, and gastric contents. Measurements obtained by this device are used in the diagnosis and treatment of barbiturate use or overdose and in monitoring levels of barbiturate to ensure appropriate therapy.(b)
Classification. Class II (special controls). A barbiturate 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).