Syntron's QuikPac II One Step Benzodiazepine assay is a rapid, qualitative, competitive binding immunoassay for the determination of Benzodiazepine in urine at the cutoff level of 200 ng/ml. The test provides only preliminary data which should be confirmed by other methods such as gas chromatography/mass spectrophotometry (GC/MS). Clinical considerations and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are indicated6. Syntron's QuikPac II One Step Benzodiazepine Test is not intended to monitor drug levels, but only to screen urines for the presence of Benzodiazepine and its metabolites.

Device Description

Syntron's QuikPac II One Step Benzodiazepine Test consists of a chromatographic absorbent device in which the drug or drug metabolites in the sample compete with a drug conjugate immobilized on a porous membrane support for the limited antibody sites. As the test sample flows through the absorbent device, the labeled antibody-dye conjugate binds to the free drug in the specimen forming an antibody:antigen complex. This complex competes with immobilized antigen conjugate in the positive reaction zone and will not produce a magenta color band when the drug is above the detection level of 200 ng/ml. Unbound dye conjugate binds to the reagent in the control zone, producing a magenta color band, demonstrating that the reagents and device are functioning correctly.

AI/ML Overview

Here's an analysis of the provided text, focusing on the acceptance criteria and the study details:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criterion	QuikPac II Performance (In-house)	QuikPac II Performance (Clinical Trial)	Predicate Device Performance (EMIT® II)	Confirmatory Method Performance (GC/MS)
Agreement within positive samples	1.000 (100%)	1.00 (100%)	Not explicitly stated for EMIT® II alone	All positive samples by either screening method were confirmed by GC/MS (200).
Agreement within negative samples	0.9740 (97.40%)	0.9542 (95.42%)	Not explicitly stated for EMIT® II alone	Not directly applicable for GC/MS comparison for negative agreement; GC/MS used to confirm presence below cutoff for false positives.
Accuracy	98.54%	97.69%	Not explicitly stated for EMIT® II alone	Not directly applicable, as accuracy here is relative to EMIT® II for the in-house study, and EMIT® II itself is compared to GC/MS for false positives.
False Positives	2 in-house	7 in clinical trial	7 false positives (in clinical trial data)	GC/MS (200) confirmed presence below 200 ng/ml for false positives.
False Negatives	0 in-house	0 in clinical trial	Not explicitly stated for EMIT® II; implied zero false negatives as positive agreement is 100%.	Not applicable, as no false negatives were reported.
Detection Level	Above 200 ng/ml	Above 200 ng/ml	Run at 200 ng/ml	Used as the cutoff for confirmation (200 ng/ml)

Note on Acceptance Criteria: The document does not explicitly state pre-defined acceptance criteria in terms of specific thresholds for accuracy, sensitivity, or specificity that the device had to meet. Instead, it presents the results of studies and implies that these results were deemed acceptable for substantial equivalence. The predicate device (Syva EMIT® II) is used as a comparator, and GC/MS is used as the gold standard for confirmation.

2. Sample Sizes and Data Provenance

Test Set Sample Sizes:
- In-house testing: Not explicitly stated, but the performance metrics (1.000 agreement for positive, 0.9740 for negative, 98.54% accuracy) were derived from testing against "samples documented to be positive by GC/MS(200)". The number of false positives (2) is mentioned for the in-house testing.
- Clinical Trial: 303 samples.
Data Provenance: The document does not explicitly state the country of origin.
- In-house testing: Performed by Syntron Bioresearch, Inc. (the sponsor).
- Clinical Trial: The samples were presumably collected as part of a clinical trial, implying prospective data collection, though not explicitly stated as such. It mentions "The testing performed by both the sponsor and the Clinical Trial site." This suggests some clinical trial data.

3. Number of Experts and Qualifications for Ground Truth

Number of Experts: Not applicable. The ground truth was established by laboratory methods, not by human expert interpretation of images or other subjective data.
Qualifications of Experts: Not applicable.

4. Adjudication Method for the Test Set

Adjudication Method: Not applicable. The "ground truth" was established through Gas Chromatography/Mass Spectrophotometry (GC/MS) at a specific cutoff (200 ng/ml), which is a definitive laboratory technique, not requiring human adjudication of differing interpretations.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

MRMC Study: No. This is a diagnostic device for substance detection in urine, not an imaging device that requires human interpretation or assistance. Therefore, an MRMC study is not relevant.
Effect size of human readers with/without AI: Not applicable.

6. Standalone (Algorithm Only) Performance

Standalone Performance: Yes. The "QuikPac II One Step Benzodiazepine Test" is a standalone device. Its performance metrics (agreement, accuracy) were measured directly against a comparator (EMIT® II) and a confirmatory gold standard (GC/MS). The results reported are the standalone performance of the device. There is no human-in-the-loop component for the device's operation or interpretation of its direct output (color band).

7. Type of Ground Truth Used

Type of Ground Truth: Chemical analysis and confirmed presence/absence of benzodiazepines. Specifically, Gas Chromatography/Mass Spectrophotometry (GC/MS) at a cutoff level of 200 ng/ml was used as the definitive method to establish the true presence or absence of the drug and its metabolites.

8. Sample Size for the Training Set

Training Set Sample Size: The document does not provide information about a separate "training set" or its size. This type of diagnostic device (immunoassay) is typically developed and validated using known samples rather than machine learning algorithms requiring a distinct training phase. The "in-house testing" and "clinical trial" refer to the validation/testing of the final device.

9. How Ground Truth for the Training Set Was Established

Ground Truth for Training Set: Not applicable, as a distinct training set is not mentioned for this type of device. The development process likely involved using samples of known benzodiazepine concentration (established by methods like GC/MS) to calibrate the assay's sensitivity and specificity, but these wouldn't typically be referred to as a "training set" in the context of AI/ML. The "in-house testing" used "samples documented to be positive by GC/MS(200)."

Summary

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K923326

510k Submission for QuikPac II One Step Benzodiazepine Test FEB 2 4 1998 Syntron Bioresearch, Inc. Page 78 of 78 Pages

Revision B 10/17/97 Printed on 11/13/97

Summary of Safety and Effectiveness

The sponsor, Syntron Bioresearch, Inc. (2774 Loker Ave. West, Carlsbad, California, 92008), has developed, manufactured, and tested under GMP/GLP guidelines a device for the qualitative testing of urine for the presence of Benzodiazepine and its metabolites in a screening format.

The trade name of the device is QuikPac II One Step Benzodiazepine Test having a designated common name of Benzodiazepine Test System and a classification as a Class II device per 21 CFR 9 862.3170. This device is intended for the medical/forensic screening of urine.

In-house testing of Syntron's QuikPac II One Step Benzodiazepine Test yielded an agreement within positive samples of 1.000 and an agreement within negative samples of 0.9740 and an accuracy of 98.54% when tested against Syva EMIT® II on samples documented to be positive by GC/MS(200). A clinical trial consisting of 303 samples was run and the combined data vielded an agreement within positive samples of 100%, an agreement within negative of 95.42% with an accuracy of 97.69% when compared to Emit II® run at 200 ng/ml. By non parametric testing the results are significantly different from one another. Emit II vielded 7 false positives. GC/MSc200) results indicated the presence of drugs, but at a level below the cutoff of 200 ng/ml.

All positive samples by either screening method were confirmed by GC/MScoo. The testing performed by both the sponsor and the Clinical Trial site did find 2 and 7 respectively false positives and no false negatives in the samples tested. GC/MSwop confirmed the presence of benzodiazepines but at levels below the cutoff of 200 ng/ml.

Additional information on this submission may be obtained by contacting Dr. Cleve W. Laird, President, Drial Consultants, Inc. at 805-522-6223(Ca) or by fax at 805-522-1526.

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Image /page/1/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle-like symbol with three curved lines representing the body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the symbol.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

FEB 24 1998

Cleve W. Laird, Ph.D. President and CEO Drial Consultants, Inc. 1420 Los Angeles Avenue, Suite 201 Simi Valley, California 93065

Re : K973326 QuikPac One Step Benzodiazepine Test Regulatory Class: II Product Code: JXM January 15, 1998 Dated: January 16, 1998 Received:

Dear Dr. Laird:

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 (for the indications for use stated in the enclosure) 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 The general controls provisions of the Act of the Act. include requirements for annual reqistration, listing of devices, qood 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 Requlations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current-Good Manufacturing Practice requirements, as setforth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory In addition, FDA may publish further announcements action. 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 requlations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770) 488-7655.

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" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours,
Steven Litman

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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510(k) Number (if Known): No Yet Assigned

Device Name: QuikPac II One Step Opiate Assay

Indications For Use:

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

Concurance of CDRH, Office of Device Evaluation (ODE)

Division Sign Off

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

Perscription Use: (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).