The OTI Benzodiazepines Intercept® MICRO-PLATE EIA is intended for use by clinical laboratories in the qualitative determination of benzodiazepines in oral fluid collected with the Intercept® Oral Fluid Drug Test Oral Specimen Collection Device using a 1.0 ng/mL cutoff. FOR IN VITRO DIAGNOSTIC USE.

The OTI Benzodiazepines Intercept® MICRO-PLATE EIA provides only a preliminary analytical test result. A more specific alternative chemical method should be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry/mass spectrometry (GC/MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drugs of abuse test result, particularly when a preliminary, positive result is observed.

Device Description

The OT1 Benzodiazepines Intercept® MICRO-PLATE EIA is a competitive micro-plate immunoassay for the detection of benzodiazepines in oral fluid collected with the Intercept® Oral Fluid Drug Test Oral Specimen Collection Device. Specimen or standard is added to an EIA well in combination with an enzyme-labeled hapten derivative. In an ELA well containing an oral fluid specimen positive for benzodiazepines, there is a competition between the drug and the enzymelabeled hapten to bind the antibody fixed onto the EIA wells are then washed, substrate is added, and color is produced. The absorbance measured for each well at 450 mm is inversely proportional to the amount of benzodiazepines present in the specimen or calibrator/control. Because currently there are no SAMHSA assigned cutoffs for benzodiazepines testing using oral fluid, OTI recommends a cutoff of 1.0 ng/mL when testing oral fluid collected with the Intercept® Oral Fluid Drug Test Oral Specimen Collection Device. This cutoff is within the limit of detection by the OTI Benzodiazepines Intercept® MICRO-PLATE EIA.

AI/ML Overview

Here's an analysis of the provided text regarding the OTI Benzodiazepines Intercept® MICRO-PLATE EIA, focusing on acceptance criteria and the supporting study:

Acceptance Criteria and Device Performance

1. Table of Acceptance Criteria and the Reported Device Performance:

The document doesn't explicitly state "acceptance criteria" as a set of predefined thresholds that the device must meet. Instead, it presents performance characteristics of the proposed device alongside those of a legally marketed predicate device (Abuscreen ONLINE® kit for Benzodiazepines). The implication is that the proposed device's performance should be "essentially equivalent" to the predicate. Therefore, the "acceptance criteria" are inferred to be the performance ranges/values of the predicate device for each characteristic, and the "reported device performance" is the measured performance of the OTI Benzodiazepines Intercept® MICRO-PLATE EIA.

Performance Characteristic	Acceptance Criteria (Predicate Device Performance)	Reported Device Performance (OTI Benzodiazepines Intercept® MICRO-PLATE EIA)
Precision
Intra-assay %CV range	2-7%	4.9-6.5%
Inter-assay %CV range	2-10%	7.6-11.4%
Limit of Detection	< 10 ng/mL	0.2 ng/mL
% Cross-Reactivity
α-Hydroxyalprazolam	112%	10%
α-Hydroxytriazolam	98%	15%
Alprazolam	96%	151%
7-Aminoflunitrazepam	Not tested (for predicate)	6%
7-Aminonitrazepam	52%	8%
Bromazepam	75%	2%
Clorazepate	43%	70%
Chlordiazepoxide	55%	6%
Clonazepam	56%	1%
Desalkylflurazepam	49%	17%
Diazepam	105%	135%
Estazolam	Not tested (for predicate)	130%
Flurazepam	61%	49%
2-Hydroxyethylflurazepam	88%	8%
Lorazepam	59%	< 1%
Medazepam	40%	17%
Midazolam	96%	49%
Nitrazepam	81%	39%
Norchlordiazepoxide	Not tested (for predicate)	3%
Oxaprozin	Not tested (for predicate)	<1%
Oxazepam	98%	7%
Prazepam	84%	107%
Temazepam	Not tested (for predicate)	55%
Triazolam	96%	26%
Clinical Accuracy	N=50 confirmed positive (Predicate) 42 positive, 8 negative (Predicate)	Summarized in a table comparing Intercept results to GC/MS/MS results for 149 specimens.

Study Proving Device Meets Acceptance Criteria:

The "Summary of Performance Data" section ({1}) describes the studies conducted to demonstrate the performance characteristics of the OTI Benzodiazepines Intercept® MICRO-PLATE EIA. The overall conclusion is that "This information concludes that the performance of this device is essentially equivalent to the legally marketed predicate device."

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

Test Set Sample Size: For the "Clinical Accuracy" study, a total of 149 specimens were collected and analyzed.
Data Provenance: The document states "Three separate population studies were performed," implying the data was collected specifically for this purpose (prospective), but does not specify the country of origin.

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

The document does not specify the number or qualifications of experts used for establishing ground truth for the test set.

4. Adjudication Method for the Test Set:

The document does not describe an adjudication method for the test set. The ground truth was established by Gas Chromatography/Mass Spectrometry/Mass Spectrometry (GC/MS/MS).

5. 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:

This device is an in vitro diagnostic (IVD) immunoassay kit, not an AI-powered diagnostic imaging or screening tool that would involve human readers interpreting results with or without AI assistance. Therefore, no MRMC comparative effectiveness study was done in the context of human reader improvement with AI. The study compares the performance of the device itself against a confirmed analytical method (GC/MS/MS).

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

Yes, the performance study for the OTI Benzodiazepines Intercept® MICRO-PLATE EIA is essentially a standalone performance study. The device, an immunoassay kit, functions as an algorithm (chemical reaction leading to a detectable signal) to detect benzodiazepines. Its results are directly compared to the gold standard (GC/MS/MS) without human interpretation as part of the core performance evaluation, though human judgment is recommended for interpreting preliminary positive results.

7. The Type of Ground Truth Used:

The primary ground truth used for verifying the clinical accuracy of the OTI Benzodiazepines Intercept® MICRO-PLATE EIA was Gas Chromatography/Mass Spectrometry/Mass Spectrometry (GC/MS/MS). The document explicitly states: "(GC/MS/MS) is the preferred confirmatory method."

8. The Sample Size for the Training Set:

The document does not specify a separate training set or its sample size. For IVD devices like this, the "development" phase involving internal testing and optimization by the manufacturer might be analogous to a training phase, but it's not structured or reported in the same way as machine learning model training sets. The reported performance data is from a test set.

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

As no distinct training set is identified or its ground truth described, this information is not provided in the document. The ground truth for the evaluation was established using GC/MS/MS.

Summary

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PREMARKET NOTIFICATION 510(k) SUMMARY (As Required By 21 CFR 807.92)

807.92 (a):

1. Submitter's Name:	OraSure Technologies, Inc.
Address:	150 Webster St., Bethlehem, PA 18015
Telephone Number:	(610) 882-1820
Contact Person:	R. Sain Niedbala, Ph.D., BCFE
Date Prepared:	April 10, 2002

1. Device Name: Benzodiazepines Intercept® MICRO-PLATE EIA Proprietary Name: Benzodiazepines Intercept® System Usual Name: Enzyme Immunoassay, Benzodiazepine Classification Name:
  Device to Which Substantial Equivalence Is Claimed: 3.
Roche Diagnostic Systems, Abuscreen ONLINE® kit for Benzodiazepines (urine); K914509
Description of Device: 4.

Principle of the Assay

న్. Intended Use Statement:

The OTI Benzodiazepines Intercept® MICRO-PLATE EIA provides only a preliminary analytical test result. A more specific alternative chemical method should be used in order to obtain a Gas chromatography/mass spectrometry/mass spectrometry confirmed analytical result. (GC/MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drugs of abuse test result, particularly when a preliminary, positive result is observed.

a. Summary of Technological Characteristics: 6.

The OTI Benzodiazenines Intercept® MICRO-PLATE EIA is based on the principle of solid phase competitive enzyme immunoassay. This application is for the OTI Benzodiazepines EIA as a screening tool for the detection of benzodiazepines using specimens collected with the OTIIntercept& Oral Fluid Drug Test Oral Specimen Collection Device.

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b. Summary of Performance Data:

and the state of the state of the states of the states

The performance characteristics of the OTI Benzodiazepines Intercept® MICRO-PLATE EIA are summarized below. This information concludes that the performance of this device is essentially equivalent to the legally marketed predicate device.

	Proposed:							Previously
	Benzodiazepines Intercept®							Cleared
	MICRO-PLATE EIA							(K914509):
								Abuscreen
								ONLINE® kit for
								Benzodiazepines
Performance Characteristics:
Precision
Intra-assay %CV range	4.9-6.5%							2-7%
Inter-assay %CV range	7.6-11.4%							2-10%
Limit of Detection	0.2 ng/mL							< 10 ng/mL
% Cross-Reactivity
α-Hydroxyalprazolam	10%							112%
α-Hydroxytriazolam	15%							98%
Alprazolam	151%							96%
7-Aminoflunitrazepam	6%							Not tested
7-Aminonitrazepam	8%							52%
Bromazepam	2%							75%
Clorazepate	70%							43%
Chlordiazepoxide	6%							55%
Clonazepam	1%							56%
Desalkylflurazepam	17%							49%
Diazepam	135%							105%
Estazolam	130%							Not tested
Flurazepam	49%							61%
2-Hydroxyethylflurazepam	8%							88%
Lorazepam	< 1%							59%
Medazepam	17%							40%
Midazolam	49%							96%
Nitrazepam	39%							81%
Norchlordiazepoxide	3%							Not tested
Oxaprozin	<1%							Not tested
Oxazepam	7%							98%
Prazepam	107%							84%
Temazepam	55%							Not tested
Triazolam	26%							96%
Clinical Accuracy	Three separate population studies were performed to						N=50 confirmed
	characterize performance of the Intercept Test. A total of						positive.
	149 specimens were collected from all three populations.						42 positive, 8
							negative

	The table below summarizes the performance of theIntercept kit with all specimens tested by immunoassay
	and GC/MS/MS.
	InterceptResult	No DrugDetectedbyGC/MS/MS	0.18-0.49	0.5-0.99ng/mL	1.0-1.5ng/mL	>1.5
	Positive	4	5	1	2	26
	Negative	93	7	3	4	4

12 ं

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES U.S.A." arranged around the perimeter. Inside the circle is a stylized design featuring three abstract shapes that resemble human figures or flowing lines.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

R. Sam Niedbala, Ph.D., BCFE Chief Science Officer OraSure Technologies, Inc. 150 Webster Street Bethlehem, PA 18015

APR 1 7 2002

Re: K013882

Trade/Device Name: OTI BENZODIAZEPINES INTERCEPT® MICRO-PLATE EIA Regulation Number: 21 CFR 862.3170 Regulation Name: Benzodiazepine test system Regulatory Class: Class II Product Code: JXM Dated: March 12, 2002 Received: March 14, 2002

Dear Dr. Niedbala:

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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Page 2 -

This letter will allow you to begin marketing your device as described in your 510(k) premarket This leater will and in your distantial equivalence of your device to a legally marketed nothloation: "The 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 1 II you desire specific and 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, (301) 591 1500 - 11 deather (1) 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 miountacturers 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/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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STATEMENT OF INDICATIONS FOR USE

510(k) Number (if known): ____________________________________________________________________________________________________________________________________________________

Device Name: OTI BENZODIAZEPINES INTERCEPT® MICRO-PLATE EIA

Indications For Use:

The OTI Benzodiazepines Intercept® MICRO-PLATE EIA is intended for use by clinical I he off Donazonalespines determination of benzodiazepines in oral fluid collected with the Intercept® Oral Fluid Drug Test Oral Specimen Collection Device using a 1.0 ng/mL cutoff. FOR IN VITRO DIAGNOSTIC USE.

The OTI Benzodiazepines Intercept® MICRO-PLATE EIA provides only a preliminary I ne OTF betwould. A more specific alternative chemical method should be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry/mass spectrometry (GC/MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drugs of abuse test result, particularly when a preliminary, positive result is observed.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)
(Division Sign-Off)	Von Dr Cooper
Division of Clinical Laboratory Devices
510(k) Number	K013882
Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use ________

c:\fda\indica.doc

. . . .

c:\fda\indica.doc

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).