The Emit® II Plus Amphetamines Assay is a homogeneous enzyme immunoassay with a 300 ng/mL cutoff, 500 ng/mL cutoff or a 1000 ng/mL cutoff (SAMHSA initial test cutoff level). The assay is intended for use in the qualitative and semiquantitative analyses of amphetamines in human urine. Emit® II Plus assays are designed for use with a number of chemistry analyzers.

The Emit® II Plus Amphetamines Assay provides only a preliminary analytical test result. A more specific alternative chemical method must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.

Device Description

The Emit® II Plus Amphetamines Assay is a homogeneous enzyme immunoassay for the qualitative and semiquantitative analysis of amphetamines in human urine.

AI/ML Overview

Here's an analysis of the provided text regarding the Syva® Emit® II Plus Amphetamines Assay, broken down by your requested criteria:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied by the reported "Percent agreement" with the reference method (GC/MS). While a specific pre-determined threshold for acceptance isn't explicitly stated as "acceptance criteria," the goal is to show a high agreement.

Cutoff Level	Acceptance Criteria (Implied)	Reported Device Performance (Percent Agreement with GC/MS)
300 ng/mL	High agreement with GC/MS	97%
500 ng/mL	High agreement with GC/MS	96%
1000 ng/mL (vs. GC/MS)	High agreement with GC/MS	86%
1000 ng/mL (vs. Predicate Device)	High agreement with predicate device	97%

Note: For the 1000 ng/mL cutoff, there are two comparisons: one against GC/MS and one against the predicate device (Syva® Emit® II Plus Monoclonal Amphetamine/Methamphetamine Assay). Both are listed in the table.

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

Sample Size for Test Set: 124 urine specimens were used for method comparison studies for each cutoff level (300 ng/mL, 500 ng/mL, and 1000 ng/mL).
Data Provenance: The document does not specify the country of origin of the data. It also does not explicitly state whether the study was retrospective or prospective. Given that specimens were "obtained" and then analyzed by both the proposed device and GC/MS, it is likely a retrospective analysis of collected urine samples.

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

This information is not provided in the document. The ground truth was established by Gas Chromatography/Mass Spectrometry (GC/MS) which is a laboratory analytical method, not typically performed by "experts" in the clinical sense (e.g., radiologists). The document does not describe who performed the GC/MS analysis or their qualifications.

4. Adjudication Method for the Test Set

This information is not applicable and therefore not provided. Adjudication typically refers to resolving discrepancies between multiple human readers or between a human reader and an AI. In this study, the primary ground truth is established by an objective analytical method (GC/MS), and the device's results are compared directly to that. There is no mention of human readers or a need for adjudication among them. Discrepancies between the device and GC/MS are reported and sometimes further analyzed semiquantitatively.

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

No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) assay designed to provide a chemical analysis of urine, not to assist human readers in interpreting images or clinical data. Therefore, there's no "human readers improve with AI vs without AI assistance" aspect to evaluate.

6. Standalone Performance (Algorithm Only without Human-in-the-Loop Performance)

Yes, a standalone performance study was done. The Syva® Emit® II Plus Amphetamines Assay is an automated enzyme immunoassay performed on a chemistry analyzer (Syva®-30R Biochemical System). The results presented are the direct output of this automated system compared to the reference method (GC/MS), without any human interpretation of the assay results before comparison. It functions as an "algorithm only" in the context of an IVD.

7. Type of Ground Truth Used

The type of ground truth used was Gas Chromatography/Mass Spectrometry (GC/MS) results. This is considered a highly specific and sensitive reference method for confirming the presence and concentration of substances in biological samples, making it an objective and reliable ground truth for in vitro diagnostic assays like this.

8. Sample Size for the Training Set

The document does not specify a discrete "training set" sample size. For an IVD assay, the development process involves optimization and calibration, which would use various samples, but this is not typically reported as a "training set" in the same way machine learning models report it. The reported studies are for performance validation rather than model training.

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

Since a distinct "training set" with established ground truth as per common AI/ML terminology is not explicitly mentioned or described for this IVD, this information is not provided. The development of the assay itself would involve internal studies and verification cycles, likely using methods such as GC/MS to establish the reference values for calibrators and controls used in the assay.

Summary

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K031004

Dade Behring Inc. 510(k) Premarket Notification Syva® Emit® II Plus Amphetamines Assay

510(k) Summary of Safety and Effectiveness Information Syva® Emit® II Plus Amphetamines Assay March 28, 2003

MANUFACTURER AND CONTACT INFORMATION I.

Manufacturer: Syva Company - Dade Behring Inc. 20400 Mariani Ave. Cupertino, CA 95014

Contact Information: Dade Behring Inc. 500 GBC Drive Newark, DE 19702 Attn: Radames Riesgo Phone: 305.480.7558 FAX: 305.552.5288

II. DEVICE NAME AND CLASSIFICATION NAME

Trade or Proprietary Name: Syva® Emit® II Plus Amphetamines Assay

Common or Usual Name: Enzyme Immunoassay, Amphetamine/Methamphetamine Amphetamine test system (21 CFR §862.3100) Methamphetamine test system (21 CFR §862.3610) Class II

IDENTIFICATION OF THE LEGALLY MARKETED DEVICE III.

Syva® Emit® II Plus Monoclonal Amphetamine/Methamphetamine Assay (K993982).

DEVICE DESCRIPTION IV.

The Emit® II Plus Amphetamines Assay is a homogeneous enzyme immunoassay for the qualitative and semiquantitative analysis of amphetamines in human urine.

V. DEVICE INTENDED USE

ﺗﻘ

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The Emit® II Plus Amphetamines Assay provides only a preliminary analytical test result. A more specific alternative chemical must be used to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC/MS) is the preferred confirmatory method. Other chemical confirmation methods are available. Clinical consideration and professional judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.

VI. SUBSTANTIAL EQIVALENCE

The Emit® II Plus Amphetamines Assay is substantially equivalent in intended use and methodology to the Emit® II Plus Monoclonal Amphetamine/Methamphetamine Assay currently in the market. The proposed device, like the predicate device is a monoclonal antibody assay intended for the qualitative and semiquantitative analysis of amphetamines in human urine.

VII. DEVICE PERFORMANCE CHARACTERISTICS

300 ng/mL Cutoff A.

Method Comparison - Qualitative

Of the sixty-six (66) samples found to be positive by GC/MS (≥ 300 ng/mL total amphetamines), sixty-two (62) were also found positive by Syva Emit II Plus Amphetamines Assay for a percent agreement of 97% (120/124). Fifty-eight (58) samples were found to be negative by GC/MS (<300 ng/mL total amphetamines) and sixty-two (62) were found to be negative by the proposed device. Four (4) discrepant samples were found by the proposed device. Semiquantitative analysis of the discrepant samples using the proposed device showed values for total amphetamines within -25% of the cutoff.

Qualitative Results 300 ng/mL Cutoff
--------------------------------------	--	--	--	--

		Reference Method (GC/MS)
		Positive	Negative
Syva® Emit® II PlusAmphetamines Assay	Positive	62	0
	Negative	4	58

Percent agreement: 97%

ﺔ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﻤﺘﻮﻗﻊ ﺍﻟﺘﻲ ﺗﻘﺮﻳﺒﺎ

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500 ng/mL Cutoff B. Method Comparison - Qualitative

The results of one hundred and twenty-four (124) urine specimens obtained with the Syva® Emit® II Plus Amphetamines Assay on the Syva®-30R Biochemical System (K912024) were compared to the results obtained with the reference method, GC/MS. The proposed method used a cutoff level of 500 ng/mL for total amphetamines. While the results of GC/MS were interpreted using the proposed SAMHSA confirmatory guidelines (amphetamine 250 ng/mL or methamphetamine 250 ng/mL and minimum amphetamine 100 ng/mL).

Fifty-nine (59) samples were found to be positive by GC/MS (proposed SAMHSA guidelines) and sixty-two (62) were found positive (≥500 ng/mL) by Syva® Emit® II Plus Amphetamines Assay for a percent agreement of 96% (119/124). Of the sixty-five (65) samples found to be negative by GC/MS, sixty-two (62) were also found to be negative by ﺎ ﺗﻘﺮ the proposed device. Five (5) discrepant samples were found. Four (4) of the five discrepant samples were identified as positive by the proposed device and were also found to have more than 500 ng/mL of total amphetamines when they were tested semiquantitatively. However, these four samples were considered negative by GC/MS regardless of the total amphetamines results because they did not meet the acceptance criterion of at least 100 ng/mL of amphetamine of the proposed SAMHSA guidelines for confirmatory test. The other discrepant sample was identified as negative by proposed device and was found to have total amphetamines within -25% of the cutoff level when analyzed semiquantitatively.

Qualitative Results 500 ng/mL Cutoff

	Reference Method (GC/MS)
	Positive	Negative
Syva® Emit® II PlusAmphetamines Assay	Positive	58	4
	Negative	1	61

Percent agreement: 96%

ﺰ 1000 ng/mL Cutoff Method Comparison - Qualitative

The results of one hundred and twenty four (124) urine specimens obtained with the Syva® Emit® II Plus Amphetamines Assay on the Syva®-30R Biochemical System (K912024) were compared to GC/MS as reference methodology. The proposed method used a cutoff level of 1000 ng/mL while the reference method used a cutoff level of 500 ng/mL according to SAMHSA confirmatory guideline (amphetamine 500 ng/mL or methamphetamine 500 ng/mL plus minimum amphetamine 200 ng/mL). In addition, the Syva® Emit® II Plus Amphetamines Assay was compared to the Syva® Emit® II Plus Monoclonal Amphetamine/Methamphetamine Assay (K993982) by evaluating the same number of urine

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specimens on the Syva®-30R Biochemical System. For this comparative study, both devices used a cutoff level of 1000 ng/mL for total amphetamines.

Sixty-five (65) samples were found to be positive by GC/MS (SAMHSA confirmatory guidelines) and sixty-two (62) were found positive (≥1000 ng/mL) by Syva® Emit® II Plus Amphetamines Assay for a percent agreement of 86% (107/124). Fifty-nine (59) samples were found to be negative by GC/MS and sixty-two (62) were found to be negative by the proposed device. Seventeen (17) discrepant samples were found. Seven (7) of the discrepant samples that were found positive by the proposed device showed semiquantitative results over 1000 ng/mL, however, they were considered negative by GC/MC because they did not meet the minimum 200 ng/mL amphetamine criterion for SAMHSA confirmatory test. Ten (10) discrepant samples were found to be negative by the proposed test and were found to have total amphetamines values within the -25% and the cutoff. ﻧﺘﻘ

Qualitative Results 1000 ng/mL Cutoff
---------------------------------------	--	--	--	--

		Reference Method (GC/MS)
		Positive	Negative
Syva® Emit® II PlusAmphetamines Assay	Positive	55	7
	Negative	10	52

Percent agreement: 86%

Sixty (60) samples were found to be positive by the comparative method and sixty-two (62) were found positive (≥1000 ng/mL) by Syva® Emit® II Plus Amphetamines Assay for a percent agreement of 97% (120/124). Sixty-four (64) samples were found to be negative by the comparative method and sixty-two (62) were found to be negative by the proposed device. Four discrepant samples were found. Three (3) of the discrepant samples that were found to be positive by the proposed device, were confirmed positive by GC/MS results. One (1) discrepant samples found to be negative by the proposed device was also confirmed as negative by GC/MS results.

Qualitative Results 1000 ng/mL Cutoff

		Comparative Method
		Positive	Negative
Syva® Emit® II PlusAmphetamines Assay	Positive	59	3
	Negative	1	61

Percent agreement: 97%

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Image /page/4/Picture/1 description: The image shows the logo for the Department of Health & Human Services USA. The logo consists of a circular arrangement of the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" surrounding a stylized eagle symbol. The eagle symbol is composed of three curved lines that form the shape of an eagle's head and wings.

JUN - 6 2003

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Rebecca S. Ayash Director. Regulatory Affairs & Compliance Dade Behring, Inc. 500 GBC Drive Newark, DE 19702

Re: K031004

Trade/Device Name: Emit® II Plus Amphetamines Assay Regulation Number: 21 CFR 862. 3100 Regulation Name: Amphetamine test system Regulatory Class: Class II Product Code: DKZ Dated: March 28, 2003 Received: March 31, 2003

Dear Ms Ayash:

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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act 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/cdrh/dsma/dsmamain.html.

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known): _K03 1004

Device Name: Emit® II Plus Amphetamines Assay

Indications for Use:

Sean Cooper
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K031004

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use
(Per 21 CFR 801.109) X

ﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤ

Over-The-Counter-Use (Optional Format 1-2-96)

Regulation Number and Section

§ 862.3100 Amphetamine test system.

(a)
Identification. An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained by this device are used in the diagnosis and treatment of amphetamine use or overdose and in monitoring levels of amphetamine to ensure appropriate therapy.(b)
Classification. Class II (special controls). An amphetamine 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).