The Emit® II Plus Cocaine Metabolite Assay is a homogeneous drugs-of-abuse enzyme immunoassay with a 150 ng/mL or 300 ng/mL cutoff (SAMSHA initial test cutoff level). The assay is intended for use in the qualitative and semiquantitative analyses of benzoylecgonine (cocaine metabolite) in human urine. Emit ® II Plus assays are designed for use with a number of chemistry analyzers.

The Emit® II Plus Cocaine Metabolite 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 judgement should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.

Device Description

The Emit® II Plus Cocaine Metabolite Assay is a homogeneous enzyme immunoassay with a 150 ng/mL or 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of benzoylecognine (cocaine metabolite) in human urine. The Emit® II Plus Cocaine Metabolite Assay and has been found to be equivalent to the predicate device: Emit® II Cocaine Metabolite Assay with regard to intended use, assay sample, and overall performance characteristics.

AI/ML Overview

The provided document describes the Emit® II Plus Cocaine Metabolite Assay, a homogeneous enzyme immunoassay for detecting benzoylecognine (cocaine metabolite) in human urine. The study presented aims to demonstrate the substantial equivalence of this new assay to a predicate device, the Emit® II Cocaine Metabolite Assay, and its correlation with Gas chromatography/mass spectrometry (GC/MS).

Here's an analysis of the acceptance criteria and the study, organized according to your requested points:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria in a quantitative manner (e.g., "sensitivity must be > X%, specificity > Y%"). Instead, it describes performance in terms of "excellent correlation" and "acceptable precision." For the purpose of this table, I will infer the implicit criteria from the reported results and the comparison to the reference methods.

Acceptance Criterion (Inferred)	Reported Device Performance
Correlation with GC/MS (150 ng/mL cutoff): High agreement with the gold standard for confirmatory results.	100% agreement. (Reported as "excellent correlation to GC/MS (reference method) for the optional 150 ng/mL cutoff level. The percent agreement between these methods was 100%.")
Correlation with Predicate Device (300 ng/mL cutoff): High agreement with the existing legally marketed device.	98% agreement. (Reported as "excellent correlation between Emit® II Cocaine Metabolite Assay and The Emit® II Cocaine Metabolite Assay (comparative method) at the 300 ng/mL cutoff level.") Note: Three discordant samples were borderline positive with the Emit® II Plus, within the precision limit of the predicate.
Qualitative Accuracy (150 ng/mL cutoff): Ability to correctly distinguish positive/negative at specified spike levels.	Negative: Known levels of benzoylecognine ≤ 112.5 ng/mL (minus 25% of 150 ng/mL cutoff) were distinguished as negative. Positive: Spiked levels ≥ 187 ng/mL (plus 25% of 150 ng/mL cutoff, up to 3000 ng/mL) were routinely distinguished as positive.
Qualitative Accuracy (300 ng/mL cutoff): Ability to correctly distinguish positive/negative at specified spike levels.	Negative: Known levels of benzoylecognine ≤ 225 ng/mL (minus 25% of 300 ng/mL cutoff) were distinguished as negative. Positive: Spiked levels ≥ 375 ng/mL (plus 25% of 300 ng/mL cutoff, up to 3000 ng/mL) were routinely distinguished as positive.
Semiquantitative Recovery (150/300 ng/mL): Accuracy of reported concentrations within a specified range.	Recovered within 20% of the nominal value for known spiked concentrations between 45 ng/mL and 900 ng/mL.
Precision (Qualitative mode): Low variability in repeated measurements.	Acceptable. - Within-run %CV for controls and cutoffs (rates) ranged from 0.4% to 0.5%. - Total precision %CV for controls and cutoffs (rates) ranged from 0.5% to 0.6%.
Precision (Semiquantitative mode): Low variability in repeated measurements of concentrations.	Acceptable. - Within-run %CV for controls and cutoffs (concentrations) ranged from 3.7% to 10.9%. - Total precision %CV for controls and cutoffs (concentrations) ranged from 5.1% to 14.9%.
Substantial Equivalence: Overall performance comparable to the predicate device.	The manufacturer concluded the device is "substantially equivalent to the Emit® II Cocaine Metabolite Assay with regard to intended use, assay sample, and overall performance characteristics." This was affirmed by the FDA's 510(k) clearance letter.

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

Sample Size for Test Set:
- For the correlation with GC/MS (150 ng/mL cutoff): The document does not specify the exact number of samples used for the full 100% agreement study. It only mentions that "All positive samples and a portion of negative samples (n=20), as assessed by the Emit® II Plus Cocaine Assay, were analyzed by GC/MS for confirmatory (positive samples) and specificity (negative samples) purposes." This implies at least 20 negative samples plus an unspecified number of positive samples were tested against GC/MS. The number of samples for the 100% agreement claim is not clearly stated.
- For the correlation with the predicate device (300 ng/mL cutoff): The sample size is not explicitly stated, beyond the mention of "three samples were discordant."
- For spiked sample recovery (qualitative and semiquantitative): The number of samples (spiked urine) and replicates is not specified.
- For precision studies: The number of samples/replicates for the precision studies is not specified, only the resulting %CVs.
Data Provenance: The document does not provide information on the country of origin of the data or whether the study was retrospective or prospective. Given the nature of in-vitro diagnostic assays for drug testing, it's typically prospective testing of collected urine samples, but this is not explicitly stated.

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

Not applicable. This device is an in-vitro diagnostic (IVD) assay for chemical analysis. The "ground truth" is established by a reference chemical method (GC/MS) or by known concentrations in spiked samples, not by expert interpretation of images or clinical findings.

4. Adjudication Method for the Test Set

Not applicable. Adjudication methods (like 2+1, 3+1) are typically used for studies involving human interpretation (e.g., radiologists, pathologists) where discrepancies need to be resolved. For an IVD device, the "adjudication" of results is based on comparison to the reference chemical method (GC/MS) or expected values for spiked samples. Discordant results are typically investigated to understand the reason (e.g., borderline concentration, interference).

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

Not applicable. This is an in-vitro diagnostic device for chemical analysis. It does not involve human readers interpreting cases or AI assistance in the context of diagnostic imaging.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the studies described are standalone performance evaluations of the Emit® II Plus Cocaine Metabolite Assay. The device (assay) itself produces quantitative or qualitative results, which are then compared to reference methods. While human operators perform the testing, the results are derived directly from the assay's chemical reactions and detection system, without an "algorithm" in the AI sense or a human performing interpretation of the assay's output that would require a human-in-the-loop study design.

7. The Type of Ground Truth Used

The ground truth used in the studies includes:

Chemical Reference Method: Gas chromatography/mass spectrometry (GC/MS) for confirmation of drug metabolite presence and concentration in real urine samples. GC/MS is considered the gold standard for drug quantification.
Known Spiked Concentrations: Urine samples spiked with known, precise concentrations of benzoylecognine for evaluating qualitative accuracy (distinguishing positive/negative at specific cutoffs) and semiquantitative recovery.

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of machine learning or AI. This is a traditional in-vitro diagnostic assay. The development of such assays involves formulation, optimization, and characterization, but not typically a "training set" in the AI sense.

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

Not applicable, as there is no "training set" for an AI algorithm described for this device. The assay itself relies on established biochemical principles and reagents, not on learning from data in the way an AI model does.

Summary

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JAN 2 7 2000

510(k) SUMMARY OF SAFETY AND EFFECTIVENESS

1. Manufacturer and Contact Information:

Manufacturer:	Syva Company- Dade Behring Inc.20400 Mariani Ave.Cupertino, CA 95014
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Contact Information: Paul Rogers Syva Company- Dade Behring Inc. 3403 Yerba Buena Road San Jose, CA 95161-9013 Tel: 408-239-2309

2. Device Classification Name:

"Cocaine metabolite test system" has been classified as Class II Reference: 21 CRF8862.3250. revised April 1, 1998

3. Intended Use:

The Emit® II Plus Cocaine Metabolite Assay is a homogeneous enzyme immunoassay with a 150 ng/mL or 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiguantitative analyses of benzoylecognine (cocaine metabolite) in human urine. The Emit® II Plus Cocaine Metabolite 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 judgement should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.

4. Device Description and Characteristics:

This 510(k) Summary of Safety and Effectiveness is being submitted in accordance with the requirements of SMDA 1990.

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Comparative Analysis:

The Emit® II Plus Cocaine Metabolite Assay showed excellent correlation to GC/MS (reference method) for the optional 150 ng/mL cutoff level. The GC/MS reference method has a limit of quantitation (LOQ) of 30 ng/mL. The percent agreement between these methods was 100%. The Emit® II Plus Cocaine Metabolite Assay showed excellent correlation between Emit® II Cocaine Metabolite Assay and The Emit® II Cocaine Metabolite Assay (comparative method) at the 300 ng/mL cutoff level. The percent agreement between these methods was 98%. Three samples were discordant and were analyzed by GC/MS. These samples were borderline positive with the Emit® II Plus 300 ng/mL Cocaine Metabolite Assay. These borderline results were with-in the precision limit of the Emit® II Cocaine Metabolite Assay (comparative method).

All positive samples and a portion of negative samples (n=20), as assessed by the Emit® 11 Plus Cocaine Assay, were analyzed by GC/MS for confirmatory (positive samples) and specificity (negative samples) purposes.

Spiked Sample Recovery:

The qualitative and semiquantitative attributes were assessed by determining the accuracy for the analyte in spiked samples by the Emit® II Plus Cocaine Metabolite Assay.

Qualitative -150 ng/mL cutoff

Known levels of benzovlecognine, spiked at levels less than or equal to the minus 25% of the 150 ng/mL cutoff (0-112.5 ng/mL) were distinguished as negative. Spiked levels greater than or equal to plus 25% for the 150 no/mL cutoff (187 – 3000 na/mL) were routinely distinguished positive.

Qualitative - 300 nq/mL cutoff

Known levels of benzoylecognine, spiked at levels less than or equal to minus 25% of the 300 ng/mL cutoff (0-225 ng/mL) were distinauished as negative. Spiked levels greater than or equal to plus 25% of the 300 ng//mL cutoff (375- 3000 ng/mL) were routinely distinguished positive.

The semiquantitative results for known spiked concentrations for the Emit® II Plus 150/300 ng/mL Cocaine Metabolite assay recovered with-in 20% of the nominal value between 45 ng/mL and 900 ng/mL.

Precision:

A precision study was performed on the two cutoff levels (150/300ng/mL) using the Emit® II Plus Cocaine Metabolite Assay in both the qualitative and semiquantitative modes. Acceptable with-in run and total precision statistics in both the qualitative and the semiquantitative assays were observed.

In the qualitative mode the with-in run precision demonstrated coefficients of variation (%CV) for controls and cutoffs (rates) ranged from 0.4 to 0.5% and the total precision with %CV's for controls and cutoff (rates) ranged from 0.5 to 0.6%.

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In the semiquantitative mode the with-in run precision demonstrated coefficient of variation (%CV) for controls and cutoffs (concentrations) ranged from 3.7 to 10.9 % and the total precision %CV's for controls and cutoff (concentrations) ranged from 5.1 to 14.9%.

5. Substantial Equivalence:

In conclusion, SYVA Company- Dade Behring Inc. considers the Emit® II Plus Cocaine Metabolite Assay to be substantially equivalent to the Emit® II Cocaine Metabolite Assay with regard to intended use, assay sample, and overall performance characteristics.

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it, and the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged in a circular fashion around the symbol. The text is in all caps and is in a sans-serif font.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JAN 2 7 2000

Mr. Paul L. Rogers, Jr. Senior Manager, Regulatory Affairs Syva Company - Dade Behring Inc. 3403 Yerba Buena Road P.O. Box 49013 San Jose, California 95161-9013

Re: K993988

Trade Name: Emit® II Plus Cocaine Metabolite Assay Regulatory Class: II Product Code: DIO Dated: November 24, 1999 Received: November 24, 1999

Dear Mr. Rogers:

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 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). 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 Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (OS) 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 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 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" (21CFR 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/dsma/dsmamain.html".

Sincerely yours,

Steven Autman

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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K 993988

Device Name: Emit® II Plus Cocaine Metabolite Assay

Indications for Use:

coger

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number 993988

(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) ✓

over-the-counter Use

(Optional Format 1-2-96)

Device Name: Emit® II Plus Cocaine Metabolite Assay

Regulation Number and Section

§ 862.3250 Cocaine and cocaine metabolite test system.

(a)
Identification. A cocaine and cocaine metabolite test system is a device intended to measure cocaine and a cocaine metabolite (benzoylecgonine) in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of cocaine use or overdose.(b)
Classification. Class II (special controls). A cocaine and cocaine metabolite 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).