The Syva Emit® II Plus Benzodiazepine Assay is a homogeneous enzyme immunoassay with a 200 ng/mL or 300 ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analyses of benzodiazepines in human urine. Syva Emit® II Plus assays are designed for use with a number of chemistry analyzers.

The Syva Emit® II Plus Benzodiazepine 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 Syva Emit® II Plus Benzodiazepine Assay is a homogenous enzyme assay intended for use in the qualitative and semiquantitative analysis of benzodiazepines in human urine.

AI/ML Overview

Acceptance Criteria and Device Performance for Syva Emit® II Plus Benzodiazepine Assay

This analysis is based on the provided 510(k) Summary of Safety and Effectiveness for the Syva Emit® II Plus Benzodiazepine Assay (K993985).

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Criteria	Reported Device Performance
Comparative Analysis	Qualitative Agreement with Predicate Device (Syva Emit® II Benzodiazepine Assay): The new device should show comparable agreement with the predicate device for both 200 ng/mL and 300 ng/mL cutoffs. While specific numerical acceptance thresholds are not explicitly stated, the context of "excellent correlation" and "substantially equivalent" implies high agreement is required. The discrepancy in calibrator drugs (lormetazepam vs. nordiazepam) is noted as an explanation for any differences, implying that the observed differences are understood and acceptable.	97% agreement for the 200 ng/mL cutoff. 84% agreement for the 300 ng/mL cutoff. The discordance is explained by different calibrator drugs (lormetazepam in Emit® II Plus vs. nordiazepam in Emit® II), with lormetazepam leading to increased apparent sensitivity.
Spiked Sample Recovery	Qualitative Correct Identification: For negative human urine specimens spiked with lormetazepam, samples <= -25% of the respective cutoff should be identified as negative, and samples >= +25% of the respective cutoff should be identified as positive, for both 200 ng/mL and 300 ng/mL cutoffs. Semiquantitative Recovery Accuracy: For negative human urine specimens spiked with lormetazepam in the range of 40 to 900 ng/mL, the calculated drug recovery using the average concentration from the assay should fall within an acceptable range of the nominal concentrations. (Specific percentage range is expected for recovery).	Qualitative: Correctly identified spiked specimens containing <= -25% of respective cutoffs as negative and >= +25% of respective cutoffs as positive for both 200 ng/mL and 300 ng/mL cutoffs. Semiquantitative: Recovery was within 85-118% of nominal concentrations of spiked analyte within the range of 40 to 900 ng/mL.
Precision	Qualitative Precision: Acceptable within-run and total precision statistics, expressed as coefficients of variation (CV), for controls and cutoff calibrator. (Specific CV ranges are expected). Semiquantitative Precision: Acceptable within-run and total precision statistics, expressed as CV, for controls and cutoff calibrator. (Specific CV ranges are expected).	Qualitative: - Within-run CV: 0.4 - 0.7% - Total precision CV: 0.7 - 1.0% Semiquantitative: - Within-run CV: 1.8 - 5.2% - Total precision CV: 2.3 - 5.6% ("Acceptable within-run and total precision statistics" were observed for both modes).
Sensitivity	The lowest concentration distinguished from 0 ng/mL with a 95% confidence level should be below a certain threshold. (Specific ng/mL value is expected).	The sensitivity level is less than 15 ng/mL. This is the lowest concentration that can be distinguished from 0 ng/mL with a 95% confidence level.

Note regarding acceptance criteria: The document often states that "acceptable" or "excellent" performance was observed, implying that the reported values met pre-defined internal acceptance criteria, even if those specific criteria (e.g., the exact percentage threshold for "acceptable" agreement or precision CVs) are not explicitly numerical in the summary provided. For example, for "Spiked Sample Recovery," the specific percentage range of 85-118% is a clear acceptance criterion met by the device.

2. Sample Size and Data Provenance

Test Set Sample Sizes:
- Comparative Analysis: Not explicitly stated how many samples were used for the 97% and 84% agreement studies.
- Spiked Sample Recovery: Not explicitly stated how many samples were used, but it involved "negative human urine specimens" spiked with lormetazepam.
- Precision: Not explicitly stated how many samples were used, but involved "rates for controls and cutoff calibrator."
- Sensitivity: Not explicitly stated how many samples were used.
Data Provenance:
- The document mentions "human urine specimens."
- The study appears to be prospective or at least specifically conducted for the purpose of this 510(k) submission, as it describes experiments ("Spiked Sample Recovery," "Precision Study") performed for the new device. There is no indication of retrospective data use.
- Country of Origin: Not explicitly stated, but the manufacturer is Syva Company - Dade Behring Inc., with listed addresses in Cupertino, CA and San Jose, CA, USA. This suggests the data was likely generated in the USA.

3. Number of Experts and Qualifications (Ground Truth for Test Set)

This device is an in vitro diagnostic (IVD) assay, not an imaging or clinical interpretation device. Therefore, the concept of "experts" establishing ground truth in the traditional sense (e.g., radiologists, pathologists) does not directly apply here.

The "ground truth" for the test set was established by:

Predicate Device Comparison: The Syva Emit® II Benzodiazepine Assay served as a reference standard, and its results were compared to the new device's results. The predicate device's performance itself would have been established through prior analytical validation.
Known Spiked Concentrations: For the spiked sample recovery studies, the ground truth was the known concentration of lormetazepam that was intentionally added to negative urine specimens. This is an analytically defined ground truth.

4. Adjudication Method for the Test Set

Given that this is an IVD assay, not a subjective interpretation task, an adjudication method (like 2+1, 3+1 for human readers) is not relevant or applicable. The results are quantitative or qualitative measurements from an automated system compared against:

The results of a predicate device (another assay).
Analytically prepared samples with known concentrations.

Discrepancies in the comparative analysis were explained by different calibrator drugs, indicating a technical understanding of the differences rather than a need for human adjudication of conflicting results.

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

No, an MRMC comparative effectiveness study was not done. This type of study is relevant for evaluating human reader performance with and without AI assistance, typically in medical imaging or interpretation tasks. The Syva Emit® II Plus Benzodiazepine Assay is an automated in vitro diagnostic test, where human interpretation of the assay result is minimal compared to the automated chemical reaction and detection.

6. Standalone Performance Study

Yes, a standalone performance study was done. The entire summary describes the intrinsic performance characteristics of the Syva Emit® II Plus Benzodiazepine Assay independently:

Spiked Sample Recovery: Assesses the device's ability to correctly identify and quantify known concentrations.
Precision: Measures the reproducibility and consistency of the device's own measurements.
Sensitivity: Determines the lowest detectable concentration of the device.

While a comparative analysis to a predicate device was also performed, these studies evaluate the "algorithm only" (or assay only) without human intervention in the result determination process (beyond operating the instrument as intended).

7. Type of Ground Truth Used

The type of ground truth used was primarily analytical ground truth:

Predicate Device Results: For the comparative analysis, the results obtained from the previously cleared Syva Emit® II Benzodiazepine Assay served as a reference.
Known Spiked Concentrations: For the spiked sample recovery experiments, the ground truth was derived from the precisely prepared, known concentrations of lormetazepam added to negative urine samples.
Reference Standards/Calibrators: For precision and sensitivity studies, the ground truth is implicitly defined by the known values of the controls and calibrators used.

There is no mention of pathology, outcomes data, or expert consensus in the traditional medical diagnostic sense, as this is a chemical assay.

8. Sample Size for the Training Set

The document does not mention a training set or any machine learning approach. This assay is a homogeneous enzyme immunoassay, which relies on chemical reactions and optical detection, not an AI/ML algorithm that requires training data. Therefore, the concept of a "training set" is not applicable here.

9. How Ground Truth for the Training Set Was Established

As there is no training set for this type of immunoassay, this question is not applicable.

Summary

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Image /page/0/Picture/1 description: The image shows a sequence of handwritten alphanumeric characters. The sequence starts with the letter 'K', followed by the numbers '993985'. The characters are written in a simple, slightly irregular style, giving them a casual, handwritten appearance.

510(k) SUMMARY OF SAFETY AND EFFECTIVENESS For Syva Emit® II Plus Benzodiazepine Assay

1. Manufacturer and Contact Information:

Manufacturer:	Syva Company - Dade Behring Inc.20400 Mariani Ave.Cupertino, CA 95014
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Paul Rogers Contact Information: Syva Company 3403 Yerba Buena Road San Jose, CA 95161-9013 Tel: 408-239-2000

2. Device Classification Name:

The Clinical Chemistry and Clinical Toxicology Devices Panel have classified "BenzodiazepineTest System" as Class II.

3. Intended Use:

The Syva Emit® II Plus Benzodiazepine Assay is a homogeneous enzyme immunoassay with a 200ng/mL or 300ng/mL cutoff. The assay is intended for use in the qualitative and semiquantitative analysis of benzodiazepines in human urine.

4. Device Description and Characteristics:

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

The Syva Emit® II Plus Benzodiazepine Assay is a homogenous enzyme assay intended for use in the qualitative and semiquantitative analysis of benzodiazepines in human urine.

The Syva Emit® II Plus Benzodiazepine Assay has been found to be equivalent to the predicate device. Syva Emit® II Benzodiazepine Assay with regard to intended use, assay sample, and overall performance characteristics.

Comparative Analysis: The Syva Emit® II Plus Benzodiazepine Assay showed excellent correlation to the predicate method. The comparative analysis to the predicate method resulted in a 97% agreement for the 200ng/mL cutoff and a 84% agreement for the 300ng/mL cutoff. The discordance between the test and predicate method can be explained by the fact that there are different calibrator drugs in the two methods. The calibrators used with the Syva Emit® II Plus Benzodiazepine Assay contain the benzodiazepine, lormetazepam, while the calibrators used with the Syva Emit® II Benzodiazepine Assay contain the benzodiazepine, The use of lormetazepam as the calibrator analyte increases the apparent sensitivity of the Syva Emit® II Plus Benzodiazepine Assay to various benzodiazepines.

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510(k) SUMMARY OF SAFETY AND EFFECTIVENESS For Syva Emit® Il Plus Benzodiazepine Assay (cont.)

Spiked Sample Recovery: In qualitative spike analysis of lormetazepam in negative human urine specimens, the Syva Emit® II Plus Benzodiazepine Assay using a cutoff of 200 ng/mL and a cutoff of 300 ng/mL correctly identified the spiked specimens containing less than or equal to minus 25% of the respective cutoffs as negative and the spiked specimens containing greater than or equal to plus 25% of the respective cutoffs as positive.

The semiquantitative attribute was assessed by determining the accuracy of recovery for analyte-spiked samples by the Syva Emit® II Plus Benzodiazepine Assay. Negative human urine specimens were spiked with concentrations of lormetazepam at levels throughout the semiguantitative range of 40 to 900 ng/mL. For each known concentration. drug recovery was calculated using the average concentration obtained by the Syva Emit® II Plus Benzodiazepine Assay. Within this range, recovery was within 85-118% of nominal concentrations of spiked analyte.

Precision: A precision study was performed using Syva Emit® II Plus Benzodiazepine Assay in both the qualitative and semiquantitative modes. Acceptable within-run and total precision statistics for both the qualitative and semiguantitative assays were observed.

Qualitative results, determined from rates for controls and cutoff calibrator, demonstrated within-run precision with coefficients of variation (CV) ranging from 0.4 - 0.7% and total precision with CV ranging from 0.7 - 1.0%.

Semiquantitative results, determined from rates for controls and cutoff calibrator, demonstrated within-run precision with CV ranging from 1.8 - 5.2% and total precision with CV ranging from 2.3 - 5.6%.

Sensitivity: The sensitivity level of the Syva Emit® II Plus Benzodiazepine Assay is less than 15 ng/mL. This level represents the lowest concentration of benzodiazepines that can be distinguished from 0 ng/mL with a confidence level of 95%.

5. Substantial Equivalence:

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

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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 stylized eagle symbol with three curved lines representing the eagle's body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the eagle symbol.

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: K993985

Trade Name: Syva Emit® II Plus Benzodiazepine Assay Regulatory Class: II Product Code: JXM Dated: November 23, 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 (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 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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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 vours.

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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K993985

Device Name: Syva Emit® II Plus Benzodiazepine Assay

Indications for Use:

Jean Cooper

(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number k 993985

(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	OR	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).