(64 days)
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.
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.
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 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 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
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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.
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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.
§ 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).