Emit II Plus Cocaine Metabolite Assay
Device Facts
| Record ID | K170293 |
|---|---|
| Device Name | Emit II Plus Cocaine Metabolite Assay |
| Applicant | Siemens Healthcare Diagnostics, Inc. |
| Product Code | DIO · Clinical Toxicology |
| Decision Date | Oct 25, 2017 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.3250 |
| Device Class | Class 2 |
| Attributes | Real-World Evidence |
Real-World Evidence
| Submission | Device | Sponsor | RWD Sources | RWE Use Summary | Key Tags |
|---|---|---|---|---|---|
| K170293 · Oct 25, 2017 | Emit II Plus Cocaine Metabolite Assay | Siemens Healthcare Diagnostics, Inc. | Native patient urine samples | Method comparison study using native patient urine samples to assess the performance of the Emit II Plus Cocaine Metabolite Assay on the Beckman Coulter DxC 700 AU analyzer compared to GC/MS. | Method comparison; Native patient samples; Analytical validation |
Clinical Evidence
| Study Design | Population | Comparator | Key Endpoints |
|---|---|---|---|
| Method comparison study | Native patient urine samples; Sample Size: 102 (150 ng/mL cutoff); 95 (300 ng/mL cutoff) | GC/MS | Qualitative and semi-quantitative agreement with GC/MS |
Indications for 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 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 judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
Device Story
Emit II Plus Cocaine Metabolite Assay is a homogeneous enzyme immunoassay for detecting benzoylecgonine in human urine. It utilizes competitive binding between drug in the specimen and enzyme-labeled drug (G6PDH) for antibody binding sites. Enzyme activity is inversely proportional to drug concentration; active enzyme converts NAD to NADH, measured spectrophotometrically at 340 nm. Used in clinical chemistry analyzers; operated by laboratory technicians. Provides preliminary qualitative or semiquantitative results; requires confirmatory testing via GC/MS. Assists clinicians in drug-of-abuse screening.
Clinical Evidence
Bench testing only. Precision evaluated per CLSI EP05-A3 (n=80 per concentration). Linearity/recovery evaluated per CLSI EP06-A (50-1000 ng/mL). Method comparison against GC/MS performed for 150 ng/mL (n=102) and 300 ng/mL (n=95) cutoffs. Analytical specificity evaluated for structurally related compounds; significant cross-reactivity noted with benzoylecgonine glucuronide.
Technological Characteristics
Homogeneous enzyme immunoassay. Reagents: sheep polyclonal antibodies to benzoylecgonine, G6PDH-labeled benzoylecgonine, G6P, NAD, HEPES buffer, BSA, preservatives. Sensing principle: spectrophotometric absorbance change at 340 nm. Form factor: liquid, ready-to-use reagents. Platform: Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer.
Indications for Use
Indicated for qualitative and semiquantitative detection of benzoylecgonine (cocaine metabolite) in human urine. Intended for use as a preliminary analytical test; requires confirmation by alternative chemical methods (e.g., GC/MS).
Regulatory Classification
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.
Special Controls
*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).
Predicate Devices
- Emit II Plus Cocaine Metabolite Assay (k993988)
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k170293
B. Purpose for Submission:
Adding a previously cleared test (Emit II Plus Cocaine Metabolite Assay) to the Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer
C. Measurand:
Benzoylecgonine
D. Type of Test:
Qualitative and semi-quantitative homogenous enzyme immunoassay
E. Applicant:
Siemens Healthcare Diagnostics, Inc.
F. Proprietary and Established Names:
Emit II Plus Cocaine Metabolite Assay
G. Regulatory Information:
| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| DIO – Cocaine and cocaine metabolic test system | Class II | 21 CFR 862.3250 | 91 - Toxicology |
H. Intended Use:
1. Intended use(s):
See indication(s) for use below.
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2. **Indication(s) for 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 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 judgment should be applied to any drug-of-abuse test result, particularly when preliminary positive results are used.
3. **Special conditions for use statement(s):**
For Prescription use only.
4. **Special instrument requirements:**
Performance data was obtained using Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer
I. **Device Description:**
The Emit II Plus Cocaine Metabolite Assay consists of two ready-to-use reagents:
Antibody/Substrate Reagent 1 consists of sheep polyclonal antibodies to benzoylecgonine (2.2 µg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers. Enzyme Reagent 2 consists of Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers.
Materials that are required but that are sold separately include the following:
- Emit Calibrators/Controls with concentrations of (0, 150, 300, 500 and 1000 ng/mL).
- Commercial controls two levels with concentrations of (0 and 1000 ng/mL)
J. **Substantial Equivalence Information:**
1. **Predicate device name(s):**
Emit II Plus Cocaine Metabolite Assay
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2. Predicate 510(k) number(s):
k993988
3. Comparison with predicate:
| Similarities | | |
| --- | --- | --- |
| Item | Emit II Plus Cocaine Metabolite Assay (Candidate) | Emit II Plus Cocaine Metabolite Assay Predicate k993988 |
| Intended Use | Same | For the qualitative and semiquantitative determination of the presence of benzoylecgonine in human urine |
| Measurant | Same | Benzoylecgonine |
| Type of Test | Same | Qualitative and semi-quantitative homogeneous enzyme immunoassay |
| Antibody | Same | Sheep polyclonal |
| Reagent Form | Same | Liquid, ready to use |
| Reagent Composition | Same | Antibody/Substrate Reagent 1 Sheep polyclonal antibodies to benzoylecgonine (2.2 μg/mL), bovine serum albumin, G6P (15 mM), NAD (12 mM), preservatives, and stabilizers Enzyme Reagent 2 Benzoylecgonine labeled with bacterial G6PDH (0.46 U/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers |
| Cutoff/controls | Same | 150ng/mL (±25%) 300 ng/mL (±25%) |
| Sample Matrix | Same | Human Urine |
| Difference | | |
| --- | --- | --- |
| Item | Emit II Plus Cocaine Metabolite Assay Candidate | Emit II Plus Cocaine Metabolite Assay k993988 Predicate |
| Instrument | Beckman Coulter DxC 700 AU Clinical Chemistry Analyzer | SYVA 30R Biochemical System |
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K. Standard/Guidance Document Referenced (if applicable):
- CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition
- CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline
- CLSI EP07-A2, Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition
- CLSI EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition
- CLSI EP12-A2, User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline – Second Edition
- CLSI EP25-A Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline
L. Test Principle:
The Emit II Plus Cocaine Metabolite Assay is based on competition between free drug in the specimen and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH), for antibody binding sites. G6PDH enzyme activity decreases upon binding to the antibody, so the drug concentration in the specimen is proportional to G6PDH activity. The G6PDH enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, which can be measured as an absorbance change spectrophotometrically at 340 nm.
M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
Precision studies were conducted in accordance with CLSI EP05-A3. Testing was performed for twenty (20) days with two (2) runs per day, two (2) replicates per run for a total of n = 80 sample replicates per test concentration. Nine (9) drug-free negative urine samples were spiked with benzolecogonine to concentrations of ±25%, ±50%, ±75%, and ±100 of each cutoff, as well as a zero drug concentration sample. The results are provided below, as determined in qualitative and semi-quantitative modes using each of the 150 ng/mL and 300 ng/mL cutoffs:
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| Qualitative Analysis (for 150 ng/mL cutoff) | | | |
| --- | --- | --- | --- |
| Concentration (ng/mL) | % of cutoff | # of determinations | Results |
| 0 | -100% | 80 | 80 Neg / 0 Pos |
| 38 | -75% | 80 | 80 Neg / 0 Pos |
| 75 | -50% | 80 | 80 Neg / 0 Pos |
| 113 | -25% | 80 | 80 Neg / 0 Pos |
| 150 | Cutoff | 80 | 9 Neg / 71 Pos |
| 188 | +25% | 80 | 80 Pos / 0 Neg |
| 225 | +50% | 80 | 80 Pos / 0 Neg |
| 263 | +75% | 80 | 80 Pos / 0 Neg |
| 300 | +100% | 80 | 80 Pos / 0 Neg |
| Semi-Quantitative Analysis (for 150 ng/mL cutoff) | | | |
| --- | --- | --- | --- |
| Concentration (ng/mL) | % of cutoff | # of determinations | Results |
| 0 | -100% | 80 | 80 Neg / 0 Pos |
| 38 | -75% | 80 | 80 Neg / 0 Pos |
| 75 | -50% | 80 | 80 Neg / 0 Pos |
| 113 | -25% | 80 | 80 Neg / 0 Pos |
| 150 | Cutoff | 80 | 9 Neg / 71 Pos |
| 188 | +25% | 80 | 80 Pos / 0 Neg |
| 225 | +50% | 80 | 80 Pos / 0 Neg |
| 263 | +75% | 80 | 80 Pos / 0 Neg |
| 300 | +100% | 80 | 80 Pos / 0 Neg |
| Qualitative Analysis (for 300 ng/mL cutoff) | | | |
| --- | --- | --- | --- |
| Concentration (ng/mL) | % of cutoff | # of determinations | Results |
| 0 | -100 | 80 | 80 Neg / 0 Pos |
| 75 | -75 | 80 | 80 Neg / 0 Pos |
| 150 | -50 | 80 | 80 Neg / 0 Pos |
| 225 | -25 | 80 | 80 Neg / 0 Pos |
| 300 | Cutoff | 80 | 54 Neg / 26 Pos |
| 375 | +25 | 80 | 80 Pos / 0 Neg |
| 450 | +50 | 80 | 80 Pos / 0 Neg |
| 525 | +75 | 80 | 80 Pos / 0 Neg |
| 600 | +100 | 80 | 80 Pos / 0 Neg |
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| Semi-Quantitative Analysis (for 300ng/mL cutoff) | | | |
| --- | --- | --- | --- |
| Concentration (ng/mL) | % of cutoff | # of determinations | Results |
| 0 | -100 | 80 | 80 Neg / 0 Pos |
| 75 | -75 | 80 | 80 Neg / 0 Pos |
| 150 | -50 | 80 | 80 Neg / 0 Pos |
| 225 | -25 | 80 | 80 Neg / 0 Pos |
| 300 | Cutoff | 80 | 54 Neg / 26 Pos |
| 375 | +25 | 80 | 80 Pos / 0 Neg |
| 450 | +50 | 80 | 80 Pos / 0 Neg |
| 525 | +75 | 80 | 80 Pos / 0 Neg |
| 600 | +100 | 80 | 80 Pos / 0 Neg |
b. Linearity/assay reportable range:
Recovery studies were conducted in accordance with CLSI EP 6-A in the semiquantitative mode using spiked drug-free urine sample pools with known concentrations of benzoylecgonine to generate eleven (11) dilutions to achieve concentrations ranging from 50 ng/mL to 1000 ng/mL. Each concentration was tested in five replicates and drug recovery was calculated using the mean concentration of the five replicates. The results are summarized below:
| Linearity/Recovery | | |
| --- | --- | --- |
| Expected Concentration (ng/mL) | Mean Concentration (ng/mL) | Mean Recovery (%) |
| 0 | 6 | N/A |
| 50 | 53 | 106.1% |
| 100 | 103 | 103.1% |
| 150 | 150 | 100.2% |
| 225 | 235 | 104.3% |
| 300 | 298 | 99.3% |
| 375 | 380 | 100.4% |
| 500 | 543 | 108.6% |
| 750 | 792 | 105.6% |
| 900 | 906 | 100.6% |
| 1000 | 1029 | 102.9% |
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
The Emit II Plus Cocaine Metabolite Assay Calibrators and Controls were previously cleared in k993755.
d. Detection limit:
Not Applicable
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e. Analytical specificity:
For analytical specificity please reference k993988. Additional structurally related compounds were evaluated by spiking each of the drugs indicated in the tables below into drug free urine, and determining the lowest concentration that produces a response equivalent to benzoylecgonine at each device cutoff.
Structurally Related Compounds, 150 ng/mL cutoff
| Compound | Concentration (ng/mL) that generates response approximately equivalent to the cutoff | % Cross-Reactivity |
| --- | --- | --- |
| Ecgonine* | 5,000 | 3% |
| Cocaine* | 29,000 | 0.5% |
| Norcocaine | 100,000 | <0.01% |
| Cocaethylene | 100,000 | <0.01% |
| Ecgonine methyl ester | Not Detected | <0.01% |
Structurally Related Compounds, 300 ng/mL cutoff
| Compound | Concentration (ng/mL) that generates response approximately equivalent to the cutoff | % Cross-Reactivity |
| --- | --- | --- |
| Ecgonine* | 15,000 | 2% |
| Cocaine* | 61,000 | 0.5% |
| Norcocaine | 100,000 | <0.01% |
| Cocaethylene | 100,000 | <0.01% |
| Ecgonine methyl ester | 100,000 | <0.01% |
*Ecgonine and cocaine tested at the concentrations above produced a result approximately equivalent to the cutoff.
Benzoylecgonine glucuronide, a metabolite of benzoylecgonine, shares structural similarities to benzoylecgonine has significant cross reactivity to the Emit II Plus Cocaine Metabolite Assay. This cross reactivity was observed in the method comparison study, where the presence of Benzoylecgonine-glucuronide produced a positive result when insufficient levels of benzoylecgonine were present to produce a positive result.
Laboratories who use this assay should use caution when confirming positive results. Confirmatory methods that do not detect benzoylecgonine glucuronide may not match the initial screening assay results (see method comparison results below).
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f. Assay cut-off:
Characterization of how the device performs analytically around the claimed cutoff concentrations of 150 ng/mL and 300 ng/mL is described in the precision section, M.1.a. above
2. Comparison studies:
a. Method comparison with predicate device:
Method comparison was conducted in accordance with CLSI EP09-A3 and CLSI EP12-A2. Benzoylecgonine values of native patient urine samples were determined and were compared to the results obtained by a comparator Gas Chromatography/Mass Spectrometry (GC/MS) method. Results were obtained in both qualitative and semi-quantitative modes, and are summarized below:
Method Comparison Results for the 150 ng/mL Cutoff (n = 102)
| | GC/MS | | | | |
| --- | --- | --- | --- | --- | --- |
| | | Negative (<75 ng/mL) | Negative (75-149 ng/mL) | Positive (150 - 225ng/mL) | Positive (>225 ng/mL) |
| Qualitative | | | | | |
| DxC700 | Positive | 2 | 7 | 10 | 51 |
| AU | Negative | 28 | 4 | 0 | 0 |
| Semi-Quantitative | | | | | |
| DxC 700 | Positive | 2 | 7 | 10 | 51 |
| AU | Negative | 28 | 4 | 0 | 0 |
| Discordant Results, 150ng/mL Cutoff, Qualitative and Semi-quantitative mode | |
| --- | --- |
| Emit II Plus Cocaine Metabolite Assay (Pos/Neg) | GC/MS concentration (ng/mL) |
| *Positive | 124 |
| *Positive | 34 |
| *Positive | 73 |
| *Positive | 83 |
| *Positive | 102 |
| *Positive | 80 |
| *Positive | 105 |
| *Positive | 101 |
| *Positive | 75 |
*All samples are found to contain conjugated Benzolecgine glucuronide molecule which shares structural similarities to Benzolecgonine and positive interference to the Emit II Plus Cocaine Metabolite Assay. Benzoylecgonine glucuronide, a metabolite of benzoylecgonine, shares structural similarities to benzoylecgonine and has significant
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cross reactivity to the Emit II Plus Cocaine Metabolite Assay. This cross reactivity produced a positive result when insufficient levels of benzoylecgonine were present to produce a positive result. When specimens were treated with glucuronidase, the concentration of benzoylecgonine in the sample was within +/- 50% of the cutoff.
Method Comparison Results for the 300 ng/mL Cutoff (n = 95)
| | GC/MS | | | | |
| --- | --- | --- | --- | --- | --- |
| | | Negative (<150 ng/mL) | Negative (150-299 ng/mL) | Positive (300-450 ng/mL) | Positive (>450 ng/mL) |
| Qualitative | | | | | |
| DxC 700
AU | Positive | 1 | 10 | 18 | 25 |
| | Negative | 40 | 1 | 0 | 0 |
| Semi-Quantitative | | | | | |
| DxC700
AU | Positive | 1 | 8 | 20 | 25 |
| | Negative | 40 | 1 | 0 | 0 |
| Discordant Results, 300ng/mL Cutoff, Qualitative and Semi-quantitative mode | |
| --- | --- |
| Emit II Plus Cocaine Metabolite Assay (Pos/Neg) | GC/MS concentration (ng/mL) |
| *Positive | 217 |
| *Positive | 240 |
| *Positive | 173 |
| *Positive | 207 |
| *Positive | 233 |
| *Positive | 143 |
| *Positive | 217 |
| *Positive | 173 |
| *Positive | 232 |
| *Positive | 157 |
| *Positive | 234 |
*All samples are found to contain conjugated Benzolecgine glucuronide molecule which shares structural similarities to Benzolecgonine and positive interference to the Emit II Plus Cocaine Metabolite Assay. Benzoylecgonine glucuronide, a metabolite of benzoylecgonine, shares structural similarities to benzoylecgonine and has significant cross reactivity to the Emit II Plus Cocaine Metabolite Assay. This cross reactivity produced a positive result when insufficient levels of benzoylecgonine were present to produce a positive result. When specimens were treated with glucuronidase, the concentration of benzoylecgonine in the sample was within +/- 50% of the cutoff.
b. Matrix comparison:
Only Urine samples are recommended for use with this assay.
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3. Clinical studies:
a. Clinical Sensitivity:
Not Applicable
b. Clinical specificity:
Not Applicable
c. Other clinical supportive data (when a. and b. are not applicable):
Not Applicable
4. Clinical cut-off:
Not Applicable
5. Expected values/Reference range:
Not Applicable
N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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