Emit® II Plus Buprenorphine Assay
Device Facts
| Record ID | K221605 |
|---|---|
| Device Name | Emit® II Plus Buprenorphine Assay |
| Applicant | Siemens Healthcare Diagnostics, Inc. |
| Product Code | DJG · Clinical Toxicology |
| Decision Date | Jul 25, 2023 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.3650 |
| Device Class | Class 2 |
Indications for Use
The Emit® II Plus Buprenorphine Assay is a homogeneous enzyme immunoassay with a 5 ng/mL cutoff. The assay is intended for use in laboratories for the qualitative and/or semiquantitative analyses of buprenorphine in human urine. Emit® II Plus assays are designed for use with a number of chemistry analyzers. The semiquantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/Mass Spectrometry (LC/MS) or permitting laboratories to establish quality control procedures. The Emit® II Plus Burrenorphine Assay provides only a preliminary analytical test result. A more specific alternative chemical method(s) must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/ MS) or LC/MS are the preferred confirmatory methods. 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. For Professional Use. Caution: Federal (USA) law restricts this device to sale by or on the order of a licensed healthcare professional. For in vitro diagnostic use.
Device Story
Homogeneous enzyme immunoassay for buprenorphine detection in human urine; utilizes competition between specimen drug and rG6PDH-labeled drug for antibody binding sites. Enzyme activity inversely proportional to drug concentration; active enzyme converts NAD to NADH, measured spectrophotometrically at 340nm. Used in clinical laboratories on DxC 500 AU chemistry analyzers; operated by laboratory technicians. Provides preliminary qualitative/semiquantitative results; requires confirmatory testing via LC/MS or GC/MS for clinical decision-making. Assists healthcare providers in identifying buprenorphine presence; supports drug-of-abuse screening programs.
Clinical Evidence
Bench testing only. Performance evaluated using 120 human urine samples compared against LC/MS/MS reference method. Precision/repeatability studies (N=80 per level) and reproducibility studies (N=225 per level) conducted per CLSI guidelines (EP05-A3). Analytical specificity, interference (endogenous/structurally unrelated), and linearity (2.2–25.6 ng/mL) were assessed. No clinical studies performed.
Technological Characteristics
Homogeneous enzyme immunoassay; liquid, ready-to-use reagents. Reagents: Mouse monoclonal antibodies to buprenorphine, NAD, G6P, and norbuprenorphine labeled with bacterial rG6PDH. Detection: Spectrophotometric absorbance change at 340nm. Instrument: Beckman Coulter DxC 500 AU. Storage: Refrigerated. No software algorithm class specified; relies on standard spectrophotometric rate measurement.
Indications for Use
Indicated for qualitative and/or semiquantitative analysis of buprenorphine in human urine for professional laboratory use. Provides preliminary analytical results requiring confirmation by alternative chemical methods (e.g., GC/MS or LC/MS).
Regulatory Classification
Identification
An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.
Special Controls
*Classification.* Class II (special controls). An opiate 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 Buprenorphine Assay (K150606)
Related Devices
- K081008 — BUPRENORPHINE ENZYME IMMUNOASSAY, CALIBRATORS AND CONTROLS FOR BECKMAN COULTER SYNCHRON SYSTEMS · Lin-Zhi International, Inc. · Dec 22, 2008
Submission Summary (Full Text)
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K221605 - Page 1 of 13
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY ONLY
## I Background Information:
A 510(k) Number
K221605
B Applicant
Siemens Healthcare Diagnostics, Inc.
C Proprietary and Established Names
Emit® II Plus Buprenorphine Assay
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| DJG | Class II | 21 CFR 862.3650 - Opiate Test System | TX - Clinical Toxicology |
## II Submission/Device Overview:
A Purpose for Submission:
Modified device
B Measurand:
Buprenorphine
C Type of Test:
Qualitative and semiquantitative immunoassay
## III Intended Use/Indications for Use:
A Intended Use(s):
See Indication(s) for Use below.
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K221605 - Page 2 of 13
## B Indication(s) for Use:
The Emit® II Plus Buprenorphine Assay is a homogeneous enzyme immunoassay with a 5 ng/mL cutoff. The assay is intended for use in laboratories for the qualitative and/or semiquantitative analyses of buprenorphine in human urine. Emit® II Plus assays are designed for use with a number of chemistry analyzers.
The semiquantitative mode is for the purpose of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Liquid Chromatography/Mass Spectrometry (LC/MS) or permitting laboratories to establish quality control procedures.
The Emit® II Plus Buprenorphine Assay provides only a preliminary analytical test result. A more specific alternative chemical method(s) must be used to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry (GC/MS) or LC/MS are the preferred confirmatory methods. 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.
For Professional Use.
Caution: Federal (USA) law restricts this device to sale by or on the order of a licensed healthcare professional.
For in vitro diagnostic use.
## C Special Conditions for Use Statement(s):
For Prescription Use Only.
## D Special Instrument Requirements:
All performance studies were conducted on the DxC 500 AU Clinical Chemistry Analyzer.
## IV Device/System Characteristics:
### A Device Description:
The Emit® II Plus Buprenorphine Assay is a homogeneous enzyme immunoassay consisting of the following components:
#### Antibody/Substrate Reagent 1
Mouse monoclonal antibodies to buprenorphine (0.53 µg/mL) NAD (6.9 mM), G6P (10.9 mM), bovine serum albumin, preservatives, and stabilizers.
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Enzyme
Reagent 2
Norbuprenorphine labeled with bacterial rG6PDH (0.50 µg/mL), HEPES buffer, bovine serum albumin, preservatives, and stabilizers.
B Principle of Operation:
The Emit® II Plus Buprenorphine Assay is a homogenous enzyme immunoassay. The assay is based upon competition between drug in the specimen and drug labeled with the recombinant glucose-6-phosphate dehydrogenase (rG6PDH) for the antibody binding sites. Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH in the presence of glucose-6-phosphate (G6P), resulting in an absorbance change that is measured spectrophotometrically.
V Substantial Equivalence Information:
A Predicate Device Name(s):
Emit® II Plus Buprenorphine Assay
B Predicate 510(k) Number(s):
K150606
C Comparison with Predicate(s):
| Device & Predicate Device(s): | Emit® II Plus Buprenorphine Assay (K221605) | Emit® II Plus Buprenorphine Assay (K150606) |
| --- | --- | --- |
| Device Trade Name | Emit® II Plus Buprenorphine Assay | Same |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | A homogeneous enzyme immunoassay with a 5 ng/ml cutoff. The assay is intended for use in laboratories for the qualitative and/or semiquantitative analyses of buprenorphine in human urine. | Same |
| General Device Characteristic Differences | | |
| Instrument | DxC 500 AU Clinical Chemistry Analyzer | Viva-E Analyzer |
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VI Standards/Guidance Documents Referenced:
CLSI Guideline EP09c, Measurement Procedure Comparison and Bias Estimation Using Patient Samples – Third Edition
CLSI Guideline EP12-A2, User Protocol for Evaluation of Qualitative Test Performance; Approved Guideline—Second Edition
CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures: Approved Guideline -Third Edition.
CLSI Guideline EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline – Second Edition
CLSI Guideline EP07, Interference Testing in Clinical Chemistry.- Third Edition
VII Performance Characteristics (if/when applicable):
1. Analytical Performance:
a. **Precision/Repeatability and Within-lab Precision:**
Repeatability and within lab precision studies were conducted using urine pools spiked with Buprenorphine into drug free human urine at 11 concentrations. For each level, samples were analyzed in duplicate twice a day, for 20 days (N=80). The precision study design was guided by recommendations in CLSI EP05-A3. The results are summarized below for the qualitative and semi-quantitative analyses.
Precision: Qualitative mode
| Sample Conc. (ng/mL) | % of the Cutoff | # of Results | Repeatability Results (Pos/Neg) | Within-Lab (Pos/Neg) |
| --- | --- | --- | --- | --- |
| 0.00 | -100% | 80 | 80 Negative | 80 Negative |
| 1.25 | -75% | 80 | 80 Negative | 80 Negative |
| 2.5 | -50% | 80 | 80 Negative | 80 Negative |
| 3.0 | -40% | 80 | 80 Negative | 80 Negative |
| 3.75 | -25% | 80 | 80 Negative | 80 Negative |
| 5.0 | 0% | 80 | 21 Negative
59 Positive | 21 Negative
59 Positive |
| 6.25 | +25% | 80 | 80 Negative | 80 Negative |
| 7.0 | +40% | 80 | 80 Negative | 80 Negative |
| 7.5 | +50% | 80 | 80 Negative | 80 Negative |
| 8.75 | +75% | 80 | 80 Negative | 80 Negative |
| 10.0 | 100% | 80 | 80 Negative | 80 Negative |
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Precision: Semi-quantitative mode
| | | | | | Repeatability | | Within-Lab Precision | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Sample Conc. (ng/mL) | % of the Cutoff | # of Results | Results (Pos/Neg) | Mean (ng/mL) | SD | %CV | SD | %CV |
| 0.00 | -100% | 80 | 80 Negative | 0.1 | 0.06 | - | 0.11 | - |
| 1.25 | -75% | 80 | 80 Negative | 1.2 | 0.08 | 6.6 | 0.08 | 6.6 |
| 2.5 | -50% | 80 | 80 Negative | 2.3 | 0.09 | 3.7 | 0.11 | 4.6 |
| 3.0 | -40% | 80 | 80 Negative | 2.7 | 0.07 | 2.8 | 0.15 | 5.7 |
| 3.75 | -25% | 80 | 80 Negative | 3.3 | 0.08 | 2.5 | 0.15 | 4.4 |
| 5.0 | 0% | 80 | 21 Negative 59 Positive | 5.1 | 0.08 | 1.6 | 0.18 | 3.5 |
| 6.25 | +25% | 80 | 80 Negative | 6.1 | 0.11 | 1.3 | 0.21 | 3.4 |
| 7.0 | +40% | 80 | 80 Negative | 6.8 | 0.08 | 1.7 | 0.24 | 3.5 |
| 7.5 | +50% | 80 | 80 Negative | 7.3 | 0.10 | 1.1 | 0.21 | 2.9 |
| 8.75 | +75% | 80 | 80 Negative | 8.8 | 0.10 | 1.1 | 0.24 | 2.8 |
| 10.0 | 100% | 80 | 80 Negative | 9.7 | 0.10 | 1.1 | 0.37 | 3.8 |
Reproducibility studies were conducted with urine samples at 3 concentration levels using the semi-quantitative mode. Samples were assayed in 5 replicates in 1 run for 5 days using 3 instruments and 3 reagent lots. The data were analyzed to calculate the following components of precision: repeatability, between-day, between-lot, between-instrument, and total reproducibility.
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| | | | Repeatability | | Between-day | | Between-lot | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Urine Conc. (ng/mL) | N | Mean (ng/mL) | SD | %CV | SD | %CV | SD | %CV |
| 3 | 225 | 3.1 | 0.11 | 3.6 | 0.06 | 1.8 | 0.03 | 0.8 |
| 5 | 225 | 5.0 | 0.11 | 2.2 | 0.07 | 1.4 | 0.00 | 0.0 |
| 7 | 225 | 7.1 | 0.12 | 1.70 | 0.08 | 1.2 | 0.05 | 0.15 |
| | | | Between-instrument | | Total Reproducibility | |
| --- | --- | --- | --- | --- | --- | --- |
| Urine Conc. (ng/mL) | N | Mean (ng/mL) | SD | %CV | SD | %CV |
| 3 | 225 | 3.1 | 0.11 | 3.4 | 0.17 | 5.3 |
| 5 | 225 | 5.0 | 0.13 | 2.6 | 0.18 | 3.7 |
| 7 | 225 | 7.1 | 0.15 | 2.1 | 0.21 | 3.0 |
b. **Linearity/assay reportable range:**
Drug free urine pools were spiked with nine concentrations of buprenorphine at levels 2.2 - 25.6 ng/mL and analyzed semi-quantitatively in five replicates using the Emit® II Plus Buprenorphine Assay system. The mean observed buprenorphine concentration was compared to the expected Buprenorphine concentration and percent recovery results shown in the table below. Expected concentrations were confirmed by Liquid Chromatography/Tandem Mass Spectrometry.
| Expected Buprenorphine Conc (ng/mL) | Mean Buprenorphine Conc. by Emit® II Plus Buprenorphine Assay (ng/mL) | % Recovery |
| --- | --- | --- |
| 2.2 | 1.9 | 86 |
| 3.2 | 2.9 | 91 |
| 4.4 | 4.1 | 93 |
| 5.1 | 4.9 | 96 |
| 8.8 | 7.6 | 86 |
| 13.1 | 11.6 | 89 |
| 18.1 | 18.1 | 100 |
| 22.9 | 22.9 | 100 |
| 25.6 | 24.7 | 96 |
c. **Analytical Specificity/Interference:**
The experimental design was one (1) reagent lot, one (1) calibrator lot, one (1) instrument, one (1) sample pool for each compound tested. The samples were assayed in five (5) replicates. The samples were evaluated on the DxC 500 AU Clinical Chemistry Analyzer.
**Buprenorphine Metabolite Recovery:**
Buprenorphine and the buprenorphine metabolites: norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide were spiked into aliquots of drug free urine
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at the levels shown and run in replicates of 5. The samples were assayed, and the mean recovery results were determined and shown in the table below.
Buprenorphine and Buprenorphine Metabolites Recovery
| Compound | Conc. tested (ng/mL) | Mean (ng/mL) | Cutoff (ng/mL) | % Cross-reactivity |
| --- | --- | --- | --- | --- |
| Buprenorphine | 5 | 4.9 | 5.0 | 98% |
| Norbuprenorphine | 5 | 5.3 | 5.0 | 106% |
| Buprenorphine Glucuronide | 1000 | 1.4 | 5.0 | 0.10% |
| Norbuprenorphine Glucuronide | 1000 | 1.4 | 5.0 | 0.10% |
Structurally Related Compounds:
Samples were prepared by spiking drug-free human urine with individual cross-reactants to the targeted level. The samples were evaluated on the DxC 500 AU analyzer. All samples were tested in replicates of 5.
Cross-Reactivity with the Structurally Related Drugs
| Compound | Conc. Tested (ng/mL) | Qual. Result (Pos/Neg) | Semi-quant. Result (Pos/Neg) | % Cross-reactivity |
| --- | --- | --- | --- | --- |
| 6-acetylcodeine | 100000 | Neg | Neg | <0.01 |
| 6-acetylmorphine | 100000 | Neg | Neg | <0.01 |
| Codeine | 100000 | Neg | Neg | <0.01 |
| Dextromethorphan | 100000 | Neg | Neg | <0.01 |
| Dihydrocodeine | 100000 | Neg | Neg | <0.01 |
| Ethyl Morphine | 100000 | Neg | Neg | <0.01 |
| Heroin | 100000 | Neg | Neg | <0.01 |
| Hydrocodone | 100000 | Neg | Neg | <0.01 |
| Hydromorphone | 100000 | Neg | Neg | <0.01 |
| Levorphanol | 100000 | Neg | Neg | <0.01 |
| Morphine | 100000 | Neg | Neg | <0.01 |
| Morphine 3-glucuronide | 100000 | Neg | Neg | <0.01 |
| Morphine 6-glucuronide | 100000 | Neg | Neg | <0.01 |
| Nalorphine | 100000 | Neg | Neg | <0.01 |
| Naloxone | 100000 | Neg | Neg | <0.01 |
| Naltrexone | 100000 | Neg | Neg | <0.01 |
| Norcodeine | 100000 | Neg | Neg | <0.01 |
| Normorphine | 100000 | Neg | Neg | <0.01 |
| Noroxycodone | 100000 | Neg | Neg | <0.01 |
| Noroxymorphone | 100000 | Neg | Neg | <0.01 |
| Oxycodone | 100000 | Neg | Neg | <0.01 |
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Oxymorphone 100000 Neg Neg <0.01
# Structurally Unrelated Compounds:
The following structurally unrelated compounds were added into drug-free urine spiked with the measurand to form two concentration levels, $\pm 40\%$ (3ng/mL and 7 ng/mL, respectively) of the cutoff concentration. All samples were tested in 5 replicates. The substances listed in the table below do not yield a false response relative to the cutoff in both qualitative and semi-quantitative mode.
| Interference (Structurally Unrelated Compounds) | Conc. Tested (μg/mL) | -40% Cutoff (3 ng/mL) | | +40% Cutoff (7 ng/mL) | |
| --- | --- | --- | --- | --- | --- |
| | | Qualit. Result Pos/Neg | Semi-quant. Result Pos/Neg | Qualit. Result Pos/Neg | Semi-quant. Result Pos/Neg |
| 10, 11-dihydrocarbamazepine | 85 | Neg | Neg | Pos | Pos |
| Acetaminophen | 1000 | Neg | Neg | Pos | Pos |
| Acetylsalicylic Acid | 1500 | Neg | Neg | Pos | Pos |
| Amitriptyline | 100 | Neg | Neg | Pos | Pos |
| Amoxicillin | 500 | Neg | Neg | Pos | Pos |
| ZT (Zidovudine) | 2000 | Neg | Neg | Pos | Pos |
| Benzoylecgonine | 1000 | Neg | Neg | Pos | Pos |
| Brompheniramine | 75 | Neg | Neg | Pos | Pos |
| Caffeine | 1000 | Neg | Neg | Pos | Pos |
| Captopril | 500 | Neg | Neg | Pos | Pos |
| Chlordiazepoxide | 100 | Neg | Neg | Pos | Pos |
| Chlorpromazine | 10 | Neg | Neg | Pos | Pos |
| Cimetidine | 1000 | Neg | Neg | Pos | Pos |
| Clomipramine | 2.5 | Neg | Neg | Pos | Pos |
| Clonidine | 1000 | Neg | Neg | Pos | Pos |
| Cyclobenzaprine | 125 | Neg | Neg | Pos | Pos |
| d-amphetamine | 700 | Neg | Neg | Pos | Pos |
| Desipramine | 800 | Neg | Neg | Pos | Pos |
| Diazepam | 100 | Neg | Neg | Pos | Pos |
| Digoxin | 0.01 | Neg | Neg | Pos | Pos |
| Diphenhydramine | 1000 | Neg | Neg | Pos | Pos |
| d-methamphetamine | 500 | Neg | Neg | Pos | Pos |
| Doxepin | 100 | Neg | Neg | Pos | Pos |
| EDDP | 1000 | Neg | Neg | Pos | Pos |
| EMDP | 100 | Neg | Neg | Pos | Pos |
| Enalapril | 500 | Neg | Neg | Pos | Pos |
| Fluoxetine | 500 | Neg | Neg | Pos | Pos |
| Glutethimide | 500 | Neg | Neg | Pos | Pos |
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| Haloperidol | 100 | Neg | Neg | Pos | Pos |
| --- | --- | --- | --- | --- | --- |
| Hydroxyzine | 500 | Neg | Neg | Pos | Pos |
| Ibuprofen | 1000 | Neg | Neg | Pos | Pos |
| Imipramine | 200 | Neg | Neg | Pos | Pos |
| Ketamine | 100 | Neg | Neg | Pos | Pos |
| Ketorolac | 400 | Neg | Neg | Pos | Pos |
| Tromethamine | | | | | |
| LAAM (L-a-acetylmethadol) | 25 | Neg | Neg | Pos | Pos |
| L-Cotinine | 100 | Neg | Neg | Pos | Pos |
| Levofloxacin | 100 | Neg | Neg | Pos | Pos |
| Levothyroxine (L-Thyroxine) | 50 | Neg | Neg | Pos | Pos |
| Lidocaine | 1000 | Neg | Neg | Pos | Pos |
| Lormetazepam | 1 | Neg | Neg | Pos | Pos |
| LSD | 10 | Neg | Neg | Pos | Pos |
| MDMA (Ecstasy) | 1000 | Neg | Neg | Pos | Pos |
| Meperidine | 800 | Neg | Neg | Pos | Pos |
| Methadone | 500 | Neg | Neg | Pos | Pos |
| Methaqualone | 600 | Neg | Neg | Pos | Pos |
| NAPA | 400 | Neg | Neg | Pos | Pos |
| Naproxen | 1000 | Neg | Neg | Pos | Pos |
| Nicotinic Acid | 500 | Neg | Neg | Pos | Pos |
| Nifedipine | 500 | Neg | Neg | Pos | Pos |
| Nordiazepam | 100 | Neg | Neg | Pos | Pos |
| Nortriptyline | 250 | Neg | Neg | Pos | Pos |
| Oxazepam | 300 | Neg | Neg | Pos | Pos |
| Perphenazine | 150 | Neg | Neg | Pos | Pos |
| Phencyclidine | 900 | Neg | Neg | Pos | Pos |
| Phenobarbital | 500 | Neg | Neg | Pos | Pos |
| Phenelzine | 100 | Neg | Neg | Pos | Pos |
| Phenytoin | 1000 | Neg | Neg | Pos | Pos |
| Procainamide | 1000 | Neg | Neg | Pos | Pos |
| Procyclidine | 800 | Neg | Neg | Pos | Pos |
| Promethazine | 100 | Neg | Neg | Pos | Pos |
| Propoxyphene | 1000 | Neg | Neg | Pos | Pos |
| Protriptyline | 200 | Neg | Neg | Pos | Pos |
| Pseudoephedrine | 1000 | Neg | Neg | Pos | Pos |
| Quinacrine | 900 | Neg | Neg | Pos | Pos |
| Ranitidine | 1000 | Neg | Neg | Pos | Pos |
| Ritalin | 1000 | Neg | Neg | Pos | Pos |
| Salicylic Acid | 500 | Neg | Neg | Pos | Pos |
| Scopolamine | 500 | Neg | Neg | Pos | Pos |
| Secobarbital | 1000 | Neg | Neg | Pos | Pos |
| Tapetal | 100 | Neg | Neg | Pos | Pos |
| THC | 100 | Neg | Neg | Pos | Pos |
| Thioridazine | 100 | Neg | Neg | Pos | Pos |
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| Tramadol | 1000 | Neg | Neg | Pos | Pos |
| --- | --- | --- | --- | --- | --- |
| Trazodone | 5 | Neg | Neg | Pos | Pos |
| Trimethoprim | 1000 | Neg | Neg | Pos | Pos |
| Triprolidine (zymine) | 50 | Neg | Neg | Pos | Pos |
| Tyramine | 100 | Neg | Neg | Pos | Pos |
| Verapamil | 500 | Neg | Neg | Pos | Pos |
| Zolpidem | 100 | Neg | Neg | Pos | Pos |
## Endogenous Substances Interference:
Each compound was spiked into samples with -40% cutoff and +40% cutoff concentration pools which were prepared by spiking buprenorphine to aliquots of drug-free human urine. The results show that the tested endogenous substances at the levels tested caused no interference relative to the 5 ng/mL cutoff. Testing was conducted using both the qualitative and semi-quantitative modes. Results are provided in the table below.
| Interference (Endogenous Substances) | Conc. Tested (μg/mL) | -40% Cutoff (3 ng/mL) | | +40% Cutoff (7 ng/mL) | |
| --- | --- | --- | --- | --- | --- |
| | | Qualit. Result Pos/Neg | Semi-quant. Result Pos/Neg | Qualit. Result Pos/Neg | Semi-quant. Result Pos/Neg |
| Acetone | 1.0 g/dL | Neg | Neg | Pos | Pos |
| Ascorbic Acid | 1.5 g/dL | Neg | Neg | Pos | Pos |
| Conjugated Bilirubin | 2.0 mg/dL | Neg | Neg | Pos | Pos |
| Unconjugated Bilirubin | 2.0 mg/dL | Neg | Neg | Pos | Pos |
| Creatinine | 0.5 g/dL | Neg | Neg | Pos | Pos |
| Ethanol | 1.0 g/dL | Neg | Neg | Pos | Pos |
| IgG | 0.5 g/dL | Neg | Neg | Pos | Pos |
| Glucose | 2.0 g/dL | Neg | Neg | Pos | Pos |
| Hemoglobin | 115 mg/dL | Neg | Neg | Pos | Pos |
| Human Serum Albumin | 0.5 g/dL | Neg | Neg | Pos | Pos |
| Oxalic Acid | 0.1 g/dL | Neg | Neg | Pos | Pos |
| Riboflavin | 7.5 mg/dL | Neg | Neg | Pos | Pos |
| Sodium Chloride | 6.0 g/dL | Neg | Neg | Pos | Pos |
| Urea | 6.0 g/dL | Neg | Neg | Pos | Pos |
| Sodium Azide | 1% w/v | Neg | Neg | Pos | Pos |
| Sodium Fluoride | 1% w/v | Neg | Neg | Pos | Pos |
| Galactose | 1.0 g/dL | Neg | Neg | Pos | Pos |
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Specific Gravity and pH:
Negative urine pools with specific gravity values ranging from 1.002–1.035 and pH values ranging from 3.0–11.0 were tested in the presence of two levels of controls at +/- 40% (3 and 7 ng/mL) of the cutoff concentration. All samples were tested in triplicates and no interference was observed.
d. Assay Reportable Range:
See linearity section (1 b.) above.
e. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
Emit® II Plus Specialty Drug Calibrator/Control is traceable to a commercially available standard.
f. Detection Limit:
Not applicable.
g. Assay Cut-Off:
Analytical performance of the device around the claimed cutoff is described in the precision section (section VII, A1) above.
2. Comparison Studies:
a. Method comparison
One-hundred twenty (120) unaltered human urine samples were qualitatively and semi-quantitatively evaluated using the Emit® II Plus Buprenorphine Assay system and compared with the results obtained by the reference method LC/MS/MS. The results are presented below:
Emit® II Plus Buprenorphine Assay vs. LC/MS/MS
Comparison Table for Qualitative and Semi-quantitative Assay Performance
| | LC/MS/MS | | | |
| --- | --- | --- | --- | --- |
| | Negative (<2.5 ng/mL) | Negative Within 50% below the cutoff (2.5 – 4.9 ng/mL) | Positive Within 50% above the cutoff (5.0-7.5 ng/mL) | Positive (>7.5 ng/mL) |
| Qualitative | | | | |
| Emit® Positive | 0 | 9 | 23 | 40 |
| Emit® Negative | 32 | 16 | 0 | 0 |
| Semiquantitative | | | | |
| Emit® Positive | 0 | 9 | 23 | 40 |
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| Emit® Negative | 32 | 16 | 0 | 0 |
| --- | --- | --- | --- | --- |
Discordant Samples LC/MS/MS Analysis Results
| Sample ID | DxC 500 AU (ng/mL) | LC/MS/MS | | Emit +/- | LC/MS/MS +/- |
| --- | --- | --- | --- | --- | --- |
| | | Bup (ng/mL) | NorBup (ng/mL) | | |
| BUP35 | 6.1 | 0 | 4.2 | + | - |
| BUP45 | 6.0 | 0 | 4.6 | + | - |
| BUP51 | 6.1 | 0 | 4.3 | + | - |
| BUP60 | 5.6 | 0 | 3.8 | + | - |
| BUP62 | 6.1 | 0 | 3.9 | + | - |
| BUP87 | 5.5 | 0 | 4.3 | + | - |
| BUP95 | 5.6 | 0 | 4.5 | + | - |
| BUP101 | 6.3 | 0 | 4.8 | + | - |
| BUP109 | 5.0 | 0 | 4.3 | + | - |
Bup = Buprenorphine; NorBup = Norbuprenorphine
b. **Matrix Comparison:**
Not Applicable. The device is only intended to be used with urine samples.
3. Clinical Studies:
1. Clinical Sensitivity:
Not applicable.
2. Clinical Specificity:
Not applicable.
3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable.
B Clinical Cut-Off:
Not applicable.
C Expected Values/Reference Range:
Not applicable.
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VIII Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
