Immunalysis Tapentadol Urine HEIA
Device Facts
| Record ID | K203527 |
|---|---|
| Device Name | Immunalysis Tapentadol Urine HEIA |
| Applicant | Lmmunalysis Corporation |
| Product Code | DJG · Clinical Toxicology |
| Decision Date | May 9, 2022 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.3650 |
| Device Class | Class 2 |
Indications for Use
For in vitro diagnostic use. The Immunalysis Tapentadol Urine HEIA™ is a homogeneous enzyme immunoassay with a cutoff of 200 ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of tapentadol in human urine with automated clinical chemistry analyzers. This assay is calibrated against tapentadol. This in vitro diagnostic device is for prescription use only. The Immunalysis Tapentadol Urine HEIA™ provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any test result, particularly when preliminary positive results are used. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation using a confirmatory method such as Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).
Device Story
The Immunalysis Tapentadol Urine HEIA™ is a homogeneous enzyme immunoassay used in clinical laboratories to detect tapentadol in human urine. The device utilizes automated clinical chemistry analyzers to process samples. It functions by measuring the presence of tapentadol against a 200 ng/mL cutoff. The assay provides qualitative or semi-quantitative results; the latter assists laboratories in determining appropriate specimen dilutions for subsequent confirmatory testing via GC-MS or LC-MS/MS. The device is intended for prescription use only. Healthcare providers use these preliminary results to inform clinical decision-making, though they must be confirmed by more specific chemical methods. The device benefits patients by facilitating rapid screening for tapentadol, a centrally acting analgesic and Schedule II controlled substance, supporting clinical monitoring and toxicology workflows.
Clinical Evidence
Bench testing only. Method comparison study performed on 160 deidentified clinical urine samples using the Beckman Coulter AU480 analyzer compared to LC-MS/MS. Results showed 100% positive percent agreement (PPA) and 100% negative percent agreement (NPA). Precision studies (N=80 per panel member) demonstrated consistent qualitative and semi-quantitative results across three reagent lots. Specificity and interference studies confirmed no significant cross-reactivity or interference from structurally related/unrelated compounds, endogenous substances, pH (3.0-11.0), or specific gravity (1.000-1.030).
Technological Characteristics
Homogeneous enzyme immunoassay; two-reagent system (antibody/substrate and enzyme-labeled conjugate). Calibrated against tapentadol. Cutoff: 200 ng/mL. Analyte: Tapentadol. Antibody: Recombinant FAB antibody. Instrumentation: Automated clinical chemistry analyzer (e.g., Beckman Coulter AU480). Storage: 2-8°C. Linearity range: 100-1100 ng/mL.
Indications for Use
Indicated for the qualitative and semi-quantitative analysis of tapentadol in human urine for prescription use in laboratory settings. Intended for use with automated clinical chemistry analyzers to provide preliminary analytical results requiring confirmation by GC-MS or LC-MS/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
- Immunalysis Tramadol Urine Enzyme Immunoassay (K141803)
Submission Summary (Full Text)
{0}
FDA
U.S. FOOD & DRUG
ADMINISTRATION
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY ONLY
## I Background Information:
A 510(k) Number
K203527
B Applicant
Immunalysis Corporation
C Proprietary and Established Names
Immunalysis Tapentadol Urine HEIA™
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:
New Device
B Measurand:
Tapentadol
C Type of Test:
Qualitative and Semi-quantitative Enzyme Immunoassay
## III Intended Use/Indications for Use:
A Intended Use(s):
See Indications for Use below.
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
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K203527 - Page 2 of 15
## B Indication(s) for Use:
For in vitro diagnostic use.
The Immunalysis Tapentadol Urine HEIA™ is a homogeneous enzyme immunoassay with a cutoff of 200 ng/mL. The assay is intended for use in laboratories for the qualitative and semi-quantitative analysis of tapentadol in human urine with automated clinical chemistry analyzers. This assay is calibrated against tapentadol. This in vitro diagnostic device is for prescription use only.
The Immunalysis Tapentadol Urine HEIA™ provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method.
Clinical consideration and professional judgment should be applied to any test result, particularly when preliminary positive results are used.
The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation using a confirmatory method such as Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).
## C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
## D Special Instrument Requirements:
Beckman Coulter AU 480 chemistry analyzer.
## IV Device/System Characteristics:
### A Device Description:
The Immunalysis Tapentadol Urine HEIA™ consists of ready to use reagents as follows:
- 1 bottle (25 mL, 60 mL, 100 mL, or 500 mL) of Antibody/Substrate Reagent (Reagent A) containing recombinant antibodies to Tapentadol, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) (<0.5%) in Tris buffer with Sodium Azide as a preservative.
- 1 bottle (25 mL, 60 mL, 100 mL, or 500 mL) of Enzyme Conjugate Reagent (Reagent E) containing glucose-6-phosphate dehydrogenase (G6PDH) labeled with tapentadol (<0.5%) in Tris buffer with Sodium Azide as a preservative.
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K203527 - Page 3 of 15
B Principle of Operation:
The assay is based on the competition of tapentadol labeled enzyme glucose-6-phosphate dehydrogenase (G6PDH) and the free drug in the urine sample for the fixed amount of rabbit anti-tapentadol antibody binding sites. In the absence of the free drug in the sample, the antibody binds the drug enzyme conjugate and enzyme activity is inhibited. This creates a dose response relationship between drug concentration in the urine and enzyme activity. The enzyme G6PDH activity is determined at 340 nm spectrophotometrically by the conversion of NAD to NADH.
V Substantial Equivalence Information:
A Predicate Device Name(s):
Immunalysis Tramadol Urine Enzyme Immunoassay
B Predicate 510(k) Number(s):
K141803
C Comparison with Predicate(s):
| Device & Predicate Device(s): | K203527 | K141803 |
| --- | --- | --- |
| Device Trade Name | Immunalysis Tapentadol Urine HEIA™ | Immunalysis Tramadol Enzyme Immunoassay |
| General Device Characteristic Similarities | | |
| Intended Use | Same | For the qualitative and semi-quantitative analysis of an opioid in human urine with automated clinical chemistry analyzers. |
| Test Principle | Same | Homogeneous enzyme immunoassay |
| User Environment | Same | For use in laboratories |
| Sample Matrix | Same | Human urine |
| Mass Spectrometry Confirmation | Same | Required for preliminary positive analytical results |
| General Device Characteristic Differences | | |
| Antibody | Recombinant FAB antibody to Tapentadol | Goat Polyclonal Antibody to Tramadol |
| Calibrator | Tapentadol | Tramadol |
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VI Standards/Guidance Documents Referenced:
- ISO 14971:2007 Medical Devices – Application of Risk Management to Medical Devices
- EN ISO 14971:2012 Medical Devices – Application of Risk Management to Medical Devices
VII Performance Characteristics (if/when applicable):
A Analytical Performance:
1. Precision/Reproducibility:
A precision study was performed over 20 days, two runs per day in duplicates (20 x 2 x 2 replicates per panel member) for a total of 80 replicates (N=80) per sample on 3 lots of reagent. Nine panel members were prepared using drug free negative urine as the base sample and 8 panel members were spiked to concentrations of assay cutoff and ±25%, ±50%, ±75%, ±100% of the cutoff (200 ng/mL). The concentrations used for spiking were confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS).
Summary of Precision – Qualitative
| Concentration (ng/mL) | % of cutoff | # of determinations | Result |
| --- | --- | --- | --- |
| Lot# 1 | | | |
| 0 | -100% | 80 | 80 Negative |
| 50 | -75% | 80 | 80 Negative |
| 100 | -50% | 80 | 80 Negative |
| 150 | -25% | 80 | 80 Negative |
| 200 | Cutoff | 80 | 41 Neg / 39 Pos |
| 250 | +25% | 80 | 80 Positive |
| 300 | +50% | 80 | 80 Positive |
| 350 | +75% | 80 | 80 Positive |
| 400 | +100% | 80 | 80 Positive |
| Lot# 2 | | | |
| 0 | -100% | 80 | 80 Negative |
| 50 | -75% | 80 | 80 Negative |
| 100 | -50% | 80 | 80 Negative |
| 150 | -25% | 80 | 80 Negative |
| 200 | Cutoff | 80 | 35 Neg / 45 Pos |
| 250 | +25% | 80 | 80 Positive |
| 300 | +50% | 80 | 80 Positive |
| 350 | +75% | 80 | 80 Positive |
| 400 | +100% | 80 | 80 Positive |
K203527 - Page 4 of 15
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| Concentration (ng/mL) | % of cutoff | # of determinations | Result |
| --- | --- | --- | --- |
| Lot# 3 | | | |
| 0 | -100% | 80 | 80 Negative |
| 50 | -75% | 80 | 80 Negative |
| 100 | -50% | 80 | 80 Negative |
| 150 | -25% | 80 | 80 Negative |
| 200 | Cutoff | 80 | 42 Neg / 38 Pos |
| 250 | +25% | 80 | 80 Positive |
| 300 | +50% | 80 | 80 Positive |
| 350 | +75% | 80 | 80 Positive |
| 400 | +100% | 80 | 80 Positive |
Summary of Precision - Semi-Quantitative
| Concentration (ng/mL) | % of cutoff | # of determinations | Mean Conc. (ng/mL) | Qualitative Interpretative Result | SD | CV (%) |
| --- | --- | --- | --- | --- | --- | --- |
| Lot# 1 | | | | | | |
| 0 | -100% | 80 | -3 | 80 Negative | 8.0 | N/A |
| 50 | -75% | 80 | 48 | 80 Negative | 4.7 | 9.7 |
| 100 | -50% | 80 | 99 | 80 Negative | 7.5 | 7.6 |
| 150 | -25% | 80 | 161 | 80 Negative | 5.8 | 3.6 |
| 200 | Cutoff | 80 | 215 | 2 Neg / 78 Pos | 8.6 | 4.0 |
| 250 | +25% | 80 | 268 | 80 Positive | 10.0 | 3.7 |
| 300 | +50% | 80 | 304 | 80 Positive | 17.6 | 5.8 |
| 350 | +75% | 80 | 372 | 80 Positive | 25.4 | 6.8 |
| 400 | +100% | 80 | 431 | 80 Positive | 25.2 | 5.9 |
| Lot# 2 | | | | | | |
| 0 | -100% | 80 | -4 | 80 Negative | 8.9 | N/A |
| 50 | -75% | 80 | 50 | 80 Negative | 4.8 | 9.7 |
| 100 | -50% | 80 | 100 | 80 Negative | 7.8 | 7.7 |
| 150 | -25% | 80 | 162 | 80 Negative | 7.6 | 4.7 |
| 200 | Cutoff | 80 | 213 | 8 Neg / 72 Pos | 10.6 | 5.0 |
| 250 | +25% | 80 | 263 | 80 Positive | 12.3 | 4.7 |
| 300 | +50% | 80 | 298 | 80 Positive | 17.6 | 5.9 |
| 350 | +75% | 80 | 359 | 80 Positive | 20.2 | 5.6 |
| 400 | +100% | 80 | 417 | 80 Positive | 21.7 | 5.2 |
| Lot# 3 | | | | | | |
| 0 | -100% | 80 | -3 | 80 Negative | 7.1 | N/A |
| 50 | -75% | 80 | 49 | 80 Negative | 4.4 | 8.9 |
| 100 | -50% | 80 | 102 | 80 Negative | 6.9 | 6.8 |
K203527 - Page 5 of 15
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| Concentration (ng/mL) | % of cutoff | # of determinations | Mean Conc. (ng/mL) | Qualitative Interpretative Result | SD | CV (%) |
| --- | --- | --- | --- | --- | --- | --- |
| 150 | -25% | 80 | 162 | 80 Negative | 6.1 | 3.8 |
| 200 | Cutoff | 80 | 215 | 7 Neg / 73 Pos | 9.7 | 4.5 |
| 250 | +25% | 80 | 266 | 80 Positive | 9.9 | 3.7 |
| 300 | +50% | 80 | 303 | 80 Positive | 16.0 | 5.3 |
| 350 | +75% | 80 | 369 | 80 Positive | 20.7 | 5.6 |
| 400 | +100% | 80 | 422 | 80 Positive | 20.6 | 4.9 |
2. Linearity:
A linearity study in the semi-quantitative mode was conducted by spiking a drug free urine pool with a high concentration of tapentadol above the highest calibrator. Additional linearity samples were made by serially diluting the high concentration specimen with drug free urine to achieve concentrations ranging from 100 to 1100 ng/mL. The 0 ng/mL specimen was made from drug free urine. Each pool was tested in triplicate to calculate the mean concentration values that were used to calculate drug recovery of tapentadol. The assay drug recovery percentage ranged from 95.8 to 110.4 %. Linearity test results in semi-quantitative mode are presented below.
Linearity/Recovery – Tapentadol
| Expected Concentration (ng/mL) | Mean Concentration (ng/mL) | Recovery (%) |
| --- | --- | --- |
| 0 | 3.0 | N/A |
| 100 | 110.4 | 110.4 |
| 200 | 211.6 | 105.8 |
| 300 | 298.2 | 99.4 |
| 400 | 417.3 | 104.3 |
| 500 | 531.2 | 106.2 |
| 600 | 614.1 | 102.4 |
| 700 | 721.7 | 103.1 |
| 800 | 827.3 | 103.4 |
| 900 | 907.8 | 100.9 |
| 1000 | 980.1 | 98.0 |
| 1100 | 1054.3 | 95.8 |
K203527 - Page 6 of 15
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3. Analytical Specificity/Interference:
Cross Reactivity
Structurally and functionally similar compounds were spiked into drug free urine at levels that will yield a result that is equivalent to the cutoff. The data demonstrates all sample compounds tested were negative by both the qualitative and semi-quantitative interpretations except for N-desmethyl tapentadol and tapentadol glucuronide. The % of cross-reactivity of the semi-quantitative results was < 0.2 % for all compounds tested except for N-desmethyl tapentadol with 15.7% and tapentadol glucuronide with 0.5% of cross-reactivity. Cross-reactivity test results in qualitative mode and semi-quantitative mode are presented in below.
Cross-Reactivity – Qualitative
| Compound | Compound Conc. ng/mL) | Tapentadol Equivalent Conc. (ng/mL) | Result | Cross-Reactivity (%) |
| --- | --- | --- | --- | --- |
| Chlorpromazine | 100,000 | < 200 | NEG | <0.2 |
| Clomipramine | 100,000 | <200 | NEG | <0.2 |
| Cyclobenzaprine | 100,000 | <200 | NEG | <0.2 |
| Doxepin | 100,000 | <200 | NEG | <0.2 |
| Imipramine | 100,000 | <200 | NEG | <0.2 |
| O-desmethyl tramadol | 100,000 | <200 | NEG | <0.2 |
| O-desmethyl venlafaxine | 100,000 | <200 | NEG | <0.2 |
| N-desmethyl tapentadol | 1,275 | 200 | POS | 15.7 |
| N-desmethyl tramadol | 100,000 | <200 | NEG | <0.2 |
| N-desmethyl venlafaxine | 100,000 | <200 | NEG | <0.2 |
| Tapentadol glucuronide | 43,000 | 200 | POS | 0.5 |
| Tramadol | 100,000 | <200 | NEG | <0.2 |
| Trimipramine | 100,000 | <200 | NEG | <0.2 |
| Venlafaxine | 100,000 | <200 | NEG | <0.2 |
Cross-Reactivity – Semi-Quantitative
| Compound | Compound Conc. (ng/mL) | Tapentadol Equivalent Conc. (ng/mL) | Mean Value (ng/mL) | Result | Cross-Reactivity (%) |
| --- | --- | --- | --- | --- | --- |
| Chlorpromazine | 100,000 | < 200 | 47.3 | NEG | <0.2 |
| Clomipramine | 100,000 | <200 | 47.6 | NEG | <0.2 |
| Cyclobenzaprine | 100,000 | <200 | 1.0 | NEG | <0.2 |
| Doxepin | 100,000 | <200 | 0.9 | NEG | <0.2 |
| Imipramine | 100,000 | <200 | 69.7 | NEG | <0.2 |
K203527 - Page 7 of 15
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K203527 - Page 8 of 15
| Compound | Compound Conc. (ng/mL) | Tapentadol Equivalent Conc. (ng/mL) | Mean Value (ng/mL) | Result | Cross-Reactivity (%) |
| --- | --- | --- | --- | --- | --- |
| O-desmethyl tramadol | 100,000 | <200 | 101.0 | NEG | <0.2 |
| O-desmethyl venlafaxine | 100,000 | <200 | 1.8 | NEG | <0.2 |
| N-desmethyl tapentadol | 1,275 | 200 | 214.3 | POS | 15.7 |
| N-desmethyl tramadol | 100,000 | <200 | 6.0 | NEG | <0.2 |
| N-desmethyl venlafaxine | 100,000 | <200 | 1.9 | NEG | <0.2 |
| Tapentadol glucuronide | 43,000 | 200 | 211.7 | POS | 0.5 |
| Tramadol | 100,000 | <200 | 2.5 | NEG | <0.2 |
| Trimipramine | 100,000 | <200 | 10.8 | NEG | <0.2 |
| Venlafaxine | 100,000 | <200 | -1.6 | NEG | <0.2 |
## Interference – Structurally Unrelated Compounds
Structurally unrelated compounds were evaluated in qualitative and semi-quantitative modes by spiking the potential interferent into drug free urine containing tapentadol at $\pm 25\%$ of the cutoff. The levels of structurally unrelated compounds that did not interfere in the assay are presented below.
### Non-Interfering Structurally Unrelated Compounds
| Compound | Conc. Tested (ng/mL) |
| --- | --- |
| 4-Bromo-2,5,Dimethoxyphenethylamine | 100,000 |
| 6-Acetylcodeine | 100,000 |
| 6-Acetylmorphine | 100,000 |
| Alprazolam | 100,000 |
| 7-Aminoclonazepam | 100,000 |
| 7-Aminoflunitrazepam | 100,000 |
| 7-Aminonitrazepam | 100,000 |
| Amitriptyline | 100,000 |
| d-Amphetamine | 100,000 |
| Amobarbital | 100,000 |
| Atomoxetine | 100,000 |
| Benzoylecgonine | 100,000 |
| Benzylpiperazine | 100,000 |
| Bromazepam | 100,000 |
| Brompheniramine | 100,000 |
| Buprenorphine | 100,000 |
| Bupropion | 100,000 |
| Butabarbital | 100,000 |
| Butalbital | 100,000 |
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| Compound | Conc. Tested (ng/mL) |
| --- | --- |
| Cannabidiol | 100,000 |
| Cannabinol | 100,000 |
| Carbamazepine | 100,000 |
| Cetirizine | 100,000 |
| Chlordiazepoxide | 100,000 |
| 1-(3-Chlorophenylpiperazine) mCPP | 100,000 |
| Chlorpheniramine | 100,000 |
| Cimetidine | 100,000 |
| Citalopram | 100,000 |
| Clobazam | 100,000 |
| Clonazepam | 100,000 |
| Clozapine | 100,000 |
| Cocaine | 100,000 |
| Codeine | 100,000 |
| Cotinine | 100,000 |
| Dehydronorketamine | 50,000 |
| Demoxepam | 100,000 |
| Desakylflurazepam | 100,000 |
| Desipramine | 100,000 |
| Dextromethorphan | 100,000 |
| Dihydrohydroxcarbamazepine | 100,000 |
| Diazepam | 100,000 |
| Digoxin | 100,000 |
| Dihydrocodeine | 100,000 |
| Doxylamine | 100,000 |
| Duloxetine | 100,000 |
| Ecgonine | 100,000 |
| Ecgonine Methyl Ester | 100,000 |
| EDDP | 100,000 |
| EMDP | 100,000 |
| 1S,2R (+)-Ephedrine | 100,000 |
| Ethylmorphine | 100,000 |
| Ethyl-β-D-Glucuronide | 100,000 |
| Fentanyl | 100,000 |
| Fenfluramine | 100,000 |
| Flunitrazepam | 100,000 |
| Fluoxetine | 100,000 |
| Flurazepam | 100,000 |
| Haloperidol | 100,000 |
| Heroin | 100,000 |
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K203527 - Page 10 of 15
| Compound | Conc. Tested (ng/mL) |
| --- | --- |
| Hexobarbital | 100,000 |
| Hydrocodone | 100,000 |
| Hydromorphone | 100,000 |
| Ketamine | 100,000 |
| Lamotrigine | 100,000 |
| Levorphanol | 100,000 |
| Lidocaine | 100,000 |
| Lorazepam | 100,000 |
| Lorazepam Glucuronide | 50,000 |
| Lormetazepam | 100,000 |
| LSD | 100,000 |
| Maprotiline | 100,000 |
| MDA | 100,000 |
| MDEA | 100,000 |
| MDMA | 100,000 |
| Meperidine | 100,000 |
| Meprobamate | 100,000 |
| d-Methamphetamine | 100,000 |
| Methaquolone | 100,000 |
| Methoxetamine | 100,000 |
| Methylone | 100,000 |
| Methylphenidate | 100,000 |
| Midazolam | 100,000 |
| Morphine | 100,000 |
| Morphine-3-Glucuronide | 100,000 |
| Morphine-6-Glucuronide | 100,000 |
| Nalorphine | 100,000 |
| Naloxone | 100,000 |
| Naltrexone | 100,000 |
| Naproxen | 100,000 |
| Nitrazepam | 100,000 |
| Norbuprenorphine | 100,000 |
| Norcodeine | 100,000 |
| Nordiazepam | 100,000 |
| Norketamine | 100,000 |
| Normorphine | 100,000 |
| Noroxycodone | 100,000 |
| Norpropoxyphene | 100,000 |
| Norpseudoephedrine | 100,000 |
| Nortriptyline | 100,000 |
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K203527 - Page 11 of 15
| Compound | Conc. Tested (ng/mL) |
| --- | --- |
| Olanzapine | 100,000 |
| Oxazepam | 100,000 |
| Oxazepam glucuronide | 50,000 |
| Oxycodone | 100,000 |
| Oxymorphone | 100,000 |
| Delta-9-THC | 100,000 |
| 11-hydroxy-delta-9-THC | 100,000 |
| 11-nor-9 carboxy THC | 100,000 |
| PCP | 100,000 |
| Pentazocine | 100,000 |
| Pentobarbital | 100,000 |
| Phenobarbital | 100,000 |
| Phentermine | 100,000 |
| R(-)-Phenylephrine | 100,000 |
| Phenylpropanolamine (PPA) | 100,000 |
| Phenytoin | 100,000 |
| PMA | 100,000 |
| PMMA | 100,000 |
| Prazepam | 100,000 |
| Propoxyphene | 100,000 |
| Propranolol | 100,000 |
| Protriptyline | 100,000 |
| R,R (-)-Pseudoephedrine | 100,000 |
| S,S (+)-Pseudoephedrine | 100,000 |
| Risperidone | 100,000 |
| Ritalinic Acid | 100,000 |
| Salicylic Acid | 100,000 |
| Secobarbital | 100,000 |
| Sertraline | 100,000 |
| Sufentanil | 50,000 |
| Temazepam | 100,000 |
| Theophylline | 100,000 |
| Thioridazine | 100,000 |
| Trazadone | 100,000 |
| Triazolam | 100,000 |
| 3-Trifluoromethylphenyl-piperazine | 100,000 |
| Tyramine | 100,000 |
| Verapamil | 100,000 |
| Zolpidem | 100,000 |
| Carisoprodol | 100,000 |
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| Compound | Conc. Tested (ng/mL) |
| --- | --- |
| 1R,2S (-)-Ephedrine | 100,000 |
| Acetaminophen | 500,000 |
| Acetylsalicyclic Acid | 500,000 |
| α-hydroxyalprazolam | 100,000 |
| Barbital | 100,000 |
| Caffeine | 500,000 |
| Cyclopentobarbital | 100,000 |
| Diphenhydramine | 300,000 |
| Ibuprofen | 500,000 |
| LAAM | 100,000 |
| Labetalol | 100,000 |
| Loratadine | 100,000 |
| Mephenytoin | 100,000 |
| Methadone | 500,000 |
| Methylphenylsuccinimide (mCPP) | 100,000 |
| Mirtazapine | 100,000 |
| n-desmethylcitalopram | 100,000 |
| Nor-LAAM | 100,000 |
| Noroxymorphone | 100,000 |
| Normesuximide | 100,000 |
| PEMA | 100,000 |
| Phenazepam | 100,000 |
| Procaine | 100,000 |
## Interference – Endogenous Compounds and Urine Preservatives
Endogenous compounds and urine preservatives were evaluated in qualitative and semi-quantitative modes by spiking the potential interferent into drug free urine containing tapentadol at $\pm 25\%$ of the cutoff. Due to the interference of boric acid observed at $\pm 25\%$ of the cutoff, potential interference was also evaluated at $\pm 50\%$ of the cutoff. Endogenous compounds and urine preservative tested that did not interfere in the assay are presented below.
K203527 - Page 12 of 15
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Non-interfering Endogenous Compounds
| Compound | Concentration Tested |
| --- | --- |
| Acetone | 1.0 g/dL |
| Ascorbic Acid | 1.5 g/dL |
| Bilirubin | 0.002 g/dL |
| Creatinine | 0.5 g/dL |
| Ethanol | 1.0 g/dL |
| Galactose | 0.01 g/dL |
| γ-Globulin | 0.5 g/dL |
| Glucose | 2.0 g/dL |
| Hemoglobin | 0.3 g/dL |
| Human Serum Albumin | 0.5 g/dL |
| Oxalic Acid | 0.1 g/dL |
| Riboflavin | 0.0075 g/dL |
| Sodium Chloride | 6.0 g/dL |
| Urea | 6.0 g/dL |
Non-interfering Urine Preservative
| Compound | Concentration Tested |
| --- | --- |
| Sodium Azide | 1% w/v |
| Sodium Fluoride | 1% w/v |
Boric acid interference test results at ±50% of the cutoff in qualitative and semi-quantitative modes are presented in below.
Interference at ±50% of the Cutoff
| Compound | Concentration Tested | -50% Cutoff (50 ng/mL) | | +50% Cutoff (150 ng/mL) | |
| --- | --- | --- | --- | --- | --- |
| | | Qualitative Result | Semi-Quantitative Result | Qualitative Result | Semi-Quantitative Result |
| Boric Acid | 1% w/v | Negative | Negative | Negative | Negative |
The sponsor includes the following limitation in the labeling: "Boric Acid at 1% w/v may cause false negative results. The assay should not be used to test samples which contain boric acid."
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Interference – pH
To evaluate potential interference from the effect of urine pH on the assay’s ability to detect tapentadol, device performance in the qualitative and semi-quantitative modes was tested using a range of urine pH values (3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0 and 11.0). All test samples were prepared in drug free urine containing tapentadol at ±25% of the cutoff. No positive or negative interference was observed at urine pH values ranging from 3.0 to 11.0 for each test mode.
4. Assay Reportable Range:
Not applicable
5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
The assay calibrators are traceable to a commercially-available, certified, standard material with the concentration verified by GC-MS or LC-MS/MS.
6. Detection Limit:
Not applicable
7. Assay Cut-Off:
The assay cut-off is 200ng/mL of tapentadol in urine.
B Comparison Studies:
1. Method Comparison with Predicate Device:
A method comparison study was performed using 160 deidentified remnant unaltered clinical urine samples obtained from clinical testing laboratories. The urine samples were analyzed for tapentadol using the Immunalysis Tapentadol Urine HEIA on the Beckman Coulter AU480 chemistry analyzer in both qualitative and semi-quantitative modes and LC-MS/MS (Agilent 6430 Liquid Chromatography-Tandem Mass Spectrometry). The method results of the comparison study showed a positive percent agreement (PPA) and negative percent agreement (NPA) of 100% and 100%, respectively. The results are presented below.
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Method Comparison Results by Concentration Range
| Immunalysis Tapentadol Urine HEIA Result | LC-MS/MS Tapentadol Concentration | | | | |
| --- | --- | --- | --- | --- | --- |
| | | < 100 ng/mL (less than -50% cutoff) | 100 – 199 ng/mL (between - 50% cutoff and cutoff) | 200 - 300 ng/mL (between cutoff and +50% cutoff) | > 300 ng/mL (greater than +50% cutoff) |
| Qualitative | Positive | 0 | 0 | 14 | 81 |
| | Negative | 46 | 19 | 0 | 0 |
| Semi- Quantitative | Positive | 0 | 0 | 14 | 81 |
| | Negative | 46 | 19 | 0 | 0 |
2. Matrix Comparison:
Not applicable. The assay is intended for use only with urine samples.
C 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
D Clinical Cut-Off:
Not applicable
E Expected Values/Reference Range:
Not applicable
VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.
IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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