Immunalysis Barbiturates Urine Enzyme Immunoassay, Immunalysis Multi-Drug Calibrators
Device Facts
| Record ID | K161714 |
|---|---|
| Device Name | Immunalysis Barbiturates Urine Enzyme Immunoassay, Immunalysis Multi-Drug Calibrators |
| Applicant | Immunalysis Corporation |
| Product Code | DIS · Clinical Toxicology |
| Decision Date | Oct 14, 2016 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.3150 |
| Device Class | Class 2 |
Indications for Use
The Immunalysis Barbiturates Urine Enzyme Immunoassay 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 Barbiturates in human urine with automated clinical chemistry analyzers. This assay is calibrated against Secobarbital. This in vitro diagnostic device is for prescription use only. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography/ Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures. The Immunalysis Barbiturates Urine Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC-MS or LC-MS/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used. The Immunalysis Multi-Drug Calibrators are intended for in vitro diagnostic use for the calibration of assays for the following analytes: Benzoylecgonine, Methamphetamine, Morphine, PCP, Secobarbital and Oxazepam. The calibrators are designed for prescription use with immunoassays.
Device Story
The Immunalysis Barbiturates Urine Enzyme Immunoassay is a homogeneous enzyme immunoassay used in clinical laboratories to detect barbiturates in human urine. The device utilizes a competitive binding mechanism where barbiturates in the urine sample compete with a barbiturate-labeled enzyme (G6PDH) for a fixed number of recombinant and monoclonal antibody binding sites. In the absence of the drug, the antibody binds the enzyme conjugate, inhibiting enzyme activity. The presence of the drug in the sample results in higher enzyme activity, which is measured spectrophotometrically at 340 nm via the conversion of NAD to NADH. The assay is performed on automated clinical chemistry analyzers. Results are qualitative or semi-quantitative, providing a preliminary screen that requires confirmation by GC-MS or LC-MS/MS. The system includes multi-drug calibrators for assay calibration. The device assists healthcare providers in identifying potential drug use, necessitating clinical judgment and confirmatory testing before making final diagnostic or treatment decisions.
Clinical Evidence
Bench testing only. Precision study (n=80 per concentration) evaluated performance across 20 days. Linearity study (0-1100 ng/mL) confirmed recovery. Analytical specificity evaluated against structurally related and unrelated compounds; Boric Acid (1% w/v) identified as causing false negatives. Method comparison study (n=96 clinical urine samples) compared candidate device results to LC-MS/MS, demonstrating 100% agreement for both positive and negative samples.
Technological Characteristics
Homogeneous enzyme immunoassay. Reagents: recombinant/mouse monoclonal anti-Secobarbital antibody, G6PDH-labeled Barbiturate conjugate, G6P, NAD, HEPES buffer, Sodium Azide preservative. Measurement: spectrophotometric (340 nm). Form factor: liquid ready-to-use reagents. Connectivity: compatible with automated clinical chemistry analyzers (e.g., Beckman AU400e). Storage: 2-8°C.
Indications for Use
Indicated for the qualitative and semi-quantitative analysis of Barbiturates in human urine for clinical toxicology testing. Intended for prescription use in laboratory settings using automated clinical chemistry analyzers.
Regulatory Classification
Identification
A barbiturate test system is a device intended to measure barbiturates, a class of hypnotic and sedative drugs, in serum, urine, and gastric contents. Measurements obtained by this device are used in the diagnosis and treatment of barbiturate use or overdose and in monitoring levels of barbiturate to ensure appropriate therapy.
Special Controls
*Classification.* Class II (special controls). A barbiturate 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
- DRI ® Barbiturates EIA Assay (K955928)
Related Devices
- K032764 — BARBITURATE ENZYME IMMUNOASSAY, CA. # 0140 (500 TESTS KIT); CAT# 0141 (5000 TESTS KIT) · Lin-Zhi International, Inc. · Nov 3, 2003
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION MEMORANDUM ASSAY ONLY TEMPLATE
A. 510(k) Number:
k161714
B. Purpose for Submission:
New device
C. Measurand:
Barbiturates
D. Type of Test:
Homogenous Enzyme Immunoassay, Qualitative and Semi-quantitative.
E. Applicant:
Immunalysis Corporation
F. Proprietary and Established Names:
Immunalysis Barbiturates Urine Enzyme Immunoassay
Immunalysis Multi-Drug Calibrators
G. Regulatory Information:
1. Regulation section:
21 CFR 862.3150 Barbiturate test system
21 CFR 862.3200, Clinical toxicology calibrator
2. Classification:
Class II
3. Product code:
DIS
DKB
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4. Panel:
Toxicology (91)
H. Intended Use:
1. Intended use(s):
Refer to Indications for Use below
2. Indication(s) for use:
Immunalysis Barbiturates Urine Enzyme Immunoassay
The Immunalysis Barbiturates Urine Enzyme Immunoassay 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 Barbiturates in human urine with automated clinical chemistry analyzers. This assay is calibrated against Secobarbital. This in vitro diagnostic device is for prescription use only.
The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography/ Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures.
The Immunalysis Barbiturates Urine Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. GC-MS or LC-MS/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.
Immunalysis Multi-Drug Calibrators:
The Immunalysis Multi-Drug Calibrators are intended for in vitro diagnostic use for the calibration of assays for the following analytes: Benzoylecgonine, Methamphetamine, Morphine, PCP, Secobarbital and Oxazepam. The calibrators are designed for prescription use with immunoassays.
3. Special conditions for use statement(s):
For prescription use only.
4. Special instrument requirements:
Performance data was obtained using the Beckman AU400e clinical chemistry analyzer.
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I. Device Description:
The Immunalysis Barbiturates Urine Enzyme Immunoassay Kit reagents are provided as ready to use liquids and consist of the following reagents:
- The Antibody/ Substrate Reagent (Reagent A; 25, 100, or 500 mL) contains a recombinant antibody to Secobarbital, a mouse monoclonal antibody to Secobarbital, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in HEPES buffer with Sodium Azide as a preservative.
- The Enzyme Conjugate Reagent (Reagent E; 25, 100, or 500 mL) contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with Barbiturates in HEPES buffer with Sodium Azide as a preservative.
Immunalysis Multi-Drug Calibrators are provided separately, as five individual, liquid ready-to use drug levels (15 mL or 25 mL).
J. Substantial Equivalence Information:
1. Predicate device name(s):
DRI Barbiturates EIA Assay
2. Predicate 510(k) number(s):
k955928
3. Comparison with predicate:
| Similarities - Reagent | | |
| --- | --- | --- |
| Item | Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay | Predicate Device – DRI Barbiturates EIA Assay k955928 |
| Intended Use | Same | For the qualitative and semiquantitative determination of the presence of Barbiturates in human urine |
| Assay cutoff | Same | 200 ng/mL |
| Calibrator compound | Same | Secobarbital |
| Assay type | Same | Homogeneous enzyme immunoassay, qualitative and semi-quantitative |
| Storage conditions | Same | 2° - 8°C |
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| Differences - Reagent | | |
| --- | --- | --- |
| Item | Candidate Device – Immunalysis Barbiturates Urine Enzyme Immunoassay | Predicate Device – DRI Barbiturates EIA Assay k955928 |
| Calibrators | Provided separately | Provided with assay |
| Controls | Provided separately | Provided with assay |
| Antibody type | Recombinant and mouse monoclonal | Mouse monoclonal |
| Similarities - Calibrators | | |
| --- | --- | --- |
| Item | Candidate Device – Immunalysis Multi-Drug Calibrators (MDC) | Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 |
| Calibrator drug | Same | Secobarbital |
| Differences - Calibrators | | |
| --- | --- | --- |
| Item | Candidate Device – Immunalysis Negative and Multi-Drug Calibrators (MDC) | Predicate Device – Calibrators included with DRI Barbiturates EIA Assay k955928 |
| Calibrator Levels | Calibrator levels at 0 100, 200, 500 and 1000 ng/mL | Calibrator levels at 0, 200, and 1000 ng/mL |
## K. Standard/Guidance Document Referenced (if applicable):
- CLSI EP5-A3: Evaluation of Precision Performance of Quantitative Measurement Methods
- CLSI EP 7-A3: Interference Testing in Clinical Chemistry.
- ISO 14971 Second edition 2007-03-01, Medical devices – application of risk management to medical devices
- EN ISO 14971:2012 Medical devices. Application of risk management to medical devices
## L. Test Principle:
This assay uses a recombinant and a mouse monoclonal antibody, both directed against Secobarbital. The assay is based on the competition of Barbiturates labeled enzyme glucose-6-phosphate dehydrogenase (G6PDH) and the free drug in the urine sample for the fixed amount of 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 Nicotinamide Adenine Dinucleotide (NAD) to NADH.
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M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
A precision/cutoff characterization study was performed over 20 days, with two runs per day in duplicate (n=80) on calibrators (100 and 200 ng/mL), controls (150 and 250 ng/mL) and drug-free negative urine samples spiked with secobarbital to concentrations of 50, 300, 350, and 400 ng/mL. The spiked concentrations were confirmed by mass spectrometry (MS). The concentrations and results of the study are summarized below:
| Qualitative Analysis | | | |
| --- | --- | --- | --- |
| Concentration (ng/mL) | % of cutoff | # of determinations | Result |
| 0 | -100% | 80 | 80 neg / 0 pos |
| 50 | -75% | 80 | 80 neg / 0 pos |
| 100 | -50% | 80 | 80 neg / 0 pos |
| 150 | -25% | 80 | 80 neg / 0 pos |
| 200 | Cutoff | 80 | 33 neg / 47 pos |
| 250 | +25% | 80 | 0 neg / 80 pos |
| 300 | +50% | 80 | 0 neg / 80 pos |
| 350 | +75% | 80 | 0 neg / 80 pos |
| 400 | +100% | 80 | 0 neg / 80 pos |
| Semi -quantitative Analysis | | | |
| --- | --- | --- | --- |
| Concentration (ng/mL) | % of cutoff | # of determinations | Result |
| 0 | -100% | 80 | 80 neg / 0 pos |
| 50 | -75% | 80 | 80 neg / 0 pos |
| 100 | -50% | 80 | 80 neg / 0 pos |
| 150 | -25% | 80 | 80 neg / 0 pos |
| 200 | Cutoff | 80 | 23 neg / 57 pos |
| 250 | +25% | 80 | 0 neg / 80 pos |
| 300 | +50% | 80 | 0 neg / 80 pos |
| 350 | +75% | 80 | 0 neg / 80 pos |
| 400 | +100% | 80 | 0 neg / 80 pos |
b. Linearity/assay reportable range:
A linearity study in the semi-quantitative mode was conducted by spiking a drug-free urine pool with a high concentration of Secobarbital and generating serial dilutions to
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achieve concentrations ranging from 0 ng/mL to 1100 ng/mL. The 0 ng/mL sample utilized drug free urine and was not achieved through serial dilution. Each concentration was tested in triplicate and drug recovery calculated using the mean concentration of the replicates. The results are summarized below:
| Linearity/Recovery | | |
| --- | --- | --- |
| Expected Concentration (ng/mL) | Mean Concentration (ng/mL) | Recovery (%) |
| 0 | -0.6 | n/a |
| 100 | 93.2 | 93.2 |
| 200 | 196.0 | 98.0 |
| 300 | 314.7 | 104.9 |
| 400 | 418.1 | 104.5 |
| 500 | 487.9 | 97.6 |
| 600 | 604.1 | 100.7 |
| 700 | 724.2 | 103.5 |
| 800 | 819.3 | 102.4 |
| 900 | 891.2 | 99.0 |
| 1000 | 968.7 | 96.9 |
| 1100 | 981.8 | 89.3 |
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
## Traceability
The secobarbital in the calibrator is traceable to a commercially available secobarbital solution. This standard is diluted with synthetic negative urine to make the calibrators at the desired concentrations. The concentrations are confirmed by Gas Chromatography/Mass Spectrometry Analysis (GC/MS) and/or Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS).
## Value Assignment/Expected Values
Calibrators are manufactured and tested by mass spectrometry. The negative calibrator is a processed, drug free urine matrix. The negative calibrator is compared to a reference negative standard to ensure that it is free of analyte. The non-zero calibrators are prepared by spiking a known concentration of secobarbital into a negative calibrator matrix. If any of the analytes are not within the acceptable range, as measured by mass spectrometry, then the calibrator is adjusted and re-tested. Values are assigned to the calibrators once the mass spectrometry results are within the acceptable ranges.
## Calibrator Stability
Stability protocols and acceptance criteria for the calibrators were reviewed and found to be acceptable. The sponsor claims that when stored at 2 – 8°C calibrators
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and controls are stable for one year. The sponsor claims that once opened, the calibrators and controls are stable for 60 days when stored at 2 – 8° C.
d. Detection limit:
Not applicable.
e. Analytical specificity:
**Structurally related compounds**
The sponsor performed cross-reactivity studies in both qualitative and semi-quantitative modes by spiking various barbiturates or structurally related compounds into drug free urine at levels that will yield a result that is equivalent to the assay cutoff (200 ng/mL). The results were the same for the qualitative and semi-quantitative modes and are summarized below:
| Compound | Concentration Tested (ng/mL) | Cross-Reactivity (%) |
| --- | --- | --- |
| Secobarbital | 200 | 100 |
| Allobarbital | 690 | 29.0 |
| Alphenal | 190 | 105.3 |
| Amobarbital | 200 | 100.0 |
| Aprobarbital | 700 | 28.6 |
| Barbital | 9,000 | 2.2 |
| Butabarbital | 510 | 39.2 |
| Butalbital | 290 | 69.0 |
| Butobarbital | 190 | 105.3 |
| Cyclopentobarbital | 200 | 100.0 |
| Hexobarbital | 70,000 | 0.3 |
| Mephobarbital | 65,000 | 0.3 |
| Pentobarbital | 420 | 47.6 |
| Phenobarbital | 460 | 43.5 |
| Phenytoin | 100,000 | <0.2 |
| Talbutal | 220 | 90.9 |
| Thiopental | 3,700 | 5.4 |
**Non-structurally related compounds**
Potential interference from non-structurally related drugs and metabolites was evaluated in the qualitative and semi-quantitative modes by spiking these compounds into drug free urine containing secobarbital at ± 25% of the 200 ng/mL cutoff (150 ng/mL and 250 ng/mL respectively). The results were the same for the qualitative and semi-quantitative modes and are summarized below:
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| Structurally Unrelated Compounds (for 200 ng/mL cutoff) | | | |
| --- | --- | --- | --- |
| Compound | Concentration Tested (ng/mL) | -25% Cutoff (150 ng/mL) | +25% Cutoff (250 ng/mL) |
| | | Result | Result |
| 4-Bromo-2,5,Dimethoxyphenethylamine | 100,000 | Negative | Positive |
| Acetaminophen | 500,000 | Negative | Positive |
| Acetylsalicyclic Acid | 100,000 | Negative | Positive |
| 6-Acetylcodeine | 100,000 | Negative | Positive |
| 6-Acetylmorphine | 100,000 | Negative | Positive |
| Alprazolam | 100,000 | Negative | Positive |
| 7-Aminoclonazepam | 100,000 | Negative | Positive |
| 7-Aminoflunitrazepam | 100,000 | Negative | Positive |
| 7-Aminonitrazepam | 100,000 | Negative | Positive |
| Amitriptyline | 100,000 | Negative | Positive |
| S-(+)-Amphetamine | 100,000 | Negative | Positive |
| Benzylpiperazine | 100,000 | Negative | Positive |
| Bromazepam | 100,000 | Negative | Positive |
| Buprenorphine | 100,000 | Negative | Positive |
| Bupropion | 100,000 | Negative | Positive |
| Caffeine | 500,000 | Negative | Positive |
| Cannabidiol | 100,000 | Negative | Positive |
| Cannabinol | 100,000 | Negative | Positive |
| Carbamazepine | 100,000 | Negative | Positive |
| Carisoprodol | 100,000 | Negative | Positive |
| Chlordiazepoxide | 100,000 | Negative | Positive |
| Chlorpromazine | 100,000 | Negative | Positive |
| cis-Tramadol | 100,000 | Negative | Positive |
| Clobazam | 100,000 | Negative | Positive |
| Clomipramine | 100,000 | Negative | Positive |
| Clonazepam | 100,000 | Negative | Positive |
| Clozapine | 100,000 | Negative | Positive |
| Codeine | 100,000 | Negative | Positive |
| Cotinine | 100,000 | Negative | Positive |
| Cyclobenzaprine | 100,000 | Negative | Positive |
| Demoxepam | 100,000 | Negative | Positive |
| Desalkyflurazepam | 100,000 | Negative | Positive |
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| Structurally Unrelated Compounds (for 200 ng/mL cutoff) | | | |
| --- | --- | --- | --- |
| Compound | Concentration Tested (ng/mL) | -25% Cutoff (150 ng/mL) | +25% Cutoff (250 ng/mL) |
| | | Result | Result |
| Desipramine | 100,000 | Negative | Positive |
| Dextromethorphan | 100,000 | Negative | Positive |
| Diazepam | 100,000 | Negative | Positive |
| Digoxin | 100,000 | Negative | Positive |
| Dihydrocodeine | 100,000 | Negative | Positive |
| Diphenhydramine | 500,000 | Negative | Positive |
| Dehydronorketamine | 25,000 | Negative | Positive |
| Delta-9-THC | 100,000 | Negative | Positive |
| Doxepin | 100,000 | Negative | Positive |
| EDDP | 100,000 | Negative | Positive |
| EMDP | 100,000 | Negative | Positive |
| 1R,2S(-)-Ephedrine | 100,000 | Negative | Positive |
| 1S,2R(+)-Ephedrine | 100,000 | Negative | Positive |
| Ethyl glucuronide | 100,000 | Negative | Positive |
| Ethylmorphine | 100,000 | Negative | Positive |
| Fenfluramine | 100,000 | Negative | Positive |
| Fentanyl | 100,000 | Negative | Positive |
| Flunitrazepam | 100,000 | Negative | Positive |
| Fluoxetine | 100,000 | Negative | Positive |
| Flurazepam | 100,000 | Negative | Positive |
| Haloperidol | 100,000 | Negative | Positive |
| Heroin | 100,000 | Negative | Positive |
| Hydrocodone | 100,000 | Negative | Positive |
| Hydromorphone | 100,000 | Negative | Positive |
| 11-hydroxy-delta-9-THC | 100,000 | Negative | Positive |
| Ibuprofen | 500,000 | Negative | Positive |
| Imipramine | 100,000 | Negative | Positive |
| Ketamine | 100,000 | Negative | Positive |
| Lamotrigine | 100,000 | Negative | Positive |
| Levorphanol tartrate | 100,000 | Negative | Positive |
| Lidocaine | 100,000 | Negative | Positive |
| Lorazepam | 100,000 | Negative | Positive |
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| Structurally Unrelated Compounds (for 200 ng/mL cutoff) | | | |
| --- | --- | --- | --- |
| Compound | Concentration Tested (ng/mL) | -25% Cutoff (150 ng/mL) | +25% Cutoff (250 ng/mL) |
| | | Result | Result |
| Lorazepam Glucuronide | 50,000 | Negative | Positive |
| Lormetazepam | 100,000 | Negative | Positive |
| LSD | 100,000 | Negative | Positive |
| Maprotiline | 100,000 | Negative | Positive |
| (+)-MDA | 100,000 | Negative | Positive |
| MDEA | 100,000 | Negative | Positive |
| MDMA | 100,000 | Negative | Positive |
| Meperidine | 100,000 | Negative | Positive |
| Meprobamate | 100,000 | Negative | Positive |
| S(+)-Methamphetamine | 100,000 | Negative | Positive |
| Methadone | 500,000 | Negative | Positive |
| Methaquolone | 100,000 | Negative | Positive |
| Methoxetamine | 100,000 | Negative | Positive |
| Methylone | 100,000 | Negative | Positive |
| Methylphenidate | 100,000 | Negative | Positive |
| Midazolam | 100,000 | Negative | Positive |
| Morphine | 100,000 | Negative | Positive |
| Morphine-3-glucuronide | 100,000 | Negative | Positive |
| Morphine-6-glucuronide | 50,000 | Negative | Positive |
| N-desmethyltentadol | 100,000 | Negative | Positive |
| Nalorphine | 100,000 | Negative | Positive |
| Naloxone | 100,000 | Negative | Positive |
| Naltrexone | 100,000 | Negative | Positive |
| Naproxen | 100,000 | Negative | Positive |
| Nitrazepam | 100,000 | Negative | Positive |
| 11-nor-9 carboxy THC | 100,000 | Negative | Positive |
| Norbuprenorphine | 50,000 | Negative | Positive |
| Norcodeine | 100,000 | Negative | Positive |
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| Structurally Unrelated Compounds (for 200 ng/mL cutoff) | | | |
| --- | --- | --- | --- |
| Compound | Concentration Tested (ng/mL) | -25% Cutoff (150 ng/mL) | +25% Cutoff (250 ng/mL) |
| | | Result | Result |
| Nordiazepam | 100,000 | Negative | Positive |
| Norketamine | 100,000 | Negative | Positive |
| Normorphine | 100,000 | Negative | Positive |
| Norpropoxyphene | 100,000 | Negative | Positive |
| Norpseudoephedrine | 100,000 | Negative | Positive |
| Nortriptyline | 100,000 | Negative | Positive |
| Olanzapine | 100,000 | Negative | Positive |
| Secobarbital | 100,000 | Negative | Positive |
| Oxycodone | 100,000 | Negative | Positive |
| Oxymorphone | 100,000 | Negative | Positive |
| PCP | 100,000 | Negative | Positive |
| Pentazocine | 100,000 | Negative | Positive |
| Phentermine | 100,000 | Negative | Positive |
| Phenylephedrine | 100,000 | Negative | Positive |
| Phenylpropanolamine | 100,000 | Negative | Positive |
| PMA | 100,000 | Negative | Positive |
| Prazepam | 100,000 | Negative | Positive |
| Proproxyphene | 100,000 | Negative | Positive |
| Propranolol | 100,000 | Negative | Positive |
| Protriptyline | 100,000 | Negative | Positive |
| R,R(-)-Pseudoephedrine | 100,000 | Negative | Positive |
| S,S(+)-Pseudoephedrine | 100,000 | Negative | Positive |
| Ranitidine | 100,000 | Negative | Positive |
| Ritalinic Acid | 100,000 | Negative | Positive |
| Salicylic Acid | 500,000 | Negative | Positive |
| Sertraline | 100,000 | Negative | Positive |
| Sufentanil Citrate | 50,000 | Negative | Positive |
| Tapentadol | 100,000 | Negative | Positive |
| Temazepam | 100,000 | Negative | Positive |
| Theophylline | 100,000 | Negative | Positive |
| Thioridazine | 100,000 | Negative | Positive |
| Triazolam | 100,000 | Negative | Positive |
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| Structurally Unrelated Compounds (for 200 ng/mL cutoff) | | | |
| --- | --- | --- | --- |
| Compound | Concentration Tested (ng/mL) | -25% Cutoff (150 ng/mL) | +25% Cutoff (250 ng/mL) |
| | | Result | Result |
| Trifluoromethylphenyl-piperazine | 100,000 | Negative | Positive |
| Trimipramine | 100,000 | Negative | Positive |
| Trazodone | 100,000 | Negative | Positive |
| Venlafaxine | 100,000 | Negative | Positive |
| Verapamil | 100,000 | Negative | Positive |
| Zolpidem Tartrate | 100,000 | Negative | Positive |
Endogenous compounds. Potential interference from endogenous compounds was evaluated in the qualitative and semi-quantitative modes by spiking these compounds into drug free urine containing secobarbital at $\pm 25\%$ of the $200\mathrm{ng / mL}$ cutoff (150 ng/mL and 250 ng/mL, respectively). The results were the same for the qualitative and semi-quantitative modes and are summarized below:
| Compound | Concentration Tested (ng/mL) | -25% Cutoff (150 ng/mL) | +25% Cutoff (250ng/mL) |
| --- | --- | --- | --- |
| Acetone | 1.0 g/dL | Negative | Positive |
| Ascorbic Acid | 1.5 g/dL | Negative | Positive |
| Bilirubin | 0.002 g/dL | Negative | Positive |
| Creatinine | 0.5 g/dL | Negative | Positive |
| Ethanol | 1.0 g/dL | Negative | Positive |
| Galactose | 0.01 g/dL | Negative | Positive |
| γ-Globulin | 0.5 g/dL | Negative | Positive |
| Glucose | 2.0 g/dL | Negative | Positive |
| Hemoglobin | 0.115 g/dL | Negative | Positive |
| Human Serum Albumin | 0.5 g/dL | Negative | Positive |
| Oxalic Acid | 0.1 g/dL | Negative | Positive |
| Riboflavin | 0.0075 g/dL | Negative | Positive |
| Sodium Azide | 1% w/v | Negative | Positive |
| Sodium Chloride | 6.0 g/dL | Negative | Positive |
| Sodium Fluoride | 1% w/v | Negative | Positive |
| Urea | 6.0 g/dL | Negative | Positive |
Boric Acid. Boric Acid was also evaluated, and at a concentration of $1\%$ w/v was found to cause false negative results at both the $+25\%$ and $+50\%$ (250 ng/mL and 300
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ng/mL, respectively) at the 200 ng/mL cutoff in both the qualitative and semiquantitative modes. The following statement is provided in the limitations section of the labeling: “Boric Acid at 1% w/v may cause false negative results. Boric Acid is not recommended as a preservative for urine”.
pH and Specific Gravity. To evaluate potential interference from the pH of urine, 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 secobarbital at ± 25% of the 200 ng/mL cutoff (150 ng/mL and 250 ng/mL, respectively). No positive or negative interference was observed at urine pH values ranging from 3.0 to 11.0 for the qualitative and semi-quantitative modes.
To evaluate potential interference from the specific gravity of urine, device performance in the qualitative and semi-quantitative modes was tested using a range of urine specific gravity values (1.000, 1.002, 1.005, 1.010, 1.015, 1.020, 1.025 and 1.030). All test samples were prepared in drug free urine containing secobarbital at ± 25% of the 200 ng/mL cutoff (150 ng/mL and 250 ng/mL, respectively). No positive or negative interference was observed at urine specific gravity values ranging from 1.000 to 1.030 for the qualitative and semi-quantitative modes.
f. Assay cut-off:
Characterization of how the device performs analytically around the claimed cutoff concentration of 200 ng/mL is described in the precision section, M.1.a. above.
2. Comparison studies:
a. Method comparison with predicate device:
The method comparison study was performed in-house using unaltered, clinical urine samples obtained from clinical testing laboratories. A total of 96 samples were analyzed. Each sample was run in singlicate on a Beckman Coulter AU400e Chemistry Analyzer and the result was compared to that obtained by liquid chromatography/mass spectroscopy (LC/MS-MS). The results were the same for the qualitative and semi-quantitative modes and are summarized below.
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Candidate Device Results vs. stratified LC/MS-MS Values
| Candidate Device Results | Negative by the predicate device or less than half the cutoff concentration by GC/MS analysis | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Positive | 0 | 0 | 8 | 44 |
| Negative | 36 | 8 | 0 | 0 |
% Agreement among positives is 52/52 = 100%
% Agreement among negatives is 44/44 = 100%
b. Matrix comparison:
Not applicable. Urine is the only claimed matrix for the candidate device.
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.
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O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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