AMPHETAMINES II
Device Facts
| Record ID | K083764 |
|---|---|
| Device Name | AMPHETAMINES II |
| Applicant | Roche Diagnostics Corp. |
| Product Code | DKZ · Clinical Toxicology |
| Decision Date | Feb 3, 2010 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.3100 |
| Device Class | Class 2 |
Indications for Use
Amphetamines II (AMPII) is an in vitro diagnostic test for the qualitative and semiquantitative detection of amphetamines and methamphetamines on automated clinical chemistry analyzers at cutoff concentrations of 300 ng/mL, 500 ng/mL and 1000 ng/mL when calibrated with d-methamphetamine. Semiquantitative test results may be obtained that permit laboratories to assess assay performance as part of a quality control program. Semiquantitative assays are intended to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as gas chromatography/mass spectrometry (GC/MS). Amphetamines II 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) 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.
Device Story
In vitro diagnostic immunoassay for detection of amphetamines and methamphetamines in urine; utilizes Kinetic Interaction of Microparticles in Solution (KIMS) technology; performed on automated clinical chemistry analyzers (Roche/Hitachi 917). Reagents include conjugated drug derivatives and anti-drug monoclonal antibody-coated microparticles. Principle: drug in sample competes with drug-polymer conjugates for antibody binding sites on microparticles; inhibition of particle aggregation measured by changes in light transmission. Output: qualitative or semi-quantitative concentration relative to 300, 500, or 1000 ng/mL cutoffs. Used in clinical laboratories to screen for drug abuse; results require confirmation by GC/MS. Benefits: rapid preliminary screening to guide confirmatory testing.
Clinical Evidence
No clinical data provided. Substantial equivalence established via bench testing comparing performance characteristics, including cutoff concentrations and analytical sensitivity, against predicate devices.
Technological Characteristics
KIMS (Kinetic Interaction of Microparticles in Solution) immunoassay. Reagents: mouse monoclonal anti-drug antibodies, drug-polymer conjugates, bovine serum albumin, 0.09% sodium azide. Energy source: optical (light transmission measurement). Form factor: liquid reagent solutions for automated clinical chemistry analyzers. Storage: 2-8°C. Software: embedded firmware for analyzer control and data processing.
Indications for Use
Indicated for the qualitative and semiquantitative detection of amphetamines and methamphetamines in human urine. For prescription use only. Provides preliminary analytical results; requires confirmation by GC/MS.
Regulatory Classification
Identification
An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained by this device are used in the diagnosis and treatment of amphetamine use or overdose and in monitoring levels of amphetamine to ensure appropriate therapy.
Special Controls
*Classification.* Class II (special controls). An amphetamine 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
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k083764
B. Purpose for Submission:
New Device
C. Measurand:
Amphetamine and methamphetamine
D. Type of Test:
Qualitative and semi-quantitative immunoassay
E. Applicant:
Roche Diagnostics Corporation
F. Proprietary and Established Names:
ONLINE Amphetamines II
G. Regulatory Information:
1. Regulation section:
21 CFR § 862.3100, Enzyme Immunoassay, Amphetamine
21 CFR § 862.3610, Methamphetamine test system
2. Classification:
Class II
3. Product code:
DKZ - enzyme immunoassay, amphetamine
LAF - gas chromatography, methamphetamine
4. Panel:
91 (Toxicology)
H. Intended Use:
1. Intended use(s):
See Indications for use below.
2. Indication(s) for use:
Amphetamines II (AMPII) is an in vitro diagnostic test for the qualitative and semiquantitative detection of amphetamines and methamphetamines on automated clinical chemistry analyzers at cutoff concentrations of 300 ng/mL, 500 ng/mL and 1000 ng/mL when calibrated with d-methamphetamine. Semiquantitative test results may be obtained that permit laboratories to assess assay performance as part of a quality control program. Semiquantitative assays are intended to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as gas chromatography/mass spectrometry (GC/MS).
Amphetamines II 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) is the preferred
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confirmatory method. 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):
Amphetamines II 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) 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.
For prescription use only
4. Special instrument requirements:
Roche/Hitachi 917
I. Device Description:
ONLINE Amphetamines II assay consists of ready for use reagent solutions. Reagent 1 (R1) contains conjugated drug derivatives in buffer with bovine serum albumin (BSA) and 0.09 % sodium azide. Reagent 2 (R2) contains antibody/microparticle working solution with microparticles attached to anti-drug antibodies (mouse monoclonal) in buffer with bovine serum albumin (BSA) and 0.09 % sodium azide.
J. Substantial Equivalence Information:
1. Predicate device name(s):
Abuscreen ONLINE Amphetamines
2. Predicate 510(k) number(s):
k983699
3. Comparison with predicate:
| Feature | Amphetamines II Assay (k083764) | Predicate Device: Abuscreen ONLINE Amphetamines (K983699) |
| --- | --- | --- |
| Methodology | KIMS, Kinetic interaction of microparticles in solution | KIMS, Kinetic interaction of microparticles in solution |
| Sample Type | Urine | Urine |
| Intended Use | Qualitative and semi-quantitative detection of amphetamines and methamphetamines | Qualitative and semi-quantitative detection of amphetamine and methamphetamine |
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| Reagents | 1. Conjugate Working Solution: Conjugated amphetamine and methamphetamine, in buffer with bovine serum albumin (BSA) and 0.09% sodium azide.
2. Antibody/Microparticle Working Solution: Microparticles attached to amphetamine, and methamphetamine, antibodies (mouse monoclonal) in buffer with bovine serum albumin (BSA) and 0.09% sodium azide. | 1. Antibody Working Solution: Amphetamine and methamphetamine monoclonal antibodies (mouse) in buffer with bovine serum albumin and preservative.
2. Microparticle Working Solution: Conjugated amphetamine derivative microparticles in buffer and preservative. |
| --- | --- | --- |
K. Standard/Guidance Document Referenced (if applicable):
CLSI EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods, Approved Guideline.
L. Test Principle:
The ONLINE Amphetamines II assay is based on the kinetic interaction of microparticles in a solution (KIMS) as measured by changes in light transmission. In the absence of sample drug, soluble drug-polymer conjugates bind to antibody-bound microparticles, causing the formation of particle aggregates. As the aggregation reaction proceeds in the absence of sample, the absorbance increases. When a urine sample contains the drug in question, this drug competes with the conjugate-bound drug derivative for microparticle-bound antibody. Antibody bound to sample drug is no longer available to promote particle aggregation, and subsequent particle lattice formation is inhibited. The presence of sample drug diminishes the increasing absorbance in proportion to the concentration of drug in the sample. Sample drug content is determined relative to the value obtained for a known cutoff concentration of drug.
M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
The sponsor conducted two separate precision studies using Hitachi 917 analyzer for samples containing d-methamphetamine and d-amphetamine. Precision was determined according to a CLSI (EP5-A2) precision protocol. Samples were prepared by spiking a negative human urine pool with either d-methamphetamine or d-amphetamine at the following concentrations: zero drug, -75%, -50%, and -25% below the cutoff, cutoff, and +25%, +50%, +75%, and +100% above the cutoff. The d-methamphetamine and d-amphetamine stock solutions had an analytically confirmed concentration of 1 mg/mL based upon Certificate of Analysis. Samples were tested in 2 replicates per run, 2 runs per day for 21 days, total n=84. During precision testing with d-amphetamine, 9 calibrations were performed. During
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precision testing with d-methamphetamine, 8 calibrations were performed. Results of the study are presented below:
## d-Amphetamine:
Qualitative - 300 ng/mL Cutoff
| Sample Concentration ng/mL | Percent Cut-off (%) | # Observations | Results # Neg/ #Pos | |
| --- | --- | --- | --- | --- |
| | | | # Negative | # Positives |
| 0 | 0 | 84 | 84 | 0 |
| 128 | -75 | 84 | 84 | 0 |
| 200 | -50 | 84 | 84 | 0 |
| 262 | -25 | 84 | 84 | 0 |
| 334 | Cut-off | 84 | 9 | 75 |
| 378 | +25 | 84 | 0 | 84 |
| 438 | +50 | 84 | 0 | 84 |
| 484 | +75 | 84 | 0 | 84 |
| 555 | +100 | 84 | 0 | 84 |
Semi-Quantitative - 300 ng/mL Cutoff
| Sample Concentration ng/mL | Percent Cut-off (%) | # Observations | Results # Neg/ #Pos | |
| --- | --- | --- | --- | --- |
| | | | # Negative | # Positives |
| 0 | 0 | 84 | 84 | 0 |
| 128 | -75 | 84 | 84 | 0 |
| 200 | -50 | 84 | 84 | 0 |
| 262 | -25 | 84 | 83 | 1 |
| 334 | Cut-off | 84 | 5 | 79 |
| 378 | +25 | 84 | 0 | 84 |
| 438 | +50 | 84 | 0 | 84 |
| 484 | +75 | 84 | 0 | 84 |
| 555 | +100 | 84 | 0 | 84 |
Qualitative - 500 ng/mL Cutoff
| Sample Concentration ng/mL | Percent Cut-off (%) | # Observations | Results # Neg/ #Pos | |
| --- | --- | --- | --- | --- |
| | | | # Negative | # Positives |
| 0 | 0 | 84 | 84 | 0 |
| 143 | -75 | 84 | 84 | 0 |
| 268 | -50 | 84 | 84 | 0 |
| 392 | -25 | 84 | 84 | 0 |
| 527 | Cut-off | 84 | 8 | 76 |
| 656 | +25 | 84 | 0 | 84 |
| 723 | +50 | 84 | 0 | 84 |
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| 934 | +75 | 84 | 0 | 84 |
| --- | --- | --- | --- | --- |
| 1054 | +100 | 84 | 0 | 84 |
Semi-Quantitative - 500 ng/mL Cutoff
| Sample Concentration ng/mL | Percent Cut-off (%) | # Observations | Results # Neg/ #Pos | |
| --- | --- | --- | --- | --- |
| | | | # Negative | # Positives |
| 0 | 0 | 84 | 84 | 0 |
| 143 | -75 | 84 | 84 | 0 |
| 268 | -50 | 84 | 84 | 0 |
| 392 | -25 | 84 | 84 | 0 |
| 527 | Cut-off | 84 | 2 | 82 |
| 656 | +25 | 84 | 0 | 84 |
| 723 | +50 | 84 | 0 | 84 |
| 934 | +75 | 84 | 0 | 84 |
| 1054 | +100 | 84 | 0 | 84 |
Qualitative - 1000 ng/mL Cutoff
| Sample Concentration ng/mL | Percent Cut-off (%) | # Observations | Results # Neg/ #Pos | |
| --- | --- | --- | --- | --- |
| | | | # Negative | # Positives |
| 0 | 0 | 84 | 84 | 0 |
| 293 | -75 | 84 | 84 | 0 |
| 554 | -50 | 84 | 84 | 0 |
| 755 | -25 | 84 | 84 | 0 |
| 1093 | Cut-off | 84 | 9 | 75 |
| 1384 | +25 | 84 | 0 | 84 |
| 1629 | +50 | 84 | 0 | 84 |
| 1877 | +75 | 84 | 0 | 84 |
| 2122 | +100 | 84 | 0 | 84 |
Semi-Quantitative - 1000 ng/mL Cutoff
| Sample Concentration ng/mL | Percent Cut-off (%) | # Observations | Results # Neg/ #Pos | |
| --- | --- | --- | --- | --- |
| | | | # Negative | # Positives |
| 0 | 0 | 84 | 84 | 0 |
| 293 | -75 | 84 | 84 | 0 |
| 554 | -50 | 84 | 84 | 0 |
| 755 | -25 | 84 | 84 | 0 |
| 1093 | Cut-off | 84 | 1 | 83 |
| 1384 | +25 | 84 | 0 | 84 |
| 1629 | +50 | 84 | 0 | 84 |
| 1877 | +75 | 84 | 0 | 84 |
| 2122 | +100 | 84 | 0 | 84 |
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d-methamphetamine:
Qualitative - 300 ng/mL Cutoff
| Sample Concentration ng/mL | Percent Cut-off (%) | # Observations | Results # Neg/ #Pos | |
| --- | --- | --- | --- | --- |
| | | | # Negative | # Positives |
| 45 | 0 | 84 | 84 | 0 |
| 98 | -75 | 84 | 84 | 0 |
| 174 | -50 | 84 | 84 | 0 |
| 251 | -25 | 84 | 84 | 0 |
| 334 | Cut-off | 84 | 2 | 82 |
| 407 | +25 | 84 | 0 | 84 |
| 447 | +50 | 84 | 0 | 84 |
| 577 | +75 | 84 | 0 | 84 |
| 658 | +100 | 84 | 0 | 84 |
Semi-Quantitative - 300 ng/mL Cutoff
| Sample Concentration ng/mL | Percent Cut-off (%) | # Observations | Results # Neg/ #Pos | |
| --- | --- | --- | --- | --- |
| | | | # Negative | # Positives |
| 45 | 0 | 84 | 84 | 0 |
| 98 | -75 | 84 | 84 | 0 |
| 174 | -50 | 84 | 84 | 0 |
| 251 | -25 | 84 | 83 | 1 |
| 334 | Cut-off | 84 | 4 | 80 |
| 407 | +25 | 84 | 0 | 84 |
| 447 | +50 | 84 | 0 | 84 |
| 577 | +75 | 84 | 0 | 84 |
| 658 | +100 | 84 | 0 | 84 |
Qualitative - 500 ng/mL Cutoff
| Sample Concentration ng/mL | Percent Cut-off (%) | # Observations | Results # Neg/ #Pos | |
| --- | --- | --- | --- | --- |
| | | | Negative | Positives |
| 38 | 0 | 84 | 84 | 0 |
| 143 | -75 | 84 | 84 | 0 |
| 268 | -50 | 84 | 84 | 0 |
| 392 | -25 | 84 | 84 | 0 |
| 527 | Cut-off | 84 | 8 | 76 |
| 656 | +25 | 84 | 0 | 84 |
| 723 | +50 | 84 | 0 | 84 |
| 934 | +75 | 84 | 0 | 84 |
| 1054 | +100 | 84 | 0 | 84 |
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Semi-Quantitative - 500 ng/mL Cutoff
| Sample Concentration ng/mL | Percent Cut-off (%) | # Observations | Results # Neg/ #Pos | |
| --- | --- | --- | --- | --- |
| | | | # Negative | # Positives |
| 38 | 0 | 84 | 84 | 0 |
| 143 | -75 | 84 | 84 | 0 |
| 268 | -50 | 84 | 84 | 0 |
| 392 | -25 | 84 | 84 | 0 |
| 527 | Cut-off | 84 | 13 | 71 |
| 656 | +25 | 84 | 0 | 84 |
| 723 | +50 | 84 | 0 | 84 |
| 934 | +75 | 84 | 0 | 84 |
| 1054 | +100 | 84 | 0 | 84 |
Qualitative - 1000 ng/mL Cutoff
| Sample Concentration ng/mL | Percent Cut-off (%) | # Observations | Results # Neg/ #Pos | |
| --- | --- | --- | --- | --- |
| | | | # Negative | # Positives |
| 61 | 0 | 84 | 84 | 0 |
| 293 | -75 | 84 | 84 | 0 |
| 554 | -50 | 84 | 84 | 0 |
| 755 | -25 | 84 | 84 | 0 |
| 1093 | Cut-off | 84 | 5 | 79 |
| 1384 | +25 | 84 | 0 | 84 |
| 1629 | +50 | 84 | 0 | 84 |
| 1877 | +75 | 84 | 0 | 84 |
| 2122 | +100 | 84 | 0 | 84 |
Semi-Quantitative - 1000 ng/mL Cutoff
| Sample Concentration ng/mL | Percent Cut-off (%) | # Observations | Results # Neg/ #Pos | |
| --- | --- | --- | --- | --- |
| | | | # Negative | # Positives |
| 61 | 0 | 84 | 84 | 0 |
| 293 | -75 | 84 | 84 | 0 |
| 554 | -50 | 84 | 84 | 0 |
| 755 | -25 | 84 | 84 | 0 |
| 1093 | Cut-off | 84 | 4 | 80 |
| 1384 | +25 | 84 | 0 | 84 |
| 1629 | +50 | 84 | 0 | 84 |
| 1877 | +75 | 84 | 0 | 84 |
| 2122 | +100 | 84 | 0 | 84 |
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b. Linearity/assay reportable range:
Linearity across the range was confirmed by serially diluting a spiked urine pool containing drug in desired levels listed in the table below. Each sample was assayed on Hitachi 917 analyzer in the semi-quantitative mode. The results were averaged and compared to the expected result and the percent recovery was calculated.
Sponsor calculated the % recovery by dividing the recovered result by the target concentration and then multiplying by 100. Results are presented below:
| 300 cutoff | | | 500 cutoff | | | 1000 cutoff | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Expected | Observed | % Recovery | Expected | Observed | % Recovery | Expected | Observed | % Recovery |
| 0 | 44 | | 0 | 18 | | 0 | 38 | |
| 42.6 | 81 | 190.14 | 72 | 94 | 130.56 | 72.6 | 108 | 148.76 |
| 85.2 | 112 | 131.46 | 144 | 161 | 111.81 | 145.2 | 166 | 114.33 |
| 127.8 | 146 | 114.24 | 216 | 227 | 105.09 | 217.8 | 233 | 106.98 |
| 170.4 | 182 | 106.81 | 288 | 284 | 98.61 | 290.4 | 286 | 98.48 |
| 213 | 213 | 100 | 360 | 357 | 99.17 | 363 | 363 | 100 |
| 255.6 | 251 | 98.2 | 432 | 435 | 100.69 | 435.6 | 426 | 97.8 |
| 298.2 | 296 | 99.26 | 504 | 499 | 99.01 | 508.2 | 495 | 97.4 |
| 340.8 | 320 | 93.9 | 576 | 573 | 99.48 | 580.8 | 561 | 96.59 |
| 383.4 | 362 | 94.42 | 648 | 634 | 97.84 | 653.4 | 662 | 101.32 |
| 426 | 402 | 94.37 | 720 | 720 | 100 | 726 | 719 | 99.04 |
| | | | | | | 1240.5 | 1205 | 97.14 |
| | | | | | | 1860.75 | 1857 | 99.8 |
| | | | | | | 2481 | 2481 | 100 |
| | | | | | | 3101.25 | 3046 | 98.22 |
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
The assay is calibrated using d-methamphetamine. Calibrators for cutoff levels (300 ng/mL, 500 ng/mL, 1000 ng/mL) included in this device has been previously cleared in k060645. Control materials for three cutoff levels have been previously cleared in k080183, k090939.
The sponsor provided the stability study protocols for reagent stability, and it is based on the real time stability studies conducted at $2 - 8^{\circ}\mathrm{C}$ . The on-board stability for open vials is 56 days. The sponsor recommends that users should not freeze the reagents.
d. Detection limit:
Performance at low drug concentrations in the semi-quantitative assay was characterized by determination of recovery (see section b above).
e. Analytical specificity:
Cross-reactivity was determined by spiking various concentrations of structurally similar drug compounds into drug-free urine. The cross reactivity studies were conducted for both semiquantitative and qualitative modes to determine the approximate quantity of each compound that is equivalent in assay reactivity to the 300, 500, and $1000\mathrm{ng / mL}$ assay cutoff. The table below shows the semiquantitative
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results of the study for each assay cutoff. Similar results were generated for qualitative mode of the device.
| Compound | ng/mL Equivalent to 300 ng/mL | Approx. Percent Cross-reactivity | ng/mL Equivalent to 500 ng/mL | Approx. Percent Cross-reactivity | ng/mL Equivalent to 500 ng/mL | Approx. Percent Cross-reactivity |
| --- | --- | --- | --- | --- | --- | --- |
| MDMA | 104 | 288 | 196 | 255 | 509 | 197 |
| MDA | 249 | 120 | 394 | 127 | 771 | 130 |
| d-Amphetamine | 251 | 120 | 494 | 101 | 981 | 102 |
| MDEA | 303 | 99 | 668 | 75 | 1553 | 64 |
| d-Meth-amphetamine | 305 | 98 | 488 | 102 | 998 | 100 |
| MBDB HCl | 323 | 93 | 598 | 84 | 1175 | 85 |
| BDB HCl | 717 | 42 | 1358 | 37 | 2420 | 41 |
| l-Meth-amphetamine | 2524 | 12 | 4383 | 11 | 8748 | 11 |
| l-Amphetamine | 7085 | 4 | 13342 | 4 | 24220 | 4 |
| Phendimetrazine | 31818 | 0.94 | 65566 | 0.76 | 138504 | 0.72 |
| Phentermine | 70391 | 0.43 | 123457 | 0.41 | 238663 | 0.42 |
| d-Pseudoephedrine | 73822 | 0.41 | 112613 | 0.44 | 261780 | 0.38 |
| Tyramine | 85115 | 0.35 | 141643 | 0.35 | 284091 | 0.35 |
| l-Ephedrine | 89655 | 0.33 | 141643 | 0.35 | 308642 | 0.32 |
| d,l-Phenyl-propanolamine HCl | 211268 | 0.14 | 344828 | 0.15 | 606061 | 0.17 |
| d-Ephedrine | 215827 | 0.14 | 458716 | 0.11 | 657895 | 0.15 |
The cross-reactivity studies for structurally unrelated compounds were conducted using urine spiked with drug to low positive $(+25\%)$ concentration and a high negative $(-25\%)$ concentration for each cutoff level (300, 500, $1000~\mathrm{ng / mL}$ ) to determine the potential interference of the assay with variety of endogenous and pharmaceutical substances. Aliquots of pooled drug-free human urine and urine samples were further spiked with structurally unrelated compounds at a concentration of $100000~\mathrm{ng / mL}$ (except for LSD $[(2500~\mathrm{ng / mL}]$ and $\Delta$ -THC-9-
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carboxylic acid $[10000\mathrm{ng / mL}]$ . The results indicated that each compound listed below did not interfere with the accurate measurements of the device.
| Acetaminophen | Diphenhydramine | Morphine |
| --- | --- | --- |
| Acetylsalicylic acid | Diphenylhydanton | Naloxone |
| Amitriptyline | Doxepin | Naltrexone |
| Ascorbic Acid | Ecgonine | Naproxen |
| Aspartame | Ecgonine methyl ester | Niacinamide |
| Benzocaine | Erythromycin | Nicotine |
| Benzoylecgonine | Furosemide | Nifedipine |
| Caffeine | Guaiacol glycerol ether | Nordiazepam |
| Cannabidiol | Hydrochlorothiazide | Omeprazole |
| Cocaine | Ibuprofen | Oxazepam |
| Codeine | Ketamine | Penicillin G |
| Desipramine HCl | Levothyroxine | Phencyclidine |
| Dextromethorphan | LSD | Phenobarbital |
| Dextropropoxyphene | Meperidine | Quinine |
| Diazepam | Methadone | Secobarbital |
| Digoxin | Methaqualone | Tetracycline |
| | | Δ9-THC |
Additionally, two separate studies were conducted for amphetamine and methamphetamine to evaluate the potential interference from substances found in urine. Both studies tested in semi-quantitative and qualitative modes. For both studies, the potentially interfering compound was spiked into human urine samples containing either d-amphetamine or d-methamphetamine at concentrations roughly equivalent to the $\pm 25\%$ cutoff concentration. The d-amphetamine and d-methamphetamine stock solutions had an analytically confirmed concentration of $1\mathrm{mg / mL}$ based upon Certificate of Analysis. The results generated using a Roche/Hitachi 917 analyzer is listed below.
d-Amphetamine:
| Qualitative (ng/mL) | | 300 ng/mL Cutoff | | 500 ng/mL Cutoff | | 1000 ng/mL Cutoff | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Compound | Compound Concentration | Neg Level | Pos Level | Neg Level | Pos Level | Neg Level | Pos Level |
| Acetone | 1 % | NEG | POS | NEG | POS | NEG | POS |
| Ascorbic Acid | 1 % | NEG | POS | NEG | POS | NEG | POS |
| Conjugated Bilirubin | 0.1 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Creatinine | 2.75 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Ethanol | 1 % | NEG | POS | NEG | POS | NEG | POS |
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| Qualitative (ng/mL) | | 300 ng/mL Cutoff | | 500 ng/mL Cutoff | | 1000 ng/mL Cutoff | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Glucose | 20 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Hemoglobin | 1 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Human serum albumin | 5 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Oxalic Acid | 2 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Sodium Chloride | 0.25 M | NEG | POS | NEG | POS | NEG | POS |
| Urea | 5 % | NEG | POS | NEG | POS | NEG | POS |
## d-Methamphetamine
| Semiquantitative (ng/mL) | | 300 ng/mL Cutoff | | 500 ng/mL Cutoff | | 1000 ng/mL Cutoff | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Compound | Compound Concentration | Neg Level | Pos Level | Neg Level | Pos Level | Neg Level | Pos Level |
| Acetone | 1 % | NEG | POS | NEG | POS | NEG | POS |
| Ascorbic Acid | 1.5 % | NEG | POS | NEG | POS | NEG | POS |
| Conjugated Bilirubin | 0.1 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Creatinine | 5 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Ethanol | 1 % | NEG | POS | NEG | POS | NEG | POS |
| Glucose | 20 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Hemoglobin | 1 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Human serum albumin | 5 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Oxalic Acid | 2 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Sodium Chloride | 0.5 M | NEG | POS | NEG | POS | NEG | POS |
| Urea | 6 % | NEG | POS | NEG | POS | NEG | POS |
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There is the possibility that other substances and/or factors not listed above may interfere with the test and cause false results, e.g., technical or procedural errors.
The sponsor includes a note in the labeling about not assaying the Tina-quant Hemoglobin A1c Gen. 2 and the Amphetamines II assay on the same analyzer as follows:
"When you are running Amphetamines II, and Tina-quant Hemoglobin A1c Gen. 2 assay on a Hitachi 917 system, please avoid processing Amphetamines II as the first test from standby status. If no other testing is pending then a dummy test sample should be processed to prevent the Amphetamines II from being the first test from standby (Dummy test order any test having an R1 (not HbA1c)."
To test for possible positive and/or negative interference from specific gravity, the sponsor prepared samples containing drug at control levels (±25% of each cutoff concentration) with specific gravities ranging from 1.001 to 1.020. No positive or negative interference due to specific gravity was observed.
To test for potential negative interference from pH the sponsor prepared samples containing drug at control levels (±25% of each cutoff concentration) with pH ranging from 4.5 to 8.0. No negative interference due to pH was observed.
f. Assay cut-off:
There are three cutoff concentrations claimed for both d-amphetamine and d-methamphetamine: 300 ng/mL; 500 ng/mL; 1000 ng/mL.
2. Comparison studies:
a. Method comparison with predicate device:
The sponsor conducted an initial method comparison study to evaluate the performance of the device for d-methamphetamine. This study involved 190 unaltered clinical samples (114 negative and 76 positive) evaluated by the methamphetamine assay and also tested for methamphetamine using GC/MS. The agreement between GC/MS and new device results for both qualitative and semi-quantitative modes of the device are listed in the tables below.
Qualitative Assay Results:
| Roche ONLINE DAT AMPII assay | 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) |
| --- | --- | --- | --- | --- |
| 300 ng/mL Cutoff | | | | |
| Positive | 2 | 1 | 7 | 69 |
| Negative | 108 | 3 | 0 | 0 |
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| 500 ng/mL Cutoff | | | | |
| --- | --- | --- | --- | --- |
| Positive | 0 | 0 | 6 | 69 |
| Negative | 110 | 4 | 0 | 0 |
| 1000 ng/mL Cutoff | | | | |
| Positive | 0 | 0 | 7 | 66 |
| Negative | 110 | 5 | 0 | 1 |
Semi-Quantitative Assay Results:
| Roche ONLINE DAT AMPII assay | 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) |
| --- | --- | --- | --- | --- |
| 300 ng/mL Cutoff | | | | |
| Positive | 1 | 1 | 7 | 69 |
| Negative | 109 | 3 | 0 | 0 |
| 500 ng/mL Cutoff | | | | |
| Positive | 0 | 1 | 6 | 69 |
| Negative | 110 | 3 | 0 | 0 |
| 1000 ng/mL Cutoff | | | | |
| Positive | 0 | 0 | 7 | 66 |
| Negative | 110 | 5 | 0 | 1 |
The sponsor evaluated the cause for the discrepant results generated between the new device and GC/MS for samples tested under qualitative and semi-quantitative modes. The results are listed in the table below.
{13}
| Cutoff Value (ng/mL) | Roche ONLINE DAT Methamphetamine OBSERVED Result | Roche ONLINE DAT Methamphetamine EXPECTED Result | GC/MS (ng/mL) | Drug / Metabolite |
| --- | --- | --- | --- | --- |
| 300 (SQ & Q) | Positive | Negative | 174 | d-methamphetamine |
| 300 (SQ & Q) | Positive | Negative | 58710
278 | Pseudoephedrine
Ephedrine |
| 300 Q | Positive | Negative | 76730
124 | Pseudoephedrine
Ephedrine |
| 500 (SQ) | Positive | Negative | 181
173 | d-amphetamine
d-methamphetamine |
| 1000 (SQ & Q) | Negative | Positive | 2834 | d-amphetamine |
The sponsor conducted two additional studies for both d-amphetamine and d-methamphetamine assays. The results were compared with GC/MS results for each cutoff concentration used in the new device. The sponsor used 40 unaltered urine samples negative for amphetamine or methamphetamine, including 4 near cutoff negative samples (i.e. values between cutoff and -50% of the cutoff by GC/MS for each drug), and 40 unaltered urine samples positive for amphetamine or methamphetamine including 4 near cutoff positive samples (i.e. values between cutoff and +50% of the cutoff by GC/MS for each drug).
## New Device Results vs. stratified GC/MS Values for the d-Amphetamine assay:
The results for d-amphetamine listed in the tables below demonstrated a 92.5% negative agreement at the 300 ng/mL and 500 ng/mL cutoff concentrations with GC/MS for both the semiquantitative and qualitative assays. For d-amphetamine cutoff concentration of 1000 ng/mL, the device produced 95% and 97.5% negative agreement with GC/MS results for semiquantitative and qualitative assays, respectively. 100% positive agreement was observed between GC/MS and the new device for both semiquantitative and qualitative assays at all cutoff levels. The comparison between GC/MS and new device results are listed in the tables below.
{14}
Qualitative Assay Results:
| Roche ONLINE DAT AMPII assay | 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) |
| --- | --- | --- | --- | --- |
| 300 ng/mL Cutoff | | | | |
| Positive | 0 | 3 | 4 | 36 |
| Negative | 36 | 1 | 0 | 0 |
| 500 ng/mL Cutoff | | | | |
| Positive | 0 | 3 | 4 | 36 |
| Negative | 36 | 1 | 0 | 0 |
| 1000 ng/mL Cutoff | | | | |
| Positive | 0 | 1 | 4 | 36 |
| Negative | 36 | 3 | 0 | 0 |
Semi-quantitative Assay Results:
| Roche ONLINE DAT AMPII assay | 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) |
| --- | --- | --- | --- | --- |
| 300 ng/mL Cutoff | | | | |
| Positive | 0 | 3 | 4 | 36 |
| Negative | 36 | 1 | 0 | 0 |
| 500 ng/mL Cutoff | | | | |
| Positive | 0 | 3 | 4 | 36 |
| Negative | 36 | 1 | 0 | 0 |
| 1000 ng/mL Cutoff | | | | |
15
{15}
The sponsor evaluated the cause for the discrepant results generated between the new device and GC/MS for negative samples, and determined that the samples contained d-methamphetamine that also produced a signal due to cross-reactivity. The results between GC/MS and new device cross reactivity data for d-amphetamine at 300 ng/mL cut-off are listed in the tables below.
| Cutoff Value (ng/mL) | Roche ONLINE DAT Amphetamines OBSERVED Result | EXPECTED Result for d-amphetamine | GC/MS (ng/mL) | Drug / Metabolite |
| --- | --- | --- | --- | --- |
| 300 (SQ & Q)¹ | Positive | Negative | 157
363 | d-Amphetamine
d-Methamphetamine |
| 300 (SQ & Q) | Positive | Negative | 181
173 | d-Amphetamine
d-Methamphetamine |
| 300 (SQ & Q) | Positive | Negative | 220
171 | d-Amphetamine
d-Methamphetamine |
| 500 (SQ & Q) | Positive | Negative | 438
121 | d-Amphetamine
d-Methamphetamine |
| 500 (SQ & Q) | Positive | Negative | 457
1152 | d-Amphetamine
d-Methamphetamine |
| 500 (SQ & Q) | Positive | Negative | 443
706 | d-Amphetamine
d-Methamphetamine |
| 1000 (SQ) | Positive | Negative | 961 | d-Amphetamine |
| 1000 (SQ & Q) | Positive | Negative | 837
1163 | d-Amphetamine
d-Methamphetamine |
¹ SQ – Semi-quantitative mode; Q – Qualitative mode
## New Device Results vs. stratified GC/MS Values for d-Methamphetamine:
The results for d-methamphetamine listed in the tables below indicated that for all cutoff concentrations, 90% negative agreement with GC/MS values for both the semiquantitative and qualitative assays was observed. 100% positive agreement was seen between GC/MS and the new device for both semiquantitative and qualitative assays at all cutoff levels. The agreement between GC/MS and new device results are listed in the tables below.
{16}
Qualitative Assay Results:
| Roche ONLINE DAT AMPII assay | 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) |
| --- | --- | --- | --- | --- |
| 300 ng/mL Cutoff | | | | |
| Positive | 0 | 4 | 4 | 36 |
| Negative | 36 | 0 | 0 | 0 |
| 500 ng/mL Cutoff | | | | |
| Positive | 0 | 4 | 4 | 36 |
| Negative | 36 | 0 | 0 | 0 |
| 1000 ng/mL Cutoff | | | | |
| Positive | 0 | 4 | 4 | 36 |
| Negative | 36 | 0 | 0 | 0 |
Semi-quantitative Assay Results:
| Roche ONLINE DAT AMPII assay | 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) |
| --- | --- | --- | --- | --- |
| 300 ng/mL Cutoff | | | | |
| Positive | 0 | 4 | 4 | 36 |
| Negative | 36 | 0 | 0 | 0 |
| 500 ng/mL Cutoff | | | | |
| Positive | 0 | 4 | 4 | 36 |
| Negative | 36 | 0 | 0 | 0 |
17
{17}
| 1000 ng/mL Cutoff | | | | |
| --- | --- | --- | --- | --- |
| Positive | 0 | 4 | 4 | 36 |
| Negative | 36 | 0 | 0 | 0 |
The sponsor evaluated the root cause for the discrepant results generated between the new device and GC/MS for negative samples, and determined that the samples contained d-amphetamine that also produced a signal due to the presence of antibody targeting d-amphetamine in the device. The results between GC/MS and new device cross reactivity data for d-methamphetamine at $300\mathrm{ng / mL}$ cut-off are listed in the tables below.
| Cutoff Value (ng/mL) | Roche ONLINE DAT Amphetamines II ACTUAL Result | EXPECTED Result for d-methamphetamine | GC/MS (ng/mL) | Drug / Metabolite |
| --- | --- | --- | --- | --- |
| 300 (SQ & Q) | Positive | Negative | 173 | d-Methamphetamine |
| | | | 181 | d-Amphetamine |
| 300 (SQ & Q) | Positive | Negative | 278 | d-Methamphetamine |
| | | | 101 | d-Amphetamine |
| 300 (SQ & Q) | Positive | Negative | 220 | d-Methamphetamine |
| | | | 171 | d-Amphetamine |
| 300 (SQ & Q) | Positive | Negative | 291 | d-Methamphetamine |
| | | | 145 | d-Amphetamine |
| 500 (SQ & Q) | Positive | Negative | 488 | d-Methamphetamine |
| | | | 466 | d-Amphetamine |
| 500 (SQ & Q) | Positive | Negative | 325 | d-Methamphetamine |
| | | | 171 | d-Amphetamine |
| 500 (SQ & Q) | Positive | Negative | 291 | d-Methamphetamine |
| | | | 145 | d-Amphetamine |
| 500 (SQ & Q) | Positive | Negative | 472 | d-Methamphetamine |
| | | | 650 | d-Amphetamine |
| 1000 (SQ & Q) | Positive | Negative | 706 | d-Methamphetamine |
| | | | 443 | d-Amphetamine |
| 1000 (SQ & Q) | Positive | Negative | 540 | d-Methamphetamine |
| | | | 693 | d-Amphetamine |
{18}
| 1000 (SQ & Q) | Positive | Negative | 769
395 | d-Methamphetamine
d-Amphetamine |
| --- | --- | --- | --- | --- |
| 1000 (SQ & Q) | Positive | Negative | 572
432 | d-Methamphetamine
d-Amphetamine |
b. Matrix comparison:
Not applicable
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.
