AMPHETAMINES II ASSAY
Device Facts
| Record ID | K093664 |
|---|---|
| Device Name | AMPHETAMINES II ASSAY |
| Applicant | Roche Diagnostics Corp. |
| Product Code | DKZ · Clinical Toxicology |
| Decision Date | Jul 28, 2010 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.3100 |
| Device Class | Class 2 |
| Attributes | Real-World Evidence |
Real-World Evidence
| Submission | Device | Sponsor | RWD Sources | RWE Use Summary | Key Tags |
|---|---|---|---|---|---|
| K093664 · Jul 28, 2010 | AMPHETAMINES II ASSAY | Roche Diagnostics Corp. | Clinical laboratory urine samples | Clinical urine samples (previously screened and confirmed by GC/MS) were used to evaluate the accuracy and performance of the Amphetamines II assay compared to GC/MS results. | Accuracy study; Clinical urine samples; GC/MS confirmation |
Clinical Evidence
| Study Design | Population | Comparator | Key Endpoints |
|---|---|---|---|
| Retrospective accuracy study using clinical samples | Clinical urine samples; Sample Size: 72 total (36 negative, 36 positive) | GC/MS | Percent agreement with GC/MS |
Indications for Use
Amphetamines II (AMPII) is an in vitro diagnostic test for the qualitative and semiquantitative detection of amphetamines and methamphetamines on COBAS INTEGRA systems 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
Immunoassay for automated clinical chemistry analyzers (Integra 800); detects amphetamines/methamphetamines in urine. Principle: Kinetic interaction of microparticles in solution (KIMS). Input: Urine sample; antibody working solution; drug-microparticle conjugate. Mechanism: In absence of drug, antibody binds microparticles causing aggregation (absorbance increases). If drug present, it competes for antibody, inhibiting aggregation; absorbance change proportional to drug concentration. Output: Preliminary positive/negative result (qualitative) or concentration (semi-quantitative). Used by laboratory professionals to screen for drug abuse; results require GC/MS confirmation. Benefits: Rapid preliminary screening for clinical decision-making.
Clinical Evidence
Bench testing only. Precision was evaluated per CLSI EPS-A2 (N=84 per condition). Accuracy was determined by comparing results against GC/MS-confirmed urine samples. Qualitative and semiquantitative agreement with GC/MS was reported, with 100% agreement for high-positive samples and varying agreement for near-cutoff samples. Analytical specificity and cross-reactivity were assessed against various phenethylamines and unrelated drugs. No clinical trial data was required.
Technological Characteristics
Wet reagent immunoassay (KIMS). Reagents: Antibody working solution (mouse monoclonal) and drug-microparticle conjugate in buffer with BSA and 0.09% sodium azide. Platform: COBAS INTEGRA 800. Calibration: d-methamphetamine. Stability: 1 year closed vial (2-8°C), 56 days on-board. Connectivity: Automated analyzer.
Indications for Use
Indicated for qualitative and semiquantitative detection of amphetamines and methamphetamines in human urine. Used for preliminary screening; requires confirmation by GC/MS. Intended for professional use in clinical laboratories.
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
- ONLINE Amphetamines II Assay (k083764)
Reference Devices
- Preciset DAT Plus I Calibrators (K060645)
- Preciset DAT Plus II Calibrators (K060645)
- C.f.a.s. DAT Qualitative Plus Calibrators (K060645)
- Control Set DAT I (K080183)
- Control Set DAT II (K080183)
- Control Set DAT III (K080183)
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k093664
B. Purpose for Submission:
New device
C. Measurand:
Urine amphetamine and urine methamphetamine
D. Type of Test:
Qualitative enzyme immunoassay
E. Applicant:
Roche Diagnostics
F. Proprietary and Established Names:
Amphetamines II
G. Regulatory Information:
1. Regulation section:
21 CFR § 862.3100 Amphetamine Test System
21 CFR § 862.3610 Methamphetamine Test System
2. Classification:
II
3. Product code:
DKZ, enzyme immunoassay, amphetamine
LAF, gas chromatography, methamphetamine
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4. Panel:
Toxicology (91)
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 COBAS INTEGRA systems 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.
3. Special conditions for use statement(s):
a. Prescription use
b. 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.
c. Recommended calibrators are Preciset DAT Plus I, Preciset DAT Plus II and CFAS DAT Qualitative Plus Calibrators (k060645, k090939).
d. Recommended controls to be used are Control Set DAT I, Control Set DAT II, Control Set DAT III (k060645, k080183).
e. AMPII must not be run in parallel with Roche A1C-2. Special wash programming steps are not sufficient to overcome reagent carryover issues when Amphetamines II is run in parallel with HbA1cII. The user is instructed that AMPII cannot be run in parallel with HbA1cII.
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4. Special instrument requirements:
Integra 800
I. Device Description:
The Amphetamines II test is an immunoassay for use on automated clinical chemistry analyzers. The device consists of two wet reagents; an antibody working solution, and a drug-microparticle conjugate. During the assay, in the absence of sample drug in urine, free antibody binds to the drug-microparticle conjugates causing the formation of particle aggregates. When a urine sample contains the drug in question, this drug competes with the particle-bound drug derivative for free antibody. Antibody bound to sample drug is no longer available to promote particle aggregation, and subsequent particle lattice formation is inhibited. The rate of absorbance change is proportional to the concentration of drug in the sample. Calibrators, ranging in concentration from 0-5000 ng/mL depending on cutoff and test mode, are run with the assay. Concentrations of controls and unknowns are calculated from the standard curve in semi-quantitative mode. Results for controls or calibrators are determined as preliminary positive or negative relative to the cutoff in qualitative mode.
C.f.a.s. DAT Qualitative Clinical, C.f.a.s. DAT Qualitative Plus, C.f.a.s. DAT Qualitative Plus Clinical, Preciset DAT Plus I Calibrators, and Preciset DAT Plus II Calibrators are ready to use, multianalyte calibrators prepared by the quantitative addition of drug or drug metabolite to drug-free human urine and are available separately from the reagent.
Control Set DAT I, II, and III, and Control Set DAT Clinical are ready to use multianalyte controls prepared by the quantitative addition of drug or drug metabolite to drug-free urine and are available separately from the reagent.
J. Substantial Equivalence Information:
1. Predicate device name(s):
ONLINE Amphetamines II Assay
2. Predicate K number(s):
k083764
3. Comparison with predicate:
| Feature | Amphetamines II Assay, Integra 800 | Predicate Device: Online Amphetamines II Assay, Hitachi 917 (k083764) |
| --- | --- | --- |
| Methodology | Same | KIMS, Kinetic interaction of microparticles in solution |
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| Sample Type | Same | Urine |
| --- | --- | --- |
| Indications for Use/ Intended Use | Same | Qualitative and semi-quantitative detection of amphetamines and methamphetamines |
| Reagents | Same | Conjugate Working Solution: Conjugated amphetamine, and methamphetamine derivatives 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. |
| Cutoff | Same | 300, 500, 1,000 ng/mL |
K. Standard/Guidance Document Referenced (if applicable):
Draft Guidance for Industry and FDA Staff: Premarket Submission and Labeling Recommendations for Drugs of Abuse Screening Tests
CLSI EP-5A: Evaluation of Precision Performance of Clinical Chemistry Devices; and
Approved Guideline -2 ed
L. Test Principle:
The 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:
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Precision studies were performed according to CLSI EP5-A2. Two separate studies were conducted for d-methamphetamine and d-amphetamine for both the qualitative and semi-quantitative assays for each cutoff (300 ng/mL, 500 ng/mL, 1,000 ng/mL). Samples were prepared by spiking a negative human urine pool with the analyte of interest (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. Samples were tested using one reagent lot, in 2 replicates per run, 2 runs per day for 21 days, total n=84 using one reagent lot. For the d-amphetamine study, 10 calibrations were performed. For the d-methamphetamine study, 8 calibrations were performed.
## d-Methamphetamine (MAMP)
300 ng/mL cutoff
| Sample Concentration | Qualitative Results (#Neg/# Pos) | Semi-Quantitative Results (#Neg/# Pos) |
| --- | --- | --- |
| Zero drug | 84 neg/0 pos | 84 neg/0 pos |
| -75% | 84 neg/0 pos | 84 neg/0 pos |
| -50% | 84 neg/0 pos | 84 neg/0 pos |
| -25% | 83 neg/1 pos | 84 neg/0 pos |
| Cutoff | 27 neg/57 pos | 34 neg/50 pos |
| +25% | 0 neg/84 pos | 0 neg/84 pos |
| +50% | 0 neg/84 pos | 0 neg/84 pos |
| +75% | 0 neg/84 pos | 0 neg/84 pos |
| +100% | 0 neg/84 pos | 0 neg/84 pos |
500 ng/mL cutoff
| Sample Concentration | Qualitative Results (#Neg/# Pos) | Semi-Quantitative Results (#Neg/# Pos) |
| --- | --- | --- |
| Zero drug | 84 neg/0 pos | 84 neg/0 pos |
| -75% | 84 neg/0 pos | 84 neg/0 pos |
| -50% | 84 neg/0 pos | 84 neg/0 pos |
| -25% | 84 neg/0 pos | 84 neg/0 pos |
| Cutoff | 28 neg/56 pos | 38 neg/46 pos |
| +25% | 0 neg/84 pos | 0 neg/84 pos |
| +50% | 0 neg/84 pos | 0 neg/84 pos |
| +75% | 0 neg/84 pos | 0 neg/84 pos |
| +100% | 0 neg/84 pos | 0 neg/84 pos |
1000 ng/mL cutoff
| Sample Concentration | Qualitative Results (#Neg/# Pos) | Semi-Quantitative Results (#Neg/# Pos) |
| --- | --- | --- |
| Zero drug | 84 neg/0 pos | 84 neg/0 pos |
| -75% | 84 neg/0 pos | 84 neg/0 pos |
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-50% 84 neg/0 pos 84 neg/0 pos
-25% 84 neg/0 pos 84 neg/0 pos
Cutoff 13 neg/71 pos 25 neg/59 pos
+25% 0 neg/84 pos 0 neg/84 pos
+50% 0 neg/84 pos 0 neg/84 pos
+75% 0 neg/84 pos 0 neg/84 pos
+100% 0 neg/84 pos 0 neg/84 pos
## d-Amphetamines (AMP)
### 300 ng/mL cutoff
| Sample Concentration | Qualitative Results (#Neg/# Pos) | Semi-Quantitative Results (#Neg/# Pos) |
| --- | --- | --- |
| Zero drug | 84 neg/0 pos | 84 neg/0 pos |
| -75% | 84 neg/0 pos | 84 neg/0 pos |
| -50% | 84 neg/0 pos | 84 neg/0 pos |
| -25% | 84 neg/0 pos | 84 neg/0 pos |
| Cutoff | 2 neg/82 pos | 4 neg/80 pos |
| +25% | 0 neg/84 pos | 0 neg/84 pos |
| +50% | 0 neg/84 pos | 0 neg/84 pos |
| +75% | 0 neg/84 pos | 0 neg/84 pos |
| +100% | 0 neg/84 pos | 0 neg/84 pos |
### 500 ng/mL cutoff
| Sample Concentration | Qualitative Results (#Neg/# Pos) | Semi-Quantitative Results (#Neg/# Pos) |
| --- | --- | --- |
| Zero drug | 84 neg/0 pos | 84 neg/0 pos |
| -75% | 84 neg/0 pos | 84 neg/0 pos |
| -50% | 84 neg/0 pos | 84 neg/0 pos |
| -25% | 82 neg/2 pos | 84 neg/0 pos |
| Cutoff | 6 neg/78 pos | 0 neg/84 pos |
| +25% | 0 neg/84 pos | 0 neg/84 pos |
| +50% | 0 neg/84 pos | 0 neg/84 pos |
| +75% | 0 neg/84 pos | 0 neg/84 pos |
| +100% | 0 neg/84 pos | 0 neg/84 pos |
### 1000 ng/mL cutoff
| Sample Concentration | Qualitative Results (#Neg/# Pos) | Semi-Quantitative Results (#Neg/# Pos) |
| --- | --- | --- |
| Zero drug | 84 neg/0 pos | 84 neg/0 pos |
| -75% | 84 neg/0 pos | 84 neg/0 pos |
| -50% | 84 neg/0 pos | 84 neg/0 pos |
| -25% | 82 neg/2 pos | 84 neg/0 pos |
| Cutoff | 6 neg/78 pos | 6 neg/78 pos |
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| +25% | 1 neg/83 pos | 0 neg/84 pos |
| --- | --- | --- |
| +50% | 0 neg/84 pos | 0 neg/84 pos |
| +75% | 0 neg/84 pos | 0 neg/84 pos |
| +100% | 0 neg/84 pos | 0 neg/84 pos |
# b. Linearity/assay reportable range:
Recovery across the range was confirmed by serially diluting a spiked urine pool containing drug in desired levels listed in the tables below to cover their measuring ranges of $0 - 2,000\mathrm{ng / mL}$ and $0 - 5,000\mathrm{ng / mL}$ for both drugs. Each sample was assayed on Integra 800 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:
d-Methamphetamine
| 300 Expected | ng/mL Observed | Cutoff % Recovery | 500 Expected | ng/mL Observed | cutoff % Recovery | 1000 Expected | ng/mL Observed | cutoff % Recovery |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 0 | 12 | --- | 0 | 5 | --- | 0 | 8 | --- |
| 53.6 | 62 | 115.7 | 81.1 | 82 | 101.1 | 135.2 | 159 | 117.6 |
| 107.3 | 114 | 106.3 | 162 | 155 | 95.5 | 270.4 | 265 | 98.0 |
| 160.9 | 165 | 102.8 | 243.4 | 226 | 92.8 | 405.6 | 379 | 93.4 |
| 214.5 | 239 | 111.3 | 324.6 | 283 | 87.2 | 540.8 | 611 | 113.0 |
| 268.2 | 258 | 96.0 | 405.7 | 350 | 86.3 | 676 | 691 | 102.2 |
| 321.8 | 322 | 100.1 | 486.8 | 430 | 88.3 | 811.2 | 905 | 111.6 |
| 375.4 | 356 | 94.9 | 568 | 559 | 98.4 | 946.4 | 1029 | 108.7 |
| 429.1 | 411 | 95.7 | 649.1 | 643 | 99.1 | 1081.6 | 1269 | 117.3 |
| 482.7 | 441 | 91.3 | 730.2 | 726 | 99.4 | 1216.8 | 1382 | 113.6 |
| 536.3 | 536 | 99.9 | 811.4 | 850 | 104.8 | 1352.0 | 1509 | 111.6 |
| 590.0 | 557 | 94.4 | 1622.8 | 1767 | 108.9 | 2028 | 2028 | 100 |
| 643.6 | 604 | 93.9 | 2434.1 | 2356 | 96.8 | 2704 | 2703 | 100 |
| 858.1 | 809 | 94.2 | 3245.5 | 3256 | 100.3 | 3380 | 3372 | 99.8 |
| 1072.7 | 1072 | 99.9 | 4056.9 | 4223 | 104.1 | 4056 | 4045 | 99.7 |
| 1287.2 | 1253 | 97.4 | 4868.3 | 5290 | 108.7 | 4732 | 4296 | 90.8 |
| 1501.7 | 1538 | 102.4 | 5679.6 | 5834 | 102.7 | 5408 | 5103 | 94.4 |
| 1716.3 | 1730 | 100.8 | 6491 | 6470 | 99.7 | 6084 | 5482 | 90.1 |
| 1930.8 | 1946 | 100.8 | | 6760 | 5955 | 88.1 | | |
| 2145.3 | 2233 | 104.1 | | | | | | |
d-Amphetamine
| 300 Expected | ng/mL Observed | Cutoff % Recovery | 500 Expected | ng/mL Observed | cutoff % Recovery | 1000 Expected | ng/mL Observed | cutoff % Recovery |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
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| -14.6 | 0 | --- | 0 | -51.1 | --- | -18.5 | 0 | --- |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| 34.2 | 24 | 70.4 | 69.9 | 111 | 158.5 | 98.2 | 112 | 114 |
| 82.9 | 83 | 99.8 | 190.9 | 210 | 110.1 | 214.8 | 223 | 103.8 |
| 131.6 | 132 | 100.1 | 311.9 | 304 | 97.3 | 331.4 | 306 | 92.4 |
| 180.3 | 173 | 96.1 | 432.9 | 412 | 95.1 | 448 | 442 | 98.7 |
| 229.1 | 231 | 100.8 | 553.9 | 504 | 91.0 | 564.6 | 533 | 94.4 |
| 277.8 | 263 | 94.8 | 674.9 | 687 | 101.8 | 681.2 | 665 | 97.7 |
| 326.5 | 335 | 102.5 | 795.9 | 776 | 97.5 | 797.8 | 765 | 95.9 |
| 375.2 | 369 | 98.3 | 916.9 | 916 | 99.9 | 914.4 | 891 | 97.5 |
| 423.9 | 408 | 96.3 | 1037.9 | 1018 | 98.1 | 1031 | 1056 | 102.4 |
| 472.7 | 482 | 102 | 1158.9 | 1095 | 94.5 | 1147.6 | 1142 | 99.5 |
| 521.4 | 527 | 101.1 | 1279.9 | 1279 | 99.9 | 1264.2 | 1217 | 96.3 |
| 570.1 | 563 | 98.7 | 1400.9 | 1403 | 100.2 | 1380.8 | 1389 | 100.6 |
| 765 | 792 | 103.6 | 1884.8 | 1975 | 104.8 | 1847.3 | 1852 | 100.3 |
| 959.9 | 1009 | 105.1 | 2368.8 | 2385 | 100.7 | 2313.7 | 2324 | 100.5 |
| 1154.8 | 1162 | 100.6 | 2852.8 | 2685 | 94.1 | 2780.1 | 2745 | 98.7 |
| 1349.7 | 1464 | 108.5 | 3336.7 | 3338 | 100 | 3246.6 | 3256 | 100.3 |
| 1544.6 | 1527 | 98.9 | 3820.7 | 3546 | 92.8 | 3713 | 3918 | 105.5 |
| 1739.5 | 1732 | 99.6 | 4303.7 | 4550 | 105.7 | 4179.4 | 4284 | 102.5 |
| 1934.4 | 1909 | 98.7 | 4788.7 | 4978 | 104.0 | 4645.8 | 4477 | 96.4 |
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 have been previously cleared in k060645. Control materials for three cutoff levels have been previously cleared in k080183, k090939.
The sponsor performed both real time and accelerated stability studies for shipping, open and closed vial reagent stability, and calibration stability. The closed reagent stability at 2-8°C is one year, on-board stability is 56 days. The on-board stability for open vials is 56 days. The sponsor recommends that users should not freeze the reagents.
On board calibration stability testing was performed on the Integra 800. Calibration is stable for 28 days.
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:
**Endogenous Interfering Substances:** Potential interference from substances endogenous to urine were tested in both semi-quantitative and qualitative
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mode by spiking the potentially interfering compound into human urine samples containing either d-methamphetamine or d-amphetamine at concentrations roughly equivalent to the $\pm 25\%$ cutoff concentration. The stock solutions had an analytically confirmed concentration of $1\mathrm{mg/mL}$ based upon their Certificates of Analysis. The median of triplicate observed values for samples containing potentially interfering compounds were compared to the median of triplicate values for control urine not spiked with potentially interfering compounds. The percent recovery was calculated by dividing the median concentration of the sample containing the potentially interfering compound by the median concentration of the control and multiplying by 100. If interference was observed, the concentration of the interferent was lowered and retested until no interference was observed.
Interferent concentrations were determined independently for methamphetamines and amphetamines for both the semi-quantitative and qualitative modes. Interfering substances were added to urine containing $d$-methamphetamine (MAMP) or $d$-amphetamine (AMP) at $-25\%$ (Neg. Level) and $+25\%$ (Pos. Level) of the cutoff level at the concentration listed in the Cmpd. Conc. column. All samples were tested and the following results were obtained on a COBAS INTEGRA 800 analyzer.
For the interference study for d-methamphetamine, 1 calibration was performed during the study. For the interference study for d-amphetamine, 2 calibrations were performed during the study.
| Methamphetamine Semiquantitative (ng/mL) | | 300 ng/mL Cutoff | | 500 ng/mL Cutoff | | 1000 ng/mL Cutoff | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Compound | Cmpd. Conc. | -25% cutoff | +25% cutoff | -25% cutoff | +25% cutoff | -25% cutoff | +25% cutoff |
| Acetone | 7.9 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Ascorbic Acid | 10 mg/mL | 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 | 7.9 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Glucose | 12 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Hemoglobin | 1 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Human serum albumin | 3 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Oxalic Acid | 2 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Sodium Chloride | 23 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Urea | 60 mg/mL | NEG | POS | NEG | POS | NEG | POS |
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| Methamphetamine Qualitative (ng/mL) | | 300 ng/mL Cutoff | | 500 ng/mL Cutoff | | 1000 ng/mL Cutoff | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Compound | Cmpd. Conc. | -25% cutoff | +25% cutoff | -25% cutoff | +25% cutoff | -25% cutoff | +25% cutoff |
| Creatinine | 5mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Glucose | 12 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Albumin | 3 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| NaCl | 23 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Oxalic Acid | 2 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Urea | 60 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Acetone | 7.9 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Ascorbic acid | 10 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Ethanol | 7.9 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Hemoglobin | 1 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Conjugated bilirubin | 0.1 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Amphetamine Semiquantitative (ng/mL) | | 300 ng/mL Cutoff | | 500 ng/mL Cutoff | | 1000 ng/mL Cutoff | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Compound | Cmpd. Conc. | -25% cutoff | +25% cutoff | -25% cutoff | +25% cutoff | -25% cutoff | +25% cutoff |
| Acetone | 7.9 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Ascorbic Acid | 10 mg/mL | 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 | 7.9 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Glucose | 12 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Hemoglobin | 1 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Human serum albumin | 3 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Oxalic Acid | 2 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Sodium Chloride | 23 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Urea | 60 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Amphetamine Qualitative (ng/mL) | | 300 ng/mL Cutoff | | 500 ng/mL Cutoff | | 1000 ng/mL Cutoff | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Compound | Cmpd. Conc. | -25% cutoff | +25% cutoff | -25% cutoff | +25% cutoff | -25% cutoff | +25% cutoff |
| Creatinine | 5mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Glucose | 12 mg/mL | NEG | POS | NEG | POS | NEG | POS |
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| Albumin | 3 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| --- | --- | --- | --- | --- | --- | --- | --- |
| NaCl | 23 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Oxalic Acid | 2 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Urea | 60 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Acetone | 7.9 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Ascorbic acid | 10 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Ethanol | 7.9 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Hemoglobin | 1 mg/mL | NEG | POS | NEG | POS | NEG | POS |
| Conjugated bilirubin | 0.1 mg/mL | NEG | POS | NEG | POS | NEG | POS |
$\mathbf{pH}$ : To test for potential negative interference from $\mathsf{pH}$ , the sponsor prepared samples containing target drug at levels $\pm 25\%$ of each cutoff concentration with $\mathsf{pH}$ ranging from 4.5 to 8.0. Interference due to $\mathsf{pH}$ was $\leq 5\%$ for the semi-quantitative or qualitative modes for each cutoff for amphetamine or methamphetamine from $\mathsf{pH}4.5$ to 8.0.
Specific Gravity: Urine specific gravity samples were prepared by an outside laboratory to concentrations ranging from 1.001-1.034. Samples were analyzed in both the semiquantitative and qualitative modes for amphetamine and methamphetamine at $\pm 25\%$ of each cutoff concentration. Twenty replicates were tested in both the semi-quantitative and qualitative modes at each specific gravity level. The mean, standard deviation, and $\% \mathrm{CV}$ were calculated as well as number of crossovers. Interference due to specific gravity was $\leq 5\%$ in the semi-quantitative or qualitative modes for each cutoff for amphetamine or methamphetamine between 1.001-1.034.
Cross Reactivity: Structurally Related: Cross-reactivity to structurally related compounds was determined by spiking related compounds into drug free human urine samples to produce assay results above and below the assay cutoff. The samples were run in triplicate in both the semi-quantitative and qualitative modes to determine the approximate quantity of each compound that is equivalent in assay reactivity to the 300, 500, and $1,000\mathrm{ng / mL}$ assay cutoff. One calibration was performed during structurally related cross reactivity testing. The table below shows the semi-quantitative and qualitative results of the study for each assay cutoff.
300 ng/mL cutoff
| Compound | Concentration tested ng/mL | Semi-quantitative result | Qualitative result | ng/mL Equivalent to 300 ng/mL | Approx. Percent Cross-reactivity |
| --- | --- | --- | --- | --- | --- |
| d-Methamphetamine | 225 | Neg | Neg | 327 | 91.82 |
| | 375 | Pos | Pos | | |
| d-Amphetamine | 300 | Neg | Neg | 311 | 96.33 |
| d-Methamphetamine | 300 | Pos | Pos | 311 | 96.33 |
{11}
12
| (±) MDEA | 300 | Pos | Pos | 285 | 105.33 |
| --- | --- | --- | --- | --- | --- |
| (±) MDA | 100
325 | Neg
Pos | Neg
Pos | 249 | 120.5 |
| (±) MDMA | 100
150 | Neg
Pos | Neg
Pos | 114 | 263.61 |
| l-Methamphetamine | 1,500
3,200 | Neg
Pos | Neg
Pos | 2,754 | 10.89 |
| l-Ephedrine | 70,000
100,000 | Neg
Pos | Neg
Pos | 94,792 | 0.32 |
| Phendimetrazine | 30,000
60,000 | Neg
Pos | Neg
Pos | 156,740 | 0.63 |
| Phentermine | 50,000
100,000 | Neg
Pos | Neg
Pos | 294,118 | 0.45 |
| (±) Phenylpropanolamine
HCl | 100,000 | Neg | Neg | 1,111,111 | 0.11 |
| d-Pseudoephedrine | 50,000
100,000 | Neg
Pos | Neg
Pos | 269,542 | 0.34 |
| MBDB HCl | 250
500 | Neg
Pos | Neg
Pos | 1,194 | 88.39 |
| BDB HCl | 600
1,200 | Neg
Pos | Neg
Pos | 2,262 | 46.30 |
| l-Amphetamine | 1,000
10,000 | Neg
Pos | Neg
Pos | 23,445 | 4.66 |
| d-Ephedrine | 100,000 | Neg | Neg | 793,651 | 0.09 |
| Tyramine | 70,000
100,000 | Neg
Pos | Neg
Pos | 323,625 | 0.35 |
## 500 ng/mL cutoff
| Compound | Concentration tested ng/mL | Semi-quantitative result | Qualitative result | ng/mL Equivalent to 500 ng/mL | Approx. Percent Cross-reactivity |
| --- | --- | --- | --- | --- | --- |
| d-Methamphetamine | 375
625 | Neg
Pos | Neg
Pos | 444 | 112.61 |
| d-Amphetamine | 500 | Pos | Pos | 460 | 108.80 |
| (±) MDEA | 500 | Pos | Pos | 494 | 101.20 |
| (±) MDA | 325
600 | Neg
Pos | Neg
Pos | 433 | 115.48 |
| (±) MDMA | 150
200 | Neg
Pos | Neg
Pos | 173 | 289.06 |
| l-Methamphetamine | 3,200
7,500 | Neg
Pos | Neg
Pos | 4098 | 12.20 |
| l-Ephedrine | 100,000 | Neg | Neg | 154321 | 0.32 |
| Phendimetrazine | 60,000
100,000 | Neg
Pos | Neg
Pos | 72500 | 0.9 |
| Phentermine | 100,000 | Neg | Neg | 118483 | 0.42 |
| (±) Phenylpropanolamine
HCl | 100,000 | Neg | Neg | 390625 | 0.13 |
| d-Pseudoephedrine | 100,000 | Neg | Neg | 132275 | 0.38 |
| MBDB HCl | 500
750 | Neg
Pos | Neg
Pos | 713 | 70.08 |
| BDB HCl | 1,200 | Neg | Neg | 1209 | 41.37 |
{12}
| | 2,000 | Pos | Pos | | |
| --- | --- | --- | --- | --- | --- |
| l-Amphetamine | 10,000 | Neg | Neg | 11174 | 4.47 |
| | 20,000 | Pos | Pos | | |
| d-Ephedrine | 100,000 | Neg | Neg | 413223 | 0.12 |
| Tyramine | 100,000 | Neg | Neg | 141243 | 0.35 |
## 1,000 ng/mL cutoff
| Compound | Concentration tested ng/mL | Semi-quantitative result | Qualitative result | ng/mL Equivalent to 1000 ng/mL | Approx. Percent Cross-reactivity |
| --- | --- | --- | --- | --- | --- |
| d-Methamphetamine | 750 | Neg | Neg | 970 | 103.08 |
| | 1,250 | Pos | Pos | | |
| d-Amphetamine | 1,000 | Neg | Pos | 1024 | 97.70 |
| (±) MDEA | 1,000 | Neg | Neg | 1203 | 83.10 |
| (±) MDA | 600 | Neg | Neg | 785 | 127.38 |
| | 1,000 | Pos | Pos | | |
| (±) MDMA | 300 | Neg | Neg | 446 | 224.40 |
| | 450 | Pos | Pos | | |
| l-Methamphetamine | 7,500 | Neg | Neg | 9008 | 11.10 |
| | 120,000 | Pos | Pos | | |
| l-Ephedrine | 100,000 | Neg | Neg | 317460 | 0.32 |
| Phendimetrazine | 100,000 | Neg | Neg | 156740 | 0.34 |
| --- | --- | --- | --- | --- | --- |
| Phentermine | 100,000 | Neg | Neg | 294118 | 0.34 |
| (±) Phenylpropanolamine HCl | 100,000 | Neg | Neg | 1111111 | 0.09 |
| d-Pseudoephedrine | 100,000 | Neg | Neg | 269542 | 0.37 |
| MBDB HCl | 750 | Neg | Neg | 1194 | 93.75 |
| | 1,000 | Pos | Pos | | |
| BDB HCl | 2,000 | Neg | Neg | 2262 | 44.22 |
| | 3,500 | Pos | Pos | | |
| l-Amphetamine | 20,000 | Neg | Neg | 23445 | 4.27 |
| | 40,000 | Pos | Pos | | |
| d-Ephedrine | 100,000 | Neg | Neg | 793651 | 0.13 |
| Tyramine | 100,000 | Neg | Neg | 323625 | 0.31 |
**Cross Reactivity: Structurally Unrelated**: Potential interference from structurally unrelated compounds was tested in both semi-quantitative and qualitative mode by spiking the potentially interfering compound into human urine samples containing either d- amphetamine or d-methamphetamine at concentrations roughly equivalent to $\pm 25\%$ cutoff concentrations for each of the three cut-offs: $300~\mathrm{ng / mL}$, $500~\mathrm{ng / mL}$ and $1,000~\mathrm{ng / mL}$ for the semi-quantitative and qualitative modes. For both amphetamine and methamphetamine, the interfering compounds were tested initially at 100,000 ng/mL. The d-methamphetamine and d-amphetamine stock solutions had analytically confirmed concentrations of $1~\mathrm{mg / mL}$ based upon Certificates of Analysis. If cross-over of the cutoff occurred at this $100,000~\mathrm{ng / mL}$ level, the concentration of the cross reactant was reduced to determine the drug level at which the compound did not cause cross-over of the cutoff. Concentrations were decreased for aspartame (40,000
{13}
ng/mL), methaqualone (75,000 ng/mL), phencyclidine (40,000 ng/mL), $\triangle^9$-THC (10,000 ng/mL). None of these compounds gave values in the assay that were equal to or greater than 0.19% cross-reactivity and no results were greater than the assay cutoffs (300 ng/mL, 500 ng/mL, and 1000 ng/mL), with the following exception:
The cross-reactivity for LSD was tested at a concentration of 2500 ng/mL. The results obtained were 0.32%, and 0.71%, for the 300 ng/mL and 1000 ng/mL assay cutoffs respectively. One calibration was performed during the structurally unrelated cross reactivity testing.
The control level samples recovered properly for the 300, 500, and 1000 ng/mL cutoffs in both semiquantitative and qualitative modes. The results indicated that each compound listed below did not interfere with the measurements of the device. The list of compounds tested is below.
| Acetominophen | Diphenhydramine | Morphine |
| --- | --- | --- |
| Acetylsalicylic acid | Diphenylhydantoin | 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 | Mepriridine | Quinine |
| Diazepam | Methadone | Secobarbital |
| Digoxin | Methaqualone | Tetracycline |
| | | $\triangle^9$-THC |
## Special Wash Programming:
There may be interference between certain combinations of Roche assays and the AMPII assay. The sponsor maintains a master list of all special wash programming instructions for the INTEGRA 800 analyzer which is accessible to the user online. The master list recommends the specific order the AMPII assay is to be analyzed in combination with other assays and when cleaning steps are to be taken.
f. Assay cut-off:
See section M1a. above.
{14}
2. Comparison studies:
a. Method comparison with predicate device:
The accuracy of amphetamine and methamphetamine was determined against GC/MS results for each cutoff concentration of 300 ng/mL, 500 ng/mL and 1,000 ng/mL. The sponsor used 36 unaltered negative urine samples and 36 unaltered positive samples for each drug. Further evaluation was performed with 4 urines at concentrations from -50% of the cutoff to the cutoff, and from the cutoff to +50% of the cutoff for each of the respective drugs (N=80). An additional 4 samples were evaluated at the 500 ng/mL cutoff for methamphetamine (N=84). Near cutoff samples are categorized based on the d-amphetamine concentration only. A positive result would be expected based upon the cross reactivity of the device, Amphetamines II, towards d-amphetamine and d-methamphetamine. The positive and negative agreement between the semi-quantitative results and GC/MS and the qualitative results and GC/MS were identical for the 300 ng/mL and 500 ng/mL cutoffs for AMP and for all MAMP cutoffs. Therefore, they are represented in one table for agreement and discrepant results rather than two tables, respectively.
Amphetamine, Near Cutoff 300 ng/mL, Semi-quantitative and Qualitative
| Semi-Quant Pos/Neg | Qual Pos/Neg | AMP GC/MS ng/mL | MAMP GC/MS ng/mL | Total GC/MS ng/mL | |
| --- | --- | --- | --- | --- | --- |
| Positive | Positive | 157 | 363 | 520 | Near Cutoff Negatives (-50% to cutoff) |
| Negative | Negative | 265 | 0 | 265 | |
| Positive | Positive | 181 | 173 | 354 | |
| Positive | Positive | 220 | 171 | 391 | |
| Positive | Positive | 378 | 0 | 378 | Near Cutoff Positives (cutoff to +50%) |
| Positive | Positive | 350 | 879 | 1,229 | |
| Positive | Positive | 395 | 769 | 1,164 | |
| Positive | Positive | 356 | 1,394 | 1,750 | |
Amphetamine Percent Agreement, 300 ng/mL Semi-quantitative and Qualitative
| | Low Neg by CG/MS (< -50%) | Near Cutoff Neg by GC/MS (-50% to cutoff) | Near Cutoff Pos by GC/MS (cutoff to +50%) | High Pos by GC/MS (> +50%) | Percent agreement with GC/MS |
| --- | --- | --- | --- | --- | --- |
| Positive | 0 | 3 | 4 | 36 | 100% |
| Negative | 36 | 1 | 0 | 0 | 92.5% |
| % Samples in range | 45.0% | 5.0% | 5.0% | 45.0% | |
{15}
Amphetamine Non Discriminatory Results, Semi-quantitative and Qualitative, 300 ng/mL cutoff
| Assay type | Result | GC/MS (ng/mL) | Metabolite |
| --- | --- | --- | --- |
| Semi-quantitative
Qualitative | Positive | 157 | d-amphetamine |
| | Positive | 363 | d-methamphetamine |
| Semi-quantitative | Positive | 181 | d-amphetamine |
| Qualitative | Positive | 173 | d-methamphetamine |
| Semi-quantitative
Qualitative | Positive | 220 | d-amphetamine |
| | Positive | 171 | d-methamphetamine |
Amphetamine, Near cutoff 500 ng/mL, Semi-quantitative and Qualitative
| Semi-Quant
Pos/Neg | Qual
Pos/Neg | AMP
GC/MS
ng/mL | MAMP
GC/MS
ng/mL | Total
GC/MS
ng/mL | |
| --- | --- | --- | --- | --- | --- |
| Negative | Negative | 265 | 0 | 265 | Near Cutoff
Negatives
(-50% to cutoff) |
| Positive | Positive | 438 | 121 | 559 | |
| Positive | Positive | 457 | 1,152 | 1,609 | |
| Positive | Positive | 443 | 706 | 1,149 | |
| Positive | Positive | 650 | 472 | 1,122 | Near Cutoff
Positives
(cutoff to +50%) |
| Positive | Positive | 734 | 764 | 1,498 | |
| Positive | Positive | 598 | 241 | 839 | |
| Positive | Positive | 693 | 540 | 1,233 | |
Amphetamine Percent agreement, 500 ng/mL Semi-quantitative and Qualitative
| | Low Neg by CG/MS (< -50%) | Near Cutoff Neg by GC/MS (-50% to cutoff) | Near Cutoff Pos by GC/MS (cutoff to +50%) | High Pos by GC/MS (> +50%) | Percent agreement with GC/MS |
| --- | --- | --- | --- | --- | --- |
| Positive | 0 | 3 | 4 | 36 | 100% |
| Negative | 36 | 1 | 0 | 0 | 92.5% |
| % Samples in range | 45.0% | 5.0% | 5.0% | 45.0% | |
Amphetamine non discriminatory Results, 500 ng/mL cutoff
| Assay type | Result | GC/MS (ng/mL) | Metabolite |
| --- | --- | --- | --- |
| Semi-quantitative
Qualitative | Positive | 438 | d-amphetamine |
| | Positive | 121 | d-methamphetamine |
| Semi-quantitative
Qualitative | Positive | 457 | d-amphetamine |
| | Positive | 1152 | d-methamphetamine |
| Semi-quantitative | Positive | 443 | d-amphetamine |
| Qualitative | Positive | 706 | d-methamphetamine |
{16}
17
Amphetamine, Near cutoff 1,000 ng/mL, Semi-quantitative and Qualitative
| Semi-Quant Pos/Neg | Qual Pos/Neg | AMP GC/MS ng/mL | MAMP GC/MS ng/mL | Total GC/MS ng/mL | |
| --- | --- | --- | --- | --- | --- |
| Negative | Negative | 961 | 0 | 961 | Near Cutoff Negatives (-50% to cutoff) |
| Positive | Negative | 920 | 0 | 920 | |
| Negative | Negative | 970 | 0 | 970 | |
| Positive | Positive | 837 | 1,163 | 2,000 | |
| Positive | Positive | 1,020 | 3,124 | 4,144 | Near Cutoff Positives (cutoff to +50%) |
| Positive | Positive | 1,161 | 0 | 1,161 | |
| Positive | Positive | 1,197 | 3,853 | 5,050 | |
| Positive | Positive | 1,348 | 1,339 | 2,687 | |
Amphetamine Percent agreement, 1,000 ng/mL Semi-quantitative
| | Low Neg by CG/MS (< -50%) | Near Cutoff Neg by GC/MS (-50% to cutoff) | Near Cutoff Pos by GC/MS (cutoff to +50%) | High Pos by GC/MS (> +50%) | Percent agreement with GC/MS |
| --- | --- | --- | --- | --- | --- |
| Positive | 0 | 2 | 4 | 36 | 100% |
| Negative | 36 | 2 | 0 | 0 | 95.0% |
| % Samples in range | 45.0% | 5.0% | 5.0% | 45.0% | |
Amphetamine Percent agreement, 1,000 ng/mL Qualitative
| | Low Neg by CG/MS (< -50%) | Near Cutoff Neg by GC/MS (-50% to cutoff) | Near Cutoff Pos by GC/MS (cutoff to +50%) | High Pos by GC/MS (> +50%) | Percent agreement with GC/MS |
| --- | --- | --- | --- | --- | --- |
| Positive | 0 | 1 | 4 | 36 | 100% |
| Negative | 36 | 3 | 0 | 0 | 97.5% |
| % Samples in range | 45.0% | 5.0% | 5.0% | 45.0% | |
Amphetamine Non discriminatory Results, 1,000 ng/mL cutoff
| Assay type | Result | GC/MS (ng/mL) | Metabolite |
| --- | --- | --- | --- |
| Semi-quantitative | Positive | 920 | d-amphetamine |
| Semi-quantitative | Positive | 837 | d-amphetamine |
| Qualitative | Positive | 1163 | d-methamphetamine |
{17}
Methamphetamine, Near cutoff 300 ng/mL, Semi-quantitative and Qualitative
| Semi-Quant Pos/Neg | Qual Pos/Neg | MAMP GC/MS ng/mL | AMP GC/MS ng/mL | Total GC/MS ng/mL | |
| --- | --- | --- | --- | --- | --- |
| Positive | Positive | 173 | 181 | 354 | Near Cutoff Negatives (-50% to cutoff) |
| Positive | Positive | 278 | 101 | 379 | |
| Positive | Positive | 220 | 171 | 391 | |
| Positive | Positive | 291 | 145 | 436 | |
| Positive | Positive | 313 | 105 | 418 | Near Cutoff Positives (cutoff to +50%) |
| Positive | Positive | 356 | 174 | 530 | |
| Positive | Positive | 436 | 434 | 870 | |
| Positive | Positive | 353 | 252 | 605 | |
Methamphetamine Percent agreement, 300 ng/mL Semi-quantitative and Qualitative
| | Low Neg by CG/MS (< -50%) | Near Cutoff Neg by GC/MS (-50% to cutoff) | Near Cutoff Pos by GC/MS (cutoff to +50%) | High Pos by GC/MS (> +50%) | Percent agreement with GC/MS |
| --- | --- | --- | --- | --- | --- |
| Positive | 0 | 4 | 4 | 36 | 100% |
| Negative | 36 | 0 | 0 | 0 | 90.0% |
| % Samples in range | 45.0% | 5.0% | 5.0% | 45.0% | |
Methamphetamine non discriminatory Results, 300 ng/mL cutoff
| Assay type | Result | GC/MS (ng/mL) | Metabolite |
| --- | --- | --- | --- |
| Semi-quantitative
Qualitative | Positive | 173 | d-methamphetamine |
| | Positive | 181 | d-amphetamine |
| Semi-quantitative
Qualitative | Positive | 278 | d-methamphetamine |
| | Positive | 101 | d-amphetamine |
| Semi-quantitative | Positive | 220 | d-methamphetamine |
| Qualitative | Positive | 171 | d-amphetamine |
| Semi-quantitative | Positive | 291 | d-methamphetamine |
| Qualitative | Positive | 145 | d-amphetamine |
Methamphetamine, Near cutoff 500 ng/mL, Semi-quantitative and Qualitative
| Semi-Quant Pos/Neg | Qual Pos/Neg | MAMP GC/MS ng/mL | AMP GC/MS ng/mL | Total GC/MS ng/mL |
| --- | --- | --- | --- | --- |
{18}
19
| Positive | Positive | 488 | 466 | 954 | Near Cutoff Negatives (-50% to cutoff) |
| --- | --- | --- | --- | --- | --- |
| Positive | Positive | 325 | 171 | 496 | |
| Positive | Positive | 291 | 145 | 436 | |
| Positive | Positive | 472 | 650 | 1,122 | |
| Negative | Negative | 85 | 121 | 206 | |
| Negative | Negative | 173 | 181 | 354 | |
| Negative | Negative | 174 | 0 | 174 | |
| Negative | Negative | 204 | 0 | 204 | |
| Positive | Positive | 506 | 102 | 608 | Near Cutoff Positives (cutoff to +50%) |
| Positive | Positive | 514 | 131 | 645 | |
| Positive | Positive | 547 | 100 | 647 | |
| Positive | Positive | 694 | 688 | 1,382 | |
Methamphetamine Percent agreement, 500 ng/mL Semi-quantitative and Qualitative
| | Low Neg by CG/MS (< -50%) | Near Cutoff Neg by GC/MS (-50% to cutoff) | Near Cutoff Pos by GC/MS (cutoff to +50%) | High Pos by GC/MS (> +50%) | Percent agreement with GC/MS |
| --- | --- | --- | --- | --- | --- |
| Positive | 0 | 4 | 4 | 36 | 100% |
| Negative | 40 | 0 | 0 | 0 | 91% |
| % Samples in range | 47.6% | 4.8% | 4.8% | 42.9% | |
Methamphetamine Non discriminatory Results, 500 ng/mL cutoff
| Assay type | Result | GC/MS (ng/mL) | Metabolite |
| --- | --- | --- | --- |
| Semi-quantitative Qualitative | Positive
Positive | 325 | d-methamphetamine |
| | | 171 | d-amphetamine |
| Semi-quantitative Qualitative | Positive
Positive | 291 | d-methamphetamine |
| | | 145 | d-amphetamine |
| Semi-quantitative | Positive | 472 | d-methamphetamine |
| Qualitative | Positive | 650 | d-amphetamine |
| Semi-quantitative | Positive | 488 | d-methamphetamine |
| Qualitative | Positive | 466 | d-amphetamine |
Methamphetamine, Near cutoff 1,000 ng/mL, Semi-quantitative and Qualitative
| Semi-Quant
Pos/Neg | Qual
Pos/Neg | MAMP
GC/MS
ng/mL | AMP
GC/MS
ng/mL | Total
GC/MS
ng/mL | |
| --- | --- | --- | --- | --- | --- |
| Positive | Positive | 706 | 443 | 1,149 | Near Cutoff
Negatives
(-50% to cutoff) |
| Positive | Positive | 540 | 693 | 1,233 | |
| Positive | Positive | 769 | 395 | 1,164 | |
| Positive | Positive | 572 | 432 | 1,004 | |
{19}
20
| Positive | Positive | 1,152 | 457 | 1,609 | Near Cutoff |
| --- | --- | --- | --- | --- | --- |
| Positive | Positive | 1,394 | 356 | 1,750 | Positives |
| Positive | Positive | 1,163 | 837 | 2,000 | (cutoff to +50%) |
| Positive | Positive | 1,244 | 313 | 1,557 | |
## Methamphetamine Percent agreement, 1,000 ng/mL Semi-quantitative and Qualitative
| | Low Neg by CG/MS (< -50%) | Near Cutoff Neg by GC/MS (-50% to cutoff) | Near Cutoff Pos by GC/MS (cutoff to +50%) | High Pos by GC/MS (> +50%) | Percent agreement with GC/MS |
| --- | --- | --- | --- | --- | --- |
| Positive | 0 | 4 | 4 | 36 | 100% |
| Negative | 36 | 0 | 0 | 0 | 90.0% |
| % Samples in range | 45.0% | 5.0% | 5.0% | 45.0% | |
## Methamphetamine Non discriminatory Results, 1,000 ng/mL cutoff
| Assay type | Result | GC/MS (ng/mL) | Metabolite |
| --- | --- | --- | --- |
| Semi-quantitative | Positive | 706 | d-methamphetamine |
| Qualitative | Positive | 443 | d-amphetamine |
| Semi-quantitative | Positive | 540 | d-methamphetamine |
| Qualitative | Positive | 693 | d-amphetamine |
| Semi-quantitative | Positive | 769 | d-methamphetamine |
| Qualitative | Positive | 395 | d-amphetamine |
| Semi-quantitative | Positive | 572 | d-methamphetamine |
| Qualitative | Positive | 432 | d-amphetamine |
b. Matrix comparison:
Matrix comparison studies were not performed. This device is for human urine only.
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):
{20}
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.
21
