IMMUNALYSIS METHAMPHETAMINE ELISA FOR ORAL FLUIDS
Device Facts
| Record ID | K051577 |
|---|---|
| Device Name | IMMUNALYSIS METHAMPHETAMINE ELISA FOR ORAL FLUIDS |
| Applicant | Immunalysis Corporation |
| Product Code | LAF · Clinical Toxicology |
| Decision Date | Oct 4, 2005 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.3610 |
| Device Class | Class 2 |
Intended Use
The Immunalysis Methamphetamine ELISA test system utilizes an Enzyme Linked Immunoassay (ELISA) for the qualitative detection of methamphetamine in ORAL FLUID SAMPLES COLLECTED WITH THE QUANTISAL™ ORAL FLUID COLLECTION DEVICE ONLY using a cutoff of 50 ng/mL of d-methamphetamine. This in vitro diagnostic device is intended for clinical laboratory use only. The Immunalysis Methamphetamine ELISA Kit for Oral Fluids provides only a preliminary analytical test result. A more specific alternate chemical must be used in order to obtain a confirmed analytical result. Gas chromatography/ mass spectrometry (GS-MS) is the preferred confirmatory method . Clinical 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 ELISA test system for qualitative detection of methamphetamine in oral fluid. Input: oral fluid samples collected using Quantisal device. Principle: Enzyme Linked Immunoassay (ELISA) targeting d-methamphetamine at 50 ng/mL cutoff. Output: preliminary analytical result. Used in clinical laboratory settings by trained personnel. Results require confirmation via alternate chemical method, preferably Gas Chromatography/Mass Spectrometry (GC-MS). Clinical judgment required for interpretation of preliminary positive results.
Clinical Evidence
No clinical data provided; bench testing only.
Technological Characteristics
Qualitative ELISA immunoassay. Components: cellulose collection pad, propylene stem, polypropylene buffer tube, rabbit polyclonal antibody-coated microstrips, TMB substrate. Energy source: spectrophotometer (450/620 nm). Connectivity: standalone. Sterilization: not specified.
Indications for Use
Indicated for qualitative detection of methamphetamine in oral fluid samples from patients suspected of drug use. Intended for clinical laboratory use only. Preliminary results require confirmation via GC-MS.
Regulatory Classification
Identification
A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of methamphetamine use or overdose.
Special Controls
*Classification.* Class II (special controls). A methamphetamine 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).
Related Devices
- K051579 — IMMUNALYSIS AMPHETAMINE ELISA FOR ORAL FLUIDS · Immunalysis Corporation · Oct 21, 2005
- K080381 — QUEST DIAGNOSTICS METHAMPHETAMINE MICRO-PLATE EIA · Quest Diagnostics, Inc. · Jun 25, 2008
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE
A. 510(k) Number:
k051577
B. Purpose for Submission:
New device
C. Measurand:
Methamphetamine
D. Type of Test:
Qualitative immunoassay
E. Applicant:
Immunalysis Corporation
F. Proprietary and Established Names:
Immunalysis Methamphetamine ELISA for Oral Fluids
G. Regulatory Information:
1. Regulation section:
21 CFR §862.3610, Methamphetamine Test System
2. Classification:
Class II
3. Product code:
LAF
4. Panel:
Toxicology (91)
H. Intended Use:
1. Intended use(s):
See indications for use below.
2. Indication(s) for use:
The Immunalysis Methamphetamine ELISA test system utilizes an Enzyme Linked Immunoassay (ELISA) for the qualitative detection of methamphetamine in ORAL FLUID SAMPLES COLLECTED WITH THE QUANTISAL™ ORAL FLUID COLLECTION DEVICE ONLY using a cutoff of 50 ng/mL of d-methamphetamine. This in vitro diagnostic device is intended for clinical laboratory use only.
The Immunalysis Methamphetamine ELISA Kit for Oral Fluids 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 (GS-MS) is the preferred confirmatory method (1). Clinical 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):
See above.
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4. Special instrument requirements:
This device must be read on a spectrophotometer that reads wavelengths of 450 nm and 620 nm.
I. Device Description:
The device consists of a saliva collection device and a methamphetamine ELISA kit. An oral fluid specimen is collected by placing the collection device, a cellulose pad affixed to a propylene stem under the tongue, until approximately one milliliter saliva has saturated the pad. A blue indicator on the stem indicates when enough sample has been collected. The collector is transferred to a provided polypropylene tube containing preservative buffer (3 ml) and closed, ready for transport or storage. The ELISA assay consists of 8-well microstrips coated with high affinity purified rabbit polyclonal antibody, a plate frame, conjugated methamphetamine, negative and positive controls, a cut-off calibrator, TMB substrate, and stop reagent.
J. Substantial Equivalence Information:
1. Predicate device name(s):
DRI Amphetamines EIA Assay
2. Predicate 510(k) number(s):
k934891
3. Comparison with predicate:
| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Analyte | Methamphetamine | Methamphetamine and Amphetamine |
| Methodology | Immunoassay (EIA) | Immunoassay (ELISA) |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Test Matrix | Oral Fluid | Urine |
| Cutoff | 50 ng/mL | 1000 ng/mL |
K. Standard/Guidance Document Referenced (if applicable):
None referenced.
L. Test Principle:
Enzyme-labeled drug and drug present in the sample compete for limited anti-methamphetamine antibody binding sites. Binding of the enzyme-labeled drug inhibits its reaction with the substrate, thereby influencing the rate of absorbance change measured by the instrument. The rate of absorbance change is proportional to the concentration of drug in the sample. Concentrations of controls and unknowns are calculated from the standard curve. Results are read at 450 and 620 nm.
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M. Performance Characteristics (if/when applicable):
1. Analytical performance:
a. Precision/Reproducibility:
Precision was tested by spiking negative oral fluid with 0, 25, 50, 75, and 100 ng/mL of d-methamphetamine; this corresponded to 0, 50%, 100%, 150%, and 200% of the cutoff. One milliliter of the spiked fluids were pipetted onto the collection pad of the oral fluid collector then processed as per instructions.
Intra-assay precision was assessed with sixteen replicates of each concentration analyzed in one run:
Intra-assay Precision: Immunalysis Methamphetamine for Oral Fluid Assay
| Methamphetamine (ng/mL) | Mean OD | Std Dev | CV |
| --- | --- | --- | --- |
| 0 | 2.35 | 0.055 | 2.33 % |
| 25 (50% c/o) | 1.07 | 0.048 | 4.43 % |
| 50 (100% c/o) | 0.80 | 0.032 | 3.97 % |
| 75 (150% c/o) | 0.64 | 0.030 | 4.62 % |
| 100 (200% c/o) | 0.54 | 0.027 | 5.07 % |
Inter-assay precision was assessed by eight replicates of each concentration run in 10 different assay runs (2 per day over 5 days). Results are expressed as B/B0% where B = absorbance of sample and B0 = absorbance of the zero calibrator.
Inter-assay Precision: Immunalysis Methamphetamine for Oral Fluid Assay
| | Methamphetamine Concentration (ng/mL) | | | |
| --- | --- | --- | --- | --- |
| | 25 (50% c/o) | 50 (100% c/o) | 75 (150% c/o) | 100 (200% c/o) |
| Mean | 44.2 | 31.7 | 26.5 | 23.1 |
| Std.Dev | 2.0 | 1.6 | 1.6 | 1.1 |
| % CV | 4.6 | 5.2 | 5.9 | 4.8 |
Reproducibility of the oral fluid collection device was assessed by collecting oral fluid from 50 subjects with a pre-weighed collector and tube as per the package instructions. After the volume indicator turned blue, the collector and tube were weighed and the net weight of the saliva was determined and converted to volume (mLs).
Quantisal Oral Fluid Collection Device: Volume Adequacy Study
| Avg. Vol. (mL) | Std. Dev. | C.V. | Mean + 3 SD (mL) | Mean - 3 SD (mL) |
| --- | --- | --- | --- | --- |
| 0.993 | 0.029 | 2.88% | 1.079 | 0.907 |
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These results support the sponsor's claim that the device collects 1 mL ± 10% saliva.
b. Linearity/assay reportable range:
Not applicable. This assay is intended for qualitative use.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
All calibrator and control stock solutions are prepared from commercially available DEA-exempt solutions; d-methamphetamine concentration is confirmed by GC/MS analysis.
Claimed shelf-life of the oral fluid collection device and the ELISA kit and components is 24 months and 12 months respectively. Real-time studies are ongoing.
Stability of methamphetamine in the collection device was determined by spiking a pool of negative saliva with methamphetamine at a concentration around the cutoff and a pool at a concentration two-fold higher (2X). Samples were stored at 4°C or at room temperature. The specimens kept at room temperature were assayed in duplicate by GC-MS after 7 days, 14 days and 30 days; samples kept at 4°C were assayed were assayed in duplicate by GC-MS after 14 days and 30 days. The sponsor's acceptance criterion was recovery of ± 20% of the initial value.
Stability of Methamphetamine in Quantisal Buffer
| Stability at Room Temperature | | | | | |
| --- | --- | --- | --- | --- | --- |
| Day | Meth spike (ng/mL) | % initial value | | 2X Meth spike (ng/mL) | % initial value |
| 0 | 40.03 | 100 | | 81.90 | 100 |
| 7 | 41.30 | 103.2 | | 80.34 | 98.1 |
| 14 | 41.57 | 103.8 | | 72.70 | 88.77 |
| 21 | 39.04 | 97.53 | | 76.12 | 92.94 |
| 30 | 38.40 | 95.93 | | 69.24 | 84.54 |
| Stability at 4°C | | | | | |
| 0 | 40.03 | 100 | | 81.90 | 100 |
| 14 | 40.00 | 99.9 | | 69.40 | 84.7 |
| 30 | 36.71 | 91.7 | | 74.08 | 90.5 |
A shipping study showed that methamphetamine spiked into saliva had acceptable recovery (± 15%) after transport.
d. Detection limit:
See the Precision/Reproducibility section above for performance around the stated cutoff concentration.
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e. Analytical specificity:
Cross-reactivity of structurally similar compounds was determined by spiking concentrations of different drugs into synthetic oral fluid.
Cross-reactivity with similar compounds: Immunalysis Methamphetamine Oral Fluid Assay
| Compound | Conc. Tested (ng/mL) | Cross-Reactivity | Compound | Conc. Tested (ng/mL) | Cross-Reactivity |
| --- | --- | --- | --- | --- | --- |
| d-methamphetamine | 50 | 100% | (+) pseudoephedrine | 1000 | 3.7% |
| l-methamphetamine | 1000 | 2% | (+) pseudoephedrine | 5000 | 1.5% |
| d-amphetamine | 1000 | <1% | (-) pseudoephedrine | 500 | <1% |
| l-amphetamine | 5000 | <1% | phenolpropanolamide | 10000 | <1% |
| dl-amphetamine | 1000 | <1% | (+) ephedrine | 5000 | <1% |
| dl-MDMA | 25 | 98% | (-) ephedrine | 5000 | 2.3% |
| dl-MDMA | 50 | 78% | fenfluramine | 1000 | 1.8% |
| dl-MDA | 1000 | <1% | diphenhydramine | 10000 | <1% |
| dl-MDEA | 250 | 6.4% | | | |
Structurally unrelated compounds were spiked into synthetic oral fluid at a concentration of 10000 ng/mL; none of the compounds in the table below had an immunoassay response greater than an equivalent of 25 ng/mL d-methamphetamine.
Compounds tested for Cross-reactivity: Immunalysis Methamphetamine Oral Fluid Assay
| Acetaminophen | Ethylmorphine | Mereridine |
| --- | --- | --- |
| Amitriptyline | Flurazepam | Nalorphine |
| Amobarbital | Glutethimide | Nicotine |
| Barbital | Hexobarbital | Nordoxepin |
| Benzoylecgonine | Hydromorphone | n-Normethsuximide |
| Butabarbital | Imipramine | Nortriptyline |
| Bromazepam | Lidocaine | Oxazepam |
| Caffeine | Lorazepam | Oxycodone |
| Carbamazepine | Medazepam | Phenobarbital |
| Cocaine | Methadone | Phensuximide |
| Codeine | EDDP | Phenytoin |
| Chlorpromazine | Methaqualone | Primidone |
| Desipramine | Metharbital | Protriptyline |
| Diacetylmorphine | Mephenytoin | Quinine |
| Dihydrocarbamazepine | Methyl-propylsuccinimide | Secobarbital |
| Diazepam | Mephobarbital | Temazepam |
| Doxepin | Methyl PEMA | Theophylline |
| Dyphylline | Methsuximide | Trimipramine |
| Ethosuximide | 4-Methylprimidone | |
| Ethotoin | Morphine | |
Commonly ingested substances were tested for interference. Sugar 145 mg/mL, toothpaste 25 mg/mL, cranberry juice 25% v/v, baking soda 25
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mg/mL, orange juice 25% v/v, carbonated cola 25% v/v, cough syrup 10% v/v, mouthwash 25% v/v, distilled water. Substances were diluted or dissolved in distilled water then spiked with 25 ng/mL methamphetamine (50% cutoff) or 75 ng/mL methamphetamine (150% cutoff) and tested. Results were compared to the cutoff calibrator to determine if the sample was positive or negative; specific effects were compared to the same methamphetamine concentration in synthetic oral fluid:
## Effect of Common Compounds on Immunalysis Methamphetamine Oral Fluid Assay
| Compound | Mean Abs | B/B0% | POS/NEG | | Mean Abs | B/B0% | POS/NEG |
| --- | --- | --- | --- | --- | --- | --- | --- |
| Synthetic Oral Fluid | 2.834 | 100 | | | | | |
| 25 ng/mL methamphetamine | 1.347 | 47.5 | NEG | | | | |
| 50 ng/mL methamphetamine | 0.952 | 33.6 | Cutoff | | | | |
| 100 ng/mL methamphetamine | 0.627 | 22.1 | POS | | | | |
| | | | | | | | |
| | 25 ng/mL Methamp spike | | | | 75 ng/mL Methamp spike | | |
| Distilled water | 1.612 | 56.9 | NEG | | 0.861 | 30.4 | POS |
| Sugar water sol'n | 1.454 | 51.3 | NEG | | 0.808 | 28.5 | POS |
| Toothpaste slurry | 1.334 | 47.1 | NEG | | 0.784 | 27.6 | POS |
| Cranberry juice | 1.448 | 51.1 | NEG | | 0.834 | 29.4 | POS |
| Baking Soda sol'n | 1.501 | 53.0 | NEG | | 0.919 | 32.4 | POS |
| Orange juice | 0.944 | 33.3 | NEG | | 0.689 | 24.3 | POS |
| Cola | 1.347 | 47.5 | NEG | | 0.844 | 29.8 | POS |
| Cough syrup* | 0.193 | 6.81 | POS | | 0.165 | 5.81 | POS |
| Mouthwash | 1.528 | 53.9 | NEG | | 0.836 | 29.5 | POS |
* Cough syrup contained 2 mg/mL (+) pseudoephedrine, sufficient to cause cross-reactivity in the assay. See cross-reactivity with related compounds table above.
f. Assay cut-off:
Performance around the assay cut-off of 50 ng/mL is demonstrated in the intra-assay precision section above.
The Substance Abuse and Mental Health Services Administration (SAMHSA) has recommended 50 ng/mL as a cutoff level for methamphetamine oral fluid tests.
2. Comparison studies:
a. Method comparison with predicate device:
Oral fluid and urine samples were collected in the same visit from 185 admitted methamphetamine users in a clinical setting. Urine samples were tested by the predicate assay using a cutoff of 1000 ng/mL. Oral fluid samples
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were tested in duplicate using a screening cutoff of 50 ng/mL; all samples were tested by GC/MS at an independent facility. Thirteen samples were ±50% of the cutoff (by GC/MS).
## Comparison of Immunalysis Methamphetamine Oral Fluid Assay and the Predicate Urine Assay
| | Predicate Urine Assay | | |
| --- | --- | --- | --- |
| | | Pos | Neg |
| Methamphetamine Oral Fluid Assay | Pos | 62 | 6 |
| | Neg | 10 | 107 |
Positive agreement: 91 %
Negative agreement: 92 %
Overall agreement: 91 %
## Comparison of Immunalysis Methamphetamine Oral Fluid Assay and GC/MS
| | GC/MS | | |
| --- | --- | --- | --- |
| | | Pos | Neg |
| Methamphetamine Oral Fluid Assay | Pos | 66 | 2 |
| | Neg | 0 | 117 |
Positive agreement: 97 %
Negative agreement: 100 %
Overall agreement: 99 %
b. Matrix comparison:
Not applicable; this device is intended for use with oral fluid 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):
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.
