SEFRIA Methamphetamine Oral Fluid Enzyme Immunoassay
Device Facts
| Record ID | K203647 |
|---|---|
| Device Name | SEFRIA Methamphetamine Oral Fluid Enzyme Immunoassay |
| Applicant | Immunalysis Corporation |
| Product Code | LAF · Clinical Toxicology |
| Decision Date | Dec 22, 2021 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 862.3610 |
| Device Class | Class 2 |
Indications for Use
For In Vitro Diagnostic Use. The Immunalysis SEFRIA Methamphetamine Oral Fluid Enzyme Immunoassay is an enzyme immunoassay with a cutoff of 50 ng/mL in neat oral fluid collected by Quantisal or Quantisal II Oral Fluid Collection Device. The assay is intended for the qualitative and semi-quantitative analysis of methamphetamine in human oral fluid with clinical analyzers. This assay is calibrated against d-methamphetamine. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/Mass Spectrometry (GC-MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures. The Immunalysis SEFRIA Methamphetamine Oral Fluid Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any test result, particularly when preliminary positive results are used.
Device Story
The SEFRIA Methamphetamine Oral Fluid Enzyme Immunoassay is an in-vitro diagnostic test for detecting methamphetamine in human oral fluid. Samples are collected using the Quantisal or Quantisal II Oral Fluid Collection Device, which stores the specimen in a preservative buffer. The assay utilizes a homogeneous enzyme immunoassay principle on automated clinical chemistry analyzers (e.g., Beckman Coulter AU480). It provides qualitative or semi-quantitative results calibrated against d-methamphetamine. The device is intended for laboratory use; results are preliminary and require confirmation by GC-MS or LC-MS/MS. The semi-quantitative mode assists laboratories in determining specimen dilution for confirmation or establishing quality control. The device aids in workplace drug testing, pain management monitoring, and DUID assessments by identifying methamphetamine presence, allowing clinicians to make informed decisions regarding patient compliance or substance use.
Clinical Evidence
Bench testing only. Precision/reproducibility study (15-day, N=60 per concentration) and linearity study (20-220 ng/mL range) performed. Method comparison study (N=80 clinical samples) against LC-MS/MS showed 100% agreement in both qualitative and semi-quantitative modes. Interference testing confirmed no cross-reactivity with structurally related/unrelated compounds, endogenous substances, or common oral products.
Technological Characteristics
Homogeneous enzyme immunoassay; utilizes β-galactosidase complementation technology. Reagents: Enzyme Acceptor (EA) with recombinant antibodies and Enzyme Donor (ED) with drug conjugate. Dimensions/form factor: liquid reagents for automated clinical chemistry analyzers. Storage: 2-8°C. Standards: CLSI EP07-A2 (interference), ISO 14971 (risk management).
Indications for Use
Indicated for the qualitative and semi-quantitative analysis of methamphetamine in human oral fluid collected via Quantisal or Quantisal II devices. Intended for use in clinical laboratories to provide preliminary analytical results for methamphetamine detection.
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).
Predicate Devices
- LZI Oral Fluid Methamphetamine Enzyme Immunoassay, LZI Oral Fluid Methamphetamine Calibrators, LZI Oral Fluid Methamphetamine Controls (K131652)
Related Devices
- K972989 — STC METHAMPHETAMINE MICRO-PLATE EIA · OraSure Technologies, Inc. · Jan 28, 1998
- K080381 — QUEST DIAGNOSTICS METHAMPHETAMINE MICRO-PLATE EIA · Quest Diagnostics, Inc. · Jun 25, 2008
- K051577 — IMMUNALYSIS METHAMPHETAMINE ELISA FOR ORAL FLUIDS · Immunalysis Corporation · Oct 4, 2005
Submission Summary (Full Text)
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FDA U.S. FOOD & DRUG ADMINISTRATION
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY ONLY
## I Background Information:
A 510(k) Number
K203647
B Applicant
Immunalysis Corporation
C Proprietary and Established Names
SEFRIA™ Methamphetamine Oral Fluid Enzyme Immunoassay
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| LAF | Class II | 21 CFR 862.3610 - Methamphetamine Test System | TX - Clinical Toxicology |
## II Submission/Device Overview:
A Purpose for Submission:
New Device
B Measurand:
methamphetamine
C Type of Test:
Qualitative and Semi-quantitative Homogeneous Enzyme Immunoassay
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
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K203647 - Page 2 of 18
## III Intended Use/Indications for Use:
### A Intended Use(s):
See Indications for Use below.
### B Indication(s) for Use:
For In Vitro Diagnostic Use.
The Immunalysis SEFRIA Methamphetamine Oral Fluid Enzyme Immunoassay is an enzyme immunoassay with a cutoff of 50 ng/mL in neat oral fluid collected by Quantisal or Quantisal II Oral Fluid Collection Device. The assay is intended for the qualitative and semi-quantitative analysis of methamphetamine in human oral fluid with clinical analyzers. This assay is calibrated against d-methamphetamine.
The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as Gas Chromatography/Mass Spectrometry (GC-MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) or permitting laboratories to establish quality control procedures.
The Immunalysis SEFRIA Methamphetamine Oral Fluid Enzyme Immunoassay provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/ Mass Spectrometry (GC-MS) or Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any test result, particularly when preliminary positive results are used.
### C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
### D Special Instrument Requirements:
The SEFRIA™ Methamphetamine Oral Fluid Enzyme Immunoassay was validated using the Beckman Coulter AU480 chemistry analyzer. Confirmatory tests were run in the Agilent 6430 Liquid Chromatography-Tandem Mass Spectrometry.
## IV Device/System Characteristics:
### A Device Description:
The SEFRIA Oxycodone Oral Fluid Enzyme Immunoassay consists of ready to use reagents for use on automated clinical chemistry analyzers. The SEFRIA Oxycodone Oral Fluid Enzyme Immunoassay is provided in two kit sizes by volume: 100 mL (621OF-0100K) and 500 mL (621OF-0500K). Each kit box contains the following reagents:
- 1 X Enzyme Acceptor/Antibody Reagent (EA) - This contains EA protein and recombinant antibodies to oxycodone, in PIPES buffer with sodium azide as a preservative.
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- 1 X Enzyme Donor/Substrate Reagent (ED) - This contains ED peptide labeled with oxycodone and CPRG substrate in malic acid buffer with sodium azide as a preservative.
## B Principle of Operation:
The SEFRIA technology is based on artificial fragments of the E. coli enzyme β-galactosidase. A mutant enzyme, termed Enzyme Acceptor (EA), is created by deletion of a short sequence in the amino-terminal region of the sequence. EA is inactive, but can combine with peptides, termed Enzyme Donors (ED's), containing the deleted sequence, to form active β-galactosidase. This process is termed complementation, and the active enzyme formed as a result can be measured by hydrolysis of a chromogenic substrate such as chlorophenol red β-D-galactopyranoside (CPRG). The ED peptides can be modified by attachment of a derivative of methamphetamine, which does not interfere with the formation of active β-galactosidase. However, antibodies to methamphetamine bind to the ED- methamphetamine conjugate, and block complementation. The assay is based on the competition of methamphetamine in an oral fluid sample with the ED- methamphetamine conjugate for the fixed amount of antibody binding sites. In the absence of the free drug in the sample, the antibody binds the ED-methamphetamine conjugate, resulting in inhibition of enzyme formation. As the methamphetamine concentration in the sample increases, ED-methamphetamine becomes available for complementation, creating a dose response relationship between methamphetamine concentration in the oral fluid and enzyme formation. The β-galactosidase activity is determined spectrophotometrically at 570 nm by the conversion of CPRG (orange) to chlorophenol red (red) and galactose.
## V Substantial Equivalence Information:
A Predicate Device Name(s):
LZI Oral Fluid Methamphetamine Enzyme Immunoassay
B Predicate 510(k) Number(s):
K131652
C Comparison with Predicate(s):
| Device & Predicate Device(s): | K203647 | K131652 |
| --- | --- | --- |
| Device Trade Name | SEFRIA Methamphetamine Oral Fluid Enzyme Immunoassay | LZI Oral Fluid Methamphetamine Enzyme Immunoassay |
| General Device Characteristic Similarities | | |
| Intended Use/Indications for Use | Qualitative and semi-quantitative analysis of methamphetamine in human oral fluid | Same |
| Test Principle | Homogeneous enzyme immunoassay | Same |
| Calibrated Against | d-methamphetamine | Same |
K203647 - Page 3 of 18
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| Device & Predicate Device(s): | K203647 | K131652 |
| --- | --- | --- |
| Assay Materials | antibody reagent, drug conjugate reagent | Same |
| Cutoff Level | 50 ng/mL | Same |
| User Environment | For use in laboratories | Same |
| Sample Matrix | Human oral fluid | Same |
| Reagent Storage | 2-8°C until expiration date | Same |
| Mass Spectrometry Confirmation | Required for preliminary positive analytical results | Same |
| General Device Characteristic Differences | | |
| Sample Collection Device | Oral fluid is collected with the Quantisal or Quantisal II Oral Fluid Collection Device. | Oral fluid is collected with the LZI Oral Fluid Collector. |
VI Standards/Guidance Documents Referenced:
CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition
ISO 14971:2007 Medical Devices – Application of Risk Management to Medical Devices
EN ISO 14971:2012 Medical Devices – Application of Risk Management to Medical Devices
VII Performance Characteristics (if/when applicable):
A Analytical Performance:
1. Precision/Reproducibility:
Precision study was performed over 15 days, 2 runs per day with 2 collection devices per run (N=60), one replicate per collection device on 1 lot of reagent and 1 lot of Quantisal and 1 lot of Quantisal II oral fluid collection devices. Drug free negative oral fluid was spiked to concentrations of assay cutoff and ±25%, ±50%, ±75%, ±100% of the cutoff and was collected using the collection devices. The spiked concentrations were confirmed by liquid chromatography tandem mass spectrometry (LC-MS/MS) before collection. The study established the repeatability of the testing system, including assay and oral fluid collection device. Test results in qualitative and semi-quantitative modes are presented in the following tables.
K203647 - Page 4 of 18
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Summary of 15-Day Precision – Qualitative results
| Concentration (ng/mL) | % of cutoff | # of determinations | Result |
| --- | --- | --- | --- |
| Quantisal | | | |
| 0 | -100% | 60 | 60 Negative |
| 12.5 | -75% | 60 | 60 Negative |
| 25 | -50% | 60 | 60 Negative |
| 37.5 | -25% | 60 | 60 Negative |
| 50 | Cutoff | 60 | 26 Neg / 34 Pos |
| 62.5 | 25% | 60 | 60 Positive |
| 75 | 50% | 60 | 60 Positive |
| 87.5 | 75% | 60 | 60 Positive |
| 100 | 100% | 60 | 60 Positive |
| Quantisal II Pad A | | | |
| 0 | -100% | 60 | 60 Negative |
| 12.5 | -75% | 60 | 60 Negative |
| 25 | -50% | 60 | 60 Negative |
| 37.5 | -25% | 60 | 60 Negative |
| 50 | Cutoff | 60 | 34 Neg / 26 Pos |
| 62.5 | 25% | 60 | 60 Positive |
| 75 | 50% | 60 | 60 Positive |
| 87.5 | 75% | 60 | 60 Positive |
| 100 | 100% | 60 | 60 Positive |
| Quantisal II Pad B | | | |
| 0 | -100% | 60 | 60 Negative |
| 12.5 | -75% | 60 | 60 Negative |
| 25 | -50% | 60 | 60 Negative |
| 37.5 | -25% | 60 | 60 Negative |
| 50 | Cutoff | 60 | 31 Neg / 29 Pos |
| 62.5 | 25% | 60 | 60 Positive |
| 75 | 50% | 60 | 60 Positive |
| 87.5 | 75% | 60 | 60 Positive |
| 100 | 100% | 60 | 60 Positive |
K203647 - Page 5 of 18
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Summary of 15-Day Precision - Semi-Quantitative Results
| Concentration (ng/mL) | % of cutoff | # of determinations | Mean Conc. (ng/mL) | Result |
| --- | --- | --- | --- | --- |
| Quantisal | | | | |
| 0 | -100% | 60 | 1.1 | 60 Negative |
| | | | | |
| Concentration (ng/mL) | % of cutoff | # of determinations | Mean Conc. (ng/mL) | Result |
| 12.5 | -75% | 60 | 14.2 | 60 Negative |
| 25 | -50% | 60 | 25.3 | 60 Negative |
| 37.5 | -25% | 60 | 39.3 | 60 Negative |
| 50 | Cutoff | 60 | 50.2 | 37 Neg / 23 Pos |
| 62.5 | 25% | 60 | 68.9 | 60 Positive |
| 75 | 50% | 60 | 78.9 | 60 Positive |
| 87.5 | 75% | 60 | 93.8 | 60 Positive |
| 100 | 100% | 60 | 112.2 | 60 Positive |
| Quantisal II Pad A | | | | |
| 0 | -100% | 60 | 2.4 | 60 Negative |
| 12.5 | -75% | 60 | 14.7 | 60 Negative |
| 25 | -50% | 60 | 25.1 | 60 Negative |
| 37.5 | -25% | 60 | 38.4 | 60 Negative |
| 50 | Cutoff | 60 | 48.6 | 44 Neg / 16 Pos |
| 62.5 | 25% | 60 | 63.8 | 60 Positive |
| 75 | 50% | 60 | 74.9 | 60 Positive |
| 87.5 | 75% | 60 | 86.8 | 60 Positive |
| 100 | 100% | 60 | 109.3 | 60 Positive |
| Quantisal II Pad B | | | | |
| 0 | -100% | 60 | 3.8 | 60 Negative |
| 12.5 | -75% | 60 | 14.7 | 60 Negative |
| 25 | -50% | 60 | 24.9 | 60 Negative |
| 37.5 | -25% | 60 | 40.4 | 60 Negative |
| 50 | Cutoff | 60 | 49.0 | 42 Neg / 18 Pos |
| 62.5 | 25% | 60 | 65.8 | 60 Positive |
| 75 | 50% | 60 | 78.3 | 60 Positive |
| 87.5 | 75% | 60 | 89.0 | 60 Positive |
| 100 | 100% | 60 | 111.9 | 60 Positive |
K203647 - Page 6 of 18
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An additional 20-day study was performed on 3 lots of assay reagent to demonstrate the repeatability across multiple reagent lots. All sample concentrations ranging from -100% to -25% of the cutoff were negative and all sample concentrations ranging from +25% to +100% of cutoff were positive for both qualitative and semi-quantitative interpretations.
## 2. Linearity:
Assay linearity was evaluated in the semi-quantitative mode by spiking a drug free oral fluid pool with a high concentration of methamphetamine. Additional pools were made by serially diluting the high concentration specimen with drug free oral fluid to achieve concentrations ranging from 20 ng/mL to 220 ng/mL. The 0 ng/mL specimen was made from drug free oral fluid. Each pool was collected by Quantisal and Quantisal II oral fluid collection devices and tested in triplicate to calculate the mean concentration values that were used to calculate drug recovery. The results in semi-quantitative mode are presented in the tables below.
Linearity/Recovery – Quantisal
| Expected Concentration (ng/mL) | Mean Concentration (ng/mL) | Recovery (%) |
| --- | --- | --- |
| 0 | 1.0 | N/A |
| 20 | 20.7 | 103.3 |
| 40 | 43.1 | 107.8 |
| 50 | 51.9 | 103.8 |
| 60 | 64.8 | 107.9 |
| 80 | 81.2 | 101.5 |
| 100 | 96.8 | 96.8 |
| 120 | 127.7 | 106.4 |
| 140 | 141.4 | 101.0 |
| 160 | 150.3 | 93.9 |
| 180 | 184.6 | 102.6 |
| 200 | 194.8 | 97.4 |
| 220 | 225.3 | 102.4 |
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Linearity/Recovery – Quantisal II “Pad A”
| Expected Concentration (ng/mL) | Mean Concentration (ng/mL) | Recovery (%) |
| --- | --- | --- |
| 0 | -1.4 | N/A |
| 20 | 20.5 | 102.5 |
| 40 | 41.6 | 103.9 |
| 50 | 48.4 | 96.8 |
| 60 | 59.3 | 98.9 |
| 80 | 78.2 | 97.8 |
| 100 | 97.3 | 97.3 |
| 120 | 123.2 | 102.6 |
| 140 | 145.6 | 104.0 |
| 160 | 159.0 | 99.4 |
| 180 | 180.0 | 100.0 |
| 200 | 201.0 | 100.5 |
| 220 | 219.9 | 100.0 |
Linearity/Recovery – Quantisal II “Pad B”
| Expected Concentration (ng/mL) | Mean Concentration (ng/mL) | Recovery (%) |
| --- | --- | --- |
| 0 | 0.5 | N/A |
| 20 | 21.8 | 109.2 |
| 40 | 42.9 | 107.3 |
| 50 | 49.1 | 98.3 |
| 60 | 60.9 | 101.5 |
| 80 | 78.2 | 97.8 |
| 100 | 94.8 | 94.8 |
| 120 | 119.3 | 99.4 |
| 140 | 140.7 | 100.5 |
| 160 | 163.6 | 102.2 |
| 180 | 176.3 | 98.0 |
| 200 | 192.4 | 96.2 |
| 220 | 214.5 | 97.5 |
The study demonstrated that the SEFRIA™ Methamphetamine Oral Fluid Enzyme Immunoassay has good correlation to the expected concentration in the range from 20 ng/mL to 200 ng/mL.
K203647 - Page 8 of 18
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3. Analytical Specificity/Interference:
Structurally and functionally similar compounds were spiked into drug free pooled oral fluid at levels that will yield a result that is equivalent to the cutoff, if cross reacting. The study assessed the cross reactivity of the methamphetamine assay to related drugs and drug metabolites, in both the qualitative and semi-quantitative modes. Cross-reactivity test results in qualitative and semi-qualitative mode are presented in the tables below.
Cross-Reactivity – Qualitative
| Compound | Compound Conc. (ng/mL) | Methamphetamine Equivalent Conc. (ng/mL) | Result | Cross-Reactivity (%) |
| --- | --- | --- | --- | --- |
| l-Methamphetamine | 7500 | 50 | POS | 0.7 |
| d,l-Methamphetamine | 110 | 50 | POS | 45.5 |
| d-Amphetamine | 8,000 | 50 | POS | 0.6 |
| l-Amphetamine | 40,000 | <50 | NEG | <0.1 |
| Diphenhydramine | 40,000 | <50 | NEG | <0.1 |
| Doxylamine | 40,000 | <50 | NEG | <0.1 |
| d-Ephedrine | 40,000 | <50 | NEG | <0.1 |
| l-Ephedrine | 4,250 | 50 | POS | 1.2 |
| Fenfluramine | 5,000 | 50 | POS | 1.0 |
| Methylenedioxymethamphetamine (MDMA) | 55 | 50 | POS | 90.9 |
| (±)-3,4-Methylenedioxyethylamphetamine (MDEA) | 110 | 50 | POS | 45.5 |
| Methylenedioxyamphetamine (MDA) | 6,000 | 50 | POS | 0.8 |
| Methylone | 27,500 | 50 | POS | 0.2 |
| 4-Methoxyamphetamine (PMA) | 3,250 | 50 | POS | 1.5 |
| Para-Methoxy-N-Methylamphetamine (PMMA) | 27.75 | 50 | POS | 180.2 |
| Phenethylamine | 40,000 | <50 | NEG | <0.1 |
| Phenylephrine | 40,000 | <50 | POS | <0.1 |
| Phentermine | 40,000 | <50 | POS | <0.1 |
| Phenylpropanolamine (PPA) | 40,000 | <50 | POS | <0.1 |
| d-Pseudoephedrine | 15,000 | 50 | POS | 0.3 |
| l-Pseudoephedrine | 40,000 | 50 | NEG | 0.1* |
| Tyramine | 40,000 | <50 | NEG | <0.1 |
*As the Semi-Quantitative result is positive, the % cross reactivity is calculated based on Semi-Quantitative result.
K203647 - Page 9 of 18
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Cross-Reactivity – Semi-Quantitative
| Compound | Compound Conc. (ng/mL) | Methamphetamine Equivalent Conc. (ng/mL) | Mean Value (ng/mL) | Result | Cross-Reactivity (%) |
| --- | --- | --- | --- | --- | --- |
| l-Methamphetamine | 7,500 | 50 | 54.4 | POS | 0.7 |
| d,l-Methamphetamine | 110 | 50 | 54.1 | POS | 45.5 |
| d-Amphetamine | 8,000 | 50 | 51.2 | POS | 0.6 |
| l-Amphetamine | 40,000 | <50 | 28.9 | NEG | <0.1 |
| Diphenhydramine | 40,000 | <50 | 2.8 | NEG | <0.1 |
| Doxylamine | 40,000 | <50 | 2.3 | NEG | <0.1 |
| d-Ephedrine | 40,000 | <50 | 22.9 | NEG | <0.1 |
| l-Ephedrine | 4,250 | 50 | 50.0 | POS | 1.2 |
| Fenfluramine | 5,000 | 50 | 54.3 | POS | 1.0 |
| Methylenedioxymethamphetamine (MDMA) | 55 | 50 | 51.3 | POS | 90.9 |
| (±)-3,4-Methylenedioxyethylamphetamine (MDEA) | 110 | 50 | 50.0 | POS | 45.5 |
| Methylenedioxyamphetamine (MDA) | 6,000 | 50 | 53.7 | POS | 0.8 |
| Methylone | 27,500 | 50 | 52.2 | POS | 0.2 |
| Methoxyamphetamine (PMA) | 3,250 | 50 | 53.6 | POS | 1.5 |
| Para-Methoxy-N-Methylamphetamine (PMMA) | 27.75 | 50 | 51.5 | POS | 180.2 |
| Phenethylamine | 40,000 | <50 | 14.1 | NEG | <0.1 |
| Phenylephrine | 40,000 | <50 | 14.8 | POS | <0.1 |
| Phentermine | 40,000 | <50 | 35.2 | POS | <0.1 |
| Phenylpropanolamine (PPA) | 40,000 | <50 | 15.9 | POS | <0.1 |
| d-Pseudoephedrine | 15,000 | 50 | 52.5 | POS | 0.3 |
| l-Pseudoephedrine | 40,000 | 50 | 50.0 | POS | 0.1 |
| Tyramine | 40,000 | <50 | 15.4 | NEG | <0.1 |
## 3. Interference – Structurally Unrelated Compounds
Structurally unrelated compounds were evaluated in qualitative and semi-quantitative modes by spiking the potential interferent into drug free oral fluid containing methamphetamine at $\pm 25\%$ of the cutoff. No interference was observed at the concentrations tested with structurally unrelated compounds. The concentration levels of structurally unrelated compounds tested are presented below.
K203647 - Page 10 of 18
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Non-Interfering Structurally Unrelated Compounds
| Compound | Conc. Tested (ng/mL) |
| --- | --- |
| 4-Bromo-2,5,Dimethoxyphenethylamine | 40,000 |
| Acetaminophen | 40,000 |
| 6-Acetylcodeine | 40,000 |
| 6-Acetylmorphine | 40,000 |
| Alprazolam | 40,000 |
| 7-Aminoclonazepam | 40,000 |
| 7-Aminoflunitrazepam | 40,000 |
| 7-Aminonitrazepam | 40,000 |
| Amitriptyline | 40,000 |
| Amobarbital | 40,000 |
| Benzylpiperazine | 5,000 |
| Bromazepam | 40,000 |
| Buprenorphine | 40,000 |
| Bupropion | 40,000 |
| Butabarbital | 40,000 |
| Butalbital | 40,000 |
| Cannabidiol | 40,000 |
| Cannabinol | 40,000 |
| Carbamazepine | 40,000 |
| Carisoprodol | 40,000 |
| Chlordiazepoxide | 40,000 |
| Chlorpromazine | 40,000 |
| cis-Tramadol | 40,000 |
| Clobazam | 40,000 |
| Clomipramine | 40,000 |
| Clonazepam | 40,000 |
| Cocaine | 40,000 |
| Clozapine | 40,000 |
| Codeine | 40,000 |
| Cotinine | 40,000 |
| Cyclobenzaprine | 40,000 |
| Demoxepam | 40,000 |
| Desakylflurazepam | 40,000 |
| Desipramine | 15,000 |
| Desomorphine | 40,000 |
| Dextromethorphan | 40,000 |
| Dihydrocodeine | 40,000 |
| Diazepam | 40,000 |
| Digoxin | 40,000 |
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| Compound | Conc. Tested (ng/mL) |
| --- | --- |
| Dehydronorketamine | 40,000 |
| Delta-9-THC | 40,000 |
| Doxepin | 35,000 |
| Ecgonine | 40,000 |
| Ecgonine Methyl Ester | 40,000 |
| EDDP | 40,000 |
| EMDP | 40,000 |
| Ethyl-β-D-Glucuronide | 40,000 |
| Ethylmorphine | 40,000 |
| Fentanyl | 40,000 |
| Flunitrazepam | 40,000 |
| Fluoxetine | 15,000 |
| Flurazepam | 40,000 |
| Haloperidol | 40,000 |
| Heroin | 40,000 |
| Hydrocodone | 40,000 |
| Hydromorphone | 40,000 |
| 11-hydroxy-delta-9-THC | 40,000 |
| Imipramine | 40,000 |
| Ketamine | 40,000 |
| Lamotrigine | 40,000 |
| Levorphanol | 40,000 |
| Lidocaine | 40,000 |
| Lorazepam | 40,000 |
| Lorazepam Glucuronide | 40,000 |
| Lormetazepam | 40,000 |
| LSD | 40,000 |
| Maprotiline | 40,000 |
| Meperidine | 40,000 |
| Meprobamate | 40,000 |
| Methadone | 40,000 |
| Methaqualone | 40,000 |
| Methoxetamine | 40,000 |
| Methylphenidate | 40,000 |
| Midazolam | 40,000 |
| Morphine | 40,000 |
| Morphine-3-Glucuronide | 40,000 |
| Morphine-6-Glucuronide | 40,000 |
| N-desmethyl tapentadol | 40,000 |
| N-desmethyl tramadol | 40,000 |
| N-desmethyl venlafaxine | 40,000 |
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K203647 - Page 13 of 18
| Compound | Conc. Tested (ng/mL) |
| --- | --- |
| Nalorphine | 40,000 |
| Naloxone | 40,000 |
| Naltrexone | 40,000 |
| Naproxen | 40,000 |
| Nitrazepam | 40,000 |
| 11-nor-9 carboxy THC | 40,000 |
| Norbuprenorphine | 40,000 |
| Norcodeine | 40,000 |
| Nordiazepam | 40,000 |
| Norketamine | 40,000 |
| Normorphine | 40,000 |
| Noroxycodone | 40,000 |
| Noroxymorphone | 40,000 |
| Norpropoxyphene | 40,000 |
| Norpseudoephedrine | 40,000 |
| Nortriptyline | 20,000 |
| O-desmethyl tramadol | 40,000 |
| O-desmethyl venlafaxine | 40,000 |
| Oxycodone | 40,000 |
| Oxymorphone | 40,000 |
| Oxycodone-3-β-Glucuronide | 40,000 |
| Olanzapine | 40,000 |
| Oxazepam | 40,000 |
| PCP | 40,000 |
| Pentazocine | 40,000 |
| Pentobarbital | 40,000 |
| Phenobarbital | 40,000 |
| Phenytoin | 40,000 |
| Prazepam | 40,000 |
| Propranolol | 40,000 |
| Propoxyphene | 40,000 |
| Protriptyline | 20,000 |
| Ritalinic Acid | 40,000 |
| Salicylic Acid | 40,000 |
| Secobarbital | 40,000 |
| Sertraline | 40,000 |
| Sufentanil | 40,000 |
| Tapentadol | 40,000 |
| Temazepam | 40,000 |
| Theophylline | 40,000 |
| Thioridazine | 40,000 |
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| Compound | Conc. Tested (ng/mL) |
| --- | --- |
| Trazadone | 40,000 |
| Triazolam | 40,000 |
| 3-Trifluoromethylphenyl-piperazine | 20,000 |
| Trimipramine | 20,000 |
| Venlafaxine | 40,000 |
| Verapamil | 30,000 |
| Zolpidem | 40,000 |
## Interference – Endogenous Compounds and Exogenous Compounds
Endogenous compounds and exogenous compounds were evaluated in qualitative and semi-quantit modes by spiking the potential interferent into drug free oral fluid containing methamphetamine at ±25% of the cutoff. Additional orally used products were tested by collecting oral fluid using Qua and Quantisal II Oral Fluid Collection Devices from subjects after use of the substances. At the 1 tested, there was no interference observed with endogenous compounds, exogenous compounds an orally used compounds. Endogenous compounds and exogenous compounds, along with orally used compounds tested are presented in the tables below.
## Non-interfering Endogenous Compounds
| Compound | Concentration Tested |
| --- | --- |
| Ascorbic Acid | 2 mg/mL |
| Bilirubin | 0.15 mg/mL |
| Cholesterol | 0.45 mg/mL |
| γ-Globulin | 0.8 mg/mL |
| Hemoglobin | 2 mg/mL |
| Human Serum Albumin | 15 mg/mL |
| IgA | 1 mg/mL |
| IgG | 1 mg/mL |
| IgM | 0.5 mg/mL |
| Salivary-α-amylase | 1000 U/mL |
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Non-interfering Exogenous Compounds
| Compound | Concentration Tested |
| --- | --- |
| Acetylsalicylic Acid | 0.01 mg/mL |
| Baking Soda | 0.6% v/v |
| Denture Adhesive | 0.6% w/v |
| Ibuprofen | 0.01 mg/mL |
| Alcohol (Ethanol) | 6% v/v |
| Caffeine | 0.01 mg/mL |
| Coffee | 6% v/v |
| Cranberry Juice | 6% v/v |
| Milk | 1% v/v |
| Mouthwash | 6% v/v |
| Naproxen | 0.01 mg/mL |
| Orange Juice | 2% v/v |
| Soft Drink (Pepsi) | 6% v/v |
| Sodium Chloride | 18 mg/mL |
| Sugar | 10 mg/mL |
| Tea | 6% v/v |
| Toothpaste | 6% w/v |
Non-interfering Orally Used Exogenous Products
| Compound | Concentration Tested |
| --- | --- |
| Teeth Whitener | 2 strips |
| Cigarette | 1 cigarette |
| Hard Candy | 1 piece |
| Chewing Gum | 1 piece |
| Hydrogen Peroxide (3% OTC) | Neat (2 min. mouth rinse) |
| Sugar | 2 Teaspoons |
| Cough Syrup | 2 Teaspoons |
| Milk | 100 mL |
| Orange Juice | 100 mL |
| Ibuprofen | 200 mg |
| Acetaminophen | 1000 mg |
Interference – pH
To evaluate potential interference from the effect of oral fluid pH, device performance in the qualitative and semi-quantitative modes was tested using a range of oral fluid pH values (3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0 and 11.0). All test samples were prepared in drug free oral fluid containing oxycodone at $\pm 25\%$ of the cutoff. At the pH levels tested, there was no interference observed for each test mode.
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4. Assay Reportable Range:
The reportable range for the semi-quantitative mode is 20 ng/mL to 200 ng/mL.
5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
Traceability
The assay is traceable to a commercially available, certified, standard material with the concentration verified by GC-MS or LC-MS/MS.
Methamphetamine Stability in Oral Fluid
Drug free negative oral fluid spiked with methamphetamine at +50% of the 50 ng/mL cutoff were collected and stored in Quantisal and Quantisal II Oral Fluid Collection Devices at 2°C - 8°C, tested by LC-MS/MS at each time point and compared to the baseline concentration result. The test results indicate that oral fluid samples containing methamphetamine are stable for up to 12 months stored in Quantisal or Quantisal II Oral Fluid Collection Device at 2°C - 8°C.
Data to support 10-day storage in Quantisal or Quantisal II Oral Fluid Collection Device at ambient temperature 8°C - 25°C were reported in K183048 and K200801.
6. Detection Limit:
Not applicable.
7. Assay Cut-Off:
The assay cut-off cutoff for the qualitative and semi-quantitative analysis of methamphetamine in neat oral fluid is 50 ng/mL.
B Comparison Studies:
1. Method Comparison with Predicate Device:
Eighty (80) deidentified, unaltered clinical oral fluid samples collected by using the Quantisal and Quantisal II Oral Fluid Collection Devices were obtained from clinical research facilities, analyzed for methamphetamine at assay cutoff with the SEFRIA Methamphetamine Oral Fluid Enzyme Immunoassay in both qualitative and semi-quantitative modes and compared to Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) results using the Agilent 6430 Liquid Chromatography-Tandem Mass Spectrometry. Method comparison test results in qualitative and semi-quantitative modes are presented below.
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Method Comparison – Quantisal
| | Immunoassay Result | LC-MS/MS Methamphetamine Concentration | | | | Agreement (%) |
| --- | --- | --- | --- | --- | --- | --- |
| | | < 25 ng/mL (less than -50% cutoff) | 25 – 49 ng/mL (between -50% cutoff and cutoff) | 50 – 75 ng/mL (between cutoff and +50% cutoff) | > 75 ng/mL (greater than +50% cutoff) | |
| Qual. | Positive | 0 | 0 | 4 | 36 | 100% (40/40) |
| | Negative | 36 | 4 | 0 | 0 | 100% (40/40) |
| Semi-Quant. | Positive | 0 | 0 | 4 | 36 | 100% (40/40) |
| | Negative | 36 | 4 | 0 | 0 | 100% (40/40) |
Method Comparison – Quantisal II “Pad A”
| Immunoassay Result | LC-MS/MS Methamphetamine Concentration | | | | Agreement (%) | |
| --- | --- | --- | --- | --- | --- | --- |
| | | < 25 ng/mL (less than -50% cutoff) | 25 – 49 ng/mL (between -50% cutoff and cutoff) | 50 – 75 ng/mL (between cutoff and +50% cutoff) | | > 75 ng/mL (greater than +50% cutoff) |
| Qual. | Positive | 0 | 0 | 5 | 35 | 100% (40/40) |
| | Negative | 36 | 4 | 0 | 0 | 100% (40/40) |
| Semi-Quant. | Positive | 0 | 0 | 5 | 35 | 100% (40/40) |
| | Negative | 36 | 4 | 0 | 0 | 100% (40/40) |
Method Comparison – Quantisal II “Pad B”
| Immunoassay Result | LC-MS/MS Methamphetamine Concentration | | | | Agreement (%) | |
| --- | --- | --- | --- | --- | --- | --- |
| | | < 25 ng/mL (less than -50% cutoff) | 25 – 49 ng/mL (between -50% cutoff and cutoff) | 50 – 75 ng/mL (between cutoff and +50% cutoff) | | > 75 ng/mL (greater than +50% cutoff) |
| Qual. | Positive | 0 | 0 | 5 | 35 | 100% (40/40) |
| | Negative | 36 | 4 | 0 | 0 | 100% (40/40) |
| Semi-Quant. | Positive | 0 | 0 | 5 | 35 | 100% (40/40) |
| | Negative | 36 | 4 | 0 | 0 | 100% (40/40) |
2. Matrix Comparison:
Not applicable.
C Clinical Studies:
1. Clinical Sensitivity:
Not applicable.
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2. Clinical Specificity:
Not applicable.
3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable.
D Clinical Cut-Off:
Not applicable.
E Expected Values/Reference Range:
Not applicable.
VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.
IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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