The OralTox® Oral Fluid Drug Test is a competitive binding, lateral flow immunochromatographic assay for the qualitative and simultaneous detection of Amphetamine, Cocaine, Marijuana (THC), Methamphetamine, Opiates, Phencyclidine, Oxycodone and Methadone in human oral fluid at the cutoff concentrations listed below and their metabolites:

Test	Calibrator	Cutoff (ng/mL)
Amphetamine (AMP)	d-Amphetamine	50
Cocaine (COC)	Benzoylecgonine	20
Marijuana (THC)	Delta-9-Tetrahydrocannabinol	40
Methamphetamine (MET)	d-Methamphetamine	50
Opiates (OPI)	Morphine	40
Phencyclidine (PCP)	Phencyclidine	10
Oxycodone (OXY)	Oxycodone	20
Methadone (MTD)	Methadone	30

The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Liquid Chromatography/Mass Spectrometry/ Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method. It is not intended to detect intermittent dosing of Oxycodone. Clinical consideration and professional judgment should be exercised with any drug of abuse test result. particularly when the preliminary result is positive.

Device Description

The OralTox Oral fluid Drug Test is an immunochromatographic assay that uses a lateral flow system for the qualitative detection of Amphetamine, Cocaine, Cannabinoids, Methamphetamine, Morphine, Phencyclidine. Oxycodone and Methadone (target analytes) in human oral fluid. The products are single-use in vitro diagnostic devices. Each test kit contains a test cup, a package insert and a sample collection sponge. Each test device is sealed with a desiccant in an aluminum pouch.

AI/ML Overview

The provided document describes the OralTox® Oral fluid Drug Test, a competitive binding, lateral flow immunochromatographic assay for the qualitative and simultaneous detection of several drugs in human oral fluid. This submission is a 510(k) premarket notification, indicating the device is intended to be substantially equivalent to previously marketed devices.

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:

Acceptance Criteria and Reported Device Performance

The core acceptance criteria for this device are related to its analytical performance in detecting specific drugs at defined cutoff concentrations. The studies performed focus on demonstrating the accuracy and reliability of the device in comparison to a confirmed analytical method (LC/MS/MS).

Table of Acceptance Criteria and Reported Device Performance (Methadone and Oxycodone - as these were the focus of new data in this submission)

Test	Calibrator	Cutoff (ng/mL)	Acceptance Criteria (Implied)	Reported Device Performance (for Methadone and Oxycodone)
Methadone (MTD)	Methadone	30	Precision/Reproducibility: Consistent results across multiple runs and lots, especially around the cutoff.	Precision-Reproducibility-Cut-Off:- Lot 1 (Methadone): -100% to -50% cut-off: 60-/0+ (100% negative) -25% cut-off: 54-/6+ (90% negative, 10% positive) Cut-off: 49+/11- (81.7% positive, 18.3% negative) +25% to +100% cut-off: 55+/5- (91.7% positive), 60+/0- (100% positive)- Lot 2 (Methadone): Similar performance, with 55-/5+ at -25% cut-off and 48+/12- at cut-off.- Lot 3 (Methadone): Similar performance, with 55-/5+ at -25% cut-off and 50+/10- at cut-off.Method Comparison (Methadone):- Drug Free & < Half Cutoff: 100% correct (0 false positives)- Near Cutoff Negative: 80% correct (4 false positives out of 20)- Near Cutoff Positive: 87% correct (2 false negatives out of 15)- High Positive: 100% correct (0 false negatives)- Discordant Results (Methadone): 4 false positives slightly below cut-off (26.9-28.82 ng/mL) and 2 false negatives slightly above cut-off (31.07-31.29 ng/mL).
Oxycodone (OXY)	Oxycodone	20	Precision/Reproducibility: Consistent results across multiple runs and lots, especially around the cutoff.	Precision-Reproducibility-Cut-Off:- Lot 1 (Oxycodone): -100% to -50% cut-off: 60-/0+ (100% negative) -25% cut-off: 55-/5+ (91.7% negative, 8.3% positive) Cut-off: 50+/10- (83.3% positive, 16.7% negative) +25% to +100% cut-off: 55+/5- (91.7% positive), 60+/0- (100% positive)- Lot 2 (Oxycodone): Similar performance, with 54-/6+ at -25% cut-off and 49+/11- at cut-off.- Lot 3 (Oxycodone): Similar performance, with 56-/4+ at -25% cut-off and 49+/11- at cut-off.Method Comparison (Oxycodone):- Drug Free & < Half Cutoff: 100% correct (0 false positives)- Near Cutoff Negative: 84.4% correct (5 false positives out of 32)- Near Cutoff Positive: 86.2% correct (4 false negatives out of 29)- High Positive: 100% correct (0 false negatives)- Discordant Results (Oxycodone): 5 false positives slightly below cut-off (17.2-19.05 ng/mL) and 4 false negatives slightly above cut-off (22.04-23.29 ng/mL).
All 8 Drugs (AMP, COC, THC, MET, OPI, PCP, OXY, MTD)	Various (see table)	Various (see table)	Interference: No significant interference from common substances.Specificity: Limited cross-reactivity with structurally similar compounds.pH Effect: Performance holds across a range of oral fluid pH.Stability: Maintain performance over specified storage conditions and shelf life.	Interference: Noted that compounds at 10μg/mL showed "no interference for all eight drugs." Food items and common substances (methanol cough drops, coffee, etc.) showed "no interference" at 5% concentration. Hemoglobin (100 ug/mL) and cigarette smoking also showed no interference.Specificity: Detailed cross-reactivity tables provided for Oxycodone and Methadone, showing desired low cross-reactivity with related compounds (e.g., Hydromorphone 0.3% for Oxycodone, Alpha-Methadol 24% for Methadone). Data for other drugs implicitly reported in K171403.pH Effect: "Results were all positive for samples at and above +50% Cut-Off and all negative for samples at and below -50% Cut-Off" for pH 4-9.Stability: Devices "stable at 4-30 °C for 24 months based on accelerated stability study at 45 ℃ and real time stability study at 2-8℃ and 30℃." Oral fluid samples can be stored in the device at -20℃ for at least 3 months and shipped overnight.

Study Details

The provided document describes analytical performance studies and method comparison studies. There is no mention of clinical studies involving patients or a human-in-the-loop (MRMC) study. The device is an in-vitro diagnostic (IVD) device, and the focus is on its analytical accuracy against a gold standard lab method.

A table of acceptance criteria and the reported device performance:
- See table above. The acceptance criteria are largely implied from the nature of the tests performed and the typical expectations for an IVD device. For example, for precision/reproducibility, the expectation is that samples significantly below the cutoff are consistently negative, and samples significantly above are consistently positive, with an acceptable range of uncertainty around the cutoff itself. For method comparison, a high percentage of agreement with the confirmatory method is expected.
Sample sizes used for the test set and the data provenance:
- Precision-Reproducibility-Cut-Off: Samples were prepared at 8 concentrations (-100%, -75%, -50%, -25%, +25%, +50%, +75%, +100% of cutoff). For each concentration, tests were performed "two runs per day for 10 days per device lot." With 3 lots tested (for Oxycodone and Methadone), this means: 8 concentrations x 2 runs/day x 10 days x 3 lots = 480 samples per drug (e.g., 60 samples per concentration/lot).
- Method Comparison Studies: "Total 932 samples" were tested across all drugs. For Oxycodone, the breakdown is: 152 drug-free, 47 less than half cutoff, 32 near cutoff negative, 29 near cutoff positive, 174 high positive = 434 samples. For Methadone, the breakdown is: 277 drug-free, 13 less than half cutoff, 20 near cutoff negative, 15 near cutoff positive, 173 high positive = 498 samples. (434 + 498 = 932 total, aligning with the stated total).
- Data Provenance: The document does not explicitly state the country of origin. It indicates that the samples were "prepared by spiking drug in negative oral fluid samples" for precision studies. For method comparison, "Method comparison studies for the Oral fluid Drug Test were performed at eight testing sites with three operators at each site." This suggests retrospective sample collection and external lab testing for the LC/MS/MS ground truth, though the exact nature (e.g., banked samples, newly collected for the study) is not specified. The samples are human oral fluid.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The ground truth was established by Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC-MS/MS), which is described as the "preferred confirmatory method." LC-MS/MS is an analytical chemistry technique, not typically performed by "experts" in the clinical sense (like radiologists). The "ground truth" is derived from the analytical measurement itself, likely performed by trained laboratory technicians or biochemists following established protocols. Therefore, the concept of "number of experts" or "qualifications" beyond standard lab accreditation is not applicable in the way it would be for image interpretation.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- No adjudication method described. The test is a qualitative assay (positive/negative based on visual line presence/absence), and the ground truth is a quantitative analytical measurement (LC-MS/MS). Discrepancies between the device result and the LC-MS/MS result are reported as discordant results, not subject to further "adjudication" by human experts in this context.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No, an MRMC comparative effectiveness study was not done. This is an in-vitro diagnostic (IVD) device, not an AI-powered image interpretation device. It is a rapid immunoassay for drug detection. The "readers" are the individuals visually interpreting the test result (presence or absence of a line), not medical professionals interpreting complex images. The study focuses on the analytical performance of the device itself against a gold standard lab method.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- This is a standalone diagnostic device. The performance data presented (precision, linearity, stability, interference, specificity, pH effect, drug recovery, and method comparison studies) characterize the standalone analytical performance of the device itself. The "human-in-the-loop" component is limited to the visual interpretation of the presence/absence of a line, which is a straightforward qualitative assessment, not a complex diagnostic decision.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The ground truth used was quantitative analytical measurement via Liquid Chromatography/Mass Spectrometry/Mass Spectrometry (LC-MS/MS). For drug detection, this is typically considered the gold standard.
The sample size for the training set:
- This document describes a premarket notification for an IVD device. The methods described here relate to validation/test set studies. The document does not mention a "training set" in the context of machine learning. Lateral flow immunoassays are developed and optimized through chemical and biological engineering, not by training a machine learning algorithm on a dataset.
How the ground truth for the training set was established:
- As there is no mention of a "training set" or machine learning model in this document, this question is not applicable. The device's mechanism is based on immunochromatography (antigen-antibody reactions), not data-driven learning.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

September 20, 2018

Premier Biotech, Inc. c/o Lisa Pritchard Regulatory, Quality & Compliance Consultant DuVal & Associates 825 Nicollet Mall Suite 1820 Minneapolis, MN 55402

Re: K181305

Trade/Device Name: OralTox® Oral fluid Drug Test Regulation Number: 21 CFR 862.3610 Regulation Name: Methamphetamine test system Regulatory Class: Class II Product Code: DJC, DJG, DIG, DIO, DKZ, LCM, LDJ, DJR Dated: August 9, 2018 Received: August 10, 2018

Dear Lisa Pritchard:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration. listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

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Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Kellie B. Kelm -S

for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K181305

Device Name OralTox® Oral fluid Drug Test

Indications for Use (Describe)

Test	Calibrator	Cutoff (ng/mL)
Amphetamine (AMP)	d-Amphetamine	50
Cocaine (COC)	Benzoylecgonine	20
Marijuana (THC)	Delta-9-Tetrahydrocannabinol	40
Methamphetamine (MET)	d-Methamphetamine	50
Opiates (OPI)	Morphine	40
Phencyclidine (PCP)	Phencyclidine	10
Oxycodone (OXY)	Oxycodone	20
Methadone (MTD)	Methadone	30

Type of Use (Select one or both, as applicable)

☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)
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K181305 510(k) SUMMARY

September 19, 2018 1. Date:
1. Submitter: Premier Biotech Inc 723 Kasota Avenue SE, Minneapolis MN 55414
1. Contact person: Jackie Gale Premier Biotech Inc 723 Kasota Avenue SE, Minneapolis MN 55414

Telephone: 612-839-5565 Email: jgale@premierbiotech.com

OralTox® Oral fluid Drug Test 4. Device Name:

Classification:

Product Code	CFR #	Panel
DJC	21 CFR, 862.3610 Methamphetamine Test System	Toxicology
DIO	21 CFR, 862.3250 Cocaine Test System	Toxicology
DJG	21 CFR, 862.3650 Opiate Test System	Toxicology
DKZ	21 CFR, 862.3100 Amphetamine Test System	Toxicology
LCM	Enzyme Immunoassay Phencyclidine Test	Toxicology
LDJ	21 CFR, 862.3870 Cannabinoids Test System	Toxicology
DJR	21 CFR, 862.3610 Methadone Test System	Toxicology

5. Predicate Devices:

Predicate Device K171403: OralTox Oral Fluid Drug Test

Reference Devices K002010: OraSure Methadone Intercept Micro-plate K122809: Advin Multi-Drug Screen Test Cup

1. Intended Use
  The OralTox® Oral Fluid Drug Test is a competitive binding, lateral flow immunochromatographic assay for the qualitative and simultaneous detection of Amphetamine, Cocaine, Marijuana (THC), Methamphetamine. Opiates, Phencyclidine. Oxycodone and Methadone in human oral fluid at the cutoff concentrations listed below and their metabolites:

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Test	Calibrator	Cutoff (ng/mL)
Amphetamine (AMP)	d-Amphetamine	50
Cocaine (COC)	Benzoylecgonine	20
Marijuana (THC)	Delta-9-Tetrahydrocannabinol	40
Methamphetamine (MET)	d-Methamphetamine	50
Opiates (OPI)	Morphine	40
Phencyclidine (PCP)	Phencyclidine	10
Oxycodone (OXY)	Oxycodone	20
Methadone (MTD)	Methadone	30

The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Liquid Chromatography/Mass Spectrometry/ Mass Spectrometry (LC-MS/MS) is the preferred confirmatory method. It is not intended to detect intermittent dosing of Oxycodone. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.

7. Device Description

1. Substantial Equivalence Information
  A summary comparison of features of the OralTox Oral fluid Drug Test and the predicate devices is provided in following tables.

Table 1: Features Comparison of OralTox Oral fluid Drug Test and the Predicate and Reference Devices

Item	Subject Device	Predicate Device K171403
IntendedUse	For the qualitative determination ofdrugs of abuse in human oral fluid.	Same
Item	Subject Device	Predicate Device K171403
Calibrators	D-Amphetamine (AMP)Cocaine (COC)Delta-9-Tetrahydrocannabinol (THC)D-Methamphetamine (MET)Morphine (OPI)Phencyclidine (PCP)Oxycodone (OXY)Methadone (MTD)	D-Amphetamine (AMP)Cocaine (COC)Delta-9-Tetrahydrocannabinol(THC)D-Methamphetamine (MET)Morphine (OPI)Phencyclidine (PCP)
Methodology	Competitive binding, lateral flowimmunochromatographic assaysbased on the principle of antigenantibody immunochemistry.	Same
Type of Test	Qualitative	Same
Specimen Type	Human Oral Fluid	Same
Cut-Off Values	AMP 50 ng/mLCOC 20 ng/mLTHC 40 ng/mLMET 50 ng/mLOPI 40 ng/mLPCP 10 ng/mLOXY 20 ng/mLMTD 30 ng/mL	Same, except OXY and MTD notincluded

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9. Test Principle

The OralTox Oral Fluid Drug Test is a rapid test for the qualitative detection of Amphetamine, Cocaine, Cannabinoids, Methamphetamine, Morphine, Phencyclidine, Oxycodone and Methadone in oral fluid samples. The tests are lateral flow chromatographic immunoassays. During testing, an oral fluid specimen migrates upward by capillary action. If target drugs present in the oral fluid specimen are below the cut-off concentration, it will not saturate the binding sites of its specific monoclonal mouse antibody coated on the particles. The antibody-coated particles will then be captured by immobilized drug-conjugate and a visible colored line will show up in the test line region. The colored line will not form in the test line region if the target drug level exceeds its cutoff-concentration because it will saturate all the binding sites of the antibody coated on the

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particles. A band should form in the control region of the devices regardless of the presence of drug or metabolite in the sample to indicate that the tests have been performed properly.

10. Performance Characteristics

1. Analytical Performance
- Precision-Reproducibility-Cut-Off a.

Precision-Reproducibility-Cut-Off studies were carried out for samples with concentrations of -100% cut off, -75% cut off, -50% cut off, -25% cut off, +25% cut off, +50% cut off , +75% cut off and +100% cut off. These samples were prepared by spiking drug in negative oral fluid samples. Each drug concentration was confirmed by LC/MS/MS. All sample aliquots were blindly labeled by the person who prepared the samples and didn't take part in the sample testing. For each concentration, tests were performed two runs per day for 10 days per device lot in a randomized order. The results obtained are summarized in the following tables for Methadone and Oxycodone. The rest of the data were reported in K171403.

The results summary for methadone

	Result	-100%cut-off	-75%cut-off	-50%cut-off	-25%cut-off	Cut-off	+25%cut-off	+50%cut-off	+75%cut-off	+100%cut-off
drug	Lot 1	60-/0+	60-/0+	60-/0+	54-/6+	49+/11-	55+/5-	60+/0-	60+/0-	60+/0-
	Lot 2	60-/0+	60-/0+	60-/0+	55-/5+	48+/12-	56+/4-	60+/0-	60+/0-	60+/0-
	Lot 3	60-/0+	60-/0+	60-/0+	55-/5+	50+/10-	55+/5-	60+/0-	60+/0-	60+/0-

drug	-100%cut off	-75%cut off	-50%cut off	-25%cutoff	cut off	+25%cut off	+50%cutoff	+75%cutoff	+100%cutut off
Lot 1	60-/0+	60-/0+	60-/0+	55-/5+	50+/10-	55+/5-	60+/0-	60+/0-	60+/0-
Lot 2	60-/0+	60-/0+	60-/0+	54-/6+	49+/11-	56+/4-	60+/0-	60+/0-	60+/0-
Lot 3	60-/0+	60-/0+	60-/0+	56-/4+	49+/11-	57+/3-	60+/0-	60+/0-	60+/0-

The results summary for oxycodone

The following cut-off values for the candidate device have been verified.

Calibrator	Cut-off (ng/mL)
Methadone	30
Oxycodone	20

b. Linearity
Not applicable.
c. Stability
The devices are stable at 4-30 °C for 24 months based on the accelerated stability study at 45 ℃ and real time stability study at 2-8℃ and 30℃.

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d. Interference

Potential interfering substances were added to drug-free oral fluid and target drugs oral fluid with concentrations at 50% below and 50% above Cut-Off levels. These oral fluid samples were tested using three batches of the OralTox device. Compounds that showed no interference for all eight drugs at a concentration of 10μg/mL are summarized in the following table.

Acetaminophen	Digoxin	Nicotinamide
Acetylcodeine	Dihydrocodeine	Nicotine
Allobarbital	diltiazem HCl	Noscapine
Alprazolam	Diphenhydramine HCl	Omeprazole
Amobarbital	DL-Propranolol	Papaverine
Apomorphine	Doxylamine	Pentazocine
Atenolol	Ecgonine methylester	Phentermine
Atropine	Estradiol	Phenylpropanolamine
Baclofen	Estrone	Phenytoin
Benzocaine	Fluconazole	Pioglitazone HCl
Butabarbital	Furosemide	Prednisolone
Caffeine	Hexobarbital	Prednisone
Cannabidiol	Hydrochlorothiazide	Procainamide HCl
Carbamazepine	Ibuprofen	Procaine HCL
Chlordiazepoxide	Imipramine	Promethazine
Chlorpromazine	Lamotrigine	Quinine HCl
Cimetidine	Levetiracetam	R,R(-)-Pseudoephedrine
Citalopram HBr	Lidocaine	Salicylic Acid
Clobazam	Lormetazepam	Sertraline HCL
Clomipramine	L-Thyroxine	Simvastin
Clonazepam	Metformin HCl	Theophylline
Clonidine	Methylphenidate HCl	Thiamine
Clopidogrel bisulfate	Metoprolol	Topiramate
Cortisol	Metronidazole	Valproic Acid
Cotinine	Montelukast sodium salt	Verapamil
d,1-Salbutamol	Naloxone	Zonisamide
Deoxycorticosterone	Naltrexone
Dextromethorphan	Naproxen

Food items such as methanol cough drops, cough syrup, cola, mouthwash, coffee, tea, milk, sugar, chewing gum, alcohol, baking soda, salt, cranberry juice, orange juice, food coloring (red, blue, green), toothpaste, tomatoes and MSG were added in either drug-free oral fluid or oral fluid containing the target drug with concentrations of 50% below and 50% above cutoff levels to a concentration of 5%. None of the substances showed interference. Hemoglobin showed no interference at 100 ug/mL.

Cigarette smoking showed no interference.

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e. Specificity

To test specificity, drug metabolites and other structural related compounds that are likely to interfere in oral fluid samples were tested using three batches of the OralTox device. The results obtained are summarized in the following tables for Methadone and Oxycodone. The rest of the data were reported in K171403.

Oxycodone(Cut-off=20 ng/mL)	ResultPositive at (ng/mL)	% Cross-Reactivity
Oxycodone	20	100%
Hydrocodone	1000	2%
Hydromorphone	6250	0.3%
Naloxone	6250	0.3%
Oxymorphone	1000	2%
Dihydrocodeine	Negative at 10000	<0.2%
Buprenorphine	Negative at 10000	<0.2%
6-AM	Negative at 10000	<0.2%
Codeine	Negative at 10000	<0.2%
Heroin	Negative at 10000	<0.2%
Morphine	Negative at 10000	<0.2%
Morphine -3-β-d-glucuronide	Negative at 10000	<0.2%
Ethylmorphine	Negative at 10000	<0.2%

Methadone(Cut-off=30 ng/mL)	ResultPositive at(ng/ml)	% Cross-Reactivity
Methadone	30	100%
Alpha-Methadol	125	24%
Doxylamine	12500	0.24%
2-Ethylidene-1,5-dimethyl-3,3-diphenyl pyrolidine (EDDP)	10000	0.3%
Phencyclidine	12500	0.24%
2-Ethyl-5-methyl-3,3-diphenylpyrroline (EMDP)	100000	0.03%
LAAM	10000	0.3%

f. Effect of Oral fluid pH

To investigate the effect of oral fluid pH, oral fluid samples with pH 4 to 9 were spiked with target drugs at 50% below and 50% above Cut-Off levels. These samples were tested using three lots of the device. Results were all positive for samples at and above +50% Cut-Off and all negative for samples at and below -50% Cut-Off.

g. Drug Recovery Study

Negative oral fluid samples in glass bottles were spiked with the drug to concentrations of -50% and +50% of the cutoff. The samples were transferred to OralTox devices and stored at room temperature, at -20°C and at 40°C. Over 90% recoveries were observed for all drugs in

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the OralTox devices. Oral fluid samples can be stored in the device at -20℃ for at least 3 months. Oral fluid samples can be shipped overnight in the device for LC-MS confirmation.

2. Method Comparison Studies

Method comparison studies for the Oral fluid Drug Test were performed at eight testing sites with three operators at each site. Operators tested total 932 samples and compared to LC/MS/MS results. The results obtained are summarized in the following tables for Oxycodone and Methadone. The rest of the data were reported in K171403.

% of Cutoff	Numberofsamples	OralTox Results		The percentage ofcorrect results(%)
		No. ofPositive	No. ofNegative
Drug Free	152	0	152	100
Less than Half theCutoff Concentrationby LC/MS	47	0	47	100
Near Cutoff Negative	32	5	27	84.4
Near Cutoff Positive	29	25	4	86.2
High Positive	174	174	0	100

O-------done

Discordant Results of Oxycodone

Sites	Sample Number	LC/MS Result	Test Results
Site B	82509	18.0	Positive
Site C	66855	17.2	Positive
Site G	59102	19.05	Positive
Site G	55774	18.23	Positive
Site G	58969	18.52	Positive
Site G	58466	23.29	Negative
Site G	54039	22.04	Negative
Site G	59304	22.4	Negative
Site G	59839	22.34	Negative

Methadone

% of Cutoff	Numberofsamples	OralTox Results		The percentage ofcorrect results(%)
		No. ofPositive	No. ofNegative
Drug Free	277	0	277	100

{10}------------------------------------------------

Less than Half theCutoff Concentrationby LC/MS	13	0	13	100
Near Cutoff Negative	20	4	16	80
Near Cutoff Positive	15	13	2	87
High Positive	173	173	0	173

Discordant Results of Methadone

Sites	Sample Number	LC/MS Result	Test Results
Site D	37797	26.9	Positive
Site E	29605	27.85	Positive
Site H	59547	28.26	Positive
Site H	50075	28.82	Positive
Site D	26326	31.07	Negative
Site H	53132	31.29	Negative

3. Clinical Studies

Not applicable.

11. Conclusion

Based on the test principle and acceptable performance characteristics including precision, interference, specificity, and method comparison studies of the devices, it's concluded that the OralTox Oral fluid Drug Test is substantially equivalent to the stated predicate device.

Regulation Number and Section

§ 862.3610 Methamphetamine test system.

(a)
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.(b)
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).