(266 days)
The Oral Fluid Drug Test is a competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Cocaine, Marijuana (THC), Methamphetamine, Opiates and Phencyclidine, 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 | 40 |
| Opiates (OPI) | Morphine | 40 |
| Phencyclidine (PCP) | Phencyclidine | 10 |
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 (LC/MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.
For in vitro diagnostic use only.
The OralTox Oral fluid Drug Test is immunochromatographic assay that uses a lateral flow system for the qualitative detection of Amphetamine, Cocaine, Cannabinoids, Methamphetamine, Opiates and Phencyclidine (target analytes) in human oral fluid. The tests are the first step in a two-step process. The second step is to send the sample for laboratory testing if preliminary positive results are obtained.
The document provided is a 510(k) summary for the Premier Biotech Inc. OralTox Oral Fluid Drug Test. It describes the device, its intended use, and the performance studies conducted to demonstrate substantial equivalence to a predicate device.
Key takeaway for the Acceptance Criteria and Study:
The acceptance criteria for this device, a qualitative drug test, are primarily established through analytical performance studies, specifically assessing precision/reproducibility around the cutoff concentrations, and method comparison studies against a reference method (LC/MS/MS). The device's performance is demonstrated by the percentage of correct results for samples at various concentrations relative to the defined cutoff values.
Here's a breakdown of the requested information based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state acceptance criteria as a percentage or specific threshold for "correct results" within the tables. However, based on the presentation of "The percentage of correct results (%)", the implicit acceptance criterion is a high percentage of agreement with the LC/MS/MS reference method, especially for drug-free samples, samples less than half the cutoff, and high positive samples (where 100% agreement is consistently achieved). For "near cutoff" samples, some deviation is expected due to the nature of a qualitative test and the inherent variability around the cutoff.
Here's a consolidated table of reported device performance based on the "Method Comparison Studies" for each drug:
| Drug | Concentration Range (by LC-MS/MS) | Number of Samples | Test Results (No. Positive / No. Negative) | Percentage of Correct Results (%) |
|---|---|---|---|---|
| Methamphetamine | Drug-Free | 324 | 0 / 324 | 100 |
| Less than Half the Cutoff | 50 | 0 / 50 | 100 | |
| Near Cutoff Negative | 15 | 2 / 13 | 87 | |
| Near Cutoff Positive | 16 | 15 / 1 | 94 | |
| High Positive | 116 | 116 / 0 | 100 | |
| Cocaine | Drug-Free | 390 | 0 / 390 | 100 |
| Less than Half the Cutoff | 21 | 0 / 21 | 100 | |
| Near Cutoff Negative | 19 | 1 / 18 | 95 | |
| Near Cutoff Positive | 15 | 14 / 1 | 93 | |
| High Positive | 77 | 77 / 0 | 100 | |
| Morphine | Drug-Free | 323 | 0 / 323 | 100 |
| Less than Half the Cutoff | 50 | 0 / 50 | 100 | |
| Near Cutoff Negative | 16 | 2 / 14 | 88 | |
| Near Cutoff Positive | 19 | 18 / 1 | 95 | |
| High Positive | 114 | 114 / 0 | 100 | |
| Amphetamine | Drug-Free | 229 | 0 / 229 | 100 |
| Less than Half the Cutoff | 92 | 0 / 92 | 100 | |
| Near Cutoff Negative | 61 | 2 / 59 | 97 | |
| Near Cutoff Positive | 39 | 36 / 3 | 92 | |
| High Positive | 17 | 17 / 0 | 100 | |
| Phencyclidine | Drug-Free | 407 | 0 / 407 | 100 |
| Less than Half the Cutoff | 20 | 0 / 20 | 100 | |
| Near Cutoff Negative | 8 | 2 / 6 | 75 | |
| Near Cutoff Positive | 4 | 4 / 0 | 100 | |
| High Positive | 38 | 38 / 0 | 100 | |
| Cannabinoids | Drug-Free | 359 | 0 / 327 (Error in doc for Negative count, assumed 359) | 100 |
| Less than Half the Cutoff | 27 | 0 / 27 | 100 | |
| Near Cutoff Negative | 7 | 0 / 7 | 100 | |
| Near Cutoff Positive | 9 | 6 / 3 | 67 | |
| High Positive | 20 | 20 / 0 | 100 |
Note: There appears to be a typo in the "Cannabinoids" table for "Drug-Free" in the "No. of Negative" column (327 instead of 359). Assuming the percentage is truly 100%, the negative count should be 359.
2. Sample Size and Data Provenance
- Test Set Sample Size:
- The "Method Comparison Studies" involved a total of 852 samples across all drug types. The sample sizes for each drug category within these studies are detailed in the table above, ranging from 477 (Phencyclidine) to 852 (Methamphetamine, although the overall total is stated as 852, so these numbers represent the number of samples relevant to each specific drug).
- For the "Precision-Reproducibility-Cut-Off" studies, 60 tests were performed for each concentration of each drug across 3 lots (2 runs per day for 10 days per device lot, resulting in 2x10x3 = 60 tests per concentration). There were 9 concentrations tested for each drug, leading to 540 tests per drug type for this study (60 x 9).
- Data Provenance: The document does not specify the country of origin of the data. It mentions that the "Method comparison studies for the Oral fluid Drug Test were performed at three testing sites." The data appears to be prospective as samples were tested using the OralTox device and compared to LC/MS/MS results.
3. Number of Experts and Qualifications for Ground Truth
The document does not mention the use of "experts" in the context of establishing ground truth for the test set. The ground truth was established by Liquid Chromatography/Mass Spectrometry (LC/MS/MS), which is a highly accurate analytical method, not human expert interpretation.
4. Adjudication Method for the Test Set
Not applicable. As the ground truth was established by LC/MS/MS, a machine-based analytical method, there was no human "adjudication" process needed. The comparison was direct between the device's qualitative result and the quantitative LC/MS/MS result interpreted against the cutoff.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This device is a qualitative in vitro diagnostic assay, not an AI-assisted diagnostic tool for human readers. Therefore, an MRMC study comparing human reader performance with and without AI assistance was not conducted.
6. Standalone Performance (Algorithm Only)
The performance described in the "Analytical Performance" and "Comparison Studies" sections represents the standalone performance of the OralTox Oral Fluid Drug Test. This device is an immunochromatographic assay; it does not involve a separate "algorithm" in the typical sense of AI/ML. The results presented are the device's ability to correctly classify samples based on its chemical/biological reaction, without human interpretation beyond reading the visual result.
7. Type of Ground Truth Used
The primary ground truth used for the comparison studies was Liquid Chromatography/Mass Spectrometry (LC/MS/MS). For the precision studies, samples were prepared by spiking known concentrations of drugs into negative oral fluid samples, and these concentrations were confirmed by LC/MS/MS. This is considered an analytical, highly accurate method for determining drug concentrations.
8. Sample Size for the Training Set
The concept of "training set" is not applicable here. This device is a chemical assay, not a machine learning or AI model that requires a training set. Its "performance" is based on its inherent analytical characteristics determined through laboratory testing with controlled and real-world samples.
9. How the Ground Truth for the Training Set was Established
Not applicable, as there is no training set for this type of device.
In summary: The OralTox Oral Fluid Drug Test demonstrates its acceptance criteria through robust analytical and method comparison studies, relying on LC/MS/MS as the gold standard for ground truth. The device's performance is shown to be highly accurate, especially for drug-free and high-positive samples, with expected variability around the defined cutoff concentrations.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA text logo on the right. The text logo is in blue and reads "FDA U.S. FOOD & DRUG ADMINISTRATION".
February 2, 2018
Premier Biotech Inc % Lisa Pritchard Regulatory, Quality & Compliance Consultant DuVal & Associates 1820 Medical Arts Building, 825 Nicollet Mall Minneapolis, MN, 55402
Re: K171403
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, DIO, DJG, LCM, LDJ, DKZ Dated: January 4, 2018 Received: January 5, 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. 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.
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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR
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Part 820); 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
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,
Courtney HLias -S
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) K171403
Device Name OralTox Oral Fluid Drug Test
Indications for Use (Describe)
The Oral Fluid Drug Test is a competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Cocaine, Marijuana (THC), Methamphetamine, Opiates and Phencyclidine, 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 | 40 |
| Opiates (OPI) | Morphine | 40 |
| Phencyclidine (PCP) | Phencyclidine | 10 |
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 (LC/MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.
For in vitro diagnostic use only.
| 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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510(k) SUMMARY
- February 1, 2018 1. Date:
-
- Submitter: Premier Biotech Inc 723 Kasota Avenue SE, Minneapolis MN 55414
-
- Contact person: Jackie Gale Premier Biotech Inc 723 Kasota Avenue SE, Minneapolis MN 55414 Telephone: 612-839-5563 Email: jgale@premierbiotech.com
-
- Device Name: OralTox Oral fluid Drug Test
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 System | Toxicology |
| LDJ | 21 CFR, 862.3870 Cannabinoids Test System | Toxicology |
-
- Predicate Devices: K103227
The Oratect Oral Fluid Drug Screen Device
- Predicate Devices: K103227
6. Intended Use
The OralTox™ Oral Fluid Drug Test is a competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Cocaine, Marijuana (THC), Methamphetamine, Opiates and Phencyclidine, 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 | 40 |
| Opiates (OPI) | Morphine | 40 |
| Phencyclidine (PCP) | Phencyclidine | 10 |
The test provides only preliminary test results. A more specific alternative chemical method must be
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used in order to obtain a confirmed analytical result. Liquid Chromatography/Mass Spectrometry, Mass Spectrometry (LC/MS/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.
For in vitro diagnostic use only.
-
- Device Description
The OralTox Oral fluid Drug Test is immunochromatographic assay that uses a lateral flow system for the qualitative detection of Amphetamine, Cocaine, Cannabinoids, Methamphetamine, Opiates and Phencyclidine (target analytes) in human oral fluid. The tests are the first step in a two-step process. The second step is to send the sample for laboratory testing if preliminary positive results are obtained.
- Device Description
-
- Substantial Equivalence Information
A summary comparison of features of the OralTox Oral fluid Drug Test and the predicate devices is provided in following tables.
- Substantial Equivalence Information
Table 1: Features Comparison of OralTox Oral fluid Drug Test and the Predicate Devices
| Item | Device | Predicate - K103227 |
|---|---|---|
| Indication(s)for Use | For the qualitative determination of drugs ofabuse in human oral fluid. | Same |
| Calibrators | D-AmphetamineCocaineDelta-9-TetrahydrocannabinolD-MethamphetamineMorphinePhencyclidine | Same |
| Methodology | Competitive binding, lateral flowimmunochromatographic assays based on theprinciple of antigen antibodyimmunochemistry. | 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/mLMOP 40 ng/mLPCP 10 ng/mL | Same |
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| Intended Use | For prescription uses. | Same |
|---|---|---|
| Configurations | Cups | Testing Pad |
9. Test Principle
The OralTox Salvia Drug Test is rapid test for the qualitative detection of Amphetamine, Cocaine, Cannabinoids, Methamphetamine, Morphine and Phencyclidine 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 cutoffconcentration because it will saturate all the binding sites of the antibody coated on the 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
- a. Precision-Reproducibility-Cut-Off
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, 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 following are summaries.
| Amphetamine | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| drug | Result | -100% cut off | -75% cut off | -50% cut off | -25% cutoff | cut off | +25% cut off | +50%cut off | +75%cut off | +100%cut off |
| Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 55-/5+ | 53+/7- | 55+/5- | 60+/0- | 60+/0- | 60+/0- | |
| Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 54-/6+ | 51+/9- | 55+/5- | 60+/0- | 60+/0- | 60+/0- | |
| Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 56-/4+ | 49+/11- | 54+/6- | 60+/0- | 60+/0- | 60+/0- |
| Cocaine | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| drug | Result | -100%cut off | -75%cut off | -50%cut off | -25% cutoff | cut off | +25%cut off | +50%cut off | +75%cut off | +100%cut off |
| Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 56-/4+ | 52+/8- | 54+/6- | 60+/0- | 60+/0- | 60+/0- | |
| Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 55-/5+ | 50+/10- | 54+/6- | 60+/0- | 60+/0- | 60+/0- | |
| Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 54-/6+ | 48+/12- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Methamphetamine | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| drug | Result | -100% cut off | -75% cut off | -50% cut off | -25% cutoff | cut off | +25% cut off | +50%cut off | +75%cut off | +100%cut off |
| Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 54-/6+ | 50+/10- | 55+/5- | 60+/0- | 60+/0- | 60+/0- | |
| Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 55-/5+ | 49+/11- | 56+/4- | 60+/0- | 60+/0- | 60+/0- | |
| Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 55-/5+ | 48+/12- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
Morphine
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| drug | Result -100%cut -75%cut -50%cutoff | off | off | -25%cutoff | cut off | off | off | off | +25%cut +50%cut +75%cut +100%cutoff |
|---|---|---|---|---|---|---|---|---|---|
| Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | રહ્યાર્ટન | 48+/12- | 57+/3- | 60+/0- | 60+/0- | 60+/0- |
| Lot 2 | 60-/0+ | 60-/0+ | 60-10+ | રહ્યાર્ટન | 48+/12- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Lot 3 | 60-10+ | 60-/0+ | 60-10+ | 54-/6+ | 50+/10- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Phencyclidine | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| drug | Result | -100% cut off | -75% cut off | -50% cut off | -25% cutoff | cut off | +25% cut off | +50% cut off | +75%cut off | +100% cut off |
| Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 54-/6+ | 48+/12- | 56+/4- | 60+/0- | 60+/0- | 60+/0- | |
| Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 54-/6+ | 49+/11- | 55+/5- | 60+/0- | 60+/0- | 60+/0- | |
| Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 55-/5+ | 48+/12- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Cannabinoids | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| drug | Result | -100% cut off | -75% cut off | -50% cut off | -25% cutoff | cut off | +25% cut off | +50%cut off | +75%cut off | +100%cut off |
| Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 54-/6+ | 50+/10- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
| Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 54-/6+ | 50+/10- | 56+/4- | 60+/0- | 60+/0- | 60+/0- |
| Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 55-/5+ | 49+/11- | 55+/5- | 60+/0- | 60+/0- | 60+/0- |
The following cut-off values for the candidate devices have been verified.
| Calibrator | Cut-off (ng/mL) |
|---|---|
| d-Methamphetamine | 50 |
| Cocaine | 20 |
| Morphine | 40 |
| d-Amphetamine | 50 |
| Phencyclidine | 10 |
| Delta-9-Tetrahydrocannabinol | 40 |
b. Linearity
Not applicable.
c. Stability
The devices are stable at 4-30 ℃ for 24 months based on the accelerated stability study at 45 °C.
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 the six 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 |
8
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| 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,l-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 µg/mL.
Cigarette smoking showed no interference.
e. Specificity
To test specificity, drug metabolites and other components that are likely to interfere in oral fluid samples were tested using three batches of the OralTox device. The following are summaries.
| d-Methamphetamine | Result | % Cross-Reactivity |
|---|---|---|
| (Cut-off=50 ng/mL) | Positive at (ng/mL) | |
| D - Methamphetamine | 50 | 100% |
| L - Methamphetamine | 5000 | 1% |
| Methoxymethamphetamine | 50 | 100% |
| Ephedrine | 250 | 20% |
| Phenylephrine | 1250 | 4% |
| Procaine | 2500 | 2% |
| Methylephedrine | 500 | 10% |
| Methylenedioxyethylamphetamine | 500 | 10% |
| 3,4-methylenedioxy-methamphetamine(MDMA) | 100 | 50% |
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| Amphetamine | 100000 | 0.05% |
|---|---|---|
| L-Amphetamine | Negative at 10000 | $<0.5%$ |
| D- Amphetamine | 100000 | 0.05% |
| 3,4-methylenedioxyamphetamine | Negative at 50000 | $<0.1%$ |
| Cocaine(Cut-off=20 ng/mL) | ResultPositive at (ng/mL) | % Cross-Reactivity |
|---|---|---|
| Cocaine | 20 | 100% |
| Benzoylecgonine | 20 | 100% |
| Cocaethylene | 25 | 80% |
| Procaine | 20000 | 0.1% |
| Ecgonine | 50000 | 0.04% |
| Ecgonine methyl ester | 10000 | 0.2% |
| Norcocaine | Negative at 10000 | <0.2% |
| Morphine | Result | % Cross- |
|---|---|---|
| (Cut-off=40 ng/mL) | Positive at(ng/ml) | Reactivity |
| Morphine | 40 | 100% |
| Acetylmorphine | 100 | 40% |
| Codeine | 50 | 80% |
| Ethylmorphine | 100 | 40% |
| Heroin | 1250 | 40% |
| Dihydrocodone | 50 | 80% |
| Hydromorphone | 250 | 16% |
| Thebaine | Negative at 20000 | <0.2% |
| Norcodeine | 15000 | 0.3% |
| Morphine 6- -glucuronide | 100 | 40% |
| Oxycodone | 25000 | 0.2% |
| Oxymorphone | 25000 | 0.2% |
| Nalorphine | 25000 | 0.2% |
| Hydrocodone | 100 | 40% |
| 6-Monoacetylmorphine | 100 | 40% |
| Morphine 3- -glucuronide | 100 | 40% |
| d-Amphetamine(Cut-off=50 ng/mL) | ResultPositive at (ng/mL) | % Cross-Reactivity |
|---|---|---|
| D - Amphetamine | 50 | 100% |
| 1-Amphetamine | 4000 | 1.25% |
| D,L- Amphetamine | 50 | 100% |
| Methoxyamphetamine | 200 | 25% |
| D,L- Amphetamine | 10,000 | 0.5% |
| Methylenedioxyamphetamine(MDA) | 250 | 20% |
| Benzodioxolylbutanamine (BDB) | 10000 | 0.5% |
| 3-Hydroxy Tyramine | 5000 | 1% |
| d,l-p-Chloramphetamine | 300 | 17% |
| Phenethylamine | 300 | 17% |
| d,l-Phenylpropanolamine | Negative at 10000 | <0.5% |
| Phentermine | Negative at 10000 | <0.5% |
{9}------------------------------------------------
| Methylenedioxyethylamphetamine(MDEA) | Negative at 10000 | <0.5% |
|---|---|---|
| Methylenedioxy-methamphetamine(MDMA) | Negative at 10000 | <0.5% |
| d-Methamphetamine | Negative at 10000 | <0.5% |
| l-Methamphetamine | Negative at 10000 | <0.5% |
| Hydroxyamphetamine | Negative at 10000 | <0.5% |
| Dimethylamylamine (DMAA) | Negative at 10000 | <0.5% |
| Methylbenzodioxolylbutanamine | Negative at 10000 | <0.5% |
| para-Methoxymethamphetamine | Negative at 10000 | <0.5% |
| Phendimetrazine | Negative at 10000 | <0.5% |
| Phenmetrazine | Negative at 10000 | <0.5% |
| Ephedrine (d-, or l-, or d-l form) | Negative at 100000 | <0.05% |
| diphenhydramine | Negative at 100000 | <0.05% |
| d-Pseudoephedrine | Negative at 100000 | <0.05% |
| Fenfluramine | Negative at 100000 | <0.05% |
| Isoxsuprine | Negative at 100000 | <0.05% |
| l-Pseudoephedrine | Negative at 100000 | <0.05% |
| Mephentermine | Negative at 100000 | <0.05% |
| PCP | Result | % Cross- |
|---|---|---|
| (Cut-off=10 ng/mL) | Positive at (ng/mL) | Reactivity |
| Phencyclidine | 10 | 100% |
| Hydrocodone | 2000 | 0.5% |
| Hydromorphone | 2000 | 0.5% |
| Nalorphine | 10,000 | 0.1% |
| Tenocyclidine (TCP) | 2000 | 0.5% |
| 1-(1-phenylcyclohexyl)morpholine(PCM) | 15 | 67% |
| 4-hydroxyphencyclidine | 10 | 100% |
| EDDP | Negative at 10000 | <0.1% |
| Ketamine | Negative at 10000 | <0.1% |
| Prazepam | Negative at 10000 | <0.1% |
| Amitriptyline | Negative at 100000 | <0.01% |
| Amitriptyline | Negative at 100000 | <0.01% |
| (+) Brompheniramine | Negative at 100000 | <0.01% |
| (+) Chlorphenamine | Negative at 100000 | <0.01% |
| desmethylvenlafaxine | Negative at 100000 | <0.01% |
| Chlorpromazine | Negative at 100000 | <0.01% |
| Clomipramine | Negative at 100000 | <0.01% |
| Cyclizine | Negative at 100000 | <0.01% |
| Cyclobenzaprine | Negative at 100000 | <0.01% |
| Dexbrompheniramine | Negative at 100000 | <0.01% |
| Dextromethorphan | Negative at 100000 | <0.01% |
| Diphenhydramine | Negative at 100000 | <0.01% |
| Doxepin | Negative at 100000 | <0.01% |
| Doxylamine | Negative at 100000 | <0.01% |
| Imipramine | Negative at 100000 | <0.01% |
{10}------------------------------------------------
| Thioridazine | Negative at 100000 | <0.01% |
|---|---|---|
| Venlafaxine | Negative at 100000 | <0.01% |
| Delta-9-Tetrahydrocannabinol(Cut-off=40 ng/mL) | ResultPositive at(ng/ml) | % Cross-Reactivity |
|---|---|---|
| Delta-9-Tetrahydrocannabinol | 40 | 100% |
| 11-nor-Δ9-THC-9 COOH | 12 | 333% |
| Δ8-Tetrahydrocannabinol | 75 | 53% |
| 11-hydroxy-Δ9-THC | 300 | 13% |
| Cannabinol | 2000 | 2% |
| Cannabidol | 10,000 | 0.4% |
| 11-Nor-Δ9-THC-carboxy- glucuronide | 75 | 53% |
| (-)-11-nor-9-carboxy-Δ9-THC | 50 | 80% |
| 11-nor-Δ8-THC-9-COOH | 20 | 200% |
| 8-beta-11-dihydroxy-Δ9-THC | 300 | 13% |
| 8-beta-hydroxy-Δ9-THC | 200 | 20% |
| Exo-THC | 75 | 53% |
| 1-11-Nor-Δ9-THC-9- Carboxylic Acyl-Glucuronide | 15 | 267% |
| Δ8-THC | 82.5 | 49% |
| Δ8-THC Carboxylic Acid | 20 | 200% |
| Δ9-THC Carboxylic Acid | 12 | 333% |
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 store at room temperature, at -20℃ and at 40℃. Over 90% recoveries were observed for all drugs in 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.
Comparison Studies 2.
Method comparison studies for the Oral fluid Drug Test were performed at three testing sites with three operators at each site. Operators tested a total of 852 samples and compared to LC-MS/MS results. The results are presented in the tables below.
| Concentration Range(by LC-MS/MS) | Numberofsamples | Test Results | The percentage ofcorrect results(%) | |
|---|---|---|---|---|
| No. ofPositive | No. ofNegative | |||
| Drug-Free | 324 | 0 | 324 | 100 |
Methamnhetamine
{11}------------------------------------------------
| Concentration Range(by LC-MS/MS) | Numberofsamples | Test Results | The percentage ofcorrect results(%) | |
|---|---|---|---|---|
| Less than Half theCutoff Concentration | 50 | 0 | 50 | 100 |
| Near Cutoff Negative | 15 | 2 | 13 | 87 |
| Near Cutoff Positive | 16 | 15 | 1 | 94 |
| High Positive | 116 | 116 | 0 | 100 |
Discordant Results of Methamphetamine
| Sites | Sample Number | LC/MS Result | Test Results |
|---|---|---|---|
| Site B | 45770 | 49.4 | Positive |
| Site A | 80256 | 48.9 | Positive |
| Site B | 22566 | 55.0 | Negative |
Cocaine
| Concentration Range(by LC-MS/MS) | Numberofsamples | Test results | The percentage ofcorrect results(%) | |
|---|---|---|---|---|
| No. ofPositive | No. ofNegative | |||
| Drug-Free | 390 | 0 | 390 | 100 |
| Less than Half theCutoff Concentration | 21 | 0 | 21 | 100 |
| Near Cutoff Negative | 19 | 1 | 18 | 95 |
| Near Cutoff Positive | 15 | 14 | 1 | 93 |
| High Positive | 77 | 77 | 0 | 100 |
Discordant Results of Cocaine
| Sites | Sample Number | LC/MS Result | Test Results |
|---|---|---|---|
| Site B | 99877 | 17.0 | Positive |
| Site B | 91597 | 22.7 | Negative |
Morphine
| Concentration Range(by LC-MS/MS) | Numberofsamples | Test Results | The percentage ofcorrect results(%) | |
|---|---|---|---|---|
| No. ofPositive | No. ofNegative | |||
| Drug-Free | 323 | 0 | 323 | 100 |
| Less than Half theCutoff Concentration | 50 | 0 | 50 | 100 |
| Near Cutoff Negative | 16 | 2 | 14 | 88 |
| Near Cutoff Positive | 19 | 18 | 1 | 95 |
{12}------------------------------------------------
| High Positive | 114 | 114 | 0 | 100 |
|---|---|---|---|---|
| --------------- | ----- | ----- | --- | ----- |
| Sites | Sample Number | LC/MS Result | Test Results |
|---|---|---|---|
| Site B | 67267 | 35.4 | Positive |
| Site B | 28314 | 37.1 | Positive |
| Site B | 75525 | 42.4 | Negative |
Discordant Results of Morphine
Amphetamine
| Concentration Range(by LC-MS/MS) | Numberofsamples | Test Results | The percentage of | |
|---|---|---|---|---|
| No. ofPositive | No. ofNegative | correct results(%) | ||
| Drug-Free | 229 | 0 | 229 | 100 |
| Less than Half theCutoff Concentration | 92 | 0 | 92 | 100 |
| Near Cutoff Negative | 61 | 2 | રતે | 97 |
| Near Cutoff Positive | 39 | 36 | 3 | 92 |
| High Positive | રવ | રત | 0 | 100 |
Discordant Results of Amphetamine
| Sites | Sample Number | LC/MS Result | Test Results |
|---|---|---|---|
| Site B | 78904 | 48.3 | Positive |
| Site B | 72977 | 49.6 | Positive |
| Site A | 45520 | 53.2 | Negative |
| Site B | 65667 | 52.1 | Negative |
| Site C | 76422 | 53.5 | Negative |
Phencyclidine
| Concentration Range(by LC-MS/MS) | Numberofsamples | Test results | The percentage ofcorrect results(%) | |
|---|---|---|---|---|
| No. ofPositive | No. ofNegative | |||
| Drug-Free | 407 | 0 | 407 | 100 |
| Less than Half theCutoff Concentrationby LC/MS | 20 | 0 | 20 | 100 |
| Near Cutoff Negative | 8 | 2 | 6 | 75 |
| Near Cutoff Positive | 4 | 4 | 0 | 100 |
| High Positive | 38 | 38 | 0 | 100 |
Discordant Results of Phencyclidine
{13}------------------------------------------------
| Sites | Sample Number | LC/MS Result | Test Results |
|---|---|---|---|
| Site B | 25874 | 9.75 | Positive |
| Site B | 23049 | 9.89 | Positive |
Cannabinoids Number Test Results The percentage of Concentration Range correct results of No. of No. of (by LC-MS/MS) samples (%) Positive Negative Drug-Free 359 0 ૩૨૭ 100 Less than Half the 0 27 27 100 Cutoff Concentration 7 0 7 Near Cutoff Negative 100
9
રવ
Discordant Results of Cannabinoids
6
રવ
3
0
67
100
| Sites | Sample Number | LC/MS Result | Test Results |
|---|---|---|---|
| Site A | 25484 | 45.6 | Negative |
| Site A | 28940 | 41.2 | Negative |
| Site D | 28976 | 48.0 | Negative |
3. Clinical Studies
Near Cutoff Positive
High Positive
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 predicate.
§ 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).