Hightop® Multi-Drug Urine Test Cup tests are competitive binding, lateral flow immunochromatographic assays for qualitative and simultaneous detection of Amphetamine, Buprenorphine, Secobarbital, Oxazepam, Cocaine, 2ethylidene-1,5-dimethy1-3,3-diphenylpyrrolidine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Cannabinoids in human urine at the cutoff concentrations of:

Drug (Identifier)	Cut-off level
Amphetamine (AMP)	1000 ng/mL or 500 ng/mL
Buprenorphine (BUP)	10 ng/mL
Secobarbital (BAR)	300 ng/mL
Oxazepam (BZO)	300 ng/mL
Cocaine (COC)	300 ng/mL or 150 ng/mL
2-ethylidene-1,5-dimethy1-3,3-diphenylpyrrolidine (EDDP)	300 ng/mL
Methamphetamine (MET)	1000 ng/mL or 500 ng/mL
Methylenedioxymethamphetamine (MDMA)	500 ng/mL
Morphine (MOP 300/OPI 2000)	2000 ng/mL or 300 ng/mL
Methadone (MTD)	300 ng/mL
Oxycodone (OXY)	100 ng/mL
Phencyclidine (PCP)	25 ng/mL
Propoxyphene (PPX)	300 ng/mL
Nortriptyline (TCA)	1000 ng/mL
Marijuana (THC)	50 ng/mL

Hightop® Multi-Drug Urine Test Cup offers any combinations from 2 to 15 drugs of abuse tests but only one cutoff concentration under same drug condition will be included per device. It is for in vitro diagnostic use only. It is intended for OTC use.

The tests may vield positive results for the prescription drugs Buprenorphine, Oxazepam, Secobarbital, Propoxyphene, and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly in evaluating a preliminary positive result.

The tests provide only preliminary results. To obtain a confirmed analytical result, a more specific alternate chemical method must be used. GC/MS or LC/MS is the recommended confirmatory method.

Hightop® Multi-Drug Urine Test Cup Rx tests are competitive binding. lateral flow immunochromatographic assavs for qualitative and simultaneous detection of Amphetamine, Secobarbital, Oxazepam, Cocaine, 2ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Cannabinoids in human urine at the cutoff concentrations of:

Drug (Identifier)	Cut-off level
Amphetamine (AMP)	1000 ng/mL or 500 ng/mL
Buprenorphine (BUP)	10 ng/mL
Secobarbital (BAR)	300 ng/mL
Oxazepam (BZO)	300 ng/mL
Cocaine (COC)	300 ng/mL or 150 ng/mL
2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)	300 ng/mL
Methamphetamine (MET)	1000 ng/mL or 500 ng/mL
Methylenedioxymethamphetamine (MDMA)	500 ng/mL
Morphine (MOP 300/OPI 2000)	2000 ng/mL or 300 ng/mL
Methadone (MTD)	300 ng/mL
Oxycodone (OXY)	100 ng/mL
Phencyclidine (PCP)	25 ng/mL
Propoxyphene (PPX)	300 ng/mL
Nortriptyline (TCA)	1000 ng/mL
Cannabinoids (THC)	50 ng/mL

Hightop® Multi-Drug Urine Test Cup Rx offers any combinations from 2 to 15 drugs of abuse tests but only one cutoff concentration under same drug condition will be included per device. It is for in vitro diagnostic use only. It is intended for prescription use.

The tests may yield positive results for the prescription drugs Buprenorphine, Oxazepam, Secobarbital, Propoxyphene, and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly in evaluating a preliminary positive result.

The tests provide only preliminary results. To obtain a confirmed analytical result, a more specific alternate chemical method must be used. GC/MS or LC/MS is the recommended confirmatory method.

Device Description

The Hightop® Multi-Drug Urine Test Cup and Hightop® Multi-Drug Urine Test Cup Rx are rapid, single-use in vitro diagnostic devices. Each test kit contains a test device in one pouch. One pouch contains a test Hightop® Cup and two desiccants, and a package insert. The Hightop® Multi-Drug Urine Test Cup is intended for over-the-counter use and the Hightop® Multi-Drug Urine Test Cup Rx is intended for prescription use.

AI/ML Overview

The provided document describes the performance characteristics and studies for the Hightop® Multi-Drug Urine Test Cup and Hightop® Multi-Drug Urine Test Cup Rx. This device is an in-vitro diagnostic test.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

For an in vitro diagnostic device like this multi-drug urine test cup, the "acceptance criteria" generally refers to the expected outcomes and performance targets for sensitivity and specificity around the defined cut-off concentrations, as demonstrated by the precision and method comparison studies. The reported device performance is indicated by the agreement of the device results with LC/MS (Liquid Chromatography/Mass Spectrometry) reference results.

The precision study results show the device performance across various concentrations relative to the cutoff, aiming for all negative results below the -25% cutoff and all positive results above the +25% cutoff. The "Near Cutoff Negative" and "Near Cutoff Positive" categories show deviations which are commonly observed for immunoassay devices operating close to the clinical cutoff.

A summarized table of the stated performance for each drug at various concentrations relative to the cutoff is presented in the original document (e.g., page 11). For the purpose of this summary, a general acceptance criterion for qualitative drug screening tests is typically high agreement with a reference method, especially for samples outside the +/- 25% cutoff range, and reasonable agreement within the +/- 25% cutoff range, as these regions represent the limits of detection and decision points for such assays. The acceptance is implicitly demonstrated by the results showing high concordance for samples sufficiently above or below the cutoff.

Here is a summary of the precision data for Buprenorphine (BUP 10) as an example. Similar tables exist for each drug on pages 11-15.

Acceptance Criteria (Implicitly based on performance expectations for qualitative drug screens) and Reported Device Performance (Precision Study for BUP 10)

Concentration by LC/MS (ng/mL) (Relative to 10 ng/mL Cutoff)	Acceptance Criteria (Expected Result)	Reported Performance (Lot I, total 40 tests)	Reported Performance (Lot II, total 40 tests)	Reported Performance (Lot III, total 40 tests)
Positive Samples
+100% cutoff (20.639)	All Positive (40+)	0-/40+ (100% Positive)	0-/40+ (100% Positive)	0-/40+ (100% Positive)
+75% cutoff (18.961)	All Positive (40+)	0-/40+ (100% Positive)	0-/40+ (100% Positive)	0-/40+ (100% Positive)
+50% cutoff (16.144)	All Positive (40+)	0-/40+ (100% Positive)	0-/40+ (100% Positive)	0-/40+ (100% Positive)
+25% cutoff (12.894)	Mostly Positive	0-/40+ (100% Positive)	0-/40+ (100% Positive)	0-/40+ (100% Positive)
Cutoff (10.931)	Mix of Positive/Negative (as expected at cutoff)	12-/28+ (70% Positive)	11-/29+ (72.5% Positive)	13-/27+ (67.5% Positive)
Negative Samples
-25% cutoff (7.847)	Mostly Negative	40-/0+ (100% Negative)	40-/0+ (100% Negative)	40-/0+ (100% Negative)
-50% cutoff (4.699)	All Negative (40-)	40-/0+ (100% Negative)	40-/0+ (100% Negative)	40-/0+ (100% Negative)
-75% cutoff (2.372)	All Negative (40-)	40-/0+ (100% Negative)	40-/0+ (100% Negative)	40-/0+ (100% Negative)
-100% cutoff (0)	All Negative (40-)	40-/0+ (100% Negative)	40-/0+ (100% Negative)	40-/0+ (100% Negative)
Note: A result of "0-/40+" means 0 negative results and 40 positive results. "40-/0+" means 40 negative results and 0 positive results. "12-/28+" means 12 negative results and 28 positive results.

2. Sample Sizes Used for the Test Set and Data Provenance

Sample Size for Analytical Studies (Precision, Specificity, Interference, pH/SG effect): For each drug and each concentration point (-100%, -75%, -50%, -25%, cutoff, +25%, +50%, +75%, +100% cutoff), tests were performed two runs per day for 20 days using three lots of test Cups. This means for each concentration point, there were 2 runs/day * 20 days * 3 lots = 120 tests. For each drug, across the 9 concentration points reported in the precision studies, there were 9 * 40 * 3 = 1080 tests (40 tests per lot). For interference and specificity: results are reported for relevant concentrations.
Sample Size for Method Comparison Studies: For each drug, 80 unaltered urine samples were used (40 negative and 40 positive). These 80 samples were tested by three operators.
Sample Size for Lay-User Study:
- Configuration 1 (AMP 500, MET 500, MOP 300, COC 150): 140 participants (72 males, 68 females). Each participant presumably tested all drugs in this configuration. The results are presented for 20 samples per concentration level for each drug.
- Configuration 2 (AMP 1000, MET 1000, OPI 2000, COC 300): 140 participants (71 males, 69 females). Each participant presumably tested all drugs in this configuration. The results are presented for 20 samples per concentration level for each drug.
Data Provenance: The analytical and method comparison studies were performed "in-house" and involved spiking drugs into "drug-free urine samples" and "unaltered urine samples." The lay-user study involved recruitment from "three sites." The exact country of origin for the samples or study sites is not explicitly stated, but the manufacturer is Qingdao HIGHTOP Biotech Co., Ltd. in China, suggesting the studies likely took place in China or were managed by the Chinese manufacturer. The studies are retrospective in the sense that samples were prepared or collected and then blinded and tested.

3. Number of Experts and Qualifications for Ground Truth

Analytical and Method Comparison Studies: LC/MS (Liquid Chromatography/Mass Spectrometry) was used to confirm the concentrations of drugs in the urine samples. This is an objective, highly accurate, and quantitative chemical method. The document does not specify the number of experts or their qualifications for performing the LC/MS analysis, but LC/MS is a standard laboratory method typically performed by trained laboratory technicians or chemists.

4. Adjudication Method for the Test Set

Analytical and Method Comparison Studies: The ground truth for these studies was established by LC/MS results. There is no mention of human expert adjudication in the traditional sense (e.g., 2+1, 3+1 consensus). The device's qualitative results (positive/negative) were directly compared against the quantitative LC/MS results relative to the defined cutoff concentration.
Lay-User Study: Outcomes were reported as percentage of correct results compared to the known spiked concentrations. No explicit human adjudication method beyond comparing the lay users' interpretations to the true spiked concentrations is mentioned.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly described in the traditional sense of comparing human readers' performance with and without AI assistance for image analysis or similar tasks.
The document describes a "Lay-user study" which involves multiple users (readers) interpreting the device results, but this is a study to assess the ease of use and interpretation by non-professional users. It compares device performance (as interpreted by lay users) to LC/MS ground truth, not the improvement of human readers with AI assistance.

6. If a Standalone Study (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the device itself is a standalone qualitative immunoassay device. Its performance, as reported in the "Precision" and "Method Comparison" sections (pages 11-15 and 25-35), represents the algorithm's (test strip's) performance in detecting drugs in urine samples without human interpretive bias (beyond the operator physically performing the test and reading the line, which is standard for such devices). The "Discordant Results" tables (pages 25-35) directly compare the device's output against the LC/MS reference.

7. The Type of Ground Truth Used

LC/MS or LC/MS: For all analytical performance and method comparison studies (precision, specificity, interference, pH/SG effect, and comparison with operators), the ground truth for drug concentration was established by Liquid Chromatography/Mass Spectrometry (LC/MS) or LC/MS. This is a highly accurate and quantitative analytical method used as the gold standard for confirming drug concentrations.
Known Spiked Concentrations: For the lay-user study, the ground truth was based on urine samples prepared with known, spiked concentrations of drugs into drug-free urine, which were then confirmed by LC/MS.

8. The Sample Size for the Training Set

The document does not explicitly mention a training set in the context of an algorithm or AI model development. This device is a lateral flow immunochromatographic assay, which is a biochemical test, not a software algorithm that requires a "training set" in the machine learning sense. The performance studies described (precision, specificity, method comparison, lay-user study) are all validation studies.

9. How the Ground Truth for the Training Set was Established

As there is no mention of a traditional "training set" for an algorithm, this question is not directly applicable. The device's performance is based on its inherent biochemical properties and design, which are then validated through the studies described using LC/MS as the ground truth for drug concentrations.

Summary

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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 logo on the right. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, and "ADMINISTRATION" in a smaller font size below.

May 5, 2022

Qingdao HIGHTOP Biotech Co., Ltd. % Joe Shia Manager LSI International 504 E Diamond Ave., Suite I Gaithersburg, Maryland 20877

Re: K220685

Trade/Device Name: Hightop® Multi-Drug Urine Test Cup, Hightop® Multi-Drug Urine Test Cup Rx Regulation Number: 21 CFR 862.3100 Regulation Name: Amphetamine test system Regulatory Class: Class II Product Code: NFT. NGL. PTH. NFV. NFY. PTG. NGG. OBF.OAW. NFW. LCM Dated: March 6, 2022 Received: March 8, 2022

Dear Joe Shia:

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, ple ase 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 (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/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

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/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrl-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Marianela Perez-Torres, Ph.D. Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

K220685

Device Name Hightop® Multi-Drug Urine Test Cup

Indications for Use (Describe)

Drug (Identifier)	Cut-off level
Amphetamine (AMP)	1000 ng/mL or 500 ng/mL
Buprenorphine (BUP)	10 ng/mL
Secobarbital (BAR)	300 ng/mL
Oxazepam (BZO)	300 ng/mL
Cocaine (COC)	300 ng/mL or 150 ng/mL
2-ethylidene-1,5-dimethy1-3,3-diphenylpyrrolidine (EDDP)	300 ng/mL
Methamphetamine (MET)	1000 ng/mL or 500 ng/mL
Methylenedioxymethamphetamine (MDMA)	500 ng/mL
Morphine (MOP 300/OPI 2000)	2000 ng/mL or 300 ng/mL
Methadone (MTD)	300 ng/mL
Oxycodone (OXY)	100 ng/mL
Phencyclidine (PCP)	25 ng/mL
Propoxyphene (PPX)	300 ng/mL
Nortriptyline (TCA)	1000 ng/mL
Marijuana (THC)	50 ng/mL

The tests provide only preliminary results. To obtain a confirmed analytical result, a more specific alternate chemical method must be used. GC/MS or LC/MS is the recommended confirmatory method.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

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Indications for Use

510(k) Number (if known)

Device Name

Hightop® Multi-Drug Urine Test Cup Rx

Indications for Use (Describe)

Hightoo® Multi-Drug Urine Test Cup Rx tests are competitive binding. lateral flow immunochromatographic assavs for qualitative and simultaneous detection of Amphetamine, Secobarbital, Oxazepam, Cocaine, 2ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Cannabinoids in human urine at the cutoff concentrations of:

Drug (Identifier)	Cut-off level
Amphetamine (AMP)	1000 ng/mL or 500 ng/mL
Buprenorphine (BUP)	10 ng/mL
Secobarbital (BAR)	300 ng/mL
Oxazepam (BZO)	300 ng/mL
Cocaine (COC)	300 ng/mL or 150 ng/mL
2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)	300 ng/mL
Methamphetamine (MET)	1000 ng/mL or 500 ng/mL
Methylenedioxymethamphetamine (MDMA)	500 ng/mL
Morphine (MOP 300/OPI 2000)	2000 ng/mL or 300 ng/mL
Methadone (MTD)	300 ng/mL
Oxycodone (OXY)	100 ng/mL
Phencyclidine (PCP)	25 ng/mL
Propoxyphene (PPX)	300 ng/mL
Nortriptyline (TCA)	1000 ng/mL
Cannabinoids (THC)	50 ng/mL

The tests provide only preliminary results. To obtain a confirmed analytical result, a more specific alternate chemical method must be used. GC/MS or LC/MS is the recommended confirmatory method.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

{5}------------------------------------------------

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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510(k) SUMMARY K220685

April 29, 2022 l Date Qingdao HIGHTOP Biotech Co., Ltd. 2 Submitter No.369 Hedong Road, Qingdao, Shandong 266112 China Contact Person Joe Shia 3 LSI International Inc. 504 East Diamond Ave., Suite J Gaithersburg, MD 20877 Telephone: 240-505-7880 Fax: 301-916-6213 Email: shiajl@yahoo.com
Device Name Hightop® Multi-Drug Urine Test Cup 4 Hightop® Multi-Drug Urine Test Cup Rx
5 Classification

Class II
Product CodeTarget Drug	Regulation Section	Cup
NFTAmphetamine (AMP)	862.3100, Amphetamine Test System	Toxicology
NGLBuprenorphine (BUP)	862.3650, Opiate Test System	Toxicology
PTHSecobarbital (BAR)	862.3150, Barbiturate Test System	Toxicology
NFVOxazepam (BZO)	862.3170,Benzodiazepine Test System	Toxicology
NFYCocaine (COC)	862.3250, Cocaine Test System	Toxicology
PTG2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine(EDDP)	862.3620, Methadone Test System	Toxicology
NGGMethamphetamine(MET)	862.3610,Methamphetamine Test System	Toxicology
NGGMethylenedioxymethamphetamine (MDMA)	862.3610,Methamphetamine Test System	Toxicology
NGL	862.3650, Opiate Test System	Toxicology

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Morphine (MOP/OPI)
PTGMethadone (MTD)	862.3620, Methadone Test System	Toxicology
NGLOxycodone (OXY)	862.3650, Opiate Test System	Toxicology
LCMPhencyclidine (PCP)	Unclassified	Toxicology
QBFPropoxyphene (PPX)	862.3700 Propoxyphene test system.	Toxicology
QAWNortriptyline (TCA)	862.3910 Tricyclic antidepressant drugs test system	Toxicology
NFWCannabinoids (THC 50)	862.3870, Cannabinoids Test System	Toxicology

6. Predicate Device K182701

Wondfo T-Cup® Multi-Drug Urine Test Cup

7. Intended Use

Hightop® Multi-Drug Urine Test Cup tests are competitive binding, lateral flow immunochromatographic assays for qualitative and simultaneous detection of Amphetamine, Buprenorphine, Secobarbital, Oxazepam, Cocaine, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, Methamphetamine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Cannabinoids in human urine at the cutoff concentrations of:

Drug (Identifier)	Cut-off level
Amphetamine (AMP)	1000 ng/mL or 500 ng/mL
Buprenorphine (BUP)	10 ng/mL
Secobarbital (BAR)	300 ng/mL
Oxazepam (BZO)	300 ng/mL
Cocaine (COC)	300 ng/mL or 150 ng/mL
2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)	300 ng/mL
Methamphetamine (MET)	1000 ng/mL or 500 ng/mL
Methylenedioxymethamphetamine (MDMA)	500 ng/mL
Morphine (MOP 300/OPI 2000)	2000 ng/mL or 300 ng/mL
Methadone (MTD)	300 ng/mL
Oxycodone (OXY)	100 ng/mL
Phencyclidine (PCP)	25 ng/mL
Propoxyphene (PPX)	300 ng/mL
Nortriptyline (TCA)	1000 ng/mL
Marijuana (THC)	50 ng/mL

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The tests may yield positive results for the prescription drugs Buprenorphine, Nortriptyline, Oxazepam, Secobarbital, Propoxyphene, and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly in evaluating a preliminary positive result.

The tests provide only preliminary results. To obtain a confirmed analytical result, a more specific alternate chemical method must be used. GC/MS or LC/MS is the recommended confirmatory method.

Hightop® Multi-Drug Urine Test Cup Rx tests are competitive binding, lateral flow immunochromatographic assays for qualitative and simultaneous detection of Amphetamine, Buprenorphine, Secobarbital, Oxazepam, Cocaine, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, Methamphetamine, Methylenedioxymethamphetamine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Cannabinoids in human urine at the cutoff concentrations of:

Drug (Identifier)	Cut-off level
Amphetamine (AMP)	1000 ng/mL or 500 ng/mL
Buprenorphine (BUP)	10 ng/mL
Secobarbital (BAR)	300 ng/mL
Oxazepam (BZO)	300 ng/mL
Cocaine (COC)	300 ng/mL or 150 ng/mL
2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)	300 ng/mL
Methamphetamine (MET)	1000 ng/mL or 500 ng/mL
Methylenedioxymethamphetamine (MDMA)	500 ng/mL
Morphine (MOP 300/OPI 2000)	2000 ng/mL or 300 ng/mL
Methadone (MTD)	300 ng/mL
Oxycodone (OXY)	100 ng/mL
Phencyclidine (PCP)	25 ng/mL
Propoxyphene (PPX)	300 ng/mL
Nortriptyline (TCA)	1000 ng/mL
Cannabinoids (THC)	50 ng/mL

{9}------------------------------------------------

The tests provide only preliminary results. To obtain a confirmed analytical result, a more specific alternate chemical method must be used. GC/MS or LC/MS is the recommended confirmatory method.

Device Description 8.

Item	Proposed Device	Predicate(K182701)
Indication(s) for use	For the qualitative determination of Amphetamine, Buprenorphine, Secobarbital, Oxazepam, Cocaine, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, Methamphetamine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Cannabinoids in human urine.	Same
Methodology	Competitive binding, lateral flow immunochromatographic assay based on antigen-antibody reaction	Same
Type of Test	Qualitative	Same
Specimen Type	Human urine	Same
Target Drug andCut Off Values	Target Drug	Cutoff (ng/mL)	Same
	Amphetamine (AMP)	1000 or 500
	Buprenorphine (BUP)	10
	Secobarbital (BAR)	300
	Oxazepam (BZO)	300
	Cocaine (COC)	300 or 150

9. Substantial Equivalence Information

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	2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)	300
	Methamphetamine (MET)	1000 or 500
	Methylenedioxymethamphetamine (MDMA)	500
	Morphine (MOP 300/OPI 2000)	2000 or 300
	Methadone (MTD)	300
	Oxycodone (OXY)	100
	Phencyclidine (PCP)	25
	Propoxyphene (PPX)	300
	Nortriptyline (TCA)	1000
	Cannabinoids (THC 50)	50
Configurations	Test Cup		Cup
Intended Use	Prescription Use and over-the-counter use		For over-the-counter use

10. Test Principle

Hightop® Multi-Drug Urine Test Cup and Hightop® Multi-Drug Urine Test Cup Rx are rapid tests for the qualitative detection of Amphetamine, Buprenorphine, Secobarbital, Oxazepam, Cocaine, 2-ethylidene-1.5-dimethyl-3.3-diphenylpyrrolidine.Methamphetamine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Cannabinoids in urine samples. They are lateral flow chromatographic immunoassay. When urine sample is added to the cup device, urine is absorbed into the test strip and migrates upwards by capillary action. If the concentration of target drug presented in the urine sample is below the cutoff level, the target drug will not saturate the binding sites of its specific monoclonal antibody-coated particles. The antibody-coated particles will then be captured by immobilized drug-conjugate and a visible colored band will be formed on the test line region. If the concentration of target is beyond the cutoff level, the target drug will saturate the binding sites of its specific monoclonal antibody-particles, thus the antibody-coated particles will not be captured by immobilized drug-conjugate hence no colored band will be formed on the test line region.

A band should be formed on the control line region regardless of target drug or metabolite in the sample to indicate that the tests have been performed properly.

11. Performance Characteristics

1. Analytical Performance

a. Precision
Precision studies were carried out for samples with concentrations of -100% cut off, -75% cut off, -50% cut off, -25% cut off, cutoff, +25% cut off, +50% cut off, +75% cut off and +100% cut off. Samples with concentration of -100% cutoff were drug-free urines samples. Other samples were prepared by spiking target drug in drug-free urine samples. Each drug concentration was confirmed by LC/MS. For each concentration, tests were performed two runs per day for 20 days using three lots of test Cups. The results obtained are summarized in the following tables:

{11}------------------------------------------------

Concentration by	+100%	+75%	+50%	+25%	Cutoff	-25%	-50%	-75%	-100%
LC/MS	cutoff	cutoff	cutoff	cutoff		cutoff	cutoff	cutoff	cut-off
(ng/mL)Lot Number	20.639	18.961	16.144	12.894	10.931	7.847	4.699	2.372	0
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	12-/28+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	11-/29+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	13-/27+	40-/0+	40-/0+	40-/0+	40-/0+

Hightop® Multi-Drug Urine Test Cup BUP 10

Hightop® Multi-Drug Urine Test Cup PCP 25

Concentration byLC/MS(ng/mL)Lot Number	+100%	+75%	+50%	+25%	Cutoff	-25%	-50%	-75%	-100%
	cutoff	cutoff	cutoff	cutoff		cutoff	cutoff	cutoff	cut-off
Lot I	45.873	40.806	34.745	28.986	23.342	17.475	11.980	6.035	0
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	10-/30+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	12-/28+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	12-/28+	40-/0+	40-/0+	40-/0+	40-/0+

Hightop® Multi-Drug Urine Test Cup THC 50

Concentration byLC/MS(ng/mL)Lot Number	+100%cutoff	+75%cutoff	+50%cutoff	+25%cutoff	Cutoff	-25%cutoff	-50%cutoff	-75%cutoff	-100%cut-off
91.719	77.980	68.828	56.254	44.616	33.999	23.206	11.577	0
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	14-/26+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	15-/25+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	16-/24+	40-/0+	40-/0+	40-/0+	40-/0+

Hightop® Multi-Drug Urine Test Cup OXY 100

Concentration byLC/MS(ng/mL)Lot Number	+100%cutoff	+75%cutoff	+50%cutoff	+25%cutoff	Cutoff	-25%cutoff	-50%cutoff	-75%cutoff	-100%cut-off
	190.930	166.80	145.48	121.95	97.199	74.091	48.055	23.512	0
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	11-/29+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	13-/27+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	10-/30+	40-/0+	40-/0+	40-/0+	40-/0+

{12}------------------------------------------------

Concentration byLC/MS(ng/mL)Lot Number	+100%cutoff	+75%cutoff	+50%cutoff	+25%cutoff	Cutoff	-25%cutoff	-50%cutoff	-75%cutoff	-100%cut-off
	521.930	478.35	432.76	355.67	310.579	237.31	142.88	73.822	0
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	13-/27+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	12-/28+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	14-/26+	40-/0+	40-/0+	40-/0+	40-/0+

Hightop® Multi-Drug Urine Test Cup BAR 300

Hightop® Multi-Drug Urine Test Cup BZO 300

Concentration byLC/MS(ng/mL)Lot Number	+100%cutoff	+75%cutoff	+50%cutoff	+25%cutoff	Cutoff	-25%cutoff	-50%cutoff	-75%cutoff	-100%cut-off
	565.071	480.34	416.67	354.25	273.078	202.73	136.25	69.388	0
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	15-/25+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	13-/27+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	16-/24+	40-/0+	40-/0+	40-/0+	40-/0+

Hightop® Multi-Drug Urine Test Cup EDDP 300

Concentration byLC/MS(ng/mL)Lot Number	+100%cutoff	+75%cutoff	+50%cutoff	+25%cutoff	Cutoff	-25%cutoff	-50%cutoff	-75%cutoff	-100%cut-off
	554.757	487.55	420.46	343.50	283.163	214.94	144.88	71.416	0
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	11-/29+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	13-/27+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	14-/26+	40-/0+	40-/0+	40-/0+	40-/0+

Hightop® Multi-Drug Urine Test Cup MTD 300

Concentration byLC/MS(ng/mL)Lot Number	+100%cutoff	+75%cutoff	+50%cutoff	+25%cutoff	Cutoff	-25%cutoff	-50%cutoff	-75%cutoff	-100%cut-off
	560.075	460.6	436.87	359.45	281.504	215.81	152.45	73.320	0
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	12-/28+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	14-/26+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	11-/29+	40-/0+	40-/0+	40-/0+	40-/0+

{13}------------------------------------------------

Hightop® Multi-Drug Urine Test Cup MOP 300

Concentration by	+100%	+75%	+50%	+25%	Cutoff	-25%	-50%	-75%	-100%
LC/MS	cutoff	cutoff	cutoff	cutoff		cutoff	cutoff	cutoff	cut-off
(ng/mL)Lot Number	647.611	559.70	492.4	402.2	318.962	210.61	163.37	81.274	0
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	10-/30+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	11-/29+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	13-/27+	40-/0+	40-/0+	40-/0+	40-/0+

Hightop® Multi-Drug Urine Test Cup PPX 300

Concentration byLC/MS(ng/mL)Lot Number	+100%cutoff	+75%cutoff	+50%cutoff	+25%cutoff	Cutoff	-25%cutoff	-50%cutoff	-75%cutoff	-100%cut-off
	605.886	527.60	448.738	394.47	314.961	233.98	153.15	79.325	0
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	12-/28+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	11-/29+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	14-/26+	40-/0+	40-/0+	40-/0+	40-/0+

Hightop® Multi-Drug Urine Test Cup COC 150

Concentration byLC/MS(ng/mL)	+100%cutoff	+75%cutoff	+50%cutoff	+25%cutoff	Cutoff	-25%cutoff	-50%cutoff	-75%cutoff	-100%cut-off
	319.266	272.97	241.8	201.02	158.168	117.53	79.916	41.227	0
Lot Number
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	10-/30+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	12-/28+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	13-/27+	40-/0+	40-/0+	40-/0+	40-/0+

Hightop® Multi-Drug Urine Test Cup MDMA 500

Concentration by	+100%	+75%	+50%	+25%	Cutoff	-25%	-50%	-75%	-100%
LC/MS(ng/mL)	cutoff	cutoff	cutoff	cutoff		cutoff	cutoff	cutoff	cut-off
1064.78	933.69	805.91	656.18	532.253	405.34	264.48	130.38	0
Lot Number
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	14-/26+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	11-/29+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	11-/29+	40-/0+	40-/0+	40-/0+	40-/0+

{14}------------------------------------------------

Concentration byLC/MS(ng/mL)	+100%cutoff	+75%cutoff	+50%cutoff	+25%cutoff	Cutoff	-25%cutoff	-50%cutoff	-75%cutoff	-100%cut-off
	1826.46	1582.9	1356.8	1146.2	913.883	676.01	456.57	242.25	0
Lot Number
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	12-/28+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	12-/28+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	11-/29+	40-/0+	40-/0+	40-/0+	40-/0+

Hightop® Multi-Drug Urine Test Cup TCA 1000

Hightop® Multi-Drug Urine Test Cup AMP 500

Concentrationby LC/MS(ng/mL)	+100%cutoff	+75%cutoff	+50%cutoff	+25%cutoff	Cutoff	-25%cutoff	-50%cutoff	-75%cutoff	-100%cut-off
Lot Number	916.094	807.506	689.93	577.14	462.436	347.06	225.67	124.313	0
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	11-/29+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	13-/27+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	14-/26+	40-/0+	40-/0+	40-/0+	40-/0+

Hightop® Multi-Drug Urine Test Cup MET 500

Concentration byLC/MS(ng/mL)Lot Number	+100%cutoff	+75%cutoff	+50%cutoff	+25%cutoff	Cutoff	-25%cutoff	-50%cutoff	-75%cutoff	-100%cut-off
	952.643	814.24	679.94	578.75	476.642	357.6	241.67	131.18	0
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	10-/30+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	12-/28+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	11-/29+	40-/0+	40-/0+	40-/0+	40-/0+

Hightop® Multi-Drug Urine Test Cup OPI 2000

Concentration by	+100%	+75%	+50%	+25%	Cutoff	-25%	-50%	-75%	-100%
LC/MS(ng/mL)	cutoff	cutoff	cutoff	cutoff		cutoff	cutoff	cutoff	cut-off
	4047.51	3667.3	3241.0	2611.8	1966.56	1548.3	1080.0	535.72	0
Lot Number
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	13-/27+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	12-/28+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	11-/29+	40-/0+	40-/0+	40-/0+	40-/0+

{15}------------------------------------------------

Hightop® Multi-Drug Urine Test Cup COC 300

Concentration byLC/MS(ng/mL)Lot Number	+100%cutoff	+75%cutoff	+50%cutoff	+25%cutoff	Cutoff	-25%cutoff	-50%cutoff	-75%cutoff	-100%cut-off
	624.542	542.14	479.71	402.03	319.266	241.8	158.17	79.916	0
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	11-/29+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	10-/30+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	13-/27+	40-/0+	40-/0+	40-/0+	40-/0+

Hightop® Multi-Drug Urine Test Cup AMP 1000

Concentration by	+100%	+75%	+50%	+25%	Cutoff	-25%	-50%	-75%	-100%
LC/MS	cutoff	cutoff	cutoff	cutoff		cutoff	cutoff	cutoff	cut-off
(ng/mL)Lot Number	1814.57	1583.3	1396.3	1157.0	916.094	689.93	462.44	225.67	0
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	12-/28+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	11-/29+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	12-/28+	40-/0+	40-/0+	40-/0+	40-/0+

Hightop® Multi-Drug Urine Test Cup MET 1000

Concentration byLC/MS(ng/mL)	+100%cutoff	+75%cutoff	+50%cutoff	+25%cutoff	Cutoff	-25%cutoff	-50%cutoff	-75%cutoff	-100%cut-off
	1837.1	1593.0	1378.7	1155.5	952.643	679.94	476.64	241.67	0
Lot Number
Lot I	0-/40+	0-/40+	0-/40+	0-/40+	13-/27+	40-/0+	40-/0+	40-/0+	40-/0+
Lot II	0-/40+	0-/40+	0-/40+	0-/40+	10-/30+	40-/0+	40-/0+	40-/0+	40-/0+
Lot III	0-/40+	0-/40+	0-/40+	0-/40+	11-/29+	40-/0+	40-/0+	40-/0+	40-/0+

The following cutoff values are verified:

Target Drug	Cut-off level
Amphetamine (AMP)	1000 ng/mL or 500 ng/mL
Buprenorphine (BUP)	10 ng/mL
Secobarbital (BAR)	300 ng/mL
Oxazepam (BZO)	300 ng/mL
Cocaine (COC)	300 ng/mL or 150 ng/mL
2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP)	300 ng/mL

{16}------------------------------------------------

Methamphetamine (MET)	1000 ng/mL or 500 ng/mL
Methylenedioxymethamphetamine (MDMA)	500 ng/mL
Morphine (MOP 300/OPI 2000)	2000 ng/mL or 300 ng/mL
Methadone (MTD)	300 ng/mL
Oxycodone (OXY)	100 ng/mL
Phencyclidine (PCP)	25 ng/mL
Propoxyphene (PPX)	300 ng/mL
Nortriptyline (TCA)	1000 ng/mL
Cannabinoids (THC 50)	50 ng/mL

b. Linearity

Not applicable

c. Stability

The devices are stable at 4-30℃ for 24 months based on real-time stability studies.

d. Interference
Potential interfering substances were added to drug-free urine samples with target drugs of -25% cutoff and +25% cutoff level.

Compounds that show no interference at a concentration of 100µg/mL are summarized in the following table.

Acetaminophen	Acetophenetidin	Acetylsalicylic Acid
Acyclovir	Amiodarone Hydrochloride	Apomorphine
Afrin	Albumin (100mg/dL)	Amlodipine Mesylate
Aminophylline	Amoxicillin	Aripiprazole
Aminopyrine	Ampicillin	Aspartame
Benzilic Acid	Atropine	Atomoxetine
Benzoic Acid	Carbamazepine	Atorvastatin Calcium
Bilirubin	Cefradine	Chloramphenicol
Bupropion	Cephalexin	Chlorothiazide
Captopril	Chloral Hydrate	Chloroquine
Ciprofloxacin Hydrochloride	Clonidine	Cholesterol
Citalopram	Clopidogrel Hydrogen Sulphate	(-) Cotinine
Clarithromycin	Clozapine	chlorpheniramine
Deoxy- corticosterone	D,L-Tyrosine	D,L-Octopamine
Dextromethorphan	Digoxin	D,L-Propranolol
Diclofenac	Diphenhydramine	D-Norpropoxy- phene
Diflunisal	Dirithromycin	Domperidone

{17}------------------------------------------------

D-Pseudo- ephedrine	Ecgonine Methyl Ester	Doxylamine
Duloxetine	Effexor	Epinephrine Hydrochloride
Dicyclomine	Enalapril Maleate	Erythromycin
ẞ-Estradiol	Fentanyl Citrate	Esomeprazole Magnesium
Ethanol (1%)	Fluoxetine Hydrochloride	Furosemide
Fenofibrate	Fluvoxamine	Gabapentin
Fenoprofen	Glucose	Gentisic Acid
Glibenclamide	Haloperidol	3-Hydroxy- tyramine
Gliclazide	Hemoglobin	Isosorbide Dinitrate
Glipizide	Ketamine	Isoxsuprine
Ibuprofen	Kratom powder	Lamotrigine
Ketoconazole	Labetalol	Levofloxacin Hydrochloride
Ketoprofen	Liverite	Levonorgestrel
Lidocaine Hydrochloride	Loperamide	Levothyroxine Sodium
Lisinopril	Loratadine	Minocycline
Lithium Carbonate	Naproxen	Nalidixic Acid
Metoprolol Tartrate	Mifepristone	Niacinamide
Magnesium	Mirtazapine	Nifedipine
Meperidine	Montelukast Sodium	Nikethamide
Meprobamate	Phenelzine	Sulfamethazine
Mosapride Citrate	Pioglitazone Hydrochloride	Sulindac
Maprotiline	Piracetam	Tetrahydrocortisone 3 -acetate
Nimodipine	Pravastatin Sodium	Tetrahydrocortisone 3-(β-D-glucuronide)
Norethindrone	Prednisone	Tetrahydrozoline
N-Acetylprocain-amide	Propylthiouracil	Tetracycline
O-Hydroxyhippu-ric Acid	Promethazine	Thiamine
Olanzapine	Quetiapine Fumarate	Thioridazine
Omeprazole	Quinine	Topiramate
Oxalic Acid	Ranitidine	Tramadol Hydrochloride
Oxolinic Acid	Rifampicin	Trazodone Hydrochloride
Oxymetazoline	Risperidone	Triamterene
Ondansetran	Salicylic Acid	Trifluoperazine
Paliperidone	Serotonin	Trimethoprim
Pantoprazole	Sertraline Hydrochloride	Uric Acid
Papaverine	Sildenafil Citrate	Valproate
Paroxetine Hydrochloride	Simvastatin	Verapamil
Penfluridol	Sodium Valproate	Vitamin B2
PenicillinV Potassium	Spironolactone	Vitamin C

{18}------------------------------------------------

Specificity e.
To test the specificity, drug metabolites and other components that are likely to cross-react in urine samples were spiked into drug-free urine. These urine samples were tested using three lots of each device.

Percent cross-reactivity, provided in the below table, was calculated as the cutoff concentration divided by the concentration of analyte tested that yielded a positive result, multiplied by 100; compounds that did not yield a positive result at the highest concentration tested have relative cross reactivity results represented by a dash in the table below:

BUP 10 (Buprenorphine,Cutoff=10 ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
Buprenorphine -3-D-Glucuronide	15	66.67%
Norbuprenorphine	20	50%
Norbuprenorphine-3-D-Glucuronide	250	4%
Morphine	>100000	-
Oxymorphone	>100000	-
Hydromorphone	>100000	-

PCP (Phencyclidine)(Phencyclidine,Cutoff=25 ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
4-Hydroxyphencyclidine	12500	0.2%

THC 50(11-nor-Δ9-THC-9-COOH,Cutoff=50 ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
(-)-11-nor-9-carboxy-Δ9-THC	500	10%
11-nor-Δ8-THC-9-COOH	30	166.67%
11-nor-Δ9-THC-carboxy glucuronide	100000	0.05%
Cannabidiol	100000	0.05%
Cannabinol	100000	0.05%
Δ8- Tetrahydrocannabinol	20000	0.25%
Δ9- Tetrahydrocannabinol	20000	0.25%
11-hydroxy-Δ9-Tetrahydrocannabinol	100000	0.05%

OXY 100(Oxycodone, Cutoff=100 ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
Dihydrocodeine	10000	1%
Hydrocodone	10000	1%
Oxymorphone	500	20%

{19}------------------------------------------------

Codeine	10000	1%
Hydromorphone	50000	0.2%
Morphine	50000	0.2%
Acetylmorphine	>100000	-
Buprenorphine	>100000	-
Ethylmorphine	10000	1%
Thebaine	>100000	-

COC 150(Benzoylecgonine, Cutoff=150 ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
Cocaine	500	30%
Cocaethylene	6000	2.5%
Ecgonine	40000	0.375%
Ecgonine methyl ester	>100000	-
Norcocaine	>100000	-

BAR 300(Secobarbital, Cutoff=300ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
Amobarbital	300	100%
Alphenol	>100000	-
Aprobarbital	300	100%
Butabarbital	300	100%
Butethal	300	100%
Butalbital	2500	12%
Cyclopentobarbital	300	100%
Pentobarbital	300	100%
Phenobarbital	300	100%

BZO 300(Oxazepam, Cutoff=300ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
Alprazolam	200	150%
a-Hydroxyalprazolam	1250	24%
Bromazepam	500	60%
Chlordiazepoxide	1250	24%
Clobazam	100	300%
Clonazepam	2500	12%
Clorazepate dipotassium	200	150%
Delorazepam	1250	24%
Desalkylflurazepam	100	300%

{20}------------------------------------------------

Diazepam	100	300%
Estazolam	5000	6%
Flunitrazepam	50000	0.6%
Midazolam	12500	2.4%
Nitrazepam	100	300%
Norchlordiazepoxide	200	150%
Nordiazepam	500	60%
Temazepam	50	600%
Triazolam	2500	12%
Demoxepam	2000	15%
Flurazepam	500	60%
D,L-Lorazepam	2000	15%

EDDP 300(2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, Cutoff = 300 ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
Methadone	>100000	-
EMDP	>100000	-
Doxylamine	>100000	-
Disopyramide	>100000	-
LAAM (Levo-alpha-acetylmethadol) HCl	>100000	-
Alpha Methadol	>100000	-

MTD 300(Methadone, Cutoff=300ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
Doxylamine	>100000	-
EDDP	>100000	-
EMDP	>100000	-
LAAM	>100000	-
Alpha Methadol	>100000	-

MOP 300(Morphine, Cutoff=300ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
Normorphine	>100000	-
Codeine	300	100%
s-Monoacetylmorphine	300	100%
Ethyl Morphine	200	150%
Heroin	1250	24%
Hydrocodone	10000	3%
Hydromorphone	5000	6%

{21}------------------------------------------------

Morphinie-3-β-d-glucuronide	2500	12%
Oxycodone	>100000	-
Oxymorphone	>100000	-
Thebaine	20000	1.5%
Levorphanol	10000	3%
6-Monoacetylmorphine (6-MAM)	300	100%
Norcodeine	100000	0.3%
Procaine	>100000	-

PPX 300(d-Propoxyphene, Cutoff=300ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
d-Norpropoxyphene	5000	6%

MDMA 500(3,4-Methylenedioxymethamphetamine HCl,Cutoff=500ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
3,4-Methylenedioxyamphetamine HCl (MDA)	50000	1%
3,4-Methylenedioxyethylamphetamine (MDE)	2500	20%
d-methamphetamine	>100000	-
d-amphetamine	>100000	-
l-methamphetamine	50000	1%
l-amphetamine	>100000	-

AMP (Amphetamine) (Amphetamine,Cutoff=500ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
l-Amphetamine	500	100%
dl- Amphetamine	500	100%
(+/-) 3,4-Methylenedioxyamphetamine (MDA)	1000	50%
Phentermine	5000	10%
Hydroxyamphetamine	100000	0.5%
d-Methamphetamine	>100000	-
l-Methamphetamine	>100000	-
(+/-) 3,4-Methylenedioxyethylamphetamine (MDE)	>100000	-
(+/-)3,4-Methylenedioxymethamphetamine (MDMA)	>100000	-
β-Phenylethylamine	100000	0.5%
Tyramine	100000	0.5%
p-Hydroxynorephedrine	100000	0.5%
Phenylpropanolamine	100000	0.5%

{22}------------------------------------------------

(±)Phenylpropanolamine	>100000	-
p-Hydroxyamphetamine	100000	0.5%
d/l-Norephedrine	100000	0.5%
Benzphetamine	>100000	-
l-Ephedrine	100000	0.5%
l-Epinephrine	>100000	-
d/l-Epinephrine	>100000	-

MET 500(D(+)-Methamphetamine, Cutoff=500ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
(+/-)3,4-Methylenedioxy-n-ethylamphetamine(MDE)	25000	2%
D/L-Methamphetamine	500	100%
p-Hydroxymethamphetamine	12500	4%
D-Amphetamine	>100000	-
L-Amphetamine	>100000	-
Chloroquine	10000	5%
(+/-)-Ephedrine	25000	2%
(-)-Methamphetamine	25000	2%
(+/-)3,4-Methylenedioxyamphetamine (MDA)	>100000	-
(+/-)3,4-Methylenedioxymethamphetamine(MDMA)	5000	10%
β-Phenylethylamine	>100000	-
Trimethobenzamide	>100000	-
d,l-Amphetamine	>100000	-
Mephetermine	25000	2%
(1R,2S)-(-)-Ephedrine	50000	1%
l-phenylephrine	50000	1%
L-Methamphetamine	50000	1%

TCA 1000(Nortriptyline, Cutoff=1000ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
Nordoxepine	10000	10%
Trimipramine	20000	5%
Amitriptyline	1250	80%
Promazine	>100000	-
Desipramine	3000	33.33%
Imipramine	1000	100%
Clomipramine	40000	2.5%

{23}------------------------------------------------

Doxepin	5000	20%
Maprotiline	100000	1%
Promethazine	>100000	-
Cyclobenzaprine	10000	10%
Norclomipramine	12500	8%

COC 300(Benzoylecgonine, Cutoff=300ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
Cocaine	1000	30%
Cocaethylene	12500	2.4%
Ecgonine	50000	0.6%
Ecgonine methyl ester	>100000	-
Norcocaine	>100000	-

AMP 1000(d-Amphetamine, Cutoff=1000ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
l-Amphetamine	1000	100%
dl- Amphetamine	1000	100%
(+/-)3,4-Methylenedioxyamphetamine (MDA)	2000	50%
Phentermine	10000	10%
Hydroxyamphetamine	>100000	-
d-Methamphetamine	>100000	-
l-Methamphetamine	>100000	-
(+/-)3,4-Methylenedioxyethylamphetamine(MDE)	>100000	-
(+/-)3,4-Methylenedioxymethamphetamine(MDMA)	>100000	-
β-Phenylethylamine	100000	1%
Tyramine	100000	1%
p-Hydroxynorephedrine	100000	1%
Phenylpropanolamine	>100000	-
(±)Phenylpropanolamine	>100000	-
p-Hydroxyamphetamine	100000	1%
d/l-Norephedrine	>100000	-
Benzphetamine	>100000	-
l-Ephedrine	100000	1%
l-Epinephrine	>100000	-
d/l-Epinephrine	>100000	-

{24}------------------------------------------------

MET 1000(D(+)-Methamphetamine, Cutoff=1000ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
(+/-)3,4-Methylenedioxy-n-ethylamphetamine(MDE)	50000	2%
D/L-Methamphetamine	1000	100%
p-Hydroxymethamphetamine	25000	4%
D-Amphetamine	>100000	-
L-Amphetamine	>100000	-
Chloroquine	50000	2%
(+/-)-Ephedrine	50000	2%
(-)-Methamphetamine	50000	2%
(+/-)3,4-Methylenedioxyamphetamine (MDA)	>100000	-
(+/-)3,4-Methylenedioxymethamphetamine(MDMA)	8000	12.5%
β-Phenylethylamine	>100000	-
Trimethobenzamide	>100000	-
d,l-Amphetamine	>100000	-
Mephetermine	50000	2%
(1R,2S)-(-)-Ephedrine	>100000	-
1-phenylephrine	>100000	-
L-Methamphetamine	100000	1%

OPI 2000(Morphine, Cutoff=2000ng/mL)	Minimum concentrationrequired to obtain apositive result (ng/mL)	% Cross-Reactivity
Normorphine	>100000	-
Codeine	5000	40%
s-Monoacetylmorphine	2000	100%
Ethyl Morphine	10000	20%
Heroin	>100000	-
Hydrocodone	25000	8%
Hydromorphone	25000	8%
Morphinie-3-β-d-glucuronide	2000	100%
Oxycodone	>100000	-
Oxymorphone	>100000	-
Thebaine	>100000	-
Levorphanol	50000	4%
6-Monoacetylmorphine (6-MAM)	25000	8%
Norcodeine	>100000	-
Procaine	>100000	-

{25}------------------------------------------------

f. Effect of Urine Specific Gravity and Urine pH
To investigate the effect of urine specific gravity, urine samples with specific gravity from 1.000 to 1.035 were spiked with target drugs at +25% cutoff and -25% cutoff levels. Three Operators tested each sample using test devices from three different lots. The results were all positive for samples at +25% cutoff and all negative for samples at -25% cutoff, indicating that urine specific gravity between 1.000 and 1.035 has no effect on the accuracy and precision of the test device.

To investigate the effect of urine pH, urine samples with pH value from 4 to 9 were spiked with target drugs at +25% cutoff and -25% cutoff levels. Three Operators tested each sample using test devices from three different lots. The results were all positive for samples at +25% cutoff and all negative for samples at -25% cutoff, indicating that urine pH value between 4.0 and 9.0 has no effect on the accuracy and precision of the test device.

1. Comparison Studies
  The method comparison studies for Hightop® Multi-Drug Urine Test Cup were performed in-house with three operators.

Operators ran 80 (40 negative and 40 positive) unaltered urine samples were blind labeled and compared to LC/MS results. The results are presented in the table below:

For Hightop® Multi-Drug Urine Test Cup:

Hightop® Cup		Drug-Free	Low Negative by LC/MS (less than -50%)	Near Cutoff Negative by LC/MS (Between -50% and the Cutoff)	Near Cutoff Positive by LC/MS (Between the cutoff and +50%)	High Positive by LC/MS (greater than +50%)
Operator A	Positive	0	0	1	18	22
A	Negative	8	16	15	0	0
Operator B	Positive	0	0	2	18	22
B	Negative	8	16	14	0	0
Operator C	Positive	0	0	2	18	22
C	Negative	8	16	14	0	0

AMP 500

Discordant Results for AMP 500:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator A	00013426	476.193	+
Operator B	00013400	484.179	+
Operator B	00013096	489.928	+
Operator C	00013426	476.193	+
Operator A	00013096	489.928	+

{26}------------------------------------------------

BUP	10
-----	----

Hightop®Cup		Drug-Free	LowNegative byLC/MS (lessthan -50%)	Near CutoffNegative byLC/MS(Between -50%and the Cutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	High Positiveby LC/MS(greater than+50%)
OperatorA	Positive	0	0	1	18	21
	Negative	8	15	16	1	0
OperatorB	Positive	0	0	2	19	21
	Negative	8	15	15	0	0
OperatorC	Positive	0	0	0	19	21
	Negative	8	15	17	0	0

Discordant Results for BUP 10:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator A	1035421349	12.071	-
Operator A	1035423433	8.613	+
Operator B	1035423433	8.613	+
Operator B	1035422023	9.159	+

BAR 300

Hightop®Cup		Drug-Free	Low Negative byLC/MS (lessthan -50%)	Near CutoffNegative byLC/MS(Between -50%and the Cutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	High Positiveby LC/MS(greater than+50%)
OperatorA	Positive	0	0	1	19	20
OperatorA	Negative	8	16	15	1	0
OperatorB	Positive	0	0	1	20	20
OperatorB	Negative	8	16	15	0	0
OperatorC	Positive	0	0	1	18	20
OperatorC	Negative	8	16	15	2	0

Discordant Results for BAR 300:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator A	1035421235	252.898	+
Operator B	1035421036	257.522	+
Operator C	1035421142	254.749	+

{27}------------------------------------------------

Operator A	1035420985	307.065	-
Operator C	1035420985	307.065	-
Operator C	1035422170	316.751	-

BZO 300

Hightop®Cup		Drug-Free	LowNegative byLC/MS (lessthan -50%)	Near CutoffNegative byLC/MS(Between -50%and the Cutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	High Positiveby LC/MS(greater than+50%)
Operator	Positive	0	0	1	16	23
A	Negative	8	16	15	1	0
Operator	Positive	0	0	1	16	23
B	Negative	8	16	15	1	0
Operator	Positive	0	0	3	16	23
C	Negative	8	16	13	1	0

Discordant Results for BZO 300:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator A	1035422739	291.117	+
Operator B	1035422739	291.117	+
Operator C	1035422739	291.117	+
Operator C	1035422210	267.676	+
Operator C	1035422651	290.721	+
Operator A	1035422395	301.084	-
Operator B	1035422395	301.084	-
Operator C	1035422395	301.084	-

COC 150

Hightop®Cup		Drug-Free	LowNegative byLC/MS(less than -50%)	Near CutoffNegative byLC/MS(Between -50% and theCutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	HighPositive byLC/MS(greaterthan +50%)
Operator A	Positive	0	0	1	16	24
	Negative	8	16	15	0	0
Operator B	Positive	0	0	0	16	24
	Negative	8	16	16	0	0
Operator C	Positive	0	0	1	16	24
	Negative	8	16	15	0	0

{28}------------------------------------------------

Discordant Results for COC 150:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator A	00012562	132.433	+
Operator C	00012562	132.433	+

EDDP 300

Hightop®Cup		Drug-Free	LowNegative byLC/MS (lessthan -50%)	Near CutoffNegative byLC/MS(Between -50% and theCutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	High Positiveby LC/MS(greater than+50%)
Operator A	Positive	0	0	1	21	19
	Negative	8	16	16	0	0
Operator B	Positive	0	0	1	21	19
	Negative	8	16	16	0	0
Operator C	Positive	0	0	0	21	19
	Negative	8	16	17	0	0

Discordant Results for EDDP 300:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator A	00011835	284.508	+
Operator B	00011900	285.830	+

MET 500

Hightop®Cup
		Drug-Free	LowNegative byLC/MS (lessthan -50%)	Near CutoffNegative byLC/MS(Between -50%and the Cutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	High Positiveby LC/MS(greater than+50%)
Operator	Positive	0	0	2	19	21
A	Negative	8	14	16	0	0
Operator	Positive	0	0	0	19	21
B	Negative	8	14	18	0	0
Operator	Positive	0	0	1	19	21
C	Negative	8	14	17	0	0

Discordant Results for MET 500:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator A	00012486	467.910	+
Operator A	00012066	491.588	+
Operator C	00012486	467.910	+

MDMA 500

{29}------------------------------------------------

Hightop® Cup		Drug-Free	Low Negative by LC/MS (less than -50%)	Near Cutoff Negative by LC/MS (Between -50% and the Cutoff)	Near Cutoff Positive by LC/MS (Between the cutoff and +50%)	High Positive by LC/MS (greater than +50%)
Operator A	Positive	0	0	1	22	18
	Negative	8	16	15	0	0
Operator B	Positive	0	0	1	22	18
	Negative	8	16	15	0	0
Operator C	Positive	0	0	0	21	18
	Negative	8	16	16	1	0

Discordant Results for MDMA 500:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator A	00010229	492.926	+
Operator B	00010229	492.926	+
Operator C	00009611	508.877	-

MOP 300

Hightop®Cup		Drug-Free	LowNegative byLC/MS (lessthan -50%)	Near CutoffNegative byLC/MS(Between -50%and the Cutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	High Positiveby LC/MS(greater than+50%)
Operator	Positive	0	0	0	21	19
A	Negative	8	14	18	0	0
Operator	Positive	0	0	0	21	19
B	Negative	8	14	18	0	0
Operator	Positive	0	0	1	21	19
C	Negative	8	14	17	0	0

Discordant Results for MOP 300:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator C	00011769	296.790	+

MTD 300

Hightop®Cup	Drug-Free	LowNegative by	Near CutoffNegative byLC/MS	Near CutoffPositive byLC/MS	High Positiveby LC/MS
-----------------	-----------	--------------------	-------------------------------------	-------------------------------------	---------------------------

{30}------------------------------------------------

			LC/MS (lessthan -50%)	(Between -50%and the Cutoff)	(Between thecutoff and+50%)	(greater than+50%)
Operator	Positive	0	0	0	18	20
A	Negative	8	17	15	2	0
Operator	Positive	0	0	2	20	20
B	Negative	8	17	13	0	0
Operator	Positive	0	0	0	20	20
C	Negative	8	17	15	0	0

Discordant Results for MTD 300:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator B	00012658	287.804	+
Operator B	00011740	296.375	+
Operator A	00011815	327.246	-
Operator A	00012146	341.195	-

OXY 100

Hightop® Cup		Drug-Free	Low Negative by LC/MS (less than -50%)	Near Cutoff Negative by LC/MS (Between -50% and the Cutoff)	Near Cutoff Positive by LC/MS (Between the cutoff and +50%)	High Positive by LC/MS (greater than +50%)
Operator A	Positive	0	0	2	20	20
Operator A	Negative	8	16	14	0	0
Operator B	Positive	0	0	1	20	20
Operator B	Negative	8	16	15	0	0
Operator C	Positive	0	0	2	19	20
Operator C	Negative	8	16	14	1	0

Discordant Results for OXY 100:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator A	00013642	96.266	+
Operator C	00013741	97.870	+
Operator A	00013878	99.691	+
Operator B	00013878	99.691	+
Operator C	00013878	99.691	+
Operator C	00012547	100.512	-

PCP 25

Hightop®Cup	Drug-Free	LowNegative by	Near CutoffNegative byLC/MS	Near CutoffPositive byLC/MS	High Positiveby LC/MS
-----------------	-----------	--------------------	-------------------------------------	-------------------------------------	---------------------------

{31}------------------------------------------------

		LC/MS (lessthan -50%)	(Between -50%and the Cutoff)	(Between thecutoff and+50%)	(greater than+50%)
Operator	Positive	0	0	1	17	20
A	Negative	8	16	15	3	0
Operator	Positive	0	0	0	20	20
B	Negative	8	16	16	0	0
Operator	Positive	0	0	0	18	20
C	Negative	8	16	16	2	0

Discordant Results for PCP 25:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator A	00009369	21.999	+
Operator A	00008179	27.262	-
Operator A	00008152	27.660	-
Operator C	00008152	27.660	-
Operator A	00012809	27.671	-
Operator C	00012809	27.671	-

PPX 300

Hightop®Cup		Drug-Free	LowNegative byLC/MS (lessthan -50%)	Near CutoffNegative byLC/MS(Between -50%and the Cutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	High Positiveby LC/MS(greater than+50%)
OperatorA	Positive	0	0	0	14	24
	Negative	8	16	16	2	0
OperatorB	Positive	0	0	1	16	24
	Negative	8	16	15	0	0
OperatorC	Positive	0	0	2	16	24
	Negative	8	16	14	0	0

Discordant Results for PPX 300:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator C	00009392	289.027	+
Operator B	00013736	299.806	+
Operator C	00013736	299.806	+
Operator A	00007439	308.846	-
Operator A	00010214	325.332	-

{32}------------------------------------------------

TCA 1000

Hightop®Cup		Drug-Free	LowNegative byLC/MS (lessthan -50%)	Near CutoffNegative byLC/MS(Between -50%and the Cutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	High Positiveby LC/MS(greater than+50%)
OperatorA	Positive	0	0	0	17	21
	Negative	8	17	15	2	0
OperatorB	Positive	0	0	0	16	21
	Negative	8	17	15	3	0
OperatorC	Positive	0	0	0	19	21
	Negative	8	17	15	0	0

Discordant Results for TCA 1000:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator A	00012850	1001.210	-
Operator A	00013628	1009.815	-
Operator B	00012850	1001.210	-
Operator B	00013628	1009.815	-
Operator B	00011935	1015.492	-

THC 50

Hightop®Cup		Drug-Free	LowNegative byLC/MS (lessthan -50%)	Near CutoffNegative byLC/MS(Between -50%and the Cutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	High Positiveby LC/MS(greater than+50%)
Operator	Positive	0	0	2	21	19
A	Negative	8	16	14	0	0
Operator	Positive	0	0	0	19	19
B	Negative	8	16	16	2	0
Operator	Positive	0	0	2	21	19
C	Negative	8	16	14	0	0

Discordant Results for THC 50:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator A	1035422469	40.426	+
Operator C	1035422620	42.267	+
Operator C	1035423426	49.136	+
Operator A	1035423426	49.136	+

{33}------------------------------------------------

Operator B	1035423067	50.150	-
Operator B	1035421602	50.970	-

AMP 1000

Hightop®Cup		Drug-Free	LowNegative byLC/MS (lessthan -50%)	Near CutoffNegative byLC/MS(Between -50%and the Cutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	High Positiveby LC/MS(greater than+50%)
Operator	Positive	0	0	0	16	21
A	Negative	8	17	15	3	0
Operator	Positive	0	0	0	18	21
B	Negative	8	17	15	1	0
Operator	Positive	0	0	1	16	21
C	Negative	8	17	14	3	0

Discordant Results for AMP 1000:

Operator	Sample Number	LC/MS Result (ng/mL)	Hightop Result
Operator C	00013637	967.618	+
Operator A	00013639	1001.742	-
Operator C	00013639	1001.742	-
Operator A	00011718	1008.830	-
Operator B	00011718	1008.830	-
Operator C	00011718	1008.830	-
Operator A	00013437	1009.916	-
Operator C	00013437	1009.916	-

COC 300

Hightop®Cup		Drug-Free	Low Negative byLC/MS (lessthan -50%)	Near CutoffNegative byLC/MS(Between -50%and the Cutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	High Positiveby LC/MS(greater than+50%)
OperatorA	Positive	0	0	2	19	21
	Negative	8	17	13	0	0
OperatorB	Positive	0	0	2	19	21
	Negative	8	17	13	0	0
OperatorC	Positive	0	0	1	19	21
	Negative	8	17	14	0	0

Discordant Results for COC 300:

{34}------------------------------------------------

Operator	Sample Number	LC/MS Result	Hightop Result
Operator A	00012552	267.123	+
Operator B	00012552	267.123	+
Operator A	00012542	274.118	+
Operator B	00011814	283.062	+
Operator C	00011814	283.062	+

MET 1000

Hightop®Cup		Drug-Free	LowNegative byLC/MS (lessthan -50%)	Near CutoffNegative byLC/MS(Between -50%and the Cutoff)	Near CutoffPositive byLC/MS(Between thecutoff and+50%)	High Positiveby LC/MS(greater than+50%)
Operator	Positive	0	0	0	20	18
A	Negative	8	17	15	2	0
Operator	Positive	0	0	0	22	18
B	Negative	8	17	15	0	0
Operator	Positive	0	0	0	21	18
C	Negative	8	17	15	1	0

Discordant Results for MET 1000:

Operator	Sample Number	LC/MS Result	Hightop Result
Operator A	00013726	1037.600	-
Operator A	00012643	1041.167	-
Operator C	00012643	1041.167	-

OPI 2000

Hightop®Cup		Drug-Free	LowNegative byLC/MS (lessthan -50%)	Near CutoffNegative byLC/MS(Between -50%and the Cutoff)	Near CutoffPositive byLC/MS(Between thecutoff and +50%)	High Positiveby LC/MS(greater than+50%)
Operator	Positive	0	0	0	18	20
A	Negative	8	17	15	2	0
Operator	Positive	0	0	0	20	20
B	Negative	8	17	15	0	0
Operator	Positive	0	0	0	18	20
C	Negative	8	17	15	2	0

Discordant Results for OPI 2000:

Operator	Sample Number	LC/MS Result	Hightop Result
Operator A	00007823	2000.404	-

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Operator A	00013647	2007.513	-
Operator C	00007823	2000.404	-
Operator C	00013647	2007.513	-

Lay-user study:

A lay user study was performed using urine samples prepared at the following concentrations; -100%, +/-75%, +/-50%, +/-25% of the cutoff by spiking drug(s) into drug free-pooled urine specimens. The concentrations of the samples were confirmed by LC/MS or LC/MS. Each sample was aliquoted into individual containers and blind-labeled. A total of 280 participants with diverse educational and professional backgrounds aged 20 years and older were recruited from three sites. Seventy-two males and 68 females tested Hightop® Multi-Drug Urine Test Cup Configuration 1 (including AMP 500, MET 500, MOP 300, COC 150); 71 male and 69 females tested Hightop® Multi-Drug Urine Test Cup Configuration 2 (including AMP 1000, MET 1000, MOP 2000 (OPI), COC 300). Each participant was provided one package insert, one blind labeled test solution, and one test device. The results are summarized below:

Lay-User Study Results for Hightop® Multi-Drug Urine Test Cup Configuration 1 (including AMP 500, MET 500, MOP 300, COC 150):

Assay	Results	Concentration
		-100%cutoff	-75%cutoff	-50%cutoff	-25%cutoff	+25%cutoff	+50%cutoff	+75%cutoff
	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
AMP 500	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
	Negative	20	20	20	19	1	0	0
	Positive	0	0	0	1	19	20	20
BAR 300	Total	20	20	20	20	20	20	20
	Percentage of
	correct results (%)	100%	100%	100%	95%	95%	100%	100%
	Negative	20	20	20	19	1	0	0
	Positive	0	0	0	1	19	20	20
BZO 300	Total	20	20	20	20	20	20	20
	Percentage of
	correct results (%)	100%	100%	100%	95%	95%	100%	100%
	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
BUP 10	Total	20	20	20	20	20	20	20
	Percentage of
	correct results (%)	100%	100%	100%	100%	100%	100%	100%

COC 150	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
EDDP 300	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
MDMA 500	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
MET 500	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
MOP 300	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
MTD 300	Negative	20	20	20	18	0	0	0
	Positive	0	0	0	2	20	20	20
	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	90%	100%	100%	100%
OXY 100	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
PCP 25	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
PPX 300	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20

	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
TCA 1000	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
	Negative	20	20	20	20	0	0	0
THC 50	Positive	0	0	0	0	20	20	20
	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%

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Lay-User Study Results for Hightop® Multi-Drug Urine Test Cup Configuration 2 (AMP 1000, MET 1000, MOP 2000 (OPI), COC 300):

Assay	Results	Concentration
		-100%cutoff	-75%cutoff	-50%cutoff	-25%cutoff	+25%cutoff	+50%cutoff	+75%cutoff
	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
AMP 1000	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
	Negative	20	20	20	19	1	0	0
	Positive	0	0	0	1	19	20	20
BAR 300	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	95%	95%	100%	100%
	Negative	20	20	20	19	0	0	0
	Positive	0	0	0	1	20	20	20
BZO 300	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	95%	100%	100%	100%
	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
BUP 10	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
	Negative	20	20	20	19	1	0	0
	Positive	0	0	0	1	19	20	20
COC 300	Total	20	20	20	20	20	20	20
	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	95%	95%	100%	100%
	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
EDDP 300	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
MDMA 500	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
MET 1000	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
OPI 2000	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
	Negative	20	20	20	19	1	0	0
	Positive	0	0	0	1	19	20	20
MTD 300	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	95%	95%	100%	100%
	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
OXY 100	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
PCP 25	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
	Negative	20	20	20	20	0	0	0
PPX 300	Positive	0	0	0	0	20	20	20
	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
TCA 1000	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%
THC 50	Negative	20	20	20	20	0	0	0
	Positive	0	0	0	0	20	20	20
	Total	20	20	20	20	20	20	20
	Percentage ofcorrect results (%)	100%	100%	100%	100%	100%	100%	100%

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Participants were given surveys on the ease of understanding the instruction for use. All participants indicated that the device instruction is easy to understand and follow. A Flesch-Kincaid reading analysis was performed on each package insert and the scores revealed a reading Grade Level of 7.

Clinical Studies:

Not applicable.

12. Conclusion

Based on the test principle and performance characteristics of the device including precision, cut-off, interference, specificity, method comparison and lay-user studies of the devices, it's concluded that Hightop® Multi-Drug Urine Test Cup and Hightop® Multi-Drug Urine Test Cup Rx are substantially equivalent to the predicate devices.

Regulation Number and Section

§ 862.3100 Amphetamine test system.

(a)
Identification. An amphetamine test system is a device intended to measure amphetamine, a central nervous system stimulating drug, in plasma and urine. Measurements obtained by this device are used in the diagnosis and treatment of amphetamine use or overdose and in monitoring levels of amphetamine to ensure appropriate therapy.(b)
Classification. Class II (special controls). An amphetamine test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).