BIO-VENTURE Rapid Multi-Drug Test Easy Cup for OTC Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for OTC Use is a rapid lateral flow immunoassay for the qualitative detection of d-Amphetamine, Oxazepan, Benzoylecgonine, d-Methamphetamine, Morphine and Delta-9-THC-COOH in human urine. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry 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 test is intended for over the counter use.

BIO-VENTURE Rapid Multi-Drug Test Easy Cup for Rx Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for Rx Use is a rapid lateral flow immunoasay for the qualitative detection of d-Amphetamine, Oxazepam, Benzoylecgonine, d-Methamphetamine, Morphine and Delta-9-THC-COOH in human urine. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry 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 test is intended for prescription use.

Device Description

BIO-VENTURE Rapid Multi-Drug Test Easy Cup for OTC Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for OTC Use, BIO-VENTURE Rapid Multi-Drug Test Easy Cup for Rx Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for Rx Use is immunochromatographic assays that use a lateral flow system for the qualitative detection of d-Amphetamine, Oxazepam, Benzoylecgonine, d-Methamphetamine, Morphine and 11-Nor-A9-Tetrahydrocannabinol-9-COOH (target analytes) in human urine. 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.

AI/ML Overview

It seems you're asking for a structured summary of the acceptance criteria and study results for the "BIO-VENTURE Rapid Multi-Drug Test Easy Cup" and "Split Key Cup" devices, based on the provided FDA 510(k) summary.

Please note that this document describes a qualitative diagnostic test, not an AI-powered device or an imaging system. Therefore, some of your requested points related to AI/MRMC studies, expert readers, and ground truth establishment for complex image analysis are not applicable to this type of device. I will address only the relevant information from the provided text.

Here's the breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided FDA 510(k) summary:

Acceptance Criteria and Device Performance for BIO-VENTURE Rapid Multi-Drug Test Easy Cup / Split Key Cup

Device Description:
The BIO-VENTURE Rapid Multi-Drug Test Easy Cup and Split Key Cup are rapid lateral flow immunoassays for the qualitative detection of specific drugs (d-Amphetamine, Oxazepam, Benzoylecgonine, d-Methamphetamine, Morphine, and Delta-9-THC-COOH) in human urine. They provide preliminary test results, and a confirmatory chemical method (e.g., GC/MS) is required for confirmed analytical results.

1. Table of Acceptance Criteria and Reported Device Performance

The document presents performance data through precision studies, specificity studies, interference studies, effect of urine specific gravity and pH studies, and comparison to GC/MS studies (clinical samples), as well as a lay-user study.

Acceptance Criteria (Implicit from Study Design and Passed Results):
The acceptance criteria are implicitly defined by the successful demonstration of the device's ability to consistently provide correct qualitative results (positive or negative) within specified concentration ranges relative to the cut-off levels, when compared to a gold standard (GC/MS) and under various testing conditions. For precision, a high concordance rate around the cut-off is expected. For linearity, showing all positive above +25% cut-off and all negative below -25% cut-off. For interference and specificity, showing no false positives or negatives due to common interfering substances or closely related compounds (unless cross-reactivity is expected and quantified). For lay-user studies, a high percentage of correct results by untrained users.

Reported Device Performance (Key Findings from Studies):

Precision Studies (Analytical Performance):

Sample Concentrations: -100%, -75%, -50%, -25%, Cut off, +25%, +50%, +75%, +100% of cut-off.
Method: Samples prepared by spiking drug in negative urine, confirmed by GC/MS. Blindly labeled.
Results (Summary across all drugs and both cup types):
- Amphetamine, Cocaine, Oxazepam, Methamphetamine, Morphine, THC:
  - All samples concentrated at or below -25% cut-off consistently showed Negative results (e.g., typically 50-/0+ for all concentrations from -100% to -25%).
  - All samples concentrated at or above +25% cut-off consistently showed Positive results (e.g., typically 50+/0- for all concentrations from +25% to +100%).
  - Samples at the cut-off concentration showed a mix of positive and negative results, which is expected for a qualitative immunoassay at its detection threshold (e.g., for AMP Split Key Cup, Cut off: 22-/28+ to 25-/25+ across batches, meaning 22-25 negative and 25-28 positive out of 50 samples). This demonstrates the device's ability to discriminate around the cut-off.

Linearity (Analytical Performance):

Results: "Not applicable" in the document, as it's a qualitative test. However, the Cut-off verification study (5.8.1.d) serves a similar purpose.
Cut-off Verification: A total of 375 samples per device type (Easy Cup, Split Key Cup) across -50%, -25%, Cut-Off, +25%, +50% concentrations.
- Results: "Results were all positive at and above +25% Cut-off and all negative at and below -25% Cut-off for Amphetamine, Cocaine, Oxazepam, Methamphetamine, Morphine and Marijuana." This verifies the device's threshold performance.

Stability:

Result: Stable at 2-30 ℃ for 24 months based on real-time stability.

Interference and Specificity (Analytical Performance):

Interference: Various physiological/pathological substances (e.g., Naltrexone, Aspirin, Bilirubin, Ethanol) were tested at high concentrations (100 µg/mL or 1% for Ethanol) in drug-free urine and urine spiked at +/- 25% of cut-off.
- Result: "Compounds that showed no interference at a concentration of 100µg/mL and Ethanol at 1% are summarized in the following tables." The tables list numerous compounds that did not interfere, indicating good specificity against common physiological/pharmaceutical substances.
Specificity (Cross-Reactivity): Related drug metabolites and other components were tested.
- Result: Tables provided the lowest concentration causing a positive result and the % cross-reactivity for various substances (e.g., for Amphetamine, D/L-Amphetamine showed 66.7% cross-reactivity at 1500ng/mL; MDMA shows <1% cross-reactivity at >100,000 ng/mL). This quantifies how other substances react with the test and confirms appropriate specific binding.

Effect of Urine Specific Gravity and Urine pH (Analytical Performance):

Method: Urine samples with SG 1.002-1.036 or pH 4-9 spiked at +/- 25% of cut-off.
Result: "Results were all positive for samples at and above +25% Cutoff and all negative for samples at and below -25% Cut-Off. There were no differences observed for different devices." This confirms robust performance across a range of physiological urine conditions.

2. Sample Sizes and Data Provenance

Training Set: The document does not explicitly state a separate "training set" in the context of machine learning, as this is a traditional immunoassay device. The analytical and comparison studies effectively serve as the validation of the device's performance characteristics.
Test Set (Analytical Performance - Precision):
- Sample Size: Each drug concentration (9 levels per drug) for 3 lots, tested by 6 operators, with 9 samples per operator per day for 25 days. This results in: 9 concentrations * 3 lots * 6 operators * 9 samples/operator/day * 25 days = 36,450 individual test results for each drug (AMP, COC, OXA, MET, MOP, THC) across all precision studies.
- Data Provenance: Samples were "prepared by spiking drug in negative samples" and confirmed by GC/MS. This suggests controlled laboratory conditions. The document is for a Chinese manufacturer (Shanghai Venture Bio-Tech Co., Ltd.), so the studies were likely conducted in China or a related territory, but this is not explicitly stated. It's a prospective study as samples were prepared and tested to evaluate device precision.
Test Set (Clinical Comparison Study):
- Sample Size:
  - Amphetamine: 87 samples
  - Cocaine: 80 samples
  - Oxazepam: 80 samples
  - Methamphetamine: 81 samples
  - Morphine: 81 samples
  - Marijuana: 82 samples
- Data Provenance: "unalred clinical samples" tested "in-house." The specific country of origin for these clinical samples is not stated, but given the manufacturer, it's likely China. This is a retrospective study in the sense that existing clinical samples were tested.
Test Set (Lay-User Study):
- Sample Size: 20 samples per concentration level (-100%, -75%, -50%, -25%, +25%, +50%, +75% of cut-off) for each of the 6 drugs and each cup format (Easy Cup, Split Key Cup). Total samples: 7 concentration levels * 20 samples/level = 140 samples per drug per cup type. Multiplying by 6 drugs and 2 cup types gives 1,680 total tests by lay users. Each participant was provided with 1 blind labeled sample and a device.
- Data Provenance: Samples "prepared at the following concentrations... by spiking drug(s) into drug free-pooled urine specimens." Confirmed by GC/MS. The "lay users" were diverse in background and age, but their geographic location is not specified beyond "three intended user sites" which likely refers to testing locations rather than sample origin. This is a prospective study.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Their Qualifications

Ground Truth Method: The primary ground truth for the analytical and clinical comparison studies was Gas Chromatography/Mass Spectrometry (GC/MS). GC/MS is a highly accurate and established analytical method used in toxicology for confirmed analytical results of drug concentrations.
Experts for GC/MS: The document does not specify the number or qualifications of experts operating the GC/MS. GC/MS testing typically requires trained laboratory professionals, but they are not "experts" in the sense of clinical interpretation as in imaging studies. Their expertise lies in analytical chemistry and operating the GC/MS equipment according to established protocols.
Experts for Device Studies: The clinical comparison studies were performed "in-house with three laboratory assistants for each device." These assistants performed the device testing, but the ground truth was GC/MS. For the lay-user study, the results were compared against GC/MS concentrations.

4. Adjudication Method for the Test Set

For Lab-based (Precision & Clinical Comparison): The results of the rapid test were compared directly to the quantitative GC/MS results. Discordant results are explicitly listed and discussed. There's no specific "adjudication method" among human readers mentioned, as this is a chemical test, not subjective interpretation.
For Lay-User Study: The lay users performed the test, and their qualitative results were compared against the GC/MS quantitative concentration data. There was no adjudication mentioned for the lay-user results themselves; rather, their output (positive/negative) was assessed for correctness against the GC/MS reference.

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

No, an MRMC comparative effectiveness study was not done. This type of study is specifically relevant for imaging devices where human readers interpret medical images, and the AI assists or performs this interpretation. This document describes a qualitative immunoassay (drug test), which does not involve human readers interpreting complex cases in the same way. The studies focused on the analytical performance of the device itself and its accuracy against a chemical gold standard (GC/MS).

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

Yes, in essence, the analytical performance and comparison studies represent the "standalone" performance of the device.

The device itself provides a qualitative result (visible line or no line).
The precision studies, cut-off verification, interference, and specificity sections evaluate the device's performance in a controlled lab setting, without human interpretation variability being the primary focus (though lab assistants operated the device).
The comparison study also evaluates the device's direct output (positive/negative) against GC/MS, effectively assessing its standalone accuracy.
The lay-user study assesses how accurately untrained individuals can use and interpret the device, which is different from "human-in-the-loop" in an AI diagnostic context.

7. The Type of Ground Truth Used

The primary ground truth used for all performance evaluations (precision, linearity/cut-off, clinical comparison, lay-user study) was Gas Chromatography/Mass Spectrometry (GC/MS). For an immunoassay, GC/MS provides a highly accurate and quantitative measurement of the target drug concentration, which serves as the definitive reference for determining whether a sample is truly positive or negative relative to a defined cut-off.

8. The Sample Size for the Training Set

As mentioned, this document does not describe an AI/machine learning device. Therefore, a distinct "training set" in the machine learning sense is not applicable. The development and optimization of the immunoassay itself would have involved numerous experiments and iterations (e.g., antibody selection, membrane optimization), but these are part of the device's manufacturing process, not a data-driven training phase for an algorithm.

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

Since there is no "training set" in the context of an AI algorithm, this point is not applicable. The device's "ground truth" for development and validation was established by using precisely prepared samples with known drug concentrations, confirmed by GC/MS.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there is a seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" surrounding a graphic. To the right of the seal, there is a blue square with the letters "FDA" in white. Next to the blue square, the words "U.S. FOOD & DRUG ADMINISTRATION" are written in blue.

December 14, 2018

SHANGHAI VENTURE BIO-TECH CO., LTD. % Ethan Liu, RA Specialist Shanghai Thinkwell Consulting Co., Ltd. Floor 6. No.211. Xin Ling Road. Minhang District Shanghai, 201100 China

Re: K180879

Trade/Device Name: BIO-VENTURE Rapid Multi-Drug Test Easy Cup for OTC Use BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for OTC Use BIO-VENTURE Rapid Multi-Drug Test Easy Cup for Rx Use BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for Rx Use Regulation Number: 21 CFR 862.3100 Regulation Name: Amphetamine test system Regulatory Class: Class II Product Code: DKZ, JXM, NFT, DIO, NFY, NFV, DJC, NGG, DNK, NGL, LDJ, NFW Dated: October 30, 2018 Received: November 5, 2018

Dear Ethan Liu:

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

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

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

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

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

Sincerely,

Kellie B. Kelm -S

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

Enclosure

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Indications for Use

510(k) Number (if known)

K180879

Device Name

BIO-VENTURE Rapid Multi-Drug Test Easy Cup for OTC Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for OTC Use

Indications for Use (Describe)

Test	Calibrators	Cut-off Level
Amphetamine (AMP)	d-Amphetamine	1000ng/ml
Oxazepam	Oxazepam	300ng/ml
Cocaine (COC)	Benzoylecgonine	300ng/ml
Methamphetamine (MET)	d-Methamphetamine	1000ng/ml
Morphine(MOP)	Morphine	300ng/ml
Marijuana (THC)	Delta-9-THC-COOH	50ng/ml

Easy cup test and Split Key Cup test may be configured as single drug tests or multiple drug tests in any combination of the drug analytes listed in the table above up to a maximum of 6 analytes.

The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry 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 test is intended for over the counter use.

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.

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.

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:

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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Indications for Use

510(k) Number (if known) K180879

Device Name

BIO-VENTURE Rapid Multi-Drug Test Easy Cup for Rx Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for Rx Use

Indications for Use (Describe)

Test	Calibrators	Cut-off Level
Amphetamine (AMP)	d-Amphetamine	1000ng/ml
Oxazepam	Oxazepam	300ng/ml
Cocaine (COC)	Benzoylecgonine	300ng/ml
Methamphetamine (MET)	d-Methamphetamine	1000ng/ml
Morphine(MOP)	Morphine	300ng/ml
Marijuana (THC)	Delta-9-THC-COOH	50ng/ml

Easy cup test and split key cup test may be configured as single drug tests in any combination of the drug analytes listed in the table above up to a maximum of 6 analytes.

For in vitro diagnostic use only. The test is intended for prescription use.

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.

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

K180879

This summary of 510(k) safety and effectiveness information is being submitted in accordance with requirements of 21 CFR Part 807.92.

5.1 Submitter

Submitted by:	SHANGHAI VENTURE BIO-TECH Co., Ltd.Room 313, Building 2, No. 2715 Longwu Road.Xuhui District, Shanghai, China.
Contact Person:	Ethan Liu
	Phone: 0086-15216699240
	Fax: 0086-21-60732022
	Email: xtdeepwater@126.com
Date Prepared:	Dec 14, 2018

5.2 Device

5.2.1 Trade name

BIO-VENTURE Rapid Multi-Drug Test Easy Cup for OTC Use BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for OTC Use BIO-VENTURE Rapid Multi-Drug Test Easy Cup for Rx Use BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for Rx Use

5.2.2 Classification

Product Code	CFR #	Panel
--------------	-------	-------

5-1

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DKZ, NFT	21 CFR,	862.3100	ToxicologyAmphetamine Test System
JXM, NFV	21 CFR,	862.3170	ToxicologyBenzodiazepine TestSystem
DIO, NFY	21 CFR,	862.3250	ToxicologyCocaine and cocaine metabolite testsystem.
DJC, NGG	21 CFR,	862.3610	ToxicologyMethamphetamine TestSystem
LDJ, NFW	21 CFR,	862.3870	ToxicologyCannabinoid Test System
DNK, NGI	21 CFR,	862.3640	ToxicologyMorphine test system

5.3 Predicate Device

K173303

INSTANT-VIEW plus Multi-Drug of Abuse Urine Test - Simple Cup (OTC Use)

INSTANT-VIEW plus Multi-Drug Urine Test - Simple Cup (Prescription Use)

5.4 Device Description

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5.5 Indication for Use

Test	Calibrators	Cut-off Level
Amphetamine (AMP)	d-Amphetamine	1000ng/ml
Oxazepam	Oxazepam	300ng/ml
Cocaine (COC)	Benzoylecgonine	300ng/ml
Methamphetamine (MET)	d-Methamphetamine	1000ng/ml
Morphine(MOP)	Morphine	300ng/ml
Marijuana(THC)	Delta-9-THC-COOH	50ng/ml

Easy cup test and Split key cup test may be configured as single drug tests or multiple drug tests in any combination of the drug analytes listed in the table above up to a maximum of 6 analytes.

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 test is intended for over the counter use.

BIO-VENTURE Rapid Multi-Drug Test Easy Cup for Rx Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for Rx Use is a rapid lateral flow immunoassay for the qualitative detection of d-Amphetamine, Oxazepam, Benzoylecgonine, d-Methamphetamine, Morphine and Delta-9-THC-COOH in human urine. The test cutoff concentrations and the compounds the tests are calibrated to are as follows:

Test	Calibrators	Cut-off Level
Amphetamine (AMP)	d-Amphetamine	1000ng/ml

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Oxazepam	Oxazepam	300ng/ml
Cocaine (COC)	Benzoylecgonine	300ng/ml
Methamphetamine (MET)	d-Methamphetamine	1000ng/ml
Morphine(MOP)	Morphine	300ng/ml
Marijuana(THC)	Delta-9-THC-COOH	50ng/ml

Easy cup test and Split key cup test may be configured as single drug tests or multiple drug tests in any combination of the drug analytes listed in the table above up to a maximum of 6 analytes.

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 test is intended for prescription use.

5.6 Substantial Equivalence

A summary comparison of features of the BIO-VENTURE Rapid Multi-Drug Test Easy Cup for OTC Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for OTC Use, BIO-VENTURE Rapid Multi-Drug Test Easy Cup for Rx Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for Rx Use and the predicate devices is provided in following tables.

Item	Device	PredicateDevice-K173303
Indication(s) forUse	For the qualitative determination ofdrugs of abuse in human urine.	Same
Calibrator	d-Amphetamine	Same
Methodology	Competitive binding, lateral flowimmunochromatographic assays basedon the principle of antigen antibodyimmunochemistry.	Same
Type of Test	Qualitative	Same

Table 1: Features comparison of Amphetamine Tests and the Predicate Devices.

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Specimen Type	Human Urine	Same
Cut-off Values	1000ng/mL	Same
Intended Use	For over-the-counter and prescriptionuses.	Same
Configurations	Easy Cup and Split Key Cup	Cassette, EasyCup, Split KeyCup and DipCard

Table 2: Features comparison of Cocaine Tests and the Predicate Devices.

Item	Device	Predicate
		Device-K173303
Indication(s) for Use	For the qualitative determination of drugs of abuse in human urine.	Same
Calibrator	Cocaine	Same
Methodology	Competitive binding, lateral flow immunochromatographic assays based on the principle of antigen antibody immunochemistry.	Same
Type of Test	Qualitative	Same
Specimen Type	Human Urine	Same
Cut-off Values	300ng/mL	Same
Intended Use	For over-the-counter and prescription uses.	Same
Configurations	Easy Cup and Split Key Cup	Cassette, Easy Cup, Split Key Cup and Dip Card

Table 3: Features comparison of Oxazepam Test Kits and the Predicate Devices.

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Item	Device	PredicateDevice-K173303
Indication(s) forUse	For the qualitative determination ofdrugs of abuse in human urine.	Same
Calibrator	Oxazepam	Same
Methodology	Competitive binding, lateral flowimmunochromatographic assays basedon the principle of antigen antibodyimmunochemistry.	Same
Type of Test	Qualitative	Same
Specimen Type	Human Urine	Same
Cut-off Values	300ng/mL	Same
Intended Use	For over-the-counter and prescriptionuses.	Same
Configurations	Easy Cup and Split Key Cup	Cassette, EasyCup, Split KeyCup and DipCard

Table 4: Features comparison of Methamphetamine Tests and the Predicate Devices.

Item	Device	PredicateDevice-K173303
Indication(s) forUse	For the qualitative determination ofdrugs of abuse in human urine.	Same
Calibrator	d-Methamphetamine	Same
Methodology	Competitive binding, lateral flowimmunochromatographic assays basedon the principle of antigen antibodyimmunochemistry.	Same
Type of Test	Qualitative	Same

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Specimen Type	Human Urine	Same
Cut-off Values	1000ng/mL	Same
Intended Use	For over-the-counter and prescriptionuses.	Same
Configurations	Easy Cup and Split Key Cup	Cassette, EasyCup, Split KeyCup and DipCard

Table 5: Features comparison of Morphine Tests and the Predicate Devices.

Item	Device	Predicate
		Device-K173303
Indication(s) forUse	For the qualitative determination ofdrugs of abuse in human urine.	Same
Calibrator	Morphine	Same
Methodology	Competitive binding, lateral flowimmunochromatographic assays basedon the principle of antigen antibodyimmunochemistry.	Same
Type of Test	Qualitative	Same
Specimen Type	Human Urine	Same
Cut-off Values	300ng/mL	2000 ng/mL
Intended Use	For over-the-counter and prescriptionuses.	Same
Configurations	Easy Cup and Split Key Cup	Cassette, EasyCup, Split KeyCup and DipCard

Table 6: Features comparison of Marijuana Tests and the Predicate Devices.

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Item	Device	Predicate
		Device-K173303
Indication(s)for Use	For the qualitative determination of drugsof abuse in human urine.	Same
Calibrator	11-Nor-Δ9-Tetrahydrocannabinol-9-COOH	Same
Methodology	Competitive binding, lateral flowimmunochromatographic assays based onthe principle of antigen antibodyimmunochemistry.	Same
Type of Test	Qualitative	Same
SpecimenType	Human Urine	Same
Cut-off Values	50ng/mL	Same
Intended Use	For over-the-counter and prescription uses.	Same
Configurations	Easy Cup and Split Key Cup	Cassette, EasyCup, Split KeyCup and DipCard

5.7 Test Principle

BIO-VENTURE Rapid Multi-Drug Test Easy Cup for OTC Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for OTC Use, BIO-VENTURE Rapid Multi-Drug Test Easy Cup for Rx Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for Rx Use are rapid tests for the qualitative detection of d-Amphetamine, Oxazepam, d-Methamphetamine, Morphine Benzoylecgonine, 11-Nor-49-Tetrahydrocannabinol-9-COOH in urine samples. The tests are lateral flow chromatographic immunoassays. During testing, a urine specimen migrates upward by capillary action. If target drugs present in the urine specimen are below the cut-off concentration, it will not saturate the binding sites of its specific monoclonal mouse antibody coated on the particles.

The antibody-coated particles will then be captured by immobilized drug-conjugate and a visible colored line will show up in the test line region. The colored line will not form in the test line region if the target drug level exceeds its cutoff-concentration because it

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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.

5.8 Performance Characteristics

5.8.1 Analytical Performance

a. Precision

Precision studies were carried out for samples with concentrations of -100% cut off, -50% cut off, -25% cut off, +25% cut off, +50% cut off and +100% cut off, These samples were prepared by spiking drug in negative samples. Each drug concentration was confirmed by GC/MS. All sample aliquots were blindly labeled by the person who prepared the samples and didn't take part in the sample testing. Each concentration has three lots, and 6 operators have joined the performance. Each operator performs 9 samples for 25 days per device in a randomized order. The results obtained are summarized in the following tables.

AMP Assay

Batch	-100%	-75%	-50%	-25%	Cut off	25%	50%	75%	100%
Number	cut off	cut off	cut off	cut off		cut off	Cutoff	cut off	cut off
C11100064	50-/0+	50-/0+	50-/0+	50-/0+	22-/28+	50+/0-	50+/0-	50+/0-	50+/0-
C11100065	50-/0+	50-/0+	50-/0+	50-/0+	25-/25+	50+/0-	50+/0-	50+/0-	50+/0-
C11100066	50-/0+	50-/0+	50-/0+	50-/0+	24-/26+	50+/0-	50+/0-	50+/0-	50+/0-

Split Key Cup

Easy Cup

BatchNumber	-100%cut off	-75%cut off	-50%cut off	-25%cut off	Cut off	25%cut off	50%Cut off	75%cut off	100%cut off
11100061	50-/0+	50-/0+	50-/0+	50-/0+	22-/28+	50+/0-	50+/0-	50+/0-	50+/0-

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

11100062	50-/0+	50-/0+	50-/0+	50-/0+	25-/25+	50+/0-	50+/0-	50+/0-
11100063	50-/0+	50-/0+	50-/0+	50-/0+	24-/26+	50+/0-	50+/0-	50+/0-

COC Assay

Split Key Cup

Batch	-100%	-75%	-50%	-25%	Cut off	25%	50%	75%	100%
Number	cut off	cut off	cut off	cut off		cut off	Cutoff	cut off	cut off
C11100064	50-/0+	50-/0+	50-/0+	50-/0+	24-/26+	50+/0-	50+/0-	50+/0-	50+/0-
C11100065	50-/0+	50-/0+	50-/0+	50-/0+	25-/25+	50+/0-	50+/0-	50+/0-	50+/0-
C11100066	50-/0+	50-/0+	50-/0+	50-/0+	25-/25+	50+/0-	50+/0-	50+/0-	50+/0-

Easy Cup

BatchNumber	-100%cut off	-75%cut off	-50%cut off	-25%cut off	Cut off	25%cut off	50%Cutoff	75%cut off	100%cut off
11100061	50-/0+	50-/0+	50-/0+	50-/0+	24-/26+	50+/0-	50+/0-	50+/0-	50+/0-
11100062	50-/0+	50-/0+	50-/0+	50-/0+	23-/27+	50+/0-	50+/0-	50+/0-	50+/0-
11100063	50-/0+	50-/0+	50-/0+	50-/0+	22-/28+	50+/0-	50+/0-	50+/0-	50+/0-

Oxazepam Assay

Split Key Cup

BatchNumber	-100%cut off	-75%cut off	-50%cut off	-25%cut off	Cut off	25%cut off	50%Cut off	75%cut off	100%cut off
C11100064	50-/0+	50-/0+	50-/0+	50-/0+	25-/25+	50+/0-	50+/0-	50+/0-	50+/0-

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

C11100065	50-/0+	50-/0+	50-/0+	50-/0+	24-/26+	50+/0-	50+/0-	50+/0-
C11100066	50-/0+	50-/0+	50-/0+	50-/0+	26-/24+	50+/0-	50+/0-	50+/0-

Easy Cup

BatchNumber	-100%cut off	-75%cut off	-50%cut off	-25%cut off	Cut off	25%cut off	50%Cutoff	75%cut off	100%cut off
11100061	50-/0+	50-/0+	50-/0+	50-/0+	26-/24+	50+/0-	50+/0-	50+/0-	50+/0-
11100062	50-/0+	50-/0+	50-/0+	50-/0+	23-/27+	50+/0-	50+/0-	50+/0-	50+/0-
11100063	50-/0+	50-/0+	50-/0+	50-/0+	23-/27+	50+/0-	50+/0-	50+/0-	50+/0-

MET Assay

Split Key Cup

BatchNumber	-100%cut off	-75%cut off	-50%cut off	-25%cut off	Cut off	25%cut off	50%Cut off	75%cut off	100%cut off
C11100064	50-/0+	50-/0+	50-/0+	50-/0+	9-/41+	50+/0-	50+/0-	50+/0-	50+/0-
C11100065	50-/0+	50-/0+	50-/0+	50-/0+	10-/40+	50+/0-	50+/0-	50+/0-	50+/0-
C11100066	50-/0+	50-/0+	50-/0+	50-/0+	11-/39+	50+/0-	50+/0-	50+/0-	50+/0-

Easy Cup

BatchNumber	-100%cut off	-75%cut off	-50%cut off	-25%cut off	Cut off	25%cut off	50%Cutoff	75%cut off	100%cut off
11100061	50-/0+	50-/0+	50-/0+	50-/0+	12-/38+	50+/0-	50+/0-	50+/0-	50+/0-

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

11100062	50-/0+	50-/0+	50-/0+	50-/0+	10-/40+	50+/0-	50+/0-	50+/0-	50+/0-
11100063	50-/0+	50-/0+	50-/0+	50-/0+	12-/38+	50+/0-	50+/0-	50+/0-	50+/0-

MOP Assay

Split Key Cup

Batch	-100%	-75%	-50%	-25%	Cut off	25%	50%	75%	100%
Number	cut off	cut off	cut off	cut off		cut off	Cutoff	cut off	cut off
C11100064	50-/0+	50-/0+	50-/0+	50-/0+	19-/31+	50+/0-	50+/0-	50+/0-	50+/0-
C11100065	50-/0+	50-/0+	50-/0+	50-/0+	20-/30+	50+/0-	50+/0-	50+/0-	50+/0-
C11100066	50-/0+	50-/0+	50-/0+	50-/0+	20-/30+	50+/0-	50+/0-	50+/0-	50+/0-

Easy Cup

BatchNumber	-100%cut off	-75%cut off	-50%cut off	-25%cut off	Cut off	25%cut off	50%Cut off	75%cut off	100%cut off
11100061	50-/0+	50-/0+	50-/0+	50-/0+	19-/31+	50+/0-	50+/0-	50+/0-	50+/0-
11100062	50-/0+	50-/0+	50-/0+	50-/0+	20-/30+	50+/0-	50+/0-	50+/0-	50+/0-
11100063	50-/0+	50-/0+	50-/0+	50-/0+	20-/30+	50+/0-	50+/0-	50+/0-	50+/0-

THC Assay

Split Key Cup

BatchNumber	-100%cut off	-75%cut off	-50%cut off	-25%cut off	Cut off	25%cut off	50%Cut off	75%cut off	100%cut off
C11100064	50-/0+	50-/0+	50-/0+	50-/0+	36-/14+	50+/0-	50+/0-	50+/0-	50+/0-

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

C11100065	50-/0+	50-/0+	50-/0+	50-/0+	38-/12+	50+/0-	50+/0-	50+/0-	50+/0-
C11100066	50-/0+	50-/0+	50-/0+	50-/0+	35-/15+	50+/0-	50+/0-	50+/0-	50+/0-

Easy Cup

BatchNumber	-100%cut off	-75%cut off	-50%cut off	-25%cut off	Cut off	25%cut off	50%Cut off	75%cut off	100%cut off
11100061	50-/0+	50-/0+	50-/0+	50-/0+	36-/14+	50+/0-	50+/0-	50+/0-	50+/0-
11100062	50-/0+	50-/0+	50-/0+	50-/0+	38-/12+	50+/0-	50+/0-	50+/0-	50+/0-
11100063	50-/0+	50-/0+	50-/0+	50-/0+	35-/15+	50+/0-	50+/0-	50+/0-	50+/0-

b. Linearity

Not applicable

c. Stability

The devices are stable at 2-30 ℃ for 24 months based on the real time stability at room temperature.

d. Cut-off

A total of 375 samples equally distributed at concentrations of -50% Cut-Off; -25% Cut-Off; Cut-Off; +25% Cut-Off; +50% Cut-Off were tested using three different lots of each device by three different operators. Results were all positive at and above +25% Cut-off and all negative at and below -25% Cut-off for Amphetamine, Cocaine, Oxazepam, Methamphetamine, Morphine and Marijuana.

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

Calibrator	Cut-off(ng/mL)
d-Amphetamine	1000

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

Cocaine	300
Oxazepam	300
d-Methamphetamine	1000
Morphine	300
(-)-11-Nor- $\Delta$ 9-Tetrahydrocannabinol-9-COOH	50

Interference e.

Potential interfering substances found in human urine of physiological or pathological conditions were added to drug-free urine and target drugs urine with concentrations at 25% below and 25% above Cut-Off levels. These urine samples were tested using three batches of each device. Compounds that showed no interference at a concentration of 100µg/mL and Ethanol at 1% are summarized in the following tables.

AMP Assay

Methadone	Naltrexone	Naloxone	Morphine
Gatifloxacin	Procaine	Amitriptyline	ChlorpheniramineMaleate
Promethazine	Amoxicillin	Methoxyphenamine	KetamineHydrochloride
Ranitidine	Tramadol	Buprenorphine	Phenobarbital
Nifedipine	Diazepam	Dextromethorphan	Cocaine
Theophylline	Aspirin	Acetaminophen	$Δ9-THC$
Ascorbic Acid	Hemoglobin	Bilirubin	Ibuprofen
Dolantin	Hydroxyketone	EDDP	Phencyclidine
Propoxyphene	Aminopyrine	Cotinine	Fentanyl
Benzoylecgonine	Secobarbital	Angiotensin	Adrenaline
Oxazepam	Uric Acid	Triglyceride	Oxalic Acid
Prednisoloneacetate	Cholesterol	Hydrocortisone	Oxycodone
Ethanol

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

Methadone	Naltrexone	Naloxone	Morphine
Ephedrine	Pseudo Ephedrine	Gatifloxacin	Procaine
Amitriptyline	ChlorpheniramineMaleate	Promethazine	Amoxicillin
Methoxyphenamine	KetamineHydrochloride	Ranitidine	Tramadol
Buprenorphine	Phenobarbital	Nifedipine	Methamphetamine
Dextromethorphan	Cocaine	Theophylline	Aspirin
Acetaminophen	Δ²-THC	Hydrocortisone	Oxycodone
Ascorbic Acid	Hemoglobin	Bilirubin	Ibuprofen
Dolantin	Hydroxyketone	EDDP	Phencyclidine
Propoxyphene	Aminopyrine	Cotinine	Fentanyl
Benzoylecgonine	Secobarbital	Angiotensin	Adrenaline
MDMA	Uric Acid	Triglyceride	Oxalic Acid
Prednisoloneacetate	Cholesterol	Amphetamine	Ethanol

Oxazepam Assay

COC Assay

Methadone	Naltrexone	Naloxone	Morphine
Ephedrine	Pseudo Ephedrine	Gatifloxacin	Procaine
Amitriptyline	ChlorpheniramineMaleate	Promethazine	Amoxicillin
Methoxyphenamine	KetamineHydrochloride	Ranitidine	Tramadol
Buprenorphine	Phenobarbital	Nifedipine	Methamphetamine
Dextromethorphan	Diazepam	Theophylline	Aspirin
Acetaminophen	Δ⁹-THC	Hydrocortisone	Oxycodone
Ascorbic Acid	Hemoglobin	Bilirubin	Ibuprofen
Dolantin	Hydroxyketone	EDDP	Phencyclidine

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

Propoxyphene	Aminopyrine	Cotinine	Fentanyl
Secobarbital	Angiotensin	Adrenaline	Oxalic Acid
Oxazepam	Uric Acid	Triglyceride	Prednisoloneacetate
Cholesterol	MDMA	Amphetamine	Ethanol

MET Assay

Methadone	Naltrexone	Naloxone	Morphine
Ephedrine	Pseudo Ephedrine	Gatifloxacin	Procaine
Amitriptyline	ChlorpheniramineMaleate	Promethazine	Amoxicillin
Methoxyphenamine	KetamineHydrochloride	Ranitidine	Tramadol
Buprenorphine	Phenobarbital	Nifedipine	Diazepam
Dextromethorphan	Cocaine	Theophylline	Aspirin
Acetaminophen	Δ⁹-THC	Hydrocortisone	Oxycodone
Ascorbic Acid	Hemoglobin	Bilirubin	Ibuprofen
Dolantin	Hydroxyketone	EDDP	Phencyclidine
Propoxyphene	Aminopyrine	Cotinine	Fentanyl
Benzoylecgonine	Secobarbital	Angiotensin	Adrenaline
Oxazepam	Uric Acid	Triglyceride	Oxalic Acid
Prednisoloneacetate	Cholesterol	Ethanol

MOP Assay

Methadone	Naltrexone	Naloxone	Cocaine
Ephedrine	Pseudo Ephedrine	Gatifloxacin	Procaine
Amitriptyline	ChlorpheniramineMaleate	Promethazine	Amoxicillin
Methoxyphenamine	Ketamine	Ranitidine	Tramadol

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

	Hydrochloride
Buprenorphine	Phenobarbital	Nifedipine	Methamphetamine
Dextromethorphan	Diazepam	Theophylline	Aspirin
Acetaminophen	$ Δ9-THC $	Cholesterol	Hydrocortisone
Ascorbic Acid	Hemoglobin	Bilirubin	Ibuprofen
Dolantin	Hydroxyketone	EDDP	Phencyclidine
Propoxyphene	Aminopyrine	Cotinine	Fentanyl
Benzoylecgonine	Secobarbital	Angiotensin	Adrenaline
Oxazepam	Uric Acid	Triglyceride	Oxalic Acid
Prednisolone acetate	Amphetamine	MDMA	Ethanol

THC Assay

Methadone	Naltrexone	Naloxone	Morphine
Ephedrine	Pseudo Ephedrine	Gatifloxacin	Procaine
Amitriptyline	ChlorpheniramineMaleate	Promethazine	Amoxicillin
Methoxyphenamine	KetamineHydrochloride	Ranitidine	Tramadol
Buprenorphine	Phenobarbital	Nifedipine	Methamphetamine
Dextromethorphan	Diazepam	Theophylline	Aspirin
Acetaminophen	Cocaine	Amphetamine	MDMA
Ascorbic Acid	Hemoglobin	Bilirubin	Ibuprofen
Dolantin	Hydroxyketone	EDDP	Phencyclidine
Propoxyphene	Aminopyrine	Cotinine	Fentanyl
Benzoylecgonine	Secobarbital	Angiotensin	Adrenaline
Oxazepam	Uric Acid	Triglyceride	Oxalic Acid
Prednisoloneacetate	Cholesterol	Hydrocortisone	Oxycodone
Ethanol

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

f. Specificity

To test specificity, drug metabolites and other components that are likely to interfere in urine samples were tested using three batches of each device. The lowest concentration that caused a positive result for each compound is listed below. There were no differences observed for different devices.

AMP Assay

Drugs	Concentration(ng/mL)	%Cross Reactivity
D-Amphetamine	1000	100%
D/L- Amphetamine	1500	66.7%
Phentermine	3000	33.3%
L-Amphetamine	3000	33.3%
Hydroxyamphetamine	10000	10%
Methylenedioxyamphetamine(MDA)	10000	10%
3,4-methylenedioxy-methamphetamine(MDMA)	>100,000	<1%
Methylenedioxyethylamphetamine(MDE)	>100,000	<1%
Ephedrine	>100,000	<1%
Pseudophedrine	>100,000	<1%
D-Methamphetamine	>100,000	<1%
L-Methamphetamine	>100,000	<1%
D/L-Methamphetamine	>100,000	<1%

COC Assay

Drugs	Concentration(ng/mL)	%Cross Reactivity
Cocaine HCl	5000	6%
Norcocaine	25000	1.2%
Ecgonine HCl	50000	0.6%

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

Cocaethylene	>100000	<0.3%
Benzoylecgonine	300	100%

Oxazepam Assay

Drugs	Concentration(ng/mL)	%Cross Reactivity
Oxazepam	300	100%
Diazepam	1000	30%
Alprazolam	1000	30%
α-Hydroxyalprazolam	5000	6%
Bromazepam	10000	3%
Chlordiazepoxide	10000	3%
Clobazam	500	60%
Clonazepam	3000	10%
Delorazepam	5000	6%
Estazolam	10000	3%
Flunitrazepam	5000	6%
Midazolam	50000	0.6%
Nitrazepam	500	60%
Nordiazepam	5000	6%
Temazepam	500	60%
Triazolam	10000	3%
Lorazepam	25000	1.2%
Clorazepate Dipotassium	> 100000	<0.3%
Desalkylflurazepam	>100000	<0.3%
Norchlordiazepoxide	> 100000	<0.3%

MET Assay

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

Drugs	Concentration(ng/mL)	%CrossReactivity
(±)3,4-methylenedioxy-n-ethylamphetamine(MDEA)	5000	20%
D-Methamphetamine	1000	100%
L-Methamphetamine	10000	10%
D/L- Methamphetamine	3000	33.3%
p-Hydroxymethamphetamine	50000	2%
(±)3,4-Methylenedioxyamphetamine(MDA)	20000	5%
(±)3,4-Methylenedioxymethamphetamine(MDMA)	3000	33.3%
D/L-Amphetamine	>100,000	<1%
D- Amphetamine	>100,000	<1%
L-Amphetamine	>100,000	<1%

MOP Assay

Drugs	Concentration	%CrossReactivity
Acetylmorphine	6000	5%
Hydromorphone	3000	10%
Hydrocodone	50000	0.6%
Levorphanol	1500	20%

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

Oxycodone	50000	0.6%
Dimethylmorphine	3000	10%
Morphine-3- Glucuronide	>100,000	<0.3%
Morphine	300	100%
Codeine	300	100%
Heroin	300	100%
O6- Monoacetylmorphine	300	100%
Ethylmorphine	> 100000	<0.3%

THC Assay

Drugs	Concentration	%CrossReactivity
(-)-11-Nor-Δ9-Tetrahydrocannabinol-9-COOH	50	100%
11-Hydroxy-Δ9-Tetrahydrocannabinol	10000	0.5%
11- Nor-Δ8-Tetrahydrocannabinol-9-COOH	2500	2%
Cannabinol	5000	1%
11-Nor-Δ9-THC-carboxy glucuronide	5000	1%
(-)-11-nor-9-carboxy-Δ9-THC	10000	0.5%
Δ8- Tetrahydrocannabinol	>50000	<0.1%
Δ9- Tetrahydrocannabinol	>50000	<0.1%
Cannabidiol	>50000	<0.1%

g. Effect of Urine Specific Gravity and Urine pH

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

To investigate the effect of urine specific gravity and urine pH, urine samples, with 1.002 to 1.036 specific gravity or urine samples with pH 4 to 9 were spiked with target drugs at 25% below and 25% above Cut-off levels. These samples were tested using three lots of each device. Results were all positive for samples at and above +25% Cutoff and all negative for samples at and below -25% Cut-Off. There were no differences observed for different devices.

5.8.2. Comparison Study

Method comparison studies for BIO-VENTURE Rapid Multi-Drug Test Easy Cup for OTC Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for OTC Use, BIO-VENTURE Rapid Multi-Drug Test Easy Cup for Rx Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for Rx Use were performed in-house with three laboratory assistants for each device. Operators ran unaltered clinical samples, 87 samples for amphetamine, 80 samples for cocaine, 80 samples for Oxazepam, 81 samples for Methamphetamine, 81 samples for Morphine, 82 samples for Marijuana. The samples were blind labeled and compared to GC/MS results. The results are presented in the tables below:

Amphetamine

Cup	Results	NegativeUrine	<-50% cutoff	-50% cut off-cut off	Cut off-+50% cut off	>+50% cutoff
Operator1	Negative	19	16	11	1	0
	Positive	0	0	0	13	27
Operator2	Negative	19	16	10	1	0
	Positive	0	0	1	13	27
Operator3	Negative	19	16	10	0	0
	Positive	0	0	1	14	27

Discordant Results of Amphetamine Cup

Operator	GC/MS Result(ng/mL)	Candidate Device Result
1	989	Negative
2	989	Positive
3	989	Positive
1	1035	Positive

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

2	1035	Negative
3	1035	Positive
1	1062	Negative
2	1062	Positive
3	1062	Positive

SplitKey Cup	Results	NegativeUrine	<-50% cutoff	-50% cut off-cut off	Cut off-+50% cut off	>+50% cutoff
Operator1	Negative	19	16	11	1	0
Operator1	Positive	0	0	0	13	27
Operator2	Negative	19	16	10	1	0
Operator2	Positive	0	0	1	13	27
Operator3	Negative	19	16	10	0	0
Operator3	Positive	0	0	1	14	27

Discordant Results of Amphetamine Split Key Cup

Operator	GC/MS Result(ng/mL)	Candidate Device Result
1	989	Negative
2	989	Positive
3	989	Positive
1	1035	Positive
2	1035	Negative
3	1035	Positive
1	1062	Negative
2	1062	Positive
3	1062	Positive

Cocaine

Cup	Results	NegativeUrine	<-50% cutoff	-50% cutoff	Cut off-+50% cut off	>+50% cutoff

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

Operator		Negative	18	13	11	2
	Positive	0	0	0	15	21
Operator2	Negative	18	13	11	1	0
	Positive	0	0	0	16	21
Operator3	Negative	18	13	10	0	0
	Positive	0	0	1	17	21

Discordant Results of Cocaine Cup

Operator	GC/MS Result(ng/mL)	Candidate Device Result
1	285	Negative
2	285	Negative
3	285	Positive
1	313	Negative
2	313	Negative
3	313	Positive
1	321	Negative
2	321	Positive
3	321	Positive

SplitKey Cup	Results	NegativeUrine	<-50% cut off	-50% cut off- cut off	Cut off-+50% cut off	>+50% cut off
Operator 1	Negative	18	13	11	1	0
	Positive	0	0	0	16	21
Operator 2	Negative	18	13	11	1	0
	Positive	0	0	0	16	21
Operator 3	Negative	18	13	10	0	0
	Positive	0	0	1	17	21

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

Operator	GC/MS Result(ng/mL)	Candidate Device Result
1	285	Negative
2	285	Negative
3	285	Positive
1	313	Negative
2	313	Negative
3	313	Positive
1	321	Negative
2	321	Positive
3	321	Positive

Discordant Results of Cocaine Split Key Cup

Oxazepam

Cup	Results	NegativeUrine	<-50% cutoff	-50% cut off-cut off	Cut off-+50% cut off	>+50% cutoff
Operator1	Negative	15	10	15	1	0
	Positive	0	0	0	19	20
Operator2	Negative	15	10	15	0	0
	Positive	0	0	0	20	20
Operator3	Negative	15	10	14	0	0
	Positive	0	0	1	20	20

Discordant Results of Oxazepam Cup

Operator	GC/MS Result(ng/mL)	Candidate Device Result
1	333	Negative
2	333	Positive
3	333	Positive

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

1	298	Negative
2	298	Negative
3	298	Positive

SplitKey Cup	Results	NegativeUrine	<-50% cutoff	-50% cut off-cut off	Cut off-+50% cut off	>+50% cutoff
Operator1	Negative	15	10	15	1	0
	Positive	0	0	0	19	20
Operator2	Negative	15	10	15	0	0
	Positive	0	0	0	20	20
Operator3	Negative	15	10	15	0	0
	Positive	0	0	0	20	20

Discordant Results of Oxazepam Split Key Cup

Operator	GC/MS Result(ng/mL)	Candidate Device Result
1	333	Negative
2	333	Positive
3	333	Positive

Methamphetamine

Cup	Results	NegativeUrine	<-50%off	-50% cut off-cut off	Cut off-+50% cut off	>+50%off
Operator1	Negative	17	16	8	0	0
	Positive	0	0	0	11	29
Operator2	Negative	17	16	8	1	0
	Positive	0	0	0	10	29
Operator3	Negative	17	16	7	0	0
	Positive	0	0	1	11	29

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

Operator	GC/MS Result(ng/mL)	Candidate Device Result
1	1025	Positive
2	1025	Negative
3	1025	Positive
1	984	Negative
2	984	Negative
3	984	Positive

SplitKey Cup	Results	NegativeUrine	<-50% cutoff	-50% cut off-cut off	Cut+50% cut off	>+50% cutoff
Operator1	Negative	17	16	8	0	0
	Positive	0	0	0	11	29
Operator2	Negative	17	16	8	1	0
	Positive	0	0	0	10	29
Operator3	Negative	17	16	7	0	0
	Positive	0	0	1	11	29

Discordant Results of Methamphetamine Split Key Cup

Operator	GC/MS Result(ng/mL)	Candidate Device Result
1	1025	Positive
2	1025	Negative
3	1025	Positive
1	984	Negative
2	984	Negative
3	984	Positive

Morphine

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

Cup	Results	Negative Urine	<-50% cut off	-50% cut off- cut off	Cut off-+50% cut off	>+50% cut off
Operator 1	Negative	19	9	13	0	0
	Positive	0	0	0	15	25
Operator 2	Negative	19	9	13	2	0
	Positive	0	0	0	13	25
Operator 3	Negative	19	9	12	0	0
	Positive	0	0	1	15	25

Discordant Results of Morphine Cup

Operator	GC/MS Result(ng/mL)	Candidate Device Result
1	323	Positive
2	323	Negative
3	323	Positive
1	335	Positive
2	335	Negative
3	335	Positive
1	293	Positive
2	293	Negative
3	293	Positive

SplitKey Cup	Results	NegativeUrine	<-50% cutoff	-50% cut off-cut off	Cut+50% cut off	>+50% cutoff
Operator1	Negative	19	9	12	0	0
	Positive	0	0	1	15	25
Operator2	Negative	19	9	13	1	0
	Positive	0	0	0	14	25
Operator3	Negative	19	9	12	0	0
	Positive	0	0	1	15	25

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Operator	GC/MS Result(ng/mL)	Candidate Device Result
1	323	Positive
2	323	Negative
3	323	Positive
1	293	Positive
2	293	Negative
3	293	Positive

Discordant Results of Morphine Split Key Cup

Marijuana

Cup	Results	NegativeUrine	<-50%cutoff	cut	-50% cut off-cut off	Cutoff-+50% cut off
Operator1	Negative	18	11	13	3	0
	Positive	0	0	0	13	24
Operator2	Negative	18	11	13	2	0
	Positive	0	0	0	14	24
Operator3	Negative	18	11	13	0	0
	Positive	0	0	0	16	24

Discordant Results of Marijuana Cup

Operator	GC/MS Result(ng/mL)	Candidate Device Result
1	61	Negative
2	61	Negative
3	61	Positive
1	61	Negative
2	61	Positive
3	61	Positive
1	59	Negative

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2	59	Negative
3	59	Positive

SplitKey Cup	Results	NegativeUrine	<-50% cutoff	-50% cut off-cut off	Cut+50% cut off	>+50% cutoff
Operator1	Negative	18	11	13	3	0
	Positive	0	0	0	13	24
Operator2	Negative	18	11	13	1	0
	Positive	0	0	0	15	24
Operator3	Negative	18	11	13	0	0
	Positive	0	0	0	16	24

Discordant Results of Marijuana Split Key Cup

Operator	GC/MS Result(ng/mL)	Candidate Device Result
1	61	Negative
2	61	Negative
3	61	Positive
1	61	Negative
2	61	Positive
3	61	Positive
1	59	Negative
2	59	Positive
3	59	Positive

Lay-user study

A lay user study was performed at three intended user sites for BIO-VENTURE Rapid Multi-Drug Test Easy Cup for OTC Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for OTC Use, BIO-VENTURE Rapid Multi-Drug Test Easy Cup for Rx Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for Rx Use separately. The lay

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users had diverse educational and professional backgrounds and ranged in age from 20 to > 50 years. Urine samples were prepared at the following concentrations; negative, +/-75%, +/-50%, +/-25% of the cutoff by spiking drug(s) into drug free-pooled urine specimens. The concentrations of the samples were confirmed by GC/MS. Each sample was aliquoted into individual containers and blind-labeled. Each participant was provided with the package insert, 1 blind labeled sample and a device. Each device was tested.

Comparison between GC/MS and Lay Person Results for Amphetamine Cup
Format

% of cut off	Numberofsamples	d-AmphetamineConcentrationbyGC/MS(ng/mL)	NumberofPositive	NumberofNegative	Percentage ofCorrectResults (%)
-100% cutoff	20	0	0	20	100%
-75% cut off	20	248	0	20	100%
-50% cut off	20	492	0	20	100%
-25% cut off	20	741	2	18	90%
+25% cutoff	20	1262	20	0	100%
+50% cutoff	20	1506	20	0	100%
+75% cutoff	20	1744	20	0	100%

Comparison between GC/MS and Lay Person Results for Amphetamine Split Key Cup Format

% of cut off	Number of samples	d-Amphetamine Concentration by GC/MS(ng/mL)	Number Positive	Number Negative	Percentage of Correct Results (%)
-100% cut off	20	0	0	20	100%
-75% cut off	20	248	0	20	100%
-50% cut off	20	492	0	20	100%
-25% cut off	20	741	2	18	90%

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+25%off	cut	20	1262	20	0	100%
+50%off	cut	20	1506	20	0	100%
+75%off	cut	20	1744	20	0	100%

Comparison between GC/MS and Lay Person Results for Cocaine Cup

% of cut off	Number of samples	CocaineConcentrationbyGC/MS(ng/mL)	Number of Positive	Number of Negative	Percentage of CorrectResults(%)
-100% cut off	20	0	0	20	100%
-75% cut off	20	62	0	20	100%
-50% cut off	20	135	0	20	100%
-25% cut off	20	212	1	19	95%
+25% cut off	20	365	20	0	100%
+50% cut off	20	444	20	0	100%
+75% cut off	20	533	20	0	100%

Comparison between GC/MS and Lay Person Results for Cocaine Split Key Cup

% of cut off	Number ofsamples	CocaineConcentrationbyGC/MS(ng/mL)	Number ofPositive	Number ofNegative	Percentage ofCorrectResults(%)
-100% cut off	20	0	0	20	100%
-75% cut off	20	62	0	20	100%
-50% cut off	20	135	0	20	100%
-25% cut off	20	212	1	19	95%

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+25%off	cut	20	365	19		વેરી જેવી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તે
+50%off	cut	20	444	20	0	100%
+75%off	cut	20	533	20	0	100%

Comparison between GC/MS and Lay Person Results for Oxazepam Cup

% of cut off	Number of samples	OxazepamConcentrationbyGC/MS(ng/mL)	Number Positive	Number Negative	Percentage ofCorrectResults(%)
-100% cut off	20	0	0	20	100%
-75% cut off	20	64	0	20	100%
-50% cut off	20	141	0	20	100%
-25% cut off	20	221	1	19	95%
+25% cut off	20	362	18	2	90%
+50% cut off	20	440	20	0	100%
+75% cut off	20	530	20	0	100%

Comparison between GC/MS and Lay Person Results for Oxazepam Split Key Cup

% of cut off	Number of samples	Oxazepam Concentration by GC/MS(ng/mL)	Number of Positive	Number of Negative	Percentage of Correct Results(%)
-100% cut off	20	0	0	20	100%
-75% cut off	20	64	0	20	100%

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-50% cut off	20	141	0	20	100%
-25% cut off	20	221	0	20	100%
+25%cutoff	20	362	18	2	90%
+50%cutoff	20	440	20	0	100%
+75%cutoff	20	530	20	0	100%

Comparison between GC/MS and Lay Person Results for Methamphetamine Cup Format

% of cut off	Number ofsamples	d-MethamphetamineConcentration byGC/MS(ng/mL)	Number ofPositive	Number ofNegative	Percentageof CorrectResults (%)
-100% cutoff	20	0	0	20	100%
-75% cutoff	20	248	0	20	100%
-50% cutoff	20	489	0	20	100%
-25% cutoff	20	734	0	20	100%
+25% cutoff	20	1284	18	2	90%
+50% cutoff	20	1535	20	0	100%
+75% cutoff	20	1783	20	0	100%

Comparison between GC/MS and Lay Person Results for Methamphetamine Split Key Cup Format

% of cut off	Number of samples	d-Methamphetamine Concentration by GC/MS(ng/mL)	Number of Positive	Number of Negative	Percentage of Correct Results (%)
-100% cut off	20	0	0	20	100%

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-75%off	cut	20	248	0	20	100%
-50%off	cut	20	489	0	20	100%
-25%off	cut	20	734	0	20	100%
+25%off	cut	20	1284	20	0	100%
+50%off	cut	20	1535	20	0	100%
+75%off	cut	20	1783	20	0	100%

Comparison between GC/MS and Lay Person Results for Morphine Cup

% of cut off	Number ofsamples	MorphineConcentrationbyGC/MS(ng/mL)	Number ofPositive	Number ofNegative	Percentage ofCorrectResults(%)
-100% cutoff	20	0	0	20	100%
-75% cut off	20	70	0	20	100%
-50% cut off	20	136	0	20	100%
-25% cut off	20	228	2	18	90%
+25% cutoff	20	378	20	0	100%
+50% cutoff	20	445	20	0	100%
+75% cutoff	20	510	20	0	100%

Comparison between GC/MS and Lay Person Results for Morphine Split Key Cup

% of cut off	Number of samples	Morphine Concentration by	Number Positive	Number of Negative	Percentage of Correct Results(%)
--------------	-------------------	---------------------------	-----------------	--------------------	----------------------------------

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	GC/MS(ng/mL)
-100% cut off	20	0	0	20	100%
-75% cut off	20	70	0	20	100%
-50% cut off	20	136	0	20	100%
-25% cut off	20	228	1	19	95%
+25% cut off	20	378	20	0	100%
+50% cut off	20	445	20	0	100%
+75% cut off	20	510	20	0	100%

Comparison between GC/MS and Lay Person Results for Marijuana Cup Format

% of cut off	Number of samples	MarijuanaConcentrationbyGC/MS(ng/mL)	Number ofPositive	Number ofNegative	Percentage ofCorrectResults(%)
-100% cut off	20	0	0	20	100%
-75% cut off	20	10	0	20	100%
-50% cut off	20	24	0	20	100%
-25% cut off	20	36	0	20	100%
+25% cut off	20	60	19	1	95%
+50% cut off	20	73	20	0	100%
+75% cut off	20	82	20	0	100%

Comparison between GC/MS and Lay Person Results for Marijuana Split Key Cup Format

% of cut off	Number of samples	Marijuana Concentration by	Number Positive	Number Negative	Percentage of Correct
--------------	-------------------	----------------------------	-----------------	-----------------	-----------------------

{40}------------------------------------------------

		GC/MS(ng/mL)			Results(%)
-100% cut off	20	0	0	20	100%
-75% cut off	20	10	0	20	100%
-50% cut off	20	24	0	20	100%
-25% cut off	20	36	0	20	100%
+25% cut off	20	60	20	0	100%
+50% cut off	20	73	20	0	100%
+75% cut off	20	82	20	0	100%

Lay-users were also given surveys on the ease of understanding the package insert instructions. All lay users indicated that the device instructions can be easily followed. A Flesch-Kincaid reading analysis was performed on each package insert and the scores revealed a reading Grade Level of 7.

Clinical Study

Not applicable.

5.9 Conclusion

In accordance with the Federal Food, Drug and Cosmetic Act, 21 CFR Part 807, Based on the information provided in this premarket notification, SHANGHAI VENTURE BIO-TECH CO., LTD has demonstrated that proposed device BIO-VENTURE Rapid Multi-Drug Test Easy Cup for OTC Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for OTC Use, BIO-VENTURE Rapid Multi-Drug Test Easy Cup for Rx Use, BIO-VENTURE Rapid Multi-Drug Test Split Key Cup for Rx Use are substantially equivalent to the predicate.

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).