BioSieve Marijuana Test Panel 50; BioSieve Marijuana Test Strip 50; BioSieve Dx Marijuana Test Strip 20; BioSieve Dx Marijuana Test Strip 50; BioSieve Dx Marijuana Test Panel 20; BioSieve Dx Marijuana Test Panel 50

Q: Who is the manufacturer of BioSieve Marijuana Test Panel 50; BioSieve Marijuana Test Strip 50; BioSieve Dx Marijuana Test Strip 20; BioSieve Dx Marijuana Test Strip 50; BioSieve Dx Marijuana Test Panel 20; BioSieve Dx Marijuana Test Panel 50?

Vivachek Biotech (Hangzhou) Co., Ltd. filed the 510(k) submission for BioSieve Marijuana Test Panel 50; BioSieve Marijuana Test Strip 50; BioSieve Dx Marijuana Test Strip 20; BioSieve Dx Marijuana Test Strip 50; BioSieve Dx Marijuana Test Panel 20; BioSieve Dx Marijuana Test Panel 50 (K231978).

Q: What is the FDA product code for BioSieve Marijuana Test Panel 50; BioSieve Marijuana Test Strip 50; BioSieve Dx Marijuana Test Strip 20; BioSieve Dx Marijuana Test Strip 50; BioSieve Dx Marijuana Test Panel 20; BioSieve Dx Marijuana Test Panel 50?

NFW. It is classified under 21 CFR 862.3870 as a Class 2 device in the Clinical Toxicology panel.

Q: What is the regulatory pathway for BioSieve Marijuana Test Panel 50; BioSieve Marijuana Test Strip 50; BioSieve Dx Marijuana Test Strip 20; BioSieve Dx Marijuana Test Strip 50; BioSieve Dx Marijuana Test Panel 20; BioSieve Dx Marijuana Test Panel 50?

510(k) clearance (submission type: Traditional).

Q: Who can help prepare an FDA 510(k) submission like BioSieve Marijuana Test Panel 50; BioSieve Marijuana Test Strip 50; BioSieve Dx Marijuana Test Strip 20; BioSieve Dx Marijuana Test Strip 50; BioSieve Dx Marijuana Test Panel 20; BioSieve Dx Marijuana Test Panel 50?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

K231978 · Vivachek Biotech (Hangzhou) Co., Ltd. · NFW · Aug 31, 2023 · Clinical Toxicology

Device Facts

Record ID	K231978
Device Name	BioSieve Marijuana Test Panel 50; BioSieve Marijuana Test Strip 50; BioSieve Dx Marijuana Test Strip 20; BioSieve Dx Marijuana Test Strip 50; BioSieve Dx Marijuana Test Panel 20; BioSieve Dx Marijuana Test Panel 50
Applicant	Vivachek Biotech (Hangzhou) Co., Ltd.
Product Code	NFW · Clinical Toxicology
Decision Date	Aug 31, 2023
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 862.3870
Device Class	Class 2

Intended Use

BioSieve™ Dx Marijuana Test Panel 20 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 20 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only. BioSieve™ Dx Marijuana Test Strip 20 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 20 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only. BioSieve™ Dx Marijuana Test Panel 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only. BioSieve™ Dx Marijuana Test Strip 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only. BioSieve™ Marijuana Test Panel 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only. BioSieve™ Marijuana Test Strip 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.

Device Story

Lateral flow immunochromatographic assay for qualitative detection of marijuana metabolites in human urine; competitive binding principle. Urine sample migrates via capillary action; target drug competes with drug-conjugate for binding sites on monoclonal antibody-coated particles. Absence of colored test line indicates positive result (drug concentration above cutoff); presence of colored test line indicates negative result. Control line confirms proper test performance. Single-use device; available as test strip or panel. Used in point-of-care or home settings; operated by lay users or healthcare professionals. Provides preliminary results; requires confirmatory testing via GC/MS or LC/MS for clinical decision-making. Benefits include rapid, accessible screening for marijuana presence.

Clinical Evidence

No clinical trials performed. Evidence consists of analytical performance (precision, specificity, interference, and matrix effects) and a lay-user study. Lay-user study (n=280) across three sites demonstrated high accuracy (95-100%) compared to LC/MS/MS across various concentrations relative to the 50 ng/mL cutoff. Analytical performance confirmed by LC/MS/MS.

Technological Characteristics

Lateral flow immunochromatographic assay; competitive binding format. Single-use test strip or panel. Analyte: 11-Nor-△⁹-THC-9-COOH. Cutoffs: 20 ng/mL or 50 ng/mL. No electronic components or software. Visual readout via colored bands.

Indications for Use

Indicated for qualitative detection of Marijuana (11-nor-Δ9-THC-9-COOH) in human urine at 20 ng/mL or 50 ng/mL cutoff concentrations. Intended for prescription and over-the-counter use as a preliminary screening test. Not for quantitative measurement. Confirmatory testing required via GC/MS or LC/MS.

Regulatory Classification

Identification

A cannabinoid test system is a device intended to measure any of the cannabinoids, hallucinogenic compounds endogenous to marihuana, in serum, plasma, saliva, and urine. Cannabinoid compounds include delta-9-tetrahydrocannabinol, cannabidiol, cannabinol, and cannabichromene. Measurements obtained by this device are used in the diagnosis and treatment of cannabinoid use or abuse and in monitoring levels of cannabinoids during clinical investigational use.

Special Controls

*Classification.* Class II (special controls). A cannabinoid test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (*e.g.,* programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).

Predicate Devices

BIOEASY Marijuana Test Dip Card and BIOEASY Marijuana Test Strip (K192301)

Related Devices

K191924 — SAFECARE® THC Urine Strip Test · Safecare Biotech (Hangzhou) Co., Ltd. · Aug 16, 2019
K192515 — BIOEASY Marijuana Test Dip Card 40, BIOEASY Marijuana Test Dip Card 20, BIOEASY Marijuana Test Strip 40, BIOEASY Marijuana Test Strip 20 · Shenzhen Bioeasy Biotechnology Co., Ltd. · Oct 11, 2019
K192301 — BIOEASY Marijuana Test Dip Card, BIOEASY Marijuana Test Strip · Shenzhen Bioeasy Biotechnology Co., Ltd. · Sep 20, 2019

Submission Summary (Full Text)

{0}------------------------------------------------ Image /page/0/Picture/0 description: The image contains 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 ADMINISTRATION' in blue text. VivaChek Biotech (Hangzhou) Co., Ltd % Joe Shia Director LSI International Inc 504 E Diamond Ave., Suite H Gaithersburg. Maryland 20877 ## Re: K231978 Trade/Device Name: BioSieve™ Marijuana Test Panel 50; BioSieve™ Marijuana Test Strip 50; BioSieve™ Dx Marijuana Test Strip 20; BioSieve™ Dx Marijuana Test Strip 50; BioSieve™ Dx Marijuana Test Panel 20; BioSieve™ Dx Marijuana Test Panel 50 Regulation Number: 21 CFR 862.3870 Regulation Name: Cannabinoid Test System Regulatory Class: Class II Product Code: NFW Dated: June 27, 2023 Received: July 3, 2023 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, 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. 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 {1}------------------------------------------------ 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/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/cdrh-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, Joseph A. Digitally signed by Kotarek -S Date: 2023.08.31 Kotarek -S 16:55:57 -04'00' Joseph Kotarek Branch Chief Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health Enclosure {2}------------------------------------------------ # Indications for Use 510(k) Number (if known) K231978 #### Device Name BioSieve™ Dx Marijuana Test Panel 20; BioSieve™ Dx Marijuana Test Panel 50 BioSieve™ Dx Marijuana Test Strip 20 BioSieve™ Dx Marijuana Test Strip 50 #### Indications for Use (Describe) BioSieve™ Dx Marijuana Test Panel 20 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 20 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only. BioSieve™ Dx Marijuana Test Strip 20 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 20 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only. BioSieve™ Dx Marijuana Test Panel 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only. BioSieve™ Dx Marijuana Test Strip 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only. | Type of Use (Select one or both, as applicable) | |------------------------------------------------------------------------------------------------------| | <div> <input checked="true" type="checkbox"/> Prescription Use (Rx - 21 CFR 801 Subpart D) </div> | | <div> <input type="checkbox"/> Over-The-Counter Use (21 CFR 801 Subpart C) </div> | | > 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." {3}------------------------------------------------ # Indications for Use 510(k) Number (if known) K231978 Device Name BioSieve™ Marijuana Test Panel 50 BioSieve™ Marijuana Test Strip 50 #### Indications for Use (Describe) BioSieve™ Marijuana Test Panel 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only. BioSieve™ Marijuana Test Strip 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only. | Type of Use (Select one or both, as applicable) | |-------------------------------------------------| |-------------------------------------------------| Prescription Use (Part 21 CFR 801 Subpart D) X 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." {4}------------------------------------------------ ## 510(k) SUMMARY K231978 | 1 | Date | August 31, 2023 | |---|----------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------| | 2 | Submitter | VivaChek Biotech (Hangzhou) Co., Ltd. Level 2, Block 2, 146 East Chaofeng Rd. Hangzhou, China | | 3 | Contact Person | Joe Shia LSI International Inc. 504 East Diamond Ave., Suite J Gaithersburg, MD 20877 Telephone: 240-505-7880 Fax: 301-916-6213 Email: shiajl@yahoo.com | | 4 | Device Name | BioSieve™ Dx Marijuana Test Panel 20 BioSieve™ Dx Marijuana Test Panel 50 | - BioSieve™ Dx Marijuana Test Strip 20 BioSieve™ Dx Marijuana Test Strip 50 BioSieve™ Marijuana Test Panel 50 BioSieve™ Marijuana Test Strip 50 Class II - 5 Classification | Product Code Target Drug | Regulation Section | Panel | |-----------------------------|---------------------------------------|------------| | NFW Cannabinoids | 862.3870, Cannabinoids Test System | Toxicology | - 6. Predicate Device BIOEASY Marijuana Test Dip Card and BIOEASY Marijuana Test Strip (K192301) - 7. Intended Use BioSieve™ Dx Marijuana Test Panel 20 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 20 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. For in vitro diagnostic use only. BioSieve™ Dx Marijuana Test Panel 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. {5}------------------------------------------------ For in vitro diagnostic use only. BioSieve™ Dx Marijuana Test Strip 20 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 20 ng/mL The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. For in vitro diagnostic use only. BioSieve™ Dx Marijuana Test Strip 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. For in vitro diagnostic use only. BioSieve™ Marijuana Test Panel 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. For in vitro diagnostic use only. BioSieve™ Marijuana Test Strip 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. For in vitro diagnostic use only. - 8. Device Description The BioSieve™ Marijuana Test Panel (Strip) and the BioSieve™ Dx Marijuana Test Panel (Strip) tests are immunochromatographic assays that use a lateral flow system for the qualitative detection of Marijuana in human urine. The products are single-use in vitro diagnostic devices. Each test kit contains a Test Device and a package insert. Each test device is sealed with a desiccant in an aluminum pouch. - Proposed Device Item Predicate (K192301) For the qualitative determination of marijuana in human urine. Indication(s) for Same use #### Substantial Equivalence Information 9. {6}------------------------------------------------ | Methodology | Competitive binding, lateral flow immunochromatographic assay based on antigen-antibody reaction | Same | |----------------------------------|--------------------------------------------------------------------------------------------------|------------------| | Type of Test | Qualitative | Same | | Specimen Type | Human urine | Same | | Calibrator and Cut-Off Values | 11-Nor-Δ9-THC-9-COOH 20 ng/mL or 50 ng/mL | Same 50 ng/mL | | Configurations | Strip and Panel | Same | | Intended Use | Prescription Use and over-the-counter use | Over-the-counter | ### 10. Test Principle The BioSieve™ Marijuana Test Panel and the BioSieve™ Marijuana Test Strip tests are rapid tests for the qualitative detection of marijuana in urine samples. They are lateral flow chromatographic immunoassay. When urine sample is added to the 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 at three different testing sites. Samples with concentration of -100% cutoff were drug-free urines samples. Other samples were prepared by spiking 11-Nor-△9-THC-9-COOH in drug-free urine samples. Each 11-Nor-△9-THC-9-COOH concentration was confirmed by LC/MS. For each concentration, tests were performed two runs per day at each site for each lot for 10 days. The results obtained are summarized in the following tables: | drug | Result | | | | | | | | | |-------|------------------|-----------------|-----------------|-----------------|---------|-----------------|-----------------|-----------------|------------------| | | -100% cut off | -75% cut off | -50% cut off | -25% cut off | cut off | +25% cut off | +50% cut off | +75% cut off | +100% cut off | | Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 42-/18+ | 32+/28- | 46+/14- | 60+/0- | 60+/0- | 60+/0- | | Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 43-/17+ | 35+/25- | 42+/18- | 60+/0- | 60+/0- | 60+/0- | | Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 41-/19+ | 33+/27- | 45+/15- | 60+/0- | 60+/0- | 60+/0- | For Strip Format of 20 ng/mL Cut-off: For Panel Format 20 ng/mL Cut-off: {7}------------------------------------------------ | Result | -100% | -75% | -50% | -25% | cut off | +25% | +50% | +75% | +100% | |---------------------------------------|---------|---------|---------|---------|---------|---------|---------|---------|---------| | drug | cut off | cut off | cut off | cut off | cut off | cut off | cut off | cut off | cut off | | Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 43-/17+ | 34+/26- | 44+/16- | 60+/0- | 60+/0- | 60+/0- | | Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 44-/16+ | 35+/25- | 46+/14- | 60+/0- | 60+/0- | 60+/0- | | Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 43-/17+ | 37+/23- | 45+/15- | 60+/0- | 60+/0- | 60+/0- | | For Strip Format of 50 ng/mL Cut-off: | | | | | | | | | | | Result | -100% | -75% | -50% | -25% | cut off | +25% | +50% | +75% | +100% | | drug | cut off | cut off | cut off | cut off | cut off | cut off | cut off | cut off | cut off | | Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 24-/36+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- | | Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 22-/38+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- | | Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 23-/37+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- | | For Panel Format 50 ng/mL Cut-off: | | | | | | | | | | | Result | -100% | -75% | -50% | -25% | cut off | +25% | +50% | +75% | +100% | | drug | cut off | cut off | cut off | cut off | cut off | cut off | cut off | cut off | cut off | | Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 30-/30+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- | | Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 26-/34+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- | | Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 28-/32+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- | The following cutoff values are verified: | Test Device | Cut-off values | |--------------------------------|----------------| | BioSieve™ Marijuana Test Panel | 20 or 50 ng/mL | | BioSieve™ Marijuana Test Strip | 20 or 50 ng/mL | ### b. Linearity Not applicable ### c. Stability The devices are stable at 4-30°C for 24 months based on accelerated and 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 and tested with 50ng/mL cut-off strip and panel devices. Potential interfering substances were added to drug-free urine samples with target drugs of -50% cutoff and +50% cutoff level and tested with 20ng/mL cut-off strip and panel devices. Compounds that show no interference at a concentration of 100µg/mL (albumin was tested at 100 mg/dL and ethanol was tested at 1%) are summarized in the following table. | Acetaminophen | β-Estradiol | Oxalic acid | |----------------------|------------------|---------------| | Acetophenetidin | Erythromycin | Oxolinic acid | | N-Acetylprocainamide | Ethanol (1% v/v) | Oxymetazoline | {8}------------------------------------------------ | Acetylsalicylic acid | Fenoprofen | Papaverine | |-----------------------|------------------------|--------------------------------------------| | Albumin (100 mg/dL) | Furosemide | Penicillin G | | Aminopyrine | Gentisic acid | Perphenazine | | Amoxicillin | Hemoglobin | Phenelzine | | Ampicillin | Hydralazine | Prednisone | | Apomorphine | Hydrochlorothiazide | (±)-Propranolol | | Ascorbic acid | Hydrocortisone | Pseudoephedrine | | Aspartame | O-Hydroxyhippuric acid | Quinine | | Atropine | 3-Hydroxytyramine | Ranitidine | | Benzilic acid | Ibuprofen | Salicylic acid | | Benzoic acid | Isoproterenol | Serotonin (5- Hydroxytyramine) | | Bilirubin | Isoxsuprine | Sulfamethazine | | Chloral hydrate | Ketamine | Sulindac | | Chloramphenicol | Ketoprofen | Tetrahydrocortisone 3-(β- Dglucuronide) | | Chlorothiazide | Labetalol | Tetrahydrocortisone 3-acetate | | Chlorpromazine | Loperamide | Tetrahydrozoline | | Cholesterol | Meperidine | Thiamine | | Clonidine | Meprobamate | Thioridazine | | Cortisone | Methoxyphenamine | Triamterene | | (-)-Cotinine | Nalidixic acid | Trifluoperazine | | Creatinine | Naloxone | Trimethoprim | | Deoxycorticosterone | Naltrexone | DL-Tryptophan | | Dextromethorphan | Naproxen | Tyramine | | Diclofenac | Niacinamide | DL-Tyrosine | | Diflunisal | Nifedipine | Uric acid | | Digoxin | Norethindrone | Verapamil | | Diphenhydramine | Noscapine | Zomepirac | | Ecgonine methyl ester | (±)-Octopamine | | - 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: | THC(Cannabinoids) (11-nor-Δ9-THC-9-COOH, Cut-off = 20 ng/mL) | Result | % Cross-Reactivity | |-----------------------------------------------------------------|--------|--------------------| | 11-nor-Δ9-THC-9-COOH | 20 | 100% | | 11-Hydroxy-Δ9-Tetrahydrocannabinol | 2000 | 1% | {9}------------------------------------------------ | 11-Nor-Δ8-Tetrahydrocannabinol-9-COOH | 20 | 100% | |---------------------------------------|--------|------| | Cannabinol | 100000 | -- | | Δ8-Tetrahydrocannabinol | 6000 | 0.5% | | Δ9-Tetrahydrocannabinol | 6000 | 0.5% | | Cannabidiol | 100000 | -- | | 11-Nor-Δ9-THC-carboxy glucuronide | 40 | 50% | | (-)-11-nor-9-carboxy-Δ9-THC | 20 | 100% | | THC(Cannabinoids) | Result | % Cross-Reactivity | |--------------------------------------------|--------|--------------------| | (11-nor-Δ9-THC-9-COOH, Cut-off = 50 ng/mL) | | | | 11-nor-Δ9-THC-9-COOH | 50 | 100% | | 11-Hydroxy-Δ9-Tetrahydrocannabinol | 5000 | 1% | | 11-Nor-Δ8-Tetrahydrocannabinol-9-COOH | 50 | 100% | | Cannabinol | 100000 | -- | | Δ8-Tetrahydrocannabinol | 15000 | 0.5% | | Δ9-Tetrahydrocannabinol | 15000 | 0.5% | | Cannabidiol | 100000 | -- | | 11-Nor-Δ9-THC-carboxy glucuronide | 100 | 50% | | (-)-11-nor-9-carboxy-Δ9-THC | 50 | 100% | #### 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 for the 50 ng/mL cut-off devices. And the same urine specific gravity samples were spiked with target drugs at +50% cutoff and -50% cutoff levels for the 20 ng/mL cut-off devices. Three Operators tested each sample using test devices from three different lots. The results were all positive for samples at +25% cutoff or +50% cutoff and all negative for samples at -25% cutoff or -50% cutoff, indicating that urine specific gravity between 1.000 and 1.035 has no effect on the accuracy and precision of the test devices. 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 for the 50 ng/mL cut-off devices. And the same urine pH samples were spiked with target drugs at +50% cutoff and -50% cutoff levels for the 20 ng/mL cut-off devices. Three Operators tested each sample using test devices from three different lots. The results were all positive for samples at +25% or +50% cutoff and all negative for samples at -25% or -50% cutoff, indicating that urine pH value between 4.0 and 9.0 has no effect on the accuracy and precision of the test device. #### 2. Comparison Studies The method comparison studies for BioSieve™ Marijuana Test Panel and BioSieve™ Marijuana Test Strip were performed with six operators. Operators ran 80 (40 negative and 40 positive) unaltered {10}------------------------------------------------ urine samples. The samples were blind labeled and compared to LC/MS results. The results are presented in the table below: | For BioSieve™ Dx Marijuana Test Strip 20 | | | | |------------------------------------------|--|--|--| | | | | | | | | Drug-Free | Low Negative by LC-MS/MS (less than - 50%) | Near Cutoff Negative by LC-MS/MS (Between -50% and the Cutoff) | Near Cutoff Positive by LC- MS/MS (Between the cutoff and +50%) | High Positive by LC-MS/MS (greater than +50%) | |------------|----------|-----------|--------------------------------------------------------|----------------------------------------------------------------------------|--------------------------------------------------------------------------------|--------------------------------------------------------| | Operator A | Positive | 0 | 0 | 1 | 17 | 22 | | | Negative | 10 | 16 | 13 | 1 | 0 | | Operator B | Positive | 0 | 0 | 2 | 16 | 22 | | | Negative | 10 | 16 | 12 | 2 | 0 | | Operator C | Positive | 0 | 0 | 2 | 16 | 22 | | | Negative | 10 | 16 | 12 | 2 | 0 | ## Discordant Results: | Operator | Sample Number | LC/MS Result (ng/mL) | BioSieve™ Result | |------------|---------------|----------------------|------------------| | Operator A | 22181 | 19.6 | + | | Operator B | 22181 | 19.6 | + | | Operator B | 22042 | 19.5 | + | | Operator C | 22005 | 19.3 | + | | Operator C | 22181 | 19.6 | + | | Operator A | 22006 | 21.5 | - | | Operator B | 22241 | 23.1 | - | | Operator B | 22279 | 23.7 | - | | Operator C | 22006 | 21.5 | - | | Operator C | 22161 | 23.2 | - | For BioSieve™ Dx Marijuana Test Panel 20 | | | Drug-Free | Low Negative by LC-MS/MS (less than - 50%) | Near Cutoff Negative by LC-MS/MS (Between -50% and the Cutoff) | Near Cutoff Positive by LC- MS/MS (Between the cutoff and +50%) | High Positive by LC-MS/MS (greater than +50%) | |------------|----------|-----------|--------------------------------------------------------|----------------------------------------------------------------------------|--------------------------------------------------------------------------------|--------------------------------------------------------| | Operator A | Positive | 0 | 0 | 2 | 16 | 22 | | | Negative | 10 | 16 | 12 | 2 | 0 | | Operator B | Positive | 0 | 0 | 2 | 17 | 22 | | | Negative | 10 | 16 | 12 | 1 | 0 | | Operator C | Positive | 0 | 0 | 1 | 16 | 22 | {11}------------------------------------------------ | | Negative | 10 | 16 | 13 | 2 | 0 | |--|----------|----|----|----|---|---| |--|----------|----|----|----|---|---| Discordant Results: | Operator | Sample Number | LC/MS Result (ng/mL) | BioSieve™ Result | |------------|---------------|----------------------|------------------| | Operator D | 22071 | 19.3 | + | | Operator D | 22073 | 19.6 | + | | Operator E | 22071 | 19.3 | + | | Operator E | 22204 | 19.5 | + | | Operator F | 22073 | 19.6 | + | | Operator D | 22205 | 23.7 | - | | Operator D | 22302 | 21.5 | - | | Operator E | 22302 | 21.5 | - | | Operator F | 22016 | 23.2 | - | | Operator F | 22302 | 21.5 | - | For BioSieve™ Marijuana Test Strip 50 | | | Drug-Free | Low Negative by LC-MS/MS (less than - 50%) | Near Cutoff Negative by LC-MS/MS (Between -50% and the Cutoff) | Near Cutoff Positive by LC- MS/MS (Between the cutoff and +50%) | High Positive by LC-MS/MS (greater than +50%) | |------------|----------|-----------|--------------------------------------------------------|----------------------------------------------------------------------------|--------------------------------------------------------------------------------|--------------------------------------------------------| | Operator A | Positive | 0 | 0 | 2 | 16 | 22 | | | Negative | 10 | 16 | 12 | 2 | 0 | | Operator B | Positive | 0 | 0 | 2 | 16 | 22 | | | Negative | 10 | 16 | 12 | 2 | 0 | | Operator C | Positive | 0 | 0 | 1 | 16 | 22 | | | Negative | 10 | 16 | 13 | 2 | 0 | ## Discordant Results: | Operator | Sample Number | LC/MS Result (ng/mL) | BioSieve™ Result | |------------|---------------|----------------------|------------------| | Operator A | 22172 | 49.2 | + | | Operator A | 22318 | 46.8 | + | | Operator B | 22115 | 47.8 | + | | Operator B | 22172 | 49.2 | + | | Operator C | 22172 | 49.2 | + | | Operator A | 22013 | 50.5 | - | | Operator A | 22237 | 50.9 | - | | Operator B | 22237 | 50.9 | - | | Operator B | 22284 | 53.9 | - | | Operator C | 22013 | 50.5 | - | | Operator C | 22237 | 50.9 | - | {12}------------------------------------------------ | | | Drug-Free | Low Negative by LC-MS/MS (less than - 50%) | Near Cutoff Negative by LC-MS/MS (Between -50% and the Cutoff) | Near Cutoff Positive by LC- MS/MS (Between the cutoff and +50%) | High Positive by LC-MS/MS (greater than +50%) | |------------|----------|-----------|--------------------------------------------------------|----------------------------------------------------------------------------|--------------------------------------------------------------------------------|--------------------------------------------------------| | Operator A | Positive | 0 | 0 | 1 | 16 | 22 | | | Negative | 10 | 16 | 13 | 2 | 0 | | Operator B | Positive | 0 | 0 | 1 | 16 | 22 | | | Negative | 10 | 16 | 13 | 2 | 0 | | Operator C | Positive | 0 | 0 | 2 | 16 | 22 | | | Negative | 10 | 16 | 12 | 2 | 0 | ## Discordant Results: | Operator | Sample Number | LC/MS Result (ng/mL) | BioSieve™ Result | |------------|---------------|----------------------|------------------| | Operator D | 22217 | 46.8 | + | | Operator E | 22206 | 49.2 | + | | Operator F | 22017 | 47.8 | + | | Operator F | 22206 | 49.2 | + | | Operator D | 22137 | 50.9 | - | | Operator D | 22152 | 53.9 | - | | Operator E | 22103 | 50.5 | - | | Operator E | 22137 | 50.9 | - | | Operator F | 22103 | 50.5 | - | | Operator F | 22152 | 53.9 | - | Lay-user study: A lay user study was performed at three intended user sites with 280 lay persons for the devices. The lay users had diverse educational and professional backgrounds and ranged in age from 18 to > 50 years. Urine samples were prepared at the following concentrations; negative, +/- 75%, +/-50%, +/-25% of the 50 ng/mL cutoff by spiking 11-Nor-△9-THC-9-COOH into drug free-pooled urine specimens. The concentrations of the samples were confirmed by LC/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. Summary results are shown below. ## The results summary for strip format: | % of Cutoff | Number of samples | Drug Concentration by LC/MS/MS(ng/mL) | Lay person Results | | The percentage of correct results (%) | |-------------|----------------------|---------------------------------------------|--------------------|--------------------|------------------------------------------| | | | | No. of Positive | No. of Negative | | {13}------------------------------------------------ | -100% Cutoff | 20 | 0 | 0 | 20 | 100 | |--------------|----|------|----|----|-----| | -75% Cutoff | 20 | 12 | 0 | 20 | 100 | | -50% Cutoff | 20 | 24.5 | 0 | 20 | 100 | | -25% Cutoff | 20 | 36.2 | 1 | 19 | 95 | | +25% Cutoff | 20 | 60.9 | 20 | 0 | 100 | | +50% Cutoff | 20 | 76.2 | 20 | 0 | 100 | | +75% Cutoff | 20 | 90.5 | 20 | 0 | 100 | The results summary for panel format: | % of Cutoff | Number of samples | Drug Concentration by LC/MS/MS(ng/mL) | Lay person Results | | The percentage of correct results (%) | |--------------|----------------------|---------------------------------------------|--------------------|--------------------|------------------------------------------| | | | | No. of Positive | No. of Negative | | | -100% Cutoff | 20 | 0 | 0 | 20 | 100 | | -75% Cutoff | 20 | 12 | 0 | 20 | 100 | | -50% Cutoff | 20 | 24.5 | 0 | 20 | 100 | | -25% Cutoff | 20 | 36.2 | 1 | 19 | 95 | | +25% Cutoff | 20 | 60.9 | 19 | 1 | 95 | | +50% Cutoff | 20 | 76.2 | 20 | 0 | 100 | | +75% Cutoff | 20 | 90.5 | 20 | 0 | 100 | 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 BioSieve™ Marijuana Test Panel and BioSieve™ Marijuana Test Strip are substantially equivalent to the predicate device.