K Number
K232604
Date Cleared
2024-01-10

(135 days)

Product Code
Regulation Number
862.3870
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The LYHER® Urine Multi-Drug Test Kit (Cup), LYHER® Urine Multi- Drug Test Kit (Cassette), and LYHER® Urine Multi-Drug Test Kit (Dipcard) are rapid lateral flow immunoassays for the qualitative detection of d-Amphetamine, d-Methamphetamine, Benzoylecgonine, Morphine, Phencyclidine and THC-COOH in human urine. The test cut-off concentrations and the compounds the tests are calibrated to are as follows:

TestCalibratorCut-off (ng/mL)
Amphetamine (AMP)d-Amphetamine1000
Cocaine (COC)Benzoylecgonine300
Marijuana (THC)11-nor-Δ9-THC-9-COOH50
Methamphetamine (MET)d-Methamphetamine1000
Opiates(OPI)Morphine2000
Phencyclidine (PCP)Phencyclidine25

The single or multi-test panels can consist of the above listed analytes in any combination, up to a maximum of 6 analytes. The drug screen tests are intended for prescription use only. The tests provide only a preliminary result. A more specific alternative chemical method should be used in order to obtain a confirmed presumptive result. Gas Chromatography/Mass Spectrometry (GC/MS), Liquid Chromatography / Mass Spectrometry (LC/MS) and their tandem mass-spectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.

Device Description

The LYHER® Urine Multi-Drug Test Kit(Cup), LYHER® Urine Multi-Drug Test Kit(Cassette), LYHER® Urine Multi-Drug Test Kit(Dipcard) are immunochromatographic assays that use a lateral flow system for the qualitative detection of d-Amphetamine, d-Methamphetamine, Benzoylecgonine, Morphine, Phencyclidine and THC-COOH in human urine. The LYHER® Urine Multi-Drug Test Kit (Cup) device consists of 25 or 40 cup devices and a package insert. The LYHER® Urine Multi-Drug Test Kit (Dipcard) device consists of 10/15/20/25 Dip Card devices, a package insert. The LYHER® Urine Multi-Drug Test Kit (Cassette) device consists of 10/15/20/25 cassette devices, 10/15/20/25 droppers, a package insert.

AI/ML Overview

The provided text describes the 510(k) summary for the LYHER® Urine Multi-Drug Test Kits, which are rapid lateral flow immunoassays for the qualitative detection of several drugs in human urine. The study presented is a method comparison study to demonstrate substantial equivalence to a predicate device, not a study to establish acceptance criteria for a new AI/ML device. Therefore, much of the requested information (e.g., AI/ML specific details, number of experts, adjudication methods, MRMC study, sample size for training set) is not applicable or directly available from this document because it pertains to a different type of device and study.

However, based on the provided text, I can extract information related to the acceptance criteria (cut-off values) and the performance of the device in relation to these criteria.

1. Table of acceptance criteria and the reported device performance:

The acceptance criteria for these devices are defined by the cut-off concentrations for each drug. The reported device performance is demonstrated through in-house method comparison studies using various concentrations around these cut-offs. The precision studies indicate that samples at or below -25% of the cut-off were consistently negative, and samples at or above +25% of the cut-off were consistently positive. The method comparison tables provide more detailed performance around the cut-off by showing the number of positive and negative results at different concentration ranges compared to LC/MS results.

Here is a summary table, combining the listed cut-off values and inferring the performance based on the precision study description:

TestCalibratorAcceptance Criteria (Cut-off, ng/mL)Device Performance at/below -25% Cut-offDevice Performance at/above +25% Cut-off
Amphetamine (AMP)d-Amphetamine1000All NegativeAll Positive
Cocaine (COC)Benzoylecgonine300All NegativeAll Positive
Marijuana (THC)11-nor-Δ9-THC-9-COOH50All NegativeAll Positive
Methamphetamine (MET)d-Methamphetamine1000All NegativeAll Positive
Opiates(OPI)Morphine2000All NegativeAll Positive
Phencyclidine (PCP)Phencyclidine25All NegativeAll Positive

Note: The precision study states that "The test results of the specimens at the concentrations at and below -25% of the cut off obtained by all the three personnel were all negative while the test results of the specimens at the concentration at and above +25% of the cut off value were all positive." This broadly defines the performance against the cut-off. The method comparison tables offer more granular data but are too extensive to fully replicate here for each drug and each device type. These tables show that most results within the -25% to +25% cut-off range are discordant (either positive by LC/MS and negative by device, or vice-versa), which is expected for qualitative tests around the cut-off.

2. Sample size used for the test set and the data provenance:

  • Sample Size for Precision Studies: For each drug and each concentration (-100%, -75%, -50%, -25%, +25%, +50%, +75%, +100% cut off), 50 replicates were analyzed by each of 6 operators using three lots of the product. This means for one drug and one concentration, there were 50 replicates * 3 lots * 6 operators = 900 tests. Across 8 concentrations, this would be 7,200 tests per drug. Since there are 6 drugs, the total number of tests in the precision study is substantial.
  • Sample Size for Method Comparison Studies:
    • AMP Cassettes, Dipcards, Cups: 43 negative urine samples, and a varying number of samples at different concentrations relative to the cut-off (e.g., for AMP Cassettes, 12 samples in -50% cut offcut off, 23 samples in Cut off+50%cut off, 17 samples >+50%cut off). The total number of unique samples is not explicitly stated but can be inferred by summing up the categories for each operator. For AMP Cassettes, for Operator 1, this totals 43 (negative) + 12 (<-25%to cutoff) + 23 (cutoff to >+25%) + 17 (>+25%) = 95 unique samples. This was done for 3 operators for each of the 3 device types (cassette, dipcard, cup).
    • Similar sample distributions are provided for COC, MET, OPI, PCP, and THC across the cassette, dipcard, and cup formats.
  • Data Provenance: The method comparison studies were performed "in-house" and used "unaltered clinical samples." The document does not specify the country of origin of the data, but the submitter is Hangzhou Laihe Biotech Co., Ltd., China. The studies are assumed to be retrospective as they involve "unaltered clinical samples" compared to a reference method.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This information is not applicable as the device is an in-vitro diagnostic test. "Experts" in the context of IVD performance usually refer to the highly accurate reference method. In this case:

  • Ground Truth Method: Gas Chromatography/Mass Spectrometry (GC/MS), Liquid Chromatography / Mass Spectrometry (LC/MS) and their tandem mass-spectrometer versions are preferred confirmatory methods, and LC/MS was used to confirm drug concentrations in the precision studies and as the comparator (ground truth) in the method comparison studies.
  • Number/Qualifications of Experts: The document does not refer to human experts establishing ground truth for individual samples, but rather mentions "three laboratory assistants" who "ran samples" for the method comparison studies and "6 operators" for the precision studies. These personnel are performing the tests, not establishing the ground truth. The ground truth is established by chemical analysis (LC/MS).

4. Adjudication method for the test set:

This information is not applicable as the device is an in-vitro diagnostic test and the ground truth is established by a quantitative chemical analysis (LC/MS), not through human expert consensus or qualitative review that would require adjudication.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:

This is not applicable. The device is a rapid lateral flow immunoassay, not an AI/ML powered device, and no human reader assistance is involved in the interpretation beyond visual reading of the test lines. Therefore, an MRMC study related to AI assistance is not relevant.

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

This is not applicable. The device is not an algorithm or AI system. It is a physical immunoassay kit.

7. The type of ground truth used:

The ground truth used for establishing performance and comparing results in the method comparison study is LC/MS (Liquid Chromatography / Mass Spectrometry), which is a highly accurate chemical method for quantifying drug concentrations in urine.

8. The sample size for the training set:

This is not applicable as the device is not an AI/ML system and does not have a "training set" in that context. The device's performance is inherently based on its biochemical design.

9. How the ground truth for the training set was established:

This is not applicable for the same reason as above. If considering the "training" analogous to R&D and optimization of the immunoassay, the performance characteristics (e.g., specificity, cross-reactivity) would have been established using controlled spiking experiments and comparison to reference methods like LC/MS. The document mentions "These samples were prepared by spiking drug in negative samples. Each drug concentration was confirmed by LC/MS" in the precision studies, which indicates how known concentrations were established for performance evaluation.

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

Hangzhou Laihe Biotech Co., Ltd. % Ethan Liu RA specialist Shanghai Thinkwell Consulting Co., Ltd Xinling Rd., 211/6F Shanghai, Shanghai 201100 China

Re: K232597

Trade/Device Name: LYHER® Urine Multi-Drug Test Kit(Cup), LYHER® Urine Multi-Drug Test Kit(Cassette), LYHER® Urine Multi-Drug Test Kit(Dipcard) Regulation Number: 21 CFR 862.3650 Regulation Name: Opiate test system Regulatory Class: Class II Product Code: DJG, DIO, DKZ, LDJ, DJC, LCM Dated: November 27, 2023 Received: December 1, 2023

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 mediation-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, Digitally signed by Jos Joseph A. A Kotarek -S Date: 2024.01.09 14:04:36 Kotarek -S Joseph Kotarek, PhD 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

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Indications for Use

510(k) Number (if known) K232597

Device Name

L YHER® Urine Multi-Drug Test Kit(Cup), LYHER® Urine Multi-Drug Test Kit(Cassette), LYHER® Urine Multi-Drug Test Kit(Dipcard)

Indications for Use (Describe)

The LYHER® Urine Multi-Drug Test Kit (Cup), LYHER® Urine Multi- Drug Test Kit (Cassette), and LYHER® Urine Multi-Drug Test Kit (Dipcard) are rapid lateral flow immunoassays for the qualitative detection of d-Amphetamine, d-Methamphetamine, Benzoylecgonine, Morphine, Phencyclidine and THC-COOH in human urine. The test cut-off concentrations and the compounds the tests are calibrated to are as follows:

TestCalibratorCut-off (ng/mL)
Amphetamine (AMP)d-Amphetamine1000
Cocaine (COC)Benzoylecgonine300
Marijuana (THC)11-nor-Δ9-THC-9-COOH50
Methamphetamine (MET)d-Methamphetamine1000
Opiates(OPI)Morphine2000
Phencyclidine (PCP)Phencyclidine25

The single or multi-test panels can consist of the above listed analytes in any combination, up to a maximum of 6 analytes. The drug screen tests are intended for prescription use only. The tests provide only a preliminary result. A more specific alternative chemical method should be used in order to obtain a confirmed presumptive result. Gas Chromatography/Mass Spectrometry (GC/MS), Liquid Chromatography / Mass Spectrometry (LC/MS) and their tandem mass-spectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)☐ Over-The-Counter Use (21 CFR 801 Subpart C)
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Image /page/3/Picture/0 description: The image shows the logo for Hangzhou Laihe Biotech Co., Ltd. The logo consists of the company name in a stylized font. The letters 'LY' are colored in yellow, while the rest of the letters are in green. The company's name is written in black below the logo.

510(k) Summary 510(k) Number: K232597

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:Hangzhou Laihe Biotech Co., Ltd.
Address: Room 401-406, F1-3, Building 1,No.425Miaohouwang Road, Xixing Street, BinjiangDistrict,Hangzhou, 310051 Zhejiang P.R. China
Tel.: +86 571 8765 3090
Fax: +86 571 8665 8000
www.lyher.com
Contact Person:Ethan Liu
Shanghai Thinkwell Consulting Co., Ltd
Address:Xinling Rd., 211/6F Shanghai, 201100,P.R. China
Phone:0086-15216699240
Email:xtdeepwater@126.com
Date Prepared:Dec 29, 2023

5.2 Device

LYHER® Urine Multi-Drug Test Kit(Cup) LYHER® Urine Multi-Drug Test Kit(Cassette) LYHER® Urine Multi-Drug Test Kit(Dipcard)

Classification:

TestProduct CodeCFR #Panel
Opiates(OPI)DJG862.3650/Opiate test system.Toxicology
Cocaine (COC)DIO862.3250/Cocaine andcocaine metabolite testsystem.Toxicology
Amphetamine (AMP)DKZ862.3100/Amphetamine TestSystemToxicology
Marijuana (THC)LDJ862.3870/Cannabinoid testsystem.Toxicology
Methamphetamine(MET)DJC862.3610/Methamphetaminetest system.Toxicology
Phencyclidine (PCP)LCMUnclassifiedToxicology

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Image /page/4/Picture/0 description: The image shows the logo for LYHER, a company named Hangzhou Laihe Biotech Co., Ltd. The logo is in green and yellow, with the letters "LY" in yellow and the rest of the letters in green. The company name is written in black below the logo.

5.3 Predicate Device:

ATTEST Drug Screen Cup, ATTEST Drug Screen Dip Card, K182123

5.4 Device Description

The LYHER® Urine Multi-Drug Test Kit(Cup), LYHER® Urine Multi-Drug Test Kit(Cassette), LYHER® Urine Multi-Drug Test Kit(Dipcard) are immunochromatographic assays that use a lateral flow system for the qualitative detection of d-Amphetamine, d-Methamphetamine, Benzoylecgonine, Morphine, Phencyclidine and THC-COOH in human urine. The LYHER® Urine Multi-Drug Test Kit (Cup) device consists of 25 or 40 cup devices and a package insert. The LYHER® Urine Multi-Drug Test Kit (Dipcard) device consists of 10/15/20/25 Dip Card devices, a package insert. The LYHER® Urine Multi-Drug Test Kit (Cassette) device consists of 10/15/20/25 cassette devices, 10/15/20/25 droppers, a package insert.

5.5 Indication for Use:

The LYHER® Urine Multi-Drug Test Kit(Cup), LYHER® Urine Multi-Drug Test Kit(Cassette), LYHER® Urine Multi-Drug Test Kit(Dipcard) are rapid lateral flow immunoassays for the qualitative detection of d-Amphetamine, d-Methamphetamine, Benzoylecgonine, Morphine, Phencyclidine and THC-COOH in human urine. The test cut-off concentrations and the compounds the tests are calibrated to are as follows:

TestCalibratorCut-off (ng/mL)
Amphetamine (AMP)d-Amphetamine1000
Cocaine (COC)Benzoylecgonine300
Marijuana (THC)11-nor-\u03949-THC-9-COOH50
Methamphetamine (MET)d-Methamphetamine1000
Opiates(OPI)Morphine2000
Phencyclidine (PCP)Phencyclidine25

The single or multi-test panels can consist of the above listed analytes in any combination, up to a maximum of 6 analytes. The drug screen tests are intended for prescription use only. The tests provide only a preliminary result. A more specific alternative chemical method should be used in order to obtain a confirmed presumptive positive result. Gas Chromatography/Mass Spectrometry (GC/MS), Liquid Chromatography/Mass Spectrometry (LC/MS) and their tandem massspectrometer versions are the preferred confirmatory methods. Careful consideration and judgment should be applied to any drugs of abuse screen test result, particularly when evaluating preliminary positive results.

5.8 Substantial Equivalence

A summary comparison of features of the LYHER® Urine Multi-Drug Test Kit(Cup/Cassette/Dipcard) and the predicate devices is provided in following tables.

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Section 5 510(k) Summary

Hangzhou Laihe Biotech Co., Ltd.

ItemProposed DevicePredicate Device-K182123
Indicationsfor UseFor the qualitative determination of drugs ofabuse and/or their metabolites in human urine.Same
MethodologyLateral flow immunochromatographic assaybased on competitive bindingSame
Type of TestQualitativeSame
SpecimenTypeHuman UrineSame

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Image /page/6/Picture/0 description: The image shows the logo for LYHER. The "LY" is in yellow, and the "HER" is in green. There is a registered trademark symbol next to the "R".

Section 5 510(k) Summary

Hangzhou Laihe Biotech Co., Ltd.

Cut-off Values
TestCalibratorCut-off ng/mLTestCalibratorCutoff ng/ml
Opiates(OPI)Morphine20006-Acetylmorphine6-monoacetyl-morphine10
Cocaine (COC)Benzoylecgonine300Amphetamine500d-amphetamine500
Amphetamine(AMP)d-Amphetamine1000Amphetamine1000d-amphetamine1000
Marijuana (THC)11-nor-Δ9-THC-9-COOH50BarbituratesSecobarbital300
Methamphetamine(MET)d-Methamphet-amine1000BenzodiazepineOxazepam300
Phencyclidine (PCP)Phencyclidine25BuprenorphineBuprenorphine10
Cocaine150Benzoylecgonine150
Cocaine300Benzoylecgonine300
EDDP2-ethylidene-1,5-dimethyl-3-3-diphenyl-pyrrolidine300
Ecstasyd/l-methylenedioxy-meth-amphetamine500
Methamphet-amine 500d-methamphetamine500
Methamphet-amine 1000d-methamphetamine1000
Methadoned/l-methadone300
MorphineMorphine300
OpiatesMorphine2,000
OxycodoneOxycodone100
PhencyclidinePhencyclidine25
Propoxyphened-propoxyphene300
TricyclicsNortriptyline1,000
MarijuanaTHC-COOH5
Intended UseFor prescription uses.Same
Configura-tionsCup,Dip Card, CassetteCup, Dip Card

5.9 Test Principle

Each device employs lateral flow immunochromatographic technology and is based on the principle of competitive binding. The product contains membrane strips coated with drug-protein conjugates on the T zone, goat anti-rabbit polycolonal antibody at the C zone, and a conjugate pad which 5-4

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contains colloidal gold particles coated with mouse monoclonal antibodies specific against to the corresponding drugs and colloidal gold particles coated with rabbit IgG.

If the level of drug in the urine specimen is below the cutoff concentration, the T line appears as a visible burgundy line. If the level of drug in the urine specimen is above the cutoff, no T line develops.The control line (C line) serves as an internal quality control line should always appear as a burgundy-colored band regardless of the drug, if enough sample volume has been added to the test and if the sample has correctly migrated up the test strip. Testing is based on the principle of a competitive immunochemical reaction between a chemically labeled drug (drug-protein conjugate) and the drug or drug metabolites which may be present in the urine sample competing for the limited antibody binding sites.

5.10 Performance Characteristics

5.10.1 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, +25% cut off, +50% cut off, +75% cut off and +100% cut off, These samples were prepared by spiking drug in negative samples. Each drug concentration was confirmed by LC/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 specimen was analyzed in 50 replicates by each of the testing personnel at each Lab site by using three lots of the product separately.

The test results of the specimens at the concentrations at and below -25% of the cut off obtained by all the three personnel were all negative while the test results of the specimens at the concentration at and above +25% of the cut off value were all positive.

  • b. Linearity
    Not applicable

Stability ﻥ

The devices are stable at 2-30 °C for 24 months based on the accelerated stability study.

d. Cut-off

Dilute the solution by negative urine to the concentration of +50% cut off, +25%cut off, -25%cut off, -50%cut off respectively. To test all these above specimens by three different batches of the candidate product and each concentration will be tested for 25 replicates.

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

TestCalibratorCut-off (ng/mL)
Opiates(OPI)Morphine2000
Cocaine (COC)Benzoylecgonine300
Amphetamine(AMP)d-Amphetamine1000

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Marijuana (THC)11-nor-Δ9-THC-9-COOH50
Methamphetamine(MET)d-Methamphetamine1000
Phencyclidine(PCP)Phencyclidine25

e. Interference

Potential interfering substances found in human urine of physiological conditions were added to drug-free urine and target drugs urine with concentrations at 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 are summarized in the following tables. There were no differences observed for different devices

Amphetamine:

SubstanceSubstanceSubstance
AcetaminophenErythromycinPenicillin-G
AcetoneEthanolPheniramine
Acetylsalicylic acidFurosemidePhenothiazine
AlbuminGabapentinPregablin
AmpicillinGlucoseProcaine
Ascorbic acidGuaiacol glyceryl etherPropoxyphene
AspartameHemoglobinQuinidine
AtropineIbuprofenRanitidine
BenzocaineIsoproterenolRiboflavin
BilirubinIsoproterenolSertraline
CaffeineKetamineSodium chloride
ChloroquineLidocaineSulindac
ChlorpheniramineI-PhenylephrineTheophylline
CreatineMethadoneTyramine
DexbrompheniramineMethylephedrineβ-Phenylethylamine
DextromethorphanNaproxenPhencyclidine(PCP)
DimenhydrinateNiacinamideCocaine
DimethylaminoantipyrineNicotineMorphine
DiphenhydramineNorephedrineΔ9-tetrahydrocannabinol
DopamineOxalic acid
EDDPOxycodone

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EphedrinePantoprazole
-------------------------

Cocaine(COC)

SubstanceSubstanceSubstance
AcetaminophenErythromycinPenicillin-G
AcetoneEthanolPheniramine
Acetylsalicylic acidFurosemidePhenothiazine
AlbuminGabapentinPregablin
AmpicillinGlucoseProcaine
Ascorbic acidGuaiacol glyceryl etherPropoxyphene
AspartameHemoglobinQuinidine
AtropineIbuprofenRanitidine
BenzocaineIsoproterenolRiboflavin
BilirubinIsoproterenolSertraline
CaffeineKetamineSodium chloride
ChloroquineLidocaineSulindac
Chlorpheniraminel-PhenylephrineTheophylline
CreatineMethadoneTyramine
DexbrompheniramineMethylephedrineβ-Phenylethylamine
DextromethorphanNaproxenPhencyclidine(PCP)
DimenhydrinateNiacinamideMorphine
DimethylaminoantipyrineNicotineMethylamphetamine
DiphenhydramineNorephedrineMDMA
DopamineOxalic acidΔ9-tetrahydrocannabinol
EDDPOxycodoneAmphetamine
EphedrinePantoprazole

MET

SubstanceSubstanceSubstance
AcetaminophenErythromycinPenicillin-G
AcetoneEthanolPheniramine
Acetylsalicylic acidFurosemidePhenothiazine
AlbuminGabapentinPregablin
AmpicillinGlucoseProcaine
Ascorbic acidGuaiacol glyceryl etherPropoxyphene
AspartameHemoglobinQuinidine
AtropineIbuprofenRanitidine
BenzocaineIsoproterenolRiboflavin
BilirubinIsoproterenolSertraline
CaffeineKetamineSodium chloride
ChloroquineLidocaineSulindac
Chlorpheniraminel-PhenylephrineTheophylline

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

Image /page/10/Picture/0 description: The image shows the word "LYHER" in a stylized font. The "L" and "HER" are in green, while the "Y" is in orange. There is a registered trademark symbol next to the "R".

CreatineMethadoneTyramine
DexbrompheniramineMethylephedrineβ-Phenylethylamine
DextromethorphanNaproxenPhencyclidine(PCP)
DimenhydrinateNiacinamideCocaine
DimethylaminoantipyrineNicotineMorphine
DiphenhydramineNorephedrineΔ9-tetrahydrocannabinol
DopamineOxalic acid
EDDPOxycodone
EphedrinePantoprazole

OPI

OPI
SubstanceSubstanceSubstance
AcetaminophenErythromycinPenicillin-G
AcetoneEthanolPheniramine
Acetylsalicylic acidFurosemidePhenothiazine
AlbuminGabapentinPregablin
AmpicillinGlucoseProcaine
Ascorbic acidGuaiacol glyceryl etherPropoxyphene
AspartameHemoglobinQuinidine
AtropineIbuprofenRanitidine
BenzocaineIsoproterenolRiboflavin
BilirubinIsoproterenolSertraline
CaffeineKetamineSodium chloride
ChloroquineLidocaineSulindac
ChlorpheniramineL-PhenylephrineTheophylline
CreatineMethadoneTyramine
DexbrompheniramineMethylephedrineβ-Phenylethylamine
DextromethorphanNaproxenPhencyclidine(PCP)
DimenhydrinateNiacinamideCocaine
DimethylaminoantipyrineNicotineMethylamphetamine
DiphenhydramineNorephedrineMDMA
DopamineOxalic acidAmphetamine
EDDPOxycodoneΔ9-tetrahydrocannabinol
EphedrinePantoprazole

РСР

SubstanceSubstanceSubstance
AcetaminophenErythromycinPenicillin-G
AcetoneEthanolPheniramine
Acetylsalicylic acidFurosemidePhenothiazine
AlbuminGabapentinPregablin
AmpicillinGlucoseProcaine

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

Image /page/11/Picture/0 description: The image shows the word "LYHER" in a stylized font. The "LY" portion of the word is in orange, while the "HER" portion is in green. The letters are bold and have a rounded appearance. There is a registered trademark symbol next to the "R".

Ascorbic acidGuaiacol glyceryl etherPropoxyphene
AspartameHemoglobinQuinidine
AtropineIbuprofenRanitidine
BenzocaineIsoproterenolRiboflavin
BilirubinIsoproterenolSertraline
CaffeineKetamineSodium chloride
ChloroquineLidocaineSulindac
ChlorpheniramineI-PhenylephrineTheophylline
CreatineMethadoneTyramine
DexbrompheniramineMethylephedrineβ-Phenylethylamine
DextromethorphanNaproxenCocaine
DimenhydrinateNiacinamideMorphine
DimethylaminoantipyrineNicotineMethylamphetamine
DiphenhydramineNorephedrineMDMA
DopamineOxalic acidAmphetamine
EDDPOxycodoneΔ9-tetrahydrocannabinol
EphedrinePantoprazole

THC

SubstanceSubstanceSubstance
AcetaminophenErythromycinPenicillin-G
AcetoneEthanolPheniramine
Acetylsalicylic acidFurosemidePhenothiazine
AlbuminGabapentinPregablin
AmpicillinGlucoseProcaine
Ascorbic acidGuaiacol glyceryl etherPropoxyphene
AspartameHemoglobinQuinidine
AtropineIbuprofenRanitidine
BenzocaineIsoproterenolRiboflavin
BilirubinIsoproterenolSertraline
CaffeineKetamineSodium chloride
ChloroquineLidocaineSulindac
Chlorpheniraminel-PhenylephrineTheophylline
CreatineMethadoneTyramine
DexbrompheniramineMethylephedrineβ-Phenylethylamine
DextromethorphanNaproxenPhencyclidine(PCP)
DimenhydrinateNiacinamideCocaine
DimethylaminoantipyrineNicotineMorphine
DiphenhydramineNorephedrineMethylamphetamine
DopamineOxalic acidMDMA
EDDPOxycodoneAmphetamine
EphedrinePantoprazole

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

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 are listed below. There were no differences observed for different devices.

CompoundConcentration(ng/mL)%Cross Reactivity
Amphetamine (AMP)
D-Amphetamine1000100%
D,L-Amphetamine sulfate250040%
β-Phenylethylamine600001.67%
(±)3,4-Methylenedioxyamphetamine (MDA)150066.7%
Phentermine250040%
Tryptamine600001.67%
Tyramine500020%
L-amphetamine1000001%
COCAINE (COC)ng/ml
Benzoylecgonine300100%
Cocaine75040%
Cocaethylene100003%
Ecgonine200001.5%
Ecgonine methylester500000.6%
MARIJUANA (THC)
Cannabinol200000.25%
11-nor-Δ8-THC-9 COOH30167%
11-nor-Δ9 -THC-9 COOH50100%
△8 -THC150000.33%
△9 -THC150000.33%
(±)-11-Hydroxy-Δ9-THC50001%
Cannabidiol200000.25%
METHAMPHETAMINE (MET)
p-Hydroxymethamphetamine300003.33%
D-Methamphetamine1000100%
L-Methamphetamine800012.5%
(±)-3,4-Methylenedioxymethamphetamine200050%
Mephentermine500002%
D-Amphetamine1000001%
CompoundConcentration(ng/mL)%Cross Reactivity
L-Amphetamine1000001%
(1R, 2S)-(-)-Ephedrine1000001%
(+/-) 3,4-Methylenedioxy-nethylamphetamine (MDEA)300003.33%
OPIATES (OPI)
Morphine2000100%
Codeine1500133%
Ethylmorphine300006.67%
Hydrocodone800002.5%
Hydromorphone1000020%
Levophanol500040%
6-Monoacetylmorphine2000100%
Morphine 3-β-D-glucuronide500040%
Norcodeine300006.67%
Normorphone1000002%
Oxycodone1000002%
Oxymorphone1000002%
Procaine600003.33%
Thebaine300006.67%
6-Acetylmorphine (6-AM)2000100%
Diacetylmorphine (heroin)500040%
Phencyclidine (PCP)
Phencyclidine25100%
4-hydroxy-PCP125000.2%

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

Image /page/13/Picture/0 description: The image shows the word "LYHER" in a stylized font. The "LY" is in orange, while the "HER" is in green. There is a registered trademark symbol to the right of the "R".

g. Effect of Urine Specific Gravity and Urine pH

To investigate the effect of urine specific gravity and urine pH, urine samples, with 1.003 to 1.032 specific gravity or urine samples with pH 3 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% Cut-off and all negative for samples at and below -25% Cut-Off. There were no differences observed for different devices.

5.10.2 Method comparison

Method comparison studies for the LYHER® Urine Multi-Drug Test were performed in-house with three laboratory assistants for each device. Operators ran samples unaltered clinical samples. The samples were blind labeled and compared to GC/MS results are presented in the tables below:

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Image /page/14/Picture/1 description: The image shows the logo for LYHER. The logo is green, except for the Y, which is orange. There is a registered trademark symbol to the right of the word.

AMPCassettesTest resultNegativeurine<-50% cutoff-50% cutoff~cut offCutoff~+50%cutoff>+50%cutoff
Operator 1Negative4301210
Positive0002217
Operator 2Negative4301100
Positive0012317
Operator 3Negative4301200
Positive0002317

Discordant Results of AMP Cassettes

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 259202300501994Positive
Operator 1752023005171008Negative
AMPDipcardsTest resultNegativeurine<-50% cutoff-50% cutoff~cut offCutoff~+50%cutoff>+50%cutoff
Operator 1Negative4301210
Positive0002217
Operator 2Negative4301200
Positive0002317
Operator 3Negative4301100
Positive0012317

Discordant Results of AMP Dipcards

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 359202300501994Positive
Operator 1752023005171008Negative
AMP CupsTest resultNegative urine<-50% cut off-50% cut off~cut offCut off~+50%cut off>+50%cut off
Operator 1Negative4301200
Positive0002317
Operator 2Negative4301200
Positive0002317
Operator 3Negative4301100
Positive0012317

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

Image /page/15/Picture/0 description: The image shows the word "LYHER" in a stylized font. The "LY" portion of the word is in orange, while the "HER" portion is in green. There is a registered trademark symbol to the right of the word.

Discordant Results of AMP Cups

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 359202300501994Positive

coc

COCCassettesTestresultNegativeurine<-50% cutoff-50% cutoff~cut offCutoff~+50%cutoff>+50%cutoff
Operator 1Negative4201310
Positive001375
Operator 2Negative4201400
Positive000385
Operator 3Negative4201300
Positive001385

Discordant Results of COC Cassettes

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 117202300680298Positive
Operator 317202300680298Positive
Operator 121202300684303Negative
COCDipcardsTest resultNegativeurine<-50% cutoff-50% cutoff~cut offCutoff~+50%cutoff>+50%cutoff
Operator 1Negative4201410
Positive000375
Operator 2Negative4201300
Positive001385
Operator 3Negative4201300
Positive001385

Discordant Results of COC Dipcards

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 217202300680298Positive
Operator 317202300680298Positive
Operator 121202300684303Negative
COC CupsTest resultNegative urine<-50% cut off-50% cut off~cut offCut off~+50%cut off>+50%cut off
Operator 1Negative4201400
Operator 1Positive000385

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

Image /page/16/Picture/0 description: The image shows the word "LYHER" in a stylized font. The "L" and "Y" are in yellow, while the "HER" is in green. There is a small registered trademark symbol to the right of the "R".

Operator 2Negative4201310
Positive001375
Operator 3Negative4201300
Positive001385

Discordant Results of COC Cups

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 217202300680298Positive
Operator 317202300680298Positive
Operator 221202300684303Negative

MET

METCassettesTest resultNegativeurine<-50% cutoff-50% cutoff~cut offCutoff~+50%cutoff>+50%cutoff
Operator 1Negative4301000
Positive0022416
Operator 2Negative4301100
Positive0012416
Operator 3Negative4301110
Positive0012316

Discordant Results of MET Cassettes

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 115202300331932Positive
Operator 158202300374561Positive
Operator 258202300374561Positive
Operator 358202300374561Positive
Operator 3772023003931007Negative
METDipcardsTest resultNegativeurine<-50% cutoff-50% cutoff~cut offCutoff~+50%cutoff>+50%cutoff
Operator 1Negative4301100
Positive0012416
Operator 2Negative4301100
Positive0012416
Operator 3Negative4301110
Positive0012316

Discordant Results of MET Dipcards

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

Image /page/17/Picture/0 description: The image shows the word "LYHER" in green and yellow. The "LY" is green, but the middle of the "Y" is yellow. The rest of the word is green. There is a registered trademark symbol in the upper right corner of the word.

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 158202300374561Positive
Operator 258202300374561Positive
Operator 358202300374561Positive
Operator 3772023003931007Negative
MET CupsTest resultNegative<-50% cut-50%cutCut>+50%cut
urineOffoff~cut offoff~+50%cutેન્દ્રિક રીકેની વિદ્વારા નિર્માન નામાં આવેલું એક ગામના લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં મુખ્યત્વે ખેત
ેન્દ્રિક રીકેની વિદ્વારા નિર્માન નામાં આવેલું એક ગામના લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં મુખ્યત્વે ખેત
Operator 1Negative43O1100
Positive0012416
Operator 2Negative4301100
Positive0012416
Operator 3Negative43O1110
PositiveO012316

Discordant Results of MET Cups

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 158202300374561Positive
Operator 258202300374561Positive
Operator 358202300374561Positive
Operator 3772023003931007Negative

OPI

OPICassettesTest resultNegativeurine<-50% cut off-50% cutoff~cut offCutoff~+50%cutoff>+50%cutoff
Operator 1Negative4501000
Positive000338
Operator 2Negative450910
Positive001328
Operator 3Negative4501000
Positive000338

Discordant Results of OPI Cassettes

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 2592023001802006Negative
Operator 2802023002011978Positive

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

Image /page/18/Picture/0 description: The image shows the logo for LYHER. The logo is green, except for the "Y" which is yellow. There is a small registered trademark symbol next to the "R" in the logo.

OPIDipcardsTest resultNegativeurine<-50% cutoff-50% cutoff~cut offCutoff~+50%cutoff>+50%cutoff
Operator 1Negative4501000
Positive000338
Operator 2Negative450900
Positive001338
Operator 3Negative4501010
Positive000328

Discordant Results of OPI Dipcards

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 3592023001802006Negative
Operator 2802023002011978Positive
OPI CupsTest resultNegative urine<-50% cut off-50% cut off~cut offCut off~+50%cut off>+50%cut off
Operator 1Negative4501010
Positive000328
Operator 2Negative450900
Positive001338
Operator 3Negative450900
Positive001338

Discordant Results of OPI Cups

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 1592023001802006Negative
Operator 2802023002011978Positive
Operator 3802023002011978Positive

РСР

PCPCassettesTest resultNegativeurine<-50% cutoff-50% cutoff~cut offCutoff~+50%cutoff>+50%cutoff
Operator 1Negative4521110
Positive001348
Operator 2Negative4521210
Positive000348
Operator 3Negative4521220
Positive000338

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

Image /page/19/Picture/0 description: The image shows the word "LYHER" in a stylized font. The "LY" portion of the word is in orange, while the "HER" portion is in green. There is a registered trademark symbol to the right of the word.

Discordant Results of PCP Cassettes

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 12520230081023.0Positive
Operator 23720230082225.2Negative
Operator 33720230082225.2Negative
Operator 110020230175025.2Negative
Operator 310020230175025.2Negative
PCPDipcardsTest resultNegativeurine<-50% cutoff-50% cutoff~cut offCutoff~+50%cutoff>+50%cutoff
Operator 1Negative4521200
Positive000358
Operator 2Negative4521120
Positive001338
Operator 3Negative4521200
Positive000358

Discordant Results of PCP Dipcards

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 22520230081023.0Positive
Operator 23720230082225.2Negative
Operator 210020230175025.2Negative
PCP CupsTest resultNegative urine<-50% cut off-50% cut off~cut offCut off~+50%cut off>+50%cut off
Operator 1Negative4521210
Positive000348
Operator 2Negative4521200
Positive000358
Operator 3Negative4521200
Positive000358

Discordant Results of PCP Cups

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 110020230175025.2Negative

THC

THCCassettesTest resultNegativeurine<-50% cutoff-50% cutoff~cut offCut off~+50%cutoff>+50%cutoff
--------------------------------------------------------------------------------------------------------------------------------------

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

Image /page/20/Picture/0 description: The image shows the logo for LYHER. The "LY" is in orange, and the "HER" is in green. There is a registered trademark symbol in the upper right corner of the logo.

Operator 1Negative4441710
Positive0002415
Operator 2Negative4441620
Positive0012315
Operator 3Negative4441700
Positive0002515

Discordant Results of THC Cassettes

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 11220230103650.5Negative
Operator 23620230106052.3Negative
Operator 24520230106949.6Positive
Operator 29220230165151.1Negative
THCDipcardsTest resultNegativeurine<-50% cut off-50% cut off~cut offCut off~+50%cut off>+50%cut off
Operator 1Negative4441600
Positive0012515
Operator 2Negative4441730
Positive0002215
Operator 3Negative4441710
Positive0002415

Discordant Results of THC Dipcards

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 21220230103650.5Negative
Operator 23620230106052.3Negative
Operator 14520230106949.6Positive
Operator 37520230109952.3Negative
Operator 29220230165151.1Negative
THC CupsTest resultNegative urine<-50% cut off-50% cut off~cut offCut off~+50%cut off>+50%cut off
Operator 1Negative4441600
Positive0012515
Operator 2Negative4441710
Positive0002415

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

Image /page/21/Picture/0 description: The image shows the word "LYHER" in a stylized font. The "LY" portion of the word is in yellow, while the "HER" portion is in green. There is a registered trademark symbol to the right of the word.

Operator 3 Negativeﺍﻟﻤﺴﺘﻘﻠﺔ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘ1 -
PositiveCJ1 Pﻟ

Discordant Results of THC Cups

OperatorSN.Specimen No.LC/MS resultsResults of Lyher kit
Operator 21220230103650.5Negative
Operator 33620230106052.3Negative
Operator 14520230106949.6Positive
Operator 39220230165151.1Negative

5.11 Conclusion

In accordance with the Federal Food, Drug and Cosmetic Act, 21 CFR Part 807, Based on the information provided in this premarket notification, Hangzhou Laihe Biotech Co., Ltd has demonstrated that proposed device LYHER® Urine Multi-Drug Test Kit(Cup), LYHER® Urine Multi-Drug Test Kit(Cassette), LYHER® Urine Multi-Drug Test Kit(Dipcard) are substantially equivalent to ATTEST Drug Screen Cup, ATTEST Drug Screen Dip Card, K182123.

§ 862.3870 Cannabinoid test system.

(a)
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 includedelta -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.(b)
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).