K Number
K180255
Date Cleared
2018-02-28

(29 days)

Product Code
Regulation Number
862.3150
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

CLUNGENE® Multi-Drug Test Dip Card is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Ampletamine, Oxazepam, Methamphetamine, Morphine, Oxycodone, Secobarbital and Methadone in human urine at the cutoff concentrations of:

Drug(Identifier)CalibratorCut-off level
Amphetamined-Amphetamine1000 ng/mL
OxazepamOxazepam300 ng/mL
CocaineBenzoylecgonine300 ng/mL
Marijuana11-Nor-△9-Tetrahydrocannabinol-9-COOH50 ng/mL
Methamphetamined-Methamphetamine1000 ng/mL
MorphineMorphine300 ng/mL
OxycodoneOxycodone100 ng/mL
SecobarbitalSecobarbital300 ng/mL
MethadoneMethadone300 ng/mL

Configuration of the CLUNGENE® Multi-Drug Test Dip Card can consist of any combination of the above listed drug analytes.

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

CLUNGENE® Multi-Drug Test Easy Cup is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Oxazepam, Marijuana, Methamphetamine, Morphine, Oxycodone. Secobarbital and Methadone in human urine at the cutoff concentrations of:

Drug(Identifier)CalibratorCut-off level
Amphetamined-Amphetamine1000 ng/mL
OxazepamOxazepam300 ng/mL
CocaineBenzoylecgonine300 ng/mL
Marijuana11-Nor-△9-Tetrahydrocannabinol-9-COOH50 ng/mL
Methamphetamined-Methamphetamine1000 ng/mL
MorphineMorphine300 ng/mL
OxycodoneOxycodone100 ng/mL
SecobarbitalSecobarbital300 ng/mL
MethadoneMethadone300 ng/mL

Configuration of the CLUNGENE® Multi-Drug Test Easy Cup can consist of any combination of the above listed drug analytes.

The test may yield positive results for the prescription drugs Oxazepam. Secobarbital and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternical 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.

Device Description

The CLUNGENE Multi-Drug Test Dip Card and CLUNGENE Multi-Drug Test Easy Cup are immunochromatographic assays that use a lateral flow system for the qualitative detection of Amphetamine, Oxazepam, Cocaine, Marijuana, Methamphetamine, Morphine, Oxycodone, Secobarbital and Methadone (target analytes) in human urine. The products are single-use in vitro diagnostic devices. The CLUNGENE Multi-Drug Test Dip Card kit contains a Dip Card device, a package insert and a urine cup for sample collection. The CLUNGENE Multi-Drug Test Easy Cup kit contains a Cup device, a package insert and a urine cup for sample collection. Each test device is sealed with a desiccant in an aluminum pouch.

AI/ML Overview

Based on the provided text, the device in question is the CLUNGENE Multi-Drug Test Dip Card and CLUNGENE Multi-Drug Test Easy Cup, which are competitive binding, lateral flow immunochromatographic assays for qualitative and simultaneous detection of various drugs in human urine.

Here's an analysis of the acceptance criteria and the studies performed:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state "acceptance criteria" as a separate, quantitative table with pass/fail thresholds before presenting the results. However, the performance data presented implies the criteria for "acceptable performance" for each test type. The precision study for concentrations near the cut-off would be a key indicator for quantitative acceptance. For the qualitative tests, the performance at concentrations above and below the cutoff demonstrates the criteria.

Implied Acceptance Criteria and Reported Performance from Precision Studies (for Secobarbital)

The precision study for Secobarbital demonstrates expected performance around the cut-off (300 ng/mL). A device is expected to consistently classify samples below the cut-off as negative and above as positive. At the exact cut-off, a roughly 50/50 split is typical, reflecting the analytical variation.

Test Parameter / Concentration (ng/mL)Acceptance Criteria (Implied)Reported Device Performance (CLUNGENE Multi-Drug Test Dip Card - Secobarbital)Reported Device Performance (CLUNGENE Multi-Drug Test Easy Cup - Secobarbital)Outcome
Secobarbital (Cut-off: 300 ng/mL)
0 (100% below)100% Negative50-/0+ (All negative across 3 lots)50-/0+ (All negative across 3 lots)Pass
69 (75% below)100% Negative50-/0+ (All negative across 3 lots)50-/0+ (All negative across 3 lots)Pass
147 (50% below)100% Negative50-/0+ (All negative across 3 lots)50-/0+ (All negative across 3 lots)Pass
226 (25% below)100% Negative50-/0+ (All negative across 3 lots)50-/0+ (All negative across 3 lots)Pass
286 (Cut-off)Mixed results expectedLot 1: 22-/28+, Lot 2: 26-/24+, Lot 3: 27-/23+ (Mixed positive/negative)Lot 1: 26-/24+, Lot 2: 27-/23+, Lot 3: 21-/29+ (Mixed positive/negative)Pass
370 (25% above)100% Positive50+/0- (All positive across 3 lots)50+/0- (All positive across 3 lots)Pass
457 (50% above)100% Positive50+/0- (All positive across 3 lots)50+/0- (All positive across 3 lots)Pass
510 (75% above)100% Positive50+/0- (All positive across 3 lots)50+/0- (All positive across 3 lots)Pass
559 (100% above)100% Positive50+/0- (All positive across 3 lots)50+/0- (All positive across 3 lots)Pass

Similar tables and outcomes are provided for Methadone and Oxycodone, and referenced for other drugs (Amphetamine, Oxazepam, Cocaine, Methamphetamine, Morphine, Marijuana) in previous submissions (K153741 and K161251).

Lay-User Study Performance:

The lay-user study also demonstrates adherence to an implicit acceptance criterion that a high percentage of correct results should be obtained, especially for samples significantly above or below the cutoff. For samples at +/- 25% of the cutoff, a slight reduction in accuracy is observed and expected due to the nature of qualitative assays at the analytical threshold.

Drug% of Cut-offExpected OutcomeReported % of Correct ResultsOutcome
AMP-100% to -50%100% Negative100%Pass
-25%High % Negative95% NegativePass
+25%High % Positive95% PositivePass
+50% to +75%100% Positive100%Pass
BAR, COC, BZO, MTD, MOP, OXY, THC (similar patterns across drugs)-100% to -50%100% NegativeMostly 100%Pass
-25%High % Negative90-100%Pass
+25%High % Positive90-100%Pass
+50% to +75%100% Positive100%Pass

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

  • Precision Study:

    • Sample Size: For each drug and concentration, "tests were performed two runs per day for 25 days per device," which equates to 50 individual tests per concentration per lot. With 9 concentrations tested and 3 lots, this is 50 * 9 * 3 = 1350 tests per drug type. This study was carried out for Secobarbital, Methadone, and Oxycodone. Data for other drugs were reported previously.
    • Data Provenance: Samples were "prepared by spiking drug in negative urine samples." This indicates controlled laboratory conditions. The text does not specify the country of origin of the urine samples themselves, but the manufacturer is Hangzhou Clongene Biotech Co.,Ltd. in China. The study is prospective in the sense that samples were prepared and then tested.
  • Comparison Studies (Clinical Samples):

    • Sample Size: "Operators ran 80 (40 negative and 40 positive) unaltered clinical samples for each drug." This was done for Secobarbital, Methadone, and Oxycodone. Similar studies for the other drugs were referenced in previous submissions.
    • Data Provenance: "unaltered clinical samples." The origin (e.g., country) is not specified. The study design sounds retrospective, as samples were collected clinically and then processed for the study.
  • Lay-user Study:

    • Sample Size: "A lay user study was performed at three intended user sites with 300 lay persons for each device format." Each participant tested one sample. The samples included negative and various levels around the cut-off. For each drug, the total number of samples tested with the device by lay users corresponds to the sum of samples across all concentrations (e.g., for AMP, 20+20+160+20+20+40+20 = 300 samples). This implies 300 samples per drug per device format. Given there are 9 drugs, this means 300 * 9 tests per device format.
    • Data Provenance: Urine samples were "prepared at the following concentrations; negative, +/-75%, +/-50%, +/-25% of the cutoff by spiking drugs into drug free-pooled urine specimens." This indicates controlled laboratory-prepared samples. The study was prospective in its execution. The "three intended user sites" are not specified geographically.

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

  • Precision Study: The ground truth for the prepared samples was established by LC/MS (Liquid Chromatography/Mass Spectrometry). This is a highly accurate analytical method, and no human experts are noted for establishing this specific ground truth.
  • Comparison Studies (Clinical Samples): The ground truth for the clinical samples was established by GC/MS (Gas Chromatography/Mass Spectrometry). This is explicitly stated as "The samples were blind labeled and compared to GC/MS results." No human experts are mentioned for establishing the ground truth, as GC/MS is an objective chemical analysis method.
  • Lay-user Study: The ground truth for the prepared samples was established by LC/MS (Liquid Chromatography/Mass Spectrometry). No human experts are noted for establishing this specific ground truth.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

  • For the device's reading: In the comparison studies, "three laboratory assistants" for each device (Dip Card and Easy Cup) seem to have visually read the results. The document provides tables breaking down positive/negative calls by "Viewer A, Viewer B, Viewer C". There is no explicit mention of an adjudication process (like 2+1 or 3+1) if these viewers disagreed. The data shows individual viewer results, and discordant results are listed separately, implying that their individual interpretations were recorded.
  • For the ground truth: As the ground truth for all studies was established by chemical analytical methods (LC/MS or GC/MS), no human adjudication method was needed for the ground truth itself.

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

  • No, an MRMC comparative effectiveness study was not performed in the context of AI assistance. This document describes the performance of a point-of-care, visually interpreted immunochromatographic device (dip card/easy cup drug test). The "viewers" are laboratory assistants reading the visual results, not radiologists interpreting medical images with or without AI.
  • The study is a direct comparison of the device's results against a gold standard (GC/MS or LC/MS), and a lay-user study to assess comprehensibility and ease of use. There is no AI component or human-in-the-loop AI assistance involved.

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

  • Not applicable. The device is a lateral flow immunoassay that produces a visual result inherently requiring human interpretation (either by a lay user or laboratory assistant). There is no "algorithm" in the sense of software interpreting results without human input described for this device.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

  • The ground truth for all studies (Precision, Comparison, Lay-user) was established using objective chemical analytical methods: LC/MS and GC/MS. These are considered gold standards for drug concentration determination. No expert consensus, pathology, or outcomes data were used as ground truth for this type of diagnostic device.

8. The sample size for the training set

  • This information is not provided in the document. The document describes performance testing of the final device, not the development or training of a software algorithm. For an immunochromatographic assay, the "training set" would refer to the samples used during the assay development and optimization phase to establish the device's characteristics (e.g., antibody selection, membrane properties, cutoff optimization), which is distinct from the formal performance validation studies presented here.

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

  • This information is not provided in the document, as it pertains to the device's development phase rather than its validation. However, it can be inferred that similar analytical methods (LC/MS/GC/MS) would have been used during development to characterize drug concentrations in samples used for internal optimization.

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February 28, 2018

Hangzhou Clongene Biotech Co.,Ltd. % Jesse Xia Manager LSI International 504 E Diamond Ave., Suite I Gaithersburg, MD 20877

Re: K180255

Trade/Device Name: CLUNGENE Multi-Drug Test Dip Card CLUNGENE Multi-Drug Test Easy Cup Regulation Number: 21 CFR 862.3150 Regulation Name: Barbiturate Test System Regulatory Class: Class II Product Code: PTH, PTG, NGL, NGG, NFT, NFW, NFY, NFV Dated: January 25, 2018 Received: January 30, 2018

Dear Jesse Xia:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

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803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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

For comprehensive regulatory information about mediation-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) K180255

Device Name

CLUNGENE® Multi-Drug Test Dip Card CLUNGENE® Multi-Drug Test Easy Cup

Indications for Use (Describe)

CLUNGENE® Multi-Drug Test Dip Card is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Ampletamine, Oxazepam, Methamphetamine, Morphine, Oxycodone, Secobarbital and Methadone in human urine at the cutoff concentrations of:

Drug(Identifier)CalibratorCut-off level
Amphetamined-Amphetamine1000 ng/mL
OxazepamOxazepam300 ng/mL
CocaineBenzoylecgonine300 ng/mL
Marijuana11-Nor-△9-Tetrahydrocannabinol-9-COOH50 ng/mL
Methamphetamined-Methamphetamine1000 ng/mL
MorphineMorphine300 ng/mL
OxycodoneOxycodone100 ng/mL
SecobarbitalSecobarbital300 ng/mL
MethadoneMethadone300 ng/mL

Configuration of the CLUNGENE® Multi-Drug Test Dip Card can consist of any combination of the above listed drug analytes.

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

CLUNGENE® Multi-Drug Test Easy Cup is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Oxazepam, Marijuana, Methamphetamine, Morphine, Oxycodone. Secobarbital and Methadone in human urine at the cutoff concentrations of:

Drug(Identifier)CalibratorCut-off level
Amphetamined-Amphetamine1000 ng/mL
OxazepamOxazepam300 ng/mL
CocaineBenzoylecgonine300 ng/mL
Marijuana11-Nor-△9-Tetrahydrocannabinol-9-COOH50 ng/mL
Methamphetamined-Methamphetamine1000 ng/mL
MorphineMorphine300 ng/mL
OxycodoneOxycodone100 ng/mL
SecobarbitalSecobarbital300 ng/mL
MethadoneMethadone300 ng/mL

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Configuration of the CLUNGENE® Multi-Drug Test Easy Cup can consist of any combination of the above listed drug analytes.

The test may yield positive results for the prescription drugs Oxazepam. Secobarbital and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternical 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.

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)

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510(k) SUMMARY K180255

    1. Date: February 28, 2018
  • Hangzhou Clongene Biotech Co., Ltd. 2. Submitter: 20 Longquan Road Hangzhou 311121, China
    1. Contact person: Zheng Shujian Hangzhou Clongene Biotech Co., Ltd. 20 Longquan Road Hangzhou 311121, China Telephone: 86 571 88262120 Email: frank@clongene.com.
    1. Device Name: CLUNGENE Multi-Drug Test Dip Card

CLUNGENE Multi-Drug Test Easy Cup

Classification:Class 2
Product CodeClassificationRegulation SectionPanel
NFTAmphetamineII21 CFR § 862.3100, Amphetamine Test SystemToxicology (91)
NFWCannabinoidsII21 CFR § 862.3870, Cannabinoids Test SystemToxicology (91)
NFYCocaineII21 CFR § 862.3250, Cocaine Test SystemToxicology (91)
NGGMethamphetamineII21 CFR § 862.3610, Methamphetamine Test SystemToxicology (91)
NGLMorphineII21 CFR § 862.3650, Opiate Test SystemToxicology (91)
NFVOxazepamII21 CFR § 862.3170, Benzodiazepine Test SystemToxicology (91)
NGLOxycodoneII21 CFR § 862.3650, Opiate Test SystemToxicology (91)
PTHSecobarbitalII21 CFR § 862.3150, Barbiturate Test SystemToxicology (91)
PTGMethadoneII21 CFR § 862.3620, Methadone Test SystemToxicology (91)

5. Predicate Devices: K142396

The Chemtrue® Multi-Panel Drug Screen Dip Card Tests

    1. Intended Use
      CLUNGENE® Multi-Drug Test Dip Card is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Oxazepam, Cocaine, Marijuana, Methamphetamine, Morphine, Oxycodone, Secobarbital and Methadone in human urine at the cutoff concentrations of:
Drug(Identifier)CalibratorCut-off level
Amphetamined-Amphetamine1000 ng/mL

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OxazepamOxazepam300 ng/mL
CocaineBenzoylecgonine300 ng/mL
Marijuana11-Nor-Δ⁹-Tetrahydrocannabinol-9-COOH50 ng/mL
Methamphetamined-Methamphetamine1000 ng/mL
MorphineMorphine300 ng/mL
OxycodoneOxycodone100 ng/mL
SecobarbitalSecobarbital300 ng/mL
MethadoneMethadone300 ng/mL

Configuration of the CLUNGENE® Multi-Drug Test Dip Card can consist of any combination of the above listed drug analytes.

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

CLUNGENE® Multi-Drug Test Easy Cup is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Oxazepam, Cocaine, Marijuana, Methamphetamine, Morphine, Oxycodone, Secobarbital and Methadone in human urine at the cutoff concentrations of:

Drug(Identifier)CalibratorCut-off level
Amphetamined-Amphetamine1000 ng/mL
OxazepamOxazepam300 ng/mL
CocaineBenzoylecgonine300 ng/mL
Marijuana11-Nor-Δ9-Tetrahydrocannabinol-9-COOH50 ng/mL
Methamphetamined-Methamphetamine1000 ng/mL
MorphineMorphine300 ng/mL
OxycodoneOxycodone100 ng/mL
SecobarbitalSecobarbital300 ng/mL
MethadoneMethadone300 ng/mL

Configuration of the CLUNGENE® Multi-Drug Test Easy Cup can consist of any combination of the above listed drug analytes.

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

    1. Device Description
      The CLUNGENE Multi-Drug Test Dip Card and CLUNGENE Multi-Drug Test Easy Cup are immunochromatographic assays that use a lateral flow system for the qualitative detection of

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Amphetamine, Oxazepam, Cocaine, Marijuana, Methamphetamine, Morphine, Oxycodone, Secobarbital and Methadone (target analytes) in human urine. The products are single-use in vitro diagnostic devices. The CLUNGENE Multi-Drug Test Dip Card kit contains a Dip Card device, a package insert and a urine cup for sample collection. The CLUNGENE Multi-Drug Test Easy Cup kit contains a Cup device, a package insert and a urine cup for sample collection. Each test device is sealed with a desiccant in an aluminum pouch.

    1. Substantial Equivalence Information A summary comparison of features of the CLUNGENE Multi-Drug Test Dip Card and CLUNGENE Multi-Drug Test Easy Cup and the predicate devices is provided in following tables.
Table 1: Features Comparison of CLUNGENE Multi-Drug Test Dip Card and the
Predicate Devices
D J . L T 1 1001
ItemDevicePredicate - K142396
Indication(s)for UseFor the qualitative determination of drugs ofabuse in human urine.Same (but the number ofdrugs detected is different)
Calibrator andCut-Off ValuesAmphetamine (AMP): 1,000 ng/mlOxazepam (BZO):300 ng/mlCocaine(COC): 300 ng/ml11-Nor-△9-Tetrahydrocannabinol-9-COOH(THC):50 ng/mlMethamphetamine (MET): 1,000 ng/mlMorphine (MOR): 300ng/mLOxycodone(OXY) : 100 ng/mlSecobarbital (BAR): 300 ng/mlSame
MethodologyCompetitive binding, lateral flowimmunochromatographic assays based on theprinciple of antigen antibodyimmunochemistry.Same
Type of TestQualitativeSame
Specimen TypeHuman UrineSame
Intended UseFor over-the-counterSame
ConfigurationsDip CardSame

Table 2: Features Comparison of CLUNGENE Multi-Drug Test Easy Cup Tests and the Predicate Devices

ItemDevicePredicate - K142396
Indication(s)for UseFor the qualitative determination ofdrugs of abuse in human urine.Same (but the number ofdrugs detected is different)

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Calibrator and Cut-OffValuesAmphetamine (AMP): 1,000 ng/mlOxazepam (BZO):300 ng/mlCocaine(COC): 300 ng/ml11-Nor-Δ9-Tetrahydrocannabinol-9-COOH(THC):50 ng/mlMethamphetamine (MET): 1,000 ng/mlMorphine (MOR): 300ng/mLOxycodone(OXY) : 100 ng/mlSecobarbital (BAR): 300 ng/mlMethadone (MTD): 300 ng/mlSame
MethodologyCompetitive binding, lateral flowimmunochromatographic assays based onthe principle of antigen antibodyimmunochemistry.Same
Type of TestQualitativeSame
Specimen TypeHuman UrineSame
Intended UseFor over-the-counterSame
ConfigurationsCupDip Card

9. Test Principle

The CLUNGENE Multi-Drug Test Dip Card, and CLUNGENE Multi-Drug Test Easy Cup are rapid tests for the qualitative detection of Amphetamine, Oxazepam, Cocaine, Marijuana, Methamphetamine, Morphine, Oxycodone, Secobarbital and Methadone 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 will saturate all the binding sites of the antibody coated on the particles. A band should form in the control region of the devices regardless of the presence of drug or metabolite in the sample to indicate that the tests have been performed properly.

10. Performance Characteristics

    1. Analytical Performance

a. Precision

Precision studies were carried out for samples with concentrations of -100% cut off, -75% cut off, -50% cut off, -25% cut off, cut off, +25% cut off, +50% cut off , +75% cut off and +100% cut off. These samples were prepared by spiking drug in negative urine 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. For each concentration, tests were performed two runs per day for 25 days per device in a randomized order. The results obtained are summarized in the

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following tables for Secobarbital, Methadone and Oxycodone. The data for Methamphetamine, Morphine and Marijuana were reported in K153741; and the data for Amphetamine, Oxazepam and Cocaine were reported in K161251.

Concentration byLC/MS (ng/mL)-100%Cut-off-75%Cut-off-50%Cut-off-25%Cut-offCut-offCut-off+25%Cut-off+50%Cut-off+75%Cut-off+100%
LotNumber069147226286370457510559
Lot 150-/0+50-/0+50-/0+50-/0+22-/28+50+/0-50+/0-50+/0-50+/0-
Lot 250-/0+50-/0+50-/0+50-/0+26-/24+50+/0-50+/0-50+/0-50+/0-
Lot 350-/0+50-/0+50-/0+50-/0+27-/23+50+/0-50+/0-50+/0-50+/0-

Secobarbital CLUNGENE Multi-Drug Test Dip Card

CLUNGENE Multi-Drug Test Easy Cup

Concentration byLC/ MS (ng/mL)-100%Cut-off-75%Cut-off-50%Cut-off-25%Cut-offCut-offCut-off+25%Cut-off+50%Cut-off+75%Cut-off+100%
LotNumber069147226286370457510559
Lot 150-/0+50-/0+50-/0+50-/0+26-/24+50+/0-50+/0-50+/0-50+/0-
Lot 250-/0+50-/0+50-/0+50-/0+27-/23+50+/0-50+/0-50+/0-50+/0-
Lot 350-/0+50-/0+50-/0+50-/0+21-/29+50+/0-50+/0-50+/0-50+/0-

Methadone CLUNGENE Multi-Drug Test Dip Card

Concentration byLC/MS (ng/mL)-100%Cut-off-75%Cut-off-50%Cut-off-25%Cut-offCut-off+25%Cut-off+50%Cut-off+75%Cut-off+100%Cut-off
LotNumber076140235297377431507631
Lot 150-/0+50-/0+50-/0+50-/0+26-/24+50+/0-50+/0-50+/0-50+/0-
Lot 250-/0+50-/0+50-/0+50-/0+29-/21+50+/0-50+/0-50+/0-50+/0-
Lot 350-/0+50-/0+50-/0+50-/0+27-/23+50+/0-50+/0-50+/0-50+/0-

CLUNGENE Multi-Drug Test Easy Cup

Concentration byLC/MS (ng/mL)-100%Cut-off-75%Cut-off-50%Cut-off-25%Cut-offCut-off+25%Cut-off+50%Cut-off+75%Cut-off+100%Cut-off
Lot
Number076140235297377431507631
Lot 150-/0+50-/0+50-/0+50-/0+24-/26+50+/0-50+/0-50+/0-50+/0-
Lot 250-/0+50-/0+50-/0+50-/0+27-/23+50+/0-50+/0-50+/0-50+/0-
Lot 350-/0+50-/0+50-/0+50-/0+28-/22+50+/0-50+/0-50+/0-50+/0-

Oxycodone

CLUNGENE Multi-Drug Test Dip Card

Concentration byLC/MS (ng/mL)-100%Cut-off-75%Cut-off-50%Cut-off-25%Cut-offCut-off+25%Cut-off+50%Cut-off+75%Cut-off+100%Cut-off
LotNumber0254872101119142164187
Lot 150-/0+50-/0+50-/0+50-/0+23-/27+50+/0-50+/0-50+/0-50+/0-

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

Concentration byLC/MS (ng/mL)Lot-100%Cut-off-75%Cut-off-50%Cut-off-25%Cut-offCut-off+25%Cut-off+50%Cut-off+75%Cut-off+100%Cut-off
Number0254872101119142164187
Lot 250-/0+50-/0+50-/0+50-/0+28-/22+50+/0-50+/0-50+/0-50+/0-
Lot 350-/0+50-/0+50-/0+50-/0+24-/26+50+/0-50+/0-50+/0-50+/0-
Concentration byLC/MS (ng/mL)Lot-100%Cut-off-75%Cut-off-50%Cut-off-25%Cut-offCut-off+25%Cut-off+50%Cut-off+75%Cut-off+100%Cut-off
Number0254872101119142164187
Lot 150-/0+50-/0+50-/0+50-/0+20-/30+50+/0-50+/0-50+/0-50+/0-
Lot 250-/0+50-/0+50-/0+50-/0+28-/22+50+/0-50+/0-50+/0-50+/0-
Lot 350-/0+50-/0+50-/0+50-/0+22-/28+50+/0-50+/0-50+/0-50+/0-

The following cut-off values are verified.

Drug(Identifier)Cut-off level
Secobarbital (BAR)300 ng/mL
Methadone (MTD )300 ng/mL
Oxycodone (OXY)100 ng/mL
  • b. Linearity
    Not applicable.

  • c. Stability
    The devices are stable at 4-30 ℃ for 24 months based on the accelerated stability study at 45 °C. Real time stability studies are ongoing.

  • d. Interference
    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 lots of each device. Compounds that showed no interference at a concentration of 100ug/mL are summarized in the following tables. There were no differences observed between the CLUNGENE Multi-Drug Test Dip Card and CLUNGENE Multi-Drug Test Easy Cup.

Acetominophen (4-Acetamidophenol)Ecgonine methyl esterD,L-Octopamine
AcetophenetidinEMDPOxalic acid
N-AcetylprocainamideErythromycinOxolinic acid
Acetylsalicylic acidβ-EstradiolOxymetazoline
AlbuminFenoprofenPapaverine
AminopyrineFurosemidePenicillin-G
AmoxicillinGentisic acidPerphenazine
AmpicillinHemoglobinPhenelzine
ApomorphineHydralazinePrednisone
Ascorbic acidHydrochlorothiazideDL-Propranolol

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

AspartameHydrocortisoneD-Pseudoephedrine
AtropineO-Hydroxyhippuric acidQuinine
Benzilic acid3-HydroxytyramineRanitidine
Benzoic acidIbuprofenSalicylic acid
BilirubinD,L-IsoproterenolSerotonin (5- Hydroxytyramine)
ChloralhydrateIsoxsuprineSulfamethazine
ChloramphenicolKetamineSulindac
ChlorothiazideKetoprofenTetrahydrocortisone, 3-acetate
ChlorpromazineLabetalolTetrahydrocortisone 3-(β-
CholesterolLoperamideDglucuronide)
ClonidineMaprotilineTetrahydrozoline
CortisoneMeperidineThiamine
(-) CotinineMeprobamateThioridazine
CreatinineMethoxyphenamineTriamterene
DeoxycorticosteroneNalidixic acidDL-Tyrosine
DextromethorphanNaloxoneTrifluoperazine
DiclofenacNaltrexoneTrimethoprim
DiflunisalNaproxenD L-Tryptophan
DigoxinNiacinamideTyramine
DiphenhydramineNifedipineUric acid
DisopyramideNorethindroneVerapamil
EDDPNoscapineZomepirac

To demonstrate that there are no interference from each of the nine drug analytes on the other eight drug strips, devices in both CLUNGENE Multi-Drug Test Dip Card and CLUNGENE Multi-Drug Test Easy Cup were tested using standard drug urine solutions at three fold cut-off drug concentrations of each drug analyte. Tests showed positive result only for each target drug and negative result for other drugs.

e. Specificity

To test specificity, drug metabolites and other structurally related compounds that are likely to cross-react in urine samples were spiked into negative urine and were tested using three lots of each device. The lowest concentration that caused a positive result for each compound are listed below for Secobarbital, Methadone and Oxycodone. The data for Methamphetamine, Morphine and Marijuana were reported in K153741; and the data for Amphetamine, Oxazepam and Cocaine were reported in K161251. There were no differences observed between the CLUNGENE Multi-Drug Test Dip Card and CLUNGENE Multi-Drug Test Easy Cup.

SecobarbitalResult% Cross-Reactivity
(Cut-off=300 ng/mL)Positive at (ng/mL)
Secobarbital300100%
Amobarbital300100%
Alphenol150200%
Aprobarbital200150%
Butabarbital75400%
Butathal100300%
Butalbital250012%
Cyclopentobarbital60050%
Pentobarbital300100%
Phenobarbital100300%
Methadone(Cut-off=300 ng/mL)ResultPositive at(ng/ml)% Cross-Reactivity
------------------------------------------------------------------------------------

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

Methadone300100%
Doxylamine50006%
LAAM HCl>100000<0.3%
Alpha Methadol>100000<0.3%
EDDP>100000<0.3%
EMDP>100000<0.3%
Oxycodone(Cut-off=100 ng/mL)ResultPositive at(ng/ml)% Cross-Reactivity
Oxycodone100100%
Codeine500000.2%
Dihydrocodeine125000.8%
Ethylmorphine250000.4%
Hydrocodone15626.4%
Hydromorphone125000.8%
Oxymorphone15626.4%
Thebaine500000.2%

f. Effect of Urine Specific Gravity and Urine pH

To investigate the effect of urine specific gravity and urine pH, urine samples, with 1.000 to 1.035 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% Cut-Off and all negative for samples at and below -25% Cut-Off. There were no differences observed between the CLUNGENE Multi-Drug Test Dip Card and CLUNGENE Multi-Drug Test Easy Cup.

2. Comparison Studies

Method comparison studies for the CLUNGENE Multi-Drug Test Dip Card and the CLUNGENE Multi-Drug Test Easy Cup were performed in-house with three laboratory assistants for each device. Operators ran 80 (40 negative and 40 positive) unaltered clinical samples for each drug. The samples were blind labeled and compared to GC/MS results. The results are presented in the tables below for Secobarbital, Methadone and Oxycodone. The data for Methamphetamine, Morphine and Marijuana were reported in K153741; and the data for Amphetamine, Oxazepam and Cocaine were reported in K161251.

CLUNGENEMulti-DrugTest Dip CardNegativeLowNegative byGC/MS(less than-50%)Near CutoffNegative byGC/MS(Between-50% andcutoff)Near CutoffPositive byGC/MS(Between thecutoff and+50%)High Positiveby GC/MS(greater than+50%)
ViewerAPositive0011920
ViewerANegative10151410
ViewerBPositive0002020
ViewerBNegative10151500
ViewerCPositive0012020
ViewerCNegative10151400

Discordant Results

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

ViewerSample NumberGC/MS ResultDip Card Viewer Results
Viewer ABAR79298Positive
Viewer CBAR29294Positive
Viewer ABAR14316Negative
CLUNGENEMulti-DrugTest EasyCupNegativeLow Negative by GC/MS(less than -50%)Near Cutoff Negative by GC/MS(Between -50% and cutoff)Near Cutoff Positive by GC/MS(Between the cutoff and +50%)High Positive by GC/MS(greater than +50%)
ViewerAPositive0011920
Negative10151410
ViewerBPositive0021820
Negative10151320
ViewerCPositive0011920
Negative10151410

Discordant Results

ViewerSample NumberGC/MS ResultEasy CupViewer Results
Viewer ABAR79298Positive
Viewer BBAR30296Positive
Viewer BBAR79298Positive
Viewer CBAR29294Positive
Viewer ABAR33330Negative
Viewer BBAR14316Negative
Viewer BBAR35349Negative
Viewer CBAR14316Negative

Methadone

CLUNGENEMulti-DrugTest Dip CardNegativeLowNegative byGC/MS(less than-50%)Near CutoffNegative byGC/MS(Between-50% andcutoff)Near CutoffPositive byGC/MS(Between thecutoff and+50%)High Positiveby GC/MS(greater than+50%)
ViewerAPositive0001920
ViewerANegative10151510
ViewerBPositive0012020
ViewerBNegative10151400
ViewerCPositive0012020
ViewerCNegative10151400

Discordant Results

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

ViewerSample NumberGC/MS ResultDip Card Viewer Results
Viewer BMTD28297Positive
Viewer CMTD14292Positive
Viewer AMTD29308Negative
CLUNGENEMulti-DrugTest EasyCupNegativeLowNegative byGC/MS(less than-50%)Near CutoffNegative byGC/MS(Between-50% andcutoff)Near CutoffPositive byGC/MS(Between thecutoff and+50%)High Positiveby GC/MS(greater than+50%)
ViewerPositive0021920
ANegative10151310
ViewerPositive0012020
BNegative10151400
ViewerPositive0011920
CNegative10151410

Discordant Results

ViewerSample NumberGC/MS ResultEasy CupViewer Results
Viewer AMTD14292Positive
Viewer AMTD28297Positive
Viewer BMTD28297Positive
Viewer CMTD14292Positive
Viewer AMTD29308Negative
Viewer CMTD76313Negative

Oxycodone

CLUNGENEMulti-DrugTest Dip CardNegativeLow Negative byGC/MS(less than-50%)Near CutoffNegative byGC/MS(Between-50% andcutoff)Near CutoffPositive byGC/MS(Between thecutoff and+50%)High Positiveby GC/MS(greater than+50%)
ViewerAPositive0002020
ViewerANegative10151500
ViewerBPositive0011920
ViewerBNegative10151410
ViewerCPositive0001920
ViewerCNegative10151510

Discordant Results

ViewerSample NumberGC/MS ResultDip CardViewer Results
Viewer BOXY6692Positive

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

Viewer BOXY39101Negative
Viewer COXY30102Negative
CLUNGENEMulti-DrugTest EasyCupNegativeLowNegative byGC/MS(less than-50%)Near CutoffNegative byGC/MS(Between-50% andcutoff)Near CutoffPositive byGC/MS(Between thecutoff and+50%)High Positiveby GC/MS(greater than+50%)
ViewerAPositive0001920
ViewerANegative10151510
ViewerBPositive0012020
ViewerBNegative10151400
ViewerCPositive0001920
ViewerCNegative10151510

Discordant Results

ViewerSample NumberGC/MS ResultEasy CupViewer Results
Viewer BOXY6692Positive
Viewer AOXY39101Negative
Viewer COXY30102Negative

Lay-user study

A lay user study was performed at three intended user sites with 300 lay persons for each device format. 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 cutoff by spiking drugs 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. Results are shown below.

Drugs% of Cut-offNumberofsamplesConcentration byLC/MS(ng/mL)Lay person resultsNo. ofPositiveLay person resultsNo. ofNegativeThepercentageof correctresults(%)
AMP-100% Cut-off200020100
-75% Cut-off20250020100
-50% Cut-off1605000160100
-25% Cut-off2075011995
+25% Cut-off20125019195
+50% Cut-off401500400100
+75% Cut-off201750200100
BAR-100% Cut-off200020100
-75% Cut-off2075020100
-50% Cut-off1601500160100
-25% Cut-off20225020100
+25% Cut-off2037518290
+50% Cut-off40450400100
+75% Cut-off20525200100
-100% Cut-off200020100
-75% Cut-off2075020100
-50% Cut-off1601500160100
COC-25% Cut-off2022511995
+25% Cut-off2037519195
+50% Cut-off40450400100
+75% Cut-off20525200100
-100% Cut-off200020100
-75% Cut-off2075020100
-50% Cut-off1601500160100
BZO-25% Cut-off20225020100
+25% Cut-off2037519195
+50% Cut-off40450400100
+75% Cut-off20525200100
-100% Cut-off200020100
-75% Cut-off20250020100
-50% Cut-off1605000160100
MET-25% Cut-off2075011995
+25% Cut-off201250200100
+50% Cut-off401500400100
+75% Cut-off201750200100
-100% Cut-off200020100
-75% Cut-off2075020100
-50% Cut-off1601500160100
MTD-25% Cut-off20225020100
+25% Cut-off2037518290
+50% Cut-off40450400100
+75% Cut-off20525200100
-100% Cut-off200020100
-75% Cut-off2075020100
-50% Cut-off1601500160100
MOP-25% Cut-off2022521890
+25% Cut-off20375200100
+50% Cut-off40450400100
+75% Cut-off20525200100
-100% Cut-off200020100
OXY-75% Cut-off2025020100
-50% Cut-off160500160100
-25% Cut-off207511995
+25% Cut-off20125200100
+50% Cut-off40150400100
+75% Cut-off20175200100
-100% Cut-off200020100
-75% Cut-off2012.5020100
THC-50% Cut-off160250160100
-25% Cut-off2037.5020100
+25% Cut-off2062.518290
+50% Cut-off4075400100
+75% Cut-off2087.5200100
Drugs% of Cut-offNumberofsamplesConcentration byLC/MS(ng/mL)Lay person resultsThepercentage ofcorrect results(%)
AMP-100% Cut-off200020100
-75% Cut-off20250020100
-50% Cut-off1605000160100
-25% Cut-off2075011995
+25% Cut-off20125018290
+50% Cut-off401500400100
+75% Cut-off201750200100
BAR-100% Cut-off200020100
-75% Cut-off2075020100
-50% Cut-off1601500160100
-25% Cut-off20225020100
+25% Cut-off2037518290
+50% Cut-off40450400100
+75% Cut-off20525200100
COC-100% Cut-off200020100
-75% Cut-off2075020100
-50% Cut-off1601500160100
-25% Cut-off20225020100
+25% Cut-off2037519195
+50% Cut-off40450400100
+75% Cut-off20525200100
BZO-100% Cut-off200020100
-75% Cut-off2075020100
-50% Cut-off1601500160100
-25% Cut-off2022511995
+25% Cut-off2037519195
+50% Cut-off40450400100
+75% Cut-off20525200100
MET-100% Cut-off200020100
-75% Cut-off20250020100
-50% Cut-off1605000160100
-25% Cut-off2075021890
+25% Cut-off201250200100
+50% Cut-off401500400100
+75% Cut-off201750200100
MTD-100% Cut-off200020100
-75% Cut-off2075020100
-50% Cut-off1601500160100
-25% Cut-off20225020100
+25% Cut-off2037519195
+50% Cut-off40450400100
+75% Cut-off20525200100
MOP-100% Cut-off200020100
-75% Cut-off2075020100
-50% Cut-off1601500160100
-25% Cut-off2022511995
+25% Cut-off20375200100
+50% Cut-off40450400100
+75% Cut-off20525200100
OXY-100% Cut-off200020100
-75% Cut-off2025020100
-50% Cut-off160500160100
-25% Cut-off207511995
+25% Cut-off20125200100
+50% Cut-off40150400100
+75% Cut-off20175200100
THC-100% Cut-off200020
-75% Cut-off2012.5020100
-50% Cut-off160250160100
-25% Cut-off2037.5020100
+25% Cut-off2062.519195
+50% Cut-off4075400100
+75% Cut-off2087.5200100

CLUNGENE Multi-Drug Test Dip Card

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

CLUNGENE Multi-Drug Test Easy Cup

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

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

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.

3. Clinical Studies

Not applicable.

11. Conclusion

Based on the test principle and acceptable performance characteristics including precision, cut-off, interference, specificity, method comparison, and lay-user studies of the devices, it's concluded that the CLUNGENE Multi-Drug Test Dip Card and CLUNGENE Multi-Drug Test Easy Cup are substantially equivalent to the predicate.

§ 862.3150 Barbiturate test system.

(a)
Identification. A barbiturate test system is a device intended to measure barbiturates, a class of hypnotic and sedative drugs, in serum, urine, and gastric contents. Measurements obtained by this device are used in the diagnosis and treatment of barbiturate use or overdose and in monitoring levels of barbiturate to ensure appropriate therapy.(b)
Classification. Class II (special controls). A barbiturate 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).