K Number
K151557
Date Cleared
2015-07-16

(36 days)

Product Code
Regulation Number
862.3640
Reference & Predicate Devices
Predicate For
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The EGENS Urine Test Cup Morphine - Methamphetamine is a rapid test for the qualitative detection of Morphine and Methamphetamine in human urine at a cutoff concentration of 300 ng/mL and 1000 ng/mL, respectively.

EGENS Urine Test Cup Morphine - Methamphetamine 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. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.

For in vitro diagnostic use only. The tests are intended for over-the-counter and for prescription use.

The EGENS Urine Test DipCard Morphine - Methamphetamine is a rapid test for the qualitative detection of Morphine and Methamphetamine in human urine at a cutoff concentration of 300 ng/mL and 1000 ng/mL, respectively.

EGENS Urine Test DipCard Morphine - Methamphetamine test provides only preliminary test results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. For in vitro diagnostic use only. The tests are intended for over-the-counter and for prescription use.

Device Description

EGENS Urine Test Morphine-Methamphetamine test uses immunochromatographic assays for Morphine and Methamphetamine. The test is a lateral flow system for the qualitative detection of Morphine and Methamphetamine in human urine. The test is the first step in a two-step process. The second step is to send the sample for laboratory testing if preliminary positive results are obtained.

AI/ML Overview

The provided document describes the performance characteristics of the EGENS Urine Test Cup Morphine - Methamphetamine and EGENS Urine Test DipCard Morphine - Methamphetamine devices.

Here's an analysis based on your request:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" but rather presents performance characteristics from various studies. For the purpose of this response, I infer the reported performance to be the intended criteria and thus list the results.

Morphine (MOP) and Methamphetamine (MET) Detection
Cut-off for Morphine: 300 ng/mL
Cut-off for Methamphetamine: 1000 ng/mL

Performance CharacteristicAcceptance Criteria (Inferred from data)Reported Device Performance - Morphine DipCardReported Device Performance - Methamphetamine DipCardReported Device Performance - Morphine CupReported Device Performance - Methamphetamine Cup
Precision
At -100% cut-off100% negative100% negative (50-/0+)100% negative (50-/0+)100% negative (50-/0+)100% negative (50-/0+)
At -75% cut-off100% negative100% negative (50-/0+)100% negative (50-/0+)100% negative (50-/0+)100% negative (50-/0+)
At -50% cut-off100% negative100% negative (50-/0+)100% negative (50-/0+)100% negative (50-/0+)100% negative (50-/0+)
At -25% cut-off100% negative100% negative (50-/0+)100% negative (50-/0+)100% negative (50-/0+)100% negative (50-/0+)
At cut-offMixed positive/negative (e.g., ~50% positive)62-66% positive (31-33+/17-19-) across 3 lots60-64% positive (30-32+/18-20-) across 3 lots62-66% positive (31-33+/17-19-) across 3 lots60-62% positive (30-31+/19-20-) across 3 lots
At +25% cut-off100% positive100% positive (50+/0-)100% positive (50+/0-)100% positive (50+/0-)100% positive (50+/0-)
At +50% cut-off100% positive100% positive (50+/0-)100% positive (50+/0-)100% positive (50+/0-)100% positive (50+/0-)
At +75% cut-off100% positive100% positive (50+/0-)100% positive (50+/0-)100% positive (50+/0-)100% positive (50+/0-)
At +100% cut-off100% positive100% positive (50+/0-)100% positive (50+/0-)100% positive (50+/0-)100% positive (50+/0-)
Cut-off Studies
All negative at -25% & -50% cut-off100% negative100% negative100% negative100% negative100% negative
All positive at +25% & +50% cut-off100% positive100% positive100% positive100% positive100% positive
InterferenceNo interference from listed compoundsNo interference at 100ug/mL for listed compoundsNo interference at 100ug/mL for listed compoundsNo interference at 100ug/mL for listed compoundsNo interference at 100ug/mL for listed compounds
Cross-Reactivity (Morphine)Various cross-reactivity percentages listedAchieved for listed compoundsN/AAchieved for listed compoundsN/A
Cross-Reactivity (Methamphetamine)Various cross-reactivity percentages listedN/AAchieved for listed compoundsN/AAchieved for listed compounds
Effect of Specific Gravity and Urine pHNo effect on device performanceNo effect observedNo effect observedNo effect observedNo effect observed
Laboratory Comparison Study (agreement with GC/MS)Not explicitly stated, but high agreement expected for samples not near cut-offHigh agreement (e.g., 100% outside near-cutoff range)High agreement (e.g., 100% outside near-cutoff range)High agreement (e.g., 100% outside near-cutoff range)High agreement (e.g., 100% outside near-cutoff range)
Lay-User Study (% Agreement with GC/MS)High agreement for samples outside near-cutoff rangeMorphine Dipcard: 90-100%Methamphetamine Dipcard: 90-100%Morphine Cup: 85-100% Methamphetamine Cup: 85-100%

2. Sample Size and Data Provenance

  • Precision Studies: For each concentration level (-100%, -75%, -50%, -25%, cut-off, +25%, +50%, +75%, +100% cut-off), 50 tests were performed per lot. With 3 lots and 9 concentrations, this is 50 * 3 * 9 = 1350 tests per drug for each device format (Cup/DipCard).
    • Data Provenance: Not explicitly stated, but the studies were conducted in-house. This typically implies controlled lab conditions rather than real-world patient samples, but the samples themselves are referenced as "samples with concentrations."
  • Cut-off Studies: A total of 125 morphine samples and 125 methamphetamine samples were used, equally distributed across 5 concentration levels (-50%, -25%, cut-off, +25%, +50%).
    • Data Provenance: Not explicitly stated, but implied to be controlled, spiked samples.
  • Interference/Specificity Studies: Samples were prepared by adding potential interfering substances or drug metabolites to urine containing target drugs. The quantity of samples is not explicitly given but implied to be sufficient for testing (e.g., "These samples were tested using three batches...").
    • Data Provenance: Not explicitly stated, likely controlled lab conditions.
  • Effect of Specific Gravity and Urine pH: 12 urine samples covering normal, high, and low specific gravity ranges, and urine pH adjusted to 4.00-9.00 in 1 pH unit increments. These were spiked samples.
    • Data Provenance: Not explicitly stated, likely controlled lab conditions.
  • Laboratory Comparison Studies: 80 "unaltered clinical samples" (40 negative and 40 positive) for each drug (Morphine and Methamphetamine) per device format (DipCard, Cup). This means 80 * 2 (drugs) * 2 (formats) = 320 samples in total for this part of the study.
    • Data Provenance: "Clinical samples" are explicitly stated, implying these are from actual patients rather than purely synthetic or spiked lab samples. The country of origin is not specified but the study was performed "in-house."
  • Lay-User Study: 560 lay persons. The study used 80 "drug-free samples", 240 "morphine samples", and 240 "methamphetamine samples". Within these, the document describes 20 samples per concentration level (-100%, -75%, -50%, -25%, +25%, +50%, +75% of cut-off) per drug.
    • Data Provenance: Urine samples were "spiked drugs into drug free-pooled urine specimens." So, these were controlled, spiked samples, not unalterted clinical samples.

3. Number of Experts and their Qualifications for Ground Truth

  • Laboratory Comparison Studies: "Three laboratory assistants" were involved in running the tests. Their qualifications are not specified beyond being "laboratory assistants."
  • Precision, Cut-off, Interference, Specific Gravity/pH Studies: "Three operators" repeatedly tested the samples. Their qualifications are not specified.
  • Lay-User Study: The "lay persons" were the "users" in this study, not "experts" establishing ground truth. There were 560 lay users. Their qualifications were described as having "diverse educational and professional backgrounds and ranged in age from 21 to >50 years."

4. Adjudication Method for the Test Set

  • Laboratory Comparison Studies: The collected results from the three viewers/operators were directly compared to the GC/MS results. There is no explicit mention of an adjudication process (e.g., 2+1, 3+1) among the viewers to establish a consensual device output. Each viewer's result was compared to GC/MS independently.
  • Other Studies (Precision, Cut-off, Interference, etc.): The results were aggregated from multiple operators/lots, but the tables present aggregated counts (e.g., 50-/0+, 33+/17-), not individual operator adjudication.
  • Lay-User Study: Each participant was given one blind-labeled sample and a device. Their individual results were recorded and compared to the GC/MS ground truth. No adjudication between lay users is mentioned.

5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study

There is no mention of a formal MRMC comparative effectiveness study or analysis of how much human readers improve with AI vs. without AI assistance. The study involves human readers (operators/lay users) interpreting the results of the device, but it does not compare their performance with and without an AI or advanced assistance system. It is a standalone device performance comparison against GC/MS.

6. Standalone Performance Study (Algorithm only without Human-in-the-loop)

The devices described (EGENS Urine Test Cup and DipCard) are rapid, qualitative immunoassay tests that rely on visual interpretation of results (presence or absence of colored lines). They are not "algorithms" in the computational sense, and there is no "algorithm only" or "standalone" performance without human-in-the-loop, as human interpretation of the visual result is integral to the device's function. The "laboratory comparison study" and "lay-user study" assess the device's performance when interpreted by humans.

7. Type of Ground Truth Used

  • Analytical Performance Studies (Precision, Cut-off, Interference, Specificity, Specific Gravity/pH): The ground truth was established by precise spiking of known concentrations of the target drug or interfering substances into drug-free urine.
  • Laboratory Comparison Studies: GC/MS (Gas Chromatography/Mass Spectrometry) was used as the preferred confirmatory method and thus, the primary ground truth reference.
  • Lay-User Study: GC/MS was used to confirm the concentrations of the spiked samples, serving as the ground truth.

8. Sample Size for the Training Set

The document describes premarket notification (510(k)) studies to demonstrate substantial equivalence, not the development of a predictive model or algorithm that would typically involve a "training set." Therefore, no training set size is mentioned or applicable in the context of these device types and studies. The tests are immunoassays, not machine learning models.

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

As stated above, this document does not describe the development of a device requiring a "training set" for a machine learning algorithm. The "training set" concept is not applicable here.

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Image /page/0/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of a bird or eagle with its wings spread.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

July 16, 2015

NANTONG EGENS BIOTECHNOLOGY CO., LTD. C/O JOE SHIA BUSINESS DIRECTOR 504 EAST DIAMOND AVE. SUITE I GAITHERSBURG MD 20878

Re: K151557

Trade/Device Name: EGENS Urine Test Cup Morphine - Methamphetamine. EGENS Urine Test DipCard Morphine - Methamphetamine Regulation Number: 21 CFR 862.3640 Regulation Name: Morphine test system Regulatory Class: II Product Code: DNK, LAF Dated: June 3, 2015 Received: June 10, 2015

Dear Joe Shia:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 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.

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If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Courtney

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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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

510(k) Number (if known) K151557

Device Name

EGENS Urine Test Cup Morphine - Methamphetamine

Indications for Use (Describe)

The EGENS Urine Test Cup Morphine - Methamphetamine is a rapid test for the qualitative detection of Morphine and Methamphetamine in human urine at a cutoff concentration of 300 ng/mL and 1000 ng/mL, respectively.

EGENS Urine Test Cup Morphine - Methamphetamine 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. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.

For in vitro diagnostic use only. The tests are intended for over-the-counter and for prescription use ..

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

X Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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

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

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

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

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

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Indications for Use

510(k) Number (if known) K151557

Device Name

EGENS Urine Test DipCard Morphine - Methamphetamine

Indications for Use (Describe)

The EGENS Urine Test DipCard Morphine - Methamphetamine is a rapid test for the qualitative detection of Morphine and Methamphetamine in human urine at a cutoff concentration of 300 ng/mL and 1000 ng/mL, respectively.

EGENS Urine Test DipCard Morphine - Methamphetamine 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. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.

For in vitro diagnostic use only. The tests are intended for over-the-counter and for prescription use.

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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

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

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

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

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

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510(k) SUMMARY

1. Date:July 9, 2015
Submitter:NANTONG EGENS BIOTECHNOLOGY, LTD.Building 15, 1692 Xinghu Avenue,Nantong 226010, China
2. Contact person:Yan CaoNANTONG EGENS BIOTECHNOLOGY, LTD.Building 15, 1692 Xinghu Avenue,Nantong 226010, ChinaPhone: 86-0513-85920700Email: cyhfhjn@163.com
    1. Device Name: EGENS Urine Test Cup Morphine - Methamphetamine EGENS Urine Test DipCard Morphine - Methamphetamine Classification: Class II
Product CodeCFR #Panel
DNK21 CFR, 862.3640 Morphine Test SystemToxicology
LAF21 CFR, 862.3610 Methamphetamine Test SystemToxicology
  1. Predicate Devices: K142580

Chemtrue Multi-Panel DOA DipCard Tests

    1. Intended Use:
      The EGENS Urine Test Cup Morphine - Methamphetamine is a rapid test for the qualitative detection of Morphine and Methamphetamine in human urine at a cutoff concentration of 300 ng/mL and 1000 ng/mL, respectively.

EGENS Urine Test Cup Morphine - Methamphetamine test provides only preliminary test results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. For in vitro diagnostic use only. The tests are intended for over-the-counter and for prescription use.

The EGENS Urine Test DipCard Morphine - Methamphetamine is a rapid test for the qualitative detection of Morphine and Methamphetamine in human urine at a cutoff concentration of 300 ng/mL and 1000 ng/mL, respectively.

EGENS Urine Test DipCard Morphine - Methamphetamine test provides only preliminary test results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result.

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GC/MS is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. For in vitro diagnostic use only. The tests are intended for over-the-counter and for prescription use.

    1. Device Description:
      EGENS Urine Test Morphine-Methamphetamine test uses immunochromatographic assays for Morphine and Methamphetamine. The test is a lateral flow system for the qualitative detection of Morphine and Methamphetamine in human urine. The test is the first step in a two-step process. The second step is to send the sample for laboratory testing if preliminary positive results are obtained.
ItemDevicePredicate - K142580
Indication(s)for useFor the qualitative determination ofdrugs of abuse in human urineSame
MethodologyCompetitive binding, lateral flowimmunochromatographic assaysbased on the principle of antigenantibody immunochemistry.Same
ResultsQualitativeSame
SpecimenTypeHuman urineSame
Cut Off ValuesMorphine: 300ng/mlMethamphetamine: 1000ng/mlSame for Morphine andMethamphetamine
ConfigurationsCup and DipcardDipcard
Conditions forUseOver-the-Counter & PrescriptionUseSame
    1. Substantial Equivalence Information

8. Test Principle

The EGENS Urine Test Morphine-Methamphetamine test is a rapid test for the qualitative detection of Morphine and Methamphetamine 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 below its 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.

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9. 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, at the cut-off, +25% cut-off, +75% cut-off and +100% cut-off. For each concentration, tests were performed two runs per day by three operators for 25 days. All sample aliquots were masked and randomized. The results obtained are summarized in the following tables:
ResultMOP-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 150-/0+50-/0+50-/0+50-/0+33+/17-50+/0-50+/0-50+/0-50+/0-
Lot 250-/0+50-/0+50-/0+50-/0+31+/19-50+/0-50+/0-50+/0-50+/0-
Lot 350-/0+50-/0+50-/0+50-/0+32+/18-50+/0-50+/0-50+/0-50+/0-

A. For Morphine (MOP) DipCard

B. For Methamphetamine (MET) DipCard

ResultMET-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 150-/0+50-/0+50-/0+50-/0+32+/18-50+/0-50+/0-50+/0-50+/0-
Lot 250-/0+50-/0+50-/0+50-/0+30+/20-50+/0-50+/0-50+/0-50+/0-
Lot 350-/0+50-/0+50-/0+50-/0+31+/19-50+/0-50+/0-50+/0-50+/0-

C. For Morphine (MOP) Cup

ResultMOP-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 150-/0+50-/0+50-/0+50-/0+31+/19-50+/0-50+/0-50+/0-50+/0-
Lot 250-/0+50-/0+50-/0+50-/0+32+/18-50+/0-50+/0-50+/0-50+/0-
Lot 350-/0+50-/0+50-/0+50-/0+33+/17-50+/0-50+/0-50+/0-50+/0-

D. For Methamphetamine (MET) Cup

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ResultMET-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 150-/0+50-/0+50-/0+50-/0+30+/20-50+/0-50+/0-50+/0-50+/0-
Lot 250-/0+50-/0+50-/0+50-/0+31+/19-50+/0-50+/0-50+/0-50+/0-
Lot 350-/0+50-/0+50-/0+50-/0+30+/20-50+/0-50+/0-50+/0-50+/0-

b. Linearity

Not applicable.

c. Stability

The EGENS Urine Test Morphine-Methamphetamine is stable at 4-30°C for 24 months as determined by conducting accelerated and real-time stability testing.

Control materials are not provided with the device. The labeling provides information on how to obtain control materials.

d. Cut-off

Cut-off studies were conducted using a total of 125 morphine samples and 125 methamphetamine samples equally distributed at concentrations of -50%, -25%, at the cut-off, +25%, +50% of their respective cut-offs. These samples were tested using three different lots by three different operators. Results were all positive at +25% and +50% cut-off and all negative at -25% and -50% cut-off for both morphine and methamphetamine. The following cut-off values for the test devices have been verified.

TestCalibratorCut-off(ng/ml)
Morphine (MOP )Morphine300
Methamphetamine (MET)D-Methamphetamine1000

e. Interference

Potential interfering substances found in human urine of physiological or pathological conditions were added to urine containing target drugs (morphine or methamphetamine) at 25% below and 25% above the cut-off. These urine samples were tested using three batches of the EGENS Urine Test DipCard (or Cup) Morphine-Methamphetamine by three different operators. There were no differences observed for different formats. Compounds that showed no interference at a concentration of 100ug/mL are summarized below:

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Morphine

4-AcetamidophenolEcgonine methylesterOxolinic acid
Acetaminophen(-)-Y-EphedrineOxycodone
AcetophenetidinErythromycinOxymetazoline
N-AcetvprocainamideFenoprofenPenicillin-G
AcetylsalicylateFurosemidePentobarbital
AminopyrineGentisic acidPerphenazine
AmityptylineHemoglobinPhencyclidine
AmorbarbitalHydralazinePhenelzine
AmoxicillinHydrochlorothiazidePhenobarbital
AmpicillinHydrocortisoneL-Phenylephrine
l-Ascorbic AcidO-Hydroxyhippuric acidb-Phenylethylamine
Apormorphinep-Hydroxy-methamphetaminePhenylpropanotamine
Aspartame3-HydroxytyraminePrednisone
AtropineIbuprofenPrednisolone
Benzilic acidImipramineProcaine
Benzoic acid(±)IsoproterenolD.L-Propanolol
BenzoylecgonineIsoxsuprineD-Propoxyphene
BilirubinKetamineD-Pseudoephedrine
CaffeineKetoprofenQuinine
CannabidiolLabetalolRanitidine
ChloralhydrateLoperamideSalicylic acid
ChloramphenicolLoxapine succinateSecobarbital
ChlordiazepoxideMaprotilineSerotonin
(5-Hydroxytyramine)
ChlorothiazideMeperidineSulfamethazine
ChlorpromazineMeprobamateSulindac
ChlorquineMethadoneTemazepam
CholesterolMethoxyphenamineTetracycline
Clomipramine(+)3,4-Methylenedioxy-amphetamineTetrahydrocortisone,3
Acetate
Clonidine(+)3,4-Methylenedioxy-methamphetamineTetrahydrocortisone 3
(ß-D glucuronide)
Cocaine hydrochlorideNalidixic acidTetrahydrozoline
(-)cotinineNalorphineThiamine
CreatinineNaloxoneThioridazine
DextromethlorphanNaltrexoneD.L-Tyrosine
DeoxycorticosteroneNaproxenTolbutamide
DiazepamNiacinamideTriamterene
DiclolrfenacNifedipineTrifluoperazine
DiflunisalNorethindroneTrimethoprim
DiaoxinD-NorpropoxypheneTryptamine
DiphenhydramineNoscapineD.L-Tryptophan
DoxylamineD.L-OctopamineTyramine
Ecgonine hydrochlorideOxalic acidUric acid
β-EstradiolOxazepamVerapamil
Estrone-3-sulfatePapaverineZomepirac

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Methamphetamine

4-AcetamidophenolEstrone-3-sulfateOxycodone
AcetaminophenErythromycinPapaverine
AcetophenetidinFenoprofenPenicillin-G
N-AcetylprocainamideFurosemidePentobarbital
AcetylsalicylateGentisic acidPerphenazine
AminopyrineHemoglobinPhencyclidine
AmitriptylineHydralazinePhenelzine
AmorbarbitalHydrochlorothiazidePhenobarbital
AmoxicillinHydrocodoneL-Phenylephrine
AmpicillinHydrocortisonePhenylpropanotamine
1-Ascorbic AcidO-Hydroxyhippuric acidPrednisone
Apormorphine3-HydroxytyraminePrednisolone
AspartameIbuprofenProcaine
AtropineImipramineD.L-Propanolol
Benzilic acid(±)IsoproterenolD-Propoxyphene
Benzoic acidIsoxsuprineD-Pseudoephedrine
BenzoylecgonineKetamineQuinine
BilirubinKetoprofenRanitidine
CaffeineLabetalolSalicylic acid
CannabidiolLoperamideSecobarbital
ChloralhydrateLoxapine succinateSerotonin
(5-Hydroxytyramine)
ChloramphenicolMaprotilineSulfamethazine
ChlordiazepoxideMeperidineSulindac
ChlorothiazideMeprobamateTemazepam
ChlorpromazineMethadoneTetracycline
CholesterolMethoxyphenamineTetrahydrocortisone,3 Acetate
ClomipramineMorphine-3-β-DglucuronideTetrahydrocortisone 3 (β-D
glucuronide)
ClonidineNalidixic acidTetrahydrozoline

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

Cocaine hydrochlorideNalorphineThebaine
CodeineNaloxoneThiamine
(-)cotinineNaltrexoneThioridazine
CreatinineNaproxenD.L-Tyrosine
DextromethlorphanNiacinamideTolbutamide
DeoxycorticosteroneNifedipineTriamterene
DiazepamNorethindroneTrifluoperazine
DiclolrfenacD-NorpropoxypheneTrimethoprim
DiflunisalNoscapineTryptamine
DiaoxinD.L-OctopamineD.L-Tryptophan
DiphenhydramineOxalic acidTyramine
DoxylamineOxazepamUric acid
EcgoninehydrochlorideOxolinic acidVerapamil
β-EstradiolOxymetazolineZomepirac
Ecgonine methylester

f. Specificity

To test the specificity, drug metabolites and other components that are likely to be present in urine samples were tested. The target drug (Morphine or Methamphetamine), its drug metabolites and the related compounds were studied. These samples were tested using three batches of the EGENS Urine Test DipCard (or Cup) Morphine-Methamphetamine by three different operators. The drug metabolites and other components were tested at different concentrations. The obtained lowest detectable concentration was used to calculate the cross-reactivity. Results are shown in the following tables. There were no differences observed for different formats.

MOP(Morphine,Cut-off=300 ng/mL)Result%Cross-Reactivity
MorphinePositive at 300 ng/mL100%
NormorphinePositive at 300 ng/mL100%
6-MonoacetylmorphinePositive at 300 ng/mL100%
CodeinePositive at 300 ng/mL100%
Ethyl MorphinePositive at 300 ng/mL100%
HeroinePositive at 300 ng/mL100%
HydrocodonePositive at 3,000 ng/mL10%
HydromorphonePositive at 4,000 ng/mL8%
Morphine-3-β-d-glucuronidePositive at 1,000 ng/mL30%
ThebainePositive at 15,000 ng/mL2%

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

OxycodoneNegative at 100,000 ng/mL<0.3%
OxymorphoneNegative at 100,000 ng/mL<0.3%
MET(D-Methamphetamine,Cut-off=1000 ng/mL)Result%Cross-Reactivity
D-MethamphetaminePositive at 1,000 ng/mL100%
(+/-)3,4-Methylenedioxy-n-ethylamphetamine(MDEA)Positive at 1,000 ng/mL100%
D/L-MethamphetaminePositive at 1,000 ng/mL100%
p-HydroxymethamphetaminePositive at 1,000 ng/mL100%
D-AmphetaminePositive at 50,000 ng/mL2%
L-AmphetaminePositive at 50,000 ng/mL2%
ChloroquinePositive at 50,000 ng/mL2%
(+/-)-EphedrinePositive at 20,000 ng/mL5%
L-MethamphetaminePositive at 20,000 ng/mL5%
(+/-)3,4-Methylenedioxyamphetamine (MDA)Positive at 1,000 ng/mL100%
(+/-)3,4-methylenedioxymethamphetamine(MDMA)Positive at 2,000 ng/mL50%
β-PhenylethylaminePositive at 34,000 ng/mL3%
TrimethobenzamidePositive at 8,300 ng/mL12%

g. Effect of Specific Gravity and Urine pH

Twelve urine samples of normal, high, and low specific gravity ranges (1.000 to 1.035) were collected and spiked with either Morphine or Methamphetamine at 25% below and 25% above the corresponding cut-off level. These samples were tested using three batches of the EGENS Urine Test DipCard (or Cup) Morphine-Methamphetamine by three different operators.

The pH of an aliquot negative urine pool was adjusted to pH ranges of 4.00 to 9.00 in 1 pH unit increments and spiked with Morphine or Methamphetamine at 25% below and 25% above the corresponding cut-off levels. These samples were tested using three batches of the EGENS Urine Test DipCard (or Cup) Morphine - Methamphetamine by three different operators.

The device performance was found to not be affected by varying specific gravity and pH. There were no differences observed for different formats.

    1. Comparison Studies

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The method comparison for the EGENS Urine Test DipCard (Cup) Morphine - Methamphetamine was performed in-house with three laboratory assistants for each format. Operators ran 80 (40 negative and 40 positive) unaltered clinical samples. The samples were masked and randomized. The obtained test results were compared to GC/MS results. The results are presented in the table below:

Morphine DipCard
--------------------------
GroupOperatorsNegativeLowNegative byGC/MS(less than-50%)Near CutoffNegative byGC/MS(Between-50% andcutoff)Near CutoffPositive byGC/MS(Betweenthe cutoffand +50%)HighPositive byGC/MS(greaterthan +50%)
Viewer APositive0001226
Negative10181220
Viewer BPositive0001226
Negative10181220
Viewer CPositive0001226
Negative10181220

Discordant table:

ViewerSample numberGC/MS resultViewer result
Viewer A1019308negative
Viewer A1040305negative
Viewer B1019308negative
Viewer B1040305negative
Viewer C1019308negative
Viewer C1040305negative

Morphine Cup

GroupOperatorsNegativeLowNegative byGC/MS(less than-50%)Near CutoffNegative byGC/MS(Between-50% andcutoff)Near CutoffPositive byGC/MS(Betweenthe cutoffand +50%)HighPositive byGC/MS(greaterthan +50%)
Viewer APositive0001226
Negative10181220
Viewer BPositive0001226
Negative10181220
Viewer CPositive0001226
Negative10181220

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

Discordant table:

ViewerSample numberGC/MS resultViewer result
Viewer A1019308negative
Viewer A1040305negative
Viewer B1019308negative
Viewer B1040305negative
Viewer C1019308negative
Viewer C1040305negative

Methamphetamine DipCard

GroupOperatorsNegativeLowNegative byGC/MS(less than-50%)Near CutoffNegative byGC/MS(Between-50% andcutoff)Near CutoffPositive byGC/MS(Betweenthe cutoffand +50%)HighPositive byGC/MS(greaterthan +50%)
Viewer APositive0001226
Negative10181220
Viewer BPositive0001226
Negative10181220
Viewer CPositive0001226
Negative10181220

Discordant table:

ViewerSample numberGC/MS resultviewer results
Viewer A8491045negative
Viewer A8661040negative
Viewer B8491045negative
Viewer B8661040negative
Viewer C8491045negative
Viewer C8661040negative

Methamphetamine Cup

GroupOperatorsNegativeLowNegative byGC/MS(less than-50%)Near CutoffNegative byGC/MS(Between-50% andcutoff)Near CutoffPositive byGC/MS(Betweenthe cutoffand +50%)HighPositive byGC/MS(greaterthan +50%)
Viewer APositive0001226
Viewer ANegative10181220

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

Viewer BPositive0001226
Negative10181220
Viewer CPositive0001226
Negative10181220

Discordant table:

ViewerSample numberGC/MS resultviewer results
Viewer A8491045negative
Viewer A8661040negative
Viewer B8491045negative
Viewer B8661040negative
Viewer C8491045negative
Viewer C8661040negative

Lay-user study

A lay user study was performed at three intended user sites with 560 lay persons, of which, 80 tested for drug-free samples, 240 for morphine samples, 240 for methamphetamine samples. They had diverse educational and professional backgrounds and ranged in age from 21 to >50 years. Urine samples were prepared at the following concentrations; -100%, +/-75%, +/-50%, +/-25% of the cut-off by spiking drugs into drug free-pooled urine specimens. The concentrations of the samples were confirmed by GC/MS. Each sample was aliquoted into individual containers, blind-labeled and randomized. Each participant was provided with the package insert, 1 blind labeled sample and a device. The results are summarized below:

DipCard formatOTC user% Agreement
DrugConcentrationNumber of samplesNegativePositiveWith GC/MS
Drug -free-100%20200100%
Morphine-75%20200100%
-50%20200100%
-25%2018290%
+25%2021890%
+50%20020100%
+75%20020100%
Drug -free-100%20200100%
Methamphetamine-75%20200100%
-50%20200100%
-25%2018290%
+25%2021890%
+50%20020100%
+75%20020100%

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

Cup formatOTC user% Agreement
DrugConcentrationNumber of samplesNegativePositiveWith GC/MS
Drug -free-100%20200100%
Morphine-75%20200100%
-50%20200100%
-25%2018285%
+25%2021885%
+50%20020100%
+75%20020100%
Drug -free-100%20200100%
Methamphetamine-75%20200100%
-50%20200100%
-25%2018285%
+25%2021885%
+50%20020100%
+75%20020100%

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 the package insert and the score revealed a reading grade level of less than 7.

    1. Clinical Studies
      Not applicable.

10. Conclusion

Based on the test principle and performance characteristics of the device, it's concluded that EGENS Urine Test DipCard Morphine -Methamphetamine and EGENS Urine Test Cup Morphine -Methamphetamine are substantially equivalent to the predicate.

§ 862.3640 Morphine test system.

(a)
Identification. A morphine test system is a device intended to measure morphine, an addictive narcotic pain-relieving drug, and its analogs in serum, urine, and gastric contents. Measurements obtained by this device are used in the diagnosis and treatment of morphine use or overdose and in monitoring levels of morphine and its analogs to ensure appropriate therapy.(b)
Classification. Class II (special controls). A morphine 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).