First Sign Drug of Abuse Dip Card Test, First Sign Drug of Abuse Cup Test

• K Number: K150162
• Device Name: First Sign Drug of Abuse Dip Card Test, First Sign Drug of Abuse Cup Test
• Manufacturer: W.H.P.M., Inc.
• Date Cleared: 2015-02-26 ( 31 days)
• Product Code: LAF DJG JXM
• Regulation Number: 862.3610

Intended Use

First Sign™ Drug of Abuse Tests are immunochromatographic assays for the qualitative determination of Oxazepam , Methamphetamine, and Morphine in human urine at cut-off concentrations of 300 ng/mL, and 2000 ng/mL, respectively. The tests are available in a Cup format and a Dip Card format. The tests may yield preliminary positive results even when prescription drug Oxazepam is ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of this drug. There is no uniformly recognized cutoff concentration level for oxazepam in urine. The tests provide only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. For in vitro diagnostic use only. The tests are intended for over-the-counter and for prescription use.

Device Description

First Sign™ Drug of Abuse Tests are immunochromatographic assays. Each assay test is a lateral flow system for the qualitative detection of Oxazepam , Methamphetamine , and Morphine in human urine. The products are single-use in vitro diagnostic devices, which come in the formats of DipCards or Cups. Each test kit contains a Test Device (in one of the two formats), a package insert and a urine cup for sample collection. Each test device is sealed with a desiccant in an aluminum pouch.

Predicate Devices

K052115

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies focus on immunochromatographic assays and traditional analytical methods, with no mention of AI or ML.

Therapeutic

No
This device is an in vitro diagnostic test designed to detect drugs of abuse in urine, not to treat or prevent a disease or condition.

Diagnostic

Yes.
The device is described as an "in vitro diagnostic device" in the "Device Description" section and states "For in vitro diagnostic use only" in both "Intended Use / Indications for Use" and "Intended User / Care Setting". It determines the presence of drugs in human urine, which is a diagnostic purpose.

SaMD (Software as a Medical Device)

No

The device is described as an immunochromatographic assay, which is a physical test strip or cup that uses chemical reactions to detect substances in urine. The description explicitly mentions "DipCards or Cups" and "Test Device," indicating a hardware component is central to the device's function.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

• Explicit Statement: The "Intended Use / Indications for Use" section clearly states: "For in vitro diagnostic use only."
• Device Description: The "Device Description" section also states: "The products are single-use in vitro diagnostic devices..."
• Nature of the Test: The device performs a test on a human sample (urine) to detect the presence of specific substances (drugs of abuse) for diagnostic purposes (determining if drugs are present). This aligns with the definition of an in vitro diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

First Sign™ Drug of Abuse Tests are immunochromatographic assays for the qualitative determination of Oxazepam , Methamphetamine , and Morphine in human urine at cut-off concentrations of 300 ng/mL, 1000 ng/mL, and 2000 ng/mL, respectively. The tests are available in a Cup format and a Dip Card format.

The tests may yield preliminary positive results even when prescription drug Oxazepam is ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of this drug. There is no uniformly recognized cutoff concentration level for oxazepam in urine. The tests provide only preliminary test results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.

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

Product codes (comma separated list FDA assigned to the subject device)

LAF, JXM, DJG

Device Description

First Sign™ Drug of Abuse Tests are immunochromatographic assays. Each assay test is a lateral flow system for the qualitative detection of Oxazepam , Methamphetamine , and Morphine in human urine. The products are single-use in vitro diagnostic devices, which come in the formats of DipCards or Cups. Each test kit contains a Test Device (in one of the two formats), a package insert and a urine cup for sample collection. Each test device is sealed with a desiccant in an aluminum pouch.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

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

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

1. Analytical Performance

• 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, +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 GC/MS. All sample aliquots were blind-labeled and randomized by the person who prepared samples and did not take part in the sample testing. For each concentration, tests were performed two runs per day for 25 days by three different operators for each format of devices. Different set of operators tested each format.
  • Oxazepam Dip Card Format: At cutoff, 3-/47+ for Lot D4010558, 4-/46+ for Lot D4010560, 3-/47+ for Lot D4010562 (out of 50 tests). At +25% cutoff, 50+/0- for all lots. At -25% cutoff, 50-/0+ for all lots. (Sample size: 50 tests per concentration per lot).
  • Oxazepam Cup Format: At cutoff, 3-/47+ for Lot D4010559, 3-/47+ for Lot D4010561, 4-/46+ for Lot D4010563 (out of 50 tests). At +25% cutoff, 50+/0- for all lots. At -25% cutoff, 50-/0+ for all lots. (Sample size: 50 tests per concentration per lot).
  • Methamphetamine (mAMP) Dip Card Format: At cutoff, 4-/46+ for Lot D4010558, 3-/47+ for Lot D4010560, 3-/47+ for Lot D4010562 (out of 50 tests). At +25% cutoff, 50+/0- for all lots. At -25% cutoff, 50-/0+ for all lots. (Sample size: 50 tests per concentration per lot).
  • mAMP Cup Format: At cutoff, 3-/47+ for Lot D4010559, 2-/48+ for Lot D4010561, 3-/47+ for Lot D4010563 (out of 50 tests). At +25% cutoff, 50+/0- for all lots. At -25% cutoff, 50-/0+ for all lots. (Sample size: 50 tests per concentration per lot).
  • Morphine Dip Card Format: At cutoff, 3-/47+ for Lot D4010558, 3-/47+ for Lot D4010560, 4-/46+ for Lot D4010562 (out of 50 tests). At +25% cutoff, 50+/0- for all lots. At -25% cutoff, 50-/0+ for all lots. (Sample size: 50 tests per concentration per lot).
  • Morphine Cup Format: At cutoff, 2-/48+ for Lot D4010559, 3-/47+ for Lot D4010561, 3-/47+ for Lot D4010563 (out of 50 tests). At +25% cutoff, 50+/0- for all lots. At -25% cutoff, 50-/0+ for all lots. (Sample size: 50 tests per concentration per lot).
• Linearity: Not applicable.
• Stability: The devices are stable at 4-30°C (39-86°F) for 24 months based on the accelerated stability study at 50°C.
• Cut-off: A total of 150 samples equally distributed at concentrations of -50% cut-off; -25% cut-off; cut-off; +25% cut-off; +50% cut-off were tested using three different lots of each device by three different operators. Results were all positive at and above +25% cut-off and all negative at and below -25% cut-off for Oxazepam, Methamphetamine and Morphine.
  • Oxazepam: 300 ng/mL
  • Methamphetamine: 1000 ng/mL
  • Morphine: 2000 ng/mL
• Interference: Potential interfering substances found in human urine of physiological conditions were added to drug-free urine and to urine containing target drugs at 25% below and 25% above cut-off levels. These urine samples were tested using three batches of each device for all formats. Compounds that showed no interference at a concentration of 100µg/mL were summarized in tables (detailed list provided). No differences observed for different formats.
• Specificity: Drug metabolites and other components that are likely to interfere in urine samples were tested using three batches of each device for all formats. The obtained lowest detectable concentration was used to calculate the cross-reactivity. No differences observed for different formats. Detailed cross-reactivity results provided for Oxazepam, Methamphetamine, and Morphine.
• Effect of Urine Specific Gravity and Urine pH: Urine samples with a range of 1.000 to 1.035 specific gravity or urine samples with a range of pH 4 to 9 were spiked with target drugs at 25% below and 25% above cut-off levels. These samples were tested using three batches of each device for all formats. Results were all positive for samples at and above +25% cut-off and all negative for samples at and below -25% Cut-Off. No differences observed for different formats.

2. Comparison Studies

• Method Comparison (Clinical Samples): Performed in-house with three different laboratory assistants for each format of the device. Operators ran 80 (40 negative and 40 positive) unaltered clinical samples for each drug. Samples were blind labeled and compared to GC/MS results.
  • Oxazepam Dip Card: For Viewer A, 13 positive results in "Near Cutoff Positive" and 25 in "High Positive". 2 negative results in "Near Cutoff Positive". Similar results for Viewer B and C. (Sample size: 80 clinical samples per viewer for each drug). Discordant Results (GC/MS result vs Dipcard format viewer results): Sample 94638975 (324 ng/mL) Negative, 83001567 (325 ng/mL) Negative, 83002215 (326 ng/mL) Negative, 94639027 (328 ng/mL) Negative.
  • Oxazepam Cup: For Viewer A, 14 positive results in "Near Cutoff Positive" and 25 in "High Positive". 1 negative result in "Near Cutoff Positive". Similar results for Viewer B and C. (Sample size: 80 clinical samples per viewer for each drug). Discordant Results (GC/MS result vs Cup format viewer results): Sample 83002215 (326 ng/mL) Negative, 83001567 (325 ng/mL) Negative, 94639027 (328 ng/mL) Negative.
  • Methamphetamine Dip Card: For Viewer A, 18 positive results in "Near Cutoff Positive" and 21 in "High Positive". 1 negative result in "Near Cutoff Positive". Similar results for Viewer B and C. (Sample size: 80 clinical samples per viewer for each drug). Discordant Results: Sample 83000530 (1156 ng/mL) Negative, 83001807 (1094 ng/mL) Negative, 83001811 (1065 ng/mL) Negative, 83001807 (1094 ng/mL) Negative.
  • Methamphetamine Cup: For Viewer A, 18 positive results in "Near Cutoff Positive" and 21 in "High Positive". 1 negative result in "Near Cutoff Positive". Similar results for Viewer B and C. (Sample size: 80 clinical samples per viewer for each drug). Discordant Results: Sample 83001821 (1079 ng/mL) Negative, 83001807 (1094 ng/mL) Negative.
  • Morphine Dip Card: For Viewer A, 15 positive results in "Near Cutoff Positive" and 24 in "High Positive". 1 negative result in "Near Cutoff Positive". Similar results for Viewer B and C. (Sample size: 80 clinical samples per viewer for each drug). Discordant Results: Sample 94639012 (2119 ng/mL) Negative, 83000219 (2325 ng/mL) Negative.
  • Morphine Cup: For Viewer A, 15 positive results in "Near Cutoff Positive" and 24 in "High Positive". 1 negative result in "Near Cutoff Positive". Similar results for Viewer B and C. (Sample size: 80 clinical samples per viewer for each drug). Discordant Results: Sample 83000219 (2325 ng/mL) Negative, 83000572 (2227 ng/mL) Negative, 94639012 (2119 ng/mL) Negative.
• Lay-user study:
  • Sample size: 280 lay persons tested Oxazepam devices, 280 for Methamphetamine, and 280 for Morphine. (Total of 840 lay users).
  • Data source: Urine samples prepared with known concentrations (negative, +/-75%, +/-50%, +/-25% of cutoff) by spiking drugs into drug-free pooled urine specimens. Concentrations confirmed by GC/MS. Samples aliquoted and blind-labeled.
  • Annotation protocol: Each participant was provided with the package insert, 1 blind labeled sample, and a device. Results were recorded by observation.
  • Key Results (percentage of correct results):
    • Oxazepam DipCard: 100% correct for -100% to -25% Cutoff samples. 90% correct for +25% Cutoff samples. 100% correct for +50% and +75% Cutoff samples.
    • Oxazepam Cup: 100% correct for -100% to -50% Cutoff samples. 90% correct for -25% Cutoff samples. 100% correct for +25% to +75% Cutoff samples.
    • Methamphetamine DipCard: 100% correct for negative to -25% Cutoff samples. 95% correct for +25% Cutoff samples. 100% correct for +50% and +75% Cutoff samples.
    • Methamphetamine Cup: 100% correct for negative to -25% Cutoff samples. 95% correct for +25% Cutoff samples. 100% correct for +50% and +75% Cutoff samples.
    • Morphine DipCard: 100% correct for negative to -50% Cutoff samples. 95% correct for -25% Cutoff samples. 100% correct for +25% to +75% Cutoff samples.
    • Morphine Cup: 100% correct for negative to -25% Cutoff samples. 95% correct for +25% Cutoff samples. 100% correct for +50% and +75% Cutoff samples.
  • Lay-user survey: All lay users indicated that the device instructions can be easily followed. Flesch-Kincaid reading analysis showed a reading Grade Level of 7 for package inserts.

3. Clinical Studies
Not applicable.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Values are expressed as "No. of Positive / No. of Negative" results out of total tests performed at each concentration.

Precision Study (50 tests per concentration per lot):

• Oxazepam (Cut-off 300 ng/mL):
  • At Cut-off: Range from 3-/47+ to 4-/46+ (meaning 3 or 4 negatives / 47 or 46 positives, effectively 92-94% positive agreement).
  • At +25% Cut-off (375 ng/mL): 50+/0- (100% positive agreement).
  • At -25% Cut-off (225 ng/mL): 50-/0+ (100% negative agreement).
• Methamphetamine (Cut-off 1000 ng/mL):
  • At Cut-off: Range from 2-/48+ to 4-/46+ (meaning 2 to 4 negatives / 48 to 46 positives, effectively 92-96% positive agreement).
  • At +25% Cut-off (1250 ng/mL): 50+/0- (100% positive agreement).
  • At -25% Cut-off (750 ng/mL): 50-/0+ (100% negative agreement).
• Morphine (Cut-off 2000 ng/mL):
  • At Cut-off: Range from 2-/48+ to 4-/46+ (meaning 2 to 4 negatives / 48 to 46 positives, effectively 92-96% positive agreement).
  • At +25% Cut-off (2500 ng/mL): 50+/0- (100% positive agreement).
  • At -25% Cut-off (1500 ng/mL): 50-/0+ (100% negative agreement).

Lay Person Results (Percentage of Correct Results):

• Oxazepam (DipCard & Cup):
  • Negative to -25% Cutoff (drug-free to 222 ng/mL): 100% correct.
  • +25% Cutoff (384 ng/mL): 90% correct.
  • +50% Cutoff (468 ng/mL) and +75% Cutoff (542 ng/mL): 100% correct.
• Methamphetamine (DipCard & Cup):
  • Negative to -25% Cutoff (drug-free to 729 ng/mL): 100% correct.
  • +25% Cutoff (1212 ng/mL): 95% correct.
  • +50% Cutoff (1441 ng/mL) and +75% Cutoff (1666 ng/mL): 100% correct.
• Morphine (DipCard & Cup):
  • Negative to -50% Cutoff (drug-free to 1053 ng/mL): 100% correct.
  • -25% Cutoff (1573 ng/mL): 95% correct for DipCard, 100% correct for Cup.
  • +25% Cutoff (2652 ng/mL): 100% correct for DipCard, 95% correct for Cup.
  • +50% Cutoff (3254 ng/mL) and +75% Cutoff (3711 ng/mL): 100% correct.

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K052115

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 862.3610 Methamphetamine test system.

(a)
Identification. A methamphetamine test system is a device intended to measure methamphetamine, a central nervous system stimulating drug, in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of methamphetamine use or overdose.(b)
Classification. Class II (special controls). A methamphetamine 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).

Summary

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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized symbol that resembles a human figure in profile, with three overlapping heads.

February 26, 2015

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

W.H.P.M., INC. JOHN WAN 5358 IRWINDALE AVENUE IRWINDALE CA 91706

Re: K150162 Trade/Device Name: First Sign® Drug Of Abuse Cup Test First Sign® Drug Of Abuse Dip Card Test Regulation Number: 21 CFR 862.3610 Regulation Name: Methamphetamine test system Regulatory Class: II Product Code: LAF, JXM, DJG Dated: January 19, 2015 Received: January 26, 2015

Dear Mr. John Wan:

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 (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

1

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 [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/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 [phone] or [phone] or at its Internet address

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

Sincerely yours,

Katherine Serrano -A

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) K150162

Device Name First Sign® Drug of Abuse Cup Test First Sign® Drug of Abuse Dip Card Test

Indications for Use (Describe)

First Sign™ Drug of Abuse Tests are immunochromatographic assays for the qualitative determination of Oxazepam , Methamphetamine, and Morphine in human urine at cut-off concentrations of 300 ng/mL, and 2000 ng/mL, respectively. The tests are available in a Cup format and a Dip Card format.

The tests may yield preliminary positive results even when prescription drug Oxazepam is ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of this drug. There is no uniformly recognized cutoff concentration level for oxazepam in urine. The tests provide only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.

For in vitro diagnostic use only. The 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)

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510(k) SUMMARY K150162

• February 24, 2015 1. Date: 2. Submitter W.H.P.M., Inc. 5358 Irwindale Ave. Irwindale, CA 91706 3. Contact person:
  John Wan W.H.P.M., Inc. 5358 Irwindale Ave. Irwindale, CA 91706 Telephone: [phone] Fax: [phone] Email: [e-mail]

• First Sign® Drug of Abuse Cup Test 4. Device Name: First Sign® Drug of Abuse Dip Card Test

Classification: Class II

| Product

Code	CFR #	Panel
LAF	21 CFR, 862.3610 Methamphetamine Test System	Toxicology
JXM	21 CFR, 862.3170 Benzodiazepine Test System	Toxicology
DJG	21 CFR, 862.3650 Opiate Test System	Toxicology

• 5. Predicate Devices:
     K052115 First Check Multi Drug Cup 12

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6. Intended Use

First Sign™ Drug of Abuse Tests are immunochromatographic assays for the qualitative determination of Oxazepam , Methamphetamine , and Morphine in human urine at cut-off concentrations of 300 ng/mL, 1000 ng/mL, and 2000 ng/mL, respectively. The tests are available in a Cup format and a Dip Card format.

The tests may yield preliminary positive results even when prescription drug Oxazepam is ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of this drug. There is no uniformly recognized cutoff concentration level for oxazepam in urine. The tests provide only preliminary test results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. Gas Chromatography/Mass Spectrometry is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive.

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

• 7. Device Description
     First Sign™ Drug of Abuse Tests are immunochromatographic assays. Each assay test is a lateral flow system for the qualitative detection of Oxazepam , Methamphetamine , and Morphine in human urine. The products are single-use in vitro diagnostic devices, which come in the formats of DipCards or Cups. Each test kit contains a Test Device (in one of the two formats), a package insert and a urine cup for sample collection. Each test device is sealed with a desiccant in an aluminum pouch.
• 8. Substantial Equivalence Information
     A summary comparison of features of the First Sign™ Drug of Abuse Test and the predicate device is provided in Table 1, Table 2 & Table 3.

| Item | Device | Predicate -
K052115 |
|--------------------------|-------------------------------------------------------------------------------------------------------------------------------------|------------------------|
| Indication(s)
for Use | For the qualitative determination of
Oxazepam in human urine. | Same |
| Calibrator | Oxazepam | Same |
| Methodology | Competitive binding, lateral flow
immunochromatographic assays based on
the principle of antigen antibody
immunochemistry. | Same |
| Specimen Type | Human Urine | Same |
| Cut-Off Values | 300 ng/mL | Same |

Table 1: Features Comparison of First Sign™ Oxazepam Test and the Predicate Device

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| Item | Device | Predicate -
K052115 |
|------------------------|------------------------------------------------|---------------------------------|
| Intended
Population | For over-the-counter and prescription
uses. | For
over-the-counter
use. |
| Configurations | Cup, Dip Card | Cup |

Table 2: Features Comparison of First Sign™ Methamphetamine Test and the Predicate Device

Item	Device	Predicate - K052115
Indication(s) for Use	For the qualitative determination of methamphetamine in human urine.	Same
Calibrator	D-methamphetamine	Same
Methodology	Competitive binding, lateral flow immunochromatographic assays based on the principle of antigen antibody immunochemistry.	Same
Specimen Type	Human Urine	Same
Cut-Off Values	1000 ng/mL	Same
Intended Population	For over-the-counter and prescription uses.	For over-the-counter use.
Configurations	Cup, Dip Card	Cup

Table 3: Features Comparison of First Sign™ Morphine Test and the Predicate Device

Item	Device	Predicate - K052115
Indication(s)
for Use	For the qualitative determination of
morphine in human urine.	For the qualitative
determination of
opiates in human
urine, including
morphine.
Calibrator	Morphine	Same
Methodology	Competitive binding, lateral flow
immunochromatographic assays based
on the principle of antigen antibody	Same

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Item	Device	Predicate - K052115
	immunochemistry.
Specimen Type	Human Urine	Same
Cut-Off Values	2000 ng/mL	Same
Intended	For over-the-counter and prescription	For over-the-counter
Population	uses.	use.
Configurations	Cup, Dip Card	Cup

9. Test Principle

First Sign™ Drug of Abuse Tests are rapid tests for the qualitative detection of Oxazepam . Methamphetamine , and Morphine in urine samples. Each assay test is a lateral flow chromatographic immunoassay. During testing, a urine specimen migrates upward by capillary action. If target drugs are present in the urine specimen below its cut-off concentration, it will not saturate the binding sites of its specific antibody (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 cut-off 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.

10. Performance Characteristics

1. Analytical Performance

• a. Precision
  Precision studies were carried out for samples with concentrations of -100% cut-off, -50% cut-off, -25% cut-off, at the cut-off, +25% cut-off, +75% 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 GC/MS. All sample aliquots were blind-labeled and randomized by the person who prepared samples and did not take part in the sample testing. For each concentration, tests were performed two runs per day for 25 days by three different operators for each format of devices. Different set of operators tested each format. The results obtained are summarized in the following tables:

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Oxazepam Dip Card Format

| | Result | -100%
Cut-off | -75%
Cut-off | -50%
Cut-off | -25%
Cut-off | Cut-off | +25%
Cut-off | +50%
Cut-off | +75%
Cut-off | +100%
Cut-off |
|------|---------------|------------------|-----------------|-----------------|-----------------|---------|-----------------|-----------------|-----------------|------------------|
| Drug | Lot: D4010558 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Drug | Lot: D4010560 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 4-/46+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Drug | Lot: D4010562 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |

Oxazepam Cup Format

| | Result | -100%
Cut-off | -75%
Cut-off | -50%
Cut-off | -25%
Cut-off | Cut-off | +25%
Cut-off | +50%
Cut-off | +75%
Cut-off | +100%
Cut-off |
|---------------|--------|------------------|-----------------|-----------------|-----------------|---------|-----------------|-----------------|-----------------|------------------|
| Drug | | | | | | | | | | |
| Lot: D4010559 | | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot: D4010561 | | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot: D4010563 | | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 4-/46+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |

Methamphetamine (mAMP) Dip Card Format

| | Result | -100%
Cut-off | -75%
Cut-off | -50%
Cut-off | -25%
Cut-off | Cut-off | +25%
Cut-off | +50%
Cut-off | +75%
Cut-off | +100%
Cut-off |
|------|---------------|------------------|-----------------|-----------------|-----------------|---------|-----------------|-----------------|-----------------|------------------|
| Drug | Lot: D4010558 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 4-/46+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| | Lot: D4010560 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| | Lot: D4010562 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |

(mAMP) Cup Format

| | Result | -100%
Cut-off | -75%
Cut-off | -50%
Cut-off | -25%
Cut-off | Cut-off | +25%
Cut-off | +50%
Cut-off | +75%
Cut-off | +100%
Cut-off |
|---------------|--------|------------------|-----------------|-----------------|-----------------|---------|-----------------|-----------------|-----------------|------------------|
| Drug | | | | | | | | | | |
| Lot: D4010559 | | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot: D4010561 | | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 2-/48+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot: D4010563 | | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |

Morphine Dip Card Format

| | Result | -100%
Cut-off | -75%
Cut-off | -50%
Cut-off | -25%
Cut-off | Cut-off | +25%
Cut-off | +50%
Cut-off | +75%
Cut-off | +100%
Cut-off |
|---------------|--------|------------------|-----------------|-----------------|-----------------|---------|-----------------|-----------------|-----------------|------------------|
| Drug | | | | | | | | | | |
| Lot: D4010558 | | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot: D4010560 | | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot: D4010562 | | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 4-/46+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |

8

	Result	-100% Cut-off	-75% Cut-off	-50% Cut-off	-25% Cut-off	Cut-off	+25% Cut-off	+50% Cut-off	+75% Cut-off	+100% Cut-off
Drug
Lot: D4010559		50-/0+	50-/0+	50-/0+	50-/0+	2-/48+	50+/0-	50+/0-	50+/0-	50+/0-
Lot: D4010561		50-/0+	50-/0+	50-/0+	50-/0+	3-/47+	50+/0-	50+/0-	50+/0-	50+/0-
Lot: D4010563		50-/0+	50-/0+	50-/0+	50-/0+	3-/47+	50+/0-	50+/0-	50+/0-	50+/0-

Morphine Cup Format

b. Linearity

Not applicable.

c. Stability

The devices are stable at 4-30°C (39-86°F) for 24 months based on the accelerated stability study at 50°C. Control materials are not provided with the device. The labeling provides information on how to obtain control materials.

d. Cut-off

A total of 150 samples equally distributed at concentrations of -50% cut-off; -25% cut-off; cut-off; +25% cut-off; +50% cut-off were tested using three different lots of each device by three different operators. Results were all positive at and above +25% cut-off and all negative at and below -25% cut-off for Oxazepam, Methamphetamine and Morphine. The following cut-off values for the test devices have been verified.

Test	Calibrator	Cut-off (ng/mL)
One Step Oxazepam Test	Oxazepam	300
One Step Methamphetamine Test	D-methamphetamine	1000
One Step Morphine Test	Morphine	2000

e. Interference

Potential interfering substances found in human urine of physiological conditions were added to drug-free urine and to urine containing target drugs at 25% below and 25% above cut-off levels. These urine samples were tested using three batches of each device for all formats.

Compounds that showed no interference at a concentration of 100µg/mL are summarized in the following tables. There were no differences observed for different formats.

9

Oxazepam 4-Acetamidophenol Diphenhydramine D.L-Octopamine Acetophenetidin Doxylamine Oxalic acid N-Acetvprocainamide Ecaonine dydrochloride Oxolinic acid Acetvsalicvlic acid Ecqonine methylester Pentobarbital Aminopvrine (-)-Y-Ephedrine Perphenazine Amityptvline Fenoprofen Phencyclidine Amorbarbital Phenelzine Furosemide Amoxicillin Gentisic acid Phenobarbital Ampicillin Hemoglobin Phentermine l-Ascorbic Acid Hydrocortisone L-Phenylephrine O-Hydroxyhippuric acid B-Phenylethylamine D.L-Amphetamine p-Hydroxy-Apormorphine methamphetamine Phenylpropanotamine Aspartame 3-Hydroxytyramine Prednisone Atropine Ibuprofen D.L-Propanolol Benzillic acid Imipramine D-Pseudoephedrine Benzoic acid Iproniazid Quinine Benzoylecaonine (±)Isoproterenol Ranitidine Benzphetamine Isoxsuprine Salicylic acid Bilirubin Ketamine Secobarbital Serotonin (±) Chlorpheniramine Ketoprofen (5-Hydroxytyramine) Caffeine Labetalol Sertraline Cannabidiol Loperamide Sulfamethazine Chloralhvdrate Maprotiline Sulindac Tetrahydrocortisone,(b-D Chloramphenicol Meperidine glucuronide) Chlorothiazide Meprobamate Tetrahydrozoline (±)Chlorpheniramine Thiamine Methadone Methoxyphenamine Thioridazine Chlorpromazine (+) 3,4-Methylenedioxy-Chlorquine amphetamine D.L-Tyrosine (+)3,4-Methylenedioxy-Cholesterol Tolbutamide methamphetamine Clomipramine Nalidixic acid Triamterene Clonidine Nalorphine Trifluoperazine Cocaine hydrochloride Naloxone Trimethoprim Cortisone Naltrexone Triyptamine D.L-Tryptophan (-)cotinine Naproxen

10

Creatinine	Niacinamide	Tyramine
Dextromethlorphan	Nifedipine	Uric acid
Diclolrfenac	Norethindrone	Verapamil
Diflunisal	D-Norpropoxyphene	Zomepirac
Diaoxin	Noscapine

Methamphetamine

Acetamidophen	Gentisic acid	Oxycodone
Acetophenetidin	Glucuronide	Oxymetazoline
N-Acetylprocainamide	Glutethimide	Papaverine
Acetylsalicylate	Guaifenesin	Penicillin-G
Aminopyrine	Hippuric acid	Pentazocine
Amitryptyline	Hydralazine	Pentobarbital
Amobarbital	Hydrochlorothiazide	Perphenazine
Amoxicillin	Hydrocodone	Phencyclidine
Ampicillin	Hydrocortisone	Phenelzine
Apomorphine	O-Hydroxyhippuric acid	Phenobarbital
Aspartame	3-Hydroxytyramine	Prednisolone
Atropine	Ibuprofen	Phenylpropanolamine
Benzilic acid	Imipramine	Prednisone
Benzoic acid	(-) Isoproterenol	Procaine
Benzoylecgonine	Isoxsuprine	Promazine
Butabartital	Ketamine	Promethazine
Cannabidiol	Ketoprofen	D,L-Propanolol
Chloralhydrate	Labetalol	D-Propoxyphene
Chloramphenicol	Levorphanol	D-Pseudoephedrine
Chlordiazepoxide	Loperamide	Quinidine
Chlorothiazide	Loxapine succinate	Quinine
Chlorpromazine	Maprotiline	Ranitidine
Cholesterol	Meperidine	Salicylic acid
Clomipramine	Meprobamate	Secobarbital
Clonidine	Methadone	Serotonin (5-
Hydroxytyramine)
Cocaine hydrochloride	Methaqualone	Sulfamethazine
Codeine	Methylphenidal	Sulindac
Cortisone	Methyprylon	Temazepam
(-) Cotinine	Morphine-3- $\beta$ -Dglucuronide	Tetracycline
Creatinine	Nalidixic acid	Tetrahydrocortisone
Deoxycorticosterone	Nalorphine	3 ( $\beta$ -D glucuronide)
		Tetrahydrozoline

11

Dextromethorphan	Naloxone	Thebaine
Diazepam	Naltrexone	Thiamine
Diclofenac	Naproxen	Thioridazine
Diflunisal	Niacinamide	Tolbutamine
Digoxin	Nifedipine	Triamterene
Diphenhydramine	Norcodein	Trifluoperazine
Doxylamine	Norethindrone	Trimethoprim
Ecgonine hydrochloride	Noroxymorphone	Trimipramine
Ecgonine methyl ester	D-Norpropoxyphene	D, L-Tryptophan
Erythromycin	Noscapine	Tyramine
β-Estradiol	Nylidrin	D, L-Tyrosine
Estrone-3-sulfate	D,L-Octopamine	Uric acid
Ethyl-p-aminobenzoate	Oxalic acid	Verapamil
Fenoprofen	Oxazepam	Zomepirac
Furosemide	Oxolinic acid

Morphine

4-Acetamidophenol	Ecgonine methylester	Oxolinic acid
Acetophenetidin	(-) -Y -Ephedrine	Oxymetazoline
N-Acetylprocainamide	Erythromycin	Papaverine
Acetylsalicylic acid	ẞ-Estradiol	Penicillin-G
Aminopyrine	Estrone-3-sulfate	Pentazocine
Amitryptyline	Ethyl-p-aminobenzoate	Pentobarbital
Amobarbital	Fenoprofen	Perphenazine
Amoxicillin	Furosemide	Phencyclidine
Ampicillin	Gentisic acid	Phenelzine
Ascorbic acid	Hemoglobin	Phenobarbital
D,L-Amphetamine	Hydralazine	Phentermine
Apomorphine	Hydrochlorothiazide	L-Phenylephrine
Aspartame	Hydrocortisone	ẞ-Phenylethylamine
Atropine	O-Hydroxyhippuric acid	Phenylpropanolamine
Benzilic acid	p-Hydroxy methamphetamine	Prednisone
Benzoic acid	3-Hydroxytyramine	D,L-Propanolol
Benzoylecgonine	Ibuprofen	D-Propoxyphene
Benzphetamine	Imipramine	D-Pseudoephedrine
Bilirubin (±)	Iproniazid	Quinidine
Brompheniramine	Isoproterenol	Quinine
Caffeine	Isoxsuprine	Ranitidine
Cannabidiol	Ketamine	Salicylic acid
Chloralhydrate	Ketoprofen	Secobarbital

12

| Chloramphenicol | Labetalol | Serotonin (5-
Hydroxytyramine) |
|------------------------|-------------------------------------------|-------------------------------------------|
| Chlordiazepoxide | Loperamide | Sulfamethazine |
| Chlorothiazide | Maprotiline | Sulindac |
| (±) Chlorpheniramine | Meperidine | Temazepam |
| Chlorpromazine | Meprobamate | Tetracycline |
| Chlorquine | Methadone | Tetrahydrocortisone3 (β-D
glucuronide) |
| Cholesterol | Methoxyphenamine | Tetrahydrozoline |
| Clomipramine | (+) 3,4-Methylenedioxy-
amphetamine | Thiamine |
| Clonidine | (+)3,4-Methylenedioxy-
methamphetamine | Thioridazine |
| Cocaine hydrochloride | Nalidixic acid | D, L-Tyrosine |
| Cortisone | Nalorphine | Tolbutamide |
| (-) Cotinine | Naloxone | Triamterene |
| Creatinine | Naltrexone | Trifluoperazine |
| Deoxycorticosterone | Naproxen | Trimethoprim |
| Dextromethorphan | Niacinamide | Trimipramine |
| Diazepam | Nifedipine | Tryptamine |
| Diclofenac | Norethindrone | D, L-Tryptophan |
| Diflunisal | D-Norpropoxyphene | Tyramine |
| Digoxin | Noscapine | Uric acid |
| Diphenhydramine | D,L-Octopamine | Verapamil |
| Doxylamine | Oxalic acid | Zomepirac |
| Ecgonine hydrochloride | Oxazepam | |

• f. Specificity
  To test the specificity, drug metabolites and other components that are likely to interfere in urine samples were tested using three batches of each device for all formats. The obtained lowest detectable concentration was used to calculate the cross-reactivity. There were no differences observed for different formats.

13

| Oxazepam | Result | %
Cross-Reactivity |
|-------------------------|-------------------------|-----------------------|
| Cut-off=300 ng/mL | | |
| Oxazepam | Positive at 300 ng/mL | 100% |
| Alprazolam | Positive at 125 ng/mL | 240% |
| a-Hydroxyalprazolam | Positive at 2500 ng/mL | 12% |
| Bromazepam | Positive at 1565 ng/mL | 19% |
| Chlordiazepoxide | Positive at 1560 ng/mL | 19% |
| Clobazam | Positive at 65 ng/mL | 462% |
| Clonazepam | Positive at 10000 ng/mL | 3% |
| Clorazepate dipotassium | Positive at 195ng/mL | 154% |
| Delorazepam | Positive at 1560 ng/mL | 19% |
| Desalkylflurazepam | Positive at 1560 ng/mL | 19% |
| Diazepam | Positive at 115 ng/mL | 261% |
| Estazolam | Positive at 165 ng/mL | 182% |
| Flunitrazepam | Positive at 166 ng/mL | 181% |
| Midazolam | Positive at 6500 ng/mL | 5% |
| Nitrazepam | Positive at 300 ng/mL | 100% |
| Norchlordiazepoxide | Positive at 250 ng/mL | 120% |
| Nordiazepam | Positive at 400 ng/mL | 75% |
| Temazepam | Positive at 100 ng/mL | 300% |
| Triazolam | Positive at 2500 ng/mL | 12% |
| D,L-Lorazepam | Negative at ≤ 105 ng/mL | Not Detected |
| Methamphetamine | Negative at ≤ 105 ng/mL | Not Detected |
| Morphine | Negative at ≤ 105 ng/mL | Not Detected |

14

| mAMP
(Methamphetamine,
Cut-off=1000 ng/mL) | Result | %
Cross-Reactivity |
|------------------------------------------------------|-------------------------|-----------------------|
| D-Methamphetamine | Positive at 1000 ng/mL | 100% |
| (+/-)3,4-Methylenedioxy-n-
ethylamphetamine(MDEA) | Positive at 41600 ng/mL | 2% |
| D/L-Methamphetamine | Positive at 1000 ng/mL | 100% |
| p-Hydroxymethamphetamine | Positive at 27000 ng/mL | 4% |
| (+/-)3,4-Methylenedioxy
methamphetamine (MDMA) | Positive at 8000 ng/mL | 13% |
| L-Methamphetamine | Positive at 10000 ng/mL | 10% |
| Trimethobenzamide | Negative at ≤ 105 ng/mL | Not Detected |
| Chloroquine | Negative at ≤ 105 ng/mL | Not Detected |
| Ephedrine | Negative at ≤ 105 ng/mL | Not Detected |
| Fenfluramine | Negative at ≤ 105 ng/mL | Not Detected |
| Procaine (Novocaine) | Negative at ≤ 105 ng/mL | Not Detected |
| Ranitidine (Zantac) | Negative at ≤ 105 ng/mL | Not Detected |
| D-amphetamine | Negative at ≤ 105 ng/mL | Not Detected |
| L-amphetamine | Negative at ≤ 105 ng/mL | Not Detected |
| Morphine | Negative at ≤ 105 ng/mL | Not Detected |
| Oxazepam | Negative at ≤ 105 ng/mL | Not Detected |

15

| Morphine
Cut-off=2000 ng/mL | Result | %
Cross-Reactivity |
|--------------------------------|-------------------------|-----------------------|
| Morphine | Positive at 2000 ng/mL | 100% |
| Codeine | Positive at 1000 ng/mL | 200% |
| Ethylmorphine | Positive at 560 ng/mL | 357% |
| Hydrocodone | Positive at 5000 ng/mL | 40% |
| Hydromorphone | Positive at 7315 ng/mL | 27% |
| Levorphanol | Positive at 16000 ng/mL | 13% |
| σ-Monoacetylmorphine | Positive at 1000 ng/mL | 200% |
| Morphine 3-b-D-glucuronide | Positive at 1300 ng/mL | 154% |
| Thebaine | Negative at ≤ 105 ng/mL | Not Detected |
| Norcodeine | Negative at ≤ 105 ng/mL | Not Detected |
| Normorphone | Negative at ≤ 105 ng/mL | Not Detected |
| Oxycodone | Negative at ≤ 105 ng/mL | Not Detected |
| Oxymorphine | Negative at ≤ 105 ng/mL | Not Detected |
| Procaine | Negative at ≤ 105 ng/mL | Not Detected |
| Oxazepam | Negative at ≤ 105 ng/mL | Not Detected |
| Methamphetamine | Negative at ≤ 105 ng/mL | Not Detected |

g. Effect of Urine Specific Gravity and Urine pH

To investigate the effect of urine specific gravity and urine pH, urine samples with a range of 1.000 to 1.035 specific gravity or urine samples with a range of pH 4 to 9 were spiked with target drugs at 25% below and 25% above cut-off levels. These samples were tested using three batches of each device for all formats. 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 formats.

16

2. Comparison Studies

The method comparison studies for the First Sign™ Drug Tests (Cup and Dip Card) for Oxazepam , Methamphetamine , and Morphine were performed in-house with three different laboratory assistants for each format of the 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:

	Dip Card format	Negative	Low Negative by GC/MS (less than -50%)	Near Cutoff Negative by GC/MS (Between -50% and cut-off)	Near Cutoff Positive by GC/MS (Between the cut-off and +50%)	High Positive by GC/MS (greater than +50%)
Viewer A	Positive	0	0	0	13	25
	Negative	10	10	20	2	0
Viewer B	Positive	0	0	0	14	25
	Negative	10	10	20	1	0
Viewer C	Positive	0	0	0	13	25
	Negative	10	10	20	2	0

Discordant Results of Oxazepam Dip Card

| Viewer | Sample Number | GC/MS Result | Dipcard Format
Viewer Results |
|----------|---------------|--------------|----------------------------------|
| Viewer A | 94638975 | 324 | Negative |
| Viewer A | 83001567 | 325 | Negative |
| Viewer B | 94638975 | 324 | Negative |
| Viewer C | 83002215 | 326 | Negative |
| Viewer C | 94639027 | 328 | Negative |

17

| Cup
format | | Negative | Low
Negative
by GC/MS
(less than
-50%) | Near Cutoff
Negative by
GC/MS
(Between
-50% and
cut-off) | Near
Cutoff
Positive by
GC/MS
(Between
the cut-off
and +50%) | High
Positive by
GC/MS
(greater
than +50%) |
|---------------|----------|----------|----------------------------------------------------|-------------------------------------------------------------------------|--------------------------------------------------------------------------------|--------------------------------------------------------|
| Viewer A | Positive | 0 | 0 | 0 | 14 | 25 |
| | Negative | 10 | 10 | 20 | 1 | 0 |
| Viewer B | Positive | 0 | 0 | 0 | 14 | 25 |
| | Negative | 10 | 10 | 20 | 1 | 0 |
| Viewer C | Positive | 0 | 0 | 0 | 13 | 25 |
| | Negative | 10 | 10 | 20 | 2 | 0 |

Discordant Results of Oxazepam Cup

| Viewer | Sample Number | GC/MS Result | Cup Format
Viewer Results |
|----------|---------------|--------------|------------------------------|
| Viewer A | 83002215 | 326 | Negative |
| Viewer B | 83001567 | 325 | Negative |
| Viewer C | 83001567 | 325 | Negative |
| Viewer C | 94639027 | 328 | Negative |

Methamphetamine

Dip Card			Low		Near
format		Negative	Negative
by GC/MS
(less than
-50%)	Near Cutoff
Negative by
GC/MS
(Between
-50% and
cut-off)	Cutoff
Positive by
GC/MS
(Between
the cut-off
and +50%)	High
Positive by
GC/MS
(greater
than +50%)
Viewer A	Positive	0	0	0	18	21
	Negative	10	10	20	1	0
Viewer B	Positive	0	0	0	18	21
	Negative	10	10	20	1	0
Viewer C	Positive	0	0	0	17	21
	Negative	10	10	20	2	0

18

Viewer	Sample Number	GC/MS Result	DipCard Format Viewer Results
Viewer A	83000530	1156	Negative
Viewer B	83001807	1094	Negative
Viewer C	83001811	1065	Negative
Viewer C	83001807	1094	Negative

Discordant Results of Methamphetamine DipCard

| Cup
format | | Negative | Low
Negative
by GC/MS
(less than
-50%) | Near Cutoff
Negative by
GC/MS
(Between
-50% and
cut-off) | Near
Cutoff
Positive by
GC/MS
(Between
the cut-off
and +50%) | High
Positive by
GC/MS
(greater
than +50%) |
|---------------|----------|----------|----------------------------------------------------|-------------------------------------------------------------------------|--------------------------------------------------------------------------------|--------------------------------------------------------|
| Viewer A | Positive | 0 | 0 | 0 | 18 | 21 |
| | Negative | 10 | 10 | 20 | 1 | 0 |
| Viewer B | Positive | 0 | 0 | 0 | 18 | 21 |
| | Negative | 10 | 10 | 20 | 1 | 0 |
| Viewer C | Positive | 0 | 0 | 0 | 17 | 21 |
| | Negative | 10 | 10 | 20 | 2 | 0 |

Discordant Results of Methamphetamine Cup

| Viewer | Sample Number | GC/MS Result | Cup Format
Viewer Results |
|----------|---------------|--------------|------------------------------|
| Viewer A | 83001821 | 1079 | Negative |
| Viewer B | 83001807 | 1094 | Negative |
| Viewer C | 83001821 | 1079 | Negative |
| Viewer C | 83001807 | 1094 | Negative |

19

Morphine

| DipCard

format	Morphine
	Negative	Low Negative
by GC/MS
(less than -50%)	Near Cutoff
Negative by
GC/MS
(Between -50% and
cut-off)	Near Cutoff
Positive by
GC/MS
(Between
the cut-off
and +50%)	High Positive by
GC/MS
(greater
than +50%)
Viewer A	Positive	0	0	0	15	24
	Negative	10	10	20	1	0
Viewer B	Positive	0	0	0	15	24
	Negative	10	10	20	1	0
Viewer C	Positive	0	0	0	15	24
	Negative	10	10	20	1	0

Discordant Results of Morphine DipCard

| Viewer | Sample Number | GC/MS Result | DipCard Format
Viewer Results |
|----------|---------------|--------------|----------------------------------|
| Viewer A | 94639012 | 2119 | Negative |
| Viewer B | 94639012 | 2119 | Negative |
| Viewer C | 83000219 | 2325 | Negative |

| Cup
format | | Negative | Low
Negative
by GC/MS
(less than
-50%) | Near Cutoff
Negative by
GC/MS
(Between
-50% and
cut-off) | Near Cutoff
Positive by
GC/MS
(Between
the cut-off
and +50%) | High
Positive by
GC/MS
(greater
than
+50%) |
|---------------|----------|----------|----------------------------------------------------|-------------------------------------------------------------------------|-----------------------------------------------------------------------------|-----------------------------------------------------------|
| Viewer A | Positive | 0 | 0 | 0 | 15 | 24 |
| | Negative | 10 | 10 | 20 | 1 | 0 |
| Viewer B | Positive | 0 | 0 | 0 | 15 | 24 |
| | Negative | 10 | 10 | 20 | 1 | 0 |
| Viewer C | Positive | 0 | 0 | 0 | 15 | 24 |
| | Negative | 10 | 10 | 20 | 1 | 0 |

Discordant Results of Morphine Cup

| Viewer | Sample Number | GC/MS Result | Cup Format
Viewer Results |
|----------|---------------|--------------|------------------------------|
| Viewer A | 83000219 | 2325 | Negative |
| Viewer B | 83000572 | 2227 | Negative |
| Viewer C | 94639012 | 2119 | Negative |

20

Lay-user study

A lay user study was performed at three intended user sites with 280 lay persons testing the Oxazepam devices, 280 lay persons testing the Methamphetamine devices and 280 lay persons testing the Morphine devices. A total of 139 females and 141 males tested the Oxazepam samples, 138 females and 142 males tested Methamphetamine samples, and 137 females and 143 males tested the Morphine 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; negative, +/-75%, +/-50%, +/-25% of the cutoff 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 and blind-labeled. Each participant was provided with the package insert, 1 blind labeled sample and a device. The results are summarized below.

| | Number
of
samples | Oxazepam Concentration
by GC/MS
(ng/mL) | Lay person results | | The
percentage of
correct results
(%) |
|--------------|-------------------------|-----------------------------------------------|--------------------|--------------------|------------------------------------------------|
| % of Cutoff | | | No. of
Positive | No. of
Negative | |
| -100% Cutoff | 20 | 0 | 0 | 20 | 100% |
| -75% Cutoff | 20 | 76 | 0 | 20 | 100% |
| -50% Cutoff | 20 | 145 | 0 | 20 | 100% |
| -25% Cutoff | 20 | 222 | 0 | 20 | 100% |
| +25% Cutoff | 20 | 384 | 18 | 2 | 90% |
| +50% Cutoff | 20 | 468 | 20 | 0 | 100% |
| +75% Cutoff | 20 | 542 | 20 | 0 | 100% |

Comparison between GC/MS and Lay Person Results (Oxazepam DipCard)

Comparison between GC/MS and Lay Person Results (Oxazepam Cup)

| % of Cutoff | Number
of
samples | Oxazepam Concentration
by GC/MS
(ng/mL) | Lay person results | | The
percentage of
correct results
(%) |
|--------------|-------------------------|-----------------------------------------------|--------------------|--------------------|------------------------------------------------|
| | | | No. of
Positive | No. of
Negative | |
| -100% Cutoff | 20 | 0 | 0 | 20 | 100% |
| -75% Cutoff | 20 | 76 | 0 | 20 | 100% |
| -50% Cutoff | 20 | 145 | 0 | 20 | 100% |
| -25% Cutoff | 20 | 222 | 2 | 18 | 90% |
| +25% Cutoff | 20 | 384 | 20 | 0 | 100% |
| +50% Cutoff | 20 | 468 | 20 | 0 | 100% |
| +75% Cutoff | 20 | 542 | 20 | 0 | 100% |

21

| | Number
of
samples | Methamphetamine
Concentration by GC/MS
(ng/mL) | Lay person results | | The
percentage of
correct results
(%) |
|--------------|-------------------------|------------------------------------------------------|--------------------|--------------------|------------------------------------------------|
| % of Cutoff | | | No. of
Positive | No. of
Negative | |
| -100% Cutoff | 20 | 0 | 0 | 20 | 100% |
| -75% Cutoff | 20 | 245 | 0 | 20 | 100% |
| -50% Cutoff | 20 | 488 | 0 | 20 | 100% |
| -25% Cutoff | 20 | 729 | 0 | 20 | 100% |
| +25% Cutoff | 20 | 1212 | 19 | 1 | 95% |
| +50% Cutoff | 20 | 1441 | 20 | 0 | 100% |
| +75% Cutoff | 20 | 1666 | 20 | 0 | 100% |

Comparison between GC/MS and Lay Person Results (Methamphetamine DipCard)

Comparison between GC/MS and Lay Person Results (Methamphetamine Cup)

| % of Cutoff | Number
of
samples | Methamphetamine
Concentration by GC/MS
(ng/mL) | Lay person results | | The
percentage of
correct results
(%) |
|--------------|-------------------------|------------------------------------------------------|--------------------|--------------------|------------------------------------------------|
| | | | No. of
Positive | No. of
Negative | |
| -100% Cutoff | 20 | 0 | 0 | 20 | 100% |
| -75% Cutoff | 20 | 245 | 0 | 20 | 100% |
| -50% Cutoff | 20 | 488 | 0 | 20 | 100% |
| -25% Cutoff | 20 | 729 | 0 | 20 | 100% |
| +25% Cutoff | 20 | 1212 | 19 | 1 | 95% |
| +50% Cutoff | 20 | 1441 | 20 | 0 | 100% |
| +75% Cutoff | 20 | 1666 | 20 | 0 | 100% |

Comparison between GC/MS and Lay Person Results (Morphine DipCard)

| % of Cutoff | Number
of
samples | Morphine Concentration
by GC/MS
(ng/mL) | Lay person results | | The
percentage of
correct results
(%) |
|--------------|-------------------------|-----------------------------------------------|--------------------|----|------------------------------------------------|
| -100% Cutoff | 20 | 0 | 0 | 20 | 100% |
| -75% Cutoff | 20 | 527 | 0 | 20 | 100% |
| -50% Cutoff | 20 | 1053 | 0 | 20 | 100% |
| -25% Cutoff | 20 | 1573 | 1 | 19 | 95% |
| +25% Cutoff | 20 | 2652 | 20 | 0 | 100% |
| +50% Cutoff | 20 | 3254 | 20 | 0 | 100% |
| +75% Cutoff | 20 | 3711 | 20 | 0 | 100% |

22

| % of Cutoff | Number
of
samples | Morphine Concentration
by GC/MS
(ng/mL) | Lay person results | | The |
|--------------|-------------------------|-----------------------------------------------|--------------------|--------------------|-----------------------------------------|
| | | | No. of
Positive | No. of
Negative | percentage of
correct results
(%) |
| -100% Cutoff | 20 | 0 | 0 | 20 | 100% |
| -75% Cutoff | 20 | 527 | 0 | 20 | 100% |
| -50% Cutoff | 20 | 1053 | 0 | 20 | 100% |
| -25% Cutoff | 20 | 1573 | 0 | 20 | 100% |
| +25% Cutoff | 20 | 2652 | 19 | 1 | 95% |
| +50% Cutoff | 20 | 3254 | 20 | 0 | 100% |
| +75% Cutoff | 20 | 3711 | 20 | 0 | 100% |

Comparison between GC/MS and Lay Person Results (Morphine Cup)

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 and method comparison of the devices, it's concluded that the First Sign™ Drug of Abuse Dip Card Test and First Sign™ Drug of Abuse Cup Test are substantially equivalent to the predicate.