First Sign Multi-Drug Test Dip Card, First Sign Multi-Drug Test Cup, First Sign Multi-Drug Screen Test Dip Card, First Sign Multi-Drug Screen Test Cup

K210327 · W.H.P.M., Inc. · QBF · Aug 12, 2021 · Clinical Toxicology

Device Facts

• Record ID: K210327
• Device Name: First Sign Multi-Drug Test Dip Card, First Sign Multi-Drug Test Cup, First Sign Multi-Drug Screen Test Dip Card, First Sign Multi-Drug Screen Test Cup
• Applicant: W.H.P.M., Inc.
• Product Code: QBF · Clinical Toxicology
• Decision Date: Aug 12, 2021
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3700
• Device Class: Class 2

Intended Use

First Sign Multi-Drug Test Dip Card is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Buprenorphine, Butalbital, Oxazepam. Cocaine, 2-ethylidene-1.5-dimethyl-3.3-diphenylpyrrolidine, Methamphetamine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Marijuana in human urine at the cutoff concentrations of: [Table of cut-offs]. Configuration of the First Sign Multi-Drug Test Dip Card can consist of any combination of the above listed drug analytes. The test may yield positive results for the prescription drugs Buprenorphine, Oxazepam, Butalbital, Nortriptyline, Propoxyphene and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only. First Sign Multi-Drug Test Cup is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Buprenorphine, Butalbital, Oxazepam. Cocaine, 2-ethylidene-1.5-dimethyl-3.3-diphenvlpyrrolidine, Methamphetamine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Marijuana in human urine at the cutoff concentrations of: [Table of cut-offs]. Configuration of the First Sign Multi-Drug Test Cup can consist of any combination of the above listed drug analytes. The test may yield positive results for the prescription drugs Buprenorphine, Oxazepam, Butalbital, Nortriptyline, Propoxyphene and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.

Device Story

Lateral flow immunochromatographic assay for qualitative detection of drugs of abuse in human urine; competitive binding principle. Input: human urine sample. Operation: urine migrates via capillary action; target drugs compete with drug-conjugate for binding sites on monoclonal mouse antibody-coated particles. Output: visual colored lines in test region (negative) or absence of line (positive); control line confirms proper function. Used in home or clinical settings; operated by lay users or healthcare professionals. Results are preliminary; require confirmation via GC/MS or LC/MS. Benefits: rapid, simultaneous screening for multiple substances to aid clinical decision-making.

Clinical Evidence

Bench testing only. Precision/reproducibility studies performed over 25 days using three lots. Analytical specificity/interference testing confirmed no interference from common physiological/pathological substances. Cross-reactivity evaluated for propoxyphene metabolites. Method comparison study tested 80 clinical samples (40 negative, 40 positive) against LC/MS. Lay user study conducted with 280 participants across three sites using spiked urine samples at various concentrations relative to cutoffs, demonstrating high accuracy.

Technological Characteristics

Lateral flow immunochromatographic assay; competitive binding. Single-use device. Components: Dip Card or Cup, package insert, urine collection cup. Sealed in aluminum pouch with desiccant. Qualitative detection based on antigen-antibody immunochemistry.

Indications for Use

Indicated for qualitative, simultaneous detection of drugs of abuse (Amphetamine, Buprenorphine, Butalbital, Oxazepam, Cocaine, EDDP, Methamphetamine, MDMA, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline, Marijuana) in human urine. Intended for prescription and OTC use. Not intended to distinguish between prescription use and abuse.

Regulatory Classification

Identification

A propoxyphene test system is a device intended to measure propoxyphene, a pain-relieving drug, in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of propoxyphene use or overdose or in monitoring levels of propoxyphene to ensure appropriate therapy.

Special Controls

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

Predicate Devices

• Wondfo T-Cup® Multi-Drug Urine Test Cup (K182701)

Submission Summary (Full Text)

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

August 12, 2021

W.H.P.M., Inc. % Joe Shia Manager LSI Consulting 504E Diamond Ave., Suite I Gaithersburg, Maryland 20877

| Trade/Device Name: First Sign Multi-Drug Test Dip Card |
|----------------------------------------------------------------------|
| First Sign Multi-Drug Test Cup |
| First Sign Multi-Drug Screen Test Dip Card |
| First Sign Multi-Drug Screen Test Cup |
| Regulation Number: 21 CFR 862.3700 |
| Regulation Name: Propoxyphene Test System |
| Regulatory Class: Class II |
| Product Code: QBF, NGG, NFY, NFT, NFW, NFV, NGL, PTG, LCM, PTH, QAW |
| Dated: February 2, 2021 |
| Received: February 4, 2021 |

Dear Joe Shia:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of

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Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Marianela Perez-Torres, Ph.D. Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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## Indications for Use

510(k) Number (if known) k210327

# Device Name

First Sign Multi-Drug Test Dip Card First Sign Multi-Drug Test Cup

#### Indications for Use (Describe)

First Sign Multi-Drug Test Dip Card is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Butalbital, Oxazepam, Cocaine, 2-ethylidene-1.5dimethyl-3,3-diphenylpyrrolidine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Marijuana in human urine at the cutoff concentrations of:

| Drug(Identifier) | Cut-off level |
|------------------------------------------------------------|------------------------|
| Amphetamine (AMP) | 1000ng/mL or 500 ng/mL |
| Buprenorphine (BUP) | 10 ng/mL |
| Butalbital (BAR) | 300 ng/mL |
| Oxazepam (BZO) | 300 ng/mL |
| Cocaine (COC) | 300ng/mL or 150 ng/mL |
| 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDT) | 300 ng/mL |
| Methamphetamine (MET) | 1000ng/mL or 500 ng/mL |
| Methylenedioxy-methamphetamine (MDMA) | 500 ng/mL |
| Morphine (MOP 300/OPI 2000) | 2000ng/mL or 300 ng/mL |
| Methadone (MDT) | 300 ng/mL |
| Oxycodone (OXY) | 100 ng/mL |
| Phencyclidine (PCP) | 25 ng/mL |
| Propoxyphene (PPX) | 300 ng/mL |
| Nortriptyline (TCA) | 1000 ng/mL |
| Marijuana (THC) | 50 ng/mL |

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

The test may yield positive results for the prescription drugs Buprenorphine, Oxazepam, Butalbital, Nortriptyline, Propoxyphene and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. GC/ MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.

First Sign Multi-Drug Test Cup is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Butalbital, Oxazepam, Cocaine, 2-ethylidene-1,5-dimethyl-3,3diphenylpyrrolidine, Methamphetamine, Methylenedioxymethamphetamine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Marijuana in human urine at the cutoff concentrations of:

| Drug(Identifier) | Cut-off level |
|---------------------|------------------------|
| Amphetamine (AMP) | 1000ng/mL or 500 ng/mL |
| Buprenorphine (BUP) | 10 ng/mL |
| Butalbital (BAR) | 300 ng/mL |
| Oxazepam (BZO) | 300 ng/mL |
| Cocaine (COC) | 300ng/mL or 150 ng/mL |

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| 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDT) | 300 ng/mL |
|------------------------------------------------------------|------------------------|
| Methamphetamine (MET) | 1000ng/mL or 500 ng/mL |
| Methylenedioxy-methamphetamine (MDMA) | 500 ng/mL |
| Morphine (MOP 300/OPI 2000) | 2000ng/mL or 300 ng/mL |
| Methadone (MDT) | 300 ng/mL |
| Oxycodone (OXY) | 100 ng/mL |
| Phencyclidine (PCP) | 25 ng/mL |
| Propoxyphene (PPX) | 300 ng/mL |
| Nortriptyline (TCA) | 1000 ng/mL |
| Marijuana (THC) | 50 ng/mL |

Configuration of the First Sign Multi-Drug Test Cup can consist of any combination of the above listed drug analytes. The test may yield positive results for the prescription drugs Buprenorphine, Oxazepam, Butalbital, Nortriptyline, Propoxyphene and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. GC/ MS or LC/MS is the preferred confirmatory method.

For in vitro diagnostic use only.

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

Prescription Use (Part 21 CFR 801 Subpart D)

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

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#### Indications for Use

510(k) Number (if known)

#### k210327

#### Device Name

First Sign Multi-Drug Screen Test Dip Card First Sign Multi-Drug Screen Test Cup

#### Indications for Use (Describe)

First Sign Multi-Drug Screen Test Dip Card is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Butalbital, Oxazepam, Cocaine, 2ethylidene-1,5-dimethyl-3,3-dipheny|pyrrolidine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Marijuana in human urine at the cutoff concentrations of:

| Drug(Identifier) | Cut-off level |
|------------------------------------------------------------|------------------------|
| | |
| Amphetamine (AMP) | 1000ng/mL or 500 ng/mL |
| Buprenorphine (BUP) | 10 ng/mL |
| Butalbital (BAR) | 300 ng/mL |
| Oxazepam (BZO) | 300 ng/mL |
| Cocaine (COC) | 300ng/mL or 150 ng/mL |
| 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDT) | 300 ng/mL |
| Methamphetamine (MET) | 1000ng/mL or 500 ng/mL |
| Methylenedioxy-methamphetamine (MDMA) | 500 ng/mL |
| Morphine (MOP 300/OPI 2000) | 2000ng/mL or 300 ng/mL |
| Methadone (MDT) | 300 ng/mL |
| Oxycodone (OXY) | 100 ng/mL |
| Phencyclidine (PCP) | 25 ng/mL |
| Propoxyphene (PPX) | 300 ng/mL |
| Nortriptyline (TCA) | 1000 ng/mL |
| Marijuana (THC) | 50 ng/mL |
| | |

Configuration of the First Sign Multi-Drug Screen Test Dip Card can consist of any combination of the above listed drug analytes.

The test may yield positive results for the prescription drugs Buprenorphine, Oxazepam, Butalbital, Nortriptyline, Propoxyphene and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. GC/ MS or LC/MS is the preferred confirmatory method.

For in vitro diagnostic use only. It is for prescription use.

First Sign Multi-Drug Screen Test Cup is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Butalbital, Oxazepam, Cocaine, 2ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Marijuana in human urine at the cutoff concentrations of:

| ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ | D. |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------|
| Butalbital (BAR) | 300 ng/mL |
| Buprenorphine (BUP) | 10 ng/mL |
| Amphetamine (AMP) | 1000ng/mL or 500 ng/mL |
| Drug(Identifier) | Cut-off level |
| | |

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Oxazepam (BZO) 300 ng/mL Cocaine (COC) 300ng/mL or 150 ng/mL 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDT) 300 ng/mL 1000ng/mL or 500 ng/mL Methamphetamine (MET) Methylenedioxy-methamphetamine (MDMA) 500 ng/mL Morphine (MOP 300/OPI 2000) 2000ng/mL or 300 ng/mL Methadone (MDT) 300 ng/mL Oxycodone (OXY) 100 ng/mL Phencyclidine (PCP) 25 ng/mL 300 ng/mL Propoxyphene (PPX) Nortriptyline (TCA) 1000 ng/mL Marijuana (THC) 50 ng/mL

Configuration of the First Sign Multi-Drug Screen Test Cup combination of the above listed drug analytes.

The test may yield positive results for the prescription drugs Buprenorphine, Oxazepam, Butalbital, Nortriptyline, Propoxyphene and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternative chemical must be used in order to obtain a confirmed analytical result. GC/ MS or LC/MS is the preferred confirmatory method.

For in vitro diagnostic use only. It is 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."

{6}------------------------------------------------

#### 510(k) SUMMARY k210327

- August 10, 2021 1. Date: 2. Submitter: W.H.P.M., Inc. 5358 Irwindale Ave. Irwindale, CA 91706
- 3. Contact person: Joe Shia LSI International Inc 504E Diamond Ave., Suite J Gaithersburg, MD 20877 Telephone: [phone] Email: [e-mail].
- First Sign Multi-Drug Test Dip Card 4. Device Name: First Sign Multi-Drug Test Cup First Sign Multi-Drug Screen Test Dip Card First Sign Multi-Drug Screen Test Cup

| Classification: | | | |
|--------------------------------------------------------------|----------------|---------------------------------------|------------|
| Product Code | Classification | Regulation Section | Panel |
| NFT<br>Amphetamine | II | 862.3100, Amphetamine Test System | Toxicology |
| NGL<br>Buprenorphine | II | 862.3650, Opiate Test System | Toxicology |
| PTH<br>Secobarbital | II | 862.3150, Barbiturate Test System | Toxicology |
| NFV<br>Oxazepam | II | 862.3170, Benzodiazepine Test System | Toxicology |
| NFY<br>Cocaine | II | 862.3250, Cocaine Test System | Toxicology |
| PTG<br>2-ethylidene-1,5-dimethyl-3,3-<br>diphenylpyrrolidine | II | 862.3620, Methadone Test System | Toxicology |
| NGG<br>Methamphetamine | II | 862.3610, Methamphetamine Test System | Toxicology |
| NGG<br>Methylenedioxymethamphetamine | II | 862.3610, Methamphetamine Test System | Toxicology |
| NGL<br>Morphine | II | 862.3650, Opiate Test System | Toxicology |
| PTG<br>Methadone | II | 862.3620, Methadone Test System | Toxicology |
| NGL<br>Oxycodone | II | 862.3650, Opiate Test System | Toxicology |
| LCM<br>Phencyclidine | | Unclassified | Toxicology |
| QBF<br>Propoxyphene | II | 862.3700 Propoxyphene test system. | Toxicology |

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| QAW<br>Nortriptyline | II | 862.3910 Tricyclic antidepressant<br>drugs test system | Toxicology |
|----------------------|----|--------------------------------------------------------|------------|
| NFW<br>Cannabinoids | II | 862.3870, Cannabinoids Test<br>System | Toxicology |

- 5. Predicate Devices: K182701
Wondfo T-Cup® Multi-Drug Urine Test Cup

- 6. Intended Use
First Sign Multi-Drug Test Dip Card is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Buprenorphine, Butalbital, Oxazepam. Cocaine, 2-ethylidene-1.5-dimethyl-3.3-diphenylpyrrolidine, Methamphetamine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Marijuana in human urine at the cutoff concentrations of:

| Drug (Identifier) | Cut-off level |
|----------------------------------------------------------|-------------------------|
| Amphetamine (AMP) | 1000 ng/mL or 500 ng/mL |
| Buprenorphine (BUP) | 10 ng/mL |
| Butalbital (BAR) | 300 ng/mL |
| Oxazepam (BZO) | 300 ng/mL |
| Cocaine (COC) | 300 ng/mL or 150 ng/mL |
| 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) | 300 ng/mL |
| Methamphetamine (MET) | 1000 ng/mL or 500 ng/mL |
| Methylenedioxymethamphetamine (MDMA) | 500 ng/mL |
| Morphine (MOP 300/OPI 2000) | 2000 ng/mL or 300 ng/mL |
| Methadone (MTD) | 300 ng/mL |
| Oxycodone (OXY) | 100 ng/mL |
| Phencyclidine (PCP) | 25 ng/mL |
| Propoxyphene (PPX) | 300 ng/mL |
| Nortriptyline (TCA) | 1000 ng/mL |
| Marijuana (THC) | 50 ng/mL |

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

The test may yield positive results for the prescription drugs Buprenorphine, Oxazepam, Butalbital, Nortriptyline, Propoxyphene and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.

First Sign Multi-Drug Test Cup is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Buprenorphine, Butalbital,

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Oxazepam. Cocaine, 2-ethylidene-1.5-dimethyl-3.3-diphenvlpyrrolidine, Methamphetamine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Marijuana in human urine at the cutoff concentrations of:

| Drug (Identifier) | Cut-off level |
|----------------------------------------------------------|-------------------------|
| Amphetamine (AMP) | 1000 ng/mL or 500 ng/mL |
| Buprenorphine (BUP) | 10 ng/mL |
| Butalbital (BAR) | 300 ng/mL |
| Oxazepam (BZO) | 300 ng/mL |
| Cocaine (COC) | 300 ng/mL or 150 ng/mL |
| 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) | 300 ng/mL |
| Methamphetamine (MET) | 1000 ng/mL or 500 ng/mL |
| Methylenedioxymethamphetamine (MDMA) | 500 ng/mL |
| Morphine (MOP 300/OPI 2000) | 2000 ng/mL or 300 ng/mL |
| Methadone (MTD) | 300 ng/mL |
| Oxycodone (OXY) | 100 ng/mL |
| Phencyclidine (PCP) | 25 ng/mL |
| Propoxyphene (PPX) | 300 ng/mL |
| Nortriptyline (TCA) | 1000 ng/mL |
| Marijuana (THC) | 50 ng/mL |

Configuration of the First Sign Multi-Drug Test Cup can consist of any combination of the above listed drug analytes.

The test may yield positive results for the prescription drugs Buprenorphine, Oxazepam, Butalbital, Nortriptyline, Propoxyphene and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.

First Sign Multi-Drug Screen Test Dip Card is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Buprenorphine, Butalbital, Oxazepam, Cocaine, 2-ethylidene-1,5-dimethyl-3,3diphenylpyrrolidine, Methamphetamine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Marijuana in human urine at the cutoff concentrations of:

| Drug (Identifier) | Cut-off level |
|---------------------|-------------------------|
| Amphetamine (AMP) | 1000 ng/mL or 500 ng/mL |
| Buprenorphine (BUP) | 10 ng/mL |
| Butalbital (BAR) | 300 ng/mL |
| Oxazepam (BZO) | 300 ng/mL |

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

| Cocaine (COC) | 300 ng/mL or 150 ng/mL |
|----------------------------------------------------------|-------------------------|
| 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) | 300 ng/mL |
| Methamphetamine (MET) | 1000 ng/mL or 500 ng/mL |
| Methylenedioxymethamphetamine (MDMA) | 500 ng/mL |
| Morphine (MOP 300/OPI 2000) | 2000 ng/mL or 300 ng/mL |
| Methadone (MTD) | 300 ng/mL |
| Oxycodone (OXY) | 100 ng/mL |
| Phencyclidine (PCP) | 25 ng/mL |
| Propoxyphene (PPX) | 300 ng/mL |
| Nortriptyline (TCA) | 1000 ng/mL |
| Marijuana (THC) | 50 ng/mL |

Configuration of the First Sign Multi-Drug Screen Test Dip Card can consist of any combination of the above listed drug analytes.

The test may yield positive results for the prescription drugs Buprenorphine, Oxazepam, Butalbital, Nortriptyline, Propoxyphene and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method.

For in vitro diagnostic use only. It is for prescription use.

First Sign Multi-Drug Screen Test Cup is competitive binding, lateral flow immunochromatographic assay for qualitative and simultaneous detection of Amphetamine, Buprenorphine, Butalbital, Oxazepam, Cocaine, 2-ethylidene-1,5-dimethyl-3,3diphenylpyrrolidine, Methamphetamine, Methylenedioxymethamphetamine, Morphine, Methadone, Oxycodone, Phencyclidine, Propoxyphene, Nortriptyline and Marijuana in human urine at the cutoff concentrations of:

| Drug (Identifier) | Cut-off level |
|----------------------------------------------------------|-------------------------|
| Amphetamine (AMP) | 1000 ng/mL or 500 ng/mL |
| Buprenorphine (BUP) | 10 ng/mL |
| Butalbital (BAR) | 300 ng/mL |
| Oxazepam (BZO) | 300 ng/mL |
| Cocaine (COC) | 300 ng/mL or 150 ng/mL |
| 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) | 300 ng/mL |
| Methamphetamine (MET) | 1000 ng/mL or 500 ng/mL |
| Methylenedioxymethamphetamine (MDMA) | 500 ng/mL |
| Morphine (MOP 300/OPI 2000) | 2000 ng/mL or 300 ng/mL |
| Methadone (MTD) | 300 ng/mL |
| Oxycodone (OXY) | 100 ng/mL |
| Phencyclidine (PCP) | 25 ng/mL |

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

| Propoxyphene (PPX) | 300 ng/mL |
|---------------------|------------|
| Nortriptyline (TCA) | 1000 ng/mL |
| Marijuana (THC) | 50 ng/mL |

Configuration of the First Sign Multi-Drug Screen Test Cup can consist of any combination of the above listed drug analytes.

The test may yield positive results for the prescription drugs Buprenorphine, Oxazepam, Butalbital, Nortriptyline, Propoxyphene and Oxycodone when taken at or above prescribed doses. It is not intended to distinguish between prescription use or abuse of these drugs. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary result is positive. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only. It is for prescription use.

## 7. Device Description

The First Sign Multi-Drug Test Dip Card, First Sign Multi-Drug Test Cup, First Sign Multi-Drug Screen Test Dip Card and First Sign Multi-Drug Screen Test Cup are immunochromatographic assays that use a lateral flow system for the qualitative detection of Amphetamine, Oxazepam, Cocaine, Marijuana, Methamphetamine, Morphine, Oxycodone, Butalbital, Methadone, Buprenorphine, Phencyclidine, Methylenedioxymethamphetamine, Tricyclic Antidepressants, EDDP and Propoxyphene (target analytes) in human urine. The products are single-use in vitro diagnostic devices. The Dip Card kits contain a Dip Card device, a package insert and a urine cup for sample collection. The Cup kits contain a Cup device, a package insert and a urine cup for sample collection. Each test device is sealed with a desiccant in an aluminum pouch.

- 8. Substantial Equivalence Information
A summary comparison of features of the First Sign Multi-Drug Test Dip Card and First Sign Multi-Drug Test Cup and the predicate devices is provided in following tables.

#### Table 1: Features Comparison of First Sign Multi-Drug Test Dip Card and the Predicate Devices

| Item | Device | Predicate - K182701 |
|----------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------|
| Indication(s) for Use | For the qualitative determination of drugs of abuse in human urine. | Same |
| Calibrator and<br>Cut-Off Values | Amphetamine (AMP): 1,000 ng/ml or 500 ng/mL<br>Oxazepam (BZO):300 ng/ml<br>Cocaine (COC): 300 ng/ml or 150 ng/mL<br>11-Nor-Δ9-Tetrahydrocannabinol-9-COOH (THC):50 ng/ml<br>Methamphetamine (MET): 1,000 ng/ml or 500 ng/mL<br>Morphine (OPI 2000/MOP 300): 2000ng/mL or 300 ng/mL<br>Oxycodone (OXY) : 100 ng/ml<br>Butalbital (BAR): 300 ng/ml<br>Methadone (MTD): 300 ng/ml | Same |

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

| | Buprenorphine (BUP): 10 ng/ml<br>D,L-Methylenedioxymethamphetamine (MDMA): 500 ng/ml<br>Phencyclidine (PCP): 25 ng/ml<br>Nortriptyline (TCA): 1000 ng/ml<br>2-ethylidene-1,5-dimethyl-3,3- diphenylpyrrolidine (EDDP): 300 ng/ml<br>Propoxyphene (PPX): 300 ng/ml | |
|----------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------|
| Methodology | Competitive binding, lateral flow immunochromatographic assays based on the principle of antigen antibody immunochemistry. | Same |
| Type of Test | Qualitative | Same |
| Specimen Type | Human Urine | Same |
| Intended Use | For over-the-counter | Same |
| Configurations | Dip Card | Cup |

| | Table 2: Features Comparison of First Sign Multi-Drug Test Cup Tests and the Predicate | | |
|---------|----------------------------------------------------------------------------------------|--|--|
| Devices | | | |
| | | | |

| Item | Device | Predicate - K18270 |
|----------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------|
| Indication(s)<br>for Use | For the qualitative determination of<br>drugs of abuse in human urine. | Same |
| Calibrator and<br>Cut-Off Values | Amphetamine (AMP): 1,000 ng/ml or 500 ng/mL<br>Oxazepam (BZO):300 ng/ml<br>Cocaine (COC): 300 ng/ml or 150 ng/mL<br>11-Nor-Δ9-Tetrahydrocannabinol-9-COOH (THC):50<br>ng/ml<br>Methamphetamine (MET): 1,000 ng/ml or 500 ng/mL<br>Morphine (OPI 2000/MOP 300): 2000ng/mL or 300 ng/mL<br>Oxycodone (OXY): 100 ng/ml<br>Butalbital (BAR): 300 ng/ml<br>Methadone (MTD): 300 ng/ml<br>Buprenorphine (BUP): 10 ng/ml<br>D,L-Methylenedioxymethamphetamine (MDMA): 500<br>ng/ml<br>Phencyclidine (PCP): 25 ng/ml<br>Nortriptyline (TCA): 1000 ng/ml<br>2-ethylidene-1,5-dimethyl-3,3- diphenylpyrrolidine<br>(EDDP): 300 ng/ml<br>Propoxyphene (PPX): 300 ng/ml | Same |
| Methodology | Competitive binding, lateral flow<br>immunochromatographic assays based on the principle<br>of antigen antibody immunochemistry. | Same |
| Type of Test | Qualitative | Same |

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

| Specimen Type | Human Urine | Same |
|----------------|----------------------|------|
| Intended Use | For over-the-counter | Same |
| Configurations | Cup | Cup |

## Table 3: Features Comparison of First Sign Multi-Drug Screen Test Dip Card and the Predicate Devices

| Item | Device | Predicate - K182701 |
|----------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------|
| Indication(s)<br>for Use | For the qualitative determination of drugs of abuse in human<br>urine. | Same |
| Calibrator and<br>Cut-Off Values | Amphetamine (AMP): 1,000 ng/ml or 500 ng/mL<br>Oxazepam (BZO):300 ng/ml<br>Cocaine (COC): 300 ng/ml or 150 ng/mL<br>11-Nor-Δ9-Tetrahydrocannabinol-9-COOH (THC):50 ng/ml<br>Methamphetamine (MET): 1,000 ng/ml or 500 ng/mL<br>Morphine (OPI 2000/MOP 300): 2000ng/mL or 300 ng/mL<br>Oxycodone (OXY) : 100 ng/ml<br>Butalbital (BAR): 300 ng/ml<br>Methadone (MTD): 300 ng/ml<br>Buprenorphine (BUP): 10 ng/ml<br>D,L-Methylenedioxymethamphetamine (MDMA): 500<br>ng/ml<br>Phencyclidine (PCP): 25 ng/ml<br>Nortriptyline (TCA): 1000 ng/ml<br>2-ethylidene-1,5-dimethyl-3,3- diphenylpyrrolidine (EDDP):<br>300 ng/ml<br>Propoxyphene (PPX): 300 ng/ml | Same |
| Methodology | Competitive binding, lateral flow immunochromatographic<br>assays based on the principle of antigen antibody<br>immunochemistry. | Same |
| Type of Test | Qualitative | Same |
| Specimen Type | Human Urine | Same |
| Intended Use | For prescription | For over-the-counter |
| Configurations | Dip Card | Cup |

## Table 4: Features Comparison of First Sign Multi-Drug Screen Test Cup Tests and the Predicate Devices

| Item | Device | Predicate - K18270 |
|----------------------------------|------------------------------------------------------------------------------------------------------------------|--------------------|
| Indication(s)<br>for Use | For the qualitative determination of<br>drugs of abuse in human urine. | Same |
| Calibrator and<br>Cut-Off Values | Amphetamine (AMP): 1,000 ng/ml or 500 ng/mL<br>Oxazepam (BZO):300 ng/ml<br>Cocaine (COC): 300 ng/ml or 150 ng/mL | Same |

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

| | 11-Nor-Δ9-Tetrahydrocannabinol-9-COOH (THC):50 ng/ml | |
|----------------|----------------------------------------------------------------------------------------------------------------------------------|----------------------|
| | Methamphetamine (MET): 1,000 ng/ml or 500 ng/mL | |
| | Morphine (OPI 2000/MOP 300): 2000ng/mL or 300 ng/mL | |
| | Oxycodone (OXY): 100 ng/ml | |
| | Butalbital (BAR): 300 ng/ml | |
| | Methadone (MTD): 300 ng/ml | |
| | Buprenorphine (BUP): 10 ng/ml | |
| | D,L-Methylenedioxymethamphetamine (MDMA): 500 ng/ml | |
| | Phencyclidine (PCP): 25 ng/ml | |
| | Nortriptyline (TCA): 1000 ng/ml | |
| | 2-ethylidene-1,5-dimethyl-3,3- diphenylpyrrolidine<br>(EDDP): 300 ng/ml | |
| | Propoxyphene (PPX): 300 ng/ml | |
| | Competitive binding, lateral flow<br>immunochromatographic assays based on the principle<br>of antigen antibody immunochemistry. | |
| Methodology | Competitive binding, lateral flow<br>immunochromatographic assays based on the principle<br>of antigen antibody immunochemistry. | Same |
| Type of Test | Qualitative | Same |
| Specimen Type | Human Urine | Same |
| Intended Use | For prescription | For over-the-counter |
| Configurations | Cup | Cup |

## 9. Test Principle

The First Sign Multi-Drug Test Dip Card, First Sign Multi-Drug Test Cup, First Sign Multi-Drug Screen Test Dip Card, and First Sign Multi-Drug Screen Test Cup are rapid tests for the qualitative detection of Amphetamine, Oxazepam, Cocaine, Methamphetamine, Morphine, Oxycodone, Butalbital, Methadone, Buprenorphine, Phencyclidine,

Methylenedioxymethamphetamine, Tricyclic Antidepressants, 2-ethylidene-1,5-dimethyl-3,3diphenylpyrrolidine and Propoxyphene in urine samples. The tests are lateral flow chromatographic immunoassays. During testing, a urine specimen migrates upward by capillary action. If target drugs present in the urine specimen are below the cut-off concentration, it will not saturate the binding sites of its specific monoclonal mouse antibody coated on the particles. The antibody-coated particles will then be captured by immobilized drug-conjugate and a visible colored line will show up in the test line region. The will not form in the test line region if the target drug level exceeds its cutoff-concentration because it will saturate all the binding sites of the antibody coated on the particles. A band should form in the control region of the devices regardless of the presence of drug or metabolite in the sample to indicate that the tests have been performed properly.

#### 10. Performance Characteristics

- 1. Analytical Performance
- a. Precision

Precision studies were carried out for samples with concentrations of -100% cut off, -75% cut off, -50% cut off, -25% cut off, cut off, +25% cut off, +50% cut off , +75% cut

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

off and +100% cut off. These samples were prepared by spiking drug in negative urine samples. Each drug concentration was confirmed by LC/MS. All sample aliquots were blindly labeled by the person who prepared the samples and didn't take part in the sample testing. For each concentration, tests were performed two runs per day for 25 days per device in a randomized order. The results obtained are summarized in the following tables for Propoxyphene. The data for AMP1000, COC300 and THC were reported in the cleared k142353. The data for BUP, BAR and MOP 300 were reported in the cleared k152551. The data for BZO, MET1000 and MOP 2000 were reported in the cleared k150162. The data for MTD, PCP and OXY were reported in the cleared k151441. The data for EDDP, MDMA and TCA were reported in the cleared k160793. The data for AMP 500, COC150 and MET 500 were reported in the cleared First Sign submission of k171695.

#### Propoxyphene

| Dip Card | | | | | | | | | | |
|---------------|-----------------------------------|------------------|-----------------|-----------------|-----------------|---------|-----------------|-----------------|-----------------|------------------|
| | Concentration by<br>LC/MS (ng/mL) | -100%<br>Cut-off | -75%<br>Cut-off | -50%<br>Cut-off | -25%<br>Cut-off | Cut-off | +25%<br>Cut-off | +50%<br>Cut-off | +75%<br>Cut-off | +100%<br>Cut-off |
| Lot<br>Number | | 0 | 80.7 | 165.5 | 248.1 | 339.9 | 416.8 | 497.2 | 558.1 | 677.3 |
| Lot 1 | | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 4-/46+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 2 | | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 3 | | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 4-/46+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |

| Cup | | | | | | | | | |
|----------------------------------------------------|------------------|-----------------|-----------------|-----------------|---------|-----------------|-----------------|-----------------|------------------|
| Concentration by<br>LC/MS (ng/mL)<br>Lot<br>Number | -100%<br>Cut-off | -75%<br>Cut-off | -50%<br>Cut-off | -25%<br>Cut-off | Cut-off | +25%<br>Cut-off | +50%<br>Cut-off | +75%<br>Cut-off | +100%<br>Cut-off |
| | 0 | 80.7 | 165.5 | 248.1 | 339.9 | 416.8 | 497.2 | 558.1 | 677.3 |
| Lot 1 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 3-/47+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 2 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 2-/48+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |
| Lot 3 | 50-/0+ | 50-/0+ | 50-/0+ | 50-/0+ | 2-/48+ | 50+/0- | 50+/0- | 50+/0- | 50+/0- |

The cut-off value of 300ng/mL is verified for propoxyphene.

#### b. Linearity

Not applicable.

- C. Stability
The devices are stable at 4-30 ℃ for 24 months based on the accelerated stability study at 50°C. Real time stability studies are ongoing.

#### d. Interference

Potential interfering substances found in human urine of physiological or pathological conditions were added to drug-free urine and target drugs urine with concentrations at 25% below and 25% above Cut-Off levels. These urine samples were tested using three lots of each device. Compounds that showed no interference at a concentration of 100ug/mL are summarized in the following tables. There were no differences observed between the Dip Card and the Cup formats.

| Acetaminophen | ß-Estradiol | Oxalic acid |
|----------------------|--------------|---------------|
| Acetophenetidin | Ethanol | Oxolinic acid |
| N-Acetylprocainamide | Erythromycin | Oxymetazoline |

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

| Acetylsalicylic acid | Fenoprofen | Papaverine |
|-----------------------|------------------------|--------------------------------|
| Albumin | Furosemide | Penicillin G |
| Aminopyrine | Gentisic acid | Perphenazine |
| Amoxicillin | Hemoglobin | Phenelzine |
| Ampicillin | Hydralazine | Prednisone |
| Apomorphine | Hydrochlorothiazide | (±)-Propranolol |
| Ascorbic acid | Hydrocortisone | Pseudoephedrine |
| Aspartame | O-Hydroxyhippuric acid | Quinine |
| Atropine | 3-Hydroxytyramine | Ranitidine |
| Benzilic acid | Ibuprofen | Salicylic acid |
| Benzoic acid | Isoproterenol | Serotonin (5- Hydroxytyramine) |
| Bilirubin | Isoxsuprine | Sulfamethazine |
| Chloral hydrate | Ketamine | Sulindac |
| Chloramphenicol | Ketoprofen | Tetrahydrocortisone 3-(β- |
| | | Dglucuronide) |
| Chlorothiazide | Labetalol | Tetrahydrocortisone 3-acetate |
| Chlorpromazine | Loperamide | Tetrahydrozoline |
| Cholesterol | Meperidine | Thiamine |
| Clonidine | Meprobamate | Thioridazine |
| Cortisone | Methoxyphenamine | Triamterene |
| (-)-Cotinine | Nalidixic acid | Trifluoperazine |
| Creatinine | Naloxone | Trimethoprim |
| Deoxycorticosterone | Naltrexone | DL-Tryptophan |
| Dextromethorphan | Naproxen | Tyramine |
| Diclofenac | Niacinamide | DL-Tyrosine |
| Diflunisal | Nifedipine | Uric acid |
| Digoxin | Norethindrone | Verapamil |
| Diphenhydramine | Noscapine | Zomepirac |
| Ecgonine methyl ester | (±)-Octopamine | |

#### e. Specificity

To test specificity, drug metabolites and other structurally related compounds that are likely to cross-react in urine samples were spiked into negative urine and were tested using three lots of each device. The lowest concentration that caused a positive result for each compound are listed below for Propoxyphene. The data for AMP1000, COC300 and THC were reported in the cleared k142353. The data for BUP, BAR and MOP 300 were reported in the cleared k152551. The data for BZO, MET1000 and MOP 2000 were reported in the cleared k150162. The data for MTD, PCP and OXY were reported in the cleared k151441. The data for EDDP, MDMA and TCA were reported in the cleared k160793. The data for AMP 500, COC150 and MET 500 were reported in the cleared First Sign submission of k171695. There were no differences observed between the First Sign Multi-Drug Test Dip Card and First Sign Multi-Drug Test Cup.

| Propoxyphene<br>(Cut-off=300 ng/mL) | Result<br>Positive at(ng/ml) | %<br>Cross-Reactivity |
|-------------------------------------|------------------------------|-----------------------|
| d-Propoxyphene | 300 | 100% |
| Norpropoxyphene | 1500 | 20% |

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

f. Effect of Urine Specific Gravity and Urine pH

To investigate the effect of urine specific gravity and urine pH, urine samples, with 1.000 to 1.035 specific gravity or urine samples with pH 4 to 9 were spiked with target drugs at 25% below and 25% above Cut-Off levels. These samples were tested using three lots of each device. Results were all positive for samples at and above +25% Cut-Off and all negative for samples at and below -25% Cut-Off. There were no differences observed between the First Sign Multi-Drug Test Dip Card and First Sign Multi-Drug Test Cup.

## 2. Comparison Studies

Method comparison studies for the First Sign Multi-Drug Test Dip Card and the First Sign Multi-Drug Test Cup were performed in-house with three laboratory assistants for each device. Operators ran 80 (40 negative and 40 positive) unaltered clinical samples for each drug. The samples were blind labeled and compared to LC/MS results. The results are presented in the tables below for Propoxyphene. The data for AMP1000, COC300 and THC were reported in the cleared k142353. The data for BUP, BAR and MOP 300 were reported in the cleared k152551. The data for BZO, MET1000 and MOP 2000 were reported in the cleared k150162. The data for MTD, PCP and OXY were reported in the cleared k151441. The data for EDDP, MDMA and TCA were reported in the cleared k160793. The data for AMP 500, COC150 and MET 500 were reported in the cleared First Sign submission of k171695.

## Propoxyphene

| Dip Card | | Negative | Low Negative by<br>LC/MS<br>(less than<br>-50%) | Near Cutoff<br>Negative by<br>LC/MS<br>(Between<br>-50% and<br>cutoff) | Near Cutoff<br>Positive by<br>LC/MS<br>(Between the<br>cutoff and<br>+50%) | High Positive<br>by LC/MS<br>(greater than<br>+50%) |
|----------|----------|----------|-------------------------------------------------|------------------------------------------------------------------------|----------------------------------------------------------------------------|-----------------------------------------------------|
| Viewer | Positive | 0 | 0 | 1 | 19 | 20 |
| A | Negative | 10 | 15 | 14 | 1 | 0 |
| Viewer | Positive | 0 | 0 | 1 | 20 | 20 |
| B | Negative | 10 | 15 | 14 | 0 | 0 |
| Viewer | Positive | 0 | 0 | 0 | 20 | 20 |
| C | Negative | 10 | 15 | 15 | 0 | 0 |

## Discordant Results

| Viewer | Sample Number | LC/MS Result | Dip Card<br>Viewer Results |
|----------|---------------|--------------|----------------------------|
| Viewer A | 20200406-030 | 268.2 | Positive |
| Viewer B | 20200408-001 | 277.6 | Positive |
| Viewer A | 20200407-003 | 332.0 | Negative |

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

| Cup | | Negative | Low<br>Negative by<br>LC/MS<br>(less than<br>-50%) | Near Cutoff<br>Negative by<br>LC/MS<br>(Between<br>-50% and<br>cutoff) | Near Cutoff<br>Positive by<br>LC/MS<br>(Between the<br>cutoff and<br>+50%) | High Positive<br>by LC/MS<br>(greater than<br>+50%) |
|--------|----------|----------|----------------------------------------------------|------------------------------------------------------------------------|----------------------------------------------------------------------------|-----------------------------------------------------|
| Viewer | Positive | 0 | 0 | 0 | 19 | 20 |
| A | Negative | 10 | 15 | 15 | 1 | 0 |
| Viewer | Positive | 0 | 0 | 1 | 20 | 20 |
| B | Negative | 10 | 15 | 14 | 0 | 0 |
| Viewer | Positive | 0 | 0 | 1 | 20 | 20 |
| C | Negative | 10 | 15 | 14 | 0 | 0 |

#### Discordant Results

| Viewer | Sample Number | LC/MS Result | Cup<br>Viewer Results |
|----------|---------------|--------------|-----------------------|
| Viewer B | 20200408-032 | 292.8 | Positive |
| Viewer C | 20200408-032 | 292.8 | Positive |
| Viewer A | 20200406-010 | 327.4 | Negative |

#### Lay-user study

A lay user study was performed at three intended user sites with 280 lay persons for each device format. The lay users had diverse educational and professional backgrounds and ranged in age from 18 to > 50 years. Urine samples were prepared at the following concentrations; negative, +/-75%, +/-50%, +/-25% of the cutoff by spiking drugs into drug free-pooled urine specimens. The concentrations of the samples were confirmed by LC/MS. Each sample was aliquoted into individual containers and blind-labeled. Each participant was provided with the package insert, 1 blind labeled sample and a device. Each device was tested. Typical Results are shown below.

#### First Sign Multi-Drug Test

Configuration 1 (including AMP 500, MET 500, MOP 300, COC 150):

| Assay | Results | Concentration | | | | | | |
|--------------------------------------|--------------------------------------|-----------------|----------------|----------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------|----------------|
| | | -100%<br>cutoff | -75%<br>cutoff | -50%<br>cutoff | -25%<br>cutoff | +25%<br>cutoff | +50%<br>cutoff | +75%<br>cutoff |
| | Negative | 20 | 20 | 20 | 20 | 1 | 0 | 0 |
| | Positive | 0 | 0 | 0 | 0 | 19 | 20 | 20 |
| AMP 500 | Total | 20 | 20 | 20 | 20 | 20 | 20 | 20 |
| | Percentage of<br>correct results (%) | 100% | 100% | 100% | 100% | 95% | 100% | 100% |
| | Negative | 20 | 20 | 20 | 20 | 1 | 0 | 0 |
| BAR 300 | Positive | 0 | 0 | 0 | 0 | 19 | 20 | 20 |
| | Total | 20 | 20 | 20 | 20 | 20 | 20 | 20 |
| | Percentage of | 100% | 100% | 100% | 100% | 95% | 100% | 100% |
| | correct results (%) | | | | | | | |
| BZO 300 | Negative | 20 | 20 | 20 | 20 | 0 | 0 | 0 |
| | Positive | 0 | 0 | 0 | 0 | 20 | 20 | 20 |
| | Total | 20 | 20 | 20 | 20 | 20 | 20 | 20 |
| | Percentage of<br>correct results (%) | 100% | 100% | 100% | 100% | 100%…