ONE STEP SINGLE/MULTI-DRUG TEST CUP, ONE STEP SINGLE/MULTI-DRUG TEST DIPCARD

K140748 · Co-Innovation Biotech Co., Ltd. · DJG · Aug 20, 2014 · Clinical Toxicology

Device Facts

• Record ID: K140748
• Device Name: ONE STEP SINGLE/MULTI-DRUG TEST CUP, ONE STEP SINGLE/MULTI-DRUG TEST DIPCARD
• Applicant: Co-Innovation Biotech Co., Ltd.
• Product Code: DJG · Clinical Toxicology
• Decision Date: Aug 20, 2014
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3650
• Device Class: Class 2

Indications for Use

One Step Single/Multi-drug Test Cup and One Step Single/Multi-drug Test Dipcard are lateral flow chromatographic immunoassays designed to qualitatively detect the presence of drugs and drug metabolites in human urine at the following cut-off concentrations: Buprenorphine (BUP) 10 ng/mL, 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDP) 300 ng/mL, Morphine (MOP300) 300 ng/mL, Propoxyphene (PPX) 300 ng/mL, Tricyclic Antidepressants (TCA) 1000 ng/mL. There are two formats: 1) Test Cup, 2) Test Dipcard. Each format may have from 1 to 5 drugs in any combination. The assays are intended for in vitro diagnostic use. They are intended for prescription use including point of care sites and over-the-counter use. The tests may yield preliminary positive results even when prescription drugs including Buprenorphine, Propoxyphene, or Tricyclic Antidepressants are ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of these drugs. There are no uniformly recognized cutoff concentration levels for Buprenorphine. or Tricyclic Antidepressants in urine. This assay provides only a preliminary analytical test result. Gas Chromatography/Mass spectrometry (GC/MS) or an equivalent analytical method is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are indicated.

Device Story

Lateral flow immunochromatographic competitive binding assay; detects drugs/metabolites in urine. Input: urine sample; capillary action moves sample across membrane. Principle: drug in sample competes with drug-protein conjugate for limited antibody binding sites. Output: visual colored lines; line in Test Region (T) indicates negative; absence of line indicates preliminary positive. Control line (C) confirms proper operation. Used at point-of-care or home; operated by clinicians or lay users. Provides preliminary analytical result; requires GC/MS or equivalent for confirmation. Assists clinical decision-making by identifying potential drug presence.

Clinical Evidence

Clinical performance evaluated using 80 urine specimens per drug. Results compared against GC/MS or HPLC. Study included drug-free, low-negative, near-cutoff negative, near-cutoff positive, and high-positive samples. Performance demonstrated satisfactory agreement with reference methods across all drug analytes.

Technological Characteristics

Lateral flow immunochromatographic assay; competitive binding principle. Formats: Test Cup and Test Dipcard. Urine specimen. Visual readout. No instrumentation required. Identical chemical formulation and manufacturing procedures for all strips.

Indications for Use

Indicated for qualitative detection of Buprenorphine, EDDP, Morphine, Propoxyphene, and Tricyclic Antidepressants in human urine. Intended for prescription, point-of-care, and over-the-counter use. Not intended to distinguish between prescription use and abuse.

Regulatory Classification

Identification

An opiate test system is a device intended to measure any of the addictive narcotic pain-relieving opiate drugs in blood, serum, urine, gastric contents, and saliva. An opiate is any natural or synthetic drug that has morphine-like pharmocological actions. The opiates include drugs such as morphine, morphine glucoronide, heroin, codeine, nalorphine, and meperedine. Measurements obtained by this device are used in the diagnosis and treatment of opiate use or overdose and in monitoring the levels of opiate administration to ensure appropriate therapy.

Special Controls

*Classification.* Class II (special controls). An opiate 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

• Advin Multi-Drug Screen Test Dip Card (k122809)
• Advin Multi-Drug Screen Test Cup (k122809)
• Advin Multi-Drug Screen Test Cassette (k122809)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k140748

B. Purpose for Submission:
New device

C. Measurand:
Buprenorphine, EDDP (2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine), Morphine, Propoxyphene, and Tricyclic Antidepressants

D. Type of Test:
Qualitative lateral flow immunochromatographic competitive binding assay

E. Applicant:
Co-Innovation Biotech Co., Ltd.

F. Proprietary and Established Names:
One Step Single/Multi-drug Test Cup
One Step Single/Multi-drug Test Dipcard

G. Regulatory Information:
1. Regulation section:

| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| DJG | Class II | 862.3650 Opiate test system | Toxicology (91) |
| DJR | Class II | 862.3620 Methadone test system | Toxicology (91) |
| DNK | Class II | 862.3640 Morphine test system | Toxicology (91) |
| JXN | Class II | 862.3700 Propoxyphene test system | Toxicology (91) |
| LFG | Class II | 862.3910 Tricyclic antidepressant drugs test system | Toxicology (91) |

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H. Intended Use:

1. Intended use(s):

Refer to Indications for Use below.

2. Indication(s) for use:

One Step Single/Multi-drug Test Cup and One Step Single/Multi-drug Test Dipcard are lateral flow chromatographic immunoassays designed to qualitatively detect the presence of drugs and drug metabolites in human urine at the following cut-off concentrations:

| Test | Calibrator | Cutoff Level (ng/mL) |
| --- | --- | --- |
| Buprenorphine (BUP) | Buprenorphine | 10 |
| 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDP) | 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine | 300 |
| Morphine (MOP300) | Morphine | 300 |
| Propoxyphene (PPX) | Propoxyphene | 300 |
| Tri-cyclic Antidepressants (TCA) | Nortriptyline | 1000 |

There are two formats: 1) Test Cup, 2) Test Dipcard. Each format may have from 1 to 5 drugs in any combination. The assays are intended for in vitro diagnostic use. They are intended for prescription use including point of care sites and over-the-counter use.

The tests may yield preliminary positive results even when prescription drugs including Buprenorphine, Propoxyphene, or Tricyclic Antidepressants are ingested, at prescribed doses; it is not intended to distinguish between prescription use or abuse of these drugs. There are no uniformly recognized cutoff concentration levels for Buprenorphine, Propoxyphene, or Tricyclic Antidepressant in urine.

This assay provides only a preliminary analytical test result. Gas Chromatography/Mass spectrometry (GC/MS) or an equivalent analytical method is the preferred confirmatory method. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are indicated.

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3. Special conditions for use statement(s):

These assays are intended for prescription use, including point of care and over the counter use.

4. Special instrument requirements:

Not applicable; these are visually read single use devices.

I. Device Description:

One Step Single/Multi-drug Test Cup and One Step Single/Multi-drug Test Dipcard are competitive binding, lateral flow immunochromatographic assays for the qualitative detection of Buprenorphine, 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine, Morphine, Propoxyphene, Tricyclic Antidepressants and their metabolites at or above the cut-off levels as indicated. The devices are available in both a test cup and a test card format. The test configuration comes with single drug screening test or any combinations of multiple drug screening tests. The tests are visually read.

J. Substantial Equivalence Information:

1. Predicate device name(s):

Advin Multi-Drug Screen Test Dip Card
Advin Multi-Drug Screen Test Cup
Advin Multi-Drug Screen Test Cassette

2. Predicate 510(k) number(s):

k122809

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Candidate Device | Predicate Device (k122809) |
| Matrix | Same | Urine |
| Cutoffs | Same | Buprenorphine: 10 ng/mL
EDDP: 300 ng/mL
Morphine: 300 ng/mL
Propoxyphene: 300 ng/mL
TCA: 1000 ng/mL |
| Read time | Same | Five minutes |

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| Differences | | |
| --- | --- | --- |
| Item | Candidate Device | Predicate Device (k122809) |
| Available formats | Dipcard and Cup | Cassette, Dip Card and Cup |
| Number of analytes detected | Five | Sixteen |

# K. Standard/Guidance Document Referenced (if applicable):

EN13612:2002 Stability testing of in vitro diagnostic reagents

# L. Test Principle:

One Step Single/Multi-drug Test Cup and Dip Card are competitive immunoassays used to screen for the presence of various drugs and drug metabolites in urine. They are chromatographic absorbent devices in which drugs or metabolites in a urine sample competitively combine with a limited number of drug monoclonal antibody (mouse) conjugate binding sites.

When the test is activated, the urine is absorbed into each test strip by capillary action, mixes with the respective analyte monoclonal antibody conjugate, and flows across a pre-coated membrane. When drug within the urine sample is at a level below the cutoff of the test, the drug monoclonal antibody conjugate binds to the corresponding drug-protein conjugate immobilized in the Test Region (T) of the test strip. This produces a colored Test line in the Test Region (T) of the strip that, regardless of its intensity, indicates a negative test result.

When sample drug levels are at or above the cutoff of the test, the free drug in the sample binds to the corresponding drug monoclonal antibody conjugate, preventing the respective drug monoclonal antibody conjugate from binding to the corresponding drug-protein conjugate immobilized in the Test Region (T) of the device. This prevents the development of a distinct colored band in the test region, indicating a preliminary positive result.

To serve as a procedure control, a colored line will appear at the Control Region (C) of each strip if the volume of sample applied is adequate and the test is operating properly.

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M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Drug free specimens were spiked with the analytes at 0%, -75%, -50%, -25%, cutoff, +25%, +50%, +75%, and +100% of the cutoff. All concentrations were confirmed with GC/MS, LC/MS, or HPLC. Urine specimens at each concentration were divided into aliquots. All aliquots were blindly labeled by a nonparticipant. Separate sets of the blind coded samples were assigned and randomized prior to testing. The study was conducted by three nurses at three Point-of-Care sites.

Buprenorphine - Dipcard Format - Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 2.5 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 5 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 7.5 | -25 | 10 | 50 | 12 | 48 | 8 | 52 |
| 10 | Cutoff | 38 | 22 | 36 | 24 | 34 | 26 |
| 12.5 | +25 | 54 | 6 | 50 | 10 | 52 | 8 |
| 15 | +50 | 56 | 4 | 58 | 2 | 56 | 4 |
| 17.5 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 20 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

Buprenorphine - Dipcard Format - Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 2.5 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 5 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 7.5 | -25 | 12 | 48 | 8 | 52 | 10 | 50 |
| 10 | Cutoff | 34 | 26 | 36 | 24 | 34 | 26 |
| 12.5 | +25 | 50 | 10 | 48 | 12 | 50 | 10 |
| 15 | +50 | 54 | 6 | 56 | 4 | 56 | 4 |
| 17.5 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 20 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

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Buprenorphine - Cup Format - Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 2.5 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 5 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 7.5 | -25 | 10 | 50 | 8 | 52 | 6 | 54 |
| 10 | Cutoff | 34 | 26 | 32 | 28 | 36 | 24 |
| 12.5 | +25 | 54 | 6 | 56 | 4 | 52 | 8 |
| 15 | +50 | 60 | 0 | 58 | 2 | 56 | 4 |
| 17.5 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 20 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

Buprenorphine - Cup Format - Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 0 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 2.5 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 5 | -25 | 6 | 54 | 8 | 52 | 10 | 50 |
| 7.5 | Cutoff | 32 | 28 | 36 | 24 | 34 | 26 |
| 10 | +25 | 52 | 8 | 50 | 10 | 54 | 6 |
| 12.5 | +50 | 58 | 2 | 60 | 0 | 56 | 4 |
| 15 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 17.5 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

EDDP - Dipcard Format - Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 10 | 50 | 8 | 52 | 6 | 54 |
| 300 | Cutoff | 32 | 28 | 36 | 24 | 34 | 26 |
| 375 | +25 | 54 | 6 | 52 | 8 | 50 | 10 |
| 450 | +50 | 60 | 0 | 58 | 2 | 56 | 4 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

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EDDP – Dipcard Format – Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 10 | 50 | 6 | 54 | 8 | 52 |
| 300 | Cutoff | 38 | 22 | 36 | 24 | 32 | 28 |
| 375 | +25 | 50 | 10 | 48 | 12 | 52 | 8 |
| 450 | +50 | 56 | 4 | 60 | 0 | 58 | 2 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

EDDP – Cup Format – Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 10 | 50 | 8 | 52 | 12 | 48 |
| 300 | Cutoff | 36 | 24 | 38 | 22 | 34 | 26 |
| 375 | +25 | 56 | 4 | 54 | 6 | 52 | 8 |
| 450 | +50 | 58 | 2 | 56 | 4 | 58 | 2 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

EDDP – Cup Format – Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 8 | 52 | 6 | 54 | 10 | 50 |
| 300 | Cutoff | 34 | 26 | 36 | 24 | 32 | 28 |
| 375 | +25 | 52 | 8 | 54 | 6 | 50 | 10 |
| 450 | +50 | 60 | 0 | 56 | 4 | 58 | 2 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

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Morphine – Dipcard Format – Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 6 | 54 | 4 | 56 | 8 | 52 |
| 300 | Cutoff | 36 | 24 | 38 | 22 | 34 | 26 |
| 375 | +25 | 50 | 10 | 48 | 12 | 52 | 8 |
| 450 | +50 | 56 | 4 | 58 | 2 | 60 | 0 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

Morphine – Dipcard Format – Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 8 | 52 | 12 | 48 | 10 | 50 |
| 300 | Cutoff | 36 | 24 | 34 | 26 | 38 | 22 |
| 375 | +25 | 54 | 6 | 56 | 4 | 52 | 8 |
| 450 | +50 | 58 | 2 | 60 | 0 | 56 | 4 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

Morphine – Cup Format – Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 8 | 52 | 6 | 54 | 4 | 56 |
| 300 | Cutoff | 34 | 26 | 36 | 24 | 38 | 22 |
| 375 | +25 | 54 | 6 | 50 | 10 | 52 | 8 |
| 450 | +50 | 58 | 2 | 60 | 0 | 56 | 4 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

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Morphine – Cup Format – Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 6 | 54 | 8 | 52 | 4 | 56 |
| 300 | Cutoff | 34 | 26 | 38 | 22 | 36 | 24 |
| 375 | +25 | 48 | 12 | 50 | 10 | 52 | 8 |
| 450 | +50 | 60 | 0 | 58 | 2 | 56 | 4 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

Propoxyphene – Dipcard Format – Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 4 | 56 | 8 | 52 | 6 | 54 |
| 300 | Cutoff | 36 | 24 | 34 | 26 | 38 | 22 |
| 375 | +25 | 48 | 12 | 52 | 8 | 50 | 10 |
| 450 | +50 | 56 | 4 | 58 | 2 | 58 | 2 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

Propoxyphene – Dipcard Format – Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 6 | 54 | 8 | 52 | 10 | 50 |
| 300 | Cutoff | 38 | 22 | 34 | 26 | 32 | 28 |
| 375 | +25 | 52 | 8 | 54 | 6 | 50 | 10 |
| 450 | +50 | 56 | 4 | 58 | 2 | 60 | 0 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

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Propoxyphene – Cup Format – Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 6 | 54 | 8 | 52 | 6 | 54 |
| 300 | Cutoff | 34 | 26 | 38 | 22 | 36 | 24 |
| 375 | +25 | 56 | 4 | 52 | 8 | 54 | 6 |
| 450 | +50 | 60 | 0 | 58 | 2 | 50 | 0 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

Propoxyphene – Cup Format – Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 8 | 52 | 6 | 54 | 4 | 56 |
| 300 | Cutoff | 38 | 22 | 34 | 26 | 36 | 24 |
| 375 | +25 | 54 | 6 | 50 | 10 | 52 | 8 |
| 450 | +50 | 60 | 0 | 56 | 4 | 58 | 2 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

TCA – Dipcard Format – Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 250 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 500 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 750 | -25 | 4 | 56 | 6 | 54 | 4 | 56 |
| 1000 | Cutoff | 36 | 24 | 38 | 22 | 34 | 26 |
| 1250 | +25 | 54 | 6 | 56 | 4 | 52 | 8 |
| 1500 | +50 | 58 | 2 | 60 | 0 | 56 | 4 |
| 1750 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 2000 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

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TCA - Dipcard Format - Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 250 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 500 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 750 | -25 | 8 | 52 | 6 | 54 | 10 | 50 |
| 1000 | Cutoff | 34 | 26 | 35 | 24 | 32 | 28 |
| 1250 | +25 | 50 | 10 | 52 | 8 | 50 | 10 |
| 1500 | +50 | 60 | 0 | 56 | 4 | 58 | 2 |
| 1750 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 2000 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

TCA - Cup Format - Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 250 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 500 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 750 | -25 | 8 | 52 | 4 | 56 | 6 | 54 |
| 1000 | Cutoff | 34 | 26 | 38 | 22 | 36 | 24 |
| 1250 | +25 | 50 | 10 | 48 | 12 | 52 | 8 |
| 1500 | +50 | 56 | 4 | 60 | 0 | 58 | 2 |
| 1750 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 2000 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

TCA - Cup Format - Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 250 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 500 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 750 | -25 | 4 | 56 | 8 | 52 | 6 | 54 |
| 1000 | Cutoff | 38 | 22 | 34 | 26 | 36 | 24 |
| 1250 | +25 | 52 | 8 | 48 | 12 | 50 | 10 |
| 1500 | +50 | 58 | 2 | 58 | 2 | 56 | 4 |
| 1750 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 2000 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

The original precision study data showed numerous negative results in the specimens containing drug concentrations at $+50\%$ above the cutoff. A root cause analysis was conducted by the sponsor to determine the cause of these results. The root cause was identified to be inconsistent and inadequate volume of aliquoted samples. The sponsor revised the precision study protocol to specify a sample volume per vial and supplemental precision studies were conducted to verify that the root cause was

{11}

correctly identified.

Supplemental precision studies were conducted for the single drug and multi-drug test formats using drug free urine specimens spiked at analyte concentrations of $0\%$ , $-75\%$ , $-50\%$ , $-25\%$ , cutoff, $+25\%$ , $+50\%$ , $+75\%$ , and $+100\%$ of the cutoff. All concentrations were confirmed with GC/MS, LC/MS, or HPLC. Urine specimens at each concentration were divided into aliquots. All aliquots were blindly labeled by a nonparticipant. Separate sets of the blind coded samples were assigned and randomized prior to testing. The study was conducted by three nurses at three Point-of-Care sites.

Buprenorphine - Dipcard Format - Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 2.5 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 5 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 7.5 | -25 | 8 | 52 | 4 | 56 | 6 | 54 |
| 10 | Cutoff | 34 | 26 | 32 | 28 | 36 | 24 |
| 12.5 | +25 | 56 | 4 | 54 | 6 | 52 | 8 |
| 15 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 17.5 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 20 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

Buprenorphine - Dipcard Format - Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 2.5 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 5 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 7.5 | -25 | 4 | 56 | 8 | 52 | 6 | 54 |
| 10 | Cutoff | 34 | 26 | 36 | 24 | 38 | 22 |
| 12.5 | +25 | 56 | 4 | 52 | 8 | 54 | 6 |
| 15 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 17.5 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 20 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

{12}

Buprenorphine - Cup Format - Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| | | | | | | | |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 2.5 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 5 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 7.5 | -25 | 6 | 54 | 4 | 56 | 8 | 52 |
| 10 | Cutoff | 32 | 28 | 34 | 26 | 36 | 24 |
| 12.5 | +25 | 54 | 6 | 52 | 8 | 56 | 4 |
| 15 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 17.5 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 20 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

Buprenorphine - Cup Format - Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 0 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 2.5 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 5 | -25 | 6 | 54 | 8 | 52 | 4 | 56 |
| 7.5 | Cutoff | 32 | 28 | 36 | 24 | 34 | 26 |
| 10 | +25 | 52 | 8 | 54 | 6 | 56 | 4 |
| 12.5 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 15 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 17.5 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

EDDP - Dipcard Format - Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 4 | 56 | 6 | 54 | 8 | 52 |
| 300 | Cutoff | 36 | 24 | 38 | 22 | 34 | 26 |
| 375 | +25 | 54 | 6 | 52 | 8 | 56 | 4 |
| 450 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

{13}

EDDP – Dipcard Format – Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 8 | 52 | 4 | 56 | 6 | 54 |
| 300 | Cutoff | 36 | 24 | 38 | 22 | 34 | 26 |
| 375 | +25 | 56 | 4 | 52 | 8 | 54 | 6 |
| 450 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

EDDP – Cup Format – Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 4 | 56 | 8 | 52 | 6 | 54 |
| 300 | Cutoff | 36 | 24 | 34 | 26 | 38 | 22 |
| 375 | +25 | 56 | 4 | 52 | 8 | 54 | 6 |
| 450 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

EDDP – Cup Format – Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 4 | 56 | 6 | 54 | 8 | 52 |
| 300 | Cutoff | 36 | 24 | 34 | 26 | 32 | 28 |
| 375 | +25 | 54 | 6 | 56 | 4 | 52 | 8 |
| 450 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

{14}

Morphine – Dipcard Format – Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 4 | 56 | 8 | 52 | 6 | 54 |
| 300 | Cutoff | 36 | 24 | 38 | 22 | 34 | 26 |
| 375 | +25 | 52 | 8 | 56 | 4 | 54 | 6 |
| 450 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

Morphine – Dipcard Format – Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 6 | 54 | 8 | 52 | 4 | 56 |
| 300 | Cutoff | 32 | 28 | 36 | 24 | 34 | 26 |
| 375 | +25 | 54 | 6 | 56 | 4 | 52 | 8 |
| 450 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

Morphine – Cup Format – Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 6 | 54 | 4 | 56 | 6 | 54 |
| 300 | Cutoff | 38 | 22 | 34 | 26 | 36 | 24 |
| 375 | +25 | 52 | 8 | 54 | 6 | 56 | 4 |
| 450 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

{15}

Morphine – Cup Format – Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 6 | 54 | 4 | 56 | 8 | 52 |
| 300 | Cutoff | 36 | 24 | 36 | 24 | 34 | 26 |
| 375 | +25 | 56 | 4 | 54 | 6 | 52 | 8 |
| 450 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

Propoxyphene – Dipcard Format – Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 6 | 54 | 8 | 52 | 4 | 56 |
| 300 | Cutoff | 36 | 24 | 34 | 26 | 38 | 22 |
| 375 | +25 | 56 | 4 | 52 | 8 | 54 | 6 |
| 450 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

Propoxyphene – Dipcard Format – Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 4 | 56 | 6 | 54 | 8 | 52 |
| 300 | Cutoff | 34 | 26 | 32 | 28 | 36 | 24 |
| 375 | +25 | 52 | 8 | 56 | 4 | 54 | 6 |
| 450 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

{16}

Propoxyphene – Cup Format – Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 8 | 52 | 4 | 56 | 6 | 54 |
| 300 | Cutoff | 34 | 26 | 36 | 24 | 32 | 28 |
| 375 | +25 | 52 | 8 | 56 | 4 | 54 | 6 |
| 450 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

Propoxyphene – Cup Format – Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 75 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 150 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 225 | -25 | 8 | 52 | 6 | 54 | 4 | 56 |
| 300 | Cutoff | 32 | 28 | 36 | 24 | 34 | 26 |
| 375 | +25 | 56 | 4 | 54 | 6 | 54 | 6 |
| 450 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 525 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 600 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

TCA – Dipcard Format – Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 250 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 500 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 750 | -25 | 6 | 54 | 6 | 54 | 4 | 56 |
| 1000 | Cutoff | 38 | 22 | 34 | 26 | 34 | 26 |
| 1250 | +25 | 52 | 8 | 54 | 6 | 56 | 4 |
| 1500 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 1750 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 2000 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

{17}

TCA - Dipcard Format - Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 250 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 500 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 750 | -25 | 8 | 52 | 6 | 54 | 4 | 56 |
| 1000 | Cutoff | 38 | 22 | 36 | 24 | 34 | 26 |
| 1250 | +25 | 56 | 4 | 54 | 6 | 52 | 8 |
| 1500 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 1750 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 2000 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

TCA - Cup Format - Multi

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 250 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 500 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 750 | -25 | 6 | 54 | 8 | 52 | 6 | 54 |
| 1000 | Cutoff | 36 | 24 | 38 | 22 | 34 | 26 |
| 1250 | +25 | 54 | 6 | 56 | 4 | 52 | 8 |
| 1500 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 1750 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 2000 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

TCA - Cup Format - Single

| Conc (ng/mL) | % of cutoff | Lot 1 | | Lot 2 | | Lot 3 | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | Pos | Neg | Pos | Neg | Pos | Neg |
| 0 | Neg | 0 | 60 | 0 | 60 | 0 | 60 |
| 250 | -75 | 0 | 60 | 0 | 60 | 0 | 60 |
| 500 | -50 | 0 | 60 | 0 | 60 | 0 | 60 |
| 750 | -25 | 4 | 56 | 8 | 52 | 6 | 54 |
| 1000 | Cutoff | 36 | 24 | 34 | 26 | 34 | 26 |
| 1250 | +25 | 54 | 6 | 52 | 8 | 56 | 4 |
| 1500 | +50 | 60 | 0 | 60 | 0 | 60 | 0 |
| 1750 | +75 | 60 | 0 | 60 | 0 | 60 | 0 |
| 2000 | +100 | 60 | 0 | 60 | 0 | 60 | 0 |

b. Linearity/assay reportable range:

Not applicable. The assays are intended for qualitative use.

{18}

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

External control standards are not supplied with this device; labeling states where external control materials can be obtained.

Accelerated and real time studies have been conducted for The One Step Single/Multidrug Test Cup and the One Step Single/Multi-drug Test Dipcard devices. Protocols and acceptance criteria were reviewed and found to be acceptable. The information supports the following expiration date for the unopened (shelf-life) stability: 24 months under 4 - 30° C for both the Test Cup and Dipcard formats.

d. Detection limit:

Not applicable. The assays are intended for qualitative use.

e. Analytical specificity:

Cross reactivity with structurally similar compounds was tested for each device format. Each compound was spiked into drug-free urine to a final concentration of 100 µg/mL. Each sample was tested in 5 replicates. If any positive results were observed, samples were diluted down to the lowest concentration that produced a positive result. Results were as follows:

| Buprenorphine | Compound tested | Concentration (ng/mL) | % Cross-reactivity |
| --- | --- | --- | --- |
| | Buprenorphine | 10 | 100 |
| | Norbuprenorphine | 20 | 50 |
| | Buprenorphine 3-D-glucuronide | 15 | 66.7 |
| | Norbuprenorphine3-D-glucuronide | 200 | 5 |
| EDDP | Compound tested | Concentration (ng/mL) | % Cross-reactivity |
| --- | --- | --- | --- |
| | EDDP | 300 | 100 |
| | Methadone | 100,000 | 0 |

{19}

| Morphine | Compound tested | Concentration (ng/mL) | % Cross-reactivity |
| --- | --- | --- | --- |
| | Morphine | 300 | 100 |
| | Codeine | 300 | 100 |
| | Hydrocodone | 2000 | 15 |
| | Hydromorphone | 1500 | 20 |
| | 6-Monoacetyl morphine (6-MAM) | 750 | 40 |
| | Morphine 3-β-D-glucuronide | 300 | 100 |
| | Ethylmorphine | 3500 | 8.6 |
| | Heroin | 300 | 100 |
| | Levorphanol | 5000 | 6.0 |
| | Norcodeine | 7500 | 4.0 |
| | Oxycodone | 100,000 | 0.3 |
| | Thebain | 8000 | 3.8 |
| Propoxyphene | Compound tested | Concentration (ng/mL) | % Cross-reactivity |
| --- | --- | --- | --- |
| | d-Propoxyphene | 300 | 100 |
| | d-Norpropoxyphene | 300 | 100 |
| Tricyclic Antidepressants | Compound tested | Concentration (ng/mL) | % Cross-reactivity |
| --- | --- | --- | --- |
| | Nortriptyline | 1000 | 100 |
| | Nordoxepin | 1000 | 100 |
| | Trimipramine | 5000 | 20 |
| | Promazine | 3000 | 33.3 |
| | Desipramine | 1000 | 100 |
| | Imipramine | 1000 | 100 |
| | Chomipramine | 12500 | 8 |
| | Doxepin | 2000 | 50 |
| | Maprotiline | 2000 | 50 |
| | Amitriptyline | 1000 | 100 |

{20}

# Interference Study:

The following structurally unrelated compounds were spiked at $100\mu \mathrm{g / mL}$ into samples at $-50\%$ and $+50\%$ of the cutoff for each analyte. Each test format was evaluated. None of these compounds caused any interference at the concentration tested.

| Acetaminophen | Digoxin | Nadolol | Tetrahydrozoline |
| --- | --- | --- | --- |
| Acetophenetidin | Diphenhydramine | Nalidixic acid | Thiamine |
| Amoxicillin | Ephedrine | Naproxen | Thioridazine |
| Ampicillin | β-Estradiol | Niacinamide | d, l-Thyroxine |
| Aspirin | Estrone-3-sulfate | Nicotine | Tolbutamine |
| Atenolol | Ethyl-p-aminobenzoate | Nifedipine | Tolbutamide |
| Atorvastatin | Erythromycin | Norethindrone | Trifluoperazine |
| Azlocillin | Fenoprofen | Noscapine | Tryptamine |
| Benzylpenicillin | Flucloxacillin | d,l-Octopamine | Uric acid |
| Benzoic acid | Fluoxetine | Oxalic acid | Verapamil |
| Benzilic acid | Furosemide | Oxolinic acid | Zomepirac |
| Bilirubin | Gentisic acid | Oxymetazoline | |
| Benzydamine | Hemoglobin | Oxytetracycline | |
| Caffeine | Hydralazine | Papaverine | |
| Carbamezepine | Hydrochlorothiazide | Penicillin-G | |
| Cephalexin | Hydrocortisone | Pentazocine | |
| Chloralhydrate | o-Hydroxyhippuric acid | Perphenazine | |
| Chloramphenicol | p-Hydroxytyramine | Phenelzine | |
| Chlorothiazide | Ibuprofen | Prednisolone | |
| Chlorpheniramine | Indomethacin | Prednisone | |
| d,l-Chlorpromazine | Iproniazid | Promethazine | |
| Cholesterol | d,l-Isoproterenol | d,l-Propanolol | |
| Clonidine | Isoxsuprine | d-Pseudoephedrine | |
| Cimetidine | Ketamine | Quinacrine | |
| Citalopram | Ketoprofen | Quinine | |
| Cortisone | Labetalol | Quindine | |
| Creatinine | Lisinopril | Ranitidine | |
| Deoxycorticosterone | Loperamide | Salicylic acid | |
| Dexamethasone | Meperidine | Serotonin | |
| Dextromethorphan | Meprobamate | Sulfamethazine | |
| Diclofenac | Methoxyphenamine | Sulindac | |
| Diflunisal | Methylphenidate | Tetracycline | |

{21}

Each device was also evaluated for interference from pH. Drug-free urine was adjusted to ± 50% cutoffs which were confirmed by GC/MS or LC/MS. Each test format was used for the study. The pH was tested at 3, 4, 5, 6, 7, 8, and 9. No interference from pH was observed.

Each device was evaluated for interference from specific gravity. Drug-free urine was adjusted to ± 50% cutoffs which were confirmed by GC/MS or LC/MS. Each test format was used for the study. Specific gravity was tested at 1.003, 1.010, 1.020, 1.030, and 1.040. No interference from specific gravity was observed.

f. Assay cut-off:

The cut-off characterization study results can be found in the precision section 1.M.1.a above.

2. Comparison studies:

a. Method comparison with predicate device:

Eighty clinical urine samples collected from several hospitals and a drug relief reformatory. All samples were unaltered clinical specimens and the concentrations were confirmed by GC/MS, LC/MS, or HPLC. Each sample was split between two individuals. All aliquots were blindly labeled by a nonparticipant, and randomized prior to testing such that a different sample was used each time testing was performed. Testing was conducted by four nurses at two POC sites.

Buprenorphine - Dipcard Format - Multi

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | *1 | 5 | 35 |
| Neg | 35 | 4 | 0 | 0 |

*Analysis of Discordant Results – LC/MS concentration 7.8 ng/mL buprenorphine

{22}

Buprenorphine - Dipcard Format - Single

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | *1 | 5 | 35 |
| Neg | 35 | 4 | 0 | 0 |

*Analysis of Discordant Results – LC/MS concentration 7.8 ng/mL buprenorphine

Buprenorphine - Cup Format - Multiple

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | *1 | 5 | 35 |
| Neg | 35 | 4 | 0 | 0 |

*Analysis of Discordant Results – LC/MS concentration 7.8 ng/mL buprenorphine

Buprenorphine - Cup Format - Single

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | *1 | 5 | 35 |
| Neg | 35 | 4 | 0 | 0 |

*Analysis of Discordant Results – LC/MS concentration 7.8 ng/mL buprenorphine

{23}

EDDP - Dipcard Format - Multiple

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | *1 | 7 | 33 |
| Neg | 34 | 5 | 0 | 0 |

*Analysis of Discordant Results – GC/MS concentration 285 ng/mL EDDP

EDDP - Dipcard Format - Single

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | *1 | 7 | 33 |
| Neg | 34 | 5 | 0 | 0 |

*Analysis of Discordant Results – GC/MS concentration 285 ng/mL EDDP

EDDP - Cup Format - Multi

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | *1 | 7 | 33 |
| Neg | 34 | 5 | 0 | 0 |

*Analysis of Discordant Results – GC/MS concentration 285 ng/mL EDDP

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EDDP - Cup Format - Single

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | *1 | 7 | 33 |
| Neg | 34 | 5 | 0 | 0 |

*Analysis of Discordant Results – GC/MS concentration 285 ng/mL EDDP

Morphine - Dipcard Format - Multi

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | *1 | 5 | 35 |
| Neg | 33 | 6 | 0 | 0 |

*Analysis of Discordant Results – GC/MS concentration 275 ng/mL Morphine

Morphine - Dipcard Format - Single

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | *1 | 5 | 35 |
| Neg | 33 | 6 | 0 | 0 |

*Analysis of Discordant Results – GC/MS concentration 275 ng/mL Morphine

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Morphine - Cup Format - multi

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | 1 | 5 | 35 |
| Neg | 33 | 6 | 0 | 0 |

*Analysis of Discordant Results – GC/MS concentration 275 ng/mL Morphine

Morphine - Cup Format - single

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | 1 | 5 | 35 |
| Neg | 33 | 6 | 0 | 0 |

*Analysis of Discordant Results – GC/MS concentration 275 ng/mL Morphine

Propoxyphene - Dipcard Format - multi

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | *1 | 6 | 34 |
| Neg | 34 | 5 | 0 | 0 |

*Analysis of Discordant Results – GC/MS concentration 269 ng/mL Propoxyphene

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Propoxyphene - Dipcard Format - single

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | *1 | 6 | 34 |
| Neg | 34 | 5 | 0 | 0 |

*Analysis of Discordant Results – GC/MS concentration 269 ng/mL Propoxyphene

Propoxyphene - Cup Format - multi

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | *1 | 6 | 34 |
| Neg | 34 | 5 | 0 | 0 |

*Analysis of Discordant Results – GC/MS concentration 269 ng/mL Propoxyphene

Propoxyphene - Cup Format - single

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | *1 | 6 | 34 |
| Neg | 34 | 5 | 0 | 0 |

*Analysis of Discordant Results – GC/MS concentration 269 ng/mL Propoxyphene

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TCA - Dipcard Format - multi

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | 0 | 5 | 34 |
| Neg | 35 | 5 | *1 | 0 |

*Analysis of Discordant Results – HPLC concentration 1138 ng/mL Nortriptyline

TCA - Dipcard Format - single

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | 0 | 5 | 34 |
| Neg | 35 | 5 | *1 | 0 |

*Analysis of Discordant Results – HPLC concentration 1138 ng/mL Nortriptyline

TCA - Cup Format - Multi

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | 0 | 5 | 34 |
| Neg | 35 | 5 | *1 | 0 |

*Analysis of Discordant Results – HPLC concentration 1138 ng/mL Nortriptyline

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TCA - Cup Format - Single

| Candidate device result | Negative | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration) | High Positive (greater than 50% above the cutoff concentration) |
| --- | --- | --- | --- | --- |
| Pos | 0 | 0 | 5 | 34 |
| Neg | 35 | 5 | *1 | 0 |

*Analysis of Discordant Results - HPLC concentration 1138 ng/mL Nortriptyline

b. Matrix comparison:

Not applicable. The assay is intended to be used with urine samples only.

# 3. Clinical studies:

a. Clinical Sensitivity:

Not applicable.

b. Clinical specificity:

Not applicable.

c. Other clinical supportive data (when a. and b. are not applicable):

Consumer study:

Three hundred and sixty (360) lay users were divided into two groups to test the multi-version of the test devices. One group tested with the Dipcard format, and the other group tested with the Cup format. Each lay user was provided with the package insert (in English), one blind labeled sample, and a device. Results of the lay user study are presented below.

Buprenorphine

| Conc (ng/mL) | % of cutoff | n | Dipcard | | Cup | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | Pos | Neg | Pos | Neg |
| 0 | Neg | 60 | 0 | 60 | 0 | 60 |
| 5 | -50% | 60 | 0 | 60 | 0 | 60 |
| 7.5 | -25% | 60 | 7 | 53 | 8 | 52 |
| 12.5 | +25% | 60 | 55 | 5 | 53 | 7 |
| 15 | +50% | 60 | 57 | 3 | 58 | 2 |
| 20 | +100% | 60 | 60 | 0 | 60 | 0 |

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EDDP

| Conc (ng/mL) | % of cutoff | n | Dipcard | | Cup | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | Pos | Neg | Pos | Neg |
| 0 | Neg | 60 | 0 | 60 | 0 | 60 |
| 150 | -50% | 60 | 0 | 60 | 0 | 60 |
| 225 | -25% | 60 | 6 | 54 | 5 | 55 |
| 375 | +25% | 60 | 57 | 3 | 52 | 8 |
| 450 | +50% | 60 | 60 | 0 | 58 | 2 |
| 600 | +100% | 60 | 60 | 0 | 60 | 0 |

Morphine

| Conc (ng/mL) | % of cutoff | n | Dipcard | | Cup | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | Pos | Neg | Pos | Neg |
| 0 | Neg | 60 | 0 | 60 | 0 | 60 |
| 150 | -50% | 60 | 0 | 60 | 0 | 60 |
| 225 | -25% | 60 | 2 | 58 | 3 | 57 |
| 375 | +25% | 60 | 54 | 6 | 52 | 8 |
| 450 | +50% | 60 | 59 | 1 | 58 | 2 |
| 600 | +100% | 60 | 60 | 0 | 60 | 0 |

Propoxyphene

| Conc (ng/mL) | % of cutoff | n | Dipcard | | Cup | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | Pos | Neg | Pos | Neg |
| 0 | Neg | 60 | 0 | 60 | 0 | 60 |
| 150 | -50% | 60 | 0 | 60 | 0 | 60 |
| 225 | -25% | 60 | 5 | 55 | 7 | 53 |
| 375 | +25% | 60 | 54 | 6 | 56 | 4 |
| 450 | +50% | 60 | 58 | 2 | 60 | 0 |
| 600 | +100% | 60 | 60 | 0 | 60 | 0 |

TCA

| Conc (ng/mL) | % of cutoff | n | Dipcard | | Cup | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | Pos | Neg | Pos | Neg |
| 0 | Neg | 60 | 0 | 60 | 0 | 60 |
| 500 | -50% | 60 | 0 | 60 | 0 | 60 |
| 750 | -25% | 60 | 3 | 57 | 4 | 56 |
| 1250 | +25% | 60 | 55 | 5 | 54 | 6 |
| 1500 | +50% | 60 | 59 | 1 | 60 | 0 |
| 2000 | +100% | 60 | 60 | 0 | 60 | 0 |

The original consumer study data showed some negative results in specimens containing drug concentrations at $+50\%$ above the cutoff. A root cause analysis was conducted by the

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sponsor to determine the cause of these results. The root cause was identified to be inconsistent and inadequate volume of aliquoted samples. The sponsor revised the consumer study protocol to specify a larger sample volume per vial and supplemental consumer studies were conducted to verify that the root cause was correctly identified. Results of the supplemental consumer studies were as follows:

Buprenorphine

| Conc (ng/mL) | % of cutoff | n | Dipcard | | Cup | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | Pos | Neg | Pos | Neg |
| 0 | Neg | 60 | 0 | 60 | 0 | 60 |
| 5 | -50% | 60 | 0 | 60 | 0 | 60 |
| 7.5 | -25% | 60 | 4 | 56 | 6 | 54 |
| 12.5 | +25% | 60 | 57 | 3 | 55 | 5 |
| 15 | +50% | 60 | 60 | 0 | 60 | 0 |
| 20 | +100% | 60 | 60 | 0 | 60 | 0 |

EDDP

| Conc (ng/mL) | % of cutoff | n | Dipcard | | Cup | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | Pos | Neg | Pos | Neg |
| 0 | Neg | 60 | 0 | 60 | 0 | 60 |
| 150 | -50% | 60 | 0 | 60 | 0 | 60 |
| 225 | -25% | 60 | 5 | 55 | 4 | 56 |
| 375 | +25% | 60 | 54 | 6 | 57 | 3 |
| 450 | +50% | 60 | 60 | 0 | 60 | 0 |
| 600 | +100% | 60 | 60 | 0 | 60 | 0 |

Morphine

| Conc (ng/mL) | % of cutoff | n | Dipcard | | Cup | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | Pos | Neg | Pos | Neg |
| 0 | Neg | 60 | 0 | 60 | 0 | 60 |
| 150 | -50% | 60 | 0 | 60 | 0 | 60 |
| 225 | -25% | 60 | 4 | 56 | 5 | 55 |
| 375 | +25% | 60 | 56 | 4 | 58 | 2 |
| 450 | +50% | 60 | 60 | 0 | 60 | 0 |
| 600 | +100% | 60 | 60 | 0 | 60 | 0 |

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32

Propoxyphene

| Conc (ng/mL) | % of cutoff | n | Dipcard | | Cup | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | Pos | Neg | Pos | Neg |
| 0 | Neg | 60 | 0 | 60 | 0 | 60 |
| 150 | -50% | 60 | 0 | 60 | 0 | 60 |
| 225 | -25% | 60 | 5 | 55 | 3 | 57 |
| 375 | +25% | 60 | 56 | 4 | 54 | 6 |
| 450 | +50% | 60 | 60 | 0 | 60 | 0 |
| 600 | +100% | 60 | 60 | 0 | 60 | 0 |

TCA

| Conc (ng/mL) | % of cutoff | n | Dipcard | | Cup | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | Pos | Neg | Pos | Neg |
| 0 | Neg | 60 | 0 | 60 | 0 | 60 |
| 500 | -50% | 60 | 0 | 60 | 0 | 60 |
| 750 | -25% | 60 | 6 | 54 | 2 | 58 |
| 1250 | +25% | 60 | 53 | 7 | 55 | 5 |
| 1500 | +50% | 60 | 60 | 0 | 60 | 0 |
| 2000 | +100% | 60 | 60 | 0 | 60 | 0 |

After testing, each participant was asked to fill out a questionnaire assessing ease of use of the devices. A large majority of the respondents stated that the test was easy to use and that the instructions were clear.

4. Clinical cut-off:
Not applicable

5. Expected values/Reference range:
Not applicable

N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.