LZI OXYCODONE HOMOGENEOUS ENZYME IMMUNOASSAY, LZI OXYCONDONE CALIBRATORS, LZI OXYCODONE CONTROLS

K120763 · Lin-Zhi International, Inc. · DJG · Jun 1, 2012 · Clinical Toxicology

Device Facts

• Record ID: K120763
• Device Name: LZI OXYCODONE HOMOGENEOUS ENZYME IMMUNOASSAY, LZI OXYCONDONE CALIBRATORS, LZI OXYCODONE CONTROLS
• Applicant: Lin-Zhi International, Inc.
• Product Code: DJG · Clinical Toxicology
• Decision Date: Jun 1, 2012
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3650
• Device Class: Class 2

Indications for Use

The LZI Oxycodone Enzyme Immunoassay is intended for the qualitative and semiquantitative determination of Oxycodone in human urine at the cutoff values of 100 and 300 ng/mL. The assay is designed for professional use with a number of automated clinical chemistry analyzers. The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GCMS and LCMS or (2) permitting laboratories to establish quality control procedures. The LZI Oxycodone Drugs of Abuse (DAU) Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Oxycodone Enzyme Immunoassay at the cutoff values of 100 and 300 ng/mL. The LZI Oxycodone Drugs of Abuse (DAU) Controls are for use as assayed quality control materials to monitor the precision of the LZI Oxycodone Enzyme Immunoassay at the cutoff value of 100 and 300 ng/mL. The assay provides only a preliminary analytical result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas or liquid chromatography/mass spectrometry (GC/MS or LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.

Device Story

Homogeneous enzyme immunoassay for detection of oxycodone in human urine; utilizes competitive binding between drug in sample and G6PDH-labeled drug for fixed antibody amount. Enzyme activity inversely proportional to drug concentration; active enzyme converts NAD to NADH, measured spectrophotometrically at 340 nm. Used in clinical laboratories on automated chemistry analyzers (e.g., Hitachi 717) by trained technicians. Provides preliminary screening results; requires confirmation by GC/MS or LC/MS. Assists clinicians in identifying potential drug presence for further diagnostic or forensic evaluation.

Clinical Evidence

Bench testing only. Precision evaluated using 88 determinations per concentration level. Method comparison performed on 89 clinical samples (100 ng/mL cutoff) and 101 clinical samples (300 ng/mL cutoff) against GC/MS or LC/MS. 100 ng/mL cutoff showed 93.75% positive agreement and 100% negative agreement. 300 ng/mL cutoff showed 96.1% positive agreement and 98.0% negative agreement. Linearity (0-800 ng/mL) confirmed with r2 = 0.998.

Technological Characteristics

Homogeneous enzyme immunoassay; reagents include mouse monoclonal anti-oxycodone antibody, G6PDH-labeled oxycodone, G6P, NAD, and sodium azide preservative. Spectrophotometric detection at 340 nm. Designed for automated clinical chemistry analyzers. Storage at 2-8 °C.

Indications for Use

Indicated for qualitative and semiquantitative determination of Oxycodone in human urine at 100 and 300 ng/mL cutoffs. For professional use in clinical laboratories. No specific age or gender restrictions.

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

• LZI Oxycodone Enzyme Immunoassay (k050733)

Submission Summary (Full Text)

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

A. 510(k) Number:
k120763

B. Purpose for Submission:
Modification to a previously cleared device (k050733) using a new mouse monoclonal anti-Oxycodone antibody

C. Measurand:
Oxycodone

D. Type of Test:
Qualitative or semi-quantitative enzyme immunoassay

E. Applicant:
Lin-Zhi International, Inc.

F. Proprietary and Established Names:
LZI Oxycodone Enzyme Immunoassay
LZI Oxycodone Drug of Abuse Calibrators
LZI Oxycodone Drug of Abuse Controls

G. Regulatory Information:
| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| DJG – enzyme immunoassay, opiates | II | 862.3650 | 91-Toxicology |
| DLJ -Clinical toxicology calibrator | II | 862.3200 | 91- Toxicology |
| LAS -Clinical toxicology control material | I, reserved | 862.3280 | 91- Toxicology |

H. Intended Use:
1. Intended use(s):

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See Indications for use below.

2. **Indication(s) for use:**

The LZI Oxycodone Enzyme Immunoassay is intended for the qualitative and semi-quantitative determination of oxycodone in human urine at the cutoff values of 100 and 300 ng/mL. The assay is designed for professional use with a number of automated clinical chemistry analyzers.

The semi-quantitative mode is for purposes of (1) enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as GCMS and LCMS or (2) permitting laboratories to establish quality control procedures.

The LZI Oxycodone Drug of Abuse (DAU) Calibrators are for use as calibrators in the qualitative and semi-quantitative calibration of the LZI Oxycodone Enzyme Immunoassay.

The LZI Oxycodone Drug of Abuse (DAU) Controls are for use as assayed quality control materials to monitor the precision of the LZI Oxycodone Enzyme Immunoassay.

The assay provides only a preliminary analytical result. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. Gas or Liquid Chromatography/Mass Spectrometry (GC/MS or LC/MS) is the preferred confirmatory method. Clinical consideration and professional judgment should be exercised with any drug of abuse test result, particularly when the preliminary test result is positive.

3. **Special conditions for use statement(s):**

For prescription use only.

Positive results should be confirmed by other affirmative, analytical methods (e.g., chromatography), and preferably GC/MS or LC/MS.

The test is designed for use with human urine only.

4. **Special instrument requirements:**

Performance characteristics have been validated on the Hitachi 717.

I. **Device Description:**

The assay consists of ready-to-use liquid reagents. Reagent 1 contains a mouse monoclonal anti-oxycodone antibody, glucose-6-phosphate (G6P), nicotinamide

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adenine dinucleotide (NAD), stabilizers and sodium azide (0.09%) as a preservative. Reagent 2 contains glucose-6-phosphate dehydrogenase (G6PDH) labeled with oxycodone in buffer with sodium azide (0.09%) as preservative.

The calibrators and controls are sold separately. The calibrator has 6 levels and the control has 4 levels. They consist of human urine samples containing oxycodone with sodium azide (0.09%) as preservative.

## J. Substantial Equivalence Information:

1. Predicate device name(s):

LZI Oxycodone Enzyme Immunoassay

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

k050733

3. Comparison with predicate:

| Items | LZI Oxycodone Enzyme Immunoassay (Candidate Device) | LZI Oxycodone Enzyme Immunoassay (Predicate Device) |
| --- | --- | --- |
| Similarity | | |
| Intended use /Indication for use | Same | Qualitative and semi-quantitative determination of Oxycodone in human urine. |
| Sample type | Same | Urine |
| Calibrated against | Same | Oxycodone |
| Test Principle | Same | Competitive enzyme immunoassay |
| Cutoff | Same | 100 or 300 ng/mL |
| Control Levels | Same | 100 ng/mL cutoff: 75, 125 ng/mL
300 ng/mL cutoff: 225, 375ng/mL |
| Difference | | |
| Antibody | Different mouse monoclonal anti-Oxycodone antibody | mouse monoclonal anti-Oxycodone antibody |
| Calibrator Levels | 0, 50, 100, 300, 500, 800 ng/mL | 100 ng/mL cutoff: 0, 75, 100, 225, 300 ng/mL
300 ng/mL cutoff: 0, 100, 300, 500, 800 ng/mL |

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

CLSI EP5-A, Evaluation of precision performance of clinical chemistry devices.

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L. Test Principle:

The assay is based on competition between drug in the sample and drug labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for a fixed amount of antibody in the reagent. Enzyme activity decreases upon binding to the antibody, and the drug concentration in the sample is measured in terms of enzyme activity. In the absence of drug in the sample, oxycodone-labeled G6PDH conjugate is bound to antibody, and the enzyme activity is inhibited. On the other hand, when drug is present in the sample, antibody binds to the free drug; the unbound oxycodone-labeled G6PDH then exhibits its maximal enzyme activity.

Active enzyme converts nicotinamide adenine dinucleotide (NAD) to NADH, resulting in an absorbance change that can be measured spectrophotometrically at 340 nm.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Precision of the qualitative and semi-quantitative assays was evaluated by assaying calibrator and control material in replicates of 2, two runs a day for 22 days on one Hitachi 717 analyzer (n =88 per sample). Results are summarized below for each cutoff for qualitative and semi-quantitative protocols.

Semi-Quantitative

| 100 ng/mL Cutoff Result: | | Within Run | | Total Precision | |
| --- | --- | --- | --- | --- | --- |
| Sample Concentration | % of Cutoff | Number of Determination | Immunoassay Result | Number of Determination | Immunoassay Result |
| 0 ng/mL | -100.0% | 22 | 22 Negative | 88 | 88 Negative |
| 25 ng/mL | -75.0% | 22 | 22 Negative | 88 | 88 Negative |
| 50 ng/mL | -50.0% | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | -25.0% | 22 | 22 Negative | 88 | 88 Negative |
| 100 ng/mL | 100.0% | 22 | 9 Pos/13 Neg | 88 | 39 Pos/49 Neg |
| 125 ng/mL | +25.0% | 22 | 22 Positive | 88 | 88 Positive |
| 150 ng/mL | +50.0% | 22 | 22 Positive | 88 | 88 Positive |
| 175 ng/mL | +75.0% | 22 | 22 Positive | 88 | 88 Positive |
| 200 ng/mL | +100.0% | 22 | 22 Positive | 88 | 88 Positive |
| 300 ng/mL Cutoff Result: | | Within Run | | Total Precision | |
| --- | --- | --- | --- | --- | --- |
| Sample Concentration | % of Cutoff | Number of Determination | Immunoassay Result | Number of Determination | Immunoassay Result |

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| 0 ng/mL | -100.0% | 22 | 22 Negative | 88 | 88 Negative |
| --- | --- | --- | --- | --- | --- |
| 75 ng/mL | -75.0% | 22 | 22 Negative | 88 | 88 Negative |
| 150 ng/mL | -50.0% | 22 | 22 Negative | 88 | 88 Negative |
| 225 ng/mL | -25.0% | 22 | 22 Negative | 88 | 88 Negative |
| 300 ng/mL | 100.0% | 22 | 3 Pos/ 19 Neg | 88 | 26 Pos/ 62 Neg |
| 375 ng/mL | +25.0% | 22 | 22 Positive | 88 | 88 Positive |
| 450 ng/mL | +50.0% | 22 | 22 Positive | 88 | 88 Positive |
| 525 ng/mL | +75.0% | 22 | 22 Positive | 88 | 88 Positive |
| 600 ng/mL | +100.0% | 22 | 22 Positive | 88 | 88 Positive |

Qualitative

| 100 ng/mL Cutoff Result: | | Within Run | | Total Precision | |
| --- | --- | --- | --- | --- | --- |
| Sample Concentration | % of Cutoff | Number of Determination | Immunoassay Result | Number of Determination | Immunoassay Result |
| 0 ng/mL | -100.0% | 22 | 22 Negative | 88 | 88 Negative |
| 25 ng/mL | -75.0% | 22 | 22 Negative | 88 | 88 Negative |
| 50 ng/mL | -50.0% | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | -25.0% | 22 | 22 Negative | 88 | 88 Negative |
| 100 ng/mL | 100.0% | 22 | 6 Pos/ 16 Neg | 88 | 25 Pos/63 Neg |
| 125 ng/mL | +25.0% | 22 | 22 Positive | 88 | 88 Positive |
| 150 ng/mL | +50.0% | 22 | 22 Positive | 88 | 88 Positive |
| 175 ng/mL | +75.0% | 22 | 22 Positive | 88 | 88 Positive |
| 200 ng/mL | +100.0% | 22 | 22 Positive | 88 | 88 Positive |
| 300 ng/mL Cutoff Result: | | Within Run | | Total Precision | |
| --- | --- | --- | --- | --- | --- |
| Sample Concentration | % of Cutoff | Number of Determination | Immunoassay Result | Number of Determination | Immunoassay Result |
| 0 ng/mL | -100.0% | 22 | 22 Negative | 88 | 88 Negative |
| 75 ng/mL | -75.0% | 22 | 22 Negative | 88 | 88 Negative |
| 150 ng/mL | -50.0% | 22 | 22 Negative | 88 | 88 Negative |
| 225 ng/mL | -25.0% | 22 | 22 Negative | 88 | 88 Negative |
| 300 ng/mL | 100.0% | 22 | 1 Pos/21 Neg | 88 | 23 Pos/65 Neg |
| 375 ng/mL | +25.0% | 22 | 22 Positive | 88 | 88 Positive |
| 450 ng/mL | +50.0% | 22 | 22 Positive | 88 | 88 Positive |
| 525 ng/mL | +75.0% | 22 | 22 Positive | 88 | 88 Positive |
| 600 ng/mL | +100.0% | 22 | 22 Positive | 88 | 88 Positive |

Conclusion:
All samples spiked at levels below the cutoff detected as negative and all samples spiked at levels above the cutoff detected as positive.

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b. Linearity/assay reportable range:

Linearity across the range was tested by spiking negative urine samples to increasing concentrations within the calibration ranges listed in the table below. Each sample was assayed in replicates of 10 in the semi-quantitative mode using all 6 calibrators for 100 ng/mL and 300 ng/mL cutoffs (0, 50, 100, 300, 500, 800 ng/mL). The results were averaged and compared to the expected result and the percent recovery was calculated.

| Target Concentration (ng/mL) | Determined Concentration (ng/mL) | % Recovery |
| --- | --- | --- |
| 800 | 801.4 | 100.2 |
| 700 | 657.1 | 93.9 |
| 600 | 585.3 | 97.6 |
| 500 | 494.4 | 98.9 |
| 400 | 383.9 | 96.0 |
| 300 | 302.9 | 101.0 |
| 200 | 190.5 | 95.2 |
| 100 | 102.2 | 102.2 |
| 50 | 50.4 | 100.8 |
| 0 | 1.6 | N/A |

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

Traceability

The controls and calibrators are prepared using commercially available Oxycodone standard the accuracy of which is ensured by purity determinations and gravimetric preparation using balances calibrated with NIST traceable weight. Concentration of drug in the controls and calibrators are confirmed by GC/MS analysis.

Stability

Real time testing is on going. Protocol and acceptance criterion were described and found to be acceptable. Data obtained so far support 41 weeks of product stability at 2-8°C for the calibrators and controls.

d. Detection limit:

Not applicable

e. Analytical specificity:

Cross-reactivity:

The parent drug, metabolites, and drugs commonly found in samples were

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tested for cross-reactivity with the assay. Test compounds were spiked into GC/MS verified negative urine and each sample was evaluated against the cut-off calibrators. The percent cross-reactivity of those compounds are presented below:

Structurally Related Oxycodone Compounds: 100 ng/mL Cutoff

| Compound | Equivalent Conc. to 100 ng/mL | Dose | % Cross Reactivity |
| --- | --- | --- | --- |
| | ng/mL | ng/mL | |
| Oxycodone | 100 | 110.4 | 110.40% |
| Hydrocodone | 22,300 | 129.6 | 0.58% |
| Hydromorphone | 14,100 | 95.6 | 0.68% |
| Oxymorphone | 200 | 117.3 | 58.65% |
| Noroxycodone | 1,100 | 106.7 | 9.70% |
| Noroxymorphone | 1,000 | 119.6 | 11.96% |
| Codeine | 60,000 | 95.3 | 0.16% |
| Dextromethorphan | 1,000,000 | 113.4 | 0.01% |
| Dihydrocodeine | 250,000 | 90.9 | 0.04% |
| Levorphanol | 60,000 | 100.1 | 0.17% |
| Naloxone | 9,000 | 84.1 | 0.93% |
| Norcodeine | 1,000,000 | 210.0 | 0.02% |
| Morphine | 50,000 | 111.3 | 0.22% |
| Oxymorphone-Glucuronide | 85 | 115.5 | 135.88% |
| Codeine-6-b-Glucuronide | 5,000 | 2.8 | 0.06% |
| Morphine-3-Glucoronide | 250,000 | 19.4 | 0.01% |
| 6-AM | 62,100 | 4.8 | 0.01% |
| NorBuprenorphine | 100,000 | 3.6 | 0.00% |

Structurally Unrelated Compounds: 100 ng/mL Cutoff

| Compound | (ng/mL) | Oxycodone Concentration | | |
| --- | --- | --- | --- | --- |
| | | 0 ng/mL | 75 ng/mL Control | 125 ng/mL Control |
| Acetaminophen | 500,000 | Neg | Neg | Pos |
| Acetylsalicylic acid | 500,000 | Neg | Neg | Pos |
| Amobarbital | 500,000 | Neg | Neg | Pos |
| Benzoylecgonine | 500,000 | Neg | Neg | Pos |
| Bromopheniramine | 100,000 | Neg | Neg | Pos |
| Bupropion | 500,000 | Neg | Neg | Pos |
| Caffeine | 500,000 | Neg | Neg | Pos |
| Chlorpheniramine | 500,000 | Neg | Neg | Pos |
| Chlorpromazine | 500,000 | Neg | Neg | Pos |
| d-l Phenylpropanolamine (Phenethylamine) | 250,000 | Neg | Neg | Pos |
| d-Ephedrine | 500,000 | Neg | Neg | Pos |
| l-Ephedrine | 300,000 | Neg | Neg | Pos |
| d- | 250,000 | Neg | Neg | Pos |

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| Methamphetamine | | | | |
| --- | --- | --- | --- | --- |
| Ecgonine (Ecgonine Methyl-ester) | 500,000 | Neg | Neg | Pos |
| Meperidine | 500,000 | Neg | Neg | Pos |
| Methadone | 500,000 | Neg | Neg | Pos |
| Nicotine | 500,000 | Neg | Neg | Pos |
| Norpropoxyphene | 100,000 | Neg | Neg | Pos |
| Phencyclidine | 250,000 | Neg | Neg | Pos |
| Promethiazine | 500,000 | Neg | Neg | Pos |
| Propranolol | 100,000 | Neg | Neg | Pos |
| Secobarbital | 500,000 | Neg | Neg | Pos |
| Trazodone | 500,000 | Neg | Neg | Pos |
| Tyramine | 500,000 | Neg | Neg | Pos |
| Valproic acid | 500,000 | Neg | Neg | Pos |

**Structurally Related Oxycodone Compounds: 300 ng/mL Cutoff**

| Compound | Equivalent Conc. to 300 ng/mL | Dose | % Cross Reactivity |
| --- | --- | --- | --- |
| | ng/mL | ng/mL | |
| Oxycodone | 300 | 306.2 | 102.07% |
| Hydrocodone | 66,000 | 302.1 | 0.46% |
| Hydromorphone | 41,800 | 227.7 | 0.54% |
| Oxymorphone | 650 | 372.2 | 57.26% |
| Noroxycodone | 3,100 | 225.3 | 7.27% |
| Noroxymorphone | 4,700 | 309.7 | 6.59% |
| Codeine | 250,000 | 268.0 | 0.11% |
| Dextromethorphan | 4,500,000 | 304.2 | 0.01% |
| Dihydrocodeine | 1,100,000 | 285.7 | 0.03% |
| Levorphanol | 300,000 | 367.6 | 0.12% |
| Naloxone | 20,000 | 319.4 | 1.60% |
| Norcodeine | 2,500,000 | 352.6 | 0.01% |
| Morphine | 125,000 | 313.8 | 0.25% |
| Oxymorphone-Glucuronide | 200 | 306.3 | 153.15% |
| Codeine-6-b-Glucuronide | 10,000 | 2.45 | 0.02% |
| Morphine-3-Glucoronide | 183,600 | 17.3 | 0.01% |
| 6-AM | 100,000 | 3.1 | 0.00% |
| NorBuprenorphine | 500,000 | 35.8 | 0.01% |
| Morphine-3-Glucose | 300 | 306.2 | 102.07% |

**Structurally Unrelated Compounds: 300 ng/mL Cutoff**

| Compound | (ng/mL) | Oxycodone Concentration | | |
| --- | --- | --- | --- | --- |
| | | 0 ng/mL | 225 ng/mL Control | 375 ng/mL Control |
| Acetaminophen | 500,000 | Neg | Neg | Pos |
| Acetylsalicylic acid | 500,000 | Neg | Neg | Pos |
| Amobarbital | 500,000 | Neg | Neg | Pos |

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| Benzoylecgonine | 500,000 | Neg | Neg | Pos |
| --- | --- | --- | --- | --- |
| Bromopheniramine | 100,000 | Neg | Neg | Pos |
| Bupropion | 500,000 | Neg | Neg | Pos |
| Caffeine | 500,000 | Neg | Neg | Pos |
| Chlorpheniramine | 500,000 | Neg | Neg | Pos |
| Chlorpromazine | 500,000 | Neg | Neg | Pos |
| d-1
Phenylpropanolamine
(Phenethylamine) | 250,000 | Neg | Neg | Pos |
| d-Ephedrine | 500,000 | Neg | Neg | Pos |
| l-Ephedrine | 300,000 | Neg | Neg | Pos |
| d-Methamphetamine | 250,000 | Neg | Neg | Pos |
| Ecgonine (Ecgonine
Methyl-ester) | 500,000 | Neg | Neg | Pos |
| Meperidine | 500,000 | Neg | Neg | Pos |
| Methadone | 500,000 | Neg | Neg | Pos |
| Nicotine | 500,000 | Neg | Neg | Pos |
| Norpropoxyphene | 100,000 | Neg | Neg | Pos |
| Phencyclidine | 250,000 | Neg | Neg | Pos |
| Promethiazine | 500,000 | Neg | Neg | Pos |
| Propranolol | 100,000 | Neg | Neg | Pos |
| Secobarbital | 500,000 | Neg | Neg | Pos |
| Trazodone | 500,000 | Neg | Neg | Pos |
| Tyramine | 500,000 | Neg | Neg | Pos |
| Valproic acid | 500,000 | Neg | Neg | Pos |

## Interference

The potential effect of endogenous compounds and pH on the recovery of Oxycodone was assessed by spiking known amounts of potentially interfering substances into GC/MS verified negative urine and urine samples with Oxycodone concentrations +/- 25% of the assay cut-off. Substances were determined not to interfere with the assay if the recovery of the negative sample was below the assay cut-off and if the +/-25% samples recovered within 10% of a sample containing no interferent.

100 ng/mL cutoff

| Interfering Substances | Spiked Conc. mg/dL | 0 ng/mL | 75 ng/mL Control | 125 ng/mL Control |
| --- | --- | --- | --- | --- |
| | | | | |
| Acetone | 1000 | Neg | Neg | Pos |
| Ascorbic Acid | 400 | Neg | Neg | Pos |
| Creatinine | 500 | Neg | Neg | Pos |
| Ethanol | 1000 | Neg | Neg | Pos |
| Galactose | 10 | Neg | Neg | Pos |
| r-Globulin | 500 | Neg | Neg | Pos |
| Glucose | 1500 | Neg | Neg | Pos |

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| Hemoglobin | 300 | Neg | Neg | Pos |
| --- | --- | --- | --- | --- |
| HSA* | 500 | Neg | Neg | Pos |
| Sodium Chloride | 3000 | Neg | Neg | Pos |
| Oxalic Acid | 100 | Neg | Neg | Pos |
| Urea | 2000 | Neg | Neg | Pos |
| pH 3 | | Neg | Neg | Pos |
| pH 4 | | Neg | Neg | Pos |
| pH 5 | | Neg | Neg | Pos |
| pH 6 | | Neg | Neg | Pos |
| pH 7 | | Neg | Neg | Pos |
| pH 8 | | Neg | Neg | Pos |
| pH 9 | | Neg | Neg | Pos |
| pH 10 | | Neg | Neg | Pos |
| pH 11 | | Neg | Neg | Pos |

*Human Serum Albumin

300 ng/mL cutoff

| Interfering Substances | Spiked Conc. | 0 ng/mL | 225 ng/mL Control | 375 ng/mL Control* |
| --- | --- | --- | --- | --- |
| | mg/dL | ng/mL | ng/mL | ng/mL |
| Acetone | 1000 | Neg | Neg | Pos |
| Ascorbic Acid | 400 | Neg | Neg | Pos |
| Creatinine | 500 | Neg | Neg | Pos |
| Ethanol | 1000 | Neg | Neg | Pos |
| Galactose | 10 | Neg | Neg | Pos |
| r-Globulin | 500 | Neg | Neg | Pos |
| Glucose | 1500 | Neg | Neg | Pos |
| Hemoglobin | 300 | Neg | Neg | Pos |
| HSA* | 500 | Neg | Neg | Pos |
| Sodium Chloride | 6000 | Neg | Neg | Pos |
| Oxalic Acid | 100 | Neg | Neg | Pos |
| Urea | 2000 | Neg | Neg | Pos |
| pH 3 | | Neg | Neg | Pos |
| pH 4 | | Neg | Neg | Pos |
| pH 5 | | Neg | Neg | Pos |
| pH 6 | | Neg | Neg | Pos |
| pH 7 | | Neg | Neg | Pos |
| pH 8 | | Neg | Neg | Pos |
| pH 9 | | Neg | Neg | Pos |
| pH 10 | | Neg | Neg | Pos |
| pH 11 | | Neg | Neg | Pos |

*Human Serum Albumin

Specific gravity: Urine samples with specific gravity value ranging from 1.000 to 1.0275 were tested with the assay in the presence of 0, 75, 225, and $375\mathrm{ng / mL}$ of Oxycodone and no interference was observed.

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Note: All endogenous substances listed above, including specific gravity, were also tested in "qualitative-mode". No interference is observed. The results are identical to the "semi-quantitative" mode as all samples gave correct positive/negative result corresponding to the cutoff values of 100 or $300\mathrm{ng / mL}$ .

f. Assay cut-off:

$100\mathrm{ng / mL}$ or $300~\mathrm{ng / mL}$

# 2. Comparison studies:

a. Method comparison with predicate device:

# 100 ng/mL cutoff

Eighty-nine (89) unaltered clinical urine specimens were tested with the LZI Oxycodone Enzyme Immunoassay and confirmed with GC/MS or LC/MS. Specimens having an Oxycodone concentration greater than $100\mathrm{ng / mL}$ by GC/MS or LC/MS are defined as positive, and specimens with lower concentrations by GC/MS or LC/MS are defined as negative in the table below. The correlation results are summarized as follows: (near cutoff samples are defined as $\pm 50\%$ of the cutoff value)

Qualitative Accuracy Study:

| 100 ng/mL Cutoff | Neg | < 50 % of the cutoff | Near Cutoff Neg. | Near Cutoff Pos. | High Pos. | % Agreement |
| --- | --- | --- | --- | --- | --- | --- |
| Positive | 0 | 0 | 0 | 7 | 38 | 93.75 % |
| Negative | 20 | 9 | 12 | 3* | 0 | 100.0 % |

Discordant samples:

| Cutoff Value (100 ng/mL) | Assay Result | Sample Testing Method |
| --- | --- | --- |
| | LZI EIA | GC/MS or LC/MS (ng/mL) |
| Sample #42* | - | 108 |
| Sample #43* | - | 110 |
| Sample #48* | - | 135 |

Semi-Quantitative Accuracy Study:

| 100 ng/mL Cutoff | Neg | < 50 % of the cutoff | Near Cutoff Neg. | Near Cutoff Pos. | High Pos. | % Agreement |
| --- | --- | --- | --- | --- | --- | --- |
| Positive | 0 | 0 | 0 | 7 | 38 | 93.75 % |
| Negative | 20 | 9 | 12 | 3* | 0 | 100.0 % |

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Discordant samples:

| Cutoff Value (100 ng/mL) | Assay Result | Sample Testing Method |
| --- | --- | --- |
| | LZI EIA | GC/MS or LC/MS (ng/mL) |
| Sample #42* | - | 108 |
| Sample #43* | - | 110 |
| Sample #48* | - | 135 |

# 300 ng/mL cutoff:

One-hundred-one (101) unaltered clinical urine specimens were tested with the LZI Oxycodone Enzyme Immunoassay and confirmed with GC/MS or LC/MS. Specimens having an Oxycodone concentration greater than 300 ng/mL by GC/MS or LC/MS are defined as positive, and specimens with lower concentrations by GC/MS or LC/MS are defined as negative in the table below. The correlation results are summarized as follows: (near cutoff samples are defined as $\pm 50\%$ of the cutoff value)

Qualitative Accuracy Study

| 300 ng/mL Cutoff | Neg | < 50 % of the cutoff | Near Cutoff Neg. | Near Cutoff Pos. | High Pos. | % Agreement |
| --- | --- | --- | --- | --- | --- | --- |
| Positive | 0 | 0 | 1* | 11 | 43 | 96.1 % |
| Negative | 20 | 18 | 11 | 2** | 0 | 98.0 % |

Discordant samples:

| Cutoff Value (300 ng/mL) | Assay Result: | Sample Testing Method |
| --- | --- | --- |
| | LZI EIA | GC/MS or LC/MS (ng/mL) |
| Sample #49* | + | 288 |
| Sample #52** | - | 309 |
| Sample #54** | - | 336 |

Semi-Quantitative Accuracy Study

| 300 ng/mL Cutoff | Neg | < 50 % of the cutoff | Near Cutoff Neg. | Near Cutoff Pos. | High Pos. | % Agreement |
| --- | --- | --- | --- | --- | --- | --- |
| Positive | 0 | 0 | 1* | 11 | 43 | 96.1 % |
| Negative | 20 | 18 | 11 | 2** | 0 | 98.0 % |

Discordant samples:

| Cutoff Value (300 ng/mL) | Assay Result: | Sample Testing Method |
| --- | --- | --- |
| | LZI EIA | GC/MS or LC/MS (ng/mL) |
| Sample #49* | + | 288 |
| Sample #52** | - | 309 |
| Sample #54** | - | 336 |

{12}

b. Matrix comparison:

Not applicable. The assay is intended for urine samples only.

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable. Clinical studies are not typically submitted for this device type.

b. Clinical specificity:

Not applicable. Clinical studies are not typically submitted for this device type.

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

Not applicable

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.