DRI Hydrocodone Assay, DRI Hydrocodone Calibrators, DRI Hydrocodone Controls

K150502 · Microgenics Corporation · DJG · Oct 9, 2015 · Clinical Toxicology

Device Facts

• Record ID: K150502
• Device Name: DRI Hydrocodone Assay, DRI Hydrocodone Calibrators, DRI Hydrocodone Controls
• Applicant: Microgenics Corporation
• Product Code: DJG · Clinical Toxicology
• Decision Date: Oct 9, 2015
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.3650
• Device Class: Class 2

Indications for Use

The DRI® Hydrocodone Assay is intended for the qualitative and semi-quantitative detection and estimation of Hydrocodone and its metabolites in human urine at a cutoff of 300 ng/mL. The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of specimen for confirmatory method such as LC-MS/MS or GC-MS and permitting laboratories to establish quality control measures. This assay provides a preliminary analytical test result. A more specific alternative chemical method must be used in order to confirm an analytical result. Gas chromatography/mass spectrometry (GC/MS) and Liquid Chromatography/tandem mass spectrometry (LC-MS/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used. The DRI® Hydrocodone Assay Calibrators are intended for the calibration of the DRI® Hydrocodone Assay. For In Vitro Diagnostic Use Only. The DRI® Hydrocodone Controls are unassayed quality control material intended for use in the DRI Hydrocodone Assay to detect and monitor systematic deviations from accuracy resulting from reagent or instrument defects. For In Vitro Diagnostics Use Only

Device Story

Homogeneous enzyme immunoassay for hydrocodone detection in human urine; utilizes competition between drug-labeled G6PDH and free drug in sample for fixed antibody binding sites. Absence of drug allows antibody binding to G6PDH, decreasing enzyme activity; presence of drug allows G6PDH to interact with substrate, increasing activity. Enzyme activity measured spectrophotometrically at 340 nm via NAD to NADH conversion. Used in clinical laboratories on automated chemistry analyzers (e.g., Beckman Coulter AU680) by trained technicians. Provides preliminary analytical results; requires confirmation by LC-MS/MS or GC-MS. Semi-quantitative mode assists in determining specimen dilution for confirmation and quality control. Results support clinical decision-making regarding drug use.

Clinical Evidence

Bench testing only. Precision (n=80) demonstrated accurate recovery at 300 ng/mL cutoff. Accuracy study (n=100) compared to LC-MS/MS showed 93% overall concordance. Linearity (r2=0.9965) confirmed across calibration range. Specificity/cross-reactivity tested against various opiates; interference testing (pH, endogenous substances, specific gravity) showed no significant impact on assay performance.

Technological Characteristics

Liquid, ready-to-use homogeneous enzyme immunoassay. Reagents: mouse monoclonal anti-hydrocodone antibody, G6PDH, G6P, NAD, Tris buffer, sodium azide preservative. Sensing principle: spectrophotometric measurement of NAD to NADH conversion at 340 nm. Form factor: kit for automated clinical chemistry analyzers. Storage: 2-8°C. Standards: CLSI EP5-2A, EP7-A2, EP9-A3.

Indications for Use

Indicated for qualitative and semi-quantitative detection of hydrocodone and metabolites in human urine at 300 ng/mL cutoff. For prescription use only.

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 Hydrocodone Enzyme Immunoassay (K141055)

Submission Summary (Full Text)

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

A. 510(k) Number:
K150502

B. Purpose for Submission:
New Device

C. Measurand:
Hydrocodone

D. Type of Test:
Qualitative and semi-quantitative homogeneous immunoassay

E. Applicant:
Microgenics Corporation

F. Proprietary and Established Names:
DRI Hydrocodone Assay
DRI Hydrocodone Calibrator
DRI Hydrocodone Control

G. Regulatory Information:

| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| DJG | II | 21 CFR § 862.3650
Opiate test system | Toxicology (91) |
| DLJ | II | 21 CFR § 862.3200
Clinical toxicology calibrator | Toxicology (91) |
| LAS | I, reserved | 21 CFR § 862.3280
Clinical toxicology control material | Toxicology (91) |

H. Intended Use:

1. Intended use(s):
See indications for use below.

2. Indication(s) for use:
The DRI Hydrocodone assay is intended for the qualitative and semi-quantitative detection and estimation of Hydrocodone and its metabolites in human urine at a cutoff of 300 ng/mL.

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The semi-quantitative mode is for purposes of enabling laboratories to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as LC-MS/MS or GC-MS and permitting laboratories to establish quality control procedures.

This assay provides a preliminary analytical test result. A more specific alternative chemical method must be used in order to confirm an analytical result. Gas chromatography/mass spectrometry (GC/MS) and Liquid Chromatography/tandem mass spectrometry (LC-MS/MS) are the preferred confirmatory methods. Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

The DRI Hydrocodone assay calibrators are intended for the calibration of the DRI Hydrocodone assay. For in vitro diagnostic use only.

The DRI Hydrocodone assay controls are unassayed quality control material intended for the use in the DRI Hydrocodone assay to detect and monitor systematic deviations from accuracy resulting from reagent or instrument defects. For in vitro diagnostic use only.

3. Special conditions for use statement(s):

For prescription use only.

4. Special instrument requirements:

Beckman Coulter AU 680 chemistry analyzer was used to generate data for this submission.

I. Device Description:

The DRI Hydrocodone assay is supplied as a liquid ready-to-use homogeneous enzyme immunoassay.

The DRI Hydrocodone Assay is a kit comprised of two reagents, Reagent A and Reagent E, which are bottled separately but sold together within the same kit.

The Reagent A solution contains: mouse monoclonal anti-hydrocodone antibody, glucose-6-phosphate (G6P) and nicotinamide adenine dinucleotide (NAD) in Tris buffer with Sodium Azide (≤0.09%) as a preservative).

The Reagent E solution contains: glucose-6-phosphate dehydrogenase (G6PDH) in Tris buffer with Sodium Azide (≤0.09%) as preservative.

The DRI Hydrocodone Enzyme Immunoassay calibrators designated for use at the 300 ng/mL cutoff contain 0 (negative), 100, 300, 500, and 1,000 ng/mL of hydrocodone in human urine with sodium azide (≤0.09%) as preservative. The calibrators are provided in liquid ready to use form as a separate kit, and are to be stored at 2° to 8° C until the expiration date on the label.

The controls are provided at a concentration of 225 and 375 ng/mL. The controls are provided in liquid ready to use form as a separate kit, and are to be stored at 2° to 8° C until the expiration date on the label.

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J. Substantial Equivalence Information:

1. Predicate device name(s):
LZI Hydrocodone Enzyme Immunoassay

2. Predicate 510(k) number(s):
K141055

3. Comparison with predicate:

| Item | DRI Hydrocodone Assay, Calibrator and Control (Candidate Device) | LZI Hydrocodone Enzyme Immunoassay, k141055 (Predicate Device) |
| --- | --- | --- |
| Intended use | For the qualitative and semi-quantitative determination of the presence of hydrocodone in human urine. For in vitro diagnostic use. | Same |
| Assay cutoff | 300 ng/mL of Hydrocodone | 100 or 300 ng/mL of Hydrocodone |
| Assay calibrated against | Hydrocodone | Same |
| Test system type | Homogenous enzyme immunoassay | Same |
| Storage conditions | 2 - 8°C until expiration date | Same |
| Calibrator form | Liquid | Same |
| Control set levels | 300 ng/mL Cutoff: Two levels (225 ng/mL and 375 ng/mL) | 100 ng/mL Cutoff: Two levels (75 ng/mL and 125 ng/mL).
300 ng/mL Cutoff: Two levels (225 ng/mL and 375 ng/mL). |
| Calibrator set levels | 300 ng/mL Cutoff: Five levels (0, 100, 300, 500 and 1000 ng/mL) | 100 ng/mL Cutoff: Five levels (0, 50, 100, 150 and 300 ng/mL).
300 ng/mL Cutoff: Five levels (0, 150, 300, 500 and 800 ng/mL). |

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

- CLSI EP5-2A, Evaluation of Precision Performance of Quantitative Measurement Methods; Second Edition, 2004.
- CLSI EP7-A2: Interference Testing in Clinical Chemistry, 2005.
- CLSI EP9-A3; Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition, 2013.

L. Test Principle:

The DRI® Hydrocodone Assay is a homogeneous enzyme immunoassay. The assay uses specific antibodies that can detect Hydrocodone and its metabolites without any significant cross-reactivity to other opiate compounds. The assay is based on competition between a drug labeled with glucose-6-phosphate dehydrogenase (G6PDH) and free drug from the urine sample, for a fixed amount of specific antibody binding sites. In the absence of free drug from the sample, mouse monoclonal anti-hydrocodone antibody binds to the drug labeled with G6PDH and causes a decrease in enzyme activity. In the presence of free drug, the free drug occupies the antibody binding sites, allowing the drug bound G6PDH to interact with the substrate, resulting in enzyme activity. This phenomenon creates a direct proportional relationship between the drug concentration in urine and enzyme activity. The enzyme activity is determined spectrophotometrically at 340 nm by measuring the conversion of nicotinamide adenine dinucleotide (NAD) to NADH.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

A precision study was performed by one trained operator following the CLSI (EP5-A2) precision guidelines. Drug free urine samples were spiked with hydrocodone at 0, 75, 150, 225, 300, 375, 450, 525 and 600 ng/mL, representing 0, 25, 50, 75, 100, 125, 150, 175 and 200% of the device cutoff (300 ng/mL). Each level sample was tested in duplicates per run, two runs per day for twenty consecutive days (total N= 80/level/reagent lot) using 2 lots on the Beckman Coulter AU680 chemistry analyzer. The results of one representative lot are shown below:

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Qualitative Precision Result:

| Concentration as % of the Cutoff Level | Target Hydrocodone concentration (ng/mL) | DRI Hydrocodone Assay # Neg / # Pos |
| --- | --- | --- |
| 0 | 0 | 80 Neg / 0 Pos |
| 25 | 75 | 80 Neg / 0 Pos |
| 50 | 150 | 80 Neg / 0 Pos |
| 75 | 225 | 80 Neg / 0 Pos |
| 100 | 300 | 46 Neg / 34 Pos |
| 125 | 375 | 0 Neg / 80 Pos |
| 150 | 450 | 0 Neg / 80 Pos |
| 175 | 525 | 0 Neg / 80 Pos |
| 200 | 600 | 0 Neg / 80 Pos |

Semi-Quantitative Precision Result:

| Concentration as % of the Cutoff Level | Target Hydrocodone concentration (ng/mL) | DRI Hydrocodone Assay # Neg / # Pos |
| --- | --- | --- |
| 0 | 0 | 80 Neg / 0 Pos |
| 25 | 75 | 80 Neg / 0 Pos |
| 50 | 150 | 80 Neg / 0 Pos |
| 75 | 225 | 80 Neg / 0 Pos |
| 100 | 300 | 40 Neg / 40 Pos |
| 125 | 375 | 0 Neg / 80 Pos |
| 150 | 450 | 0 Neg / 80 Pos |
| 175 | 525 | 0 Neg / 80 Pos |
| 200 | 600 | 0 Neg / 80 Pos |

b. Linearity/assay reportable range:

Linearity study in the semi-quantitative mode was conducted by spiking drug free urine pool with hydrocodone (serial dilutions of a high concentration hydrocodone in negative urine pool) to achieve concentrations ranging from 0ng/mL to 1000ng/mL, and testing each level on two reagent lots in replicates of five on the Beckman

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Coulter AU680 clinical chemistry analyzer. The results of one representative lot are summarized below:

| Hydrocodone (ng/mL) | Recovery (ng/mL) | % Recovery |
| --- | --- | --- |
| 0 | N/A | N/A |
| 50 | 47 | 94 |
| 75 | 76 | 101 |
| 100 | 108 | 108 |
| 150 | 171 | 114 |
| 225 | 250 | 111 |
| 300 | 302 | 101 |
| 375 | 398 | 106 |
| 450 | 472 | 105 |
| 500 | 527 | 105 |
| 750 | 844 | 113 |
| 1000 | 1014 | 101 |

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

Traceability

The primary controls and calibrators are traceable to the 1 mg/mL Hydrocodone stock solution purchased from a commercial source which is established at 99.9% purity. The concentration of the primary control and calibrator stocks is confirmed by LC-MS/MS from three independent laboratories.

Value Assignment – Calibrators and Controls

The primary controls and calibrators are used to prepare secondary controls and calibrators and the performance testing is performed on AU680 analyzers against the primary controls and calibrators, in replicates of five. The testing required two passing runs on two different AU680 analyzers. The preset acceptance criteria is that replicates have less than or equal to 5% rate (mA/min) difference between the secondary and the primary controls and calibrators. The concentration of the controls and calibrators are further corroborated with validated LC-MS/MS and the values should be within 10% of the nominal values.

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# Calibrators and Controls Stability Studies

Accelerated a stability studies in the qualitative and semi-quantitative modes were conducted on three lots of DRI Hydrocodone Controls and DRI Hydrocodone Calibrators. Real time stability studies are ongoing. The stability protocols and acceptance criteria for open and closed vial were reviewed and found acceptable. The open vial and closed vial study results support the open vial stability claim of 60 days and closed vial stability claim of thirteen months when stored at 2 to 8 °C for the DRI Hydrocodone Controls and DRI Hydrocodone Calibrators.

d. Detection limit:

Not applicable.

e. Analytical specificity:

An analytical specificity study to evaluate interference from non-structurally and structurally related compounds was performed in the qualitative and semi-quantitative mode. The study design and results are described below. Results were the same for each mode (qualitative and semi-quantitative modes).

# Structurally Related Compounds and Other Opiates

To evaluate potential cross-reactivity for the DRI Hydrocodone assay, structurally similar compounds were spiked into drug free urine at concentrations that will yield a result that is equivalent to the 300 ng/mL cutoff. Non-cross-reacting compounds were titrated to the highest levels yielding negative results in the assay. The percent cross-reactivity is presented in the table below.

| Compounds | Tested Concentration (ng/mL) | % Cross-Reactivity |
| --- | --- | --- |
| Hydrocodone | 300 | 102 |
| Hydromorphone | 250 | 122 |
| Hydromorphone 3β-D-Glucuronide | 250 | 122 |
| NorHydrocodone | 10,000 | 3.1 |
| Dihydrocodeine | 12,000 | 2.7 |
| 6-Acetyl Morphine | 1000,000 | < 0.3 |
| Buprenorphine | 1000,000 | < 0.3 |
| Buprenorphine 3β-D-Glucuronide | 100,000 | < 0.3 |
| Codeine | 150,000 | < 0.2 |
| Dextromethorphan | 250,000 | < 0.2 |
| EDDP | 150,000 | < 0.2 |
| Fentanyl | 100,000 | < 0.3 |
| Heroin | 100,000 | < 0.3 |
| Levorphanol | 12,000 | 1.7 |

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Non-Structurally Related Compounds

Potential interference from non-structurally related drugs and metabolites was evaluated in the qualitative and semi-quantitative modes, by spiking these compounds at high concentrations in drug free urine spiked with hydrocodone at $\pm 25\%$ of the cutoff (225 and $375~\mathrm{ng / mL}$ ). Results obtained with the two reagent lots are the same.

| Cross Reactants | Spiked Concentration (ng/mL) | Spiked Hydrocodone Concentration | | |
| --- | --- | --- | --- | --- |
| | | 0 ng/mL | -25% Cutoff (225 ng/mL) | +25% Cutoff (375 ng/mL) |
| Acetaminophen | 500,000 | Negative | Negative | Positive |
| Acetylsalicylic acid | 500,000 | Negative | Negative | Positive |
| Amitryptyline | 100,000 | Negative | Negative | Positive |
| Amoxicillin | 100,000 | Negative | Negative | Positive |
| Amphetamine | 1,000,000 | Negative | Negative | Positive |
| Benzoylecgonine | 1,000,000 | Negative | Negative | Positive |
| Caffeine | 100,000 | Negative | Negative | Positive |
| Carbamazepine | 500,000 | Negative | Negative | Positive |
| Chlorpromazine | 100,000 | Negative | Negative | Positive |
| Clomipramine | 100,000 | Negative | Negative | Positive |
| Cimetidine | 500,000 | Negative | Negative | Positive |
| Desipramine | 100,000 | Negative | Negative | Positive |
| Dexamethasone | 100,000 | Negative | Negative | Positive |
| Doxorubicin | 100,000 | Negative | Negative | Positive |
| Doxorubicin + 5-FU | 100,000 | Negative | Negative | Positive |
| Doxorubicin + 5-FU + 5-FU + 5-FU + 5-FU + 5-FU + 5-FU + 5-FU + 5-FU + 5-FU + 5-FU + 5-FU + 5-FU + 5-FU | 100,000 | Negative | Negative | Negative |

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| Diphenhydramine | 100,000 | Negative | Negative | Positive |
| --- | --- | --- | --- | --- |
| Doxepine | 100,000 | Negative | Negative | Positive |
| Ephedrine | 1,000,000 | Negative | Negative | Positive |
| Fluoxethine | 100,000 | Negative | Negative | Positive |
| Fluphenazine | 100,000 | Negative | Negative | Positive |
| Ibuprofen | 500,000 | Negative | Negative | Positive |
| Imipramine | 100,000 | Negative | Negative | Positive |
| Maprotiline | 100,000 | Negative | Negative | Positive |
| Nortryptiline | 100,000 | Negative | Negative | Positive |
| Oxazepam | 250,000 | Negative | Negative | Positive |
| Phencyclidine | 100,000 | Negative | Negative | Positive |
| Phenobarbital | 100,000 | Negative | Negative | Positive |
| Ranitidine | 500,000 | Negative | Negative | Positive |
| Secobarbital | 100,000 | Negative | Negative | Positive |
| Thioridazine | 100,000 | Negative | Negative | Positive |

## Endogenous Compounds

Potential interference from endogenous compounds commonly found in urine was evaluated in the qualitative and semi-quantitative modes, by spiking these compounds into drug free urine containing hydrocodone at $\pm 25\%$ of the $300~\mathrm{ng/mL}$ cutoff (225 and $375~\mathrm{ng/mL}$). Results obtained with the two reagent lots are the same.

| Compounds | Concentration tested (mg/dL) | -25% Cutoff (225ng/mL) | +25% Cutoff (375ng/mL) |
| --- | --- | --- | --- |
| No added compound | N/A | Negative | Positive |
| Acetaminophen | 10 | Negative | Positive |
| Acetone | 500 | Negative | Positive |
| Acetyl Salicylic Acid | 10 | Negative | Positive |
| Ascorbic Acid | 150 | Negative | Positive |
| Caffeine | 10 | Negative | Positive |
| Creatinine | 400 | Negative | Positive |
| Ethanol | 10 | Negative | Positive |
| Galactose | 5 | Negative | Positive |
| Glucose | 1000 | Negative | Positive |
| Hemoglobin | 150 | Negative | Positive |
| Human Serum Albumin (HSA) | 200 | Negative | Positive |
| Ibuprophen | 10 | Negative | Positive |
| Oxalic acid | 50 | Negative | Positive |
| Riboflavin | 3 | Negative | Positive |
| Sodium Chloride | 1000 | Negative | Positive |
| Urea | 1000 | Negative | Positive |

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pH and Specific Gravity

For potential interference from the pH of urine, device performance in the qualitative and semi-quantitative modes was tested using a range of urine pH values (4.0, 5.0, 6.0, 7.0, 8.0, 9.0 and 10.0). All test samples were prepared in drug free urine containing hydrocodone at ± 25% of the cutoff (225 ng/mL and 375 ng/mL hydrocodone concentrations). No positive or negative interference was observed at urine pH values ranging from 4.0 to 10.0 for each test mode.

For potential interference from the specific gravity of urine, device performance in the qualitative and semi-quantitative modes was tested using a range of urine specific gravity values (1.000, 1.006, 1.007, 1.010, 1.013, 1.018, 1.021, 1.025, 1.028, 1.034 and 1.036). All test samples were prepared in drug free urine containing hydrocodone at ± 25% of the cutoff (225 ng/mL and 375 ng/mL hydrocodone concentrations). No positive or negative interference was observed at urine specific gravity values ranging from 1.000 to 1.036 for each test mode.

f. Assay cut-off:

Characterization of how the device performs analytically around the claimed cutoff concentration of 300 ng/mL hydrocodone is described in the precision section, M.1.a. above.

2. Comparison studies:

a. Method comparison with predicate device:

A total of 100 unaltered urine samples from pain management laboratories were analyzed by two lots of the candidate device in the qualitative and semi-quantitative modes on the Beckman Coulter AU680 clinical chemistry analyzer and the comparative mass spectrometry based quantitative method (LC-MS/MS). LC-MS/MS and immunoassay qualitative results are based on a 300 ng/mL cutoff. The results from the study in the two modes were same and are summarized below:

Qualitative and Semi-quantitative Mode

| Candidate Device Results | Negative | <50% of cutoff concentration by LC/MS (< 150ng/mL) | Near Cutoff Negative (Between 50% below the cutoff and the cutoff concentration by LC/MS) (150 ~ 299 ng/mL) | Near Cutoff Positive (Between the cutoff and 50% above the cutoff concentration by LC/MS) (300 ~ 450 ng/mL) | High Positive (Greater than 50% above the cutoff concentration by LC/MS) > 450 ng/mL |
| --- | --- | --- | --- | --- | --- |
| Positive | 0 | 1* | 5** | 10 | 39 |
| Negative | 31 | 6 | 7 | 1 | 0 |

* and ** are oxycodone positive samples that contained 41,240 ng/mL and 37,000 ng/mL oxycodone respectively.
% Agreement among positives is 98%.
% Agreement among negatives is 88%.

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% Overall agreement is 93%.

# Discordant Result Table for the Discrepant Samples near cutoff

| Sample # | Qualitative EIA | LC-MS/MS (ng/mL) | | |
| --- | --- | --- | --- | --- |
| | | Hydrocodone | Hydromorphone | Hydromorphone 3β-D Glucuronide |
| 33 | Positive | 143.3 | <LLOQ+ | 67.6 |
| 70* | Positive | 138.4 | <LLOQ | <LLOQ |
| 75** | Positive | 216.7 | <LLOQ | <LLOQ |
| 76 | Positive | 198.8 | <LLOQ | 42.6 |
| 83 | Positive | 78.4 | <LLOQ | 110.1 |
| 89 | Positive | 192.3 | <LLOQ | 56.2 |
| 96 | Negative | 303.3 | <LLOQ | 50.1 |

ng/mL oxycodone respectively.
+LLOQ = Lowest Limit of Quantitation is 40 ng/mL

# b. Matrix comparison:

Not applicable. Urine is the only claimed matrix for the candidate device.

# 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):

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.