K Number
K091653
Date Cleared
2009-11-02

(146 days)

Product Code
Regulation Number
862.3350
Reference & Predicate Devices
Predicate For
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The ARK™ Levetiracetam Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of levetiracetam in human serum or plasma on automated clinical chemistry analyzers. Levetiracetam concentrations can be used as an aid in management of patients treated with levetiracetam. The ARKTM Levetiracetam Calibrator is intended for use in calibration of the ARK Levetiracetam Assay. The ARK™ Levetiracetam Control is intended for use in quality control of the ARK Levetiracetam Assay.

Device Description

The ARK Levetiracetam Assay is a homogeneous immunoassay based on competition between drug in the specimen and levetiracetam labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenyzme NAD functions only with the bacterial enzyme used in the assay. The ARK Levetiracetam Assay consists of reagents RI anti-levetiracetam polyclonal antibody with substrate and R2 levetiracetam labeled with bacterial G6PDH enzyme. The ARK Levetiracetam Calibrator consists of a six-level set to calibrate the assay, and the ARK Levetiracetam Control consists of a three-level set used for quality control of the assay.

AI/ML Overview

Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Device Performance for ARK™ Levetiracetam Assay

1. Table of Acceptance Criteria and Reported Device Performance

Performance CharacteristicAcceptance CriteriaReported Device Performance
Limit of Quantitation (LOQ)20% CV with ±15% recovery2.0 µg/mL (not explicitly stated if it met the 20% CV & ±15% recovery, but implied as the determined LOQ)
Accuracy (Analytical Recovery)Not explicitly stated, but implied to be acceptable based on percent recovery within reasonable limits.Range of 94.6% to 105.3% recovery for concentrations 2.0 to 100.0 µg/mL.
LinearityPercent difference ±10% between 1st and 2nd order regressed values, or ±15% below 3.0 µg/mL.Linear relationship demonstrated between 2.0 and 100.0 µg/mL. All % Differences were within the specified ±10% (for values ≥3.0 µg/mL) and ±15% (for values <3.0 µg/mL, observed at 13.2% for 2.0 µg/mL which is within 15%).
Precision<10% total CVARK Levetiracetam Control:LOW (7.5 µg/mL): 4.5% total CVMID (29.4 µg/mL): 3.7% total CVHIGH (73.4 µg/mL): 4.2% total CVHuman Serum:LOW (6.9 µg/mL): 4.8% total CVMID (30.2 µg/mL): 4.1% total CVHIGH (75.5 µg/mL): 4.4% total CV
Interfering SubstancesMeasurement of levetiracetam resulted in ≤10% error.Measurement of levetiracetam resulted in ≤10% error in the presence of tested interfering substances (Albumin, Bilirubin, Cholesterol, Gamma-Globulin, Hemoglobin, Intralipid®, Rheumatoid Factor, Triglycerides, Uric Acid).
Metabolite Cross-Reactivity (ucb L057)Measurement of levetiracetam resulted in ≤10% error.Measurement of levetiracetam resulted in ≤10% error. Specifically, percent interference was -3.0% (at 15 µg/mL Levetiracetam) and 6.6% (at 50 µg/mL Levetiracetam). Percent cross-reactivity was -0.2% and 1.3%.
Drug InterferenceMeasurement of levetiracetam resulted in ≤10% error.Measurement of levetiracetam resulted in ≤10% error in the presence of various anti-epileptic or co-administered drugs tested. All percentage recoveries listed for 15 µg/mL and 50 µg/mL Levetiracetam were within 10% of the expected value (i.e., between 90% and 110%).
AnticoagulantsNo significant difference between recovery in serum or plasma.Results indicate no significant difference between the recovery of levetiracetam in serum or plasma.
Sample StabilityNot explicitly stated beyond "stable for at least...".Stable for at least 48 hours at room temperature (22 °C), 40 days when refrigerated (2-8 °C), and after three successive freeze/thaw cycles.
Calibration Curve StabilityNot explicitly stated beyond "effective up to...".Effective up to 40 days.
Reagent On-Board StabilityNot explicitly stated beyond "effective for up to at least...".Effective for up to at least 40 days.

2. Sample Size and Data Provenance

  • Accuracy: Not explicitly stated, but "highly pure levetiracetam was added volumetrically to human serum negative for levetiracetam, representing drug concentrations across the assay range." Six replicates of each sample were assayed. Data provenance not specified (retrospective/prospective, country of origin).
  • Linearity: Not explicitly stated, but a 100.0 µg/mL serum sample was prepared and dilutions were made proportionally with human serum negative for levetiracetam. Data provenance not specified.
  • Method Comparison: Number of samples = 305. Data provenance not specified.
  • Precision: 160 measurements for each of the 6 levels (3 control levels, 3 human serum pools). This equates to 8 measurements per level per day (quadruplicate twice a day) over 20 days. Data provenance not specified.
  • Interfering Substances: For each interfering substance, serum with known levels of levetiracetam (approx. 15 and 50 µg/mL) was evaluated. A serum control was also used. Amount of samples for each interfering substance is not explicitly stated. Data provenance not specified.
  • Metabolites: Not explicitly stated for metabolite cross-reactivity. Data provenance not specified.
  • Drug Interference: For each compound, normal human serum with known levels of levetiracetam (approx. 15 and 50 µg/mL) was spiked and assayed along with a serum control. Total number of samples is not explicitly stated. Data provenance not specified.
  • Anticoagulants: Not explicitly stated. Data provenance not specified.

3. Number of Experts and Qualifications for Ground Truth

Not applicable. This is an in-vitro diagnostic device (immunoassay) for quantitative determination of a drug. Ground truth is established by spiked concentrations, a reference method (LC/MS/MS), or intrinsic characteristics of known substances. No human expert interpretation of images or other subjective data is involved.

4. Adjudication Method

Not applicable. For an immunoassay, the "ground truth" is typically verifiable concentrations of the analyte or comparison to a gold standard analytical method. There is no subjective assessment that would require expert adjudication.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No. This is an in-vitro diagnostic device for quantitative chemical analysis, not an imaging device or a device involving human interpretation where MRMC studies would be relevant.

6. Standalone Performance

Yes, the studies described are solely for the performance of the ARK™ Levetiracetam Assay system (algorithm/device only). There is no "human-in-the-loop" component to its stated intended use or the performance studies presented.

7. Type of Ground Truth Used

  • Limit of Quantitation, Accuracy, Linearity, Interfering Substances, Metabolites, Drug Interference: Ground truth was established by known, spiked concentrations of levetiracetam and/or interfering substances into human serum, or by using highly pure reference materials.
  • Method Comparison: Ground truth for comparison was established by a reference LC/MS/MS method.
  • Precision: Ground truth was established by known concentrations in control materials and pooled human serum samples.

8. Sample Size for the Training Set

Not applicable. This is an immunoassay, which does not typically involve training a machine learning model in the same way as, for example, an AI for image analysis. The "training" in this context would be the development and optimization of the chemical reagents and assay parameters during the R&D phase, for which specific sample sizes and datasets for "training" are not usually reported in this manner.

9. How the Ground Truth for the Training Set Was Established

Not applicable. As noted above, this is not a machine learning device that uses a "training set" in the conventional sense. The "ground truth" for the development of the assay would involve fundamental chemical and biological principles to ensure proper antibody-antigen binding specificity and enzyme activity, calibrated against known standards.

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K091653

510(k) SUMMARY

2009 - 2 2009

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is K091653.

807.92 (a)(1): Name: ARK Diagnostics, Inc.

· Address: 1190 Bordeaux Drive Sunnyvale, CA 94089

Owner Operator Number: 10027663 Establishment Registration: 3005755244

Phone:(408) 747-0700
FAX:(408) 747-0783
Contact:Kenneth C. Kasper, PhD – (408) 747-0708Executive Director of Quality and Regulatory Affairs

Date prepared: October 23, 2009

807.92 (a)(2): Device name- trade name and common name, and classification

Trade name:ARK™ Levetiracetam Assay
ARK™ Levetiracetam Calibrator
ARK™ Levetiracetam Control
Common Name:Homogeneous Enzyme Immunoassay
Classification:21 CFR 862.3350 NWM Diphenylhydantoin Test System; Class II(21 CFR 862.3200 DLJ, 21 CFR 862.3280 LAS)

807.92 (a)(3): Identification of the legally marketed predicate device

K083799 (bundled) ARKTM Topiramate Assay r ARKTM Topiramate Calibrator ARK™ Topiramate Control

ARK Diagnostics, Inc. - 510(k) Summary ARK Levetiracetam Assay

page 1 of 1 l

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807.92 (a)(4): Device Description

The ARK Levetiracetam Assay is a homogeneous immunoassay based on competition between drug in the specimen and levetiracetam labeled with the enzyme glucose-6-phosphate dehydrogenase (G6PDH) for binding to the antibody reagent. As the latter binds antibody, enzyme activity decreases. In the presence of drug from the specimen, enzyme activity increases and is directly proportional to the drug concentration. Active enzyme converts the coenzyme nicotinamide adenine dinucleotide (NAD) to NADH that is measured spectrophotometrically as a rate of change in absorbance. Endogenous serum G6PDH does not interfere with the results because the coenyzme NAD functions only with the bacterial enzyme used in the assay.

The ARK Levetiracetam Assay consists of reagents RI anti-levetiracetam polyclonal antibody with substrate and R2 levetiracetam labeled with bacterial G6PDH enzyme. The ARK Levetiracetam Calibrator consists of a six-level set to calibrate the assay, and the ARK Levetiracetam Control consists of a three-level set used for quality control of the assay.

807.92 (a)(5): Intended Use / Indications for Use

The ARK™ Levetiracetam Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of levetiracetam in human serum or plasma on automated clinical chemistry analyzers. Levetirations can be used as an aid in management of patients treated with levetiracetam.

The ARKTM Levetiracetam Calibrator is intended for use in calibration of the ARK Levetiracetam Assay.

The ARK™ Levetiracetam Control is intended for use in quality control of the ARK Levetiracetam Assay.

ARK Diagnostics, Inc. - 510(k) Summary ARK Levetiracetam Assay

page 2 of 11

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807.92 (a)(6): Technological Similarities and Differences to the Predicate

SUBSTANTIAL EQUIVALENCE COMPARATIVE CHART

CharacteristicDevicePredicate
ARK™ Levetiracetam AssayARK™ Topiramate Assay K083799
Intended UseThe ARK™ Levetiracetam Assay is intendedfor the quantitative determination oflevetiracetam in human serum or plasma onautomated clinical chemistry analyzers.The ARK™ Topiramate Assay is intendedfor the quantitative determination oftopiramate in human serum or plasma onautomated clinical chemistry analyzers.
Indications for UseThe results obtained are used in the diagnosisand treatment of levetiracetam overdose andin monitoring levels of levetiracetam to helpensure appropriate therapy.The results obtained are used in the diagnosisand treatment of topiramate overdose and inmonitoring levels of topiramate to helpensure appropriate therapy.
SampleSerum or plasmaSerum or plasma
MethodologyHomogenous enzyme immunoassay (EIA)Homogenous enzyme immunoassay (EIA)
ReagentComponentsTwo (2) reagent system:Anti-levetiracetam Antibody/SubstrateReagent (R1) containing rabbit polyclonalantibodies to levetiracetam, glucose-6-phosphate, nicotinamide adeninedinucleotide, bovine serum albumin,preservatives, and stabilizersEnzyme Reagent (R2) containinglevetiracetam labeled with bacterial G6PDH,buffer, bovine serum albumin, preservatives,and stabilizersTwo (2) reagent system:Anti-topiramate Antibody/Substrate Reagent(R1) containing rabbit polyclonal antibodiesto an epitope of topiramate, glucose-6-phosphate, nicotinamide adeninedinucleotide, bovine serum albumin,preservatives, and stabilizersEnzyme Reagent (R2) containing topiramateepitope labeled with bacterial G6PDH,buffer, bovine serum albumin, preservatives,and stabilizers
Platform requiredAutomated clinical chemistry analyzerAutomated clinical chemistry analyzer
Accessory reagentsCalibrators (six levels) and controls (threelevels)Calibrators (six levels) and controls (threelevels)
TestingenvironmentRoutine clinical laboratoryRoutine clinical laboratory
Reagent conditionand storageLiquid, 2-8° CLiquid, 2-8° C

Comparison between the ARK™ Levetiracetam Assay and the ARK™ Topiramate Assay

ARK Diagnostics, Inc. - 510(k) Summary ARK Levetiracetam Assay

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807.92 (b)(1) and 807.92 (b)(2): Brief Description of Nonclinical and Clinical Data

Limit of Quantitation (LOO)

The LOQ of the ARK Levetiracetam Assay was determined according to CLSI EP17-A and is defined as the lowest concentration for which acceptable inter-assay precision and recovery is observed (20% CV with ±15% recovery). The LOQ was determined to be 2.0 µg/mL.

Accuracy

Accuracy (analytical recovery) was performed by adding concentrated leveiracetam drug into human serum negative for levetiracetam. A stock concentrate of highly pure levetiracetam was added volumetrically to human serum negative for levetiracetam, representing drug concentrations across the assay range. Six replicates of each sample were assayed on an automated clinical chemistry analyzer. The results were averaged and compared to the target concentration and percent recovery calculated. Results are shown below.

$% Recovery = 100 X$$\frac{Mean recovered concentration}{Theoretical concentration}$
-----------------------------------------------------------------------------------------
TheoreticalConcentration(µg/mL)Mean RecoveredConcentration(µg/mL)PercentRecovery
2.01.995.8
4.03.894.6
10.010.0100.0
20.019.295.9
45.044.198.0
80.079.399.1
100.0105.3105.3

ARK Diagnostics, Inc. - 510(k) Summary ARK Levetiracetam Assay

page 4 of 11

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Linearity

Linearity studies were performed as suggested in CLSUNCCLS Protocol EP6-A. A 100.0 µg/mL serum sample was prepared and dilutions were made proportionally with human serum negative for levetiracetam. Levetiracetam concentrations ranged from 1.0 to 100.0 µg/mL. Linearity at specific dilutions was considered acceptable if the percent difference was ±10% between the predicted 14 and 2nd order regressed values or ±15% below 3.0 µg/mL. A linear relationship was demonstrated between 2.0 and 100.0 µg/mL. Results are shown below.

.

Estimated Value(µg/mL)Results(µg/mL)1st OrderPredictedResults2nd OrderPredictedResults% Difference(AcceptanceCriteria: ±10%)
2.01.92.12.413.2
3.03.23.13.47.6
4.04.14.24.34.8
5.05.35.25.33.1
6.06.46.26.32.0
7.07.67.27.31.3
8.08.48.38.30.7
9.09.59.39.30.3
10.010.710.310.3-0.1
20.020.720.620.4-1.3
30.031.031.030.5-1.4
40.041.341.340.8-1.2
50.051.951.651.1-0.9
60.060.361.961.6-0.5
70.071.272.272.1-0.1
80.081.482.582.80.3
90.093.792.893.50.7
100.0104.6103.1104.31.2

ARK Diagnostics, Inc. - 510(k) Summary ARK Levetiracetam Assay

page 5 of 1 l

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Assay Range

The range of the assay is 2.0 to 100.0 ug/mL. Report results below this range as <2.0 ug/mL or below the analyzer-specific lower LOQ established in your laboratory. Report results above this range as >100.0 ug/mL or above the analyzer-specific upper LOQ established in your laboratory.

Specimens testing initially above the assay range may be diluted in Calibrator A and retested. Multiply the assay result by the dilution factor to obtain the concentration of levetiracetam in the undiluted specimen.

Method Comparison

Correlation studies were performed using CLSI/NCCLS Protocol EP9-A2. Results from the ARK Levetiracetam assay were compared with results from a reference LC/MS/MS method. The levetiracetam concentrations ranged from 2.0 ug/mL to 86.4 ug/mL. Results of the Passing-Bablok regression analysis for the study are shown below (with 95% confidence limits).

Slope1.01(0.99 to 1.03)
y-intercept0.25(-0.24 to 0.63)
Correlation Coefficient (r2)0.97(0.96 to 0.97)
Number of Samples305

Image /page/5/Figure/6 description: This image is a scatter plot comparing two different assays, ARK Levetiracetam Assay and LC/MS/MS, both measured in micrograms per milliliter. The x-axis represents the LC/MS/MS assay, while the y-axis represents the ARK Levetiracetam Assay. The plot includes a line of identity and a Passing & Bablok fit line, represented by the equation y = 0.25 + 1.01x.

ARK Diagnostics, Inc. - 510(k) Summary ARK Levetiracetam Assay

page 6 of 11

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Precision

Precision was determined as described in CLSI/NCCLS Protocol EP5-A2. Trilevel controls and three human serum pooled specimens containing levetiracetam were used in the study. Each level was assayed in quadruplicate twice a day for 20 days. Each of the runs per day was separated by at least two hours. The within run, between day, total SD, and percent CVs were calculated. Results are shown below. Acceptance criteria: <10% total CV.

Within RunBetween DayTotal
SampleNMean(µg/mL)SDCV(%)SDCV(%)SDCV(%)
ARK Levetiracetam Control
LOW1607.50.253.40.233.20.344.5
MID16029.40.852.90.832.81.083.7
HIGH16073.42.142.92.032.83.084.2
Human Serum
LOW1606.90.263.80.223.10.334.8
MID16030.20.872.91.103.71.234.1
HIGH16075.52.192.92.353.13.314.4

ARK Diagnostics, Inc. - 510(k) Summary ARK Levetiracetam Assay

.page 7 of 11

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Interfering Substances

Interference studies were conducted using CLSI/NCCLS Protocol EP7-A2 as a guideline. Clinically high concentrations of the following potentially interfering substances in serum with known levels of levetiracetam (approximately 15 and 50 ug/mL) were evaluated. Each sample was assayed using the ARK Levetiracetam Assay, along with a serum control of levetiracetam. Measurement of levetiracetam resulted in ≤10% error in the presence of interfering substances at the levels tested.

InterferingSubstanceInterferentConcentration
Albumin12 g/dL
Bilirubin70 mg/dL
Cholesterol535 mg/dL
Gamma-Globulin12 g/dL
Hemoglobin1000 mg/dL
Intralipid®1500 mg/dL
Rheumatoid Factor1100 IU/mL
Triglycerides1033 mg/dL
Uric Acid30 mg/dL

Metabolites

Levetiracetam is hydrolyzed to its major metabolite 2-pyrrolidone-N-butyric acid (ucb·L057) and two minor metabolites.3 The metabolite ucb L057 was tested for cross-reactivity.

Measurement of levetiracetam resulted in ≤ 10% error in the presence of ucb L057 (2-pyrolidone-N-butyric acid) at the level tested.

Metaboliteucb L057(µg/mL)Percent Cross-ReactivityPercent Interference
Levetiracetam15 µg/mLLevetiracetam50 µg/mLLevetiracetam15 µg/mLLevetiracetam50 µg/mL
ucb L057:
2-pyrrolidone-N-butyric acid250.0-0.21.3-3.06.6

ARK Diagnostics, Inc. - 510(k) Summary ARK Levetiracetam Assay

page 8 of 1 l

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Drug Interference

Levetiracetam-selective antibody did not crossreact with other anti-epileptic or coadministered drugs tested. A high concentration of each compound was spiked into normal human serum with known levels of levetiracetam (approximately 15 and 50 µg/mL) and assayed along with a serum control of levetiracetam. Measurement of levetiracetam resulted in ≤ 10% error in the presence of drug compounds at the levels tested.

CompoundConc.Tested(µg/mL)Percentage Recovery15 µg/mLLevetiracetamPercentage Recovery50 µg/mLLevetiracetam
Acetaminophen20099.397.5
Acetyl Salicyclic acid1000103.298.9
Amitriptyline2098.4100.7
Caffeine10095.497.7
Carbamazepine120101.199.7
Clonazepam50100.2100.4
Cyclosporin A4099.998.4
Diazepam50100.398.6
Digoxin4092.9100.2
Erythromycin20099.097.9
Ethosuxamide25098.1101.1
Felbamate250100.897.9
Gabapentin100101.396.3
Heparin200units/mL97.097.2
Hydrochlorothiazide2098.298.9
Ibuprofen50098.599.2
Lamotrigine25094.3102.4
Naproxen50099.0101.3
Nortriptyline2099.397.8
Oxcarbazepine5095.5100.4
Phenobarbital20098.899.4
Phenytoin20097.896.8
Primidone10097.797.3
Probenecid600100.5101.5
Salicylic Acid50095.198.4
CompoundConc.Tested(µg/mL)Percentage Recovery15 µg/mLLevetiracetamPercentage Recovery50 µg/mLLevetiracetam
Sulfamethoxazole40097.996.3
Sulfisoxazole400100.6100.4
Theophylline25096.6101.1
Tiagabine20099.097.5
Topiramate25094.799.2
Trimethoprim40102.099.3
Valproic Acid50098.796.2
Verapamil100100.396.4
Vigabatrin15094.097.1
Warfarin25096.6102.3
Zonisamide250100.3101.7

ARK Diagnostics, Inc. - 510(k) Summary ARK Levetiracetam Assay

page 9 of 11

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Anticoagulants

Studies were conducted to determine the performance characteristics of the assay for both serum and plasma samples containing levetiracetam.

The results indicate that there is no significant difference between the recovery of levetiracetam in serum or plasma.

Sample Stability

Serum specimens were shown to be stable for at least forty-eight (48) hours at room temperature (22 °C), forty (40) days when refrigerated (2-8 °C) and after three (3) successive freeze/thaw cycles.

On-Board Stability

Calibration Curve Stability: A stored calibration was effective up to 40 days based on supporting data.

Reagent on-board stability: Reagents were effective when stored after transfer to analyzer specific reagent containers for up to at least 40 days based on supporting data. In-use stability of calibrator and controls was also demonstrated.

ARK Diagnostics, Inc. - 510(k) Summary ARK Levetiracetam Assay

page 10 of 11

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807.92 (b)(3): Conclusions from Nonclinical Testing

As summarized above, the ARK Levetiracetam Assay, the ARK Levetiracetam Calibrator and the ARK Levetiracetam Control are substantially equivalent to the ARK™ Topiramate Assay system. The ARK Levetiracetam Assay system was shown to be safe and effective for its intended use based on performance studies.

ARK Diagnostics, Inc. - 510(k) Summary ARK Levetiracetam Assay

page 11 of 11

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Image /page/11/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or bird in flight, composed of three curved lines.

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

Image /page/11/Picture/3 description: The image shows a date, "JUN 09 2019". The month is June, the day is the 9th, and the year is 2019. The text is in bold font.

ARK Diagnostics C/O Mr. Johnny Valdez 1190 Bordeaux Drive Sunnyvale, CA 94089

Re: K091653

Trade/Device Name: ARK Levetiracetam Assay, ARK Levetiracetam Calibrators and ARK Levetiracetam Controls Regulation Number: 21 CFR 862.3350 Regulation Name: Diphenylhydantoin Test System Regulatory Class: Class II Product Code: ORI, LAS, DLJ Dated October 20, 2009 Received October 21, 2009

Dear Mr. Valdez:

This letter corrects our substantially equivalent letter of November 2, 2009.

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or ( 301 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely vours.

CA

Courtney C. Harper, Ph.D. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indication for Use

510(K) Number (if known): K091653

Device Name:

· ARK™ Levetiracetam Assay ARKTM Levetiracetam Calibrator ARKIM Levetiracetam Control

Indications for Use:

The ARK™ Levetiracetam Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of levetiracetam in human serum or plasma on automated clinical chemistry analyzers.

Levetiracetam concentrations can be used as an aid in management of patients treated with levetiracetam.

The ARK™ Levetiracetam Calibrator is intended for use in calibration of the ARK Levetiracetam Assay.

The ARK™ Levetiracetam Control is intended for use in quality control of the .ARK Levetiracetam Assay.

Prescription Use __ X (21 CFR Part 801 Subpart D)

And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

signature

Divjsion Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K091653

ARK Levetiracetam Assay - Indications/Intended Use ARK Diagnostics, Inc.

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Indication for Use

510(K) Number (if known): K091653

Device Name:

ARKTM Levetiracetam Assay ARKTM Levetiracetam Calibrator ARKTM Levetiracetam Control

Indications for Use:

The ARK™ Levetiracetam Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of levetiracetam in human serum or plasma on automated clinical chemistry analyzers.

Levetiracetam concentrations can be used as an aid in management of patients treated with levetiracetam.

The ARKTM Levetiracetam Calibrator is intended for use in calibration of the ARK Levetiracetam Assay.

The ARK™ Levetiracetam Control is intended for use in quality control of the ARK Levetiracetam Assay.

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

f

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Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

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Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K091653

ARK Levetiracetam Assay - Indications/Intended Use ARK Diagnostics, Inc.

§ 862.3350 Diphenylhydantoin test system.

(a)
Identification. A diphenylhydantoin test system is a device intended to measure diphenylhydantoin, an antiepileptic drug, in human specimens. Measurements obtained by this device are used in the diagnosis and treatment of diphenylhydantoin overdose and in monitoring levels of diphenylhydantoin to ensure appropriate therapy.(b)
Classification. Class II.