(172 days)
The ARK™ Lamotrigine Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of lamotrigine in human serum or plasma on automated clinical chemistry analyzers. Lamotrigine concentrations can be used as an aid in management of patients treated with lamotrigine.
The ARKTM Lamotrigine Calibrator is intended for use in calibration of the ARK Lamotrigine Assay.
The ARKTM Lamotrigine Control is intended for use in quality control of the ARK Lamotrigine Assay.
The ARK Lamotrigine Assay is a homogeneous immunoassay based on competition between drug in the specimen and lamotrigine 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 Lamotrigine Assay consists of reagents R1 anti-lamotrigine polyclonal antibody with substrate and R2 lamotrigine labeled with bacterial G6PDH enzyme. The ARK Lamotrigine Calibrator consists of a six-level set to calibrate the assay, and the ARK Lamotrigine Control consists of a three-level set used for quality control of the assay.
The ARK™ Lamotrigine Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of lamotrigine in human serum or plasma. The device performance was evaluated through various studies, including limit of quantitation (LOQ), assay range, recovery, linearity, method comparison, precision, interfering substances, specificity, and anticoagulant studies.
1. Acceptance Criteria and Reported Device Performance:
| Study/Characteristic | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Limit of Quantitation (LOQ) | <20% CV with ±15% recovery | 0.85 µg/mL |
| Assay Range | Not explicitly stated as acceptance criteria, but defined as the operational range. | 0.85 to 40.00 µg/mL |
| Recovery | Not explicitly stated as acceptance criteria, but individual recovery values are presented. | Mean percent recovery: 99.2%. Individual recoveries ranged from 95.8% to 105.1%. |
| Linearity | Percent difference ±10% between predicted and 2nd order regressed values. | All tested concentrations showed a percentage difference within ±10% (range -0.4% to 7.1%). |
| Method Comparison (Study 1 - HPLC) | Not explicitly stated as acceptance criteria, but presented with 95% confidence limits. | Slope: 1.01 (0.99 to 1.03), y-intercept: 0.37 (0.22 to 0.55), Correlation Coefficient (r²): 0.97 (0.96 to 0.98) |
| Method Comparison (Study 2 - Turbidimetric Immunoassay) | Not explicitly stated as acceptance criteria, but presented with 95% confidence limits. | Slope: 0.93 (0.89 to 0.97), y-intercept: 0.41 (0.07 to 0.74), Correlation Coefficient (r²): 0.96 (0.94 to 0.97) |
| Precision | ≤10% total CV | All tested samples (low, mid, high controls, and human serum pools) showed total CVs well within 10% (range 4.1% to 8.8%). |
| Interfering Substances | ≤10% error in the presence of interfering substances. | Measurement of lamotrigine resulted in ≤10% error in the presence of various interfering substances (e.g., albumin, bilirubin, cholesterol, hemoglobin, etc.) at tested levels. |
| Specificity (Metabolites) | Not explicitly stated as acceptance criteria for cross-reactivity percentage. | Metabolites showed low cross-reactivity: Lamotrigine-2-N-glucuronide (1.09-2.91%), Lamotrigine-2-N-methyl (0.02-0.24%), Lamotrigine-2-N-oxide (1.30-3.94%). |
| Specificity (Drug Interference) | ≤10% error in the presence of co-administered drugs. | Measurement of lamotrigine resulted in ≤10% error in the presence of a wide range of co-administered drugs at tested levels. |
| Cross-Reacting Drug (Trimethoprim) | Caution advised if trimethoprim is administered, no explicit error threshold for this specific drug. | Trimethoprim at 40.0 µg/mL showed 4.4% cross-reactivity at 3 µg/mL lamotrigine and 3.0% cross-reactivity at 15 µg/mL lamotrigine. Percentage recovery was 156.0% (at 3 µg/mL Lamotrigine) and 108.0% (at 15 µg/mL Lamotrigine), indicating significant interference. |
| Anticoagulants | No significant difference between serum and plasma recovery. | Results indicated no significant difference between the recovery of lamotrigine in serum or plasma. |
| Sample Stability | Defined stability periods. | Serum specimens stable for at least 6 months frozen, 50 hours at room temperature (22°C), 37 days refrigerated (2-8°C), and after 3 freeze/thaw cycles. |
| On-Board Stability (Calibration Curve) | Calibration curve stability for 30 days. | Calibration curve stability for a period of 30 days is supported by data. |
| On-Board Stability (Reagent) | Reagents effective for up to 30 days. | Reagents were effective when stored on-board for up to at least 30 days. |
| On-Board Stability (Calibrator/Controls) | In-use stability demonstrated; 12 months opened at 2-8°C after accelerated stability. | In-use stability of calibrators and controls was demonstrated. Accelerated OPEN stability at 37°C for 7 days showed stability. Once opened, vials may be stored at 2-8°C for 12 months. |
2. Sample Size and Data Provenance for Test Set:
- Recovery: Not explicitly stated, but "six replicates of each sample" were assayed across various concentrations, implying a total of 48 individual assays. Data provenance is human serum negative for lamotrigine, spiked with concentrated drug.
- Linearity: Not explicitly stated, but dilutions from a 48.00 µg/mL serum sample were made. Data provenance is human serum negative for lamotrigine, spiked with drug.
- Method Comparison (Study 1 - HPLC): 193 samples. Provenance not explicitly stated (e.g., country of origin, retrospective/prospective), but implied to be clinical samples or samples prepared to simulate clinical range.
- Method Comparison (Study 2 - Turbidimetric Immunoassay): 77 samples. Provenance not explicitly stated.
- Precision: Tri-level controls and three human serum pooled specimens. Each level assayed in quadruplicate twice a day for 20 days (160 measurements per control/pool level).
- Interfering Substances: Clinically high concentrations of substances in human serum with known lamotrigine levels (approximately 3 and 15 µg/mL).
- Specificity (Metabolites): Metabolites spiked into two separate samples each containing low (3 µg/mL) and high (15 µg/mL) therapeutic levels of lamotrigine.
- Specificity (Drug Interference): High concentration of each compound spiked into normal human serum with known lamotrigine levels (approximately 3 and 15 µg/mL).
- Anticoagulants: Not explicitly stated but implies a set of serum and plasma samples were tested.
- Sample Stability: Not explicitly stated, but samples were subject to various conditions (frozen, room temp, refrigerated, freeze/thaw cycles).
3. Number of Experts and their Qualifications for Ground Truth:
This type of device (quantitative immunoassay) relies on analytical performance against established reference methods or known concentrations, rather than expert interpretation of images or clinical data. Therefore, the concept of "experts establishing ground truth" as it applies to subjective assessments is not directly applicable here. The ground truth for analytical studies like recovery and linearity are based on gravimetric dilutions/known concentrations, and for method comparisons, the reference methods themselves (HPLC, predicate immunoassay) serve as the comparative standard.
4. Adjudication Method for the Test Set:
Not applicable for this type of analytical device validation. The studies involve quantitative measurements and comparisons to reference methods or known values, not subjective interpretations requiring adjudication.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No, an MRMC comparative effectiveness study was not done. This type of study is typically performed for diagnostic devices requiring human interpretation of results, such as imaging studies, where the AI's effect on human reader performance is evaluated. This device is an automated immunoassay for quantitative measurement.
6. Standalone (Algorithm Only) Performance:
Yes, the entire submission describes the standalone performance of the ARK™ Lamotrigine Assay. The studies (LOQ, assay range, recovery, linearity, method comparison, precision, interference, specificity, stability) evaluate the device's analytical performance independently. The device operates on automated clinical chemistry analyzers without human intervention for result generation.
7. Type of Ground Truth Used:
- Known Concentrations/Gravimetric Dilutions: For studies such as Limit of Quantitation, Recovery, Linearity, Precision, Interfering Substances, Specificity (Metabolites, Drug Interference), and Anticoagulants, the ground truth is established by preparing samples with known, precise concentrations of lamotrigine or interfering substances through gravimetric dilutions.
- Reference Methods: For method comparison studies, the reference methods are High Performance Liquid Chromatography (HPLC) and a predicate turbidimetric immunoassay (QMS® Lamotrigine, K062966).
8. Sample Size for the Training Set:
Not applicable. This device is a quantitative immunoassay with "wet lab" validation, not an AI/ML algorithm that typically requires a large clinical "training set" to learn patterns. The validation process involves demonstrating analytical performance against known standards and comparative methods.
9. How Ground Truth for the Training Set Was Established:
Not applicable, as there isn't a "training set" in the context of an AI/ML algorithm. The device's analytical characteristics are determined through laboratory experiments using carefully prepared samples with known concentrations or by comparison to reference methods.
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K/01305
પુદા 2 પુ ટેપાર
510(k) SUMMARY
ARK™ Lamotrigine Assay ARK™ Lamotrigine Calibrator ARK™ Lamotrigine Control
ARK Diagnostics, Inc. - 510(k) Summary ARK Lamotrigine Assay
page 1 of 15
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510(k) SUMMARY
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 K101305.
807.92 (a)(1): Name: ARK Diagnostics, Inc. Address: 1190 Bordeaux Drive Sunnyvale, CA 94089 Owner Operator Number: 10027663 Establishment Registration: 3005755244 (400) スイフ 0700 n.
| Phone: | (408) 747-0700 |
|---|---|
| FAX: | (408) 747-0783 |
| Contact: | Johnny Valdez – (408) 747-0706President |
Date prepared: October 20, 2010
807.92 (a)(2): Device name- trade name and common name, and classification
| Trade name: | ARK TM Lamotrigine Assay |
|---|---|
| ARK TM Lamotrigine Calibrator | |
| ARK TM Lamotrigine 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
QMS® Lamotrigine, calibrators and controls (K062966)
ARK Diagnostics, Inc. - 510(k) Summary ARK Lamotrigine Assay
page 2 of 15
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807.92 (a)(4): Device Description
The ARK Lamotrigine Assay is a homogeneous immunoassay based on competition between drug in the specimen and lamotrigine 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 Lamotrigine Assay consists of reagents R1 anti-lamotrigine polyclonal antibody with substrate and R2 lamotrigine labeled with bacterial G6PDH enzyme. The ARK Lamotrigine Calibrator consists of a six-level set to calibrate the assay, and the ARK Lamotrigine 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™ Lamotrigine Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of lamotrigine in human serum or plasma on automated clinical chemistry analyzers. Lamotrigine concentrations can be used as an aid in management of patients treated with lamotrigine.
The ARKTM Lamotrigine Calibrator is intended for use in calibration of the ARK Lamotrigine Assay.
The ARKTM Lamotrigine Control is intended for use in quality control of the ARK Lamotrigine Assay.
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807.92 (a)(6): Technological Similarities and Differences to the Predicate
:
SUBSTANTIAL EQUIVALENCE COMPARATIVE CHART
| Characteristic | Device | Predicate |
|---|---|---|
| ARK™ Lamotrigine Assay | QMS® Lamotrigine K062966 | |
| Intended Use | The ARK™ Lamotrigine Assay isintended for the quantitativedetermination of lamotrigine in humanserum or plasma on automated clinicalchemistry analyzers. | The QMS Lamotrigine is intended forthe quantitative determination oflamotrigine in human serum or plasmaon automated clinical chemistryanalyzers. |
| Indications forUse | Lamotrigine concentrations can be usedas an aid in management of patientstreated with lamotrigine. | Lamotrigine concentrations can be usedas an aid in management of patientstreated with lamotrigine. |
| Sample | Serum or plasma | Serum or plasma |
| Methodology | Homogenous enzyme immunoassay(EIA) | Homogeneous particle-enhancedturbidimetric immunoassay (particleagglutination) |
| ReagentComponents | Two (2) reagent system:Anti-LamotrigineAntibody/Substrate Reagent(R1) containing rabbitpolyclonal antibodies tolamotrigine, glucose-6-phosphate, nicotinamide adeninedinucleotide, bovine serumalbumin, preservatives, andstabilizers Enzyme Reagent (R2)containing lamotrigine labeledwith bacterial G6PDH, buffer,bovine serum albumin,preservatives, and stabilizers | Two (2) reagent system:Anti-Lamotrigine AntibodyReagent (R1) in bufferscontaining stabilizers withsodium azide Lamotrigine-coatedMicroparticle Reagent (R2) inbuffer containingstabilizers with sodium azide |
| Platform required | Automated clinical chemistry analyzer | Automated clinical chemistry analyzer |
| Accessoryreagents | Calibrators (six levels) and controls(three levels) | Calibrators (six levels) and controls(three levels) |
| Testingenvironment | Routine clinical laboratory | Routine clinical laboratory |
| Reagentcondition andstorage | Liquid, 2-8° C | Liquid, 2-8° C |
.
Comparison between the ARK™ Lamotrigine Assay and the OMS® Lamotrigine Assay
ARK Diagnostics, Inc. – 510(k) Summary ARK Lamotrigine Assay
page 4 of 15
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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 Lamotrigine 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 0.85 µg/mL, and may depend on analyzer-specific performance.
Assay Range
The range of the assay is 0.85 to 40.00 µg/mL. Report results below this range as <0.85 µg/mL or below the analyzer-specific lower LOQ established in your laboratory. Report results above this range as >40.00 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 lamotrigine in the undiluted specimen.
Recovery
Accuracy (analytical recovery) was performed by adding concentrated lamotrigine drug into human serum negative for lamotrigine. A stock concentrate of highly pure lamotrigine was added volumetrically to human serum negative for lamotrigine, 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.
| TheoreticalConcentration(µg/mL) | Mean RecoveredConcentration(µg/mL) | PercentRecovery |
|---|---|---|
| 0.85 | 0.84 | 98.2 |
| 1.00 | 0.99 | 99.2 |
| 2.50 | 2.48 | 99.3 |
| 5.00 | 5.25 | 105.1 |
| 11.00 | 10.97 | 99.7 |
| 15.00 | 14.80 | 98.7 |
| 30.00 | 29.16 | 97.2 |
| 40.00 | 38.33 | 95.8 |
| % Recovery = 100 X Mean recovered concentration | |||
|---|---|---|---|
| Theoretical concentration |
Mean percent recovery: 99.2
page 5 of 15
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Linearity
Linearity studies were performed as suggested in CLSI/NCCLS Protocol EP6-A. A 48.00 µg/mL serum sample was prepared and dilutions were made proportionally with human serum negative for lamotrigine. Lamotrigine concentrations ranged from 1.00 to 48.00 ug/mL. Linearity at specific dilutions was considered acceptable if the percent difference was ±10% between the predicted 155 and 2nd order regressed values. Results are shown below.
| EstimatedValue (µg/mL) | Results(ug/mL) | 1st OrderPredictedResults | 2nd OrderPredictedResults | % Difference(AcceptanceCriteria:+10%) |
|---|---|---|---|---|
| 1.00 | 0.96 | 1.13 | 1.21 | 7.1 |
| 2.00 | 2.08 | 2.11 | 2.17 | 3.1 |
| 4.00 | 4.16 | 4.06 | 4.10 | 0.9 |
| 8.00 | 8.18 | 7.97 | 7.96 | -0.1 |
| 12.00 | 12.01 | 11.88 | 11.83 | -0.4 |
| 16.00 | 16.18 | 15.78 | 15.72 | -0.4 |
| 24.00 | 22.78 | 23.60 | 23.53 | -0.3 |
| 32.00 | 30.84 | 31.41 | 31.39 | -0.1 |
| 40.00 | 40.13 | 39.23 | 39.30 | 0.2 |
| 48.00* | 46.88 | 47.04 | 47.27 | 0.5 |
*Concentration exceeds the reportable limit.
Method Comparison
Correlation studies were performed using CLSI/NCCLS Protocol EP9-A2. Results from the ARK Lamotrigine Assay on the Roche/Hitachi 917 system were compared with results from high performance liquid chromatography (HPLC, Study 1) and a turbidimetric immunoassay (Study 2).
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Study 1
Lamotrigine concentrations by HPLC ranged 1.00 to 36.70 µg/mL. ARK lamotrigine values ranged 0.97 to 36.32 µg/mL. Results of the Passing-Bablok' regression analysis for the study are shown below (with 95% confidence limits).
| Slope | 1.01 | (0.99 to 1.03) |
|---|---|---|
| y-intercept | 0.37 | (0.22 to 0.55) |
| Correlation Coefficient (r2) | 0.97 | (0.96 to 0.98) |
| Number of Samples | 193 |
Image /page/6/Figure/3 description: This image is a scatter plot comparing two different methods of measuring Lamotrigine concentration. The x-axis represents the concentration measured by HPLC in micrograms per milliliter, while the y-axis represents the concentration measured by ARK Lamotrigine Assay, also in micrograms per milliliter. The plot includes a line of identity and a Passing & Bablok fit line, which is described by the equation y = 0.37 + 1.01x.
ARK Diagnostics, Inc. - 510(k) Summary ARK Lamotrigine Assay
page 7 of 15
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Study 2
Lamotrigine concentrations by the turbidimetric immunoassay ranged from 2.28 µg/mL to 37.70 µg/mL. ARK lamotrigine values ranged 2.51 to 36.32 µg/mL. Results of the Passing-Bablok" regression analysis for the study are shown below (with 95% confidence limits).
| Slope | 0.93 | (0.89 to 0.97) |
|---|---|---|
| y-intercept | 0.41 | (0.07 to 0.74) |
| Correlation Coefficient (r2) | 0.96 | (0.94 to 0.97) |
| Number of Samples | 77 |
Image /page/7/Figure/3 description: This figure is a scatter plot comparing two different assays for measuring Lamotrigine. The x-axis represents the Turbidimetric Immunoassay in μg/mL, while the y-axis represents the ARK Lamotrigine Assay in μg/mL. The plot includes a Passing & Bablok fit line, represented by the equation (0.41 + 0.93x), along with an identity line for reference.
page 8 of 15
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Precision
Precision was determined as described in CLSI/NCCLS Protocol EP5-A2. Tri-level controls and three human serum pooled specimens containing lamotrigine 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 Run | Between Day | Total | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Sample | N | Mean(µg/mL) | SD | CV(%) | SD | CV(%) | SD | CV(%) | |
| ARK Lamotrigine Control | |||||||||
| LOW | 160 | 2.08 | 0.07 | 3.4 | 0.05 | 2.5 | 0.08 | 4.1 | |
| MID | 160 | 11.70 | 0.42 | 3.6 | 0.28 | 2.4 | 0.49 | 4.2 | |
| HIGH | 160 | 24.23 | 0.99 | 4.1 | 1.06 | 4.4 | 1.47 | 6.1 | |
| Calibrator/ControlMatrix | 40 | 38.04 | 2.05 | 5.4 | 0.95 | 2.5 | 2.27 | 6.0 | |
| Human Serum | |||||||||
| LOW | 160 | 2.41 | 0.08 | 3.5 | 0.09 | 3.7 | 0.12 | 5.2 | |
| MID | 160 | 10.75 | 0.41 | 3.8 | 0.42 | 3.9 | 0.59 | 5.5 | |
| HIGH | 160 | 25.84 | 1.33 | 5.2 | 1.12 | 4.3 | 1.88 | 7.3 | |
| Pooled HumanSerum | 40 | 38.24 | 2.78 | 7.3 | 0.61 | 1.6 | 3.38 | 8.8 |
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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 lamotrigine (approximately 3 and 15 µg/mL) were evaluated. Each sample was assayed using the ARK Lamotrigine Assay, along with a serum control of lamotrigine. Measurement of lamotrigine resulted in ≤10% error in the presence of interfering substances at the levels tested.
| Percentage Recovery | |||
|---|---|---|---|
| InterferingSubstance | InterferentConcentration | 3 $\mu$ g/mLLamotrigine | 15 $\mu$ g/mLLamotrigine |
| Albumin | 12 g/dL | 101.5 | 103.4 |
| Bilirubin - conjugated | 70 mg/dL | 93.6 | 102.6 |
| Bilirubin - unconjugated | 70 mg/dL | 97.1 | 105.0 |
| Cholesterol | 623 mg/dL | 98.9 | 103.8 |
| Gamma-Globulin | 12 g/dL | 106.8 | 104.4 |
| Hemoglobin | 1000 mg/dL | 98.2 | 97.0 |
| Intralipid® | 1000 mg/dL | 94.5 | 94.3 |
| Rheumatoid Factor | 1100 IU/mL | 107.3 | 108.9 |
| Triglycerides | 618 mg/dL | 101.7 | 104.0 |
| Uric Acid | 30 mg/dL | 101.0 | 99.6 |
Specificity
Lamotrigine's major metabolite, medications that may be routinely co-administered with lamotrigine and other anti-evileptic drugs were tested to determine whether these compounds affect the quantitation of lamotrigine concentrations using the ARK Lamotrigine Assay. High levels of these compounds were spiked into serum pools containing low (3 µg/mL) and high (15 µg/mL) therapeutic levels of lamotrigine. The samples were analyzed and the lamotrigine concentrations of samples containing interferent were compared to the serum control.
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Metabolites
Lamotrigine is metabolized predominantly by UDP-glucuronyltransferase to form a pharmacologically inactive metabolite, 2-N-glucuronide. Lamotrigine-2-N-methyl has been detected in human plasma by HPLC and capillary electrophoresis. Other minor metabolites, lamotrigine-2-N-oxide, and lamotrigine-5-N-glucuronide have been proposed. Lamotrigine-2-N-glucuronide, Lamotrigine-2-N-methyl and Lamotrigine-2-N-oxide metabolites were tested for cross-reactivity. These metabolites were spiked into two separate samples each containing low and high lamotrigine concentrations of 3 and 15 µg/mL, respectively.
| Metabolite* | MetaboliteConcentration(\u03bcg/mL) | Percentage Cross-Reactivity | |
|---|---|---|---|
| Lamotrigine(3 \u03bcg/mL) | Lamotrigine(15 \u03bcg/mL) | ||
| Lamotrigine-2-N-glucuronide | 50.0 | 2.41 | 1.86 |
| Lamotrigine-2-N-glucuronide | 25.0 | 2.57 | 1.09 |
| Lamotrigine-2-N-glucuronide | 12.5 | 2.91 | 1.92 |
| Lamotrigine-2-N-glucuronide | 9.0 | 2.15 | 1.57 |
| Lamotrigine-2-N-methyl | 400.0 | 0.04 | 0.21 |
| Lamotrigine-2-N-methyl | 200.0 | 0.07 | 0.02 |
| Lamotrigine-2-N-methyl | 80.0 | 0.10 | 0.24 |
| Lamotrigine-2-N-oxide | 80 | 3.69 | 3.63 |
| Lamotrigine-2-N-oxide | 40 | 3.94 | 3.64 |
| Lamotrigine-2-N-oxide | 20 | 3.72 | 3.14 |
| Lamotrigine-2-N-oxide | 10 | 3.88 | 1.30 |
- The literature suggests there is weak evidence for the presence of minor metabolites in human plasma.
Drug Interference
Lamotrigine-selective antibody did not crossreact with most other anti-epileptic or coadministered drugs tested. Due to structural similarities with lamotrigine, high trimethoprim levels may interfere. A high concentration of each compound was spiked into normal human serum with known levels of lamotrigine (approximately 3 and 15 ug/mL) and assayed along with a serum control of lamotrigine. Measurement of lamotrigine resulted in ≤10% error in the presence of drug compounds at the levels tested.
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| Conc.Tested(µg/mL) | Percentage Recovery | ||
|---|---|---|---|
| Compound | 3 µg/mL Lamotrigine | 15 µg/mLLamotrigine | |
| Acetaminophen | 200 | 103.7 | 99.1 |
| Acetazolamide | 100 | 101.2 | 99.2 |
| Acetylsalicylic acid | 1000 | 100.8 | 100.7 |
| Amikacin | 100 | 95.7 | 97.0 |
| Amitriptyline | 20 | 99.0 | 97.9 |
| Amoxapine | 40 | 104.7 | 101.2 |
| Amphotericin B | 100 | 94.0 | 91.6 |
| Ampicillin | 100 | 97.7 | 94.1 |
| Ascorbic Acid | 100 | 98.5 | 94.4 |
| Baclofen | 100 | 95.8 | 90.9 |
| Buproprion | 40 | 98.8 | 106.2 |
| Caffeine | 100 | 101.3 | 103.2 |
| Carbamazepine | 120 | 104.3 | 103.2 |
| Carbamazepine-10, 11epoxide | 120 | 101.7 | 99.0 |
| 10-Hydroxycarbamazepine | 100 | 96.2 | 94.3 |
| Chloramphenicol | 250 | 103.7 | 98.4 |
| Chlorpromazine | 20 | 97.2 | 95.0 |
| Citalopram | 20 | 98.0 | 97.5 |
| Clobazam | 100 | 103.4 | 105.6 |
| Clonazepam | 20 | 97.6 | 96.4 |
| Cyclosporin A | 40 | 101.7 | 99.4 |
| Diazepam | 20 | 101.1 | 97.7 |
| Digoxin | 80 | 103.4 | 97.6 |
| Doxepin | 20 | 101.6 | 103.1 |
| Erythromycin | 200 | 103.6 | 103.9 |
| Ethanol | 4000 | 94.0 | 98.2 |
| Ethotoin | 100 | 101.3 | 101.9 |
| Ethosuximide | 250 | 101.0 | 96.4 |
| Felbamate | 250 | 103.0 | 101.4 |
| Fluoxetine | 20 | 102.2 | 97.0 |
| Furosemide | 100 | 99.8 | 97.1 |
| Gentamicin | 100 | 99.8 | 98.6 |
| Conc.Tested(µg/mL) | Percentage Recovery | ||
| Compound | 3 µg/mL Lamotrigine | 15 µg/mL Lamotrigine | |
| Haloperidol | 20 | 104.1 | 100.3 |
| Heparin | 200U/mL | 99.0 | 100.5 |
| Ibuprofen | 500 | 101.6 | 96.2 |
| Imipramine | 20 | 99.6 | 97.7 |
| Kanamycin B | 200 | 98.5 | 100.5 |
| Gabapentin | 200 | 103.8 | 98.1 |
| Levetiracetam | 400 | 103.6 | 101.9 |
| Lidocaine | 100 | 101.6 | 101.8 |
| Lincomycin | 1000 | 106.0 | 99.7 |
| Mephenytoin | 100 | 95.7 | 103.9 |
| Mesoridazine | 40 | 97.6 | 101.7 |
| Methicillin | 250 | 95.2 | 99.4 |
| Naproxen | 600 | 97.3 | 104.8 |
| Neomycin | 1000 | 100.8 | 101.6 |
| Niacin | 100 | 97.8 | 105.8 |
| Nitrazepam | 20 | 101.5 | 103.9 |
| Nortriptyline | 20 | 96.6 | 104.9 |
| Olanzapine | 20 | 99.5 | 102.2 |
| Oxcarbazepine | 200 | 97.3 | 100.5 |
| Paroxetine | 40 | 101.6 | 100.0 |
| 2-phenyl-ethyl-malonamide (PEMA) | 1000 | 100.1 | 100.9 |
| Penicillin V | 100 | 100.4 | 101.4 |
| Perphenazine | 100 | 99.5 | 103.2 |
| Phenobarbital | 200 | 101.0 | 98.9 |
| Phenytoin | 200 | 100.0 | 100.8 |
| Pregabalin | 200 | 99.6 | 98.4 |
| Primidone | 100 | 98.7 | 102.5 |
| Procainamide | 100 | 100.6 | 101.9 |
| Prochlorperazine | 40 | 99.4 | 90.3 |
| Ranitidine | 100 | 104.0 | 97.8 |
| Rifampin | 100 | 101.6 | 97.7 |
| Risperidone | 20 | 98.0 | 100.2 |
| Sertraline | 100 | 101.5 | 101.9 |
| Compound | Conc.Tested(µg/mL) | Percentage Recovery | |
| 3 µg/mL Lamotrigine | 15 µg/mL Lamotrigine | ||
| Spectinomycin | 100 | 97.7 | 103.1 |
| Stiripentol | 100 | 102.3 | 101.6 |
| Sulfamethoxazole | 400 | 99.2 | 99.2 |
| Theophylline | 200 | 98.7 | 97.9 |
| Thioridazine | 20 | 102.9 | 101.3 |
| Tobramycin | 100 | 98.8 | 96.9 |
| Tiagabine | 200 | 100.9 | 97.8 |
| Topiramate | 250 | 100.3 | 96.7 |
| Valproic Acid | 600 | 100.8 | 96.8 |
| Vancomycin | 250 | 96.5 | 95.0 |
| Vigabatrin | 150 | 97.8 | 101.0 |
| Zonisamide | 400 | 97.9 | 99.6 |
ARK Diagnostics, Inc. – 510(k) Summary ARK Lamotrigine Assay
page 12 of 15
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ARK Diagnostics, Inc. – 510(k) Summary ARK Lamotrigine Assay
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page 13 of 15
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Drug that Cross-Reacts
Cross-reactivity of the antibody to trimethoprim at the following concentration was tested. A high concentration was spiked into normal human serum with known levels of lamotrigine (approximately 3 and 15 ug/mL) and assayed along with a serum control of lamotrigine. The results are shown below.
| Trimethoprim(µg/mL) | Percent Cross-Reactivity | Percent Recovery | ||
|---|---|---|---|---|
| Lamotrigine(3 µg/mL) | Lamotrigine(15 µg/mL) | Lamotrigine(3 µg/mL) | Lamotrigine(15 µg/mL) | |
| 40.0 | 4.4 | 3.0 | 156.0 | 108.0 |
Care should be taken when interpreting ARK Lamotrigine results if trimethoprim is also being administered to the patient.
Anticoagulants
Studies were conducted to determine the performance characteristics of the assay for both serum and plasma samples containing lamotrigine.
The results indicate that there is no significant difference between the recovery of lamotrigine in serum or plasma.
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Sample Stability
Serum specimens were shown to be stable for at least six (6) months frozen, at least fifty (50) hours at room temperature (22°C), at least thirty-seven (37) days when refrigerated (2-8°C) and after three (3) successive freeze/thaw cycles.
On-Board Stability
Calibration Curve Stability: Calibration curve stability for a period of 30 days is supported by data.
Reagent on-board stability:
Reagents were effective when stored after transfer to analyzer specific reagent containers for up to at least 30 days as supported data. In-use stability of calibrator and controls was also demonstrated.
Accelerated OPEN stability of calibrators and controls: Calibrators and controls were shown to be stable OPEN in accelerated stability at 37℃ for seven (7) days. Once opened vials may be stored at 2-8℃ for 12 months.
Traceabiliity of Calibrators and Controls
There is no internationally recognized standard for lamotrigine. ARK Lamotrigine Calibrators and ARK Lamotrigine Controls are prepared by gravimetric dilution of high purity lamotrigine into a synthetic proteinaceous matrix free of lamotrigine.
The calibrator/control matrix was shown to be equivalent to human serum with supporting data.
807.92 (b)(3): Conclusions from Nonclinical Testing
The ARK Lamotrigine Assay, the ARK Lamotrigine Calibrator and the ARK Lamotrigine Control are substantially equivalent to the QMS Lamotrigine Assay system. The ARK Lamotrigine Assay system was shown to be safe and effective for its intended use based on performance studies.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Image /page/15/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, rendered in a simple, stylized manner.
Food & Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993
ARK Diagnostics, Inc.
c/o Dr. Kenneth Kasper
Executive Director, Quality & Regulatory Affairs
1190 Bordeaux Drive
Sunnyvale, CA 94089
OCT 29 2010
Re: K101305 Trade Name: ARK™ Lamotrigine Assay, ARK™ Lamotrigine Calibrator, and ARK™ Lamotrigine Control
Regulation Number: 21 CFR 862.3350 Regulation Name: Diphenylhydantoin Test System. Regulatory Class: Class II Product Codes: ORH, DLJ, LAS Dated: October 28, 2010 Received: October 29, 2010
Dear Dr. Kasper:
We have reviewed your Section 510(k) premarket notification of intent to market the we have reviewed your Bookers = exermined 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 m interslate commerce proof to may 20, 2014 11:55 am accordance with the provisions of Annemallens, or to do roos mar metic Act (Act) that do not require approval of a premarket the Federal I ood, Drag, and Ocomens , therefore, market the device, subject to the general approval apprication (1 Mr 1). controls provisions of the rictration, 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 II your device is classified (500 above) into controls. Existing major regulations affecting (PMA), II may be subject to such additional controllar controllations (CFR), Parts 800 to 895. your device can be found in This 21, Occo ecceming 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 mean that FDA has made a determination these and regulations administered by other requirements of the Act of any Podern stall the Act's requirements, including, but not Federal agencies. Tou must compry with an the 100 row would be (21 CFR Parts 801 and 809);
Imited to: registration and listing (21 CFR Part 807); labeling (21 CFR medical device reporting (reporting of medical device-related adverse events) (21 CFR)
medical device reporting (reporting of medical device-related adverse evelity avatems medical device reporting (reporting of medical device forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2 -
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), 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 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) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
CJC.
Courtney 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):
101305
OCT 2 9 2010
Device Name:
ARKTM Lamotrigine Assay ARKTM Lamotrigine Calibrator ARKTM Lamotrigine Control
Indications for Use:
The ARK™ Lamotrigine Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of lamotrigine in human serum or plasma on automated clinical chemistry analyzers.
Lamotrigine concentrations can be used as an aid in management of patients treated with lamotrigine.
The ARKTM Lamotrigine Calibrator is intended for use in calibration of the ARK Lamotrigine Assay.
The ARK™ Lamotrigine Control is intended for use in quality control of the ARK Lamotrigine 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 (OVD)
Division Sign Off
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K101305
ARK Lamotrigine 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.