(193 days)
The ARK Levetiracetam II 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 II 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 related 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 coenzyme NAD functions only with the bacterial enzyme used in the assay.
The ARK Levetiracetam II Assay consists of reagents R1 anti-levetiracetam monoclonal antibody with substrate and R2 levetiracetam labeled with bacterial G6PDH enzyme.
The provided text describes the performance of a diagnostic assay (ARK Levetiracetam II Assay), not an AI/ML-enabled medical device. Therefore, many of the requested criteria related to AI/ML evaluation (such as MRMC studies, training set details, expert ground truth establishment for AI) are not applicable.
However, I can extract the relevant acceptance criteria and performance data for this in-vitro diagnostic device:
Device Name: ARK Levetiracetam II Assay
Regulatory Class: Class II
Product Code: ORI
Intended Use: Quantitative determination of levetiracetam in human serum or plasma on automated clinical chemistry analyzers, as an aid in management of patients treated with levetiracetam.
Here's the information based on the provided document:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria (Implicit from study design/CLSI guidelines) | Reported Device Performance (ARK Levetiracetam II Assay) |
|---|---|---|
| Limit of Quantitation (LoQ) | ≤20% CV precision and ±15% recovery | 2.0 µg/mL (at 2.80% CV and 95.0% recovery) |
| Measurement Range | Not explicitly stated as acceptance criterion, but established. | 2.0 - 100.0 µg/mL |
| Recovery | ±10% of the expected sample concentration | All tested concentrations (2.0-100.0 µg/mL) showed %Recovery within ±10% (e.g., 95.0% to 102.6%) |
| Linearity | Percent difference (Deviation) ±10% between predicted and observed results | All tested concentrations (2.0-100.0 µg/mL) showed %Deviation within ±10% (e.g., -6.1% to 9.5%) |
| Precision (Total CV) | <10% Total CV | For all control and human serum samples, Total CV ranged from 1.6% to 2.9% |
| Interfering Substances | ≤10% error (relative to serum control mean result) | All tested interferents showed ≤10% error (e.g., 91.0% to 102.7% recovery) |
| Metabolites (Cross-reactivity) | ≤10% error (relative to serum control mean result) | ucb L057 showed 0.0% cross-reactivity and ≤10% interference (0.8% and 0.1% for 15 and 50 µg/mL Levetiracetam, respectively) |
| Drug Interference (Other Anti-Epileptic/Coadministered Drugs) | ≤10% error (relative to serum control mean result) | All tested drugs (except brivaracetam) showed ≤10% error. |
| Sample Stability | Not explicitly stated (implied sufficient stability for clinical use) | Stable for 48 hours at 22°C, 40 days at 2-8°C, and after 3 freeze/thaw cycles. |
| Product Stability (Shelf-life) | Not explicitly stated (implied sufficient shelf-life) | 18 months when stored unopened at 2-8°C. |
| On-Board Stability (Reagents) | Not explicitly stated (implied sufficient stability) | Stable up to 96 days. |
| Calibration Curve Stability | Not explicitly stated (implied sufficient stability) | Effective up to at least 28 days. |
2. Sample Size Used for the Test Set and Data Provenance
- LoQ: 40 replicates (8 replicates x 5 runs) for each of 3 concentrations (pooled human serum supplemented with levetiracetam).
- Recovery: 6 replicates (3 replicates x 2 analytical runs) for each concentration (human serum negative for levetiracetam, spiked with drug).
- Linearity: 6 replicates (3 replicates x 2 analytical runs) for each dilution (human serum, spiked with drug and diluted).
- Method Comparison: 104 samples (levetiracetam concentrations 3.4 ug/mL to 98.3 ug/mL). No specific provenance (e.g., country of origin) is mentioned, but the samples are clinical human samples or quality control materials. The study is a prospective analytical study comparing two assays.
- Precision: 160 replicates per sample/control level (quadruplicate twice a day for 20 non-consecutive days) for tri-level controls and three human serum samples.
- Interfering Substances: 6 replicates (3 replicates x 2 analytical runs) for each interfering substance level in two known levetiracetam concentrations (human serum).
- Metabolites/Drug Interference: Not explicitly stated, but similar to interfering substances: "high concentration of each compound was spiked into normal human serum with known levels of levetiracetam."
The data provenance is from analytical studies conducted by the manufacturer, likely in a laboratory setting, using human serum/plasma samples/materials. The document does not specify country of origin for the samples/data, beyond "human serum/plasma". These are prospective analytical studies designed to characterize the device's performance.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Experts
This section is not applicable as the document describes an in-vitro diagnostic assay for quantitative determination of a drug. The "ground truth" for such an assay is established by the known concentrations of calibrators, controls, and spiked samples, and comparison to a legally marketed predicate device using analytical methods (e.g., spectrophotometry). There are no human "experts" establishing a "ground truth" in the sense of image interpretation or clinical diagnosis.
4. Adjudication Method for the Test Set
Not applicable. This is an in-vitro diagnostic device providing quantitative measurements. There is no qualitative assessment or interpretation by multiple readers that would require an adjudication method.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done
No. This is an in-vitro diagnostic assay, not an AI/ML medical device where human readers interact with AI.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
Yes, in essence. The performance studies (LoQ, Recovery, Linearity, Precision, Interference) demonstrate the "standalone" performance of the assay itself, as an automated clinical chemistry analyzer performs the measurements. There is no human-in-the-loop variable in the measurement process of an immunoassay. The output is a quantitative value, not a diagnostic interpretation that a human would then use as "assistance."
7. The Type of Ground Truth Used
The ground truth used for performance evaluation is primarily:
- Known concentrations: For LoQ, Recovery, Linearity, Interfering Substances, Metabolites, and Drug Interference studies, concentrations of levetiracetam and potential interferents are precisely measured, prepared, or spiked into matrices.
- Reference Method/Predicate Device: For Method Comparison, the predicate ARK Levetiracetam Assay performed on the Roche/Hitachi 917 serves as the comparative "reference" for evaluating the substantial equivalence of the new assay. This is a common practice for IVD assays.
8. The Sample Size for the Training Set
Not applicable. This is a reagent-based immunoassay, not an AI/ML algorithm that requires a training set in the typical sense for machine learning. The "development" or "training" of such a diagnostic involves chemical formulation, antibody development, and optimization of reaction conditions, not data-driven model training.
9. How the Ground Truth for the Training Set Was Established
Not applicable. As explained above, there is no AI/ML training set in this context.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
ARK Diagnostics, Inc. Dionne Labatore Director, Regulatory Affairs and Quality Assurance 48089 Fremont Boulevard Fremont, California 94538
Re: K232522
Trade/Device Name: ARK Levetiracetam II Assay Regulation Number: 21 CFR 862.3350 Regulation Name: Diphenylhydantoin test system Regulatory Class: Class II Product Code: ORI Dated: January 12, 2024 Received: January 12, 2024
Dear Dionne Labatore:
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 (the Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
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.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Image /page/1/Picture/6 description: The image shows the name "Joseph A. Kotarek -S" in a simple, sans-serif font. The name is arranged in two lines, with "Joseph A." on the first line and "Kotarek -S" on the second line. The text is black against a white background.
Digitally signed by Joseph A. Kotarek -S Date: 2024.02.27 17:40:26 -05'00'
Joseph Kotarek Branch Chief for Toxicology Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
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Indications for Use
510(k) Number (if known) K232522
Device Name ARK Levetiracetam II Assay
Indications for Use (Describe)
ARK Levetiracetam II Assay: The ARK Levetiracetam II 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.
Type of Use (Select one or both, as applicable)
| Prescription Use (Part 21 CFR 801 Subpart D) | |
|---|---|
| -- | ---------------------------------------------- |
| Over-The-Counter Use (21 CFR 801 Subpart C) | |
|---|---|
| -- | --------------------------------------------- |
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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 K232522.
| 807.92 (a)(1): Name: | ARK Diagnostics, Inc. | ||
|---|---|---|---|
| Address: | 48089 Fremont BoulevardFremont, CA 94538 | ||
| Owner Operator Number: | Establishment Registration: | 100276633005755244 | |
| Phone:FAX:Contact: | (510) 270-6276(510) 270-6298Dionne LabatoreDirector, Regulatory Affairs and Quality AssuranceEmail: dionne@ark-tdm.com | ||
| Direct phone: (510) 270-6276 |
Date prepared: August 18, 2023
807.92 (a)(2): Device name- trade name and common name, and classification
| Trade name: | ARK Levetiracetam II Assay |
|---|---|
| Common Name: | Homogeneous Enzyme Immunoassay |
| Classification: | 21 CFR 862.3350 ORI Diphenylhydantoin Test System; Class II |
| 807.92 (a)(3): Identification of the legally marketed predicate device | |
| Predicate Device Name: | ARK Levetiracetam Assay |
Predicate Device 510(k) Number: K091653
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807.92 (a)(4): Device Description
The ARK Levetiracetam II 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 related 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 coenzyme NAD functions only with the bacterial enzyme used in the assay.
The ARK Levetiracetam II Assay consists of reagents R1 anti-levetiracetam monoclonal antibody with substrate and R2 levetiracetam labeled with bacterial G6PDH enzyme.
807.92 (a)(5): Intended Use / Indications for Use
ARK Levetiracetam II Assay
The ARK Levetiracetam II 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.
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807.92 (a)(6): Technological Similarities and Differences to the Predicate
SUBSTANTIAL EQUIVALENCE COMPARATIVE CHART
| Characteristic | Predicate Device | Candidate Device |
|---|---|---|
| ARK Levetiracetam Assay (K091653) | ARK Levetiracetam II Assay | |
| Intended Use | The ARK Levetiracetam Assay is intendedfor the quantitative determination oflevetiracetam in human serum or plasma onautomated clinical chemistry analyzers. | Same |
| Indications for Use | Levetiracetam concentrations can be used asan aid in management of patients treated withlevetiracetam. | Same |
| Sample | Serum or plasma | Same |
| Methodology | Homogeneous enzyme immunoassay (EIA) | Same |
| ReagentComponents | Two (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 stabilizers | Two (2) reagent system:Anti-levetiracetam Antibody/SubstrateReagent (R1) containing rabbit monoclonalantibodies to levetiracetam, glucose-6-phosphate, nicotinamide adeninedinucleotide, bovine serum albumin, sodiumazide, and stabilizersEnzyme Reagent (R2) containinglevetiracetam labeled with bacterial G6PDH,buffer, bovine serum albumin, sodium azide,and stabilizers |
| Platform required | Automated clinical chemistry analyzer | Same |
| Accessory reagents | Calibrators (six levels) and controls (threelevels) | Same |
| Testingenvironment | Routine clinical laboratory | Same |
| Reagent conditionand storage | Liquid, 2-8° C | Same |
Comparison between the ARK Levetiracetam Assay and the ARK Levetiracetam II Assay
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807.92 (b)(1) and 807.92 (b)(2): Brief Description of Nonclinical and Clinical Data
The following performance characteristics were obtained on the Beckman Coulter AU680 automated clinical chemistry analyzer.
Limit of Quantitation (LoQ)
The LoQ of the ARK Levetiracetam II Assay was determined to be 2.0 µg/mL and may depend on analyzer specific performance. The LoO was determined according to CLSI EP17-A2 and is defined as the lowest concentration for which acceptable inter-assay precision (≤20% CV) and recovery (±15%) is observed. Pooled human serum was supplemented with levetiracetam to give concentrations of 1.0, 2.0, and 3.0 µg/mL. Eight (8) replicates of each sample were tested in each of five (5) runs to give a minimum of 40 replicates of each LoQ sample tested.
| NominalConcentration(ug/mL) | N | Grand Mean(ug/mL) | RMS SD | CV |
|---|---|---|---|---|
| 1.0 | 40 | 0.9 | 0.044 | 4.91 |
| 2.0 | 40 | 1.9 | 0.052 | 2.80 |
| 3.0 | 40 | 3.0 | 0.077 | 2.55 |
Measurement Range
The measurement range of the ARK Levetiracetam II Assay is 2.0 - 100.0 µg/mL.
Recovery
Analytical recovery throughout the measurement range was performed by adding concentrated levetiracetam 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. Two analytical runs of three replicates of each sample were assayed on an automated clinical chemistry analyzer. The results of the six replicates of each sample were averaged and compared to the target concentration and percent recovery calculated. Recovery at all concentrations tested was ±10% of the expected sample concentration.
| Theoretical ConcentrationTested (ug/mL) | Mean (ug/mL) | %Recovery |
|---|---|---|
| 2.0 | 1.9 | 95.0 |
| 4.0 | 3.9 | 97.5 |
| 10.0 | 9.8 | 98.0 |
| 20.0 | 20.1 | 100.5 |
| 45.0 | 46.2 | 102.6 |
| 80.0 | 77.8 | 97.3 |
| 100.0 | 100.3 | 100.3 |
Linearity
Linearity studies were performed as suggested in CLSI Protocol EP06-Ed2. A 120.0 ug/mL levetiracetam serum sample was prepared, and dilutions were made proportionally with human
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serum negative for levetiracetam. Levetiracetam concentrations ranged from 2.0 to 100.0 µg/mL. Two analytical runs of three replicates of each sample were assayed on an automated clinical chemistry analyzer. The results of the six replicates of each sample were averaged. A weighted linear regression analysis was performed. Linearity was acceptable if the percent difference (% Deviation) was ±10% between the predicted results and the observed results. The regression equation calculated according to EP06-Ed2 is y=1.003x. A linear relationship was demonstrated between 2.0 to 100.0 µg/mL.
| Nominal(Estimated) Value(µg/mL) | Observed Results(µg/mL) | Predicted Results(ug/mL) | % Deviation |
|---|---|---|---|
| 0.0 | NA | NA | NA |
| 2.0 | 1.9 | 2.0 | -6.1 |
| 3.0 | 3.2 | 3.0 | 4.7 |
| 4.0 | 3.9 | 4.0 | -3.2 |
| 6.0 | 6.1 | 6.0 | 1.1 |
| 10.0 | 11.0 | 10.0 | 9.5 |
| 20.0 | 20.0 | 20.1 | -0.3 |
| 40.0 | 42.0 | 40.1 | 4.7 |
| 60.0 | 62.1 | 60.2 | 3.2 |
| 80.0 | 78.9 | 80.2 | -1.7 |
| 100.0 | 105.4 | 100.3 | 5.1 |
Weighted Linear Regression Analysis
Method Comparison
Correlation studies were performed using CLSI Protocol EP9-A3. Results from the ARK Levetiracetam II Assay performed on the Beckman Coulter AU680 were compared with results from the predicate ARK Levetiracetam Assay performed on the Roche/Hitachi 917. Levetiracetam concentrations ranged from 3.4 ug/mL to 98.3 ug/mL. Results of the Passing-Bablok regression analysis for the study are shown below (with 95% confidence limits).
| Slope | 1.04 | (1.03 to 1.06) |
|---|---|---|
| y-intercept | -0.30 | (-0.78 to 0.11) |
| Correlation Coefficient ( $r^2$ ) | 0.99 | (0.985 to 0.993) |
| Number of Samples | 104 |
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Image /page/8/Figure/0 description: This image is a scatter plot comparing two assays, ARK Levetiracetam II Assay and ARK Levetiracetam Assay - Predicate, both measured in micrograms per milliliter. The plot includes data points, a gray line representing identity, and a blue line representing the Passing & Bablok (I) fit, with the equation (-0.30 + 1.04x). The values on both axes range from 0 to 100, with the data points closely clustered around the lines.
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Precision
Precision was determined as described in CLSI Protocol EP05-A3. Tri-level controls and three samples of levetiracetam in pooled human serum were used in the study. Data were collected on a single analyzer over twenty (20) non-consecutive days. Each level was assayed in quadruplicate twice a day. 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 Levetiracetam II Control | ||||||||
| LOW | 160 | 7.6 | 0.16 | 2.1 | 0.09 | 1.2 | 0.18 | 2.3 |
| MID | 160 | 30.5 | 0.45 | 1.5 | 0.34 | 1.1 | 0.60 | 2.0 |
| HIGH | 160 | 75.7 | 1.41 | 1.9 | 0.99 | 1.3 | 2.19 | 2.9 |
| Human Serum | ||||||||
| LOW | 160 | 7.7 | 0.11 | 1.4 | 0.06 | 0.8 | 0.12 | 1.6 |
| MID | 160 | 32.6 | 0.47 | 1.4 | 0.34 | 1.1 | 0.61 | 1.9 |
| HIGH | 160 | 80.5 | 1.62 | 2.0 | 0.80 | 1.0 | 1.79 | 2.2 |
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Interfering Substances
Interference studies were conducted using CLSI EP07-A3 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. Two analytical runs of three replicates of each sample (6 replicates total) were assayed using the ARK Levetiracetam II Assay, along with a serum control of levetiracetam. The mean results of levetiracetam were calculated and the percentage recovery relative to the serum control mean result was determined. Measurement of levetiracetam resulted in ≤10% error in the presence of interfering substances at the levels tested.
| Interfering Substance | Interferent Concentration | Percentage Recovery (%) | |
|---|---|---|---|
| 15 µg/mL Levetiracetam | 50 µg/mL Levetiracetam | ||
| Human Albumin | 12 g/dL | 98.7 | 99.9 |
| Conjugate Bilirubin | 72 mg/dL | 100.2 | 100.9 |
| Unconjugated Bilirubin | 72 mg/dL | 101.7 | 97.1 |
| Cholesterol | 620 mg/dL | 94.9 | 100.8 |
| Human IgG | 12 g/dL | 102.7 | 98.7 |
| Hemoglobin | 1050 mg/dL | 100.9 | 95.8 |
| Rheumatoid Factor | 1080 IU/mL | 98.8 | 94.5 |
| Triglycerides | 1670 mg/dL | 98.6 | 95.9 |
| Uric Acid | 30 mg/dL | 91.0 | 98.8 |
Metabolites
ARK Levetiracetam II Assay serum and plasma results are unlikely to be affected by metabolism of levetiracetam drug, since plasma levels of metabolites are usually not clinically significant. The following metabolite was tested for crossreactivity. Measurement of levetiracetam resulted in ≤ 10% error in the presence of ucb L057 (2-pyrrolidone-N-butyric acid) at the level tested.
| Metabolite | ucbL057(µg/mL) | PercentCross-ReactivityLevetiracetam15 µg/mL | PercentCross-ReactivityLevetiracetam50 µg/mL | PercentInterferenceLevetiracetam15 µg/mL | PercentInterferenceLevetiracetam50 µg/mL |
|---|---|---|---|---|---|
| ucb L057:2-pyrrolidone-N-butyric acid | 250.0 | 0.0 | 0.0 | 0.8 | 0.1 |
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Drug Interference
Due to structural similarities, brivaracetam (Briviact®) crossreacts substantially in the ARK Levetiracetam II Assay. Measurements of levetiracetam should not be made with the ARK assay when both drugs are present in circulation.
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.
| Compound | Concentration(µg/mL) | Compound | Concentration(µg/mL) |
|---|---|---|---|
| Acetaminophen | 500 | Nortriptyline | 20 |
| Acetylsalicylic acid | 1000 | Oxcarbazepine | 50 |
| Amitriptyline | 20 | Phenobarbital | 200 |
| Caffeine | 100 | Phenytoin | 200 |
| Carbamazepine | 120 | Primidone | 100 |
| Clonazepam | 50 | Probenecid | 600 |
| Cyclosporin A | 40 | Salicylic Acid | 500 |
| Diazepam | 50 | Sulfamethoxazole | 400 |
| Digoxin | 40 | Sulfisoxazole | 400 |
| Erythromycin | 200 | Theophylline | 250 |
| Ethosuximide | 250 | Tiagabine | 200 |
| Felbamate | 250 | Topiramate | 250 |
| Gabapentin | 100 | Trimethoprim | 40 |
| Heparin | 200 units/mL | Valproic Acid | 500 |
| Hydrochlorothiazide | 20 | Verapamil | 100 |
| Ibuprofen | 500 | Vigabatrin | 150 |
| Lamotrigine | 250 | Warfarin | 250 |
| Naproxen | 500 | Zonisamide | 250 |
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Anticoagulants
Serum and plasma were accepted as equivalent matrices for the measurement of levetiracetam in the predicate submission K091653.
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.
Product Stability
Accelerated stability studies and real time stability studies support a shelf-life stability claim of up to 18 months for the ARK Levetiracetam II Reagents when stored unopened at 2-8°C.
On-Board Stability
Reagents were stable up to 96 days when stored on-board the instrument based on supporting data.
Calibration Curve Stability
A stored calibration curve was effective up to at least 28 days based on supporting data. Calibration curve stability may depend on individual laboratory performance.
807.92 (b)(3): Conclusions from Nonclinical Testing
As summarized above, the ARK Levetiracetam II Assay is substantially equivalent to the ARK Levetiracetam Assay system K091653. The ARK Levetiracetam II Assay system was shown to be safe and effective for its intended use based on performance studies.
§ 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.