(193 days)
Not Found
No
The device description and performance studies detail a standard homogeneous enzyme immunoassay. There is no mention of AI, ML, or any computational methods beyond basic data processing for spectrophotometric measurements. The "Mentions AI, DNN, or ML" section explicitly states "Not Found".
No
This device is an in vitro diagnostic assay used for the quantitative determination of levetiracetam in human serum or plasma, which aids in managing patients treated with levetiracetam. It does not provide any treatment or therapeutic effect.
Yes
Explanation: The device is intended for the "quantitative determination of levetiracetam in human serum or plasma" and states that "Levetiracetam concentrations can be used as an aid in management of patients treated with levetiracetam," indicating it provides information that helps in patient management, which is a diagnostic purpose.
No
The device is an in vitro diagnostic assay that consists of chemical reagents for the quantitative determination of levetiracetam in human serum or plasma. It is not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "quantitative determination of levetiracetam in human serum or plasma." This involves testing a sample taken from the human body in vitro (outside the body).
- Device Description: The description details a "homogeneous enzyme immunoassay" that uses reagents to measure a substance in a biological sample. This is a characteristic method used in IVD devices.
- Performance Studies: The performance studies describe testing the assay's characteristics (LoQ, measurement range, recovery, linearity, method comparison, precision, interference) using human serum and plasma samples. This is standard practice for validating an IVD.
- Predicate Device: The mention of a "Predicate Device" (K091653; ARK Levetiracetam Assay) is common in regulatory submissions for IVDs, indicating a comparison to a previously cleared device of the same type.
All these elements strongly indicate that the ARK Levetiracetam II Assay is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
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.
Product codes (comma separated list FDA assigned to the subject device)
ORI
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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Routine clinical laboratory
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Limit of Quantitation (LoQ)
Study Type: LoQ determination according to CLSI EP17-A2.
Sample Size: 40 replicates for each concentration (1.0, 2.0, 3.0 µg/mL).
Key Results: The LoQ was determined to be 2.0 µg/mL. Precision (CV) at 2.0 µg/mL was 2.80% and at 3.0 µg/mL was 2.55%.
Recovery
Study Type: Analytical recovery.
Sample Size: Two analytical runs of three replicates of each sample (6 replicates total) at various concentrations.
Key Results: Recovery at all concentrations tested was +/-10% of the expected sample concentration.
Linearity
Study Type: Linearity studies as suggested in CLSI Protocol EP06-Ed2.
Key Results: A linear relationship was demonstrated between 2.0 to 100.0 µg/mL. The regression equation was y=1.003x. Percent Deviation was within +/-10%.
Method Comparison
Study Type: Correlation studies using CLSI Protocol EP9-A3.
Sample Size: 104 samples.
Key Results: Results from the ARK Levetiracetam II Assay (Beckman Coulter AU680) were compared with results from the predicate ARK Levetiracetam Assay (Roche/Hitachi 917).
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)
Precision
Study Type: Precision determined as described in CLSI Protocol EP05-A3.
Sample Size: 160 for each of the three control levels and three human serum samples.
Key Results: Total CVs were all below 10%, ranging from 1.6% to 2.9% for both controls and human serum samples.
Interfering Substances
Study Type: Interference studies using CLSI EP07-A3.
Key Results: Measurement of levetiracetam resulted in
§ 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.
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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 Boulevard | ||
| Fremont, CA 94538 | |||
| Owner Operator Number: | Establishment Registration: | 10027663 | |
| 3005755244 | |||
| Phone: | |||
| FAX: | |||
| Contact: | (510) 270-6276 | ||
| (510) 270-6298 | |||
| Dionne Labatore | |||
| Director, Regulatory Affairs and Quality Assurance | |||
| Email: 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 intended | |
| for the quantitative determination of | ||
| levetiracetam in human serum or plasma on | ||
| automated clinical chemistry analyzers. | Same | |
| Indications for Use | Levetiracetam concentrations can be used as | |
| an aid in management of patients treated with | ||
| levetiracetam. | Same | |
| Sample | Serum or plasma | Same |
| Methodology | Homogeneous enzyme immunoassay (EIA) | Same |
| Reagent | ||
| Components | Two (2) reagent system: | |
| Anti-levetiracetam Antibody/Substrate | ||
| Reagent (R1) containing rabbit polyclonal | ||
| antibodies to levetiracetam, glucose-6- | ||
| phosphate, nicotinamide adenine | ||
| dinucleotide, bovine serum albumin, | ||
| preservatives, and stabilizers | ||
| Enzyme Reagent (R2) containing | ||
| levetiracetam labeled with bacterial G6PDH, | ||
| buffer, bovine serum albumin, preservatives, | ||
| and stabilizers | Two (2) reagent system: | |
| Anti-levetiracetam Antibody/Substrate | ||
| Reagent (R1) containing rabbit monoclonal | ||
| antibodies to levetiracetam, glucose-6- | ||
| phosphate, nicotinamide adenine | ||
| dinucleotide, bovine serum albumin, sodium | ||
| azide, and stabilizers | ||
| Enzyme Reagent (R2) containing | ||
| levetiracetam 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 (three | |
| levels) | Same | |
| Testing | ||
| environment | Routine clinical laboratory | Same |
| Reagent condition | ||
| and 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.
| Nominal
Concentration
(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 Concentration
| Tested (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: