(105 days)
No
The device description details a homogeneous enzyme immunoassay based on chemical reactions and spectrophotometric measurement, with no mention of AI or ML algorithms for data analysis or interpretation.
No
This device is an immunoassay designed for the quantitative determination of methotrexate levels in human serum, used for monitoring treatment, not for directly providing therapy or treatment itself.
Yes
This device is intended for the quantitative determination of Methotrexate in human serum to monitor drug levels and help ensure appropriate therapy, which is a diagnostic purpose.
No
The device is a homogeneous enzyme immunoassay, which involves chemical reagents and their interaction with a specimen, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states "intended for the quantitative determination of Methotrexate in human serum". This involves testing a sample taken from the human body (serum) outside of the body (in vitro) to obtain diagnostic information (monitoring levels of methotrexate to help ensure appropriate therapy).
- Device Description: The description details a laboratory assay using reagents to measure a substance in a biological sample.
- Performance Studies: The document includes performance studies like accuracy, linearity, method comparison, and precision, which are typical for IVD devices to demonstrate their analytical performance.
- Predicate Device: The mention of a predicate device (K932615; Abbott TDx®/TDxFLx® METHOTREXATE II) which is also an IVD for methotrexate measurement further supports this classification.
All these elements align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The ARK Methotrexate Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of methotrexate in human serum or plasma on automated clinical chemistry analyzers. The measurements obtained are used in monitoring levels of methotrexate to help ensure appropriate therapy.
The ARK Methotrexate Calibrator is intended for the ARK Methotrexate Assay.
The ARK Methotrexate Control is intended for the quality control of the ARK Methotrexate Assay.
Specimens from patients who have received glucarpidase (carboxypentidase G2) as a high dose methotrexate rescue therapy should not be tested with the ARK Methotrexate Assay.
Product codes
LAO, DLJ, LAS
Device Description
The ARK Methotrexate Assay is a homogeneous immunoassay based on competition between drug in the specimen and Methotrexate 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 Methotrexate Assay consists of reagents R1 anti-Methotrexate polyclonal antibody with substrate and R2 Methotrexate labeled with bacterial G6PDH enzyme. The ARK Methotrexate Calibrator consists of a six-level set to calibrate the assay, and the ARK Methotrexate Control consists of a six-level set used for quality control of the assay (tri-level calibration range set and tri-level high range set). The ARK Methotrexate Dilution Buffer is equivalent to zero calibrator (Calibrator A).
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
Nonclinical testing was performed.
Limit of Quantitation (LOQ)
Determined according to CLSI EP17-A.
Limit of Blank (LoB): 0.01 mol/L (N = 60)
Limit of Detection (LoD): 0.02 mol/L (N = 60)
Limit of Quantitation (LoQ): 0.04 mol/L (N = 40)
Accuracy (analytical recovery)
Method: Adding concentrated methotrexate drug into human serum negative for methotrexate.
Procedure: A certified stock concentrate of highly pure methotrexate was added volumetrically to human serum negative for methotrexate, representing drug concentrations across the assay calibration range. Six replicates of each sample were assayed on an automated clinical chemistry analyzer.
Results: Mean percentage recovery: 102.1%. Individual theoretical vs. mean recovered concentrations are provided, with percentage recovery ranging from 98.3% to 111.1%.
Linearity
Per CLSI/NCCLS Protocol EP6-A.
Method: A 1.30 umol/L serum sample was prepared and dilutions were made proportionally with human serum negative for methotrexate.
Acceptance criteria: Percent difference ±10% between predicted 1st and 2nd order regressed values for concentrations >0.10 umol/L or ±0.01 umol/L at concentrations ≤ 0.10 µmol/L.
Results: Linear regression was satisfactory throughout the range. Details on theoretical vs observed results, and 1st/2nd order predicted results are provided. Samples up to 1200 umol/L diluted into the calibration range showed linear regression.
Assay Range
Measurement range: 0.04 - 1.20 umol/L. Higher concentrations require dilution.
Method Comparison
Per CLSI/NCCLS Protocol EP9-A2.
Comparison: ARK Methotrexate Assay vs. Fluorescence Polarization Immunoassay method (monoclonal FPIA).
Sample Size: 102 specimens within the measurement range (0.04 to 1.19 μM) and 147 specimens including those above the measurement range (0.04 to 1440 μM).
Results (Passing-Bablok regression analysis):
For range 0.04 to 1.19 μM:
Slope: 1.00 (95% CI: 1.00 to 1.02)
y-intercept: 0.01 (95% CI: 0.00 to 0.01)
Correlation Coefficient (r2): 0.978 (95% CI: 0.968 to 0.985)
For range 0.04 to 1440 μM:
Slope: 0.99 (95% CI: 0.96 to 1.00)
y-intercept: 0.01 (95% CI: 0.01 to 0.01)
Correlation Coefficient (r2): 0.998 (95% CI: 0.997 to 0.998)
Precision
Per CLSI/NCCLS Protocol EP5-A2.
Method: Six-level ARK Methotrexate Control and pooled human specimens containing methotrexate. Each level assayed in quadruplicate twice a day for 20 days. Runs separated by at least two hours.
Acceptance criteria: 0.10 µmol/L, SD ≤0.01 at ≤0.10 µmol/L.
Results: Detailed tables for ARK Methotrexate Control and Patient Pool showing N, Mean, Within Run SD and %CV, Between Day SD and %CV, and Total SD and %CV. All results met acceptance criteria.
Interfering Substances
Per CLSI/NCCLS Protocol EP7-A2.
Method: Clinically high concentrations of endogenous substances (Albumin, Bilirubin, Cholesterol, Gamma-Globulin, Hemoglobin, Intralipid®, Rheumatoid Factor, Triglycerides, Uric Acid) in serum with known levels of methotrexate (approximately 0.05 and 0.50 umol/L) were evaluated.
Results: Measurement of methotrexate was not substantially affected by tested endogenous substances.
Specificity (Drug Interference)
Crossreactivity to 7-Hydroxymethotrexate (major metabolite): Did not crossreact (≤ 0.07%).
Crossreactivity to 2,4-diamino-N18-methylpteroic acid (DAMPA, minor, inactive metabolite): Crossreacts substantially (64.3% to 100%). Device should not be used during glucarpidase compassionate therapy.
Drugs that crossreact: Slight crossreactivity with triamterene and trimethoprim.
Crossreactivity to folate analogs and other compounds: Did not crossreact (≤ 0.01%) at ≥ 1000 umol/L for a list of compounds including Adriamycin, Cyclophosphamide, Folic Acid, etc.
Anticoagulants
Results showed no significant difference in methotrexate recovery between serum and plasma samples.
Sample Stability
Human specimens stable frozen (at least 15 months), 48 hours at room temperature, refrigerated (at least 21 days), and after three (3) successive freeze/thaw cycles.
On-Board Stability
Calibration Curve Stability: Effective up to at least 19 days.
Reagent on-board stability: Effective up to at least 25 days after transfer to analyzer specific reagent containers. In-use stability of calibrator and controls also demonstrated.
Key Metrics
Limit of Quantitation (LOQ)
Limit of Blank (LoB): 0.01 mol/L
Limit of Detection (LoD): 0.02 mol/L
Limit of Quantitation (LoQ): 0.04 mol/L
Accuracy (analytical recovery)
Mean percentage recovery: 102.1
Method Comparison (Correlation Coefficient (r2))
Range 0.04 to 1.19 μM: 0.978
Range 0.04 to 1440 μM: 0.998
Precision (Total %CV)
ARK Methotrexate Control:
LOW (0.06 µmol/L): 10.6%
MID (0.37 µmol/L): 3.8%
HIGH (0.76 µmol/L): 6.4%
5 (4.8 µmol/L): 4.1%
50 (48 µmol/L): 5.6%
500 (470 µmol/L): 7.0%
Patient Pool:
LOW (0.07 µmol/L): 11.7%
MID (0.41 µmol/L): 7.2%
HIGH (0.82 µmol/L): 6.9%
5 (4.6 µmol/L): 5.3%
50 (45 µmol/L): 6.5%
500 (460 µmol/L): 6.4%
Predicate Device(s)
Abbott TDx®/TDxFLx® METHOTREXATE II (K932615)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
N/A
0
OCT 1 8 2011
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 K111904.
| 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) 747-0708 |
| Executive Director of Quality and Regulatory Affairs |
Date prepared: September 7, 2011
807.92 (a)(2): Device name- trade name and common name, and classification
| Trade name: | ARKTM Methotrexate Assay
ARKTM Methotrexate Calibrator
ARKTM Methotrexate Control |
|-----------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Common Name: | Homogeneous Enzyme Immunoassay |
| Classification: | 21 CFR 862 Clinical Chemistry Test System - Toxicology
Test Code LAO; Enzyme Immunoassay, Methotrexate
Pre-Amendment Device, Unclassified
(21 CFR 862.3200 DLJ, 21 CFR 862.3280 LAS) |
807.92 (a)(3): Identification of the legally marketed predicate device
Abbott TDx®/TDxFLx® METHOTREXATE II (K932615)
... «
1
807.92 (a)(4): Device Description
The ARK Methotrexate Assay is a homogeneous immunoassay based on competition between drug in the specimen and Methotrexate 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 Methotrexate Assay consists of reagents R1 anti-Methotrexate polyclonal antibody with substrate and R2 Methotrexate labeled with bacterial G6PDH enzyme. The ARK Methotrexate Calibrator consists of a six-level set to calibrate the assay, and the ARK Methotrexate Control consists of a six-level set used for quality control of the assay (tri-level calibration range set and tri-level high range set). The ARK Methotrexate Dilution Buffer is equivalent to zero calibrator (Calibrator A).
807.92 (a)(5): Intended Use / Indications for Use
The ARK Methotrexate Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of methotrexate in human serum or plasma on automated clinical chemistry analyzers. The measurements obtained are used in monitoring levels of methotrexate to help ensure appropriate therapy.
The ARK Methotrexate Calibrator is intended for the ARK Methotrexate Assay.
The ARK Methotrexate Control is intended for the quality control of the ARK Methotrexate Assay.
Specimens from patients who have received glucarpidase (carboxypentidase G2) as a high dose methotrexate rescue therapy should not be tested with the ARK Methotrexate Assay.
2
807.92 (a)(6): Technological Similarities and Differences to the Predicate
SUBSTANTIAL EQUIVALENCE COMPARATIVE CHART
| Characteristic | Device | Predicate |
|---|---|---|
| ARK™ Methotrexate Assay | Abbott TDx®/TDxFLx® Methotrexate II (K932615) | |
| Intended Use | The ARK™ Methotrexate Assay is intended for the quantitative determination of methotrexate in human serum or plasma on automated clinical chemistry analyzers. | The TDx®/TDxFLx® Methotrexate II assay is a reagent system for the quantitative measurement of methotrexate, an antineoplastic drug, in serum or plasma. |
| Indications for Use | The measurements obtained are used in monitoring levels of methotrexate to help ensure appropriate therapy. | The measurements obtained are used in monitoring levels of methotrexate to ensure appropriate therapy. |
| Sample | Serum or plasma | Serum or plasma |
| Methodology | Homogenous enzyme immunoassay (EIA) | Fluorescence polarization immunoassay (FPIA) |
| Reagent Components | Two (2) reagent system: | |
| Anti-Methotrexate Antibody/Substrate Reagent (RI) containing rabbit polyclonal antibodies to Methotrexate, glucose-6-phosphate, nicotinamide adenine dinucleotide, bovine serum albumin, preservatives, and stabilizers | ||
| Enzyme Reagent (R2) containing Methotrexate labeled with bacterial G6PDH, buffer, bovine serum albumin, preservatives, and stabilizers | Reagent Pack: | |
| W = Wash solution, solvent, sodium azide | ||
| S = Methotrexate Antibody (mouse monoclonal), buffer, protein and sodium azide | ||
| T = Methotrexate Fluorescein Tracer, buffer, protein, surfactant and sodium azide | ||
| P = Pretreatment Solution, protein, surfactant and sodium azide | ||
| Platform required | Automated clinical chemistry analyzer | TDx clinical chemistry analyzer |
| Accessory reagents | Calibrators (six levels) and controls (six levels) in a synthetic matrix; Dilution Buffer | Calibrators (six levels) and controls (six levels) in human serum; Dilution Buffer |
| Testing environment | Routine clinical laboratory | Routine clinical laboratory |
| Reagent condition and storage | Liquid, 2-8° C | Liquid, 2-8° C |
Comparison between the ARK™ Methotrexate Assay and TDx®/TDxFLx® Methotrexate II Assay
3
807.92 (b)(1) and 807.92 (b)(2): Brief Description of Nonclinical and Clinical Data
Limit of Quantitation (LOQ)
The following characteristics were determined according to CLSI EP17-A for the ARK Methotrexate Assay. Analyzer-specific performance may vary.
| Criterion | MTX Concentration ( $ $ mol/L) |
|---|---|
| Limit of Blank (LoB); N = 60 | 0.01 |
| $ $ B + 1.645 SD, where SD = 0.005 | |
| Limit of Detection (LoD); N = 60 | 0.02 |
| LoB + 1.652 SD, where SD = 0.005 | |
| Limit of Quantitation (LoQ); N = 40 | 0.04 |
| LoQ-2 SD > LoD |
Each laboratory is responsible for determining reporting criteria for methotrexate concentrations. The following suggestion from CLSI EP17-A may be appropriate:
| Result ≤ LoB | report "not detected; concentration 0:10 umol/L or ±0.01 umol/L at concentrations ≤ 0.10 µmol/L. Results are shown below.
| Theoretical
(µmol/L) | Observed
Results
(µmol/L) | 1st Order
Predicted
Results | 2nd Order
Predicted
Results | Difference
(µmol/L or %) |
|-------------------------|---------------------------------|-----------------------------------|-----------------------------------|-----------------------------|
| 0.00 | 0.00 | 0.009 | -0.003 | na |
| 0.02 | 0.02 | 0.026 | 0.016 | -0.010 µmol/L |
| 0.04 | 0.04 | 0.042 | 0.034 | -0.008 µmol/L |
| 0.05 | 0.06 | 0.059 | 0.053 | -0.006 µmol/L |
| 0.07 | 0.08 | 0.076 | 0.072 | -0.004 µmol/L |
| 0.11 | 0.11 | 0.110 | 0.109 | -0.7 % |
| 0.18 | 0.17 | 0.178 | 0.183 | 3.1 % |
| 0.36 | 0.34 | 0.347 | 0.364 | 4.8 % |
| 0.65 | 0.63 | 0.618 | 0.639 | 3.4 % |
| 0.72 | 0.72 | 0.686 | 0.705 | 2.9 % |
| 0.86 | 0.84 | 0.821 | 0.835 | 1.7 % |
| 1.01 | 0.99 | 0.957 | 0.960 | 0.4 % |
| 1.15 | 1.06 | 1.092 | 1.082 | -1.0 % |
| 1.30* | 1.19 | 1.228 | 1.199 | -2.3 % |
*Concentration exceeds the claimed calibration range.
Samples containing methotrexate between 2 and 1200 umol/L were prepared proportionally in pooled human serum and then diluted into the calibration range with ARK Methotrexate Dilution Buffer. Regression of assayed methotrexate concentrations was linear throughout the range.
6
Assay Range
The measurement range of the ARK Methotrexate Assay is 0.04 - 1.20 umol/L. Specimens containing methotrexate in higher concentrations are assayed by dilution of the specimen. Report assayed values exceeding the LoD according to the information provided for LoQ. Multiply the assayed result by the dilution factor for specimens containing methotrexate above the measurement range.
Method Comparison
Correlation studies were performed using CLSI/NCCLS Protocol EP9-A2. Results from the ARK Methotrexate Assay were compared with results from Fluorescence Polarization Immunoassay method (monoclonal FPIA).
Methotrexate concentrations by FPIA ranged 0.04 to 1440 umol/L (uM). ARK Methotrexate values ranged 0.04 to 1500 umol/L. Results of the Passing-Bablok regression analysis for the study are shown below (with 95% confidence limits) for 102 specimens within the measurement range as well as for all 147 specimens including those above the measurement range requiring dilution.
| Parameter | Range 0.04 to 1.19 μM | Range 0.04 to 1440 μM | |||
|---|---|---|---|---|---|
| Slope | 1.00 | (1.00 to 1.02) | 0.99 | (0.96 to 1.00) | |
| y-intercept | 0.01 | (0.00 to 0.01) | 0.01 | (0.01 to 0.01) | |
| Correlation Coefficient (r2) | 0.978 | (0.968 to 0.985) | 0.998 | (0.997 to 0.998) | |
| Number of Samples | 102 | na | 147 | na |
7
Precision
Precision was determined as described in CLSI/NCCLS Protocol EP5-A2. The six-level ARK Methotrexate Control and pooled human specimens containing methotrexate 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: 0.10 µmol/L, SD ≤0.01 at ≤0.10 µmol/L.
| Sample | N | Mean
(µmol/L) | Within Run | | Between Day | | Total | |
|--------------------------|-----|------------------|------------|-----|-------------|-----|-------|------|
| | | | SD | %CV | SD | %CV | SD | %CV |
| ARK Methotrexate Control | | | | | | | | |
| LOW | 160 | 0.06 | 0.005 | 8.1 | 0.005 | 7.1 | 0.007 | 10.6 |
| MID | 160 | 0.37 | 0.011 | 3.1 | 0.008 | 2.2 | 0.014 | 3.8 |
| HIGH | 160 | 0.76 | 0.039 | 5.1 | 0.029 | 3.8 | 0.048 | 6.4 |
| 5 | 160 | 4.8 | 0.13 | 2.8 | 0.013 | 2.8 | 0.19 | 4.1 |
| 50 | 160 | 48 | 1.40 | 2.9 | 2.13 | 4.4 | 2.71 | 5.6 |
| 500 | 160 | 470 | 15.63 | 3.3 | 27.64 | 5.8 | 33.35 | 7.0 |
| Patient Pool | | | | | | | | |
| LOW | 160 | 0.07 | 0.006 | 9.1 | 0.005 | 7.5 | 0.008 | 11.7 |
| MID | 160 | 0.41 | 0.013 | 3.3 | 0.026 | 6.4 | 0.030 | 7.2 |
| HIGH | 160 | 0.82 | 0.037 | 4.5 | 0.042 | 5.1 | 0.057 | 6.9 |
| 5 | 160 | 4.6 | 0.14 | 3.1 | 0.18 | 4.0 | 0.24 | 5.3 |
| 50 | 160 | 45 | 1.31 | 2.9 | 2.62 | 5.9 | 2.92 | 6.5 |
| 500 | 160 | 460 | 11.55 | 2.5 | 27.21 | 5.9 | 29.63 | 6.4 |
8
Interfering Substances
Interference studies were conducted using CLSI/NCCLS Protocol EP7-A2 as a guideline. Clinically high concentrations of the following potentially interfering endogenous substances in serum with known levels of methotrexate (approximately 0.05 and 0.50 umol/L) were evaluated. Fach sample was assayed using the ARK Methotrexate Assay, along with a serum control of methotrexate. Measurement of methotrexate was not substantially affected at the levels of endogenous substances tested.
| | | Methotrexate
(~ 0.05 µmol/L) | | Methotrexate
(~ 0.50 µmol/L) | |
|--------------------------|------------------------------|---------------------------------|------|---------------------------------|---------------------|
| Interfering
Substance | Interferent
Concentration | Serum
Control | Test | Serum
Control | Test
(% Control) |
| Albumin | 12 g/dL | 0.05 | 0.06 | 0.48 | 0.45 ( 92.8) |
| Bilirubin - conjugated | 70 mg/dL | 0.05 | 0.06 | 0.48 | 0.51 (105.5) |
| Bilirubin - unconjugated | 70 mg/dL | 0.05 | 0.06 | 0.48 | 0.52 (106.9) |
| Cholesterol | 400 mg/dL | 0.05 | 0.06 | 0.47 | 0.49 (105.4) |
| Gamma-Globulin | 12 g/dL | 0.05 | 0.06 | 0.48 | 0.51 (105.5) |
| Hemoglobin | 1000 mg/dL | 0.04 | 0.05 | 0.49 | 0.45 ( 92.8) |
| Intralipid® | 500 mg/dL | 0.05 | 0.05 | 0.43 | 0.45 (105.1) |
| Rheumatoid Factor | 1100 IU/mL | 0.05 | 0.06 | 0.43 | 0.41 ( 96.1 ) |
| Triglycerides | 749 mg/dL | 0.04 | 0.04 | 0.49 | 0.45 ( 91.4) |
| Uric Acid | 30 mg/dL | 0.05 | 0.04 | 0.48 | 0.50 (102.8) |
Specificity - Drug Interference
Crossreactivity to 7-Hydroxymethotrexate, the major metabolite
The ARK Methotrexate Assay did not crossreact (≤ 0.07%) with the major metabolite 7-Hydroxymethotrexate.
Crossreactivity to the minor, inactive metabolite 2,4-diamino-N18-methylpteroic acid (DAMPA)
The ARK Methotrexate Assay crossreacts substantially with the minor metabolite DAMPA. Tests were performed in the absence of the parent drug methotrexate. Crossreactivity to DAMPA ranged 64.3 to 100%. The assay should not be used during possible compassionate therapy with glucarpidase (carboxypeptidase G2) that rapidly converts circulating methotrexate to DAMPA.
Drugs that crossreact
The ARK Methotrexate Assay crossreacts slightly with triamterene and trimethoprim, however these drugs may be contraindicated for methotrexate cancer treatement due to additional adverse effects if co-administered. The structures of these compounds closely match the pteridine ring moiety of methotrexate.
ARK Diagnostics, Inc. - 510(k) Summary ARK Methotrexate Assay
9
| | | Methotrexate Absent | | Methotrexate Present
0.05 µmol/L | | Methotrexate Present
0.50 µmol/L | |
|--------------|--------------------|---------------------|----------------------------|-------------------------------------|----------------------------|-------------------------------------|----------------------------|
| Compound | Tested
(µmol/L) | MTX
(µmol/L) | Cross
Reactivity
(%) | MTX
(µmol/L) | Cross
Reactivity
(%) | MTX
(µmol/L) | Cross
Reactivity
(%) |
| Triamterene | 25 | 0.46 | 1.85 | 0.89 | 3.32 | 1.04 | 2.31 |
| Trimethoprim | 100 | 0.17 | 0.17 | 0.16 | 0.12 | 0.99 | 0.54 |
Crossreactivity to folate analogs and other compounds
The ARK Methotrexate Assay did not crossreact (≤ 0.01%) with folate analogs or other compounds at ≥ 1000 umol/L as tested.
| Compound | Tested
(µmol/L) |
|---------------------------------------|--------------------|
| Adriamycin | 1000 |
| Cyclophosphamide | 1500 |
| Cytosine | 1000 |
| Dihydrofolic Acid | 1000 |
| DL-6-Methyl-5,6,7,8-Tetrahydropterine | 1000 |
| Folic Acid | 1000 |
| Folinic Acid (leucovorin) | 1000 |
| 5-Fluorouracil | 3000 |
| 6-Mercaptopurine | 1000 |
| 5-Methyltetrahydrofolic acid | 1000 |
| Prednisolone | 1000 |
| Pyrimethamine | 1000 |
| Sulfamethoxazole | 1600 |
| Tetrahydrofolic Acid | 1000 |
| Vinblastine | 1000 |
| Vincristine | 1000 |
Anticoagulants
Studies were conducted to determine the performance characteristics of the assay for both serum and plasma samples containing methotrexate.
The results indicate that there is no significant difference between the recovery of methotrexate in serum or plasma.
10
Sample Stability
Human specimens were shown to be stable frozen (at least 15 months), forty-eight (48) hours at room temperature, refrigerated (at least 21 days) and after three (3) successive freeze/thaw cycles.
On-Board Stability
Calibration Curve Stability: A stored calibration was effective up to at least 19 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 25 days based on supporting data. In-use stability of calibrator and controls was also demonstrated.
807.92 (b)(3): Conclusions from Nonclinical Testing
As summarized above, the ARK Methotrexate Assay System, including the ARK Methotrexate Calibrator, ARK Methotrexate Control and ARK Methotrexate Dilution Buffer, is substantially equivalent to the Abbott TDx®/TDxFLx® METHOTREXATE II Assay system. The ARK Methotrexate Assay system was shown to be safe and effective for its intended use based on performance studies.
11
Image /page/11/Picture/0 description: The image shows the logo of the Department of Health & Human Services (HHS) of the United States. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, which is the official emblem of the HHS.
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
ARK Diagnostics, Inc c/o Kenneth C. Kasper, PhD 1190 Bordeaux Dr. Sunnyvale, CA 94089
OCT 1 8 2011
Re: K111904
Trade/Device Name: ARK™ Methotrexate Assay, ARK™ Methotrexate Calibrator, ARK™ Methotrexate Control Regulatory Class: Unclassified, 510(k) required Product Code: LAO, DLJ, LAS Dated: September 7, 2011 Received: September 8, 2011
Dear Dr. Kasper:
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 application (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 class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
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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/MedicalDevicesforYou/Industry/default.htm.
Sincerely yours,
jz
Courtney H. Lias, 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): K111904
Device Name:
ARKTM Methotrexate Assay ARKTM Methotrexate Calibrator ARKTM Methotrexate Control
Indications for Use:
The ARK™ Methotrexate Assay is a homogeneous enzyme immunoassay intended for the quantitative determination of Methotrexate in human serum or automated clinical chemistry analyzers. The measurements obtained are used in monitoring levels of methotrexate to help ensure appropriate therapy.
The ARK™ Methotrexate Calibrator is intended for use in calibration of the ARK Methotrexate Assay.
The ARKTM Methotrexate Control is intended for use in quality control of the ARK Methotrexate Assay.
Specimens from patients who have received glucarpidase (carboxypeptidase G2) as a high dose methotrexate rescue therapy should not be tested with the ARK Methotrexate Assay.
Prescription Use ____X (21 CFR Part 801 Subpart D) Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
And/Or
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Ritte charles
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
111904 510(k)
ARK Methotrexate Assay - Indications/Intended Use ARK Diagnostics, Inc.
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