(123 days)
Not Found
No
The device description details a homogeneous enzyme-immunoassay based on a competitive binding reaction and photometric measurement of NADH formation. There is no mention of AI, ML, or any computational algorithms beyond standard data processing for quantitative determination. The performance studies focus on analytical characteristics typical of in vitro diagnostic assays, not AI/ML model performance metrics.
No
This device is an in vitro diagnostic test used for monitoring levels of methotrexate in human serum and plasma. It provides information for appropriate therapy but does not directly treat or prevent a disease, which is the function of a therapeutic device.
Yes
The device is an in vitro test that quantitatively determines methotrexate levels in human serum and plasma, which is used for monitoring drug levels to ensure appropriate therapy. This falls under the definition of a diagnostic device as it provides information for disease management or treatment monitoring.
No
The device is an in vitro diagnostic (IVD) assay that utilizes chemical reagents and is performed on a hardware system (cobas c systems). It is not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the device is an "in vitro test for the quantitative determination of methotrexate in human serum and plasma". This clearly indicates that the device is intended to be used outside of the body to analyze biological samples.
- Device Description: The "Device Description" further reinforces this by describing the assay as an "in vitro test" and detailing the reagents and methodology used to analyze serum and plasma samples.
- Nature of the Test: The test measures the concentration of methotrexate in biological fluids (serum and plasma) to monitor therapeutic levels. This is a classic example of an in vitro diagnostic test used for patient management.
N/A
Intended Use / Indications for Use
ONLINE TDM Methotrexate is an in vitro test for the quantitative determination of methotrexate in human serum and plasma on cobas c systems. The determination of methotrexate is used for monitoring levels of methotrexate to ensure appropriate therapy.
Product codes (comma separated list FDA assigned to the subject device)
LAO
Device Description
The ONLINE TDM Methotrexate assay is an in vitro test for the quantitative determination of methotrexate in human serum and plasma on cobas c systems. The determination of methotrexate is used for monitoring levels of methotrexate to ensure appropriate therapy.
The ONLINE TDM MTX assay is a two-reagent system used for the detection of methotrexate in serum and plasma. In this technology drug hapten attached to the enzyme glucose 6 phosphate dehydrogenase (G6PDH) serves as the binding partner to anti-methotrexate antibody. A competitive reaction to a limited amount of specific anti-methotrexate antibody takes place between the enzyme bound hapten and free methotrexate in the sample. Enzyme activity is reduced with bound antibody. Only active enzymes reduce NAD+ to NADH. The rate of NADH formation during the reaction correlates to the methotrexate concentration and is measured photometrically.
The ONLINE TDM MTX assay is a homogeneous enzyme-immunoassay.
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
Not Found
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)
Performance characteristics were evaluated with ONLINE TDM Methotrexate on cobas c 503. All acceptance criteria were met.
Precision (Repeatability and Intermediate Precision):
Repeatability (n = 84) and intermediate precision (2 aliquots per run, 2 runs per day, 21 days) results were obtained on the cobas c 503 analyzer according to CLSI EP05-A3. Results for controls and human serum samples are provided with mean, SD, and CV.
Analytical Sensitivity (Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ)):
LoB: Determined according to CLSI EP17-A2 using one analyte-free sample measured with three reagent lots in 6 runs (10-fold determination each) over 3 days on one cobas c 503 analyzer. Claimed LoB is ≤ 0.0250 µmol/L.
LoD: Determined according to CLSI EP17-A2 using 5 serum samples (spiked with methotrexate) measured on three lots with 2-fold determination per run on one cobas c 503 analyzer over 3 days. Claimed LoD is
N/A
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the seal of the Department of Health & Human Services. To the right of that is the FDA logo in blue, with the words "U.S. FOOD & DRUG" stacked on top of the word "ADMINISTRATION".
Roche Diagnostics Operations Elina Voronovsky Regulatory Affairs Manager 9115 Hague Road Indianapolis, Indiana 46250
Re: K233454
Trade/Device Name: ONLINE TDM Methotrexate Regulatory Class: Unclassified Product Code: LAO Dated: January 12, 2024 Received: January 12, 2024
Dear Elina Voronovsky:
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).
1
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,
Joseph A. Digitally signed by
Joseph A. Joseph A. Joseph A. Kotarek -S Kotarek -S Date: 2024.02.20
Joseph Kotarek Branch Chief Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
Submission Number (if known)
Device Name
ONLINE TDM Methotrexate
Indications for Use (Describe)
ONLINE TDM Methotrexate is an in vitro test for the quantitative determination of methotrexate in human serum and plasma on cobas c systems. The determination of methotrexate is used for monitoring levels of methotrexate to ensure appropriate therapy.
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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3
ONLINE TDM Methotrexate K233454 – 510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92
| Submitter Name | Roche Diagnostics |
|---|---|
| Address | 9115 Hague Road |
| P.O. Box 50416 | |
| Indianapolis, IN 46250-0457 | |
| Contact | Elina Voronovsky |
| Phone: (317) 478-3317 | |
| Email: elina.voronovsky.ev1@roche.com | |
| Date Prepared | February 20, 2024 |
| Proprietary Name | ONLINE TDM Methotrexate |
| Common Name | ONLINE TDM Methotrexate |
| Classification Name | Enzyme Immunoassay, Methotrexate |
| Product Codes, | |
| Regulation Numbers | LAO, Unclassified |
| Predicate Devices | ARK Methotrexate Assay (K111904) |
| Establishment Registration | Roche Diagnostics GmbH Mannheim, Germany: 9610126 |
| Roche Diagnostics GmbH Penzberg, Germany: 9610529 | |
| Roche Diagnostics Indianapolis, IN United States: 1823260 |
4
DEVICE DESCRIPTION 1.
The ONLINE TDM Methotrexate assay is an in vitro test for the quantitative determination of methotrexate in human serum and plasma on cobas c systems. The determination of methotrexate is used for monitoring levels of methotrexate to ensure appropriate therapy.
The ONLINE TDM MTX assay is a two-reagent system used for the detection of methotrexate in serum and plasma. In this technology drug hapten attached to the enzyme glucose 6 phosphate dehydrogenase (G6PDH) serves as the binding partner to anti-methotrexate antibody. A competitive reaction to a limited amount of specific anti-methotrexate antibody takes place between the enzyme bound hapten and free methotrexate in the sample. Enzyme activity is reduced with bound antibody. Only active enzymes reduce NAD+ to NADH. The rate of NADH formation during the reaction correlates to the methotrexate concentration and is measured photometrically.
The ONLINE TDM MTX assay is a homogeneous enzyme-immunoassay.
Reagents - working solutions
R1: Anti-methotrexate antibody (rabbit monoclonal), 3 µg/mL; NAD, G6P, bovine serum albumin in water, pH 6.3; preservative
R3: Methotrexate hapten conjugated to G6PDH, 0.3 µg/mL; bovine serum albumin in buffer, pH 7.8; preservative
2. INDICATIONS FOR USE
ONLINE TDM Methotrexate is an in vitro test for the quantitative determination of methotrexate in human serum and plasma on cobas c systems. The determination of methotrexate is used for monitoring levels of methotrexate to ensure appropriate therapy.
5
TECHNOLOGICAL CHARACTERISTICS 3.
The following table compares the ONLINE TDM Methotrexate assay on cobas c 503 with its predicate device, ARK Methotrexate Assay (K111904).
| | Candidate Device:
ONLINE TDM
Methotrexate Assay | Predicate Device:
ARK Methotrexate
Assay (K111904) |
|---------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use /
Indications for Use | The Roche ONLINE TDM
Methotrexate Assay is
intended as the In vitro test
for the quantitative
determination of
methotrexate in human
serum and plasma on cobas
c systems. The
determination of
methotrexate is used for
monitoring levels of
methotrexate to ensure
appropriate therapy. | The ARK™ Methotrexate
Assay is intended for the
quantitative determination
of methotrexate in human
serum or plasma on
automated clinical chemistry
analyzers. |
| Assay Method | Same | Homogenous enzyme
immunoassay (EIA) |
| Detection Method | Same | Absorbance |
| Instrument Platform | Same | Automated clinical
chemistry analyzer |
| Sample Type/Matrix | Same | Serum or plasma |
| Calibrator | Roche MTX Calibrator | ARK Methotrexate
Calibrator |
| Calibration Method | 1 calibrator diluted to 6
levels by the instrument.
The calibrator consists of a
synthetic protein matrix and
1.2 µmol/L. | Six-level set to calibrate the
assay. The calibrators
consist of a synthetic protein
matrix and the levels are
0.00 umol/L, 0.05 umol/L,
0.15 umol/L, 0.25 umol/L,
0.50 umol/L and 1.2 umol/L |
| Calibration Interval | - after reagent lot change
every 2 weeks
as required following
quality control
procedures | - Whenever a new lot
number of reagents is
used
Whenever indicated by
quality control results
Whenever required by
standard laboratory
protocols |
| Controls | Roche TDM Control | ARK Methotrexate Control |
| | Candidate Device:
ONLINE TDM
Methotrexate Assay | Predicate Device:
ARK Methotrexate
Assay (K111904) |
| Traceability/
Standardization | Roche MTX Calibrator is
prepared to contain known
quantities of methotrexate in
a synthetic proteinaceous
matrix free of methotrexate
and is traceable to USP
reference standard. | ARK Methotrexate
Calibrators and controls are
prepared by volumetric
dilution of high purity,
certified Methotrexate
solution into a synthetic
proteinaceous matrix free of
Methotrexate |
| Reagent Stability | Shelf life at 2-8 °C: See
expiration date on cobas c
pack label
On-board in use and
refrigerated on the analyzer:
12 weeks | When not in use, reagents
must be stored at 2-8°C
(36-46°F), upright and with
screw caps tightly closed. If
stored as directed, reagents
are stable until the
expiration date printed on
the label. |
| Measuring Range | Same | 0.04 – 1.20 µmol/L
Specimens containing
methotrexate in higher
concentrations are assayed
by dilution of the specimen. |
| Lower Limits of
Measurement | LoB = 0.0250 µmol/L
LoD = 0.0350 µmol/L
LoQ = 0.0400 µmol/L | LoB = 0.01 µmol/L
LoD = 0.02 µmol/L
LoQ = 0.04 µmol/L |
Table 1: ONLINE TDM Methotrexate Technical Characteristics
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4. NON-CLINICAL PERFORMANCE EVALUATION
Performance characteristics were evaluated with ONLINE TDM Methotrexate on cobas c 503 and are briefly summarized below.
All acceptance criteria were met.
Precision 4.1.
Repeatability and Intermediate Precision 4.1.1.
Precision was determined in accordance with the CLSI EP05-A3 requirements with repeatability (n = 84) and intermediate precision (2 aliquots per run, 2 runs per day, 21 days). Results for repeatability and intermediate precision were obtained on the cobas c 503 analyzer. The results are summarized below. All acceptance criteria were met.
7
| Repeatability | Mean | SD | CV |
|---|---|---|---|
| µmol/L | µmol/L | % | |
| Control 1 | 0.0863 | 0.00376 | 4.4 |
| Control 2 | 0.485 | 0.00421 | 0.9 |
| Control 3 | 0.849 | 0.00567 | 0.7 |
| Human Serum 1 | 0.0872 | 0.00350 | 4.0 |
| Human Serum 2 | 0.526 | 0.00427 | 0.8 |
| Human Serum 3 | 0.889 | 0.00648 | 0.7 |
| Human Serum 4 | 4.85 | 0.0491 | 1.0 |
| Human Serum 5 | 44.2 | 1.76 | 4.0 |
| Human Serum 6 | 449 | 16.6 | 3.7 |
| Human Serum 7 | 1334 | 41.8 | 3.1 |
| Intermediate
| precision | Mean | SD | CV |
|---|---|---|---|
| µmol/L | µmol/L | % | |
| Control 1 | 0.0737 | 0.00804 | 10.9 |
| Control 2 | 0.487 | 0.00561 | 1.2 |
| Control 3 | 0.841 | 0.00664 | 0.8 |
| Human Serum 1 | 0.0752 | 0.00845 | 11.2 |
| Human Serum 2 | 0.526 | 0.00683 | 1.3 |
| Human Serum 3 | 0.889 | 0.00971 | 1.1 |
| Human Serum 4 | 4.91 | 0.0970 | 2.0 |
| Human Serum 5 | 44.2 | 2.36 | 5.3 |
| Human Serum 6 | 449 | 28.5 | 6.3 |
| Human Serum 7 | 1316 | 67.3 | 5.1 |
Analytical Sensitivity 4.2.
Limit of Blank (LoB) 4.2.1.
For determination of LoB, one analyte-free sample was measured with three reagent lots in 6 runs, each run with 10-fold determination, distributed over 3 days, on one cobas c 503 analyzer. The LoB was determined according to CLSI EP17-A2. The LoB claim in the labeling will be set to ≤ 0.0250 µmol/L.
8
Limit of Detection (LoD) 4.2.2.
For determination of LoD, 5 serum samples (spiked with methotrexate) were measured on three lots with 2-fold determination per run on one cobas c 503 analyzer. Six runs were distributed over 3 days. The LoD was determined according to CLSI EP17-A2. The LoD claim in the labeling will be set to