(147 days)
No
The summary describes a fully automated system using photometric measurements and a CMOS sensor, but there is no mention of AI or ML algorithms being used for analysis or interpretation. The performance studies focus on traditional analytical metrics like sensitivity, specificity, and agreement with predicate devices.
No.
This device is an in vitro diagnostic (IVD) system used to evaluate renal, urinary, hepatic, and metabolic disorders by analyzing urine analytes. It provides diagnostic information rather than directly treating or preventing a disease or condition in a patient.
Yes.
The device is intended for "in vitro qualitative or semi-quantitative determination of urine analytes... useful in the evaluation of renal, urinary, hepatic and metabolic disorders," which directly indicates its use in the diagnosis or detection of diseases or conditions.
No
The device is a system comprised of both hardware (analyzer) and software (inbuilt computer, operating system, database). The description explicitly details the physical components of the analyzer and its functions.
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 system is "intended for the in vitro qualitative or semi- quantitative determination of urine analytes". "In vitro" means "in glass" or "outside the body," which is a key characteristic of IVD devices.
- Sample Type: The device analyzes urine, which is a biological sample taken from the human body.
- Purpose: The measurements are described as "useful in the evaluation of renal, urinary, hepatic and metabolic disorders," indicating a diagnostic purpose.
- Test Strips: The system uses test strips with reagents that react with components in the urine sample to produce a measurable result, a common method in IVD testing.
- Clinical Laboratory Setting: The intended user is "trained operators in clinical laboratories," which is the typical environment for IVD testing.
N/A
Intended Use / Indications for Use
The cobas u 601 urinalysis test system is comprised of the cobas u 601 urine analyzer and the cobas u pack.
The cobas u 601 urine analyzer when used with the cobas u pack is a fully automated urinalysis system intended for the in vitro qualitative or semi- quantitative determination of urine analytes, nitrite, protein, glucose, ketones, urobilinogen, bilirubin, color and erythrocytes, as well as clarity. These measurements are useful in the evaluation of renal, urinary, hepatic and metabolic disorders. This system is intended to be used by trained operators in clinical laboratories.
The cobas u pack is a cassette loaded with cobas u 601 test strips for the in vitro qualitative or semi-quantitative determination of pH, leukocytes, nitrite, protein, glucose, ketones, urobilinogen, bilirubin, color and erythrocytes in urine with the cobas u 601 urine analyzer. These measurements are useful in the evaluation of renal, urinary, hepatic and metabolic disorders.
Product codes
JIL, JIO, CDM, CEN, JIN, JIR, JJB, JMT, LJX, KQO
Device Description
The cobas u 601 Urinalysis Test System consists of the following components:
- cobas u 601 urine analyzer
- cobas u pack
The cobas u 601 urine analyzer is a fully automated urine analysis system. It is optimized for high throughput workloads in the professional environment. The cobas u 601 urine analyzer performs a maximum theoretical throughput of up to 240 samples per hour.
The cobas u 601 analyzer consists of several major components:
- Rack transport system
- Liquid handling system
- Test strip cassette compartment
- Automated test strip processing area
- Photometer which is a 4 wavelength reflectance measuring unit based on a Complementary Metal Oxide Semiconductor chip used in digital cameras (CMOS sensor)
- Physical Measurement Cell (PMC): flow cell connected to an optical detector ●
- Touch Screen
- Inbuilt Computer
The functions of the cobas u 601 urine analyzer include:
- Sample loading and transport ●
- Sample identification
- Robotic pipetting of samples onto test pads on test strips
- Robotic aspiration of samples into the PMC
- Controlled incubation
- Photometric measurement of test strips
- Optical determination in the PMC
- Automatic disposal of used test strips ●
- Result readout
- Result memory
- Optional formats for data output including electronic result communication
The operating system will be a Microsoft Windows for embedded devices. The system will use a Postgres/SQL database.
The cobas u 601 urine analyzer is designed to be inter-connected mechanically and electronically with another urine sediment analyzer (cobas u 701) in order to create a urine work area (cobas® 6500).
The cobas u pack is a cassette containing 400 tests strips. The cobas u 601 analyzer will use the cobas u pack to dispense single test strips for each sample.
Each test strip has ten individual test pads that are used to test for different substances or characteristics. The test strips are analyzed automatically through the analyzer. One test strip is used per sample. When a strip is dispensed for use by the cobas u 601, an aliquot of the urine sample is pipetted onto each of the test pads. The resulting color changes are measured photometrically.
The test strip in the cobas u pack cassette ("cassette test strip") is a multi-parameter urine analysis test strip, with test pads for blood (Erythrocytes), Leukocytes, Nitrite, Proteins, Glucose, Ketones, Bilirubin, Urobilinogen, Color and pH.
The cobas u pack is technically identical to the marketed Urisys 2400 Cassette with 400 test strips (cleared under K012397) with the following modifications:
- Added RFID-tag (ISO15693; 13.56 MHz)
- own labeling and own Id. No.
- different brand
The RFID-tag is used for storing test strip related information to improve the safety and the convenience of the system. The following data is stored on the RFID-Tag:
- generic product data
- strip cassette data
- test strip related data
- cassette number
- lot number
- expiry date
- load date
- check sum
The on-board time is checked by the instrument and an alarm is triggered if the on-board time of a strip cassette (identified through its RFID-tag) exceeds its specified on-board stability.
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
This system is intended to be used by trained operators in clinical laboratories.
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
Non-Clinical Performance Evaluation
Linearity/Reportable Results
The reportable results are determined by the analytical sensitivity and method comparison studies. The results support the following reportable results:
- NIT: Neg/Pos
- GLU: Norm to 1000 mg/dL
- KET: Neg to 150 mg/dL
- BIL: Neg to 6 mg/dL
- UBG: Norm to 12 mg/dL
- PRO: Neg to 500 mg/dL albumin
- ERY: Neg to 250 Ery/μL
- LEU: Neg to 500 Leu/μL
- pH: 5 to 9
- COL: Pale yellow, yellow, amber, brown, orange, red, green, others
- SG: 1.000 to 1.050 g/cm³
- Clarity: Clear, light turbid, turbid
Analytical Sensitivity
The sensitivity study was performed to determine the concentration at which the analyte on the cobas u pack changed from negative to the lowest positive color range. Samples were prepared by spiking the negative urine pool with the appropriate agent to yield the desired concentrations of analyte. Multiple samples were tested for each analyte. Each sample was measured 20 times on each of the 3 instruments using 3 reagent test strip lots. Sensitivity is defined as the lowest concentration where ≥90% of the overall results are positive.
Results:
- LEU: 10-30 Leu/μL (meets criteria at 10 Leu/μL)
- NIT: 0.03 – 0.07 mg/dL (meets criteria at 0.045 mg/dL)
- PRO: 7 - 13 mg/dL albumin (meets criteria at 9 mg/dL albumin)
- GLU: 25 – 45 mg/dL (meets criteria at 25 mg/dL)
- KET: 3 – 7 mg/dL (meets criteria at 4 mg/dL)
- BIL: 0.4 – 0.6 mg/dL (meets criteria at 0.6 mg/dL)
- UBG: 1.0 – 1.6 mg/dL (meets criteria at 1.15 mg/dL)
- ERY: 5-15 Ery/μL (meets criteria at 7 Ery/μL)
Drug and Endogenous Interferences
Interference studies were performed to assess the interfering effect of various therapeutic drugs and endogenous substances. A urine pool was tested in the normal/negative and first positive range with therapeutic drug solutions (multiple of maximal daily dosage, maximal daily dosage) and endogenous substances (high pathological concentration, intermediate concentration). Multiple replicates were measured on two cobas u 601 urine analyzers. In case of interference, further concentrations were tested to evaluate the maximum interferent concentration with no influence on results.
Color Interference
This study verified the color compensation functionality of the cobas u 601 urine analyzer. Two analyte solutions (negative/normal and color block with color compensation) were prepared and spiked with interferents (Erythrocytes, Bilirubin, Urobilinogen, Hemoglobin, Sunset Yellow, Lignin) to produce red, orange, or brown colors. Samples were tested in 10-fold determinations. Results indicated 100% agreement for negative results and for exact agreement in positive results, except for Leukocytes with Hemoglobin (90% for negative, 20% for positive with Sunset Yellow).
Stability
Shelf-life (real-time) and on-board stability of the cobas u pack were determined.
Real-time stability: Tested on two analyzers with three lots, at time 0, 3, 13, and 16 months. Samples included native urine, artificial urine, and spiked urine (low/high analyte concentration). Each sample had 10 determinations.
Result: The cobas u pack is stable at room temperature for 15 months.
On-board stability: Tested with one lot on one analyzer over 15 days at 32°C and 80% relative humidity. 400 tests were performed over 11 time points from a single cassette using native and artificial urine samples.
Result: The cobas u pack is stable up to 14 days during operation on the system.
Expected Values
Expected values are listed for various analytes, including Erythrocytes (0-5 Ery/μL), Leukocytes (
§ 862.1340 Urinary glucose (nonquantitative) test system.
(a)
Identification. A urinary glucose (nonquantitative) test system is a device intended to measure glucosuria (glucose in urine). Urinary glucose (nonquantitative) measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, hypoglycemia, and hyperglycemia.(b)
Classification. Class II.
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: on the left, there is an emblem of the Department of Health and Human Services, which features a stylized caduceus with a triple helix. To the right of the emblem, there is the FDA acronym in a blue square, followed by the words "U.S. FOOD & DRUG" in bold, blue letters, and below that, the word "ADMINISTRATION" in smaller, blue letters.
May 7, 2019
Roche Diagnostics Angela Clements Regulatory Affairs Principal 9115 Hague Road Indianapolis, IN 46250
Re: K183432
Trade/Device Name: cobas u 601 urinalysis test system Regulation Number: 21 CFR 862.1340 Regulation Name: Urinary glucose (nonquantitative) test system Regulatory Class: Class II Product Code: JIL, JIO, CDM, CEN, JIN, JIR, JJB, JMT, LJX, KQO Dated: March 22, 2019 Received: March 25, 2019
Dear Angela Clements:
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. 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 located 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.
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
1
- for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); 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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Kellie B. Kelm, Ph.D. Acting Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K183432
Device Name cobas u 601 urinalysis test system
Indications for Use (Describe)
The cobas u 601 urinalysis test system is comprised of the cobas u 601 urine analyzer and the cobas u pack.
The cobas u 601 urine analyzer when used with the cobas u pack is a fully automated urinalysis system intended for the in vitro qualitative or semi- quantitative determination of urine analytes, nitrite, protein, glucose, ketones, urobilinogen, bilirubin, color and erythrocytes, as well as clarity. These measurements are useful in the evaluation of renal, urinary, hepatic and metabolic disorders. This system is intended to be used by trained operators in clinical laboratories.
The cobas u pack is a cassette loaded with cobas u 601 test strips for the in vitro qualitative or semi-quantitative determination of pH, leukocytes, nitrite, protein, glucose, ketones, urobilinogen, bilirubin, color and erythrocytes in urine with the cobas u 601 urine analyzer. These measurements are useful in the evaluation of renal, urinary, hepatic and metabolic disorders.
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
cobas u 601 Urinalysis Test System 510(k) Summary K183432
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
In accordance with 21 CFR 807.87, Roche Diagnostics hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Premarket Notification 510(k).
The purpose of this Traditional 510(k) Premarket Notification is to obtain FDA review and clearance for the cobas u 601 Urinalysis Test System.
4
| Submitter Name | Roche Diagnostics |
|---|---|
| Address | 9115 Hague Road |
| P.O. Box 50416 | |
| Indianapolis, IN 46250-0457 | |
| Contact | Angie Clements |
| Phone: (317) 521-7338 | |
| FAX: (317) 521-2324 | |
| Email: angie.clements@roche.com |
Michael Leuther
Phone: (317) 521-3930
FAX: (317) 521-2324
Email: Michael.leuther@roche.com |
| Date Prepared | December 10, 2018 |
| Proprietary Name | cobas u 601 Urinalysis Test System |
| Common Name | Automated urinalysis system
Reagent strip for urinalysis |
| Product Codes,
Regulation Numbers | See Table 1 |
| Predicate Devices | cobas u 411 (K093555) |
| Establishment Registration | For the cobas u 601 Urinalysis Test System the establishment registration
number for Roche Diagnostics GmbH in Mannheim, Germany is 9610126. The
establishment registration number for Roche Diagnostics in the United States is
1823260. |
Table 1: Product Codes and Regulation Numbers
| Device/Analyte | Product Code | Classification | Regulation | Panel |
|---|---|---|---|---|
| Automated urinalysis | ||||
| system | KQO | Class I | 21 CFR 862.2900 | 75 Chemistry |
| Glucose, urinary, non- | ||||
| quantitative | JIL | Class II | 21 CFR 862.1340 | 75 Chemistry |
| Blood, occult, | ||||
| colorimetric, in urine | JIO | Class II | 21 CFR 864.6550 | 81 Hematology |
| Urobilinogen, urinary, | ||||
| non-quantitative | CDM | Class I | 21 CFR 862.1785 | 75 Chemistry |
5
| Device/Analyte | Product Code | Classification | Regulation | Panel |
|---|---|---|---|---|
| pH, urinary, non- | ||||
| quantitative | CEN | Class I | 21 CFR 862.1550 | 75 Chemistry |
| Ketones, non- | ||||
| quantitative | JIN | Class I | 21 CFR 862.1435 | 75 Chemistry |
| Protein or albumin, | ||||
| urinary, non- | ||||
| quantitative | JIR | Class I | 21 CFR 862.1645 | 75 Chemistry |
| Nitrite, non- | ||||
| quantitative | JMT | Class I | 21 CFR 862.1510 | 75 Chemistry |
| Leukocyte, peroxidase | ||||
| test | LJX | Class I | 21 CFR 864.7675 | 81 Hematology |
| Bilirubin and its | ||||
| conjugates, urinary, | ||||
| non-quantitative | JJB | Class I | 21 CFR 862.1115 | 75 Chemistry |
| Color | No regulation | |||
| Clarity | No regulation |
6
DEVICE DESCRIPTION 1.
The cobas u 601 Urinalysis Test System consists of the following components:
- . cobas u 601 urine analyzer
- . cobas u pack
1.1. cobas u 601 urine analyzer
The cobas u 601 urine analyzer is a fully automated urine analysis system. It is optimized for high throughput workloads in the professional environment. The cobas u 601 urine analyzer performs a maximum theoretical throughput of up to 240 samples per hour.
The cobas u 601 analyzer consists of several major components:
- Rack transport system
- Liquid handling system
- Test strip cassette compartment
- Automated test strip processing area
- Photometer which is a 4 wavelength reflectance measuring unit based on a Complementary Metal Oxide Semiconductor chip used in digital cameras (CMOS sensor)
- Physical Measurement Cell (PMC): flow cell connected to an optical detector ●
- Touch Screen
- Inbuilt Computer
The functions of the cobas u 601 urine analyzer include:
- Sample loading and transport ●
- . Sample identification
- Robotic pipetting of samples onto test pads on test strips
51(k) Premarket Notification Print Date: May 6, 2019
7
- Robotic aspiration of samples into the PMC
- . Controlled incubation
- . Photometric measurement of test strips
- Optical determination in the PMC
- Automatic disposal of used test strips ●
- . Result readout
- Result memory
- Optional formats for data output including electronic result communication
The operating system will be a Microsoft Windows for embedded devices. The system will use a Postgres/SQL database.
The cobas u 601 urine analyzer is designed to be inter-connected mechanically and electronically with another urine sediment analyzer (cobas u 701) in order to create a urine work area (cobas® 6500).
1.2. cobas u pack
The cobas u pack is a cassette containing 400 tests strips. The cobas u 601 analyzer will use the cobas u pack to dispense single test strips for each sample.
Each test strip has ten individual test pads that are used to test for different substances or characteristics. The test strips are analyzed automatically through the analyzer. One test strip is used per sample. When a strip is dispensed for use by the cobas u 601, an aliquot of the urine sample is pipetted onto each of the test pads. The resulting color changes are measured photometrically.
The test strip in the cobas u pack cassette ("cassette test strip") is a multi-parameter urine analysis test strip, with test pads for blood (Erythrocytes), Leukocytes, Nitrite, Proteins, Glucose, Ketones, Bilirubin, Urobilinogen, Color and pH.
8
The cobas u pack is technically identical to the marketed Urisys 2400 Cassette with 400 test strips (cleared under K012397) with the following modifications:
- Added RFID-tag (ISO15693; 13.56 MHz)
- own labeling and own Id. No.
- . different brand
The RFID-tag is used for storing test strip related information to improve the safety and the convenience of the system. The following data is stored on the RFID-Tag:
- . generic product data
- strip cassette data
- test strip related data
- . cassette number
- lot number
- expiry date
- load date
- check sum
The on-board time is checked by the instrument and an alarm is triggered if the on-board time of a strip cassette (identified through its RFID-tag) exceeds its specified on-board stability.
2. INDICATIONS FOR USE
The cobas u 601 urinalysis test system is comprised of the cobas u 601 urine analyzer and the cobas u pack. The cobas u 601 urine analyzer when used with the cobas u pack is a fully automated urinalysis system intended for the in vitro qualitative or semiquantitative determination of urine analytes, including pH, leukocytes, nitrite, protein, glucose, ketones, urobilinogen, bilirubin, color and erythrocytes, as well as clarity. These
9
measurements are useful in the evaluation of renal, urinary, hepatic and metabolic disorders. This system is intended to be used by trained operators in clinical laboratories.
The cobas u pack is a cassette loaded with cobas u 601 test strips for the in vitro qualitative or semi-quantitative determination of pH, leukocytes, nitrite, protein, glucose, ketones, urobilinogen, bilirubin, color and erythrocytes in urine with the cobas u 601 urine analyzer. These measurements are useful in the evaluation of renal, urinary, hepatic and metabolic disorders.
TECHNOLOGICAL CHARACTERISTICS 3.
The following tables compare the cobas u 601 Urinalysis Test System with its predicate device, cobas u 411 (K093555).
| Feature | cobas u 411 (Predicate Device) | cobas u 601 Urinalysis Test
System (proposed device) |
|------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The cobas u 411 urine analyzer is a semi-
automated, benchtop analyzer which is designed
to read the Chemstrip 10 UA (Combur10 Test M)
test strips for urinalysis for the measurement of
bilirubin,
blood,
glucose,
ketone,
leukocytes,
nitrite,
pH,
protein,
specific gravity,
urobilinogen and
color (if selected).
These measurements are useful in the evaluation
of renal, urinary and metabolic disorders. Tests | The cobas u 601 urine analyzer
when used with the cobas u pack
is a fully automated urinalysis
system intended for the in vitro
qualitative or semi-quantitative
determination of urine analytes,
including
pH,
leukocytes,
nitrite,
protein,
glucose,
ketones,
urobilinogen,
bilirubin, color and erythrocytes,
as well as clarity.
These measurements are useful
in the evaluation of renal, urinary
and metabolic disorders. This |
| | performed using the cobas u 411 are intended for
prescription, in vitro diagnostic use only. | system is intended to be used by
trained operators in professional
laboratories. |
| Submission | K093555 | N/A |
| Feature | cobas u 411 (Predicate Device) | cobas u 601 Urinalysis Test
System (proposed device) |
| Automation | Semi-Automated | Fully Automated |
| Specimen | Urine | same |
| Analyzer Technology | Reflectance photometry | Reflectance photometry for
• pH,
• Leukocytes,
• Nitrite,
• Protein,
• Glucose,
• Ketones,
• Urobilinogen,
• Bilirubin, and
• Erythrocytes (blood). |
| Reagent Strip Format | Chemstrip 10 UA test strip | cobas u pack loaded with cobas
u 601 test strips |
| | Width: 5.0 mm | Width: 4.2 mm |
| | Length: 121 mm (with handle area) | Length: 104.9 mm (no handle
area) |
| | Number of pads: 11 | Number of pads: 10 (without
specific gravity)
Same distance between pads |
| | Sequence of pads:
- specific gravity,
- pH,
- leukocytes,
- nitrite,
- protein,
- glucose,
- ketone,
- urobilinogen,
- bilirubin,
- blood,
- color
pH pad: no underlying paper | Sequence of pads: - Blood,
- leukocytes,
- nitrite,
- ketone,
- glucose,
- protein,
- urobilinogen,
- bilirubin,
- color,
- pH
(no specific gravity)
pH pad: underlying paper
(different height) |
| | leukocytes: 1x underlying paper | Leukocytes: no underlying paper
(different height) |
| Feature | cobas u 411 (Predicate Device) | cobas u 601 Urinalysis Test
System (proposed device) |
| | nitrite: 1x underlying paper | nitrite: no underlying paper
(different height) |
| | protein: 2 x protein layer | protein: 1 x protein layer
(different color density) |
| | Glucose | Same format |
| | Ketone | Same format |
| | Urobilinogen | Same format |
| | Bilirubin | Same format |
| | Blood | Same format |
| | Color | Same format |
| Strip Delivery | Measurement of single strips, insert manually into
the instrument out of a vial | Automated test strip delivery
from cassette |
| Test Principles | pH: color change with the indicators methyl red,
phenolphthalein and bromothymol blue. | Same |
| | Leukocytes: esterases cleave an indoxyl ester,
and the indoxyl reacts with a diazonium salt to
produce a purple color.
Nitrite: based on the principle of the Griess test.
Nitrite, if present, reacts with an aromatic amine to
give a diazonium salt, which yields a red-violet azo
dye. | Same |
| | Protein: based on the "protein error of pH
indicators" involving
tetrachlorophenoltetrabromosulfophthalein | Same |
| | Glucose: based on the specific glucose
oxidase/peroxidase reaction (GOD/POD
method). | Same |
| | Ketone: based on the principle of Legal's
test involving use of sodium nitroprusside. | Same |
| | Urobilinogen: Urobilinogen is coupled
with 4-methoxybenzene-diazonium-
tetrafluoroborate in an acid medium to
form a red azo dye. | Same |
| Feature | cobas u 411 (Predicate Device) | cobas u 601 Urinalysis Test
System (proposed device) |
| | Bilirubin: based on the, coupling of
bilirubin with a diazonium salt. | Same |
| | Blood: The peroxidase-like action of hgb and
myoglobin catalyzes the oxidation of the indicator
by the organic peroxide. | Same |
| Light sources | LEDs | LEDs |
| Wavelengths | Light Emitting Diodes (LEDs)
Wavelength:
Orange: 620 nm
Green: 555 nm
Blue: 470 nm | Light Emitting Diodes (LEDs)
Wavelength:
Red: 615 nm
Green: 560 nm
True Green: 525 nm
Blue: 465 nm |
| Remission Sensor | 11 wide range photo sensors | Camera with CMOS
(Complementary Metal Oxide
Semiconductor) sensor |
| Sample Preparation | 1. Remove the test strip from the vial and close the
vial - Dip all test pads of the test strip completely in
the sample and wipe off excessive urine on the
edge of the sample tube. - Position the test strip on the test strip tray for
analysis | 1. Preparation of sample racks
and tubes - Loading the rack(s) onto the
analyzer - Start (automatic) analysis of
samples |
| Sample application | Manually dip of the strip | Robotic pipetting of samples onto
test pads on test strips |
| Calibration method | Calibration strips with specific reflectance values
for calibration. | Same |
| Intrinsic color compensation | Area not impregnated with reagents, allows
instrumental compensation for the intrinsic color of
the urine while testing | Same |
| Feature | cobas u 411 (Predicate Device) | cobas u 601 Urinalysis Test
System (proposed device) |
| Output values | The operator can view the
concentration ranges for each test parameter. | |
| | Units:
conventional,
SI,
Arbitrary,
SI & Arbitrary
Conventional & Arbitrary | Same |
| | ERY neg / 10 / 25 / 50 / 150 / 250 p/μl | Same |
| | LEU neg / 25 / 100 / 500 p/µl | Same |
| | NIT neg / pos | Same |
| | PRO neg / 15 / 30 / 100 / 500 mg/dl | Same |
| | GLU norm / 50 / 100 / 250 / 1000 mg/dl | Same |
| | KET neg / 5 / 15 / 50 / 150 mg/dl | Same |
| | BIL neg / 1 / 3 / 6 mg/dl | Same |
| | pH 5 / 6 / 6.5 / 7 / 8 / 9 | Same |
| | UBG norm / 1 / 4 / 8 / 12 mg/dl | Same |
| Strip Detector | Two strip detectors | Automatic strip transportation
system |
| Strip packaging | In vials of 100 strips | In cassette of 400 strips |
| Feature | cobas u 411 (Predicate Device) | cobas u 601 Urinalysis Test
System (proposed device) |
| Strip storage | Store at 20°C - 30°C.
Close vial immediately after use. | Store at 20°C - 30°C.
After loading the cassette into
the analyzer, the test strips are
stable within the tightly closed
cassette compartment for 14
days.
After this period, the cassette
has to be replaced by a new one. |
| Operating Conditions | Temperature:
operational: 15 - 32 °C
storage: -25 - 60 °C
Humidity:
operational: 30 - 80%
storage: 10 - 95% | Temperature:
operational: 15 - 32 °C
storage: 5 - 40 °C
Humidity:
operational: 30 - 80%
storage: 10 - 85% |
| Storage Medium | USB stick | USB stick |
| Sample identification | Sample identification with optional external
barcode scanner | Internal barcode reader for rack
ID and sample ID recognition |
| Printer | Integrated thermal paper | Optional external printer |
| Controlled incubation | Controlled incubation period after placing the wet
strip on the test strip tray | Controlled incubation period after
sample pipetting onto test pads
on test strips |
| Result Memory | Memory for 1000 entries (pending samples and
results) | Result memory is available |
Table 2: Similarities and Differences between the cobas u 601 Urinalysis Test System and the cobas u411 System
10
11
12
13
14
NON-CLINICAL PERFORMANCE EVALUATION 4.
4.1. Linearity/Reportable Results
The reportable results are determined by the analytical sensitivity and method comparison studies (Sections 4.2 and 5.1.3).
The results of those studies support the following reportable results:
15
| Parameter | Unit of Measure | Reportable Results |
|---|---|---|
| NIT | NA | Neg/Pos |
| GLU | mg/dL | Norm to 1000 |
| KET | mg/dL | Neg to 150 |
| BIL | mg/dL | Neg to 6 |
| UBG | mg/dL | Norm to 12 |
| PRO | mg/dL | |
| albumin | Neg to 500 | |
| ERY | ERY/µL | Neg to 250 |
| LEU | LEU/ µL | Neg to 500 |
| pH | NA | 5 to 9 |
| COL | NA | Pale yellow, yellow, amber, brown, |
| orange, red, green, others | ||
| SG | g/cm³ | 1.000 to 1.050 |
| Clarity | NA | Clear, light turbid, turbid |
Table 3: Reportable Results for each Parameter
4.2. Analytical Sensitivity
The sensitivity study was performed to determine the concentration at which the analyte on the cobas u pack changed from negative to the lowest positive color range. Samples were prepared by spiking the negative urine pool with the appropriate agent to yield the desired concentrations of analyte. Multiple samples were tested for each analyte. Each sample was measured 20 times on each of the 3 instruments using 3 reagent test strip lots. Sensitivity is defined as the lowest concentration where ≥90% of the overall results are positive.
The results summary and labeling claims are listed below.
Table 4: Summary and Labeling Claims for Analytical Sensitivity
| Parameter | Analytical Sensitivity Claim for cobas u pack | Point at which sensitivity meets
criteria of ≥90% detection |
|-----------|-----------------------------------------------|----------------------------------------------------------------|
| LEU | 10-30 Leu/μL | 10 Leu/μL |
| NIT | 0.03 – 0.07 mg/dL | 0.045 mg/dL |
| PRO | 7 - 13 mg/dL albumin | 9 mg/dL albumin |
| GLU | 25 – 45 mg/dL | 25 mg/dL |
| KET | 3 – 7 mg/dL | 4 mg/dL |
16
| Parameter | Analytical Sensitivity Claim for cobas u pack | Point at which sensitivity meets
criteria of ≥90% detection |
|-----------|-----------------------------------------------|----------------------------------------------------------------|
| BIL | 0.4 – 0.6 mg/dL | 0.6 mg/dL |
| UBG | 1.0 – 1.6 mg/dL | 1.15 mg/dL |
| ERY | 5-15 Ery/µL | 7 Ery/µL |
4.3. Drug and Endogenous Interferences
Interference studies were performed to assess the interfering effect of various therapeutic drugs and endogenous substances. Each analyte was tested in the normal/negative range and in the first positive range. A urine pool was prepared using fresh normal/negative urine and urine samples spiked with analytes in the first positive range. Each urine pool was tested at 2 concentrations of the pharmaceutical compounds/endogenous substances. The pharmaceutical compound solutions were prepared at a multiple of the maximum daily dosage and at the therapeutic concentration (maximal daily dosage). The endogenous substances were tested at a high pathological concentration and an intermediate concentration. Multiple replicates of the urine pool and the spiked interferent samples were measured. Testing was performed with two cobas u 601 urine analyzers. In the case of interference, further interferent concentrations were tested to evaluate the maximum interferent concentration which shows no influence on the measurement results.
Summaries and labeling claims are listed in the tables below.
| Parameter | Unit | Concentration Tested | |
|---|---|---|---|
| Negative/Normal | 1st Positive Range | ||
| ERY | Ery/µL | Negative | 10 |
| LEU | Leu/µL | Negative | 25 |
| NIT | mg/dL | Negative | 0.1 |
| PRO | mg/dL | Negative | 15 |
| GLU | mg/dL | Normal | 50 |
| KET | mg/dL | Negative | 5 |
| UBG | mg/dL | Normal | 1 |
| BIL | mg/dL | Negative | 1 |
Table 5: Analyte Concentrations of Samples Tested
17
| Therapeutic drug | Interferent c1:
a multiple of the maximal daily
dosage
[mg/L] | Interferent c2:
Maximal daily dosage under
medication
[mg/L] |
|------------------------------|------------------------------------------------------------------------|-----------------------------------------------------------------------|
| Acetaminophen | 3000 | 500 |
| Amoxicillin | 13333 | 2667 |
| Ascorbic acid | 4000 | 400 |
| Biotin | 1000 | 200 |
| Cefoxitin | 12000 | 2000 |
| Furosemide | 2000 | 400 |
| Gabapentin | 12000 | 2400 |
| Gentamycin Sulfate | 400 | 80 |
| Ibuprofen | 2500 | 500 |
| Levodopa | 1250 | 250 |
| Lisinopril | 267 | 53.4 |
| Metformin | 8500 | 1700 |
| Methyldopa | 2000 | 200 |
| Methenamine + Methylene blue | 400 + 66.5 | 80 + 13.3 |
| N-Acetyl-Cysteine | 200 | 100 |
| Ofloxacin | 900 | 100 |
| Phenazopyridine | 300 | 50 |
| Salicyluric acid | 6000 | 100 |
| Tetracycline | 500 | 100 |
Table 6: Potentially Interfering Therapeutic Drug Substances and Initial Test Concentrations
Table 7: Potentially Interfering Endogenous Substances and Initial Test Concentrations
| Endogenous substances | Interferent c1:
High pathological dosage
[mg/L] | Interferent c2:
Intermediate dosage
[mg/L] |
|-----------------------|-------------------------------------------------------|--------------------------------------------------|
| 3-Hydroxybutyrate | 4500 | 150 |
| Ammonium chloride | 25000 | 5000 |
| Bilirubin | 800 | 80 |
| Calcium chloride | 3000 | 600 |
| Creatinine | 15000 | 3000 |
| Glucose | 100000 | 70000 |
| Hemoglobin | 830 | 330 스 10000 ERY/ul |
18
| Endogenous substances | Interferent c1:
High pathological dosage
[mg/L] | Interferent c2:
Intermediate dosage
[mg/L] |
|----------------------------------|-------------------------------------------------------|--------------------------------------------------|
| human IgG | 5000 | 1000 |
| Nitrite | 110 | 2 |
| Urea | 200000 | 40000 |
| Uric acid | 1550 | 550 |
| Urobilinogen | 3000 | 120 |
| pH: 4.5; 5.5; 6.5; 7.5; 8.5; 9.0 | | |
Table 8: Summary and Labeling Claims
The following substances showed no interference at tested concentrations :
| Cefoxitin | ß-3-Hydroxybutyrat |
|---|---|
| Gentamycin Sulfate | Human IgG |
| Lisinopril | Uric acid |
| Metformin | |
| Ofloxacin | |
| Salicyluric acid | |
| Tetracycline |
The following table, which is included in the cobas u Pack method sheet, lists the therapeutic drugs which produced significant interference. Elevated positive result means that reference result = 1+ and spiking of interferent leads to results of 2+ or 3+.
Table 9: Interfering Therapeutic Drugs Listed in cobas u pack Method Sheet
| Parameter | Therapeutic drug | No Interference up to | Effect above stated concentration |
|---|---|---|---|
| ERY | Ascorbic Acid | 750 mg/L | At 1125 mg/L decreased from 10 Ery/µL / |
| 1+ to negative | |||
| (False negative results) | |||
| Parameter | Therapeutic drug | No Interference up to | Effect above stated concentration |
| Furosemide | 1800 mg/L | At 2000 mg/L decreased from 10 Ery/µL / | |
| 1+ to negative | |||
| (False negative results) | |||
| Ibuprofen | 750 mg/L | At 1250 mg/L decreased from 10 Ery/µL / | |
| 1+ to negative | |||
| (False negative results) | |||
| Levodopa | 625 mg/L | At 937.5 mg/L increased from negative / | |
| neg to pos 1 and from positive / pos 1 | |||
| to pos 2 | |||
| (False positive and elevated positive result) | |||
| Methyldopa | 800 mg/L | At 2000 mg/L increased from negative / neg | |
| to pos 1 and from | |||
| positive / pos 1 to pos 2 and | |||
| at 1200 mg/L increased from | |||
| positive / pos 1 to pos 2 | |||
| (False positive and elevated positive result) | |||
| Methenamine and | |||
| Methylene blue | 8 mg/L Methenamine | ||
| 1.3 mg/L Methylene blue | At 16 mg/L Methenamine and 2.7 mg/L | ||
| Methylene blue increased from | |||
| negative / neg to pos 1 and from | |||
| positive/pos 1 to pos 2 | |||
| (False positive and Elevated positive | |||
| results) | |||
| LEU | Amoxicillin | 10667 mg/L | At 12000 mg/L decreased from |
| 25 Leu/µL / 1+ to negative | |||
| (False negative result) | |||
| Ibuprofen | 200 mg/L | At 500 mg/L decreased from | |
| 25 Leu/µL / 1+ to negative | |||
| (False negative result) | |||
| Methenamine and | |||
| Methylene blue | 40 mg/L Methenamine | ||
| 6.7 mg/L Methylene blue | At 80 mg/L Methenamine and 13.3 mg/L | ||
| Methylene blue increased from | |||
| negative / neg to pos 1 | |||
| (False positive results) | |||
| NIT | Ascorbic Acid | 1500 mg/L | At 2000 mg/L decreased from |
| positive / pos to neg | |||
| (False negative results) | |||
| Methenamine and | |||
| Methylene blue | 28 mg/L Methenamine | ||
| 4.7 mg/L Methylene blue | At 40 mg/L Methenamine and 6.7 mg/L | ||
| Methylene blue increased from | |||
| negative / neg to pos | |||
| (False positive results) | |||
| Phenazopyridine | 120 mg/L | At 300 mg/L increased from | |
| negative / neg to pos 1 | |||
| (False positive results) | |||
| Parameter | Therapeutic drug | No Interference up to | Effect above stated concentration |
| PRO | Gabapentin | 2400 mg/L | At 3600 mg/L increased from |
| positive / pos 1 to pos 2 | |||
| (Elevated positive results) | |||
| Ibuprofen | 2250 mg/L | At 2500 mg/L decreased from | |
| positive / pos 1 to neg | |||
| (False negative results) | |||
| Methenamine and | |||
| Methylene blue | 2 mg/L Methenamine | ||
| 0.33 mg/L Methylene blue | At 80 mg/L Methenamine and 13.3. mg/L | ||
| Methylene blue increased from neg to pos 3 | |||
| and from positive / pos 1 to pos 3 and | |||
| at 8 mg/L Methenamine and 1.3 mg/L | |||
| Methylene blue increased from | |||
| positive / pos 1 to pos 2 | |||
| (False positive and elevated positive | |||
| results) | |||
| Phenazopyridine | 120 mg/L | At 300 mg/L increased from negative / neg | |
| to pos 1 and from positive / pos 1 to pos 2 | |||
| and at 240 mg/L increased from | |||
| positive / pos 1 to pos 2 | |||
| (False positive and elevated positive | |||
| results) | |||
| GLU | Ascorbic Acid | 200 mg/L | At 400 mg/L decreased from |
| positive / pos 1 to norm | |||
| (False normal results) | |||
| Methenamine and | |||
| Methylene blue | 120mg/L Methenamine | ||
| 20 mg/L Methylene blue | At 160 mg/L Methenamine and 26.6 mg/L | ||
| Methylene blue decreased from | |||
| positive / pos 1 to norm | |||
| (False normal results) | |||
| KET | N-Acetylcysteine | 30 mg/L | At 50 mg/L increased from |
| Negative / neg to pos 1 and from positive / | |||
| pos 1 to pos 2 | |||
| (False positive and elevated positive | |||
| results) | |||
| Levodopa | 1000 mg/L | At 1250 mg/L increased from | |
| positive / pos 1 to pos 2 | |||
| (Elevated positive results) | |||
| Methyldopa | 1200 mg/L | At 2000 mg/L increased from negative / neg | |
| to pos 1 and from positive / pos 1 to pos 2 | |||
| and at 1600 mg/L increased | |||
| from positive / pos 1 to pos 2 | |||
| (False positive and elevated positive | |||
| results) | |||
| Parameter | Therapeutic drug | No Interference up to | Effect above stated concentration |
| Methenamine and | |||
| Methylene blue | 160 mg/L Methenamine | ||
| 26.6 mg/L Methylene blue | At 208 mg/L Methenamine and 35 mg/L | ||
| Methylene blue decreased from | |||
| positive / pos 1 to neg | |||
| (False negative results) | |||
| UBG | Acetaminophen | 240 mg/L | At 420 mg/L increased from |
| positive / pos 1 to pos 2 | |||
| (Elevated positive results) | |||
| Gabapentin | 10800 mg/L | At 12000 mg/L decreased from | |
| positive / pos 1 to norm | |||
| (False normal results) | |||
| Methenamine and | |||
| Methylene blue | 24 mg/L Methenamine | ||
| 4 mg/L Methylene blue | At 48 mg/L Methenamine and 8 mg/L | ||
| Methylene blue increased from | |||
| positive / pos 1 to pos 2 | |||
| (Elevated positive results) | |||
| Phenazopyridine | 120mg/L | At 300 mg/L increased from normal / norm | |
| to pos 1 and from positive / pos 1 to pos 2 | |||
| and at 210 mg/L increased from positive / | |||
| pos 1 to pos 2 | |||
| (False positive and elevated positive | |||
| results) | |||
| BIL | Ascorbic Acid | 2000 mg/L | At 4000 mg/L decreased from |
| positive / pos 1 to neg | |||
| (False negative results) | |||
| Biotin | 800 mg/L | At 1000 mg/L increased from | |
| positive / pos 1 to pos 2 | |||
| (Elevated positive results) | |||
| Methenamine and | |||
| Methylene blue | 140 mg/L Methenamine | ||
| 23.3 mg/L Methylene blue | At 160 mg/L Methenamine and 26.6 mg/L | ||
| Methylene blue decreased from | |||
| positive / pos 1 to neg | |||
| (False negative results) | |||
| Phenazopyridine | 120 mg/L | At 240 mg/L increased from | |
| positive / pos 1 to pos 2 | |||
| (Elevated positive results) | |||
| Parameter | Endogenous substance | No Interference up to | Effect above stated concentration |
| ERY | Calcium chloride | 2430 mg/L | At 3000 mg/L increased from |
| positive / pos 1 to pos 2 | |||
| (Elevated positive result) | |||
| Nitrite | 40 mg/L | At 80 mg/L decreased from | |
| positive / pos 1 to neg | |||
| (False negative results) | |||
| Urobilinogen | 480 mg/L | At 3000 mg/L increased from negative / neg | |
| to pos 2 and from positive / pos 1 to pos 2 | |||
| and at 1200 mg/L increased from | |||
| negative / neg to pos 1 | |||
| (False positive and elevated positive | |||
| results) | |||
| LEU | Calcium chloride | 2430 mg/L | At 3000 mg/L decreased from |
| positive / pos 1 to neg | |||
| (False negative result) | |||
| Glucose | 10.000 mg/L | At 20.000 mg/L decreased from | |
| positive / pos 1 to neg | |||
| (False negative results) | |||
| Hemoglobin | 750 mg/L | At 830 mg/L increased from negative / neg | |
| to pos 1 | |||
| (False positive results) | |||
| pH |