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.

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.

AI/ML Overview

Here's an analysis of the provided text, focusing on the acceptance criteria and the study proving the device meets them:

Device: cobas u 601 urinalysis test system
Predicate Devices: cobas u 411 (for pH, leukocytes, nitrite, protein, glucose, ketones, urobilinogen, bilirubin, and erythrocytes), Urisys 2400 (for specific gravity, color, and clarity).

Based on the provided 510(k) Summary, the term "acceptance criteria" is not explicitly defined as a single, overarching set of numerical thresholds for all performance metrics. Instead, the document describes the studies performed and their results, implying that demonstrating acceptable performance within clinical ranges and in comparison to predicate devices constitutes meeting the "acceptance criteria" for substantial equivalence.

For each study, the "acceptance criteria" are implied by the reported results meeting the necessary performance for a diagnostic device, particularly demonstrating "exact agreement" or "agreement ± 1 block" within clinically relevant ranges and comparable to the predicate devices.

The information is extracted from the "NON-CLINICAL PERFORMANCE EVALUATION" and "CLINICAL PERFORMANCE DATA" sections.

1. Table of Acceptance Criteria (Implied) and Reported Device Performance

Since explicit numerical acceptance criteria for each test in a pass/fail format are not directly stated as "acceptance criteria," the table below presents the implied acceptance criteria (what the study aimed to demonstrate as acceptable performance) and the reported device performance as found in the document. The primary method for showing acceptance is often "exact agreement" or "agreement ± 1 block" with the predicate device/reference.

Parameter / Study Type	Implied Acceptance Criteria (Goal)	Reported Device Performance (Achieved)
Analytical Sensitivity (Lowest concentration for ≥90% detection)	To detect analytes at specified low concentrations with high confidence (≥90% detection).	LEU: 10 Leu/μL (meets criteria of ≥90% detection) NIT: 0.045 mg/dL (meets criteria of ≥90% detection) PRO: 9 mg/dL albumin (meets criteria of ≥90% detection) GLU: 25 mg/dL (meets criteria of ≥90% detection) KET: 4 mg/dL (meets criteria of ≥90% detection) BIL: 0.6 mg/dL (meets criteria of ≥90% detection) UBG: 1.15 mg/dL (meets criteria of ≥90% detection) ERY: 7 Ery/μL (meets criteria of ≥90% detection)
Drug & Endogenous Interferences	No significant interference from tested therapeutic drugs and endogenous substances at specified concentrations, that would impact clinical interpretation. Reported interferences are acknowledged and included in labeling claims.	No Interference: Acetaminophen, Amoxicillin, Biotin, Cefoxitin, Furosemide, Gabapentin, Gentamycin Sulfate, Ibuprofen, Levodopa, Lisinopril, Metformin, Methyldopa, Methenamine + Methylene blue, N-Acetyl-Cysteine, Ofloxacin, Phenazopyridine, Salicyluric acid, Tetracycline, ß-3-Hydroxybutyrate, Human IgG, Uric acid. Interference (listed in method sheet): Specific interferences with various analytes (ERY, LEU, NIT, PRO, GLU, KET, UBG, BIL) by therapeutic drugs and endogenous substances were identified and reported in tables showing "No Interference up to" a certain concentration, and the "Effect above stated concentration." These are noted in the product labeling.
Color Interference	The system's color compensation functionality should ensure accurate analyte measurements despite urine color variations. For negative parameters, 100% negative results; for positive, 100% exact agreement during color compensation.	Results: For all tested parameters (Nitrite, Ketone, Glucose, Bilirubin, Urobilinogen, Erythrocytes, Leukocytes) at both negative/normal and positive concentrations, both with and without added color interferents (Bilirubin for orange, Erythrocyte for red, Urobilinogen for brown; Hemoglobin, Sunset Yellow, Lignin for specific parameters), the exact agreement was consistently 100% when color compensation was active, with minor exceptions (e.g., Leu: 90% and 20% exact agreement for Sunset Yellow at 40 Leu/µL, though the table notes 100% for negative). The summary implies the system performs as expected.
Shelf-life Stability	cobas u pack stable for 15 months at room temperature.	The cobas u pack is stable at room temperature for 15 months.
On-board Stability	cobas u pack stable for 14 days during operation on the system.	The cobas u pack is stable up to 14 days during operation on the system.
Repeatability (Within-run precision)	100% exact agreement for controls (negative/normal and positive analyte concentrations).	Achieved: 100% exact agreement for all analytes (pH, ERY, LEU, PRO, GLU, KET, UBG, BIL, COL) at both Level 1 (Neg/Norm) and Level 2 (high positive) controls.
Intermediate Precision	High percentage of exact agreement for controls.	Achieved: 100% exact agreement for most analytes (pH, ERY, PRO, GLU, KET, UBG, BIL, COL). LEU Level 2 had 95.2% exact agreement.
Method Comparison (vs. cobas u 411)	High exact agreement and overall agreement with predicate, along with acceptable sensitivity and specificity. Thresholds varied by parameter.	ERY: Exact Agreement (100% fit): 85-100% (6/6 ranges passed); Overall: 99%; Specificity: 99%; Sensitivity: 99%. LEU: Exact Agreement: 88-99% (4/4 ranges passed); Overall: 99%; Specificity: 99%; Sensitivity: 97%. NIT: Exact Agreement: 99-100% (2/2 ranges passed); Overall: 100%; Specificity: 99%; Sensitivity: 100%. KET: Exact Agreement: 88-99% (5/5 ranges passed); Overall: 99%; Specificity: 99%; Sensitivity: 97%. GLUC: Exact Agreement: 86-100% (5/5 ranges passed); Overall: 99%; Specificity: 99%; Sensitivity: 100%. PRO: Exact Agreement: 87-98% (5/5 ranges passed); Overall: 99%; Specificity: 98%; Sensitivity: 100%. BIL: Exact Agreement: 91-100% (4/4 ranges passed); Overall: 99%; Specificity: 100%; Sensitivity: 98%. UBG: Exact Agreement: 87-99% (5/5 ranges passed); Overall: 99%; Specificity: 99%; Sensitivity: 98%. pH: Exact Agreement: 70-97% (6/6 ranges passed); Overall: 95%; Specificity: 98%.
Method Comparison (vs. Urisys 2400 for Color)	High agreement rates for color classification.	Agreement rates: Pale yellow (81%), Yellow (70%), Amber (65%), Brown (88%), Orange (68%), Red (91%). Overall agreement implied by diagonal matches.
Method Comparison (vs. Urisys 2400 for Clarity)	High exact agreement and agreement ± 1 color block.	Exact agreement (%): Clear (89%), Light Turbid (80%), Turbidity (84%). Agreement ± 1 color block: 100% for all clarity categories.
Sample Carryover	No risk to patient safety due to carryover.	Results met pre-defined acceptance criteria for BIL, GLU, KET, LEU, ERY, NIT, PRO, UBG, pH, COL and SG. Deviations were observed for Clarity but considered to pose no risk due to low medical relevance.

2. Sample Sizes and Data Provenance

Test Set Sample Sizes:
- Analytical Sensitivity: Multiple samples tested for each analyte, each sample measured 20 times on each of 3 instruments using 3 reagent test strip lots. (e.g., 20 measurements x 3 instruments x 3 lots = 180 total per sample condition per analyte if all combinations were tested). Specific number of "samples" (unique spiked concentrations) not explicitly stated for each analyte.
- Drug and Endogenous Interferences: Urine pools (negative/normal and first positive range) tested at 2 concentrations of interferents. Multiple replicates measured. Number of replicates not specified for each condition.
- Color Interference: Final test solutions (for each parameter) tested in a 10-fold determination. (e.g., 10 measurements per condition).
- Stability:
  - Real-time: Defined set of samples (native urine, artificial urine, low/high spiked urine) measured with n=10 determinations at each time point (0, 3, 13, 16 months).
  - On-board: 400 tests over 15 days from a single cassette (using native and artificial urine samples).
- Precision (Repeatability): Controls measured in 2 runs, 21 determinations each, producing n=42 results per control.
- Precision (Intermediate Precision): Controls measured in 21 days with 2 runs per day and duplicate measurements per control, producing n=84 results per control.
- Method Comparison (cobas u 411): "fresh samples" used to cover claimed ranges. Specific total number of samples for comparison is not explicitly stated.
- Method Comparison (Urisys 2400):
  - Color: 478 total samples.
  - Clarity: 1364 total samples.
- Sample Carryover: Not specified, but involved testing low/negative and high concentration samples.
Data Provenance: The document does not explicitly state the country of origin for the data or whether the studies were retrospective or prospective. Given it's a 510(k) submission for an in vitro diagnostic device, these are typically prospective laboratory studies conducted by the manufacturer, often at their R&D facilities or contracted clinical sites.

3. Number of Experts and Qualifications for Ground Truth

The document does not specify the number of experts used to establish ground truth for the test sets.
It also does not specify the qualifications of these experts.
For urinalysis strips, ground truth is typically established by reference methods such as quantitative chemical assays or microscopic examination, rather than relying solely on human expert consensus on visual interpretation of the strips themselves. The comparison is made against a "reference system" which implies an objective and validated method.

4. Adjudication Method for the Test Set

The document does not mention any adjudication method (e.g., 2+1, 3+1) for the test sets. For objective chemical measurements like those performed by this device, human adjudication of "ground truth" is typically less relevant than the use of quantitative reference methods.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

A MRMC comparative effectiveness study was not conducted. This device is an automated urinalysis system, and its performance is evaluated against established analytical methods and predicate devices, not by comparing human reader performance with and without AI assistance. The "AI" component is implicit in the automated analysis of reflectance, which is a core function of the machine's software, but it's not presented as an AI-assistive tool for human readers.

6. Standalone (Algorithm Only) Performance

Yes, the performance data presented (e.g., Analytical Sensitivity, Accuracy/Method Comparison studies) represents the standalone performance of the cobas u 601 urinalysis test system. It is an automated device designed to perform urinalysis without human interpretation of the test strip results; the human role is in operating the system and interpreting the numerical/qualitative results provided by the machine.

7. Type of Ground Truth Used

The ground truth used for these studies generally aligns with:
- Reference System/Predicate Device Comparison: For the method comparison studies, the cobas u 411 and Urisys 2400 systems served as "reference systems" against which the new device's qualitative and semi-quantitative results were compared.
- Spiked Samples/Defined Concentrations: For sensitivity, interference, stability, and precision studies, the ground truth was established by preparing urine samples with precisely known concentrations of analytes or interfering substances ("spiking the negative urine pool with the appropriate agent," "known concentrations").
- Control Materials: For precision studies, standardized control materials with known values were used.

8. The Sample Size for the Training Set

The document does not provide information regarding the sample size for a "training set." This type of device, based on reflectance photometry and chemical reactions, typically relies on predetermined algorithms derived from extensive analytical characterization of the strip chemistry and optical properties, rather than "training" an AI model in the conventional machine learning sense using a large, distinct "training set" of patient data. The development process would involve calibration and algorithm refinement using controlled samples, but not necessarily a "training set" as defined in AI/ML contexts with expert-labeled ground truth for each case.

9. How the Ground Truth for the Training Set Was Established

Since there's no explicit mention of a "training set" in the context of an AI/ML model for this device, the question of how ground truth was established for it is not applicable in the provided document. The "training" in this context would refer to the calibration and algorithm development process, which relies on the principles of analytical chemistry and physics inherent to reflectance photometry to accurately read the color changes on the test strips. This would involve precise chemical and optical characterization using known standards and samples.

Summary

{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.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{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 RoadP.O. Box 50416Indianapolis, IN 46250-0457
Contact	Angie ClementsPhone: (317) 521-7338FAX: (317) 521-2324Email: angie.clements@roche.comMichael LeutherPhone: (317) 521-3930FAX: (317) 521-2324Email: Michael.leuther@roche.com
Date Prepared	December 10, 2018
Proprietary Name	cobas u 601 Urinalysis Test System
Common Name	Automated urinalysis systemReagent 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 registrationnumber for Roche Diagnostics GmbH in Mannheim, Germany is 9610126. Theestablishment registration number for Roche Diagnostics in the United States is1823260.

Table 1: Product Codes and Regulation Numbers

Device/Analyte	Product Code	Classification	Regulation	Panel
Automated urinalysissystem	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, peroxidasetest	LJX	Class I	21 CFR 864.7675	81 Hematology
Bilirubin and itsconjugates, 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 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.

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.

{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.

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 TestSystem (proposed device)
Intended Use	The cobas u 411 urine analyzer is a semi-automated, benchtop analyzer which is designedto read the Chemstrip 10 UA (Combur10 Test M)test strips for urinalysis for the measurement ofbilirubin,blood,glucose,ketone,leukocytes,nitrite,pH,protein,specific gravity,urobilinogen andcolor (if selected).These measurements are useful in the evaluationof renal, urinary and metabolic disorders. Tests	The cobas u 601 urine analyzerwhen used with the cobas u packis a fully automated urinalysissystem intended for the in vitroqualitative or semi-quantitativedetermination of urine analytes,includingpH,leukocytes,nitrite,protein,glucose,ketones,urobilinogen,bilirubin, color and erythrocytes,as well as clarity.These measurements are usefulin the evaluation of renal, urinaryand metabolic disorders. This
	performed using the cobas u 411 are intended forprescription, in vitro diagnostic use only.	system is intended to be used bytrained operators in professionallaboratories.
Submission	K093555	N/A
Feature	cobas u 411 (Predicate Device)	cobas u 601 Urinalysis TestSystem (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 cobasu 601 test strips
	Width: 5.0 mm	Width: 4.2 mm
	Length: 121 mm (with handle area)	Length: 104.9 mm (no handlearea)
	Number of pads: 11	Number of pads: 10 (withoutspecific gravity)Same distance between pads
	Sequence of pads:1. specific gravity,2. pH,3. leukocytes,4. nitrite,5. protein,6. glucose,7. ketone,8. urobilinogen,9. bilirubin,10. blood,11. colorpH pad: no underlying paper	Sequence of pads:1. Blood,2. leukocytes,3. nitrite,4. ketone,5. glucose,6. protein,7. urobilinogen,8. bilirubin,9. color,10. 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 TestSystem (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 intothe instrument out of a vial	Automated test strip deliveryfrom 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 toproduce a purple color.Nitrite: based on the principle of the Griess test.Nitrite, if present, reacts with an aromatic amine togive a diazonium salt, which yields a red-violet azodye.	Same
	Protein: based on the "protein error of pHindicators" involvingtetrachlorophenoltetrabromosulfophthalein	Same
	Glucose: based on the specific glucoseoxidase/peroxidase reaction (GOD/PODmethod).	Same
	Ketone: based on the principle of Legal'stest involving use of sodium nitroprusside.	Same
	Urobilinogen: Urobilinogen is coupledwith 4-methoxybenzene-diazonium-tetrafluoroborate in an acid medium toform a red azo dye.	Same
Feature	cobas u 411 (Predicate Device)	cobas u 601 Urinalysis TestSystem (proposed device)
	Bilirubin: based on the, coupling ofbilirubin with a diazonium salt.	Same
	Blood: The peroxidase-like action of hgb andmyoglobin catalyzes the oxidation of the indicatorby the organic peroxide.	Same
Light sources	LEDs	LEDs
Wavelengths	Light Emitting Diodes (LEDs)Wavelength:Orange: 620 nmGreen: 555 nmBlue: 470 nm	Light Emitting Diodes (LEDs)Wavelength:Red: 615 nmGreen: 560 nmTrue Green: 525 nmBlue: 465 nm
Remission Sensor	11 wide range photo sensors	Camera with CMOS(Complementary Metal OxideSemiconductor) sensor
Sample Preparation	1. Remove the test strip from the vial and close thevial2. Dip all test pads of the test strip completely inthe sample and wipe off excessive urine on theedge of the sample tube.3. Position the test strip on the test strip tray foranalysis	1. Preparation of sample racksand tubes2. Loading the rack(s) onto theanalyzer3. Start (automatic) analysis ofsamples
Sample application	Manually dip of the strip	Robotic pipetting of samples ontotest pads on test strips
Calibration method	Calibration strips with specific reflectance valuesfor calibration.	Same
Intrinsic color compensation	Area not impregnated with reagents, allowsinstrumental compensation for the intrinsic color ofthe urine while testing	Same
Feature	cobas u 411 (Predicate Device)	cobas u 601 Urinalysis TestSystem (proposed device)
Output values	The operator can view theconcentration ranges for each test parameter.
	Units:conventional,SI,Arbitrary,SI & ArbitraryConventional & 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 transportationsystem
Strip packaging	In vials of 100 strips	In cassette of 400 strips
Feature	cobas u 411 (Predicate Device)	cobas u 601 Urinalysis TestSystem (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 intothe analyzer, the test strips arestable within the tightly closedcassette compartment for 14days.After this period, the cassettehas to be replaced by a new one.
Operating Conditions	Temperature:operational: 15 - 32 °Cstorage: -25 - 60 °CHumidity:operational: 30 - 80%storage: 10 - 95%	Temperature:operational: 15 - 32 °Cstorage: 5 - 40 °CHumidity:operational: 30 - 80%storage: 10 - 85%
Storage Medium	USB stick	USB stick
Sample identification	Sample identification with optional externalbarcode scanner	Internal barcode reader for rackID and sample ID recognition
Printer	Integrated thermal paper	Optional external printer
Controlled incubation	Controlled incubation period after placing the wetstrip on the test strip tray	Controlled incubation period aftersample pipetting onto test padson test strips
Result Memory	Memory for 1000 entries (pending samples andresults)	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/dLalbumin	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 meetscriteria 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 meetscriteria 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 dailydosage[mg/L]	Interferent c2:Maximal daily dosage undermedication[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 1to pos 2(False positive and elevated positive result)
	Methyldopa	800 mg/L	At 2000 mg/L increased from negative / negto pos 1 and frompositive / pos 1 to pos 2 andat 1200 mg/L increased frompositive / pos 1 to pos 2(False positive and elevated positive result)
	Methenamine andMethylene blue	8 mg/L Methenamine1.3 mg/L Methylene blue	At 16 mg/L Methenamine and 2.7 mg/LMethylene blue increased fromnegative / neg to pos 1 and frompositive/pos 1 to pos 2(False positive and Elevated positiveresults)
LEU	Amoxicillin	10667 mg/L	At 12000 mg/L decreased from25 Leu/µL / 1+ to negative(False negative result)
	Ibuprofen	200 mg/L	At 500 mg/L decreased from25 Leu/µL / 1+ to negative(False negative result)
	Methenamine andMethylene blue	40 mg/L Methenamine6.7 mg/L Methylene blue	At 80 mg/L Methenamine and 13.3 mg/LMethylene blue increased fromnegative / neg to pos 1(False positive results)
NIT	Ascorbic Acid	1500 mg/L	At 2000 mg/L decreased frompositive / pos to neg(False negative results)
	Methenamine andMethylene blue	28 mg/L Methenamine4.7 mg/L Methylene blue	At 40 mg/L Methenamine and 6.7 mg/LMethylene blue increased fromnegative / neg to pos(False positive results)
	Phenazopyridine	120 mg/L	At 300 mg/L increased fromnegative / 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 frompositive / pos 1 to pos 2(Elevated positive results)
	Ibuprofen	2250 mg/L	At 2500 mg/L decreased frompositive / pos 1 to neg(False negative results)
	Methenamine andMethylene blue	2 mg/L Methenamine0.33 mg/L Methylene blue	At 80 mg/L Methenamine and 13.3. mg/LMethylene blue increased from neg to pos 3and from positive / pos 1 to pos 3 andat 8 mg/L Methenamine and 1.3 mg/LMethylene blue increased frompositive / pos 1 to pos 2(False positive and elevated positiveresults)
	Phenazopyridine	120 mg/L	At 300 mg/L increased from negative / negto pos 1 and from positive / pos 1 to pos 2and at 240 mg/L increased frompositive / pos 1 to pos 2(False positive and elevated positiveresults)
GLU	Ascorbic Acid	200 mg/L	At 400 mg/L decreased frompositive / pos 1 to norm(False normal results)
	Methenamine andMethylene blue	120mg/L Methenamine20 mg/L Methylene blue	At 160 mg/L Methenamine and 26.6 mg/LMethylene blue decreased frompositive / pos 1 to norm(False normal results)
KET	N-Acetylcysteine	30 mg/L	At 50 mg/L increased fromNegative / neg to pos 1 and from positive /pos 1 to pos 2(False positive and elevated positiveresults)
	Levodopa	1000 mg/L	At 1250 mg/L increased frompositive / pos 1 to pos 2(Elevated positive results)
	Methyldopa	1200 mg/L	At 2000 mg/L increased from negative / negto pos 1 and from positive / pos 1 to pos 2and at 1600 mg/L increasedfrom positive / pos 1 to pos 2(False positive and elevated positiveresults)
Parameter	Therapeutic drug	No Interference up to	Effect above stated concentration
	Methenamine andMethylene blue	160 mg/L Methenamine26.6 mg/L Methylene blue	At 208 mg/L Methenamine and 35 mg/LMethylene blue decreased frompositive / pos 1 to neg(False negative results)
UBG	Acetaminophen	240 mg/L	At 420 mg/L increased frompositive / pos 1 to pos 2(Elevated positive results)
	Gabapentin	10800 mg/L	At 12000 mg/L decreased frompositive / pos 1 to norm(False normal results)
	Methenamine andMethylene blue	24 mg/L Methenamine4 mg/L Methylene blue	At 48 mg/L Methenamine and 8 mg/LMethylene blue increased frompositive / pos 1 to pos 2(Elevated positive results)
	Phenazopyridine	120mg/L	At 300 mg/L increased from normal / normto pos 1 and from positive / pos 1 to pos 2and at 210 mg/L increased from positive /pos 1 to pos 2(False positive and elevated positiveresults)
BIL	Ascorbic Acid	2000 mg/L	At 4000 mg/L decreased frompositive / pos 1 to neg(False negative results)
	Biotin	800 mg/L	At 1000 mg/L increased frompositive / pos 1 to pos 2(Elevated positive results)
	Methenamine andMethylene blue	140 mg/L Methenamine23.3 mg/L Methylene blue	At 160 mg/L Methenamine and 26.6 mg/LMethylene blue decreased frompositive / pos 1 to neg(False negative results)
	Phenazopyridine	120 mg/L	At 240 mg/L increased frompositive / 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 frompositive / pos 1 to pos 2(Elevated positive result)
	Nitrite	40 mg/L	At 80 mg/L decreased frompositive / pos 1 to neg(False negative results)
	Urobilinogen	480 mg/L	At 3000 mg/L increased from negative / negto pos 2 and from positive / pos 1 to pos 2and at 1200 mg/L increased fromnegative / neg to pos 1(False positive and elevated positiveresults)
LEU	Calcium chloride	2430 mg/L	At 3000 mg/L decreased frompositive / pos 1 to neg(False negative result)
	Glucose	10.000 mg/L	At 20.000 mg/L decreased frompositive / pos 1 to neg(False negative results)
	Hemoglobin	750 mg/L	At 830 mg/L increased from negative / negto pos 1(False positive results)
	pH	< pH 5.5	At pH 4.5 decreased frompositive / pos 1 to neg(False negative results)
	Bilirubin	400 mg/L	At 800 mg/L increased from negative / negto pos 1(False positive results)
	Urobilinogen	120 mg/L	At 3000 mg/L decreased from positive / pos1 to neg and at 150 mg/L increased fromnegative / neg to pos 1(False positive results and false negativeresults)
	SG	1.030	At SG 1.040 decreased from positive / pos1 to neg(False negative results)
NIT	Bilirubin	400 mg/L	At 800 mg/L decreased from positive / pos1 to neg(False negative results)
	Urobilinogen	90 mg/L	At 105 mg/L increased fromnegative / neg to pos 1(False positive results)
Parameter	Endogenous substance	No Interference up to	Effect above stated concentration
PRO	Ammonium chloride	1725 mg/L	At 5000 mg/L decreased frompositive / pos 1 to neg(False negative results)
	Calcium chloride	2430 mg/L	At 3000 mg/L decreased frompositive / pos 1 to neg(False negative results)
	Creatinine	2850 mg/L	At 15000 mg/L increased from negative /neg to pos 1 and from positive / pos 1 topos 2 and at 4200 mg/L increased frompositive / pos 1 to pos 2(False positive and elevated positive result)
	Hemoglobin	66 mg/L	At 130 mg/L increased frompositive / pos 1 to pos 2(False positive and false elevated resultsdue to unspecific protein detection mayoccur)
	Urea	52000 mg/L	At 200000 mg/L increased from negative /neg to pos 2 and from positive / pos 1 topos 2 and at 89000 mg/L increased frompositive / pos 1 to pos 2(False positive and elevated positive result)
	Urobilinogen	120 mg/L	At 3000 mg/L increased from negative / negto pos 3 and from positive / pos 1 to pos 3and at 240 mg/L increased from positive /pos 1 to pos 2(False positive and elevated positive result)
	Bilirubin	400 mg/L	At 600 mg/L increased form negative / negto pos 1(False positive results)
GLU	Ammonium chloride	10300 mg/L	At 15200 mg/L decreased frompositive / pos 1 to norm(False normal results)
	Urea	89000 mg/L	At 126000 mg/L increased frompositive / pos 1 to norm(False normal results)
	Bilirubin	400 mg/L	At 800 mg/L decreased from positive / pos1 to norm(False normal results)
	Urobilinogen	1250 mg/L	At 1500 mg/L decreased frompositive / pos 1 to norm(False normal results)
KET	Bilirubin	400 mg/L	At 800 mg/L decreased from positive / pos1 to neg(False negative results)
Parameter	Endogenous substance	No Interference up to	Effect above stated concentration
	Urobilinogen	900 mg/L	At 3000 mg/L decreased frompositive / pos 1 to neg(False negative results)
UBG	Nitrite	7 mg/L	At 14 mg/L decreased frompositive / pos 1 to norm(False normal results)
	Bilirubin	400 mg/L	At 600 mg/L decreased from positive /pos 1 to norm(False normal results)
BIL	Nitrite	7 mg/L	At 14 mg/L decreased frompositive / pos 1 to neg(False negative results)
	Urobilinogen	60 mg/L	At 120 mg/L increased from negative / negto pos 2 and from positive / pos 1 to pos 2and at 70 mg/L increased from positive /pos 1 to pos 2(False positive and elevated positiveresults)

{19}------------------------------------------------

{20}------------------------------------------------

{21}------------------------------------------------

The following table, which is included in the cobas u Pack Method Sheet, lists the endogenous substances which produced significant interference. Elevated positive result means that reference result = 1+ and spiking of interferent leads to results of 2+ or 3+.

Table 10: Interfering Endogenous Substances Listed in the cobas u pack Method Sheet

{22}------------------------------------------------

{23}------------------------------------------------

{24}------------------------------------------------

4.4. Color Interference

The purpose of this study was to verify the color compensation functionality of the cobas u 601 urine analyzer.

Two analyte solutions per parameter were prepared, a negative/normal solution and a solution in a color block that uses color compensation.

Each of the test solutions prepared above were spiked with the following concentrations of interferent to produce a red, orange or brown color:

Table 11: Interferent Concentration

Interferent	0	c1	c2
ERY (red color)	0 Ery/μL(~67% REM)	15050 Ery/μL(~58% REM)	3550 Ery/μL(~65% REM)
BIL (orange color)	0 mg/dL(~67% REM)	31 mg/dL(~58% REM)	8 mg/dL(~65% REM)
UGB (brown color)	0 mg/dL(~67% REM)	100 mg/dL(~58% REM)	12 mg/dL(~65% REM)

{25}------------------------------------------------

Interferent	0	c1	c2
Color compensation active	No	Yes	No

The following concentrations of interferent were tested for LEU (red, orange and brown), NIT (brown) and UBG (brown):

Table 12: Interferent Concentration

Interferent	0	c1	c2
Hemoglobin (red color)	0 Ery/μL(~67% REM)	750 mg/L25,000 Ery/ μL(~58% REM)	300 mg/L10,000 Ery/μL(~65% REM)
SunsetYellow (orange color)	0 mg/dL(~67% REM)	312.5 mg/L(~58% REM)	150 mg/L(~66% REM)
Lignin (brown color)	0 mg/L(~67% REM)	1 mg/L(~58% REM)	0.4 mg/L(~66% REM)
Color compensation active	No	Yes	No

For the red colored urine two further concentrations were measured. One at pathological concentration level (c3 = 500 ERY/uL = 15 mg/L hemoglobin, including 66 % safety margin) and one at physiological concentration level (c4 = 30 ERY/μL = 0.9 mg/L hemoglobin).

The final test solutions were tested in a 10-fold determination for each parameter.

{26}------------------------------------------------

	Parameterconcentration	Orange coloring		Red Coloring		Brown Coloring
Parameter		Bilirubinconcentration	Resulta	ErythrocyteConcentration	Resulta	UrobilinogenConcentration	Resulta
	Neg	Neg	100	Neg	100	---	---
	Neg	31 mg/dL	100	15050 Ery/μL	100	---	---
	Neg	8 mg/dL	100	3550 Ery/ μL	100	---	---
Nitrite	0.1 mg/dL	Neg	100	Neg	100	---	---
	0.1 mg/dL	31 mg/dL	100	15050 Ery/μL	100	---	---
	0.1 mg/dL	8 mg/dL	100	3550 Ery/ μL	100	---	---
	Neg	Neg	100	Neg	100	Neg	100
	Neg	31 mg/dL	100	15050 Ery/μL	100	100 mg/dL	100
	Neg	8 mg/dL	100	3550 Ery/ μL	100	12 mg/dL	100
Ketone	4 mg/dL	Neg	100	Neg	100	Neg	100
	4 mg/dL	31 mg/dL	100	15050 Ery/μL	100	100 mg/dL	100
	4 mg/dL	8 mg/dL	100	3550 Ery/ μL	100	12 mg/dL	100
	Normal	Neg	100	Neg	100	Neg	100
	Normal	31 mg/dL	100	15050 Ery/μL	100	100 mg/dL	100
	Normal	8 mg/dL	100	3550 Ery/ μL	100	12 mg/dL	100
Glucose	50 mg/dL	Neg	100	Neg	100	Neg	100
	50 mg/dL	31 mg/dL	100	15050 Ery/μL	100	100 mg/dL	100
	50 mg/dL	8 mg/dL	100	3550 Ery/ μL	100	12 mg/dL	100
	Neg	---	---	Neg	100	---	---
	Neg	---	---	15050 Ery/μL	100	---	---
	Neg	---	---	3550 Ery/ μL	100	---	---
Bilirubin	1 mg/dL	---	---	Neg	100	---	---
	1 mg/dL	---	---	15050 Ery/μL	100	---	---
	1 mg/dL	---	---	3550 Ery/ μL	100	---	---
	Normal	Neg	100	Neg	100	---	---
	Normal	31 mg/dL	100	15050 Ery/μL	100	---	---
	Normal	8 mg/dL	100	3550 Ery/ μL	100	---	---
Urobilinogen	1.6 mg/dL	Neg	100	Neg	100	---	---
	1.6 mg/dL	31 mg/dL	100	15050 Ery/μL	100	---	---
	1.6 mg/dL	8 mg/dL	100	3550 Ery/ μL	100	---	---
	Neg	Neg	100	---	---	Neg	100
Erythrocytes	Neg	31 mg/dL	100	---	---	100 mg/dL	100
	Neg	8 mg/dL	100	---	---	12 mg/dL	100
Parameter	Parameterconcentration	Orange coloring		Red Coloring		Brown Coloring
		Bilirubinconcentration	Resulta	ErythrocyteConcentration	Resulta	UrobilinogenConcentration	Resulta
	75 Ery/μL	Neg	100	---	---	Neg	100
	75 Ery/μL	31 mg/dL	100	---	---	100 mg/dL	100
	75 Ery/μL	8 mg/dL	100	---	---	12 mg/dL	100

Table 13: Summary of Color Interference Testing

51(k) Premarket Notification Print Date: May 6, 2019

{27}------------------------------------------------

4Results: For each negative parameter concentration: the results expressed as % negative results

For each positive parameter concentration: the results expressed as % exact agreement

Table 14: Summary of Color Interference Testing

		Orange coloring		Red Coloring		Brown Coloring
Parameter	Parameterconcentration	SunsetYellowConcentration	Resulta	HemoglobinConcentration	Resulta	LigninConcentration	Resulta
Nitrite	Neg	---	---	---	---	Neg	100
	Neg	---	---	---	---	1 mg/L	100
	Neg	---	---	---	---	0.4 mg/L	100
	0.1 mg/dL	---	---	---	---	Neg	100
	0.1 mg/dL	---	---	---	---	0.1 mg/L	100
	0.1 mg/dL	---	---	---	---	0.4 mg/L	100
Bilirubin	Neg	---	---	---	---	Neg	100
	Neg	---	---	---	---	1 mg/L	100
	Neg	---	---	---	---	0.4 mg/L	100
	1 mg/dL	---	---	---	---	Neg	100
	1 mg/dL	---	---	---	---	0.1 mg/L	100
	1 mg/dL	---	---	---	---	0.4 mg/L	100
Leukocytes	Neg	Neg	100	Neg	100	Neg	100
	Neg	312.5 mg/L	100	750 mg/L	90	100 mg/dL	100
	Neg	150 mg/L	100	300 mg/L	100	12 mg/dL	100
	40 Leu/µL	Neg	100	Neg	100	Neg	100
	40 Leu/µL	312.5 mg/L	20	750 mg/L	100	100 mg/dL	100
	40 Leu/μL	150 mg/L	100	300 mg/L	100	12 mg/dL	100

4 Results: For each negative parameter concentration: the results expressed as % negative results

For each positive parameter concentration: the results expressed as % exact agreement

{28}------------------------------------------------

4.5. Stability

Shelf-life (real-time) and on-board stability of the cobas u pack were determined on cobas u 601.

Real-time stability of the cobas u pack on the cobas u 601 urine analyzer was determined using two analyzers and three lots of cobas u pack. Stability testing was performed at time 0 (after manufacturing), and 3, 13 and 16 months after storage.

For each testing point a fresh cassette was placed on the calibrated urine analyzer and a defined set of samples was measured. Those sample materials include native urine, artificial urine, urine spiked with low analyte concentration and urine with high analyte concentration (for the qualitative parameters NIT only three, and for pH only two different urine sample materials were tested). All samples were measured with n=10 determinations.

The cobas u pack is stable at room temperature for 15 months.

On-board stability of the cobas u pack on the cobas u 601 urine analyzer was determined using one lot of cobas u pack on one analyzer. The cobas u pack, which contains 400 reagent test strips in a single cassette, was stored on the cobas u 601 urine analyzer over a period of 15 days at 32°C and 80% relative humidity. Parameters were tested at 11 different time points with a total of 400 tests over the period of 15 days from a single cassette. Native and artificial urine samples at abnormal concentration were used for the on board stability study.

The cobas u pack is stable up to 14 days during operation on the system.

4.6. Expected Values

The expected values are listed in the table below:

{29}------------------------------------------------

Table 15: Expected Values

Analyte	Expected Value
Erythrocytes	0-5 Ery/µL
Leukocytes	< 10 Leu/µL
Nitrite	Negative
Ketone	< 5 mg/dL
Glucose	< 30 mg/dL
Protein	< 10 mg/dL
Bilirubin	< 0.2 mg/dL
Urobilinogen	< 1 mg/dL
pH	4.8 - 7.4

{30}------------------------------------------------

5. CLINICAL PERFORMANCE DATA

5.1. Precision

Precision was comprised of experiments for repeatability and Intermediate precision.

Repeatability 5.1.1.

Controls were measured for the within-run precision study of the test strip parameters. Controls with negative / normal and positive analyte concentrations were measured in 2 runs, 21 determinations each, thereby producing n = 42 results per control.

Table 16: Repeatability

Parameter	Control	Result	Exact Agreement
pH	Level 1	6	100%
pH	Level 2	7	100%
ERY	Level 1	Neg	100%
ERY	Level 2	250 Ery/μL	100%
LEU	Level 1	Neg	100%
LEU	Level 2	500 Ery/μL	100%
PRO	Level 1	Neg	100%
PRO	Level 2	100 mg/dL	100%
GLU	Level 1	Norm	100%
GLU	Level 2	1000 mg/dL	100%
KET	Level 1	Neg	100%
KET	Level 2	150 mg/dL	100%
UBG	Level 1	Norm	100%
UBG	Level 2	8 mg/dL	100%
BIL	Level 1	Neg	100%
BIL	Level 2	6 mg/dL	100%
COL	Level 1	Yellow	100%
COL	Level 2	Brown	100%

{31}------------------------------------------------

5.1.2. Intermediate Precision

Controls were measured for the intermediate study of the test strip parameters. Controls with negative / normal and positive analyte concentrations were measured in 21 days with 2 runs per day and duplicate measurements per control, thereby producing n = 84 results per control.

Parameter	Control	Result	Exact Agreement
pH	Level 1	6	100%
pH	Level 2	7	100%
ERY	Level 1	Neg	100%
ERY	Level 2	250 Ery/μL	100%
LEU	Level 1	Neg	100%
LEU	Level 2	500 Ery/μL	95.2%
PRO	Level 1	Neg	100%
PRO	Level 2	100 mg/dL	100%
GLU	Level 1	Norm	100%
GLU	Level 2	1000 mg/dL	100%
KET	Level 1	Neg	100%
KET	Level 2	150 mg/dL	100%
UBG	Level 1	Norm	100%
UBG	Level 2	8 mg/dL	100%
BIL	Level 1	Neg	100%
BIL	Level 2	6 mg/dL	100%
COL	Level 1	Yellow	100%
COL	Level 2	Brown	100%

Table 17: Intermediate Precision

5.1.3. Method Comparison versus Reference System

Method comparison studies were conducted to evaluate the performance of the cobas u 601 urinalysis test system. The cobas u 411 is the predicate for pH, leukocytes, nitrite, protein, glucose, ketones, urobilinogen, bilirubin, and erythrocytes. The Urisys 2400 is the predicate for specific gravity, color and clarity. Testing was performed externally using fresh samples in order to cover the claimed ranges.

{32}------------------------------------------------

Table 18: Summary of comparison to cobas u 411

Summary Method comparison
Test Strip Parameter	exact agreement (100% fit)		exact agreement(fit ± 1 block)	Overall agreement (%)	Specificity (%)	Sensitivity (%)
	Ranges passed	agreement rates (%)
ERY	Ery/μL	6/6	85 - 100	100	99	99	99
LEU	Leu/μL	4/4	88 - 99	100	99	99	97
NIT	-	2/2	99 - 100	100	100	99	100
KET	mg/dL	5/5	88 - 99	100	99	99	97
GLUC	mg/dL	5/5	86 - 100	100	99	99	100
PRO	mg/dL	5/5	87 - 98	100	99	98	100
BIL	mg/dL	4/4	91 - 100	100	99	100	98
UBG	mg/dL	5/5	87 - 99	100	99	99	98
pH (pH 5+6)	-	2/2	87 - 90	100	98
pH (pH 8+9)	-	2/2	86 - 97	100	98
pH	-	6/6	70 - 97	100	95

Table 19: Summary of comparison to Urisys 2400 for Color

COL	Urisys 2400
	Paleyellow	Yellow	Amber	Brown	Orange	Red
cobas u 601	Paleyellow	126	7	0	0	0	0	133
	Yellow	23	85	2	0	0	0	110
	Amber	1	29	58	0	0	0	88
	Brown	0	0	24	50	0	0	74

{33}------------------------------------------------

	Orange	5	0	5	7	15	3	35
	Red	0	0	0	0	7	31	38
	Σ	155	121	89	57	22	34	478

Agreement Rate	81	70	65	88	68	91
(%):	87

Table 20: Summary of Comparison to Urysis 2400 for Clarity

Clarity	URISYS 2400
		clear	light turbid	turbid	Σ
cobas u 601	clear	921	23	0	944
	light turbid	114	173	18	305
	turbid	2	21	92	115
	Σ	1037	217	110	1364

Exact agreement (%)	89%	80%	84%
agreement ±1 color block	100%	100%	100%

5.2. Sample Carryover

Sample carryover studies were performed to assess the amount of sample carried over by the cobas u 601 from one specimen reaction into the subsequent specimen reactions. This consisted of testing low concentration/negative samples and high concentration samples. The negative pool was tested to determine a baseline value (reference). Then, the samples were tested by alternate pipetting of the low concentration/negative sample and high concentration samples. Carryover effects were assessed by comparing the baseline (reference) results of the low concentration/negative samples when tested after the high concentration samples.

The results obtained for BIL, GLU, KET, LEU, ERY, NIT, PRO, UBG, pH, COL and SG met the pre-defined acceptance criteria. Deviations were observed for Clarity but there will be no risk for patient safety because of the low medical relevance of this parameter.

{34}------------------------------------------------

CONCLUSION 6.

The information provided in this premarket notification 510(k) will support a determination of substantial equivalence for the cobas u 601 Urinalysis Test System as compared to the predicate devices.

Regulation Number and Section

§ 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.