(147 days)
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.
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.
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.
§ 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.