(224 days)
The cobas u 701 microscopy analyzer is a fully automated urine microscopy system intended for the in vitro quantitative determination of erythrocytes and leukocytes, the semi-quantitative determination of squamous epithelial cells, bacteria, and hyaline casts and the qualitative determination of non-squamous epithelial cells, crystals, yeasts, mucus and sperm in urine.
This system is intended to be used by trained operators in clinical laboratories. All instrument analyte image decisions may be reviewed and reclassified by a trained operator.
The cobas u 701 microscopy analyzer is a fully automated urine analysis system. It is optimized for the high-volume professional laboratory market. The cobas u 701 microscopy analyzer performs a maximum theoretical throughput of up to 116 samples per hour.
The cobas u 701 microscopy analyzer consists of several major components:
- Rack transport system
- Liquid handling system
- Cuvette cassette compartment
- Centrifuge
- Built-in reverse microscope with movable objective lens for focusing procedure
- High resolution camera system
- Touch Screen
- Inbuilt Computer with the imaging and evaluation software for analyzing the sediment pictures
Key functions include sample loading and transport, sample identification, sample homogenization, sample pipetting into cuvettes, centrifugation of cuvettes, image acquisition with a camera, image assessment, automatic disposal of used cuvettes, result readout, result and image memory, optional manual classification and / or re-classification of particles, manual or Automatic validation of the result, optional formats for data output including electronic result communication, data export, remote service, quality control, processing of diluted samples, washing, filling water tank, emptying liquid and solid waste.
The cobas u cuvette is used by the cobas u 701 microscopy analyzer to transport, centrifuge and analyze patient and control samples.
No calibration of the device is necessary for its intended use. However, there is a microscope check utilizing a reference cuvette.
Here's a summary of the acceptance criteria and the study proving the device meets them, based on the provided text:
Acceptance Criteria and Device Performance for cobas u 701 microscopy analyzer
The cobas u 701 microscopy analyzer is a fully automated urine microscopy system for a range of urine particle determinations.
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state a single table of "acceptance criteria" against "reported device performance." Instead, it presents various performance studies (Precision, Analytical Sensitivity, Linearity, Dilution, Interferences, Assay Cut-Off, and Method Comparison) and states that "All predefined acceptance criteria were met" for each, or provides detailed results that demonstrate meeting criteria. The closest to reported performance criteria vs. actual results are in the Method Comparison section.
Here's an aggregated table focusing on the method comparison to the reference method, as this directly compares the device's output to a recognized standard or clinical assessment.
| Parameter | Acceptance Criteria (Implied by Cohen's Kappa, PPA, NPA) | Reported Device Performance (All Sites Combined) |
|---|---|---|
| Quantitative Parameters | ||
| RBC (P/L) | Slope close to 1, Intercept close to 0, High r | Slope: 1.00 (0.99, 1.01) |
| Intercept: -0.67 (-1.65, 0.16) | ||
| r: 0.99 | ||
| Negative Agreement: High (>90%) | 99% | |
| Positive Agreement: High (>90%) | 92% | |
| WBC (P/L) | Slope close to 1, Intercept close to 0, High r | Slope: 0.98 (0.97, 0.99) |
| Intercept: -0.99 (-1.91, 0.04) | ||
| r: 0.98 | ||
| Negative Agreement: High (>90%) | 98% | |
| Positive Agreement: High (>90%) | 98% | |
| Semi-Quantitative Parameters | ||
| Bacteria (BAC) | Cohen's Kappa: High (e.g., >0.80) | 0.88 |
| PPA: High (>90%) | 93% (90%) | |
| NPA: High (>90%) | 95% (93%) | |
| Squamous Epithelial Cells (SEC) | Cohen's Kappa: High (e.g., >0.80) | 0.86 |
| PPA: High (>90%) | 93% (90%) | |
| NPA: High (>90%) | 95% (94%) | |
| Hyaline Casts (HYA) | Cohen's Kappa: High (e.g., >0.80) | 0.83 |
| PPA: High (>90%) | 91% (89%) | |
| NPA: High (>90%) | 97% (95%) | |
| Qualitative Parameters | ||
| Crystals (CRY) | Cohen's Kappa: High (e.g., >0.80) | 0.95 |
| PPA: High (>90%) | 98% (93%) | |
| NPA: High (>90%) | 97% (95%) | |
| Mucus (MUC) | Cohen's Kappa: High (e.g., >0.80) | 0.93 |
| PPA: High (>90%) | 94% (91%) | |
| NPA: High (>90%) | 99% (98%) | |
| Non-Squamous Epithelial Cells (NEC) | Cohen's Kappa: High (e.g., >0.80) | 0.84 |
| PPA: High (>85%) | 94% (88%) | |
| NPA: High (>85%) | 90% (88%) | |
| Pathological Casts (PAT) | Cohen's Kappa: High (e.g., >0.80) | 0.82 |
| PPA: High (>85%) | 89% (80%) | |
| NPA: High (>90%) | 93% (91%) | |
| Sperm (SPRM) | Cohen's Kappa: High (e.g., >0.80) | 0.89 |
| PPA: High (>85%) | 94% (85%) | |
| NPA: High (>90%) | 95% (93%) | |
| Yeast (YEA) | Cohen's Kappa: High (e.g., >0.80) | 0.88 |
| PPA: High (>85%) | 91% (82%) | |
| NPA: High (>90%) | 97% (95%) |
Note: The document generally states "All predefined acceptance criteria were met" for various studies. For quantitative parameters (RBC, WBC), the acceptance criteria are implied by the excellent regression and correlation results. For semi-quantitative and qualitative parameters, the acceptance criteria are implied by the high Cohen's Kappa, PPA, and NPA values, indicating very good agreement with the reference method.
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison Study: 689 samples
- Reference Range Study: 621 "urine healthy" residual samples.
- Total Clinical Evaluation Samples: 1310 samples (689 for method comparison + 621 for reference range, with interferences evaluated using these same samples).
- Data Provenance: Clinical samples (residual amounts from routine) were used. The studies were conducted at three sites: two European sites (Site 1, Site 2) and one site located in the US (Site 3). The samples were from patients with an age range of 1 month to 98 years. This indicates mixed geographic origin (local to the three sites) and a retrospective component (residual amounts from routine).
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The ground truth for the method comparison study was established using manual microscopy with KOVA slides as the comparator method. The document does not specify the number of experts, or their specific qualifications (e.g., number of years of experience, certification). It only refers to "visual counting." For the qualitative and semi-quantitative parameters, the "agreement rates" (PPA, NPA, Cohen's Kappa) are reported relative to this manual KOVA method, performed by human operators.
4. Adjudication Method for the Test Set
The document does not explicitly describe an adjudication method (like 2+1, 3+1). It refers to the manual KOVA counting method as the "reference method." This implies that the KOVA results were considered the ground truth without further multi-reader adjudication for the ground truth itself. However, the "Method Comparison" section does state that "All instrument analyte image decisions may be reviewed and reclassified by a trained operator" as part of the device's intended use, which is a form of human-in-the-loop review, but not necessarily a part of establishing the initial ground truth for the study.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
The document does not describe a Multi-Reader Multi-Case (MRMC) comparative effectiveness study directly comparing human readers with AI assistance versus without AI assistance. The study compares the device's performance (algorithm only) to a manual reference method. The device's indications for use mention that "All instrument analyte image decisions may be reviewed and reclassified by a trained operator," implying human-in-the-loop use, but the presented studies are for standalone device performance against a manual method.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study
Yes, a standalone study was done. The precision, analytical sensitivity, linearity, dilution, and interference studies directly evaluate the performance of the "cobas u 701 microscopy analyzer." The method comparison study also assesses the "cobas u 701 microscopy analyzer" against manual microscopy, effectively evaluating the standalone performance of the automated system. The results presented (Passing Bablok regression, agreement rates) are for the device's output.
7. Type of Ground Truth Used
The ground truth used for the method comparison study was manual microscopy using KOVA slides. This is a well-established laboratory method for urine sediment analysis and can be considered a form of expert consensus or reference method consensus if performed by trained laboratory professionals.
8. Sample Size for the Training Set
The document does not explicitly mention the sample size used for the training set for the device's image processing and evaluation software. The reported sample sizes (1310 total clinical samples) are for the non-clinical performance evaluation and external (clinical) testing (test set).
9. How the Ground Truth for the Training Set Was Established
The document does not provide details on how the ground truth for the training set was established. It describes the "cobas u 701 microscopy analyzer" as evaluating images with "an image processing software which is able to detect and further classify the following urine particles," suggesting a machine learning or rule-based system. However, the methodology for creating the labeled data (ground truth) used to develop or train this software is not described in the provided text.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food & Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
November 6, 2020
Roche Diagnostics Teresa Carrow Regulatory Affairs Principal 9115 Hague Road Indianapolis, Indiana 46256
Re: K200811
Trade/Device Name: cobas u 701 microscopy analyzer Regulation Number: 21 CFR 864.5200 Regulation Name: Automated Cell Counter Regulatory Class: Class II Product Code: LKM Dated: March 26, 2020 Received: March 27, 2020
Dear Teresa Carrow:
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
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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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Lea Carrington Division Director Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K200811
Device Name cobas u 701 microscopy analyzer
Indications for Use (Describe)
The cobas u 701 microscopy analyzer is a fully automated urine microscopy system intended for the in vitro quantitative determination of erythrocytes and leukocytes, the semi-quantitative determination of squamous epithelial cells, bacteria, and hyaline casts and the qualitative determination of non-squamous epithelial cells, crystals, yeasts, mucus and sperm in urine.
This system is intended to be used by trained operators in clinical laboratories. All instrument analyte image decisions may be reviewed and reclassified by a trained operator.
| 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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cobas u 701 microscopy analyzer 510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
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 701 microscopy analyzer.
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| Submitter Name | Roche Diagnostics |
|---|---|
| Address | 9115 Hague RoadP.O. Box 50416Indianapolis, IN 46250-0457 |
| Contact | Teresa CarrowPhone: (317) 521-2963FAX: (317) 521-2324Email: teresa.carrow@roche.comKelli TurnerPhone: (317) 521-4515FAX: (317) 521-2324Email: kelli.turner@roche.com |
| Date Prepared | September 2, 2020 |
| Proprietary Name | cobas u 701 microscopy analyzercobas u cuvette |
| Common Name | Automated urine microscopy systemcuvette for urine microscopy |
| Classification Name | Automated urine microscopy systemcuvette |
| Product Codes,Regulation Numbers | See Table 1 |
| Predicate Devices | IRIS IQ 200 (K022774) |
| Establishment Registration | For the cobas u 701 microscopy analyzer the establishment registration number forRoche Diagnostics GmbH Mannheim, Germany: 9610126Roche Diagnostics GmBH Penzberg, Germany: 9610529Roche Diagnostics Indianapolis, IN United States: 1823260. |
Table 1: Product Code and Regulation Number
The Urine Particle Counter is a Class II device under 21 CFR 864.5200.
| Device/Analyte | Product Code | Classification | Regulation | Panel |
|---|---|---|---|---|
| Urine Particle Counter | LKM | II | §864.5200 | Hematology |
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DEVICE DESCRIPTION 1.
| Component | Description |
|---|---|
| cobas u 701 microscopy analyzer | Instrument with external color touch panel |
| cobas u cuvette (400 cuvettes) | Cuvette cassette with 400 microscopy cuvettes |
| Racks | Standard rack, different types |
| Optional | |
| Waste box carton | Carton for easy disposal of used test strips |
| Connectivity | |
| Mouse | Alternative for touch screen input |
| Keyboard | Alternative for touch screen input |
| Printer | Commonly available laser printers |
| Host/LIS connectivity | ASTM standard |
| Data transfer | USB-stick |
The cobas u 701 microscopy analyzer consists of the following components:
cobas u 701 microscopy analyzer 1.1.
The cobas u 701 microscopy analyzer is a fully automated urine analysis system. It is optimized for the high-volume professional laboratory market. The cobas u 701 microscopy analyzer performs a maximum theoretical throughput of up to 116 samples per hour.
The cobas u 701 microscopy analyzer consists of several major components:
- Rack transport system o
- Liquid handling system o
- Cuvette cassette compartment o
- Centrifuge o
- Built-in reverse microscope with movable objective lens for focusing procedure o
- High resolution camera system o
- Touch Screen o
- Inbuilt Computer with the imaging and evaluation software for analyzing the sediment o pictures
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Key functions of the cobas u 701 microscopy analyzer include:
| Key Functions |
|---|
| Sample loading and transport |
| Sample identification |
| Sample homogenization |
| Sample pipetting into cuvettes |
| Centrifugation of cuvettes |
| Image acquisition with a camera |
| Image assessment |
| Automatic disposal of used cuvettes |
| Result readout |
| Result and image memory |
| Optional manual classification and / or re-classification of particles (manual entries are flagged) |
| Manual or Automatic validation of the result |
| Optional formats for data output including electronic result communication |
| Additional Functions |
| Data export |
| Remote Service |
| Quality Control (optional with RFID tagged controls) |
| Processing of diluted samples |
| Washing |
| Filling Water tank. Emptying liquid and solid waste |
The operating system will be Microsoft Windows 10. The system will use a Postgres/SQL database.
The cobas u 701 microscopy analyzer is a stand-alone system, and it is designed to be interconnected mechanically and electronically with the cobas u 601 Urine Analyzer in order to create a urine work area (cobas 6500). The cobas u 601 System was previously FDA-cleared under K183432. The connectivity to the cobas u 701 microscopy analyzer to form the cobas 6500 is not the subject of this submission.
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cobas u cuvette (400 cuvettes) 1.2.
The cobas u cuvette is used by the cobas u 701 microscopy analyzer to transport, centrifuge and analyze patient and control samples. They are provided separately from the analyzer, in a box holding 400 disposable cuvettes.
Calibrator 1.3.
No calibration of the device is necessary for its intended use. However, there is a microscope check, which is not a calibration of the device. This microscope check ensures proper functioning of the focusing mechanism of the microscope utilizing a reference cuvette.
The reference cuvette is a cuvette with the same dimensions as the sample cuvette, which contains a transparent material with a standardized number of erythrocyte like particles etched in it. For differentiation from the sample cuvettes, the reference cuyette is green and marked with the letter R on the top. This microscope check confirms that the instrument is able to focus accurately on the position of the particles and to count correctly the number of the cells. This microscope check needs to be performed every 4 weeks. A message from the instrument informs the operator when it is due.
INDICATIONS FOR USE 2.
cobas u 701 microscopy analyzer 2.1.
The cobas u 701 microscopy analyzer is a fully automated urine microscopy system intended for the in vitro quantitative determination of erythrocytes and leukocytes, the semi-quantitative determination of squamous epithelial cells, bacteria, and hyaline casts and the qualitative determination of non-squamous epithelial cells, crystals, yeasts, pathological casts, mucus and sperm in urine.
This system is intended to be used by trained operators in clinical laboratories. All instrument analyte image decisions may be reviewed and reclassified by a trained operator.
cobas u cuvette 2.2.
The cobas u cuvette is a cassette, containing cuvettes for the in vitro quantitative determination of erythrocytes and leukocytes, the semi-quantitative determination of squamous epithelial cells,
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bacteria, and hyaline casts and the qualitative determination of non-squamous epithelial cells, crystals, yeasts, pathological casts, mucus, and sperm in urine with the cobas u 701 microscopy analyzer. For professional use only.
Note: For convenience, erythrocytes are referred to as RBC and leukocytes are referred to as WBC throughout this submission.
3. TECHNOLOGICAL CHARACTERISTICS
The following table compares the cobas u 701 microscopy analyzer with its predicate device, IRIS IQ 200 (K022774).
| Feature | Predicate Device | Candidate Device |
|---|---|---|
| IRIS IQ 200 (K022774) | cobas u 701 microscopy analyzer | |
| Intended Use | The iQ200 system is an in-vitrodiagnostic device used to automate thecomplete urinalysis profile, includingurine test strip chemistry panel andmicroscopic sediment analysis.Optionally, the iQ200 Analyzer can beused as a stand-alone unit, or theresults from the iQ200 Analyzer canbe combined with other urinechemistry results received from anLIS. It produces quantitative orqualitative counts of all formedsediment elements present in urine,including cells, casts, crystals andorganisms. A competent humanoperator can set criteria for auto-reporting and flagging specimens forreview.All instrument analyte imagedecisions may be reviewed andoverridden by a trained technologist. | The cobas u 701 microscopy analyzeris a fully automated urine microscopysystem intended for the in vitroquantitative determination oferythrocytes and leukocytes, the semi-quantitative determination ofsquamous epithelial cells, bacteria,and hyaline casts and the qualitativedetermination of non-squamousepithelial cells, crystals, yeasts,pathological casts, mucus and spermin urine. This system is intended to beused by trained operators in clinicallaboratories. All instrument analyteimage decisions may be reviewed andreclassified by a trained operator. |
| Submission | K022774 | N/A |
| Date Cleared | 21 October 2002 | N/A |
| Automation | Automated | Same |
| Feature | Predicate DeviceIRIS IQ 200 (K022774) | Candidate Devicecobas u 701 microscopy analyzer |
| Specimen | Urine in barcode labeled tubes | Same |
| Change ofmachineassignment | All instrument analyte imagedecisions may be reviewed andoverridden by a trained technologist. | An appropriately trained laboratoryoperator may manually re-classify or(sub-) sub-classify particles. |
| Principle ofOperation | The iQ200 System auto-identifies andprocesses barcoded tubespecimens in 10-position racks bymixing, sampling, and analyzingautomatically. The iQ200 systemincorporates an iQ200 AutomatedUrine Microscopy Analyzer, in whicha sample is presented as a laminasandwiched between envelopinglayers of suspending fluid to amicroscope coupled to a CCD (chargecoupling device) video camera.This lamination positions thespecimen exactly within the depth offocus and field of view of theobjective lens of the microscope.Lamination is the planar equivalent ofaxial hydrodynamic focusing, used toposition cells in certain types of bloodcell counters and flow cytometers. Ithas the added advantage of achievingorthoscopic particle orientation,thereby presenting asymmetricparticles with their largest profilefacing the direction of view.A CCD digital camera captures fivehundred frames per sample, as eachmicroscopic field of view isilluminated by the flash of a strobelamp. The resulting pictures aredigitized and delivered to the AnalysisProcessor computer. A previouslystored image of a blank background issubtracted from the individual fieldsof view, enhancing the morphology ofthe captured particle.Individual particle images are isolatedwithin each frame. The Auto- | The analyzer auto-identifies andprocesses barcoded tube specimens in5-position racks by mixing, sampling,and analyzing automatically.cobas u 701 microscopy analyzerincorporates a robotic liquid handlingsystem that pipettes an aliquot of thespecimen into a disposable cuvette.The filled cuvette is forwarded to thebuilt-in centrifuge for centrifugationof the non-soluble particles. After thecentrifugation, all particles are broughtto one monolayer to ensure they are allat the same focal plane. A built incamera takes pictures through a builtin microscope at several positions ofthe sediment. All images are evaluatedby an image processing softwarewhich is able to detect and furtherclassify the following urine particles• Red blood cells• White blood cells• Squamous epithelial cells• Bacteria• Hyaline casts• Non-squamous epithelial cells• Crystals• Yeast• Pathological casts• Mucus• Sperm |
| An appropriately trained laboratoryuser may manually re-classify or sub-classify particles on the basis of theacquired pictures | ||
| Feature | Predicate DeviceIRIS IQ 200 (K022774) | Candidate Devicecobas u 701 microscopy analyzer |
| Particle Recognition (APRTM) software, a highly trained neural network, uses size, shape, contrast and texture features to classify each image into one of 12 categories: RBCs, WBCs, WBC Clumps, Hyaline Casts, Unclassified Casts, Squamous Epithelial Cells, Non-squamous Epithelial Cells, Bacteria, Yeast, Crystals, Mucus and Sperm. Particle concentration is calculated using the number of images and the volume scanned. User-defined release criteria are checked and results are sent to an operator review screen or directly uploaded to the LIS based on these criteria. Specimen results can be edited, archived, retrieved, imported, exported and formatted into custom reports. | Particle concentration is calculated using the average count from the assessed images. | |
| Detected andcountedparticlespresent in aspecimen | Red Blood Cells White Blood Cells White Blood Cell Clumps Non-Squamous Epithelial Cells Squamous Epithelial Cells Hyaline Casts Bacteria Crystals Yeast Artifact Unclassified Casts It is possible to manually sub classify Unclassified Crystals, Unclassified Casts, Yeast and Non-Squamous Epithelial Cells.It is possible to manually identify the following particles | Red blood cells White blood cells Squamous epithelial cells Bacteria Hyaline casts Non-squamous epithelial cells Crystals Yeast Pathological casts Mucus Sperm Not proposedIt is possible to manually sub classify particles (e.g. RBC morphologies, CRY) |
| Sperm | It is possible to manually identify further particles (e.g. trichomonas, red | |
| Feature | Predicate DeviceIRIS IQ 200 (K022774) | Candidate Devicecobas u 701 microscopy analyzer |
| • Mucus | blood cell clumps, oval fat bodies,artifacts.) | |
| • Trichomonas | ||
| • Fat Red Blood Cell Clumps | ||
| • Oval Fat Bodies | ||
| QC | IQ Control material | Recommendation of commerciallyavailable control solutions |
| Calibration | Monthly focus with iQ Focus andcalibration with IQ® CalibratorMaterial (suspension of fixed humanred blood cells in a particulate-freesolution) | No calibration needed due to differentparticle detection technology |
| Maintenance | Daily and periodic maintenance | Same |
| SpecimenVolume | Minimum volume 3 mL of un-spunurine. Aspiration volume approx. 1.3mL. | Minimum volume 2 mL of un-spunurine. Aspiration volume < 0.8 mL |
| MeasurementPrinciple | Flow digital imaging | Digital imaging after automatedcentrifugation |
| Workstation | Computer withmonitor/keyboard/mouse | Integrated PC with external touchscreen, optional keyboard/mouse |
| Weight | Microscopy module 100 lbs = 45.4kgs | Microscopy module 176 lbs. = 80kg |
| Fluid Waste | Waste is pumped from the instrumentto a sink, floor drain or suitablecontainer. Drain must be below or atsame height as bench and should beless than 10 feet (3 meters) from theback of the instrument. | Waste container capacity is 5L. Thiscapacity is sufficient to run 400 tests.A direct waste discharge is possible(max. height = instrument level). |
Technical Characteristics Comparison Table between cobas u 701 Microscopy Table 2: Analyzer and the IRIS IQ 200
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NON-CLINICAL PERFORMANCE EVALUATION 4.
The following performance data are provided in support of the substantial equivalence determination:
- Precision according to CLSI EP5-A3 .
- Detection Limit: LoB, LoD and LoQ according to CLSI EP17-A2 。
- Linearity according to CLSI EP6-A o
- Interferences 。
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- Method Comparison to Reference Method o
All performance specifications were met.
Precision 4.1.
Precision was comprised of experiments for Repeatability and Intermediate precision.
Repeatability and Intermediate Precision 4.1.1. -
4.1.1.1.1. Repeatability
To assess the repeatability (within-run precision) of the cobas u 701 microscopy analyzer, a within-run precision study was performed. For the experiment, control samples as well as human specimens (residual amounts from routine) were used. Depending on the parameter methodology (quantitative, semi-quantitative, qualitative) up to three controls and up to three sample concentrations were measured. All predefined acceptance criteria were met.
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| Run 1 | Run 2 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Site | Parameter | Number of Runs | N Total | Control Level* | Target Range (p/μL) | Mean (p/μL) | SD (p/μL) | CV (%) | Mean (p/μL) | SD (p/μL) | CV (%) |
| Site 1 | RBC | 2 | 42 | 1 | 0-25 | 0.00 | 0.00 | NA | 0.00 | 0.00 | NA |
| Site 1 | RBC | 2 | 42 | 2 | 425-1280 | 803 | 39.4 | 4.91 | 764 | 54.2 | 7.10 |
| Site 1 | RBC | 2 | 42 | 3 | 50-120 | 70.6 | 9.19 | 13.0 | 53.8 | 7.94 | 14.8 |
| Site 1 | WBC | 2 | 42 | 1 | 0-25 | 0.00 | 0.00 | NA | 0.00 | 0.00 | NA |
| Site 1 | WBC | 2 | 42 | 2 | 75-240 | 138 | 15.0 | 10.9 | 133 | 11.6 | 8.71 |
| Site 1 | WBC | 2 | 42 | 3 | 50-70 | 59.1 | 5.37 | 9.09 | 51.5 | 7.57 | 14.7 |
| Site 2 | RBC | 2 | 42 | 1 | 0-25 | 0.04 | 0.19 | 458 | 0.08 | 0.26 | 316 |
| Site 2 | RBC | 2 | 42 | 2 | 425-1280 | 641 | 31.9 | 4.97 | 890 | 48.3 | 5.42 |
| Site 2 | RBC | 2 | 42 | 3 | 50-120 | 76.4 | 8.45 | 11.1 | 112 | 10.7 | 9.52 |
| Site 2 | WBC | 2 | 42 | 1 | 0-25 | 0.00 | 0.00 | NA | 0.00 | 0.00 | NA |
| Site 2 | WBC | 2 | 42 | 2 | 75-240 | 131 | 11.5 | 8.78 | 146 | 10.4 | 7.13 |
| Site 2 | WBC | 2 | 42 | 3 | 50-70 | 62.7 | 6.74 | 10.8 | 67.4 | 7.34 | 10.9 |
ble 3: Repeatability for Quantitative Parameters Using Contr
Birtical Liquish oone instally.
controls depend on dilution factor).
NOTE: CV (%) cannot be calculated when mean = 0; these instances are marked as NA
Table 4: Repeatability for Quantitative Parameters Using Human Samples
| Site | Parameter | No. of Runs | N Total | Concentration | Run 1Mean (p/μL) | Run 1SD (p/μL) | Run 1CV (%) | Run 2Mean (p/μL) | Run 2SD (p/μL) | Run 2CV (%) |
|---|---|---|---|---|---|---|---|---|---|---|
| Site 1 | RBC | 2 | 42 | Neg | 0.75 | 0.98 | 129 | 1.17 | 1.05 | 89.8 |
| Site 1 | RBC | 2 | 42 | Low pos | 17.4 | 4.90 | 28.1 | 80.3 | 16.8 | 20.9 |
{14}------------------------------------------------
| Run 1 | Run 2 | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Site | Parameter | No. of Runs | N Total | Concentration | Mean (p/μL) | SD (p/μL) | CV (%) | Mean (p/μL) | SD (p/μL) | CV (%) |
| e 1 | RBC | 2 | 42 | Pos | 1336 | 155 | 11.6 | 899 | 48.0 | 5.34 |
| e 1 | WBC | 2 | 42 | Neg | 2.26 | 1.26 | 55.8 | 2.58 | 2.38 | 92.3 |
| e 1 | WBC | 2 | 42 | Low pos | 14.1 | 4.06 | 28.8 | 63.9 | 8.86 | 13.9 |
| e 1 | WBC | 2 | 42 | Pos | 813 | 29.2 | 3.59 | 631 | 29.0 | 4.59 |
| e 2 | RBC | 2 | 42 | Neg | 0.92 | 1.02 | 111 | 0.59 | 1.12 | 192 |
| e 2 | RBC | 2 | 42 | Low pos | 125 | 11.3 | 9.03 | 13.0 | 4.48 | 34.4 |
| e 2 | RBC | 2 | 42 | Pos | 989 | 74.4 | 7.52 | 1175 | 50.8 | 4.33 |
| e 2 | WBC | 2 | 42 | Neg | 0.53 | 0.82 | 154 | 0.00 | 0.00 | NA |
| e 2 | WBC | 2 | 42 | Low pos | 22.8 | 5.28 | 23.2 | 56.4 | 7.18 | 12.7 |
| e 2 | WBC | 2 | 42 | Pos | 496 | 56.6 | 11.4 | 620 | 90.2 | 14.5 |
Brorda Liquioned Control levels moreles: Lover I, Lover & (Low polition for and the series
depend on dilution factor).
NOTE: CV (%) cannot be calculated when mean = 0; these
| 1 |
|---|
| Table 5: Repeatability for Semi-Quantitative and Qualitative Parameters1 |
| Site | Parameter | No. of Runs | N Total | Concentration | Run 1Mean (p/μL) | Run 1SD (p/μL) | Run 1CV (%) | Run 2Mean (p/μL) | Run 2SD (p/μL) | Run 2CV (%) |
|---|---|---|---|---|---|---|---|---|---|---|
| Site 1 | BAC | 2 | 42 | Neg | 79.6 | 12.7 | 15.9 | 32.7 | 5.88 | 18.0 |
| Site 1 | BAC | 2 | 42 | Low pos | 107 | 8.83 | 8.23 | 176 | 10.1 | 5.73 |
| Site 1 | BAC | 2 | 42 | Pos | 2380 | 169 | 7.10 | 1175 | 38.3 | 3.26 |
| Site 1 | CRY | 2 | 42 | Neg | 0.21 | 0.58 | 279 | 0.61 | 0.87 | 144 |
| Site 1 | CRY | 2 | 42 | Pos | 22.5 | 7.07 | 31.5 | 81.7 | 19.1 | 23.4 |
| Site 1 | HYA | 2 | 42 | Neg | 0.08 | 0.18 | 211 | 0.10 | 0.24 | 226 |
| Site | Parameter | No. of Runs | N Total | Concentration | Run 1Mean (p/μL) | Run 1SD (p/μL) | Run 1CV (%) | Run 2Mean (p/μL) | Run 2SD (p/μL) | Run 2CV (%) |
| Site 1 | HYA | 2 | 42 | Low pos | 4.00 | 1.16 | 29.1 | 6.81 | 2.09 | 30.6 |
| Site 1 | HYA | 2 | 42 | Pos | 14.4 | 3.40 | 23.7 | 15.4 | 3.62 | 23.5 |
| Site 1 | MUC | 2 | 42 | Neg | 26.5 | 8.63 | 32.5 | 4.44 | 2.55 | 57.5 |
| Site 1 | MUC | 2 | 42 | Pos | 298 | 41.1 | 13.8 | 618 | 88.1 | 14.3 |
| Site 1 | NEC | 2 | 42 | Neg | 0.21 | 0.30 | 143 | 0.00 | 0.00 | NA |
| Site 1 | NEC | 2 | 42 | Pos | 27.7 | 3.89 | 14.1 | 7.08 | 2.23 | 31.5 |
| Site 1 | PAT | 2 | 42 | Neg | 0.08 | 0.30 | 357 | 0.02 | 0.10 | 458 |
| Site 1 | PAT | 2 | 42 | Pos | 2.10 | 0.90 | 43.0 | 3.25 | 1.05 | 32.5 |
| Site 1 | SEC | 2 | 42 | Neg | 0.21 | 0.58 | 279 | 0.00 | 0.00 | NA |
| Site 1 | SEC | 2 | 42 | Low pos | 14.4 | 2.49 | 17.4 | 15.9 | 4.25 | 26.7 |
| Site 1 | SEC | 2 | 42 | Pos | 44.4 | 14.3 | 32.2 | 67.2 | 14.9 | 22.1 |
| Site 1 | SPRM | 2 | 42 | Neg | 0.04 | 0.13 | 316 | 0.00 | 0.00 | NA |
| Site 1 | SPRM | 2 | 42 | Pos | 17.7 | 5.87 | 33.1 | 36.7 | 5.98 | 16.3 |
| Site 1 | YEA | 2 | 42 | Neg | 0.06 | 0.16 | 251 | 0.00 | 0.00 | NA |
| Site 1 | YEA | 2 | 42 | Pos | 16.6 | 4.98 | 30.1 | 14.9 | 3.87 | 26.1 |
| Site 2 | BAC | 2 | 42 | Neg | 26.9 | 4.22 | 15.7 | 21.4 | 2.04 | 9.55 |
| Site 2 | BAC | 2 | 42 | Low pos | 117 | 8.11 | 6.95 | 151 | 8.32 | 5.51 |
| Site 2 | BAC | 2 | 42 | Pos (2+) | 239 | 13.8 | 5.80 | 250 | 10.4 | 4.17 |
| Site 2 | BAC | 2 | 42 | Pos | 1612 | 30.1 | 1.87 | 845 | 55.0 | 6.52 |
| Site 2 | CRY | 2 | 42 | Neg | 0.59 | 0.49 | 83.3 | 0.82 | 0.73 | 88.9 |
| Site 2 | CRY | 2 | 42 | Pos | 62.2 | 7.13 | 11.5 | 26.5 | 4.89 | 18.5 |
| Site 2 | HYA | 2 | 42 | Neg | 0.00 | 0.00 | NA | 0.02 | 0.10 | 458 |
| Site 2 | HYA | 2 | 42 | Low pos | 2.89 | 1.33 | 46.0 | 3.86 | 1.32 | 34.2 |
| Site | Parameter | No. of Runs | N Total | Concentration | Run 1Mean (p/μL) | Run 1SD (p/μL) | Run 1CV (%) | Run 2Mean (p/μL) | Run 2SD (p/μL) | Run 2CV (%) |
| Site 2 | HYA | 2 | 42 | Pos | 20.9 | 3.51 | 16.8 | 17.0 | 4.10 | 24.1 |
| Site 2 | MUC | 2 | 42 | Neg | 0.63 | 1.21 | 192 | 9.32 | 4.72 | 50.6 |
| Site 2 | MUC | 2 | 42 | Pos | 491 | 34.8 | 7.08 | 426 | 52.9 | 12.4 |
| Site 2 | NEC | 2 | 42 | Neg | 0.04 | 0.13 | 316 | 0.02 | 0.10 | 458 |
| Site 2 | NEC | 2 | 42 | Pos | 7.50 | 1.97 | 26.2 | 8.21 | 1.96 | 23.9 |
| Site 2 | PAT | 2 | 42 | Neg | 0.00 | 0.00 | NA | 0.02 | 0.10 | 458 |
| Site 2 | PAT | 2 | 42 | Pos | 10.9 | 2.29 | 21.0 | 7.56 | 1.72 | 22.8 |
| Site 2 | SEC | 2 | 42 | Neg | 0.00 | 0.00 | NA | 0.02 | 0.10 | 458 |
| Site 2 | SEC | 2 | 42 | Low pos | 10.5 | 3.07 | 29.1 | 14.8 | 3.21 | 21.7 |
| Site 2 | SEC | 2 | 42 | Pos | 53.9 | 9.09 | 16.9 | 63.8 | 6.40 | 10.0 |
| Site 2 | SPRM | 2 | 42 | Neg | 0.00 | 0.00 | NA | 0.00 | 0.00 | NA |
| Site 2 | SPRM | 2 | 42 | Pos | 16.7 | 3.08 | 18.4 | 8.65 | 2.00 | 23.1 |
| Site 2 | YEA | 2 | 42 | Neg | 0.00 | 0.00 | NA | 0.00 | 0.00 | NA |
| Site 2 | YEA | 2 | 42 | Pos | 268 | 19.6 | 7.31 | 236 | 33.0 | 14.0 |
{15}------------------------------------------------
{16}------------------------------------------------
NOTE: CV (%) cannot be calculated when mean = 0; these instances are marked as NA.
{17}------------------------------------------------
ermediate Preci 1.1.2
stability of the human urine samples were measured for the intermediate precision study. This assessment was limited assess long-term precision of the cobas u 701 microscopy analyzer an intermediate precision according to CLSI EPS-A3 was performed. parameter included in the control material (RBC, WBC). All predefined acceptance criteria were m
| Site 2 | Repeatability | Between-Run | Between-Day | Intermediate(Within-site) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parameter | Numberof runs | NTotal | ControlLevel | Mean(p/μL) | Target Value | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| RBC | 2 | 84 | 1 | 0.15 | 0 - 25 p/μL | 0.49 | 334 | 0.00 | 0.00 | 0.27 | 187 | 0.56 | 383 |
| RBC | 2 | 84 | 2 | 813 | 425 - 1280 p/μL | 42.8 | 5.26 | 20.3 | 2.50 | 30.0 | 3.69 | 56.1 | 6.90 |
| RBC | 2 | 84 | 3 | 69.5 | 50 - 70 p/μL | 8.32 | 12.0 | 0.41 | 0.59 | 3.35 | 4.82 | 8.98 | 12.9 |
| WBC | 2 | 84 | 1 | 0.00 | 0 - 25 p/μL | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| WBC | 2 | 84 | 2 | 140 | 75 - 240 p/μL | 9.36 | 6.69 | 2.31 | 1.65 | 8.17 | 5.84 | 12.6 | 9.03 |
| WBC | 2 | 84 | 3 | 62.8 | 50 - 70 p/μL | 8.09 | 12.9 | 2.17 | 3.46 | 2.47 | 3.93 | 8.74 | 13.9 |
ntermediate Precision for Controls at
Note:
Rad Liquichex control level , Level 2 , Level 3 (Low Dositive control prepared by tiluting Bio-Rad Level 1 and Lev
Liquichek control Level 1 and Level 2 samples, Target Valu
For Liquichek control Level 1 and Level 2 samples, Target Values are from package insert;
For prepared low positive control samples, Target Values will be affected by the variability of the control material.
{18}------------------------------------------------
| Parameter | Numberof runs | NTotal | ControlLevel | Mean(p/μL) | Target Value | Repeatability | Between-Run | Between-Day | Intermediate(Within-site) | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||||||
| RBC | 2 | 84 | 1 | 0.105 | 0 - 25 p/μL | 0.33 | 317 | 0.14 | 130 | 0.00 | 0.00 | 0.36 | 343 |
| RBC | 2 | 84 | 2 | 751 | 425 - 1280 p/μL | 47.1 | 6.26 | 18.5 | 2.46 | 33.6 | 4.47 | 60.7 | 8.08 |
| RBC | 2 | 84 | 3 | 54.3 | 50 - 70 p/μL | 6.64 | 12.2 | 4.37 | 8.03 | 6.14 | 11.3 | 10.0 | 18.5 |
| WBC | 2 | 84 | 1 | 0.000 | 0 - 25 p/μL | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| WBC | 2 | 84 | 2 | 139 | 75 - 240 p/μL | 14.2 | 10.2 | 5.06 | 3.65 | 8.23 | 5.93 | 17.1 | 12.3 |
| WBC | 2 | 84 | 3 | 58.5 | 50 - 70 p/μL | 8.43 | 14.4 | 0.00 | 0.00 | 6.93 | 11.8 | 10.9 | 18.7 |
| Parameter | Numberof Runs | NTotal | ControlLevel | Mean(p/μL) | Target Value | Repeatability(Within-Run)SD(p/μL) | Repeatability(Within-Run)CV(%)* | Between-RunSD(p/μL) | Between-RunCV(%)* | Between-DaySD(p/μL) | Between-DayCV(%)* | Intermediate(Within-Site)SD(p/μL) | Intermediate(Within-Site)CV(%)* |
| RBC | 2 | 84 | 1 | 0.23 | 0 - 25 p/μL | 0.65 | 283 | 0.00 | 0.00 | 0.00 | 0.00 | 0.65 | 283 |
| RBC | 2 | 84 | 2 | 375 | 160 - 495 p/μL** | 18.7 | 5.00 | 15.3 | 4.09 | 21.5 | 5.75 | 32.4 | 8.65 |
| RBC | 2 | 84 | 3 | 63.4 | 50 - 70 p/μL | 6.99 | 11.0 | 4.01 | 6.32 | 0.00 | 0.00 | 8.05 | 12.7 |
| WBC | 2 | 84 | 1 | 0.00 | 0 - 25 p/μL | 0.00 | NA | 0.00 | NA | 0.00 | NA | 0.00 | NA |
| WBC | 2 | 84 | 2 | 170 | 75 - 240 p/μL | 13.8 | 8.13 | 0.00 | 0.00 | 6.90 | 4.05 | 15.5 | 9.09 |
| WBC | 2 | 84 | 3 | 58.8 | 50 - 70 p/μL | 6.56 | 11.1 | 1.85 | 3.14 | 0.00 | 0.00 | 6.81 | 11.6 |
able 7: Intermediate Precision for Controls at Site
Note:
BioBad Liquicheck control level 1, Level 3, Level 3, Level 3 (Lov positie contol priphing Bio-Rad Level 1and Level
For Liquichek control Level 1 and Level 2 samples, Target V
text
All Values
2 Sample t-Level
Control Level
For prepared low positive control samples, Target Values will be affected by the variability of the control material.
{19}------------------------------------------------
able 8: Intermediate Precision for Controls at Site
*CV(%) cannot be calculated when mean = 0; these instances are marked as NA.
OVV%) canno be calculated when man = 0. level 3 lews (Low cosine contol prepared by liuling Bio-Rad Level 1 and Level 1 and Level 1 and Level 1 and Level 1 and Level 1
This
For Liquichek control Level 1 and Level 2 samples, Target Values are from package insert.
**This lot had a lower claim for the RBC in Level 2 than the two external sites
For prepared low positive control samples, Target Values will be affected by the variability of the control material.
{20}------------------------------------------------
eproducibili 4.1.2.
roducibility measurements for quantitative parameters WBC and RBC were performed intermediate precision datasets three study sites each using one cobas u 701 microscopy analyze
| Parameter | N Total | Concentration Level | Mean (p/μL) | Target Value | Repeatability(Within-Run) | Between-Run | Between-Day | Reproducibility(Within-Site) | Between-Site | Reproducibility(Within-System) | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SD (p/μL) | CV (%)* | SD (p/μL) | CV (%)* | SD (p/μL) | CV (%)* | SD (p/µL) | CV (%)* | SD (p/μL) | CV (%)* | SD (p/μL) | CV (%)* | |||||
| RBC | 252 | 1 | 0.16 | 0 - 25 p/μL | 0.51 | 316 | 0.00 | 0.00 | 0.09 | 56.4 | 0.52 | 321 | 0.03 | 21.1 | 0.52 | 322 |
| RBC | 252 | 2 | 846 | 425 - 1280 p/μL** | 46.2 | 5.46 | 27.9 | 3.30 | 41.5 | 4.90 | 68.1 | 8.05 | 113 | 13.4 | 132 | 15.6 |
| RBC | 252 | 3 | 62.4 | 50 - 70 p/µL | 7.35 | 11.8 | 3.43 | 5.50 | 4.03 | 6.45 | 9.06 | 14.5 | 7.50 | 12.0 | 11.8 | 18.8 |
| WBC | 252 | 1 | 0.00 | 0 - 25 p/μL | 0.00 | NA | 0.00 | NA | 0.00 | NA | 0.00 | NA | 0.00 | NA | 0.00 | NA |
| WBC | 252 | 2 | 150 | 75 - 240 p/μL | 12.6 | 8.45 | 0.00 | 0.00 | 7.79 | 5.21 | 14.9 | 9.92 | 17.6 | 11.8 | 23.0 | 15.4 |
| WBC | 252 | 3 | 60.0 | 50 - 70 p/µL | 7.74 | 12.9 | 0.00 | 0.00 | 4.20 | 6.99 | 8.80 | 14.7 | 2.09 | 3.48 | 9.05 | 15.1 |
lble 9: Reproducibility for Combined Data from Three S
ethod Used: SAS 9.4 proc mixed method=type1 covtest; model result=; random site siteday siteday*run; by parameter concentration_level;
*CV(%) cannot be calculated when mean = 0; these instances are marked as NA.
hod beat. SAS 9.4 proc mixed moder rada result, randm site site day tir day inclusival procenconcentiacio _leve;
(%) canot be alculated when mean = these instrica s he rairea
*Mannheim data fix added: Result for RBC Concentration Level 2 Multiplied by a factor of 2.595
{21}------------------------------------------------
Recover 4.1.3.
Recovery measurements for semi-quantitative parameters BAC, HYA, and SEC were performed in triplicate on the cobas u 701 microscopy analy at two sites each using one cobas u 701 microscopy analyzer. Additionally, one measurement was performed using the manual KOVA countin nethod. All predefined acceptance criteria were me
| 7 |
|---|
| 0 |
| ਹੈ |
| 1 |
| Table 10: Recovery for Semi-quantitative Parameters at Site 2COLLECTION COLLECTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTION CONSULTIO |
| Parameter | Target Value | N | Raw Count (bacteria or p/μL) | Result | KOVAResult | ExactAgreement [%] | 2 of 3 results withinthe specifiedconcentration block [Yes/No] | Agreement within 2adjacentconcentration ranges [%] | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1st | 2nd | 3rd | 1st | 2nd | 3rd | |||||||
| Negative (NaCl) | 3 | 2.64 | 4.84 | 1.76 | neg | neg | neg | neg | 100 | Yes | 100 | |
| BAC | 1+ | 3 | 169 | 157 | 170 | 1+ | 1+ | 1+ | 1+ | 100 | Yes | 100 |
| 2+ | 3 | 496 | 565 | 533 | 2+ | 2+ | 2+ | 2+ | 100 | Yes | 100 | |
| 3+ | 3 | 1066 | 1280 | 1253 | 3+ | 3+ | 3+ | 3+ | 100 | Yes | 100 | |
| Negative (Urine) | 3 | 0.00 | 0.00 | 0.00 | neg | neg | neg | 0.00 | 100 | Yes | 100 | |
| HYA | 5 p/μL | 3 | 6.16 | 4.40 | 8.80 | 5 | 5 | 15 | 5.50 | 66.7 | Yes | 100 |
| 15 p/μL | 3 | 15.4 | 8.80 | 15.4 | 15 | 15 | 15 | 18.7 | 100 | Yes | 100 | |
| Negative (Urine) | 3 | 0.88 | 0.88 | 0.44 | neg | neg | neg | 1.10 | 100 | Yes | 100 | |
| SEC | 15 p/μL | 3 | 20.7 | 11.4 | 13.6 | 15 | 15 | 15 | 17.6 | 100 | Yes | 100 |
| 40 p/μL | 3 | 49.3 | 36.5 | 47.1 | 40 | 40 | 40 | 56.1 | 100 | Yes | 100 | |
| Parameter | Target Value | N | Raw Count(bacteria or p/μL) | Result | KOVAResult | ExactAgreement[%] | 2 of 3 results withinthe specifiedconcentration block[Yes/No] | Agreement within 2adjacentconcentration ranges[%] | ||||
| cobas u 701 | ||||||||||||
| 1st | 2nd | 3rd | 1st | 2nd | 3rd | |||||||
| BAC | Negative (NaCl) | 3 | 0.44 | 11.9 | 5.72 | neg | neg | neg | neg | 100 | Yes | 100 |
| BAC | 1+ | 3 | 134 | 123 | 130 | 1+ | 1+ | 1+ | 1+ | 100 | Yes | 100 |
| BAC | 2+ | 3 | 407 | 413 | 394 | 2+ | 2+ | 2+ | 2+ | 100 | Yes | 100 |
| BAC | 3+ | 3 | 896 | 888 | 891 | 3+ | 3+ | 3+ | 3+ | 100 | Yes | 100 |
| HYA | Negative (Urine) | 3 | 0.00 | 0.00 | 0.00 | neg | neg | neg | 0.00 | 100 | Yes | 100 |
| HYA | 5 p/μL | 3 | 3.96 | 3.52 | 8.36 | 5 | 5 | 15 | 2.75 | 66.7 | Yes | 100 |
| HYA | 15 p/μL | 3 | 12.8 | 11.4 | 12.8 | 15 | 15 | 15 | 13.8 | 100 | Yes | 100 |
| SEC | Negative (Urine) | 3 | 0.00 | 0.00 | 0.00 | neg | neg | neg | 0.00 | 100 | Yes | 100 |
| SEC | 15 p/μL | 3 | 11.0 | 16.3 | 13.6 | 15 | 15 | 15 | 13.2 | 100 | Yes | 100 |
| SEC | 40 p/μL | 3 | 43.1 | 55.0 | 50.6 | 40 | 40 | 40 | 52.8 | 100 | Yes | 100 |
{22}------------------------------------------------
Table 11: Recovery for Semi-quantitative Parameters at Site 1
{23}------------------------------------------------
Analytical Sensitivity 4.2.
4.2.1. Limit of Blank (LoB)
Limit of Blank (LoB) of the cobas u 701 microscopy analyzer was determined using one lot of cobas u cuvette and three cobas u 701 microscopy analyzers.
The Limit of Blank (LoB) is the highest observed measured value for samples free of analyte. The Limit of Blank was determined as the 95th percentile of the measurement of blank samples. All predefined acceptance criteria were met.
Limit of Detection (LoD) 4.2.2.
Limit of Detection (LoD) of the cobas u 701 microscopy analyzer were determined using one lot of cobas u cuvette and three cobas u 701 microscopy analyzers.
Limit of Detection (LoD) determines the detection limit for samples with low analyte concentration. The LoD was determined as the lowest amount of analyte in a sample that can be detected with a 95% probability. All predefined acceptance criteria were met.
Limit of Quantitation (LoQ) 4.2.3.
Limit of Quantitation (LoQ) of the cobas u 701 microscopy analyzer were determined using one lot of cobas u cuvette and three cobas u 701 microscopy analyzers.
Limit of Quantitation (LoO) is defined as the lowest analyte concentration in a sample that can be reproducibly measured. All predefined acceptance criteria were met.
Linearity/Assay Reportable Range 4.3.
- Deviation to Higher Order Polynomial/Percentage for "Significant Level of 4.3.1. Deviation"
Linearity of the cobas u 701 microscopy analyzer was determined for the two quantitative parameters Red Blood Cells (RBC) and White Blood Cells (WBC) using one lot of cobas u cuvette and one cobas u 701 microscopy analyzer. Linear regression was calculated according CLSI EP6-A.
{24}------------------------------------------------
4.4. Dilution
The dilution study assessed the performance of the cobas u 701 microscopy analyzer when diluted samples are evaluated.
Note: Dilution of urine is not advisable however, when sample dilution is performed using saline as the diluent, with immediate evaluation on the cobas u 701 microscopy analyzer, results will be obtained.
Interferences 4.5.
The interference study assessed the potential interferences that may occur on the cobas u 701 microscopy analyzer due to its measurement technology; clinical samples were assessed for the individual interferents.
Native human urine samples containing the following interfering particles were measured on the cobas u 701 microscopy analyzer: high concentrations of mucus strands, artefacts, clumps, cell fragments, dysmorphic cells, shining particles, crowded samples, highly viscous samples and high turbidity (Intralipid) samples. Furthermore, challenging native urine samples including amorphous crystals and trichomonas were evaluated.
Assay Cut-Off Determination 4.6.
For semi-quantitative and qualitative assay cut-off determination, range limits had to be set. Range limits were set using empirical and theoretical information from literature, knowledge from clinical practice and the available data from external performed studies.
EXTERNAL (CLINICAL) TESTING 5.
The clinical evaluation included a total of 1310 samples, 689 for the method comparison study and 621 for the reference range study, which were used to execute 3 studies including method comparison for all parameters and reference value assessment for Red Blood Cells (RBC) and White Blood Cells (WBC), executed at two European sites (Site 1, Site 2) and one site located in the US (Site 3). In addition, those same samples were used for evaluation of interferences.
{25}------------------------------------------------
Method Comparison 5.1.
Method Comparison versus Reference Method 5.1.1.
To assess the accuracy of the cobas u 701 microscopy analyzer, the method comparison study was performed with manual microscopy using KOVA slides as the comparator method utilizing clinical samples.
The tables below (Table 13 – Table 15) summarize the results of the method comparison studies performed between cobas u 701 microscopy analyzer and visual counting using the Kova chamber. All obtained statistical results from the single sites as well as for the compiled data sets were within the defined specifications and confirmed the substantial equivalence of the automated cobas u 701 microscopy analyzer with the manual Kova counting method.
Below is the compiled demographics and information about the age range at the study sites. As there are no known differences related to race and ethnicity, this information was not taken into consideration in the demographic information.
| Site | Sample size | Age Range | Female | Male | Pediatrics |
|---|---|---|---|---|---|
| All sites | 689 | 1 month - 98 years | 355 | 334 | 91 |
| Site 3 | 208 | 1 month - 98 years | 112 | 96 | 59 |
| Site 2 | 235 | 1 month - 92 years | 121 | 114 | 17 |
| Site 1 | 246 | 1.5 years - 89 years | 122 | 124 | 15 |
Table 12: Sample Size and Distribution Measured at the Different Sites
{26}------------------------------------------------
| Parameter | N* | Range of values | Passing Bablok regression | Pearson's | Agreement rates (%)** | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| cobas u 701 | KOVA | Slope (LCL, UCL) | Intercept (LCL, UCL) | r | R2 | p=value (r=0) | Neg | Pos | ||
| RBC | 305 | 5-1746 | 5-1769 | 1.00 (0.99, 1.01) | -0.67 (-1.65, 0.16) | 0.99 | 0.97 | <0.001 | 99% | 92% |
| WBC | 384 | 5-806 | 5-875 | 0.98 (0.97, 0.99) | -0.99 (-1.91, 0.04) | 0.98 | 0.97 | <0.001 | 98% | 98% |
3: Method Comparison – Passing-Bablok Regression Analysis for Quantitative Paramet
Includes all data within the range of cob measuring rods 01
ncludes all data within the defined measuring range on cobas u 701
inegative agreement calculation includes results below measuring range for RBC / WBC
able 14: Method Comparison – Agreement Rates for Semi-quantitative Paramete
| Cohen's Kappa | 0.88 | 0.86 | 0.83 | |
|---|---|---|---|---|
| All sites | PPA (LCL | 193%તે જેવી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્ | (96%99% | (89%94% |
| NPA (LCL | (95%,97% | (95%)97% | (97%98% | |
| N | 680 | 670 | 672 | |
| Parameter | BAC | SEC | HYA |
= negative percentage agreement; PPA = positive percentage agreement; LCL = lower confidence
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| Parameter | N | NPA (LCL) | PPA (LCL) | Cohen's Kappa |
|---|---|---|---|---|
| CRY | 670 | 97% (95%) | 98% (93%) | 0.95 |
| MUC | 670 | 99% (98%) | 94% (91%) | 0.93 |
| NEC | 675 | 90% (88%) | 94% (88%) | 0.84 |
| PAT | 670 | 93% (91%) | 89% (80%) | 0.82 |
| SPRM | 670 | 95% (93%) | 94% (85%) | 0.89 |
| YEA | 670 | 97% (95%) | 91% (82%) | 0.88 |
Table 15: Method Comparison – Agreement Rates for Qualitative Parameter
NPA = negative percentage agreement; PPA = positive percentage agreement; LCL = lower confidence limit
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5.2. Reference range
To establish reference values for Red Blood cells (RBC) and White Blood cells (WBC) on the cobas u 701 microscopy analyzer, "urine healthy" residual samples were measured. Measurements were performed at the three sites, each using one cobas u 701 microscopy analyzer and a total of four cobas u cuvette lots.
| Site | Gender | N | Min | Max | Mean | Median | 97.5th percentile(90% CI) | 99th percentile(90% CI) |
|---|---|---|---|---|---|---|---|---|
| All sitesCombined | Female | 310 | 0.00 | 7.92 | 1.20 | 0.88 | 6.16 (5.28, 7.92) | 7.92 (6.16, 7.92) |
| Male | 311 | 0.00 | 9.68 | 1.13 | 0.00 | 6.16 (5.28, 7.92) | 7.92 (6.16, 9.68) | |
| Total | 621 | 0.00 | 9.68 | 1.16 | 0.00 | 6.16 (5.28, 7.92) | 7.92 (7.04, 7.92) |
Table 16: Reference Range Study Results for RBC
Table 17: Reference Range Study Results for WBC
| Site | Gender | N | Min | Max | Mean | Median | 97.5th percentile (90% CI) | 99th percentile (90% CI) |
|---|---|---|---|---|---|---|---|---|
| All sites Combined | Female | 310 | 0.00 | 17.8 | 1.72 | 0.66 | 10.6 (7.26, 13.9) | 13.2 (11.9, 17.8) |
| Male | 311 | 0.00 | 15.8 | 1.02 | 0.00 | 5.94 (5.28, 12.5) | 9.90 (5.94, 15.8) | |
| Total | 621 | 0.00 | 17.8 | 1.37 | 0.66 | 7.92 (5.94, 11.9) | 12.5 (9.90, 16.5) |
6. CONCLUSIONS
The submitted information in this premarket notification 510(k) supports a substantial equivalence decision for the cobas u 701 microscopy analyzer as compared to the predicate device.
§ 864.5200 Automated cell counter.
(a)
Identification. An automated cell counter is a fully-automated or semi-automated device used to count red blood cells, white blood cells, or blood platelets using a sample of the patient's peripheral blood (blood circulating in one of the body's extremities, such as the arm). These devices may also measure hemoglobin or hematocrit and may also calculate or measure one or more of the red cell indices (the erythrocyte mean corpuscular volume, the mean corpuscular hemoglobin, or the mean corpuscular hemoglobin concentration). These devices may use either an electronic particle counting method or an optical counting method.(b)
Classification. Class II (performance standards).