cobas u 701 microscopy analyzer

K200811 · Roche Diagnostics · LKM · Nov 6, 2020 · Hematology

Device Facts

• Record ID: K200811
• Device Name: cobas u 701 microscopy analyzer
• Applicant: Roche Diagnostics
• Product Code: LKM · Hematology
• Decision Date: Nov 6, 2020
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.5200
• Device Class: Class 2
• Attributes: Pediatric

Intended Use

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. These measurements are useful in the evaluation of renal, urinary and metabolic disorders. 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.

Device Story

The cobas u 701 is a fully automated urine microscopy analyzer for clinical laboratories. It processes barcoded urine samples in racks, using a robotic liquid handling system to pipette aliquots into disposable cuvettes. The system centrifuges samples to bring particles to a single monolayer focal plane. A built-in reverse microscope and high-resolution camera capture images of the sediment. Image processing software detects and classifies particles (RBC, WBC, epithelial cells, bacteria, casts, crystals, yeast, mucus, sperm). Quantitative results are calculated from average counts; semi-quantitative and qualitative results are also reported. Operators review and can reclassify images via a touchscreen. The system automates sediment analysis, reducing manual microscopy requirements, and aids in diagnosing renal, urinary, and metabolic disorders.

Clinical Evidence

Method comparison study against manual KOVA chamber counting using 680 clinical samples (355 female, 334 male, 91 pediatric) across three sites. Quantitative parameters (RBC, WBC) showed high correlation (Pearson's r ≥ 0.98) and Passing-Bablok regression slopes near 1.0. Semi-quantitative and qualitative parameters demonstrated high agreement (NPA/PPA typically >90%). Precision studies (repeatability, intermediate precision) met acceptance criteria. Linearity confirmed for RBC (5-2160 p/μL) and WBC (5-1080 p/μL).

Technological Characteristics

Fully automated, stand-alone urine particle analyzer. Uses robotic liquid handling, disposable cuvettes, and built-in centrifuge for monolayer particle preparation. Features a reverse microscope with movable objective lens and high-resolution camera. Connectivity via touchscreen and inbuilt computer. No calibration required; monthly microscope check using reference cuvette. Software performs automated image processing and classification. Throughput up to 116 samples/hour.

Indications for Use

Indicated for in vitro quantitative determination of erythrocytes and leukocytes, semi-quantitative determination of squamous epithelial cells, bacteria, and hyaline casts, and qualitative determination of non-squamous epithelial cells, crystals, yeasts, pathological casts, mucus, and sperm in human urine. Intended for use by trained clinical laboratory operators for evaluation of renal, urinary, and metabolic disorders.

Regulatory Classification

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.

Predicate Devices

• IRIS Iq 200 (K022774)

Submission Summary (Full Text)

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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 ([e-mail]) or phone [phone] 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) | |
|------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------|
| <div> <span> <span style="font-size:16px">☑</span> Prescription Use (Part 21 CFR 801 Subpart D) </span> </div> | <div> <span> <span style="font-size:16px">☐</span> Over-The-Counter Use (21 CFR 801 Subpart C) </span> </div> |

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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 Road<br>P.O. Box 50416<br>Indianapolis, IN 46250-0457 |
| Contact | Teresa Carrow<br>Phone: [phone]<br>FAX: [phone]<br>Email: [e-mail]<br><br>Kelli Turner<br>Phone: [phone]<br>FAX: [phone]<br>Email: [e-mail] |
| Date Prepared | September 2, 2020 |
| Proprietary Name | cobas u 701 microscopy analyzer<br>cobas u cuvette |
| Common Name | Automated urine microscopy system<br>cuvette for urine microscopy |
| Classification Name | Automated urine microscopy system<br>cuvette |
| Product Codes,<br>Regulation Numbers | See Table 1 |
| Predicate Devices | IRIS IQ 200 (k022774) |
| Establishment Registration | For the cobas u 701 microscopy analyzer the establishment registration number for<br>Roche Diagnostics GmbH Mannheim, Germany: 9610126<br>Roche Diagnostics GmBH Penzberg, Germany: 9610529<br>Roche 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 Device<br>IRIS IQ 200 (k022774) | Candidate Device<br>cobas u 701 microscopy analyzer |
| Specimen | Urine in barcode labeled tubes | Same |
| Change of<br>machine<br>assignment | All instrument analyte image<br>decisions may be reviewed and<br>overridden by a trained technologist. | An appropriately trained laboratory<br>operator may manually re-classify or<br>(sub-) sub-classify particles. |
| Principle of<br>Operation | The iQ200 System auto-identifies and<br>processes barcoded tube<br>specimens in 10-position racks by<br>mixing, sampling, and analyzing<br>automatically. The iQ200 system<br>incorporates an iQ200 Automated<br>Urine Microscopy Analyzer, in which<br>a sample is presented as a lamina<br>sandwiched between enveloping<br>layers of suspending fluid to a<br>microscope coupled to a CCD (charge<br>coupling device) video camera.<br>This lamination positions the<br>specimen exactly within the depth of<br>focus and field of view of the<br>objective lens of the microscope.<br>Lamination is the planar equivalent of<br>axial hydrodynamic focusing, used to<br>position cells in certain types of blood<br>cell counters and flow cytometers. It<br>has the added advantage of achieving<br>orthoscopic particle orientation,<br>thereby presenting asymmetric<br>particles with their largest profile<br>facing the direction of view.<br>A CCD digital camera captures five<br>hundred frames per sample, as each<br>microscopic field of view is<br>illuminated by the flash of a strobe<br>lamp. The resulting pictures are<br>digitized and delivered to the Analysis<br>Processor computer. A previously<br>stored image of a blank background is<br>subtracted from the individual fields<br>of view, enhancing the morphology of<br>the captured particle.<br>Individual particle images are isolated<br>within each frame. The Auto- | The analyzer auto-identifies and<br>processes barcoded tube specimens in<br>5-position racks by mixing, sampling,<br>and analyzing automatically.<br>cobas u 701 microscopy analyzer<br>incorporates a robotic liquid handling<br>system that pipettes an aliquot of the<br>specimen into a disposable cuvette.<br>The filled cuvette is forwarded to the<br>built-in centrifuge for centrifugation<br>of the non-soluble particles. After the<br>centrifugation, all particles are brought<br>to one monolayer to ensure they are all<br>at the same focal plane. A built in<br>camera takes pictures through a built<br>in microscope at several positions of<br>the sediment. All images are evaluated<br>by an image processing software<br>which is able to detect and further<br>classify the following urine particles<br>• Red blood cells<br>• White blood cells<br>• Squamous epithelial cells<br>• Bacteria<br>• Hyaline casts<br>• Non-squamous epithelial cells<br>• Crystals<br>• Yeast<br>• Pathological casts<br>• Mucus<br>• Sperm |
| | | An appropriately trained laboratory<br>user may manually re-classify or sub-<br>classify particles on the basis of the<br>acquired pictures |
| Feature | Predicate Device<br>IRIS IQ 200 (k022774) | Candidate Device<br>cobas 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 and<br>counted<br>particles<br>present in a<br>specimen | 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.<br>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 proposed<br>It 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 Device<br>IRIS IQ 200 (k022774) | Candidate Device<br>cobas u 701 microscopy analyzer |
| | • Mucus | blood cell clumps, oval fat bodies,<br>artifacts.) |
| | • Trichomonas | |
| | • Fat Red Blood Cell Clumps | |
| | • Oval Fat Bodies | |
| QC | IQ Control material | Recommendation of commercially<br>available control solutions |
| Calibration | Monthly focus with iQ Focus and<br>calibration with IQ® Calibrator<br>Material (suspension of fixed human<br>red blood cells in a particulate-free<br>solution) | No calibration needed due to different<br>particle detection technology |
| Maintenance | Daily and periodic maintenance | Same |
| Specimen<br>Volume | Minimum volume 3 mL of un-spun<br>urine. Aspiration volume approx. 1.3<br>mL.…