(90 days)
The Sysmex® UD-10 Fully Automated Urine Particle Digital Imaging Device for locating, digitally storing and displaying microscopic images captured from urine specimens. The Sysmex® UD-10 locates and presents particles and cellular elements based on size ranges. The images are displayed for review and classification by a qualified clinical laboratory technologist on the Urinalysis Data Manager (UDM). This device is intended for in vitro diagnostic use in conjunction with a urine particle counter for screening patient populations found in clinical laboratories.
The Sysmex® UD-10 is a medical device that captures images of cells and particles found in urine with a camera and displays the images on a display screen. The displayed data consists of images of individual particles that are extracted from the original captured whole field images. The device sorts urine particle images based on their size into eight groups (Class 1-8). These images are transferred to the UDM (Urinalysis Data Manager), where the operator enters the classification of the particle images based on their visual examination. The classification of the particles by the operator is a designation of what type of particles are observed (e.g., WBCs, RBCs, casts, bacteria).
The Sysmex UD-10 is a device for locating, digitally storing, and displaying microscopic images captured from urine specimens. It presents particles and cellular elements based on size ranges for review and classification by a qualified clinical laboratory technologist.
Here's an analysis of the acceptance criteria and the studies performed:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria values for agreement percentages in the precision, repeatability, and method comparison studies (except for the minimum requirement for overall agreement in reproducibility and repeatability). However, it does provide conclusions based on the results meeting statistical thresholds. The carryover study had an acceptance criterion within ±1.00%.
| Study Type | Metric | Acceptance Criteria | Reported Device Performance |
|---|---|---|---|
| Reproducibility | Overall Agreement | Lower 95% Confidence Limit > 80.9% (minimum requirement) | 97.9% (95% CI: 95.2%, 99.1%) |
| Repeatability | Overall Agreement | Lower 95% Confidence Limit > 85.2% (minimum requirement) | 100.0% (95% CI: 97.8%, 100.0%) |
| Carryover | Carryover Effect | Within ±1.00% | RBC: 9.82x10^-23% to 4.16x10^-14% (PASS) BACT: 0.00% to -2.57x10^-6% (PASS) WBC: 1.05x10^-12% to 100.00% (FAIL at one site, but deemed clinically insignificant) |
| Method Comparison | Overall Agreement (UD-10 vs. Manual Microscopy) | Exceed 85.2% (proposed requirement) | 92.0% (95% CI: 89.8%, 93.7%) |
2. Sample Size and Data Provenance
Reproducibility Study:
- Sample size: 240 evaluations (from 120 samples of abnormal and normal QC material, processed twice a day for a minimum of 5 days).
- Data provenance: Prospective, U.S. clinical sites (4 sites). Commercially available MAS® UA control material was used.
Repeatability Study:
- Sample size: 170 evaluations (from an unspecified number of normal residual urine samples, each assayed in 5 replicates).
- Data provenance: Prospective, U.S. clinical sites (4 sites). Normal residual urine samples, collected without preservatives.
Carryover Study:
- Sample size: Not explicitly stated as a total number of samples, but involved High and Low concentration samples for BACT (4 sites), WBC (3 sites), and RBC (3 sites). Each sample was split into 3 aliquots (3 high, 3 low) and run consecutively. Results are presented for 3 replicates of high and 3 replicates of low samples per parameter per site.
- Data provenance: Prospective, U.S. clinical sites (4 sites for BACT, 3 for WBC and RBC). Residual urine samples, collected without preservatives.
Method Comparison Study:
- Sample size: 746 abnormal and normal urine samples.
- Data provenance: Prospective, U.S. clinical sites (4 sites). Residual urine samples from daily routine laboratory workload, collected without preservatives.
3. Number of Experts and Qualifications for Ground Truth
Reproducibility Study:
- Number of experts: One technologist per site (total of 4 technologists across 4 sites).
- Qualifications: "Technologist." No specific experience level is mentioned.
Repeatability Study:
- Number of experts: Two technologists per sample per site, who independently reviewed and identified particle images.
- Qualifications: "Technologist." No specific experience level is mentioned.
Carryover Study:
- Number of experts: One technologist per site.
- Qualifications: "Technologist." No specific experience level is mentioned.
Method Comparison Study:
- Number of experts: Two technologists per sample per site. One classified elements on the UD-10, and a second performed visual read using manual light microscopy.
- Qualifications: "One technologist" and "a second technologist." No specific experience level is mentioned.
4. Adjudication Method
Reproducibility, Repeatability, and Carryover Studies:
- No explicit adjudication method is described. For repeatability, two technologists independently reviewed images, and "Each technologist's results were treated and recorded as an independent observation."
Method Comparison Study:
- No explicit adjudication method is described. One technologist used the UD-10, and another used manual microscopy. Their results were compared.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
There is no mention of a formal MRMC comparative effectiveness study in the sense of evaluating how much human readers improve with AI vs. without AI assistance. The study compares the UD-10 device's performance (which incorporates digital imaging and sorting for human review) against manual microscopy. The UD-10 is a digital imaging device, not strictly an 'AI' device in the typical sense of providing automated diagnosis or enhanced AI assistance to human readers for diagnostic interpretation (beyond presenting sorted images). The study is essentially a method comparison between the UD-10-assisted workflow and traditional manual microscopy.
6. Standalone Performance (Algorithm Only)
The Sysmex UD-10 is described as a device that "locates and presents particles and cellular elements based on size ranges. The images are displayed for review and classification by a qualified clinical laboratory technologist." This indicates that the device requires human-in-the-loop for classification and is not a standalone diagnostic algorithm. Its performance is implicitly tied to how well technologists can use the displayed images. The "Overall Agreement" metrics in the studies reflect the performance of the system (device + technologist).
7. Type of Ground Truth Used
Reproducibility Study:
- Ground truth: Expected results from commercially available MAS® UA control material (Level 1 and Level 2).
Repeatability Study:
- Ground truth: Reference results provided by screening samples with the Sysmex UF-1000i urine analyzer (K070910).
Carryover Study:
- Ground truth: Determined by Sysmex UF-1000i results for high and low concentration samples.
Method Comparison Study:
- Ground truth: For the initial comparison, manual microscopy was considered the comparative method. For the referee comparison, the Sysmex UF-1000i (K070910) was used as the referee method to evaluate agreement between UD-10 and manual microscopy.
8. Sample Size for the Training Set
The document is a 510(k) summary for a medical device that captures and displays images for human review, not an AI/ML algorithm that requires a "training set" in the conventional sense of machine learning model development. Therefore, there is no mention of a training set sample size. The device uses size ranges to sort images, indicating a rule-based or conventional image processing approach rather than a complex AI model that learns from diverse training data.
9. How the Ground Truth for the Training Set Was Established
As noted above, this device does not appear to involve a machine learning training set in the way a typical AI algorithm would. Thus, this question is not applicable based on the provided information.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and 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.
October 30, 2018
Sysmex America, Inc. Jessica Rivera-Montejo Regulatory Affairs Project Manager 577 Aptakisic Road Lincolnshire, Illinois 60069
Re: K182062
Trade/Device Name: Sysmex UD-10 Fully Automated Urine Particle Digital Imaging Device Regulation Number: 21 CFR 864.5260 Regulation Name: Automated cell-locating device Regulatory Class: Class II Product Code: JOY Dated: July 31, 2018 Received: August 1, 2018
Dear Jessica Rivera-Montejo:
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 mav, 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 avare 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 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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Leonthena R. Carrington -S
Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known)
Device Name
Sysmex® UD-10 Fully Automated Urine Particle Digital Imaging Device
Indications for Use (Describe)
The Sysmex® UD-10 Fully Automated Urine Particle Digital Imaging Device for locating, digitally storing and displaying microscopic images captured from urine specimens. The Sysmex® UD-10 locates and presents particles and cellular elements based on size ranges. The images are displayed for review and classification by a qualified clinical laboratory technologist on the Urinalysis Data Manager (UDM). This device is intended for in vitro diagnostic use in conjunction with a urine particle counter for screening patient populations found in clinical laboratories.
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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510(k) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92. The assigned 510(k) number is K182062.
| 807.92 (a)(1): Name: | Jessica Rivera-Montejo |
|---|---|
| Address: | 577 Aptakisic Rd.Lincolnshire, IL 60069 |
| Phone: | (224)543-9650 |
|---|---|
| Email: | riveramontej@sysmex.com |
| Contact: | Jessica Rivera-Montejo |
807.92 (a)(2): Device name- trade name and common name, and classification
Trade name:
Sysmex UD-10 Fully Automated Urine Particle Digital Imaging Device
Common Name: Automated cell-locating device (urine sediments)
Classification: 21 CFR 864.5260
807.92 (a)(3): Identification of the legally marketed predicate devices
MICRO21 with Urine Sediment Analysis (Triangle Biomedical Sciences, Palm Beach Gardens, FL), cleared under K982301.
807.92 (a)(4): Device Description
The Sysmex® UD-10 is a medical device that captures images of cells and particles found in urine with a camera and displays the images on a display screen. The displayed data consists of images of individual particles that are extracted from the original captured whole field images. The device sorts urine particle images based on their size into eight groups (Class 1-8). These images are transferred to the UDM (Urinalysis Data Manager), where the operator enters the classification of the particle images based on their visual examination. The classification of the particles by the operator is a designation of what type of particles are observed (e.g., WBCs, RBCs, casts, bacteria).
The size ranges of cells and particles that fall under each size group (Class 1-8) are provided below, along with the number of display images for each group.
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| Size Group | Size Range (µm) | Number of displayimages |
|---|---|---|
| Class 1 | 2-6 | 100 |
| Class 2 | 6-10 | 100 |
| Class 3 | 10-16 | 100 |
| Class 4 | 16-36 | 50 |
| Class 5 | 36-71 | 50 |
| Class 6 | 71-101 | 20 |
| Class 7 | 101-151 | 20 |
| Class 8 | 151 or more | 20 |
Size Range and Number of Display Images
An overview of the basic operation of the Sysmex® UD-10 device is provided in below.
Image /page/4/Figure/3 description: The image shows the title of a document or presentation. The title is "Overview of Sysmex® UD-10 Device Basic Operation". The text is in bold font and is centered on the image. The Sysmex logo includes the registered trademark symbol.
Image /page/4/Figure/4 description: This image shows a flowchart of a system process. The process starts with "Start the System (UDM and Analyzer)" and ends with "Check Detailed Information on Imaging Results (Browser on UDM)". There are 8 steps in the process, each represented by a blue rectangle with text inside.
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807.92 (a)(5): Intended Use
The Sysmex® UD-10 Fully Automated Urine Particle Digital Imaging Device for locating. digitally storing and displaying microscopic images captured from urine specimens. The Sysmex® UD-10 locates and presents particles and cellular elements based on size ranges. The images are displayed for review and classification by a qualified clinical laboratory technologist on the Urinalysis Data Manager (UDM). This device is intended for in vitro diagnostic use in conjunction with a urine particle counter for screening patient populations found in clinical laboratories.
807.92 (a)(6): Technological Similarities and Differences to the Predicate
The Sysmex UD-10 is substantially equivalent to the Micro21® with Urine Sediment Analysis, K982301.
| Device | Predicate | |
|---|---|---|
| Device | Sysmex® UD-10 | MICR021® with Urine SedimentAnalysis |
| Regulation | 864.5260Class II | Same |
| Product Code | JOY | Same |
| DeviceClassificationName | Automated Cell Locating Device | Same |
| Intended Use | The Sysmex® UD-10 Fully Automated UrineParticle Digital Imaging Device for locating,digitally storing and displaying microscopicimages captured from urine specimens. TheSysmex® UD-10 locates and presents particlesand cellular elements based on size ranges. Theimages are displayed for review andclassification by a qualified clinical laboratorytechnologist on the Urinalysis Data Manager(UDM). This device is intended for in vitrodiagnostic use in conjunction with a urineparticle counter for screening patientpopulations found in clinical laboratories. | Intelligent Medical Imaging, Inc.'sMICR021® with Urine SedimentAnalysis is a laboratory instrument forlocating, digitally storing and displayingmicroscopic fields of view from urinesediments in a urine slide for examinationby a qualified individual for use inreporting a urine microscopic result. |
| Specimen Type | Urine | Same |
| SamplePreparation | None | Slides prepared from resuspension offresh urine sediment. |
| Staining | No staining is performed. | Sternheimer-Malbin stain is added to thesediment prior to placement upon theslide. |
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807.92 (b)(1): Brief Description of Nonclinical Data
Precision- Reproducibility
The objective was to determine if technologists can use the UD-10 device to reproducibly identify the presence of elements in an abnormal quality control (OC) sample (L2), and the absence of elements in normal QC (L1) sample, over time. The study was conducted at four (4) US clinical sites using commercially available MAS® UA control material (Level 1 and Level 2). Three aliquots of each level of control was poured into sample tubes, barcoded with a unique identifier and processed in a random order on the UD-10. The samples were processed twice per day for a minimum of five days (the days were not consecutive). One technologist reviewed and identified particle images (RBCs and WBCs) displayed in each class (one to eight) and recorded the results of each sample.
The results of the precision (reproducibility) study from all sites combined are presented in the table below.
| Cell/ParticleGroup | Site | Time(Days) | PP * | PA * | AP * | AA * | PPA (%)(95% CI) * | NPA (%)(95% CI) * | Overall (%)(95% CI) * |
|---|---|---|---|---|---|---|---|---|---|
| All | All | All | 120 | 5 | 0 | 115 | 100.0%(96.9%, 100.0%) | 95.8%(90.6%, 98.2%) | 97.9%(95.2%, 99.1%) |
| UD-10 Precision (Reproducibility) - Overall Agreement of Cells (WBC, RBC) & Sites | |||
|---|---|---|---|
-
PP: Present in both UD-10 and quality control samples (expected results).
-
PA: Present in UD-10 samples and Absent in quality control samples (unexpected results).
-
AP: Absent in UD-10 samples and Present in quality control samples (unexpected results).
-
AA: Absent in both UD-10 and quality control samples (expected results).
-
Positive Agreement (PPA): % and 95% (2-sided) confidence interval on %.
-
Negative Agreement (NPA): % and 95% (2-sided) confidence interval on %.
-
Overall Agreement (PP + AA): % and 95% (2-sided) confidence interval on %.
Results Conclusion
The reproducibility study, completed for four clinical sites, resulted in a total of 240 evaluations of images displayed on the UD-10 using MAS UA abnormal control material and normal control (containing WBCs and RBCs).
Overall, technologists reported the presence of elements in only five cases when testing the normal control material, which was not element free. The remaining 235 evaluations, inclusive of the 120 cases of negatives (normal), were concordant with the QC material, resulting in 97.9% overall agreement with a 95.2% lower confidence limit. In that this limit exceeds the 80.9% minimum requirement, the reproducibility primary study objective was statistically achieved as planned at 97.5% confidence (1-sided).
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Precision (Repeatability)
The study objective was to determine if technologists can use the UD-10 device to repeatedly identify the presence of elements in both abnormal and normal urine samples. The study was conducted at four (4) US clinical sites using normal residual urine samples, collected without preservatives. Each site aimed to obtain one abnormal and one normal sample from each cell/particle group as outlined in the below. An individual sample may be representative of one or more cell/particle groups (e.g., RBCs and WBCs). Five replicates of each sample were assayed on the UD-10. Reference results were provided by screening the samples with the Sysmex UF-1000i urine analyzer (K070910).
Two technologists independently reviewed and identified the particle images displayed in each class (one to eight) for each sample run. Each technologist's results were treated and recorded as an independent observation.
| GroupNumber | Cell/ParticleGroup | Urine Sample Contents |
|---|---|---|
| 1 | Microorganisms | Bacteria, Parasites, Yeast, Viral Inclusions |
| 2 | Red Blood Cells | |
| 3 | Blood Cells | White Blood Cells |
| 4 | Crystals | Calcium Oxalate, Cholesterol Plates, Cystine, Triple Phosphate,Uric Acid, Amorphous |
| 5 | Epithelial Cells | Squamous, Renal Tubular, Transitional |
| 6 | Casts | Bacterial, Broad, Cellular, Fatty, Granular, Hyaline, Red BloodCell, White Blood Cell, Waxy |
| 7 | Miscellaneous | Contaminants, Mucus Threads, Sperm |
Urine Sample Cell/Particle Groups - Per CLSI GP16-A3
The summarized results from the repeatability testing are shown below.
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| Cell/ParticleGroup | Site | Technologist | PP * | PA * | AP * | AA * | PPA (%)(95% CI) * | NPA (%)(95% CI) * | Overall (%)(95% CI) * |
|---|---|---|---|---|---|---|---|---|---|
| All | All | All | 170 | 0 | 0 | 0 | 100.0%(97.8%, 100.0%) | - | 100.0%(97.8%, 100.0%) |
UD-10 Precision (Repeatability) - Overall Agreement of Cells (All Cells and Particle Groups) & Sites
-
PP: Present in both UD-10 and UF-1000i devices (expected results).
-
PA: Present in UD-10 device and Absent in UF-1000i device (unexpected results).
-
AP: Absent in UD-10 device and Present in UF-1000i device (unexpected results)..
-
AA: Absent in both UD-10 and UF-1000i devices (expected results).
-
Positive Agreement (PPA): % and 95% (2-sided) confidence interval on %.
-
Negative Agreement (NPA): % and 95% (2-sided) confidence interval on %.
-
Overall Agreement (PP + AA): % and 95% (2-sided) confidence interval on %.
Results Conclusion
The repeatability study, completed for four clinical sites, resulted in a total of 170 evaluations of abnormal and normal urine samples representing the cell/particle groups: microorganisms, blood cells, epithelial cells, casts, crystals, and miscellaneous.
Overall, technologists correctly reported the presence of elements representing one or more of these cell/particle groups for all sample replicates. This study achieved 100.0% overall agreement. with a 97.8% lower confidence limit. In that this limit exceeds the 85.2% minimum requirement, the repeatability primary study objective was statistically achieved as planned at 97.5% confidence (1-sided).
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Carryover
The objective of this study was to determine if visual diagnostic carryover is present in low concentration samples (normal samples) when preceded by high concentration samples (abnormal samples) in consecutive order. The study was conducted at four (4) US sites for BACT and three (3) sites for WBC and RBC using residual urine samples, collected without preservatives, with high concentrations of WBCs, RBCs and bacteria (High Sample) and low concentrations of WBCs, RBCs and bacteria (Low Sample).
Sample selection was determined based on the Sysmex UF-1000i results. Urine samples with WBC. RBC and bacteria counts near the upper measurement range were used as the High Sample and urine samples with WBCs, RBCs and bacteria counts near the lower measurement range were used as the Low Sample for this study.
Each sample was mixed, split into three separate sample aliquot tubes (three high sample aliquots and three low sample aliquots), and then barcoded with a unique identifier. The three high concentration samples were assayed on the UD-10 in consecutive order, immediately followed by the three low concentration samples. A technologist reviewed images displayed in each class (one to eight) from each low sample and recorded the results of their findings as present/absent to indicate the presence or absence of WBCs, RBCs and bacteria of each low sample. The data are presented below.
| Parameter | Site | UF-1000iHighSampleCellCount | UF-1000iLowSampleCellCount | HighSampleReplicate1 | HighSampleReplicate2 | HighSampleReplicate3 | LowSampleReplicate1 | LowSampleReplicate2 | LowSampleReplicate3 |
|---|---|---|---|---|---|---|---|---|---|
| 01 | 9983.9 | 7.3 | PRESENT | PRESENT | PRESENT | ABSENT | ABSENT | ABSENT | |
| 04 | 17879.6 | 37 | PRESENT | PRESENT | PRESENT | ABSENT | ABSENT | ABSENT | |
| Bact | 05 | 10145.5 | 74.7 | PRESENT | PRESENT | PRESENT | ABSENT | ABSENT | ABSENT |
| 06 | 9517.1 | 3.5 | PRESENT | PRESENT | PRESENT | PRESENT | PRESENT | PRESENT | |
| 01 | 10314.7 | 1.4 | PRESENT | PRESENT | PRESENT | ABSENT | ABSENT | ABSENT | |
| RBC | 04 | 9967.4 | 17.8 | PRESENT | PRESENT | PRESENT | ABSENT | PRESENT | ABSENT |
| 05 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| 06 | 9574.6 | 2.4 | PRESENT | PRESENT | PRESENT | ABSENT | ABSENT | ABSENT | |
| 01 | 5326.1 | 2.2 | PRESENT | PRESENT | PRESENT | ABSENT | ABSENT | ABSENT | |
| WBC | 04 | 4735.7 | 0.2 | PRESENT | PRESENT | PRESENT | ABSENT | ABSENT | ABSENT |
| 05 | N/A | N/A | N/A | N/A | N/A | N/A | N/A | N/A | |
| 06 | 4969.1 | 0.1 | PRESENT | PRESENT | PRESENT | PRESENT | ABSENT | ABSENT |
UD-10 Carryover – Technologist's Visual Review of Images
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Discussion:
Based on the results of technologists' visual observations of images displayed on the UD-10, Site 06 (bacteria and WBCs), and Site 04 (RBCs) indicated the presence of cell/particles in Low Samples. However, the samples were not "zero" as per the reference testing, and therefore further analysis was undertaken.
Using a logistic regression model, the predicted probabilities of a technologist indicating the presence or absence of elements in low sample replicates, given its concentration value as recorded in the above table (UF-1000i, Low Sample Cell Count), were calculated for each parameter, site and replicate. Probabilities are expected to be close to 1 for high concentration samples, and close to 0 for low concentration samples. These probabilities were then used to compute the carryover effect (%) = 100(L1-L3)(H3-H3), for Low Sample replicates 1 and 3 and High Sample replicate 3. The acceptance criterion for carryover effect is within ±1.00%. The results of this analysis are provided in the following table.
| Parameter | Site | Abnormal Samples | Normal Samples | CarryoverEffect (%) | Conclusion | ||||
|---|---|---|---|---|---|---|---|---|---|
| Replicate1 | Replicate2 | Replicate3 | Replicate1 | Replicate2 | Replicate3 | ||||
| RBC | 01 | > 0.9999 | > 0.9999 | > 0.9999 | 2.75E-10 | 2.75E-10 | 2.75E-10 | 9.82E-23 | PASS |
| RBC | 04 | > 0.9999 | > 0.9999 | > 0.9999 | 0.3333 | 0.3333 | 0.3333 | 4.16E-14 | PASS |
| RBC | 06 | > 0.9999 | > 0.9999 | > 0.9999 | 1.34E-09 | 1.34E-09 | 1.34E-09 | 4.55E-22 | PASS |
| WBC | 01 | > 0.9999 | > 0.9999 | > 0.9999 | 1.05E-14 | 1.89E-34 | 3.39E-54 | 1.05E-12 | PASS |
| WBC | 04 | > 0.9999 | > 0.9999 | > 0.9999 | 5.61E-11 | 1.01E-30 | 1.81E-50 | 5.61E-09 | PASS |
| WBC | 06 | > 0.9999 | > 0.9999 | > 0.9999 | > 0.9999 | 1.43E-10 | 2.57E-30 | 100.00 | FAIL |
| BACT | 01 | > 0.9999 | > 0.9999 | > 0.9999 | 1.10E-11 | 1.10E-11 | 1.10E-11 | -1.12E-17 | PASS |
| BACT | 04 | > 0.9999 | > 0.9999 | > 0.9999 | 2.53E-20 | 2.53E-20 | 2.53E-20 | -2.57E-26 | PASS |
| BACT | 05 | > 0.9999 | > 0.9999 | > 0.9999 | 8.68E-12 | 8.68E-12 | 8.68E-12 | -8.85E-18 | PASS |
| BACT | 06 | > 0.9999 | > 0.9999 | > 0.9999 | > 0.9999 | > 0.9999 | > 0.9999 | 0.00 | PASS |
UD-10 Carryover: Logistic Regression Analysis-Technologist Observation of Bact, RBC and WBC
Discussion Conclusion
As demonstrated in the above table, the carryover effect for RBC had a site range of 9.82x102-3% to 4.16x10-14%. The carryover effect for BACT had a site range of 0.00% to -2.57x10-6%. The carryover effect for WBC had a site range of 1.05x10-12% to 100.00%.
These above results demonstrated that there was no carryover for RBC and BACT for any site but minimal carryover for WBC at Site 06 where the technologist indicated the presence of one (1) WBC seen in the Low Sample #1. The presence of one (1) WBC was determined to be clinically insignificant as it would not shift the patient from one diagnostic group to another.
As standard laboratory practice, the identification of cell/particle images displayed on the UD-10 by a technologist should be used as a part of an overall diagnosis including clinical symptoms and other examination results.
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Method Comparison
The objective of the study was to determine if independent technologists, using the UD-10 device and manual microscopy (reference method), can comparably identify the presence of elements in abnormal and normal urine samples. Also, due to the subjective nature of sediment analysis, the UF-1000i was included as a referee method. The identification of the presence of elements using the UD-10 and manual microscopy was evaluated per element (cell/particle group) across sites and by site. This relationship was quantified in terms of positive, and overall % agreement.
The study was conducted at four (4) US clinical sites using residual urine samples, collected without preservatives, from the daily routine laboratory workload. Samples were transferred to two sample tubes without preservatives and de-identified to ensure the identity of the subject was not known. Sample selection for the evaluation included a mix of normal and abnormal samples which were determined based on the Sysmex UF-1000i Urine Particle Counter results, i.e., normal samples (results without flags and within the established reference range) and abnormal samples (results with flags and outside the established reference range). UF-1000i reportable parameters include RBC, WBC, epithelial cells, casts and bacteria, and flagging parameters include pathological cast, crystals, sperm, yeast-like cell and mucus.
One technologist classified cell and formed elements displayed on the UD-10 imaging device, while a second technologist performed classification and identification of cells and formed elements by visual read using the manual light microscopy method All testing was done in a blinded fashion. The time interval between sample analyses on both methods was less than or equal to 1 hour.
Overall Comparison of UD-10 Results to Manual Microscopy Results
The results of the agreement analysis between UD-10 and manual microscopy for all cell/particle groups and sites combined are provided in the following table in accordance with CLSI Document EP12-A2. The comparison is provided as overall agreement, positive percent agreement (PPA) and negative percent agreement (NPA) along with the 95% confidence interval for overall cell/particle groups and sites.
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| Cell/ParticleGroup | Site | PP * | PA * | AP * | AA * | PPA (%)(95% CI) * | NPA (%)(95% CI) * | Overall (%)(95% CI) * |
|---|---|---|---|---|---|---|---|---|
| All | All | 652 | 43 | 17 | 34 | 97.5%(96.0%, 98.4%) | 44.2%(33.6%, 55.3%) | 92.0%(89.8%, 93.7%) |
| Cell/ParticleGroup | Site | PP * | PA * | AP * | AA * | PPA (%)(95% CI) * | NPA (%)(95% CI) * | Overall (%)(95% CI) * |
| Microorganism | All | 337 | 43 | 144 | 222 | 70.1%(65.8%, 74.0%) | 83.8%(78.9%, 87.7%) | 74.9%(71.7%, 77.9%) |
| 01 | 70 | 16 | 41 | 103 | 63.1%(53.8%, 71.5%) | 86.6%(79.3%, 91.6%) | 75.2%(69.3%, 80.4%) | |
| 04 | 43 | 18 | 20 | 97 | 68.3%(56.0%, 78.4%) | 84.3%(76.6%, 89.9%) | 78.7%(72.1%, 84.0%) | |
| 05 | 56 | 6 | 83 | 22 | 40.3%(32.5%, 48.6%) | 78.6%(60.5%, 89.8%) | 46.7%(39.3%, 54.3%) | |
| 06 | 168 | 3 | 0 | 0 | 100.0%(97.8%, 100.0%) | 0.0%(0.0%, 56.1%) | 98.2%(95.0%, 99.4%) | |
| RBCs | All | 274 | 111 | 81 | 280 | 77.2%(72.5%, 81.2%) | 71.6%(66.9%, 75.9%) | 74.3%(71.0%, 77.3%) |
| 01 | 76 | 39 | 25 | 90 | 75.2%(66.0%, 82.6%) | 69.8%(61.4%, 77.0%) | 72.2%(66.1%, 77.6%) | |
| 04 | 16 | 36 | 18 | 108 | 47.1%(31.5%, 63.3%) | 75.0%(67.3%, 81.4%) | 69.7%(62.6%, 75.9%) | |
| 05 | 64 | 28 | 18 | 57 | 78.0%(67.9%, 85.6%) | 67.1%(56.5%, 76.1%) | 72.5%(65.2%, 78.7%) | |
| 06 | 118 | 8 | 20 | 25 | 85.5%(78.7%, 90.4%) | 75.8%(59.0%, 87.2%) | 83.6%(77.4%, 88.4%) | |
| WBCs | All | 422 | 103 | 71 | 150 | 85.6%(82.2%, 88.4%) | 59.3%(53.1%, 65.2%) | 76.7%(73.5%, 79.6%) |
| 01 | 139 | 23 | 24 | 44 | 85.3%(79.0%, 89.9%) | 65.7%(53.7%, 75.9%) | 79.6%(73.9%, 84.3%) | |
| 04 | 61 | 27 | 22 | 68 | 73.5%(63.1%, 81.8%) | 71.6%(61.8%, 79.7%) | 72.5%(65.5%, 78.5%) | |
| 05 | 90 | 41 | 8 | 28 | 91.8%(84.7%, 95.8%) | 40.6%(29.8%, 52.4%) | 70.7%(63.4%, 77.0%) | |
| 06 | 132 | 12 | 17 | 10 | 88.6%(82.5%, 92.8%) | 45.5%(26.9%, 65.3%) | 83.0%(76.7%, 87.9%) | |
| Crystals | All | 138 | 36 | 67 | 505 | 67.3%(60.6%, 73.4%) | 93.3%(90.9%, 95.2%) | 86.2%(83.5%, 88.5%) |
| 01 | 50 | 16 | 15 | 149 | 76.9%(65.4%, 85.5%) | 90.3%(84.8%, 93.9%) | 86.5%(81.5%, 90.3%) | |
| 04 | 31 | 10 | 13 | 124 | 70.5%(55.8%, 81.8%) | 92.5%(86.8%, 95.9%) | 87.1%(81.4%, 91.2%) | |
| 05 | 28 | 1 | 20 | 118 | 58.3%(44.3%, 71.2%) | 99.2%(95.4%, 99.9%) | 87.4%(81.5%, 91.6%) | |
| 06 | 29 | 9 | 19 | 114 | 60.4%(46.3%, 73.0%) | 92.7%(86.7%, 96.1%) | 83.6%(77.4%, 88.4%) | |
| Cell/ParticleGroup | Site | PP * | PA * | AP * | AA * | PPA (%)(95% CI) * | NPA (%)(95% CI) * | Overall (%)(95% CI) * |
| EC | All | 396 | 107 | 78 | 165 | 83.5%(79.9%, 86.6%) | 60.7%(54.7%, 66.3%) | 75.2%(72.0%, 78.2%) |
| 01 | 129 | 43 | 13 | 45 | 90.8%(85.0%, 94.6%) | 51.1%(40.9%, 61.3%) | 75.7%(69.7%, 80.7%) | |
| 04 | 58 | 29 | 12 | 79 | 82.9%(72.4%, 89.9%) | 73.1%(64.1%, 80.6%) | 77.0%(70.3%, 82.5%) | |
| 05 | 100 | 15 | 21 | 31 | 82.6%(74.9%, 88.4%) | 67.4%(53.0%, 79.1%) | 78.4%(71.6%, 84.0%) | |
| 06 | 109 | 20 | 32 | 10 | 77.3%(69.7%, 83.4%) | 33.3%(19.2%, 51.2%) | 69.6%(62.3%, 76.0%) | |
| Casts | All | 58 | 49 | 49 | 590 | 54.2%(44.8%, 63.3%) | 92.3%(90.0%, 94.2%) | 86.9%(84.2%, 89.1%) |
| 01 | 20 | 22 | 17 | 171 | 54.1%(38.4%, 69.0%) | 88.6%(83.3%, 92.4%) | 83.0%(77.7%, 87.3%) | |
| 04 | 4 | 2 | 0 | 172 | 100.0%(51.0%, 100.0%) | 98.9%(95.9%, 99.7%) | 98.9%(96.0%, 99.7%) | |
| 05 | 14 | 11 | 18 | 124 | 43.8%(28.2%, 60.7%) | 91.9%(86.0%, 95.4%) | 82.6%(76.2%, 87.6%) | |
| 06 | 20 | 14 | 14 | 123 | 58.8%(42.2%, 73.6%) | 89.8%(83.6%, 93.8%) | 83.6%(77.4%, 88.4%) | |
| Miscellaneous | All | 141 | 37 | 126 | 442 | 52.8%(46.8%, 58.7%) | 92.3%(89.5%, 94.3%) | 78.2%(75.0%, 81.0%) |
| 01 | 7 | 13 | 29 | 181 | 19.4%(9.8%, 35.0%) | 93.3%(88.9%, 96.0%) | 81.7%(76.2%, 86.2%) | |
| 04 | 14 | 9 | 12 | 143 | 53.8%(35.5%, 71.2%) | 94.1%(89.1%, 96.9%) | 88.2%(82.6%, 92.2%) | |
| 05 | 0 | 0 | 54 | 113 | 0.0%(0.0%, 6.6%) | 100.0%(96.7%, 100.0%) | 67.7%(60.2%, 74.3%) | |
| 06 | 120 | 15 | 31 | 5 | 79.5%(72.3%, 85.1%) | 25.0%(11.2%, 46.9%) | 73.1%(66.0%, 79.2%) |
Results of UD-10 versus Manual Microscopy- all elements and sites
-
PP: Present in both UD-10 and manual microscopy (expected results).
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PA: Present in UD-10 device and Absent in manual microscopy (unexpected results).
-
AP: Absent in UD-10 device and Present in manual microscopy (unexpected results).
-
AA: Absent in both UD-10 and manual microscopy (expected results)
-
Positive Agreement (PPA): % and 95% (2-sided) confidence interval on %.
-
Negative Agreement (NPA): % and 95% (2-sided) confidence interval on %.
-
Overall Agreement (PP + AA): % and 95% (2-sided) confidence interval on %.
Results (all) Conclusion
The method comparison study, completed for four clinical sites, utilized both UD-10 and manual microscopy to evaluate a total of 746 abnormal and normal samples representing the cell/particle groups: RBC. WBC, epithelial cells, casts, crystals, microorganisms and miscellaneous elements.
The overall level of agreement between UD-10 and manual microscopy was 92.0% with 95% (2sided) confidence interval (89.8%, 93.7%) exceeding the 85.2% proposed requirement. The results demonstrate the UD-10 can be used to identify urine elements in place of manual microscopy.
Per Element Comparison of UD-10 Results to Manual Microscopy Results
The identification of the presence of elements using the UD-10 and manual microscopy was evaluated per element (cell/particle group) across sites and by site. This relationship was quantified in terms of positive, negative, and overall % agreement. The results of the agreement analysis between UD-10 and manual microscopy for microorganisms, RBCs, WBCs, crystals, epithelial cells (ECs), casts and miscellaneous elements for all sites combined and individual sites are provided in the following table.
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Per Element Comparison of - UD-10 versus Manual Microscopy
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-
PP: Present in both UD-10 and manual microscopy (expected results).
-
PA: Present in UD-10 device and Absent in manual microscopy (unexpected results).
-
AP: Absent in UD-10 device and Present in manual microscopy (unexpected results).
-
AA: Absent in both UD-10 and manual microscopy (expected results).
-
Positive Agreement (PPA): % and 95% (2-sided) confidence interval on %.
-
Negative Agreement (NPA): % and 95% (2-sided) confidence interval on %.
-
Overall Agreement (PP + AA): % and 95% (2-sided) confidence interval on %.
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Results (per element) Conclusions
The level of agreement between UD-10 and Manual Microscopy for all sites combined for microorganisms, RBCs, WBCs, crystals, epithelial cells, casts and miscellaneous elements were 74.9%, 74.3%, 76.7%, 86.2%, 75.2%, 86.9% and 78.2% respectively, indicating good agreement between subjective methods.
Comparison of UD-10 versus Manual Microscopy as a Function of UF-1000i
Method Comparison – UD-10 and Manual Microscopy against the UF-1000i
The following compares the results of UD-10 and manual microscopy against UF-1000i results (UF-1000i are the referee results). These results include overall agreement and the associated 95% (2-sided) confidence interval for all samples combined, abnormal samples only, and normal samples only. The data demonstrated good agreement across the three methods.
Results of UD-10 versus Manual Microscopy, with UF-1000i as the Referee
| Sample Types | UD-10 vs UF-1000i | Microscopy vs UF-1000i |
|---|---|---|
| All Samples Combined | 93.2%(91.1%, 94.8%) | 89.7%(87.3%, 91.7%) |
| Abnormal Samples Only | 99.5%(98.2%, 99.9%) | 97.6%(95.6%, 98.7%). |
| Normal Samples Only | 85.3%(81.1%, 88.7%) | 79.9%(75.3%, 83.9%) |
Comparison of UD-10 and Manual Microscopy against the UF-1000i (Across Sifes)
Comparison of UD-10 and Manual Microscopy against the UF-1000i (By Site)
| Samples | Method | Site 01 | Site 04 | Site 05 | Site 06 |
|---|---|---|---|---|---|
| AllSamplesCombined | UD-10 | 96.1%(92.7%, 97.9%) | 80.3%(73.9%, 85.5%) | 95.8%(91.6%, 98.0%) | 100.0%(97.8%, 100.0%) |
| Microscopy | 91.3%(87.0%, 94.3%) | 72.5%(65.5%, 78.5%) | 95.2%(90.8%, 97.6%) | 100.0%(97.8%, 100.0%) | |
| AbnormalSamplesOnly | UD-10 | 100.0%(97.5%, 100.0%) | 97.5%(91.2%, 99.3%) | 100.0%(96.0%, 100.0%) | 100.0%(95.9%, 100.0%) |
| Microscopy | 98.0%(94.3%, 99.3%) | 91.1%(82.8%, 95.6%) | 100.0%(96.0%, 100.0%) | 100.0%(95.9%, 100.0%) | |
| NormalSamplesOnly | UD-10 | 88.8%(80.0%, 94.0%) | 66.7%(56.9%, 75.2%) | 90.7%(82.0%, 95.4%) | 100.0%(95.4%, 100.0%) |
| Microscopy | 78.8%(68.6%, 86.3%) | 57.6%(47.7%, 66.8%) | 89.3%(80.3%, 94.5%) | 100.0%(95.4%, 100.0%) |
807.92 (b)(2): Brief Description of Clinical Data
Not applicable
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807.92 (b)(3): Conclusions from Nonclinical and Clinical Data
The conclusions drawn from the data demonstrate that the device is safe and effective for its intended use.
§ 864.5260 Automated cell-locating device.
(a)
Identification. An automated cell-locating device is a device used to locate blood cells on a peripheral blood smear, allowing the operator to identify and classify each cell according to type. (Peripheral blood is blood circulating in one of the body's extremities, such as the arm.)(b)
Classification. Class II (performance standards).