(266 days)
AUTION EYE AI-4510 Urine Particle Analysis System is a fully automated urine particle analyzer for in vitro diagnostic use. AUTION EYE AI-4510 is intended for the quantitative measurement of red blood cells (WBC) and squamous epithelial cells (SQEC), the semi-quantitative measurement of bacteria (BACT) and crystals (CRYS) and the qualitative measurement of white blood cell clumps (WBCC), non-squamous epithelial cells (NSE), hyaline casts (HYAL), non-hyaline casts (NHC), yeast (YST), mucus (MUCS) and sperm (SPRM) in urine samples.
A trained operator can set criteria for flagging speciment analyte image decisions should be reviewed and reclassified as necessary by a trained technologist.
The AUTION EYE AI-4510 analyzer can be used as a standalone unit or combined with an AUTION MAX AX-4060 urine chemistry analyzer.
The AI-4510 System (AUTION EYE AI-4510) is a fully automated urine particle analyzer for in vitro diagnostic use that uses flow cell digital imaging technology in a clinical laboratory setting. Based on images captured in the flow method, the instrument automatically classifies the images of various formed elements. The AI-4510 System can quantitatively measure RBC, WBC, and SQEC; semi-quantitatively measure BACT, and CRYS; and qualitatively measure WBCC, NSE, HYAL, NHC, YST, MUCS and SPRM in urine samples. In addition, the AI-4510 System allows trained operators to manually review and reclassify all the element images collected by the system.
This document describes the validation of the AUTION EYE AI-4510 Urine Particle Analysis System. The device is intended for the quantitative, semi-quantitative, and qualitative measurement of various elements in urine samples. The validation primarily focuses on demonstrating substantial equivalence to a legally marketed predicate device (iQ200 Urine Analyzer).
Here's a breakdown of the requested information based on the provided text:
1. Acceptance Criteria and Reported Device Performance
The document doesn't explicitly list "acceptance criteria" in a single table for all performance measures. Instead, it states that "all results meeting the predefined acceptance criteria" for precision studies, and that "Quantitative, Semiquantitative and Qualitative parameters met the acceptance criteria" for the method comparison study. The reported performance is presented in various tables throughout the "Summary of Performance Data" section (5.6).
Here's an aggregated table derived from the provided performance data:
| Type of Measurement | Element | Criteria/Metric | Reported Performance |
|---|---|---|---|
| Quantitative Repeatability | RBC | %CV | Low: 16.2%, MDL: 7.7%, Mid: 3.5%, High: 3.6% |
| WBC | %CV | Low: 17.2%, MDL: 12.5%, Mid: 1.8%, High: 1.9% | |
| SQEC | %CV | Low: 14.7%, MDL: 9.4%, Mid: 4.8%, High: 4.3% | |
| Semi-Quantitative & Qualitative Repeatability | BACT | % Agreement with expected rank | Level 1-4: 100.0% |
| CRYS | % Agreement with expected rank | Level 1-5: 100.0% | |
| NSE | % Agreement with expected rank | Negative: 100.0%, Low positive: 80.0%, High Positive: 100.0% | |
| HYAL | % Agreement with expected rank | Negative: 100.0%, Low positive: 100.0%, High Positive: 100.0% | |
| NHC | % Agreement with expected rank | Negative: 100.0%, Low positive: 100.0%, High Positive: 100.0% | |
| WBCC | % Agreement with expected rank | Negative: 100.0%, Low positive: 100.0%, High Positive: 100.0% | |
| YST | % Agreement with expected rank | Negative: 100.0%, Low positive: 70.0%, High Positive: 100.0% | |
| MUCS | % Agreement with expected rank | Negative: 100.0%, Low positive: 100.0%, High Positive: 100.0% | |
| SPRM | % Agreement with expected rank | Negative: 100.0%, Low positive: 100.0%, High Positive: 100.0% | |
| Quantitative Within-Laboratory Precision | RBC | Within Laboratory %CV | Low: 25.1%, MDL: 11.9%, High: 6.2% |
| WBC | Within Laboratory %CV | Low: 26.4%, MDL: 12.7%, High: 6.2% | |
| SQEC | Within Laboratory %CV | Low: 17.0%, MDL: 8.5%, High: 4.4% | |
| Quantitative Reproducibility (All Sites Combined) | RBC | Reproducibility %CV | Low: 25.5%, Mid: 10.9%, High: 12.6% |
| WBC | Reproducibility %CV | Low: 26.5%, Mid: 8.6%, High: 7.7% | |
| SQEC | Reproducibility %CV | Low: 15.1%, High: 11.9% | |
| Linearity | RBC | Linear Range | 5-1,000 RBC/μL |
| WBC | Linear Range | 5-1,000 WBC/μL | |
| SQEC | Linear Range | 5-180 SQEC/μL | |
| Limit of Detection | RBC | LoB, LoD, LoQ | LoB: 0.0, LoD: 2.3, LoQ: 2.3 |
| WBC | LoB, LoD, LoQ | LoB: 0.0, LoD: 1.5, LoQ: 1.5 | |
| SQEC | LoB, LoD, LoQ | LoB: 0.2, LoD: 1.6, LoQ: 1.6 | |
| CRYS | LoB, LoD, LoQ | LoB: 0.0, LoD: 6.4, LoQ: 6.4 | |
| BACT | LoB, LoD, LoQ | LoB: 0.0, LoD: 6.0, LoQ: 6.0 | |
| Carryover | All 12 elements | Presence of carryover | No carryover effect detected. |
| Interference | Various elements & interferents | Concentration limit with no significant interference | See Tables 10, 11, and 12 for specific concentrations. |
| Sample Stability | All 12 elements | Stability duration | Room temperature (15-30°C) for up to 2 hours; Refrigeration (2-8°C) for up to 6 hours. |
| Method Comparison (AI-4510 (Manual) vs. iQ200 (Manual) / Manual Microscopy) | RBC | Weighted Deming R2, Intercept, Slope | R2: 0.918, Intercept: 1.501, Slope: 0.824 |
| WBC | Weighted Deming R2, Intercept, Slope | R2: 0.903, Intercept: 0.629, Slope: 0.968 | |
| SQEC | Weighted Deming R2, Intercept, Slope | R2: 0.928, Intercept: -0.451, Slope: 0.933 | |
| CRYS (vs. Manual Microscopy) | Sensitivity, Specificity | Sensitivity: 76.2%, Specificity: 83.7% | |
| BACT (vs. Manual Microscopy) | PPA, NPA | PPA: 90.5%, NPA: 98.2% | |
| NSE (vs. iQ200) | PPA, NPA | PPA: 88.7%, NPA: 84.3% | |
| NHC (vs. iQ200) | PPA, NPA | PPA: 80.2%, NPA: 83.8% | |
| HYAL (vs. iQ200) | PPA, NPA | PPA: 85.0%, NPA: 89.0% | |
| YST (vs. iQ200) | PPA, NPA | PPA: 97.1%, NPA: 99.6% | |
| WBCC (vs. iQ200) | PPA, NPA | PPA: 86.5%, NPA: 89.3% | |
| MUCS (vs. iQ200) | PPA, NPA | PPA: 81.9%, NPA: 88.0% | |
| SPRM (vs. iQ200) | PPA, NPA | PPA: 86.2%, NPA: 99.6% |
2. Sample size used for the test set and the data provenance
- Precision Studies:
- Repeatability Study: Clinical urine samples were used.
- Quantitative elements: Not explicitly stated, but "clinical urine samples in the evaluation of repeatability for all twelve (12) elements from low to high concentrations."
- Semi-quantitative and Qualitative elements: n=10 replicates per test level (e.g., Level 1, 2, 3 etc.).
- Within-Laboratory Precision Study: ARKRAY control materials prepared using clinical samples.
- Reproducibility Study: Commercially available control materials and ARKRAY control materials prepared using clinical samples were used.
- Repeatability Study: Clinical urine samples were used.
- Linearity Testing: Not specified for sample size beyond "one instrument."
- Limit of Detection: Not specified for sample size.
- Carryover Testing: High-level and low-level samples, aliquoted into 5 tubes each, measured in sequences (e.g., H1 L1 H2 L2 H3 L3 H4 L4 H5 L5, repeated 5 times).
- Interference Testing: Not specified for sample size beyond the substances tested.
- Sample Stability: Positive and negative samples for all 12 elements.
- Method Comparison:
- Population for Reference Range results: n=247
- Quantitative Elements (RBC, WBC, SQEC): n=377 (RBC), n=845 (WBC), n=382 (SQEC) for comparison between AI-4510 (M) and iQ200 (M).
- Semi-quantitative & Qualitative Elements: n=1474 (CRYS, BACT, WBCC, MUCS, SPRM), n=765 (NSE, NHC, HYAL, YST).
- Data Provenance: Clinical samples. The method comparison study was conducted at "three (3) CLIA-Moderate complexity laboratories." The document states samples were "collected fresh within two (2) hours or refrigerated up to six (6) hours post collection," implying a prospective collection directly for these studies. The country of origin is not explicitly stated, but the submission is for FDA clearance in the US, and the company and testing sites (CLIA labs) suggest operations relevant to the US market.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
The ground truth for the method comparison study (especially for semi-quantitative and qualitative elements) appears to be established by comparison to the predicate device iQ200 (Manual) and Manual Microscopy.
- For the method comparison, it refers to "CLIA-trained operators" performing testing and "A trained operator can set criteria for flagging speciment analyte image decisions should be reviewed and reclassified as necessary by a trained technologist." This indicates that trained technologists or CLIA-trained operators (which implies suitable qualifications for laboratory testing) established the "ground truth" or reference values, either by manual microscopy or using the predicate device's manual review function.
- The document does not specify the exact number of individual experts or their specific qualifications (e.g., specific years of experience, board certification as pathologists or medical technologists). It only refers to "CLIA-trained operators" and "trained technologists."
4. Adjudication method for the test set
- The document states: "All instrument analyte image decisions should be reviewed and reclassified as necessary by a trained technologist." This implies a form of human override or adjudication post-AI classification.
- For the "Method Comparison" tables (14, 15, 16), most comparisons are listed as "AI-4510 (Manual) vs. iQ200 (Manual)" or "AI-4510 (Manual) vs. Manual Microscopy." The "(M)" denotes "manually reviewed and reclassified results." This indicates that the results from both the investigational device and the predicate device/manual microscopy were subjected to manual review/adjudication by trained human operators to establish the final classification used for comparison.
- The specific method of adjudication (e.g., 2+1, 3+1 consensus) among multiple readers for establishing the ground truth is not specified. The comparison is against already "manual" classifications from the predicate or direct manual microscopy, suggesting that the human reading itself serves as the reference, likely by one or more trained technologists.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- This document describes performance characteristics of the device itself, often compared to a predicate device or manual microscopy.
- It does not describe an MRMC comparative effectiveness study where the performance of human readers with AI assistance is directly compared to human readers without AI assistance to quantify improvement or effect size. The AI-4510 System is an automated analyzer with a manual review component, not an AI assistance tool for human interpretation of images outside of the system.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- The document mentions "The software processes the recorded images, automatically identifying and classifying the formed elements based on the sorting algorithm." (Section 5.5)
- However, the indications for use explicitly state: "A trained operator can set criteria for flagging specimens. All instrument analyte image decisions should be reviewed and reclassified as necessary by a trained technologist."
- Furthermore, the "Method Comparison" tables are predominantly listed as "AI-4510 (Manual) vs. iQ200 (Manual)" or "AI-4510 (Manual) vs. Manual Microscopy," where "(M)" denotes "manually reviewed and reclassified results."
- This strongly suggests that the reported performance data for clinical claims (method comparison) represents the combined human-in-the-loop performance after technologist review and reclassification, particularly for the semi-quantitative and qualitative elements.
- While the device has an "automatic classification" function (also mentioned in section 5.4 under "Automatic Classification"), the reported clinical performance data does not appear to be purely standalone (algorithm-only) without human intervention.
- Table 11 (Interference Effect on Auto-classified Results) hints at some testing of the auto-classified performance in specific scenarios (interference), but the bulk of the clinical validation on the main intended use appears to involve human review.
7. The type of ground truth used
The ground truth used for the method comparison study was established through:
- Comparison to the iQ200 System (Manual): This means the results obtained from the predicate device after its own manual review and reclassification process.
- Manual Microscopy: This is considered the traditional gold standard for urine particle analysis, established by trained technologists.
Therefore, the ground truth is a combination of expert consensus (implied via "trained technologist" review) and comparison to a legally marketed predicate device (also with human review), with manual microscopy serving as a reference.
8. The sample size for the training set
The document provided does not contain any information about the training set for the AI-4510 System's algorithm. This K submission focuses on device performance studies for validation and comparison to a predicate, not on the developmental aspects of the AI model.
9. How the ground truth for the training set was established
As no information about the training set is provided, how its ground truth was established is also not available in this document.
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May 3, 2024
Arkray Inc. % Daya Ranamukhaarachi VP/Science and Regulatory Affairs ARKRAY, Inc. 5198 West 76th Street Minneapolis, Minnesota 55439
Re: K232416
Trade/Device Name: AUTION EYE AI-4510 Urine Particle Analysis System Regulation Number: 21 CFR 864.5200 Regulation Name: Automated cell counter Regulatory Class: Class II Product Code: LKM Dated: April 5, 2024 Received: April 5, 2024
Dear Daya Ranamukhaarachi:
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 (the 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 available 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.
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Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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,
Min Wu-S
Min Wu Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics
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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) K232416
Device Name
AUTION EYE AI-4510 Urine Particle Analysis System
Indications for Use (Describe)
AUTION EYE AI-4510 Urine Particle Analysis System is a fully automated urine particle analyzer for in vitro diagnostic use. AUTION EYE AI-4510 is intended for the quantitative measurement of red blood cells (WBC) and squamous epithelial cells (SQEC), the semi-quantitative measurement of bacteria (BACT) and crystals (CRYS) and the qualitative measurement of white blood cell clumps (WBCC), non-squamous epithelial cells (NSE), hyaline casts (HYAL), non-hyaline casts (NHC), yeast (YST), mucus (MUCS) and sperm (SPRM) in urine samples.
A trained operator can set criteria for flagging speciment analyte image decisions should be reviewed and reclassified as necessary by a trained technologist.
The AUTION EYE AI-4510 analyzer can be used as a standalone unit or combined with an AUTION MAX AX-4060 urine chemistry analyzer.
| 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 510(k) Summary of the AUTION EYE AI-4510 Urine Particle Analysis System is submitted in compliance with 21 CFR807.92 for the purposes of safety and effectiveness.
| Date Prepared: | April 03, 2024 | |
|---|---|---|
| Establishment: | ARKRAY Factory Inc.1480 Koji, Konan-cho,Koka-shiShiga Japan, 520-3306 | |
| Submitter: | ARKRAY Inc.Yousuien-nai, 59 Gansuin-cho,Kamigyo-kuKyoto Japan, 602-0008 | |
| Official US Agent: | Daya Ranamukhaarachchi, PhDARKRAY Factory USA Inc.Title: VP/Science and Regulatory AffairsPhone (408) 234-0804Email: ranamukd@arkrayusa.com | |
| Primary Contact: | Ryan HansonARKRAY Factory USA Inc.Title: Science Affairs ManagerPhone (952) 646-3121Email: hansonr@arkrayusa.com | |
| Secondary Contact: | Marissa BrooksARKRAY Factory USA Inc.Title: Regulatory Affairs Project ManagerPhone (760) 525-8405Email: brooksm@arkrayusa.com |
Device Name:
Trade Name: AUTION EYE AI-4510 Urine Particle Analysis System
Common Name: Automated cell counter (Urine particle counter)
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Predicate Device:
| Trade Name: | iQ200 Urine Analyzer (K093861) |
|---|---|
| Common Name: | Automated Urinalysis System |
5.1 Regulatory Information:
Regulatory Classification for Automated cell counter (Urine particle counter) and each of the tests are listed in Table 1.
Table 1. Regulatory Classification for the AI-4510 System
| TestDescription | Product Code | Device Class | Regulation | Device Panel |
|---|---|---|---|---|
| Urine ParticleCounter | LKM | Class II | 21 CFR864.5200 | 81- Hematology |
| AutomatedUrinalysisSystem | KQO | Class I | 21 CFR862.2900 | 75- Chemistry |
5.2 Intended Use
AUTION EYE AI-4510 Urine Particle Analysis System is a fully automated urine particle analyzer for in vitro diagnostic use. AUTION EYE AI-4510 is intended for the quantitative measurement of red blood cells (RBC), white blood cells (WBC) and squamous epithelial cells (SQEC), the semi-quantitative measurement of bacteria (BACT) and crystals (CRYS) and the qualitative measurement of white blood cell clumps (WBCC), non-squamous epithelial cells (NSE), hyaline casts (HY AL), non-hyaline casts (NHC), yeast (YST), mucus (MUCS) and sperm (SPRM) in urine samples.
A trained operator can set criteria for flagging specimens. All instrument analyte image decisions should be reviewed and reclassified as necessary by a trained technologist.
The AUTION EYE AI-4510 analyzer can be used as a standalone unit or combined with an AUTION MAX AX-4060 urine chemistry analyzer.
5.3 Device Description
The AI-4510 System (AUTION EYE AI-4510) is a fully automated urine particle analyzer for in vitro diagnostic use that uses flow cell digital imaging technology in a clinical laboratory setting. Based on images captured in the flow method, the instrument automatically classifies the images of various formed elements. The AI-4510 System can
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quantitatively measure RBC, WBC, and SQEC; semi-quantitatively measure BACT, and CRYS; and qualitatively measure WBCC, NSE, HYAL, NHC, YST, MUCS and SPRM in urine samples. In addition, the AI-4510 System allows trained operators to manually review and reclassify all the element images collected by the system.
5.4 Substantial Equivalence
The following Table 2 shows the comparisons between the predicate and candidate devices and identifies the major technological and performance characteristics.
| COMPONENT/CHARACTERISTIC | PROPOSED | PREDICATE |
|---|---|---|
| 510(K) Number | K232416 | K093861 |
| Device | AUTION EYE AI-4510 UrineParticle Analysis System | iQ200 System with LaminaCradle |
| Device Type | Automated Cell Counter | Automated Cell Counter |
| FDA Product Code | LKM, KQO | LKM, KQO |
| FDA Authorization Use | Laboratory Use | Laboratory Use |
| Intended Use andIndication for Use | AUTION EYE AI-4510 UrineParticle Analysis System is afully automated urine particleanalyzer for in vitro diagnosticuse. AUTION EYE AI-4510 isintended for the quantitativemeasurement of red blood cells(RBC), white blood cells(WBC) and squamousepithelial cells (SQEC), thesemi-quantitative measurementof bacteria (BACT) and crystals(CRYS) and the qualitativemeasurement of white bloodcell clumps (WBCC), non-squamous epithelial cells(NSE), hyaline casts (HYAL),non-hyaline casts (NHC), yeast | The iQ®200 System is an in-vitro diagnostic device used toautomate the completeurinalysis profile, includingurine test strip chemistry paneland microscopic sedimentanalysis. |
| (YST), mucus (MUCS) andsperm (SPRM) in urinesamples.A trained operator can setcriteria for flagging specimens.All instrument analyte imagedecisions should be reviewedand reclassified as necessary bya trained technologist.The AUTION EYE AI-4510analyzer can be used as astandalone unit or combinedwith an AUTION MAX AX-4060 urine chemistry analyzer. | Optionally, the iQ200 analyzercan be used as a stand-alone unit,or the results from the iQ200analyzer can be combined withother urine chemistry resultsreceived from an LIS. Itproduces quantitative orqualitative counts of all formedsediment elements present inurine, including cells, casts,crystals, and organisms. Acompetent human operator canset criteria for auto-reporting andflagging specimens for review.All instrument analyte imagedecisions may be reviewed andoverridden by a trainedtechnologist. | |
| Measurement Principle | Same as predicate | Flow digital imaging |
| Parameters | Red blood cells (RBC), Whiteblood cells (WBC), White bloodcell clumps (WBCC), Squamousepithelial cells (SQEC), Non-squamous epithelial cells (NSE),Hyaline casts (HYAL), non-hyaline casts (NHC ), Bacteria(BACT), Crystals (CRYS), Yeast(YST),Mucus (MUCS) andSperm (SPRM) | Red blood cells (RBC), Whiteblood cells (WBC), White bloodcell clumps (WBCC), Squamousepithelial cells (SQEC), Non-squamous epithelial cells (NSE),Hyaline casts (HYAL),Unclassified casts (NHC orUNCC),Bacteria (BACT), Crystals(CRYS), Yeast (YST), Mucous(MUCS),Sperm (SPRM),Dysmorphic RBC andUnclassified Crystals |
| Automatic Classification | Red blood cells (RBC), whiteblood cells (WBC), white bloodcell clumps (WBCC),squamous epithelial cells(SQEC), non-squamous epithelialcells (NSE), hyaline casts(HYAL), non-hyaline casts(NHC), bacteria (BACT), crystal(CRYS), yeast (YST), mucus(MUCS) and sperm (SPRM) | Red Blood Cells (RBC), WhiteBlood Cells (WBC), WhiteBlood Cell Clumps (WBCC),Squamous Epithelial Cells(SQEC), Non |
| (While a dysmorphic red bloodcell is counted as a red blood cell,the flag can be automaticallyassigned for the dysmorphic redblood cell.) | Squamous Epithelial Cells(NSE), Bacteria (BACT),Crystals (UNCX), Hyaline Cast(HYAL), Unclassified Cast(UNCC), Yeast (BYST/HYST),Sperm(SPRM), Mucus (MUCS) | |
| Manual Classification | Red blood cells: 2 itemsDysmorphic red blood cells(DRBC) and red blood cellclumps (RBCC) | Red blood cells: 2 itemsDysmorphic red blood cells(DRBC) and red blood cellclumps (RBCC) |
| Crystal: 10 items Calcium oxalatecrystal (CAOX), calciumphosphate crystal (CAPH),magnesium ammoniumphosphate crystal (TPO4),leucine crystal (LEUC), uric acidcrystal (URIC), calciumcarbonate crystal (CACB),cystine crystal (CYST), tyrosinecrystal (TYRO),amorphous salts (phosphoricacid, uric acid) (AMOR) andunclassified crystal (UNCX) | Crystal: 10 items Calciumoxalate crystal (CAOX),calcium phosphate crystal(CAPH), magnesiumammonium phosphate crystal(TPO4), leucine crystal (LEUC),uric acid crystal (URIC),calcium carbonate crystal(CACB), cystine crystal(CYST), tyrosine crystal(TYRO),amorphous salts (phosphoricacid, uric acid) (AMOR) andunclassified crystal (UNCX) | |
| Casts: 6 itemsGranular casts (GRAN), waxycasts (WAXY), RBC casts(RBCT), WBC casts (WBCT),epithelial casts (EPIC) and fattycasts (FATC) | Casts: 6 itemsGranular casts (GRAN), waxycasts (WAXY), RBC casts(RBCT), WBC casts (WBCT),epithelial casts (EPIC) and fattycasts (FATC) | |
| Yeast: 1 itemBudding yeast (BYST) | Yeast: 1 itemBudding yeast (BYST) | |
| Epithelial cells: 2 items Renaltubular epithelial cells (REEP),transitional epithelial cells(TREP) | Epithelial cells: 2 items Renaltubular epithelial cells (REEP),transitional epithelial cells(TREP) | |
| Fat: 2 items | Fat: 2 items | |
| Fat (FAT) and oval fat body(OVFB) | Fat (FAT) and oval fat body(OVFB) | |
| Other categories: 5 itemsTrichomonas (TRCH), inclusion | Other categories: 5 items | |
| cells (INCC), parasite (PARA),artifact (ART) and unclassified(UNCL) | Trichomonas (TRCH), inclusioncells (INCC), parasite (PARA),artifact (ART) and unclassified(UNCL) | |
| Specimen Type /Measurement Object | Urine | Urine |
| Reagents | AUTION EYE Sheath SolutionConcentrated Washing Solution 3AUTION EYE Calibrator | iQ Lamina Iris Diluent IrisSystem CleanseriQ Focus Solution |
| Quality Control Solution | AUTION EYE Control Solution(It consists of High and Lowlevels.) | iQ Positive control,iQ Negative control |
| Sample ConsumptionVolume | Maximum 1 mL | Approximately 1.3 mL |
| Required Volume | 2 mL or more | Minimum volume 3 mL |
| Measurement Time | Approximately 45 seconds/test(Excluding cases in which largenumbers of formed elements arepresent or in the case of controlmeasurement) | 101 seconds/test |
| Warm up time | Maximum 10 minutes (Durationafter the power is turned ON. Thewarm- up time is extended if areadjustment process is addedduring startup.) | The iQ200 System should beallowed to warm up for 1 or 2hours if it was turned off formore than 6 hours. |
| Memory Capacity | Measurement results (Normal):10,000 tests | Onboard storage of up to 10,000patient results |
| Number of CapturedImages | Three digital cameras capture1,500 frames per sample | A digital camera captures 500frames per sample |
| Capturing Images | Takes images with 3 differentfocal points using 3 digitalcameras | Presents a specimen to amicroscope coupled to a 1.3-megapixel CCD (chargecoupling device) digital camera |
| Power | 100 - 240 V AC, 50/60 Hz(Including fluctuations of±10%) | Microscopy module - 90-240VAC 50-60 Hz200 watts max |
| IntendedEnvironment | Indoor use only | Indoor use only |
| MeasurementEnvironment | Temperature: 59 to 86 °F,Humidity: 20 to 80% (Nocondensation) | Temperature: 15-30°C (59-86°F)Humidity: 20% - 80% non-condensing |
| Measurementsource | Strobe lamp | Strobe lamp |
| Dimensions | 530 (W) × 600 (D) × 650 (H) mm(including the sampler)530 (W) × 200 (D) × 135 (H) mm(sampler only) | Microscopy module - 56 H x 59W x 64.8 D cm (22 H x 23 W x25.5 D in.) |
| Weight | Analyzer (with the sampler):Approx. 57 kg Sampler: Approx.4 kg | Microscopy module -45.4 kg (100 lbs.) |
Table 2. Comparison Between AUTION EYE AI-4510 and iQ200 SYSTEM
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5.5 Test Principle and Technology
The principle of operation of the AI-4510 System is based on image capture and the digital processing of images for particle analysis and recognition from a locked sorting algorithm for clustering and classification.
The instrument uses flow digital imaging technology with a flow cell and Complementary Metal- Oxide- Semiconductor (CMOS) image sensors. As the urine passes through the flow cell, it is illuminated by a strobe lamp. Color images are recorded from three different focal points by the CMOS image sensors. The software processes the recorded images, automatically identifying and classifying the formed elements based on the sorting algorithm. The images and the classification of the formed elements are also displayed on the device screen for the operator. The results of the measurements of formed elements for each sample can be centrally controlled by the computer. Images that could not be classified automatically can be classified manually.
5.6 Summary of Performance Data
Clinical and bench testing were conducted to verify the performance characteristics of this device. This testing showed acceptable device performance that is substantially equivalent to the performance of the predicate device.
Precision
Precision for the AI-4510 System was evaluated to estimate repeatability, within-laboratory precision, and reproducibility for quantitative analytes: Red Blood Cell (RBC), White Blood Cell (WBC), and Squamous Epithelial Cells (SQEC), and repeatability for all semi-quantitative and qualitative elements: Bacteria (BACT), Crystals (CRYS), White blood cell clumps (WBCC), Nonsquamous epithelial cells (NSE), Hyaline casts (HYAL), non-hyaline casts (NHC), Yeast (YST), Mucus (MUCS) and Sperm (SPRM).
Precision studies were conducted in accordance with the general guidelines established in CLSI EP05-A3; (Third Edition)- Evaluation of Precision Devices; Approved Guideline
Precision studies were conducted to evaluate measurement imprecision using both controlled materials and clinical samples, with all results meeting the predefined acceptance criteria.
There were three major studies conducted to demonstrate the precision of the AI-4510 System:
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Repeatability Study- (Quantitative, Semiquantitative, and Qualitative Elements) Results were collected with one (1) instrument, at one (1) site, with one (1) operator and 10 replicates, using clinical urine samples in the evaluation of repeatability for all twelve (12) elements from low to high concentrations.
Within-Laboratory Precision Study- (Quantitative Elements) Results collected over twenty (20) days with two (2) runs per day and two (2) replicates per run using ARKAY control materials prepared using clinical samples.
Reproducibility Study-(Quantitative Elements) Results collected from three (3) sites, with one (1) analyzer per site, and testing conducted over five (5) days with two (2) runs per day and three (3) replicates per run using commercially available control materials and ARKRAY control materials prepared using clinical samples.
Results from the analysis conducted for each study is presented in Tables 3-6 below.
| Element | Test Level | Mean Value (/μL) | Repeatability | |
|---|---|---|---|---|
| SD | %CV | |||
| RBC | Low | 7.5 | 1.2 | 16.2 |
| MDL | 42.1 | 3.2 | 7.7 | |
| Mid | 468.8 | 16.6 | 3.5 | |
| High | 858.7 | 30.6 | 3.6 | |
| WBC | Low | 7.8 | 1.3 | 17.2 |
| MDL | 38.5 | 4.8 | 12.5 | |
| Mid | 425.2 | 7.8 | 1.8 | |
| High | 918.7 | 17.5 | 1.9 | |
| SQEC | Low | 6.1 | 0.9 | 14.7 |
| MDL | 39.6 | 3.7 | 9.4 | |
| Mid | 91.6 | 4.4 | 4.8 | |
| High | 161.5 | 6.9 | 4.3 |
Table 3. Repeatability Results - Quantitative Elements
Table 4. Repeatability Results - Semi-Quantitative and Qualitative Elements
| Element | n | Test Level | Avg. Conc.(/μL) | % Agreement with expectedrank |
|---|---|---|---|---|
| BACT | 10 | Level 1 | 0.0 | 100.0% |
| 10 | Level 2 | 55.7 | 100.0% | |
| 10 | Level 3 | 78.9 | 100.0% | |
| 10 | Level 4 | 166.5 | 100.0% | |
| CRYS | 10 | Level 1 | 0.0 | 100.0% |
| 10 | Level 2 | 41.7 | 100.0% | |
| 10 | Level 3 | 118.1 | 100.0% | |
| 10 | Level 4 | 200.7 | 100.0% | |
| 10 | Level 5 | 330.1 | 100.0% |
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| Element | n | Test Level | Avg. Conc.(/μL) | % Agreement with expectedrank |
|---|---|---|---|---|
| NSE | 10 | Negative | 0.0 | 100.0% |
| NSE | 10 | Low positive | 4.8 | 80.0% |
| NSE | 10 | High Positive | 15.5 | 100.0% |
| HYAL | 10 | Negative | 0.0 | 100.0% |
| HYAL | 10 | Low positive | 1.2 | 100.0% |
| HYAL | 10 | High Positive | 8.2 | 100.0% |
| NHC | 10 | Negative | 0.0 | 100.0% |
| NHC | 10 | Low positive | 1.2 | 100.0% |
| NHC | 10 | High Positive | 12.9 | 100.0% |
| WBCC | 10 | Negative | 0.0 | 100.0% |
| WBCC | 10 | Low positive | 3.3 | 100.0% |
| WBCC | 10 | High Positive | 15.5 | 100.0% |
| YST | 10 | Negative | 0.0 | 100.0% |
| YST | 10 | Low positive | 11.4 | 70.0% |
| YST | 10 | High Positive | 49.3 | 100.0% |
| MUCS | 10 | Negative | 0.1 | 100.0% |
| MUCS | 10 | Low positive | 32.8 | 100.0% |
| MUCS | 10 | High Positive | 106.2 | 100.0% |
| SPRM | 10 | Negative | 0.0 | 100.0% |
| SPRM | 10 | Low positive | 7.4 | 100.0% |
| SPRM | 10 | High Positive | 32.2 | 100.0% |
Table 5. Within-Laboratory Precision Results
| Mean Value | Repeatability | Between Run | Between Day | Within Laboratory | |||||
|---|---|---|---|---|---|---|---|---|---|
| Level | (/μL) | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| RBCLow | 8.1 | 2.0 | 24.7 | 0.3 | 3.7 | 0.2 | 2.3 | 2.0 | 25.1 |
| RBCMDL | 43.1 | 4.2 | 9.8 | 2.9 | 6.7 | 0.0 | 0.0 | 5.1 | 11.9 |
| RBCHigh | 515.7 | 22.8 | 4.4 | 18.4 | 3.6 | 13.2 | 2.6 | 32.2 | 6.2 |
| WBCLow | 7.9 | 1.7 | 21.9 | 1.2 | 14.8 | 0.0 | 0.0 | 2.1 | 26.4 |
| WBCMDL | 42.9 | 3.4 | 7.9 | 4.0 | 9.3 | 1.5 | 3.5 | 5.5 | 12.7 |
| WBCHigh | 470.1 | 13.4 | 2.8 | 23.8 | 5.1 | 10.6 | 2.3 | 29.3 | 6.2 |
| SQECLow | 8.6 | 1.4 | 16.1 | 0.0 | 0.0 | 0.5 | 5.7 | 1.5 | 17.0 |
| SQECMDL | 39.5 | 3.1 | 7.9 | 0.7 | 1.7 | 1.1 | 2.7 | 3.4 | 8.5 |
| SQECHigh | 158.0 | 6.3 | 4.0 | 2.0 | 1.3 | 2.2 | 1.4 | 7.0 | 4.4 |
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| Level | MeanValue(cells/µL) | Repeatability | Between Run | Between Day | Between Site | Reproducibility | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||
| RBC Low | 8.4 | 2.0 | 23.4 | 0.0 | 0.0 | 0.7 | 8.0 | 0.5 | 6.2 | 2.1 | 25.5 |
| RBC Mid | 86.2 | 6.6 | 7.6 | 1.5 | 1.7 | 0.9 | 1.1 | 6.5 | 7.5 | 9.4 | 10.9 |
| RBC High | 675.7 | 53.9 | 8.0 | 0.0 | 0.0 | 13.4 | 2.0 | 64.3 | 9.5 | 85.0 | 12.6 |
| WBC Low | 5.7 | 1.4 | 24.5 | 0.5 | 8.2 | 0.3 | 4.8 | 0.2 | 3.2 | 1.5 | 26.5 |
| WBC Mid | 86.8 | 6.4 | 7.4 | 2.8 | 3.2 | 1.7 | 2.0 | 1.9 | 2.2 | 7.4 | 8.6 |
| WBC High | 645.0 | 20.9 | 3.2 | 20.4 | 3.2 | 13.8 | 2.1 | 37.6 | 5.8 | 49.6 | 7.7 |
| SQEC Low | 14.9 | 2.1 | 14.4 | 0.0 | 0.0 | 0.3 | 2.0 | 0.6 | 4.2 | 2.3 | 15.1 |
| SQEC High | 87.2 | 6.5 | 7.4 | 2.8 | 3.2 | 0.0 | 0.0 | 7.6 | 8.7 | 10.3 | 11.9 |
Table 6. All Sites Combined - Reproducibility Study Results
Linearity
Linearity testing was performed for the AI-4510 System using one instrument to establish the linear interval for quantitative elements: RBC, WBC, and SQEC. The study was conducted following CLSI EP06-2" Edition and met the predefined acceptance criteria, establishing the linearity interval of the AI-4510 System quantitative elements as shown in Table 7 below.
| Table 7. AI-4510 System Linearity Interval | |
|---|---|
| Quantitative Element | Linear Range |
| RBC | 5-1,000 RBC/μL |
| WBC | 5-1,000 WBC/μL |
| SQEC | 5-180 SQEC/μL |
7 AI 4510 System Linearity Interval
Limit of Detection
Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ) were conducted for the AI-4510 System quantitative (RBC, WBC, SQEC) and semiquantitative (CRYS, BACT) elements following CLSI-EP17-A2 Evaluation of Detection Capability For Clinical Laboratory Measurement Procedures; Approved Guideline -Second Edition. Based on the results of the study, as shown below in Table 8, all elements met the predefined acceptance criteria, thereby establishing the LoB, LoD, and LoQ for each element.
| Table 8. Results of Detection Limits | |||
|---|---|---|---|
| Element(cells/µL) | LoB | LoD | LoQ |
| RBC | 0.0 | 2.3 | 2.3 |
| WBC | 0.0 | 1.5 | 1.5 |
| SQEC | 0.2 | 1.6 | 1.6 |
| Table 8. Results of Detection Limits | |||
|---|---|---|---|
| -- | -- | -------------------------------------- | -- |
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| Element(cells/µL) | LoB | LoD | LoQ |
|---|---|---|---|
| CRYS | 0.0 | 6.4 | 6.4 |
| BACT | 0.0 | 6.0 | 6.0 |
Carryover
Carryover testing was performed for the AI-4510 System to confirm that there are no carryover contaminations for all twelve (12) elements. This testing was conducted using pre-prepared concentrations of high-level and low-level samples which were aliquoted into 5 tubes each and measured alternatively as shown in Table 9 for each tested element. Based on the predefined acceptance criteria, no carryover effect was detected.
| Measurement sequence | Sample placement in rack |
|---|---|
| Set 1 | H1 L1 H2 L2 H3 L3 H4 L4 H5 L5 |
| Set 2 | H1 L1 H2 L2 H3 L3 H4 L4 H5 L5 |
| Set 3 | H1 L1 H2 L2 H3 L3 H4 L4 H5 L5 |
| Set 4 | H1 L1 H2 L2 H3 L3 H4 L4 H5 L5 |
| Set 5 | H1 L1 H2 L2 H3 L3 H4 L4 H5 L5 |
H: High level sample, L: Low level sample
Interference
Interference testing was performed on the AI-4510 System to evaluate the influence of interfering substances on the measurement of twelve (12) particle elements using the AI-4510 System. A dose dependency evaluation was performed for those substances which were confirmed to have interference effects on the measurements to determine the highest concentration at which no interference effect is observed.
The results of this interference study are summarized in Tables 10-12 below.
| Element | Interferent | ConcentrationLimit with NoSignificantInterference | Concentration of Interferent and Observed Effect |
|---|---|---|---|
| RBC | Trichomonas | 50 /μL | At 120 /µL falsely increased for negative samples |
| Turbidity | 1+ ** | At 2+ falsely decreased for positive samples | |
| Bacteria | 4000 /μL | At 6000 /µL falsely decreased for positive samples | |
| WBC | Yeast | 60 /μL | At 80 /µL falsely increased for negative samples andlow positive samples |
| Trichomonas | - * | At 10 /µL falsely increased for negative samples | |
| Red Blood Cells | 1500 /μL | At 5000 /µL falsely increased for positive samples |
Table 10. Interference Effect on Manually Reviewed and Reclassified Results
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| Turbidity | 1+ ** | At 2+ falsely decreased for low positive samples | |
|---|---|---|---|
| WBCC | Bacteria | 7500 /μL | At 15000 /μL falsely decreased for low positive samples |
| Trichomonas | 50 /μL | At 120 /μL falsely increased for negative samples | |
| SQEC | Red Blood Cells | 1200 /μL | At 1500 /μL falsely decreased for positive samples |
| Turbidity | 1+ ** | At 2+ falsely decreased for positive samples | |
| Bacteria | 7500 /μL | At 15000 /μL falsely decreased for positive samples | |
| BACT | AmorphousUrates | 120 /μL | At 160 /μL falsely increased for low positive samplesAt 200 /μL falsely increased for negative samples andhigh positive samples |
| Turbidity | 1+ ** | At 2+ falsely increased for low positive samples | |
| Yeast | 60 /μL | At 80 /μL falsely increased for low positive samples | |
| MUCS | Red Blood Cells | 1500 /μL | At 5000 /μL falsely increased for high positive samples |
| Bacteria | 6000 /μL | At 7500 /μL falsely decreased for high positive samples | |
| SPRM | Bacteria | 6000 /μL | At 7500 /μL falsely decreased for high positive samples |
- Concentration limit with no significant interference was not evaluated
** The qualitative rank as measured by an AUTION MAX AX-4060 Urine Chemistry Analyze
| Table 11. Interference Effect on Auto-classified Results | ||||||
|---|---|---|---|---|---|---|
| -- | -- | -- | -- | -- | ---------------------------------------------------------- | -- |
| Interference effect on Auto-classified results | |||
|---|---|---|---|
| Element | Interferent | Concentration limit with no significant interference | Concentration of Interferent and observed effect |
| RBC | Yeast | 40 /uL | At 60/uL falsely increased for negative samplesAt 80/uL falsely increased for low positive samples |
| Crystal | -* | At 330/uL falsely increased for negative samples | |
| Trichomonas | 50 /uL | At 120/uL falsely increased for negative samples | |
| Turbidity | 1+ ** | At 2+ falsely decreased for positive samples | |
| Bacteria | 4000/uL | At 6000/uL falsely decreased for positive samples | |
| WBC | Red blood cells | 400 /uL | At 800/uL falsely increased for negative samplesAt 1200/uL falsely increased for low positive samplesAt 1500/uL falsely increased for high positive samples |
| Yeast | 40 /uL | At 60/uL falsely increased for negative samplesAt 80/uL falsely increased for low positive samples | |
| Trichomonas | -* | At 10/uL falsely increased for negative samples andpositive samples | |
| Turbidity | 1+ ** | At 2+ falsely decreased for low positive samples | |
| Bacteria | 7500 /uL | At 15000 /uL falsely decreased for low positivesamples | |
| WBCC | Red blood cells | 1200 /uL | At 5000 /uL falsely increased for negative samples |
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| Yeast | 60 /uL | At 80 /uL falsely increased for negative samples | ||
|---|---|---|---|---|
| Trichomonas | 20 /uL | At 50 /uL falsely increased for negative samples | ||
| Red blood cells | 1200 /uL | At 1500/uL falsely decreased for positive samples | ||
| SQEC | Turbidity | 1+ ** | At 2+ falsely decreased for positive samples | |
| Bacteria | 7500 /uL | At 15000 /uL falsely decreased for positive samples | ||
| NHC | Yeast | 60 /uL | At 80 /uL falsely increased for negative samples andlow positive samples | |
| BACT | Amorphousurates | 120 /uL | At 200 /uL falsely increased for negative samples andhigh positive samples | |
| Yeast | 60 /uL | At 80 /uL falsely increased for low positive samples | ||
| Turbidity | 1+ ** | At 2+ falsely decreased for low positive samples | ||
| YST | Red blood cells | 1200 /uL | At 5000/uL falsely increased for negative samplesand low positive samples | |
| MUCS | Red blood cells | 1500 /uL | At 5000/uL falsely decreased for high positivesamples | |
| Bacteria | 6000 /uL | At 7500/uL falsely decreased for high positivesamples | ||
| SPRM | Bacteria | 6000 /uL | At 7500/uL falsely decreased for high positivesamples |
- Concentration limit with no significant interference not evaluated.
** The qualitative rank as measured by an AUTION MAX AX-4060 urine chemistry analyzer
| Element | Interfering Substances | Highest Concentration Tested with No Interference |
|---|---|---|
| RBC | Viscosity | 1.24 mPa · s |
| MUCS | 200 /μL | |
| Amorphous Urates | 320 /μL | |
| Calcium Oxalate Crystal | 330 /μL | |
| Yeast | 100 /μL | |
| WBC | Viscosity | 1.24 mPa · s |
| MUCS | 200 /μL | |
| Amorphous Urates | 320 /μL | |
| Calcium Oxalate Crystal | 330 /μL | |
| Turbidity | 2+ | |
| WBCC | Viscosity | 1.24 mPa · s |
| Red Blood Cells | 5000 /μL | |
| MUCS | 200 /μL | |
| Amorphous Urates | 320 /μL | |
| Calcium Oxalate Crystal | 330 /μL | |
| Bacteria | 15000 /μL | |
| Yeast | 100 /μL | |
| SQEC | Viscosity | 1.24 mPa · s |
| Trichomonas | 120 /μL | |
| MUCS | 200 /μL | |
| Amorphous Urates | 320 /μL | |
| Calcium Oxalate Crystal | 330 /μL | |
| Yeast | 100 /μL | |
| Turbidity | 2+ | |
| Viscosity | 1.24 mPa · s | |
| NSE | Trichomonas | 120 /μL |
| Red Blood Cells | 5000 /μL | |
| MUCS | 200 /μL | |
| Amorphous Urates | 320 /μL | |
| Calcium Oxalate Crystal | 330 /μL | |
| Bacteria | 15000 /μL | |
| Yeast | 100 /μL | |
| Turbidity | 2+ | |
| HYAL | Viscosity | 1.24 mPa · s |
| Trichomonas | 120 /μL | |
| Red Blood Cells | 5000 /μL | |
| MUCS | 200 /μL | |
| Amorphous Urates | 320 /μL | |
| Calcium Oxalate Crystal | 330 /μL | |
| Bacteria | 15000 /μL | |
| Yeast | 100 /μL | |
| Turbidity | 2+ | |
| NHC | Viscosity | 1.24 mPa · s |
| Trichomonas | 120 /μL | |
| Red Blood Cells | 5000 /μL | |
| MUCS | 200 /μL | |
| Amorphous Urates | 320 /μL | |
| Calcium Oxalate Crystal | 330 /μL | |
| Bacteria | 15000 /μL | |
| Yeast | 100 /μL | |
| BACT | Viscosity | 1.24 mPa · s |
| Trichomonas | 120 /μL | |
| Red Blood Cells | 5000 /μL | |
| MUCS | 200 /μL | |
| Calcium Oxalate Crystal | 330 /μL | |
| Turbidity | 2+ | |
| CRYS | Viscosity | 1.24 mPa · s |
| Trichomonas | 120 /μL | |
| Red Blood Cells | 5000 /μL | |
| MUCS | 200 /μL | |
| Amorphous Urates | 320 /μL | |
| Bacteria | 15000 /μL | |
| Yeast | 100 /μL | |
| Turbidity | 2+ | |
| YST | Viscosity | 1.24 mPa · s |
| Trichomonas | 120 /μL | |
| Red Blood Cells | 5000 /μL | |
| MUCS | MUCS | 200 /μL |
| Amorphous Urates | 320 /μL | |
| Calcium Oxalate Crystal | 330 /μL | |
| Bacteria | 15000 /μL | |
| Turbidity | 2+ | |
| MUCS | Viscosity | 1.24 mPa・s |
| Trichomonas | ||
| Amorphous Urates | ||
| Calcium Oxalate Crystal | ||
| Yeast | ||
| Turbidity | 2+ | |
| Viscosity | 1.24 mPa・s | |
| Trichomonas | 120 /μL | |
| SPRM | Red Blood Cells | 5000 /μL |
| MUCS | ||
| Amorphous Urates | ||
| Calcium Oxalate Crystal | ||
| Yeast | 100 /μL |
Table 12. Elements for which No Interference was Observed
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Sample Stability
Sample stability was evaluated on the AI-4510 System to confirm the sample stability of twelve (12) elements when measured with the AI-4510 System. Testing was performed on both positive and negative samples for all twelve (12) elements at room temperature (15-30°C) and under refrigeration (2-8°C). In conclusion, all samples tested for each element met the predefined acceptance criteria, therefore establishing the sample stability at room temperature (15-30°C) for up to 2 hours and under refrigeration (2-8°C) for up to 6 hours for all twelve (12) elements measured by the AI-4510 System.
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Method Comparison
A method comparison study was conducted at three (3) CLIA-Moderate complexity laboratories to evaluate the agreement of urine sample test results between the candidate device, the AI-4510 System, and the FDA-cleared predicate device, the iQ200 System (K093861) and manual microscopy. Testing was done by CLIA-trained operators using de-identified urine samples collected fresh within two (2) hours or refrigerated up to six (6) hours post collection. The study was conducted to evaluate the following 12 analytes: Quantitative analysis of red blood cells (RBC), white blood cells (WBC), and squamous epithelial cells (SQEC); Semiquantitative analysis of bacteria (BACT), and crystals (CRYS); Qualitative analysis of hyaline casts (HYAL), non-hyaline casts (NHC), non-squamous epithelial cells (NSE), yeast (YST), white blood cell clumps (WBCC), mucus (MUCS) and sperm (SPRM). Tables 13-16 summarize the reference range analysis as well as the overall clinical performance data for all sites combined. In summary, Quantitative, Semiquantitative and Qualitative parameters met the acceptance criteria.
| Element | 95% Reference Limit | 90% CI |
|---|---|---|
| RBC | 9.02 | 7.34 - 10.70 |
| WBC | 4.81 | 3.80 - 5.50 |
| SQEC | 6.46 | 4.50 - 9.30 |
| NSE | 3.21 | 2.50 - 4.54 |
| NHC | 0.11 | 0.00 - 0.30 |
| HYAL | 0.51 | 0.26 - 0.82 |
| BACT | 119.6 | 66.28 - 180.66 |
| CRYS | 0.03 | 0.00 - 0.00 |
| YST | 0 | 0.00 - 0.00 |
| WBCC | 0.05 | 0.00 - 0.30 |
| MUCS | 26.6 | 20.50 - 35.39 |
| SPRM | 0 | 0.00 - 0.00 |
Table 13. Reference Range results (n=247)
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| Weighted Deming Regression | |||||
|---|---|---|---|---|---|
| Element | Comparison | N | R2 | Intercept | Slope |
| RBC | AI(M) vs. IQ(M) | 377 | 0.918 | 1.501 (0.432, 2.569) | 0.824 (0.763, 0.886) |
| WBC | AI(M) vs. IQ(M) | 845 | 0.903 | 0.629 (-0.300. 1.558) | 0.968 (0.930, 1.006) |
| SQEC | AI(M) vs. IQ(M) | 382 | 0.928 | -0.451 (-1.269, 0.367) | 0.933 (0.883, 0.982) |
Table 14. Method Comparison Results for Quantitative Elements
- (M) denotes manually reviewed and reclassified results.
| Passing-Bablok Regression | |||||
|---|---|---|---|---|---|
| Element | Comparison | N | R2 | Intercept | Slope |
| RBC | AI(M) vs. IQ(M) | 377 | 0.918 | 0.332 (-0.500, 1.490) | 0.824 (0.774, 0.886) |
| WBC | AI(M) vs. IQ(M) | 845 | 0.903 | 1.992 (1.140, 3.067) | 0.891 (0.860, 0.925) |
| SQEC | AI(M) vs. IQ(M) | 382 | 0.928 | 0.641 (-0.066, 1.493) | 0.873 (0.826, 0.923) |
- (M) denotes manually reviewed and reclassified results.
Table 15. Method Comparison results for Semi-quantitative elements
| 511 |
|---|
| ------------- |
| AI-4510 (Manual) vs. Manual Microscopy | |
|---|---|
| N | 1474 |
| Sensitivity | 76.2% (72.9%, 79.3%) |
| Specificity | 83.7% (81.0%, 86.1%) |
CRYS
| AI-4510 (Manual) vs. Manual Microscopy | |
|---|---|
| N | 1474 |
| PPA | 90.5% (85.1%, 94.1%) |
| NPA | 98.2% (97.3%, 98.8%) |
Table 16. Method Comparison results for Qualitative elements NSE
| AI-4510 (Manual) vs. iQ200 (Manual) | |
|---|---|
| N | 765 |
| PPA | 88.7% (77.4%, 94.7%) |
| NPA | 84.3% (81.4%, 86.8%) |
NHC
| AI-4510 (Manual) vs. iQ200 (Manual) | |
|---|---|
| N | 765 |
| PPA | 80.2% (71.6%, 86.7%) |
| NPA | 83.8% (80.8%, 86.4%) |
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HYAL
| AI-4510 (Manual) vs. iQ200 (Manual) | |
|---|---|
| N | 765 |
| PPA | 85.0% (78.4%, 89.9%) |
| NPA | 89.0% (86.3%, 91.2%) |
YST
| AI-4510 (Manual) vs. iQ200 (Manual) | |
|---|---|
| N | 765 |
| PPA | 97.1% (85.1%, 99.5%) |
| NPA | 99.6% (98.8%, 99.9%) |
WBCC
| AI-4510 (Manual) vs. iQ200 (Manual) | |
|---|---|
| N | 1474 |
| PPA | 86.5% (80.5%, 90.8%) |
| NPA | 89.3% (87.5%, 90.8%) |
MUCS
| AI-4510 (Manual) vs. iQ200 (Manual) | |
|---|---|
| N | 1474 |
| PPA | 81.9% (76.3%, 86.5%) |
| NPA | 88.0% (86.1%, 89.7%) |
SPRM
| AI-4510 (Manual) vs. iQ200 (Manual) | |
|---|---|
| N | 1474 |
| PPA | 86.2% (75.1%, 92.8%) |
| NPA | 99.6% (99.2%, 99.8%) |
5.7 Proposed Labeling
Labeling adequately communicates device intended use, safety precautions and directions for use. It satisfies 21 CFR Part 809.10 for in vitro diagnostic devices.
5.8 Conclusion
ARKRAY has demonstrated the AI-4510 System is substantially equivalent to the predicate device, the iQ200 System, based upon design, test results, and indications for use. Any noted differences do not raise new issues of safety and effectiveness.
§ 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).