K Number
K201301
Manufacturer
Date Cleared
2020-10-02

(140 days)

Product Code
Regulation Number
864.5260
Reference & Predicate Devices
Predicate For
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The X100 with Field Peripheral Blood Smear Application is intended to locate and display images of white cells, red cells, and platelets acquired from fixed and stained peripheral blood smears and assists a qualified technologist in conducting a WBC differential, RBC morphology evaluation, and platelet estimate using those images. For in vitro diagnostic use only. For professional use only.

Device Description

X100 with Full Field Peripheral Blood Smear Application (Scopio's Full Field PBS) automatically locates and presents high resolution digital images from fixed and stained peripheral blood smears. The user browses through the imaged smear to gain high-level general impressions of the sample. In conducting white blood cells (WBC) differential, the user reviews the suggested classification of each automatically detected WBC, and may manually change the suggested classification of any cell. In conducting red blood cells (RBC) morphology evaluation, the user can characterize RBC morphology on observed images. In conducting platelets estimation, the user reviews each automatically detected platelet and the suggested platelet estimation, and may manually change the detections or the estimation. The X100 with Full Field Peripheral Blood Smear Application is intended to be used by skilled users, trained in the use of the device and in the identification of blood cells.

AI/ML Overview

The provided text describes the performance data for the X100 with Full Field Peripheral Blood Smear Application, comparing its results to those achieved by using a manual light microscope, which serves as the reference method.

Here's a breakdown of the requested information:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state pre-defined acceptance criteria for the percentage values (e.g., correlation coefficient, efficiency, sensitivity, specificity). However, it consistently states that "All method comparison testing met acceptance criteria." This implies that the achieved performance met internal or regulatory thresholds. Based on the provided performance data, here's a table:

Test/MeasurementAcceptance Criteria (Implicitly Met)Reported Device Performance
WBC Correlation (Deming Regression r)Met Acceptance
Neutrophil (%)Not explicitly stated98%
Lymphocyte (%)Not explicitly stated96%
Monocyte (%)Not explicitly stated95%
Eosinophil (%)Not explicitly stated98%
WBC Differential (Efficiency)Met Acceptance
Morphological AbnormalityNot explicitly stated96.82% (96.12% to 97.43% CI)
Distributional AbnormalityNot explicitly stated95.75% (94.95% to 96.46% CI)
Overall WBCNot explicitly stated96.29% (95.77% to 96.76% CI)
WBC Differential (Sensitivity)Met Acceptance
Morphological AbnormalityNot explicitly stated85.46% (80.19% to 89.78% CI)
Distributional AbnormalityNot explicitly stated88.83% (85.94% to 91.31% CI)
Overall WBCNot explicitly stated87.86% (85.38% to 90.06% CI)
WBC Differential (Specificity)Met Acceptance
Morphological AbnormalityNot explicitly stated97.79% (97.16% to 98.31% CI)
Distributional AbnormalityNot explicitly stated97.43% (96.70% to 98.03% CI)
Overall WBCNot explicitly stated97.62% (97.16% to 98.02% CI)
RBC Morphology (Overall Agreement)Met Acceptance
OverallNot explicitly stated99.77% (99.71% to 99.83% CI)
Color GroupNot explicitly stated99.49% (99.14% to 99.73% CI)
Shape GroupNot explicitly stated99.77% (99.68% to 99.84% CI)
Size GroupNot explicitly stated99.61% (99.36% to 99.78% CI)
Inclusions GroupNot explicitly stated100.00% (99.93% to 100.00% CI)
Arrangement GroupNot explicitly stated96.65% (95.52% to 97.57% CI)
Platelet Estimation (Deming Regression r)Met Acceptance
Platelets Estimation (10^3/μL)Not explicitly stated94%
Platelet Estimation (Efficiency)Met Acceptance
OverallNot explicitly stated94.89% (92.78% to 96.53% CI)
Platelet Estimation (Sensitivity)Met Acceptance
OverallNot explicitly stated90.00% (83.51% to 94.57% CI)
Platelet Estimation (Specificity)Met Acceptance
OverallNot explicitly stated96.28% (94.11% to 97.82% CI)

2. Sample size used for the test set and the data provenance

  • Sample Size for Test Set: A total of 645 specimens.
    • 335 specimens were from normal (healthy) subjects.
    • 310 specimens were from subjects with specific disease conditions.
  • Data Provenance:
    • Country of Origin: Not explicitly stated. The study was conducted at "three sites" but their geographical location is not specified.
    • Retrospective or Prospective: Not explicitly stated, but the description "specimens were collected and analyzed at three sites" with slides being "randomly selected, blinded and read" suggests a prospective or at least prospectively designed evaluation of collected samples.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

  • Number of Experts: "two examiners at each site." Since there were three sites, a total of 6 examiners were involved in establishing the ground truth.
  • Qualifications of Experts: The document states that the ground truth was established by "trained examiners" using a "manual light microscope." It also mentions elsewhere that the device is intended for "skilled users, trained in the use of the device and in the identification of blood cells." While specific certifications or years of experience are not detailed, the implication is that these examiners are qualified clinical laboratory professionals adept at manual blood smear analysis.

4. Adjudication method for the test set

  • The text states, "The slides were randomly selected, blinded and read by two examiners at each site." It does not explicitly mention a formal adjudication method (e.g., 2+1, 3+1 consensus). It simply states that results were compared between the "Test Method" (X100) and the "Reference Method" (manual light microscope). It is implied that the manual readings by the two examiners constituted the reference. There is no information provided about how discrepancies between the two examiners' manual readings (if any) were resolved or if their results were averaged.

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

  • No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study comparing human readers with AI assistance vs. without AI assistance was not the primary focus described.
  • The study primarily functions as a method comparison study, comparing the device's performance (which assists human readers) directly against the manual light microscope method (the established reference/ground truth).
  • The device "assists a qualified technologist" by locating and displaying images and suggesting classifications. The study evaluates the device-assisted technologist's performance against the manual technologist's performance.
  • Therefore, an "effect size of how much human readers improve with AI vs without AI assistance" is not reported in the context of a dedicated MRMC study.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

  • No, a standalone (algorithm-only) performance was not described or evaluated.
  • The device's intended use and the study design clearly state that it "assists a qualified technologist." The performance data reflects the combined system of the device and the human user, where the user reviews and can modify the device's suggestions (e.g., "may manually change the suggested classification of any cell," "may manually change the detections or the estimation"). It is a human-in-the-loop system.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

  • The ground truth was established by expert readings using a manual light microscope. This is effectively expert consensus if the two examiners at each site agreed, or if their readings were somehow combined to form the reference. The manual light microscope process itself is described as the "Reference Method."

8. The sample size for the training set

  • The document does not specify the sample size for the training set. The performance data provided is solely for the "Method Comparison" study, which used the 645 specimens as the test set.

9. How the ground truth for the training set was established

  • The document does not provide details on how the ground truth for the training set was established. Since the training set size is not mentioned, neither is the method for its ground truth. However, given that the device's "Analysis Technique" for WBCs uses "deterministic artificial neural networks (ANN's) trained to distinguish between classes of white blood cells," it is highly probable that the training ground truth was also established by expert classification of blood cells.

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Image /page/0/Picture/0 description: The image shows 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 2, 2020

Scopio Labs LTD. % Yarmela Pavlovic Regulatory Counsel Manatt Health 1 Embarcadero Center, 30th Floor San Francisco, California 94111

Re: K201301

Trade/Device Name: X100 with Full Field Peripheral Blood Smear (PBS) Application Regulation Number: 21 CFR 864.5260 Regulation Name: Automated Cell-Locating Device Regulatory Class: Class II Product Code: JOY Dated: May 15, 2020 Received: May 15, 2020

Dear Yarmela Pavlovic:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal

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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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-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,

Takeesha Taylor-Bell Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K201301

Device Name

X100 with Full Field Peripheral Blood Smear (PBS) Application

Indications for Use (Describe)

The X100 with Field Peripheral Blood Smear Application is intended to locate and display images of white cells, red cells, and platelets acquired from fixed and stained peripheral blood smears and assists a qualified technologist in conducting a WBC differential, RBC morphology evaluation, and platelet estimate using those images. For in vitro diagnostic use only. For professional use only.

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) Premarket Notification Summary is prepared in accordance with 21 CFR 807.92.

I. Submitter Information

Sponsor Name:Scopio Labs Ltd.
Sponsor Address:Scopio Labs Ltd.11 Tiomkin StreetTel Aviv 6578313Israel
Sponsor Email:info@scopiolabs.com
Contact Person:Contact Email:Shahar KarnyDirector of Clinical AIScopio Labsshahar@scopiolabs.com
Contact Telephone:+972-54-6542164
Date Summary Prepared:May 5, 2020

II. Device

Trade (Proprietary) Name: X100 with Full Field Peripheral Blood Smear Application Common (Usual) Name: Full Field PBS, Scopio Regulation Number: 21CFR864.5260 Regulation Name: Automated cell-locating device Regulatory Class: II JOY Product Code: Hematology Product Panel:

III. Predicate Device

Predicate A
Device Name:EasyCell Cell Locator
Device 510(k):K092116
ManufacturerMedica Corporation
Predicate B
Device Name:Romanowsky stain manual light microscopeprocess for cell classification
Device 510(k):21CFR 864.3600 Class I exempted from pre-market notification procedure

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IV. Device Description

X100 with Full Field Peripheral Blood Smear Application (Scopio's Full Field PBS) automatically locates and presents high resolution digital images from fixed and stained peripheral blood smears.

The user browses through the imaged smear to gain high-level general impressions of the sample.

In conducting white blood cells (WBC) differential, the user reviews the suggested classification of each automatically detected WBC, and may manually change the suggested classification of any cell.

In conducting red blood cells (RBC) morphology evaluation, the user can characterize RBC morphology on observed images.

In conducting platelets estimation, the user reviews each automatically detected platelet and the suggested platelet estimation, and may manually change the detections or the estimation.

The X100 with Full Field Peripheral Blood Smear Application is intended to be used by skilled users, trained in the use of the device and in the identification of blood cells.

V. Intended Use

The X100 with Full Field Peripheral Blood Smear Application is intended to locate and display images of white cells, red cells, and platelets acquired from fixed and stained peripheral blood smears and assists a qualified technologist in conducting a WBC differential, RBC morphology evaluation, and platelet estimate using those images. For in vitro diagnostic use only. For professional use only.

Comparison of Technological Characteristics with the Predicate Devices VI.

The X100 with Full Field Peripheral Blood Smear Application is substantially equivalent to its predicate devices, the EasyCell (K092116), and the manual light microscope. The subject device has the same intended use as the predicates in that all devices are intended to assist a qualified user in conducting evaluations of white blood cells, red blood cells and platelets within a fixed and stained peripheral blood smear. Additionally, the devices are also substantially equivalent with respect to technological characteristics. While the specific information provided by the subject device varies somewhat compared to the predicates, in the case of all devices the information provided must be interpreted and confirmed or adjusted by the trained user. Thus, these differences do not raise different questions of safety or effectiveness.

The similarities and differences between the subject device and the predicate devices are summarized in Table 1 below.

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Image /page/5/Picture/1 description: The image shows the logo for a company called "Scopio". The logo consists of a square made of two smaller squares, one pink and one dark blue, stacked on top of each other. To the right of the square is the company name, "Scopio", in a dark blue sans-serif font.

Table 1 Comparison of Characteristics with the Predicate Devices

ItemManual lightmicroscopic processEasyCellK092116Full Field PBS
Similarities
Intended useIntended to locate anddisplay images of whitecells, red cells, andplatelets acquired fromfixed and stainedperipheral blood smears.For in vitro diagnosticuse only. Forprofessional use onlyIntended to locate and displayimages of white cells, red cells,and platelets acquired from fixedand stained peripheral bloodsmears and assists a qualifiedtechnologist in conducting aWBC differential, RBCmorphology evaluation, andplatelet estimate using thoseimages. For in vitro diagnosticuse only. For professional useonly.Same as for EasyCell
Sample TypeStained blood film glassslides of peripheralwhole bloodSameSame
Sample PreparationRomanowsky stainSameSame
Analysis Technique:White Blood CellsWBC are manuallylocated, classified andcounted by movingaccording to thebattlement pattern(ensuring that each cellis counted only once).WBC are located/counted bymoving according to thebattlement pattern (ensuring thateach cell is counted only once).Cell images are analysed usingstandard mathematical methods,including deterministic artificialneural networks (ANN's) trainedto distinguish between classes ofwhite blood cells. The cellimages are pre-classified, and theuser reviews the suggestedclassification, and accepts orreclassifies the images.Same as for EasyCell
Analysis Technique:Red Blood CellsRed blood cells: Thedevice presents anoverview image. Theexaminers characterizered blood cellmorphology from theimage.SameSame
Daily QCN/AThe QC procedure controls forslide preparation (both smearingand staining) and EasyCellperformance. If the QCprocedure does not pass, theoperator must resolve theproblem and rerun the QC beforeprocessing samples.Same as for EasyCell
ItemManual lightmicroscopic processEasyCellK092116Full Field PBS
Differences
Analysis Technique:PlateletsPlatelets are manuallylocated and estimated bymoving according to thebattlement pattern(ensuring that each cellis counted only once).The device presents a series ofimages. The reviewers manuallycount and estimate the plateletconcentration from the imagesaccording to a procedure in theUser's Manual.Platelets are automaticallylocated/counted by movingaccording to the battlementpattern (ensuring that each cellis counted only once).The user reviews the suggestedestimate of the plateletconcentration, and accepts ormodifies the result.
Pre-classified WBCN/ACell images are grouped intoeight (8) categories:Neutrophils (Band or Segmented Lymphocytes Monocytes Eosinophils Basophils Nucleated Red Blood Cells Smudge cells Other (which is intended to hold morphologically abnormal cells.)Cell images are grouped intoeighteen (18) categories:Band Neutrophils Segmented Neutrophils Lymphocytes Atypical Lymphocytes Large Granular Lymphocytes Aberrant Lymphocytes Monocytes Eosinophils Basophils Promyelocyte Metamyelocytes Myelocytes Blasts Plasma Cells Nucleated Red Blood Cells Unclassified Smudge cells Dirt
High-ResolutionImage AcquisitionManual image viewingthrough a 100Xmagnification lens andimmersion oil.Fully automated scan and imageacquisition.Captures images at 10Xresolution to locate certain cellsand then capture images of thosecells using a 100X magnificationlens and immersion oil.Fully automated scan and imageacquisition.Captures multiple images underplurality of illuminationconditions and reconstructs a100X magnification image ofthe viewed area, without theneed for immersion oil.

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Transforming Diagnostics

Driving Hematology Forward

� Scopio

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Performance Data VII.

Method Comparison

A Method Comparison was conducted to compare the results achieved by trained examiners using the X100 with Full Field Peripheral Blood Smear Application (the Test Method) to the results achieved by using a manual light microscope.

A total of 645 specimens were collected and analyzed at three sites. 335 specimens were from normal (healthy) subjects and 310 were from subjects with specific disease conditions. Slides were prepared from each specimen. The slides were randomly selected, blinded and read by two examiners at each site.

White Blood Cells

Table 2 WBC Correlation between Reference Method and Test Method

Results from Deming regression analyses on readings between subject device and manual microscope are as follows:

Cell TypeCorrelationCoefficient (r)SlopeIntercept
Neutrophil (% )98%1.000.39
Lymphocyte (%)96%0.99-0.51
Monocyte (%)તે જેન્જી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામમાં પ્રાથમિક શાળા, પંચાયતઘર, આંગણવાડી તે0.94-0.15
Eosinophil (%)98%0.890.00

Table 3 WBC differential efficiency, sensitivity and specificity.

Measurements of distributional WBC (Band and Segmented Neutrophil, Monocyte, Lymphocyte and Eosinophil) and morphological WBC (Immature Granulocyte, Variant Forms Lymphocyte, Blast, NRBC and Plasma cell) between subject and manual microscope. In parenthesis are the calculated 95% confidence intervals.

MorphologicalAbnormalityDistributionalAbnormalityOverall
Efficiency96.82%95.75%96.29%
(96.12% to 97.43%)(94.95% to 96.46%)(95.77% to 96.76%)
Sensitivity85.46%88.83%87.86%
(80.19% to 89.78%)(85.94% to 91.31%)(85.38% to 90.06%)
Specificity97.79%97.43%97.62%
(97.16% to 98.31%)(96.70% to 98.03%)(97.16% to 98.02%)

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Image /page/8/Picture/1 description: The image shows the logo for Scorpio. The logo consists of a square with a smaller pink square overlapping the bottom left corner. To the right of the square is the word "Scorpio" in a dark blue sans-serif font. The logo is simple and modern.

Red Blood Cells

Table 4 Red Blood Cells Morphology Evaluation

Results of overall agreement for RBC morphology evaluation are as follows:

RBC MorphologyOverall Agreement with 95% CI
Overall99.77%(99.71% to 99.83%)
RBC Morphology GroupOverall Agreement with 95% CI
Color99.49%(99.14% to 99.73%)
Shape99.77%(99.68% to 99.84%)
Size99.61%(99.36% to 99.78%)
Inclusions100.00%(99.93% to 100.00%)
Arrangement96.65%(95.52% to 97.57%)

Platelets

Table 5 Platelet estimation correlation between reference method and test method

Results from Deming regression analyses on readings with subject and manual microscope are as follows:

Cell TypeCorrelationCoefficient (r)SlopeIntercept
PlateletsEstimation(103/μL)94%1.03-10.31

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Image /page/9/Picture/1 description: The image shows the logo for "Scopio". The logo consists of a square icon with a smaller magenta square overlapping the bottom left corner, followed by the word "Scopio" in a bold, dark blue font. The font appears to be sans-serif.

Table 6 Platelet estimation efficiency, sensitivity and specificity

Overall
Efficiency94.89%(92.78% to 96.53%)
Sensitivity90.00%(83.51% to 94.57%)
Specificity96.28%(94.11% to 97.82%)

All method comparison testing met acceptance criteria.

Precision (Repeatability & Reproducibility)

Repeatability

The repeatability study was performed according to the CLSI's EP05-A3 Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline-Third Edition.

A 20x2x2 repeatability study for the analyses of white blood cells differential and platelets estimation was conducted using a single instrument at a single site with 15 selected test samples. Over the course of 20 testing days, 2 daily runs were performed using 2 replicas. The selected samples represented different clinical conditions, to include all automatically located and pre-classified cell types. In total, 1,200 scans were analyzed.

For each tested sample, SD and %CV were estimated for the four variance components: repeatability, between-run (within-day), between-day and within-laboratory. The results met the predefined acceptance criteria.

Reproducibility

The reproducibility study was performed according to the CLSI's EP05-A3 Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline-Third Edition.

A 3x5x5 reproducibility study for the analyses of white blood cells differential and platelets estimation was performed across 3 different sites. The study was conducted at each site, with 10 test samples, for 5 testing days, using 5 replicas scanned with the local device. The selected samples represented different clinical conditions, to include all automatically located and pre-classified cell types. In total, 750 scans were analyzed.

For each tested sample. SD and %CV were estimated for the five variance components: repeatability, between day (within-site), within-laboratory, between site, and reproducibility. The results met the predefined acceptance criteria.

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Software Verification and Validation Testing

Software verification and validation testing were conducted and documentation was provided as recommended by FDA's guidance. The software application was considered as a "moderate" level of concern, since a malfunction failure or latent design flaw in the software could lead to an erroneous diagnosis or a delay in delivery of appropriate medical care that could lead to a minor injury.

VIII. Conclusion

Study results demonstrated that X100 with Full Field Peripheral Blood Smear Application is substantially equivalent to the predicate device.

§ 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).