(84 days)
For In Vitro Diagnostic Use
Intelligent Medical Imaging, Inc.'s MICRO21 with WBC Estimate is a laboratory instrument for locating, digitally storing and displaying white blood cells to aid the technologist in performing the WBC Estimate. Examination and determination of the results must be performed by qualified individuals.
The MICRO21 with WBC Estimate is a new intended use that follows the same process as the currently approved MICRO21 with White Blood Cell (WBC) Differential (Diff). The MICRO21 with WBC Diff, Ref. No. K925670/A, is an automated microscopic system that locates WBCs, stores digital images of the cells and displays the images in an organized manner to aid technologists in performing the WBC Diff procedure. The MICRO21 process is substantially equivalent to the manual microscopic process.
The MICRO21 with WBC Estimate is an automated microscopic procedure that calculates an estimate of WBCs/uL using the information collected during the MICRO2/ with WBC Differential. Upon completion of the review process by a technologist, an algorithm calculates the WBC Estimate by using the number of classified WBCs and the number for low-power (200x magnification) fields visited. An estimated range for the WBCs/uL is calculated and reported.
Here's an analysis of the provided text regarding the acceptance criteria and study for the MICRO21 with WBC Estimate device:
Acceptance Criteria and Study Analysis for MICRO21 with WBC Estimate
The primary objective of the studies was to demonstrate the substantial equivalence of the MICRO21 with WBC Estimate to a Manual WBC Estimate and to automated cell counter results for total WBC count.
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria with specific thresholds (e.g., "accuracy must be >X%"). Instead, it describes a correlation study where the MICRO21's performance is compared against established methods. The "acceptance" is implied by demonstrating substantial equivalence, meaning the results are comparable and within clinically acceptable ranges.
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Accuracy: Equivalence of MICRO21 WBC Estimate with automated cell counter Total WBC Count. | Correlated (specific metrics not provided, but the conclusion states "confirm that the MICRO21 with WBC Estimate is substantially equivalent to a Manual WBC Estimate" and "correlated the WBC Estimate on the MICRO21 with the total White Blood Cell Count generated by an automated cell counter"). |
| Accuracy: Equivalence of MICRO21 WBC Estimate with Manual WBC Estimate. | Confirmed substantially equivalent. |
| Precision: Intra-instrument precision (variability when processing the same specimen multiple times). | Results were used to provide intra-instrument and within specimen precision (specific metrics like CV% not provided, but implied to be acceptable for equivalence). |
| Reporting Range: Ability to report WBC estimates within a specified clinical range. | Reportable range from 100 to ≥ 25,000 WBCs/μL, displayed as MICRO21 WBC Estimate x,xxx - y,yyy WBC/μL. |
2. Sample Size and Data Provenance
- Test Set Sample Size: 86 blood smear samples.
- Data Provenance: Not explicitly stated, but given the nature of a 510(k) submission for commercialization, it is highly likely a prospective study using clinical samples. The document mentions "various sites" for automated cell counters, suggesting a multi-center data collection effort, but specific countries are not mentioned.
3. Number of Experts and Qualifications for Ground Truth
- Number of Experts:
- For Manual WBC Estimate (Accuracy Study): Three technologists.
- For MICRO21 WBC Estimate (Precision and Classification Review): One technologist for the precision study, and three technologists for the "WBC Classification Review" section, which contributed to confirming "real cells" used in the MICRO21 calculation.
- Qualifications of Experts: Described as "technologists." Specific experience levels (e.g., years of experience, certification) are not provided in the document. The conclusion states "Examination and determination of the results must be performed by qualified individuals," but doesn't detail the qualifications of those who performed the study.
4. Adjudication Method for the Test Set
The document does not describe a formal adjudication method (like 2+1 or 3+1).
- For the Manual WBC Estimate, it states "Three technologists performed the manual reviews," implying they each performed their own estimate, but it doesn't specify how their results were consolidated or if consensus was required.
- For the MICRO21 Classification Review, "Three technologists performed the MICRO21 reviews" to verify image classification. Again, it doesn't mention an adjudication process if there were disagreements among them.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
An MRMC study, specifically comparing human readers with AI assistance versus without AI assistance, was not explicitly done or reported in this document. The MICRO21 is described as an "automated microscopic system that locates WBCs, stores digital images of the cells and displays the images in an organized manner to aid technologists." The "aid" here is the display and organization of images, and then the automated calculation based on the technologist's reviewed classifications. The study focuses on the accuracy and precision of the device's estimate compared to manual/automated methods, not on the improvement in human performance due to the aid.
Therefore, no effect size of how much human readers improve with AI vs without AI assistance is provided.
6. Standalone (Algorithm Only) Performance
A standalone performance study was performed for the core calculation of the WBC Estimate. The algorithm automatically calculates the WBC Estimate based on:
- The number of classified WBCs (which are verified by a technologist, but the calculation itself is algorithmic).
- The number of low-power fields visited.
- A Correction Factor.
The "Test Method 1, Accuracy" and "Test Method 2, Precision" evaluate the output of this algorithmic estimate against established methods. While human input (technologist review) confirms the "Real Cells" used in the formula, the final calculation and the resulting "MICRO21 WBC Estimate" range are generated by the device's algorithm.
7. Type of Ground Truth Used
The ground truth used was a combination of:
- Established device measurements: Total White Blood Cell Count generated by automated cell counters (e.g., TOA Sysmex NE 9000, Coulter STKS, Technicon H2). These automated counters are considered a gold standard or a highly reliable reference for total WBC count.
- Expert Consensus/Reference Standard: Manual WBC Estimate performed by three technologists. This serves as a clinical reference method for comparison.
8. Sample Size for the Training Set
The document does not explicitly state the sample size for a training set. The 86 specimens mentioned are for the "Accuracy" test method, which appears to be the primary validation set.
There is a "Correction Factor" (CF) that was "defined as the mean value of the 86 specimens tested." This suggests that the 86 specimens were used to determine or fine-tune this factor, which could be considered a form of calibration or training data for that specific parameter. However, it's not a typical "training set" in the context of modern machine learning where a completely separate hold-out or test set would be used.
9. How the Ground Truth for the Training Set Was Established
As noted above, a distinct "training set" is not described. However, the Correction Factor was derived from the mean value of the 86 specimens tested. For these 86 specimens, the ground truth involved:
- Total WBC Counts from automated cell counters (controlled and calibrated according to manufacturer's specifications).
- Manual WBC Estimates performed by three technologists.
These established ground truths for the 86 specimens were then used to define the Correction Factor, making it essentially a calibrated parameter for the algorithm.
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510(k) Summary
Designated Point of Contact: Otto Stellner Title: Vice President, Regulatory Compliance Project Manager: Alyn J. Hansen Date: August 5, 1997
Trade Name: MICRO21 with WBC Estimate Classification Name: Automated Cell Locating Device Classification Number: 81JOY Class: II Regulation Number: 864.5260
Description
The MICRO21 with WBC Estimate is a new intended use that follows the same process as the currently approved MICRO21 with White Blood Cell (WBC) Differential (Diff). The MICRO21 with WBC Diff, Ref. No. K925670/A, is an automated microscopic system that locates WBCs, stores digital images of the cells and displays the images in an organized manner to aid technologists in performing the WBC Diff procedure. The MICRO21 process is substantially equivalent to the manual microscopic process.
NOV - 7 19
The MICRO21 with WBC Estimate is an automated microscopic procedure that calculates an estimate of WBCs/uL using the information collected during the MICRO2/ with WBC Differential. Upon completion of the review process by a technologist, an algorithm calculates the WBC Estimate by using the number of classified WBCs and the number for low-power (200x magnification) fields visited. An estimated range for the WBCs/uL is calculated and reported. A summary of the MICRO21 with WBC Estimate process is as follows:
- Patient blood smears are made on glass slides using an automated blood smearing device. 1.
- Each slide is stained with Wright's stain. 2.
- The slides are barcoded, placed into a slide frame and inserted into the MICRO21 for processing. 3.
- The MICRO21 locates WBCs and stores digital images of the cells. 4.
- The technologist reviews the stored images on a color monitor and verifies the white cell classification. న్.
- The MICRO21 automatically calculates the WBC Estimate by dividing the classified WBCs by the 6. number of low-power fields visited.
- At the completion of the procedure, the WBC Estimate is displayed as a range and is available on the 7. Final Report display and printout.
Test Method 1, Accuracy
To confirm equivalence, 86 blood smear samples with Total WBC Counts ranging from 100 to 36,100 cells/JL were used. The study correlated the WBC Estimate on the MICRO21 with the total White Blood Cell Count generated by an automated cell counter such as the TOA Sysmex NE 9000, Coulter STKS or Technicon H2 and compared the MICRO21 with WBC Estimate to the Manual WBC Estimate. The automated cell counters were controlled and culibrated according to manufacturer's specifications at the various sites.
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Test Method 2, Precision
To confirm the MICRO21 intra-instrument precision, one blood smear was prepared from each of 10 specimens. Each blood smear was processed 10 times in random order. The stored images were then presented to a technologist for review. The results were used to provide intra-instrument and within specimen precision.
Test Method 3, Correlation, WBC Classification Review
The technologist reviewed the images of nucleated cells captured by the MICRO21 and verified the image classification. The number of confirmed white blood cells (real cells) after the review was completed was the number used in the MICRO21 calculation of WBC Estimate. Non-white blood cells were reclassified as smudges, ignore or nucleated red blood cells. Three technologists performed the MICRO21 reviews.
Calculation of the MICRO21 with WBC Estimate
The method is based on the number of WBCs located within an area of optimal cell distribution and is correlated with the absolute WBC/yL of blood. The calculation of the MICRO2 / with WBC Estimate is based on the following formulation:
Real Cells x CF = MICRO21 WBC Estimate Fields
- Real Cells = the number of confirmed WBCs .
- Fields = the number of low-power (200x magnification) fields visited to capture the Real . Cells
- CF = Correction Factor, the numerical factor need to match MICRO2/ WBC Estimate with . Total WBC Count obtained using automated blood cell analyzer.
- MICRO2/WBC Estimate = WBC/uL of blood .
The Correction Factor was defined as the mean value of the 86 specimens tested.
Reporting the MICRO21 with WBC Estimate
The calculated MICRO21 WBC Estimate is displayed on the Report Screen and printed out in the Final Report. The reportable range is from 100 to ≥ 25,000 WBCs/pL and is displayed as follows:
MICRO21 WBC Estimate x , xxx - - y , yyy WBC/ uL
Manual WBC Estimate
The Manual WBC Estimate was obtained by reviewing 86 blood smears under 500 or 1,000x magnification and calculating an estimate based on white blood cells per 10 fields of view. Three technologists performed the manual reviews.
Conclusion
Results are reported in the Summary of Results section and confirm that the MICRO21 with WBC Estimate is substantially equivalent to a Manual WBC Estimate. The results of this comparison confirm the safety and effectiveness of the MICRO21 WBC Estimate for the intended use as a laboratory instrument for locating, digitally storing and displaying white blood cells to aid the technologist in performing the WBC Estimate. Examination and determination of the results must be performed by qualified individuals.
Page 4 of 22 4360 Northlake Blvd., Suite 214 · Palm Beach Gardens, FL 33410 Phone (561) 627-0344 · FAX (561) 627-0344
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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle or bird-like figure with its wings spread, rendered in a simple, bold line drawing.
Public Health Service
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Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Mr. R. Otto Stellner Vice President, Regulatory Compliance Intelligent Medical Imaging 4360 Northlake Boulevard, Suite 214 Palm Beach Gardens, Florida 33410
NOV - 7 1997
Re : K973050 Trade Name: MIRCO21™ with WBC Estimate Regulatory Class: II Product Code: JOY Dated: August 5, 1997 Received: Auqust 15, 1997
Dear Mr. Stellner:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual reqistration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval) , it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General requlation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in requlatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Regulations.
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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.
This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the requlation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"
Sincerely yours,
Steven Autman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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Page 1 of 1
510(k) Number :
Device Name: MICRO2I™ with WBC Estimate
Indications for Use:
For In Vitro Diagnostic Use
Intelligent Medical Imaging, Inc.'s MICRO21 with WBC Estimate is a laboratory instrument for locating, digitally storing and displaying white blood cells to aid the technologist in performing the WBC Estimate. Examination and determination of the results must be performed by qualified individuals.
INTELLIGENT MEDICAL IMAGING, INC. DOES NOT PROMOTE THE USE OF, PROVIDE SUPPORT FOR, MAKE CLAIMS OF EFFECTIVENESS OF OR ASSUME LIABILITY FOR THIS DEVICE IN ANY OTHER COMMERCIAL, EXPERIMENTAL OR INVESTIGATIONAL. APPLICATION.
Use of this device in any manner that is inconsistent with its intended use may be in violation of federal law.
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number
Prescription Use
(per 21 CFR 801.109)
OR
Over-The-Counter Use
(Optional Format 1-2-96)
§ 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).