The COULTER GEN S System with IRF and MRV Parameters is a quantitative, automated hematology analyzer and leukocyte differential counter For In Vitro Diagnostic Use in clinical laboratories. The COULTER GEN-S System also provides automated Reticulocyte analysis.

An automated differential cell counter is a device used to identify and classify one or more of the formed elements of blood.

Device Description

The Immature Reticulocyte Fraction expresses the number of early reticulocytes as a proportion of the total reticulocyte count. Mean reticulocyte volume (MRV) is the average cell volume of the reticulocytes, determined by the VCS Technology algorithm and is reported in femtoliters (fL). This 510(k) Premarket Notification provides information demonstrating that Coulter hematology analyzers with IRF and MRV parameters are substantially equivalent to products previously cleared for this use. The COULTER hematology analyzers with IRF and MRV parameters are compared to Sysmex™ hematology analyzers with the IRF parameter. The MRV parameter is presented as a discussion of the calculation and supported by precision data from a COULTER GEN-S System analyzer. Unlike the Sysmex R-1000, R-3000 and RAM-1 analyzers which are dedicated to the measurement of reticulocyte parameters, the COULTER hematology analyzers, including the GEN.S, measure multiple CBC and differential parameters in addition to the measurement of reticulocyte parameters.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the COULTER® Hematology Analyzers with IRF & MRV Parameters, based on the provided text:

Acceptance Criteria and Device Performance

The provided document describes a submission for substantial equivalence to predicate devices, rather than a study with pre-defined acceptance criteria for a new device. Therefore, the "acceptance criteria" are implicitly the performance metrics of the predicate devices and the demonstration of equivalent performance by the new device. The study aims to show that the COULTER® device performs comparably to or better than its predicates.

Parameter	Acceptance Criteria (Predicate Performance) - Implicit	Reported Device Performance (COULTER® GEN-S)	Outcome (vs. Predicate)
IRF Accuracy
Population Mean (Sysmex SE9500)	0.199	0.391	Differs, but without a defined threshold, it's assessed by correlation metrics.
Mean Difference	N/A (Comparative to predicate)	-0.192
SD of Difference	N/A (Comparative to predicate)	0.07953
Slope	N/A (Comparative to predicate)	0.835
Y-Intercept	N/A (Comparative to predicate)	0.225
R (Correlation Coefficient)	N/A (A high 'R' value is generally desired for good correlation)	0.757	Demonstrates a positive correlation.
IRF Imprecision
Mean Difference	0 (Ideally)	0	Meets ideal for mean difference.
S.D. of Difference	Low (Ideally)	0.04	Low, indicating good precision.
MRV Imprecision
Mean Difference	0 (Ideally)	0.04	Very close to ideal for mean difference.
S.D. of Difference	Low (Ideally)	2.33	Low, indicating good precision.

It's important to note that specific numerical "acceptance criteria" for the COULTER device itself are not explicitly stated as pass/fail thresholds in this summary. Instead, the submission relies on demonstrating substantial equivalence to the predicate devices through comparative accuracy and imprecision experiments. The values presented for the COULTER device are its performance measures, which are then compared to the predicate's performance and statistical targets like a mean difference of zero and low standard deviation for imprecision.

Study Information

Sample sizes used for the test set and the data provenance:
- IRF Accuracy Analysis (GEN-S vs Sysmex SE9500): N = 332 samples.
- IRF and MRV Paired Imprecision results (GEN-S): N = 90 samples for each.
- Data Provenance: Not explicitly stated but usually for such studies, it's clinical samples, likely from the country where the study was conducted (presumably the US, given the FDA submission). It is not specified if the data is retrospective or prospective.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is not a diagnostic imaging or classification device where ground truth is established by expert review. For hematology analyzers, the "ground truth" or reference method is typically another established, often manual or highly validated, laboratory method or a predicate device.
- In this case, for IRF accuracy, the Sysmex SE9500 (predicate device) served as the comparator method against which the COULTER GEN-S's performance was evaluated.
Adjudication method for the test set:
- Not applicable. As described above, this is a comparison against a predicate device, not an expert-adjudicated ground truth.
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. This is a study for an automated hematology analyzer, not an AI assistance tool for human readers. Therefore, an MRMC study is not relevant and was not performed.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, implicitly. The performance data presented (IRF accuracy and IRF/MRV imprecision) are for the COULTER® Hematology Analyzers as automated, standalone devices. They are designed to provide quantitative measurements without human intervention in the primary measurement and calculation process. The comparison is between two automated systems.
The type of ground truth used:
- For IRF Accuracy, the ground truth was the predicate device's measurement (Sysmex SE9500). This is a common approach in demonstrating substantial equivalence for new IVD devices by comparing them to an already legally marketed and validated device.
- For IRF and MRV Imprecision, the ground truth is internal consistency and reproducibility of the device itself over repeated measurements, rather than an external gold standard.
The sample size for the training set:
- Not specified. The document primarily focuses on the validation of the device for regulatory submission, presenting performance data (test set results). Information about the training set size (if any, for internal algorithm development) is not typically included in such summaries.
How the ground truth for the training set was established:
- Not specified. Similar to the training set size, the specifics of how internal algorithm development and potential training data ground truth were established are not part of this regulatory summary.

Summary

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K993356

Summary of Safety & Effectiveness COULTER® Hematology Analyzers with IRF & MRV Parameters

Submitted By 1.0

Stan Sugrue, Ph.D. Senior Requlatory Affairs Specialist Coulter Corporation 11800 SW 147 Avenue MC 31-B06 Miami. FL 33196 Telephone: (305) 380-4552 FAX: (305) 380-3618

APR 2, 0 2000

2.0 Date Submitted

March 28, 2000

3.0 Device Name(s)

3.1 Proprietary Names

COULTER® Hematology Analyzers with IRF & MRV Parameters

3.2 Classification Names

The product is classified as a Class III device as found in 21CFR 864.5220.

An automated differential cell counter is a device used to identify and classify one or more of the formed elements of blood. (CFR 864.5220) . The Classification Number is 81GKZ.

4.0 Predicate Device(s)

Sysmex™ w/IRF Parameter (K971736/S1), COULTER® GEN-S™ System (K962988), COULTER® New Methylene Blue Prep Retic MAXM/AL Analyzers (K925344)

5.0 Description

The Immature Reticulocyte Fraction expresses the number of early reticulocytes as a proportion of the total reticulocyte count. Mean reticulocyte volume (MRV) is the average cell volume of the reticulocytes, determined by the VCS Technology algorithm and is reported in femtoliters (fL).This 510(k) Premarket Notification provides information demonstrating that Coulter hematology analyzers with IRF and MRV parameters are substantially equivalent to products previously cleared for this use. The COULTER hematology analyzers with IRF and MRV parameters are compared to Sysmex™ hematology analyzers with the IRF parameter. The MRV parameter is presented as a discussion of the calculation and supported by precision data from a COULTER GEN-S System analyzer. Unlike the Sysmex R-1000, R-3000 and RAM-1 analyzers which are dedicated to the measurement of reticulocyte parameters, the COULTER hematology analyzers, including the GEN.S, measure multiple CBC and differential parameters in addition to the measurement of reticulocyte parameters.

6.0 Intended Use

The COULTER hematology analyzers with IRF and MRV parameters are quantitative, automated hematology analyzers and leukocyte differential counters intended For In Vitro Diagnostic Use in clinical laboratories. These systems also provide automated Reticulocyte analysis.

7.0 Comparison to Predicate(s):

The following table show the basic similarities and differences between the COULTER® GEN-S and predicate device(s).

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SIMILARITIES TO THE PREDICATE

COULTER hematology analyzers with IRF and MRV parameters	Sysmex SE & R Series
Systems provide automated reticulocyte analysis	Same
Report IRF parameter	Same*

*Reported as sum of MFR (Middle Fluorescence Ratio) and HFR (High Fluorescence Ratio)

DIFFERENCES FROM THE PREDICATE:

COULTER hematology analyzers with IRF and MRVparameters	Sysmex R Series
Quantitative, automated hematology analyzers and leukocytedifferential counters	Measures reticulocyte parameters only
Report MRV parameters	No MRV analysis
Measure CBC, 5-part differential and reticulocyte parameters	Measures reticulocyte parameters only
Use impedance for counting and sizing RBCs and platelets	No RBC or platelet analysis
Reticulocyte parameters derived from laser light scatter andnucleic acid dye (New Methylene Blue)	Reticulocyte parameters are measured byfluorescence and light scatter utilizing afluorescent dye (Auramine-O)

8.0 Summary of Performance Data:

The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence to hematology analyzers already in commercial distribution. Equivalence is demonstrated through compared sample accuracy and imprecision experiments.

PARAMETER	IRF
UNITS	Not Applicable
POPULATION MEANPredicate Method	0.199
POPULATION MEANComparator Method	0.391
MEAN DIFFERENCE	-0.192
SD OF DIFFERENCE	0.07953
SLOPE	0.835
Y-INTERCEPT	0.225
R	0.757
N	332

1RF Accuracy Analysis : GEN•S vs Sysmex SE9500

IRF and MRV Paired Imprecision results: GEN.S

	IRF	MRV
Units	Not Applicable	Femtoliters (fL)
N	90	90
Population Minimum	0.127	93.6
Population Maximum	0.372	123.2
Mean difference	0	0.04
S.D. of Difference	0.04	2.33

This summary of safety and effectiveness is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.

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Image /page/2/Picture/1 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with three lines forming its wings and body.

APR 2 0 2000

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Stan Sugrue, Ph.D. Senior Regulatory Affairs Specialist Coulter Corporation 11800 SW 147 Avenue MC 31-B06 Miami, Florida 33196

Re: K993356

Trade Name: COULTER® Hematology Analyzers with IRF & MRV Parameters Regulatory Class: III Product Code: GKZ Dated: March 28, 2000 Received: March 29, 2000

Dear Dr. Sugrue:

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 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). 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 registration, 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 requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (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 regulatory 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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Page 2

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 regulation entitled. "Misbranding by reference to premarket notification" (21CFR 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 (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsma/dsmamain.html".

Sincerely yours,

Steven Sutman

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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INDICATIONS FOR USE

993356 510(k) Number (if known):

COULTER Hematology Analyzers with IRF and MRV Parameters Device:

Indications For Use:

21 CFR 864.5220 Automated differential cell counter

An automated differential cell counter is a device used to identify and classify one or more of the formed elements of blood.

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Retu E. Maún

(Division Sign-Off)
Division of Clinical Laboratory Devices K993356
510(k) Number.

Prescription Use
(Per 21 CFR 801.109)

Over-The-Counter Use

(Optional Form 1-2-96)

Regulation Number and Section

§ 864.5220 Automated differential cell counter.

(a)
Identification. An automated differential cell counter is a device used to identify one or more of the formed elements of the blood. The device may also have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood, bone marrow, or other body fluids. These devices may combine an electronic particle counting method, optical method, or a flow cytometric method utilizing monoclonal CD (cluster designation) markers. The device includes accessory CD markers.(b)
Classification. Class II (special controls). The special control for this device is the FDA document entitled “Class II Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells; Final Guidance for Industry and FDA.”