The ADVIA™ 120 Hematology System Complete Blood Count (CBC) method is intended to quantitatively measure the following hematological parameters: White Blood Cell count (WBC) Red Blood Cell count (RBC) Total Hemoglobin concentration (HGBTotal) Cellular Hemoglobin concentration (HGBcell) Hematocrit (HCT) Mean Corpuscular Volume (MCV) Mean Corpuscular Hemoglobin (MCH) Mean Corpuscular Hemoglobin Concentration (MCHC) Corpuscular Hemoglobin Concentration Mean (CHCM) Cellular Hemoglobin Content (CH) Red Cell Volume Distribution Width (RDW) Hemoglobin Concentration Distribution Width (HDW) Platelet Count (PLT) Mean Platelet Volume (MPV)

The difference between HGBToul and HGBcen can be used to discriminate between cellassociated hemoglobin and cell-free hemoglobin as found in hemoglobin-based blood substitutes.

Device Description

Cellular hemoglobin is currently a "laboratory use only" parameter on the ADVIA 120 system. There are no changes to software, reagents, calibrators or controls necessary to derive the cellular hemoglobin parameter.

AI/ML Overview

Acceptance Criteria and Device Performance Study for ADVIA 120 Cellular Hgb Method

1. Table of Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state numerical acceptance criteria. Instead, it defines acceptance in terms of "equivalence" to the predicate device (ADVIA 120 HgbTotal method, K971998) for several performance characteristics.

Characteristic	Acceptance Criteria (Stated)	Reported Device Performance (Summary)
Accuracy	Equivalent to predicate method.	"demonstrate that the ADVIA 120 cellular Hgb Method has equivalent accuracy... substantially equivalent to the ADVIA 120 predicate method."
Precision	Equivalent to predicate method.	"demonstrate that the ADVIA 120 cellular Hgb Method has equivalent... precision... substantially equivalent to the ADVIA 120 predicate method."
Linearity	Equivalent to predicate method.	"demonstrate that the ADVIA 120 cellular Hgb Method has equivalent... linearity... substantially equivalent to the ADVIA 120 predicate method."
Carryover	Equivalent to predicate method.	"demonstrate that the ADVIA 120 cellular Hgb Method has equivalent... carryover... substantially equivalent to the ADVIA 120 predicate method."

Note: The document states that the predicate method's specifications for Accuracy, Precision, Linearity, and Carryover are "As specified in product labeling." However, these specific values are not included in this 510(k) summary. Therefore, the exact numerical benchmarks for equivalence are not provided in this excerpt.

2. Sample Size and Data Provenance for the Test Set

The document does not explicitly state the sample size used for the test set or the data provenance (e.g., country of origin, retrospective/prospective). It generally refers to "test results included in this submission" but provides no details on these aspects.

3. Number and Qualifications of Experts Used to Establish Ground Truth for the Test Set

The document does not mention the use of experts to establish ground truth for the test set. Given the nature of the device (quantitative measurement of hemoglobin in whole blood), ground truth would typically be established through comparison with a reference method or highly accurate predicate device, not expert human interpretation.

4. Adjudication Method for the Test Set

The concept of an "adjudication method" (like 2+1 or 3+1) is not applicable here as the device measures a quantitative parameter, and its performance is assessed against a predicate device or reference method, not through human consensus on image interpretation or complex diagnoses.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study is typically performed for diagnostic devices that rely on human interpretation of images or other subjective data, often to assess the impact of AI assistance on human performance. The ADVIA 120 Cellular Hgb method is a quantitative laboratory instrument, not an AI-assisted diagnostic tool requiring human interpretation. Therefore, the effect size of human readers improving with or without AI assistance is not relevant or reported.

6. Standalone Performance Study

Yes, a standalone performance study was implicitly done, as the ADVIA 120 Cellular Hgb method is itself the "algorithm" (or rather, the method of calculation) being evaluated. The submission demonstrates the performance of this method in terms of accuracy, precision, linearity, and carryover, comparing it directly to the predicate device. This evaluation is of the device's inherent capability to measure cellular hemoglobin without human-in-the-loop intervention for the measurement itself.

7. Type of Ground Truth Used

The ground truth for the test set was established by the predicate method, the ADVIA 120 HgbTotal method (K971998). The study aims to demonstrate that the new cellular Hgb method is "equivalent" or "substantially equivalent" to this established and legally marketed predicate device.

8. Sample Size for the Training Set

The document does not mention a "training set" or its sample size. This is expected as the ADVIA 120 Cellular Hgb method is based on a deterministic calculation from existing RBC/Plt channel parameters (RBC count, MCV, CHCM) and does not involve machine learning algorithms that typically require a training phase with a distinct training set. The principles of operation describe a direct calculation: "The cellular hemoglobin concentration is then calculated as the product of the RBC count, the MCV, and CHCM, then scaled by a factor of 1/1000 to obtain units of grams per dL of whole blood."

9. How the Ground Truth for the Training Set Was Established

As there is no mention of a training set or a machine learning algorithm, the concept of establishing ground truth for a training set is not applicable to this device and submission.

Summary

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510(k) Summary of Safety and Effectiveness

K022669

510(k) Summary of Safety and Effectiveness

OCT 1 5 2002

The following information provides data supporting a substantially equivalent determination between the ADVIA 120 cellular Hgb method (Hgbcel) and the ADVIA 120 Hgbrotal predicate method (K971998).

Intended Use

The ADVIA 120 Hgbcen parameter is intended to provide an in vitro diagnostic. quantitative measurement of hemoglobin concentration in a sample of whole blood.

Device Description

Principles of Operation

The ADVIA 120 cellular hemoglobin method is derived from the RBC/Plt channel of the system. The RBC/Plt channel uses optical light scattering to derive RBC cell volume and cell hemoglobin concentration on a cell-by-by cell basis. The parameters MCV (mean corpuscular volume) and CHCM (corpuscular hemoglobin concentration mean) are then calculated as the mean of the volume and hemoglobin concentration histograms respectively, along with an RBC count. These parameters have previously received 510(k) clearance in K971998. The cellular hemoglobin concentration is then calculated as the product of the RBC count, the MCV, and CHCM, then scaled by a factor of 1/1000 to obtain units of grams per dL of whole blood.

Similarities and Differences between the ADVIA 120 Cellular Hgb Method and the ADVIA 120 Hgb Predicate Method (K971998)

The following table provides similarities and differences between the ADVIA 120 cellular Hgb Method and the ADVIA 120 cyanide containing predicate method.

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		ADVIA 120	ADVIA 120
Similarities/Differences	Characteristic	Hgb Method	Cellular Hgb
Similarities	Intended Use	To provide a quantitativemeasurement ofhemoglobin concentrationin whole blood.	Same as predicatemethod.
	Accuracy	As specified in productlabeling.	Equivalent to predicatemethod.
	Precision	As specified in productlabeling.	Equivalent to predicatemethod.
	Linearity	As specified in productlabeling.	Equivalent to predicatemethod.
	Carryover	As specified in productlabeling.	Equivalent to predicatemethod.
Differences	Reagent	ADVIA 120 HGB	ADVIA 120 RBC/PLT
	Method Principle	Colorimetric method	Laser optical method
	Sample stability	72 hours for samplesstored at roomtemperature	24 hours for samplesstored at roomtemperature

Conclusion

The test results included in this submission demonstrate that the ADVIA 120 cellular Hgb Method has equivalent accuracy, precision, linearity, and carryover substantially equivalent to the ADVIA 120 predicate method.

Simuets-toke

Kenneth T. Edds, Ph.D. Manager, Regulatory Affairs Bayer Corporation 511 Benedict Avenue Tarrytown, New York 10591-5097

Date

8/09/02

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/2/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS). The seal features the department's name encircling a stylized representation of an abstract design. The design consists of three curved lines that converge at the bottom, resembling a stylized symbol. The text is arranged in a circular pattern around the symbol.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Kenneth T. Edds, Ph.D. Regulatory Affairs Manager Bayer Diagnostics 511 Benedict Avenue Tarrytown, New York 10591-5097

OCT 1 5 2002

Re: K022668

Trade/Device Name: Bayer ADVIA 120 Cellular Hemoglobin Parameter Regulation Number: 21 CFR § 864.5220 Regulation Name: Automated differential cell counter Regulatory Class: II Product Code: GKZ Dated: August 12, 2002 Received: August 12, 2002

Dear Dr. Edds:

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. 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 (PMA), 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 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2

will allow you to begin marketing your devices as described in your S1000 premarket 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 International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrb/dsma/dsmamain.html".

Sincerely yours,

Steven Toutman

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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510(k) Number:

Device Name: Bayer ADVIA 120 Hematology analyzer

Indications for Use:

The difference between HGBToul and HGBcen can be used to discriminate between cellassociated hemoglobin and cell-free hemoglobin as found in hemoglobin-based blood substitutes.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Hesheim - Lauter

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

Prescription Use (Per 21 CFR 801.109) OR

Over-The-CounterUse

(Optional Format 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.”