The Hemoglobin A1c2 (HbA1c2) reagent kit, when used in conjunction with SYNCHRON LX® System(s) and SYNCHRON® Systems HbA1c2 Calibrators, is intended for the quantitative determination of hemoglobin A1c (HbA1c2) concentration as a percentage of total hemoglobin in human whole blood.

Measurement of hemoglobin A1c is accepted as a method to measure long-term glucose control in patients with diabetes mellitus (a chronic disorder associated with disturbances in carbohydrate, fat, and protein metabolism and characterized by hyperglycemia). Determination of hemoglobin A1c provides an important diagnostic tool for monitoring the efficiency of dietary control and therapy during treatment of diabetes mellitus.

Device Description

The SYNCHRON LX® System(s) HbA1c2 reagent is designed for optimal performance on the SYNCHRON LX® System(s). The reagent kit contains two A1c2 80-test cartridges, one Hb2 160-test cartridge and one 2 mL bottle each of Hb/A1c2 Calibrator Level 2, A1c2 Calibrator Levels 3, 4 and 5.

AI/ML Overview

The provided 510(k) summary for the SYNCHRON LX® Systems Hemoglobin A1c2 (HbA1c2) Reagent focuses on demonstrating substantial equivalence to a predicate device, as is customary for such submissions. It includes performance data, but the structure of a typical 510(k) does not usually detail acceptance criteria in the same way a clinical trial protocol would, nor does it typically involve the extensive expert consensus or MRMC studies for establishing ground truth as seen in medical imaging AI device submissions.

Here's an analysis of the available information based on your request, highlighting what is present and what is not typically found in this type of submission:

Acceptance Criteria and Device Performance

The acceptance criteria are not explicitly stated in a pass/fail format with numerical thresholds. Instead, substantial equivalence is demonstrated through comparative performance metrics against predicate devices and through internal validation studies (stability, linearity, imprecision). The "acceptance" is implicitly tied to demonstrating performance comparable to the predicate.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Method Comparison	Slope close to 1, Intercept close to 0, r (correlation) close to 1 when compared to predicate methods.	SYNCHRON HbA1c (Predicate): Slope = 0.911, Intercept = 0.46, r = 0.991 (N=80)
		Tosoh A1c (Reference Method): Slope = 1.042, Intercept = -0.56, r = 0.994 (N=80)
Imprecision (Within-Run)	Low standard deviation (S.D.) and coefficient of variation (%C.V.) at different HbA1c levels.	Normal (5.5%): S.D. = 0.07%, %C.V. = 1.2% (N=80)
		Abnormal (9.8%): S.D. = 0.09%, %C.V. = 1.0% (N=80)
Imprecision (Total)	Low standard deviation (S.D.) and coefficient of variation (%C.V.) at different HbA1c levels.	Normal (5.5%): S.D. = 0.14%, %C.V. = 2.6% (N=80)
		Abnormal (9.8%): S.D. = 0.27%, %C.V. = 2.8% (N=80)

Study Information

Due to the nature of this 510(k) submission for an in vitro diagnostic (IVD) reagent, many of the requested categories (especially those related to expert consensus, adjudication, and MRMC studies, which are common for AI/imaging devices) are not applicable or not detailed in this document.

Sample Size used for the test set and the data provenance:
- Sample Size: 80 for each method comparison study (SYNCHRON HbA1c and Tosoh A1c). 80 for each imprecision study (within-run and total), for both normal and abnormal samples.
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, given it's a submission by Beckman Coulter, Inc. in Brea, California, it's highly likely to be U.S. data, and typically, these studies are prospective validation studies conducted by the manufacturer.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is not applicable in the context of an IVD reagent seeking substantial equivalence. The "ground truth" for method comparison is established by comparison to recognized reference methods or predicate devices, which are themselves validated laboratory assays. It does not involve human expert interpretation of images or clinical data in the way AI/imaging devices do.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- None (not applicable). Adjudication protocols are primarily used when subjective human interpretation is involved in establishing ground truth, such as in clinical or imaging studies.
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 (not applicable). MRMC studies are specific to evaluating the impact of AI on human readers, typically in image interpretation. This device is an automated IVD reagent.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, implicitly. The device (reagent on the SYNCHRON LX System) performs the HbA1c concentration determination quantitatively and automatically. The method comparison and imprecision studies directly reflect the standalone performance of the algorithm/reagent system. There is no "human-in-the-loop" for performing the actual analyte measurement.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The "ground truth" (or reference standard) is established by comparison to a legally marketed predicate device (SYNCHRON HbA1c) and a recognized reference method (Tosoh A1c). These methods are themselves quantitative assays, providing a numerical concentration for HbA1c.
The sample size for the training set:
- This document does not specify a separate training set size. For IVD reagents, the development process might involve numerous internal studies to optimize the reagent formulation and assay parameters. However, the 510(k) submission focuses on the validation of the final commercialized product, which is represented by the "test set" samples (80 for method comparison, 80 for imprecision). The concept of a distinct "training set" and "test set" as in machine learning is not typically used or reported in this manner for traditional IVD assays.
How the ground truth for the training set was established:
- As a distinct "training set" is not explicitly defined or reported in the context of a machine learning model, this question is not applicable to this 510(k) submission. The development and optimization of the reagent assay itself would be based on established chemistry principles and analytical methods, with the "ground truth" for these internal development efforts likely coming from well-characterized samples and reference methods.

Summary

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K042459

NOV 17 2004

510(k) Summary SYNCHRON LX® Systems Hemoglobin A1c2 (HbA1c2) Reagent

1.0 Submitted By:

Kim Walker Regulatory Affairs Manager Beckman Coulter, Inc. 200 S. Kraemer Blvd., W-104 Brea, California 92822-8000 Telephone: (714) 961-4912 FAX: (714) 961-4123

2.0 Date Submitted:

September 8, 2004

3.0 Device Name(s):

3.1 Proprietary Names

SYNCHRON LX® Systems Hemoglobin A1c2 (HbA1c2) Reagent

3.2 Classification Name

Glycosylated hemoglobin assay (21 CFR § 864.7470)

4.0 Predicate Device:

Candidate	Predicate	Manufacturer	DocketNumber
SYNCHRON LXSystemsHbA1c2 Reagent	SYNCHRONSystemsHbA1c Reagent	BeckmanCoulter, Inc.	K010748

5.0 Description:

The SYNCHRON LX® System(s) HbA1c2 reagent is designed for optimal performance on the SYNCHRON LX® System(s). The reagent kit contains two A1c2 80-test cartridges, one Hb2 160-test cartridge and one

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2 mL bottle each of Hb/A1c2 Calibrator Level 2, A1c2 Calibrator Levels 3, 4 and 5.

6.0 Intended Use:

7.0 Comparison to Predicate(s):

The following tables show similarities and differences between the predicate identified in Section 4.0 of this summary.

Reagent	Aspect/Characteristic	Comments
HbA1c2	Intended Use	Same as Beckman
Reagent	Liquid Stable Reagent	SYNCHRON HbA1cReagent
	Analytical Range
	Sample Type
	Reference Intervals
	Shelf Life Stability
	Anticoagulants Used
	Storage Temperature (+2°C to +8°C)
	Interferences
	Specificity
	Sensitivity
	Sample Size
	Methodology
	Formulation
	Calibration

Similarities to the Predicate

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Reagent	Aspect/Characteristic	Comments
HbA1c2Reagent	Sample Preparation	HbA1c2 does not require any samplepreparation whereas HbA1c requires manual(off-line) sample preparation; the systemautomatically prepares the sample (on-line).However, HbA1c2 can be prepared off-line aswell.
	Limitations	Additional limitations have been added to theHBA1c2 assay that relate to ErythrocyteSedimentation Rate and proper mixing of wholeblood.
	ReactiveIngredients	HbA1c2 contains Hemolyzing Reagent in thereagent cartridge itself whereas HbA1c reagentrequired a customer to hemolyze a sample off-line with separately purchased HemolyzingReagent.

Differences From The Predicate

8.0 Summary of Performance Data:

The data in the Premarket Notification on safety and effectiveness supports a finding of substantial equivalence to chemistry test systems already in commercial distribution. Equivalence is demonstrated through method comparison, stability, linearity, and imprecision experiments.

Method Comparison Study Results

Instrument	Slope	Intercept	r	n	Comparison Method
SYNCHRON LX	0.911	0.46	0.991	80	SYNCHRON HbA1c
SYNCHRON LX	1.042	-0.56	0.994	80	Tosoh A1c

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Sample	Mean(%)	S.D.(%)	%C.V.	N
Within-Run Imprecision
Normal	5.5	0.07	1.2	80
Abnormal	9.8	0.09	1.0	80
Total Imprecision
Normal	5.5	0.14	2.6	80
Abnormal	9.8	0.27	2.8	80

SYNCHRON LX System HbA1c2 Reagent Imprecision Results

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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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image is a circular seal with the logo of the U.S. Department of Health and Human Services. The seal features the department's emblem, which is a stylized caduceus with three snakes intertwined around a staff. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged around the upper half of the circle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV 1 7 2004

Ms. Kim Walker Regulatory Affairs Manager Beckman Coulter, Inc. 200 S. Kraemer Boulevard P.O. Box 8000 Brea, CA 92822-8000

Re: K042459

Trade/Device Name: SYNCHRON LX® Systems Hemoglobin A1c2 (HbA1c2) Reagent Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: LCP Dated: September 8, 2004 Received: September 10, 2004

Dear Ms. Walker:

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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act 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/cdrh/dsma/dsmamain.html.

Sincerely yours,

Sincerely, yours,

Cornelia B. Parks

Cornelia B. Rooks, MA Acting Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K042459

SYNCHRON LX® Systems Hemoglobin A1c2 (HbA1c2) Device Name: Reagent

Indications for Use:

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Division Sign-Off

Page 1 of ﻠﺴ

Office of In Vitro Diagnostic Device Evaluation and Safety

510k K042459

Beckman Coulter, Inc., Section 510(k) Notification SYNCHRON LX® Systems Hemoglobin A1c2 (HbA1c2) Reagent K042459 Revised Indications for Use, September 2004

Regulation Number and Section

§ 864.7470 Glycosylated hemoglobin assay.

(a)
Identification. A glycosylated hemoglobin assay is a device used to measure the glycosylated hemoglobins (A1a , A1b , and A1c ) in a patient's blood by a column chromatographic procedure. Measurement of glycosylated hemoglobin is used to assess the level of control of a patient's diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient.(b)
Classification. Class II (performance standards).