The Hemoglobin A1c- reagent, when used in coniunction with UniCel® DxC 600/800 SYNCHRON® Systems, UniCel® DxC SYNCHRON® Systems HbA1c-Calibrators and SYNCHRON® and AU® Systems Hemolyzing Reagent, is intended for the quantitative determination of hemoglobin A1c concentration in human whole blood.

Measurement of hemoglobin A1c measures long-term alvcemic control in patients with diabetes mellitus.

Device Description

The UniCel DxC SYNCHRON Systems Hemoglobin A1c- (HbA1c-) Reagent is intended for the quantitative determination of hemoglobin A1c concentration in human whole blood. The UniCel DxC Systems utilize two unique cartridges, Hband A1c-, to determine hemoglobin A1c concentration as a ratio of total hemoqlobin.

Hb- reagent is used to measure total hemoglobin concentration by a colorimetric method. The system automatically proportions the appropriate sample and reagent volumes into the cuvette. The ratio used is one part sample to 8.6 parts reagent. The system monitors the change in absorbance at 410 nanometers. This change in absorbance is directly proportional to the concentration of total hemoglobin in the sample and is used by the system to calculate and express total hemoglobin concentration.

A1c- reagent is used to measure the hemoglobin A1c concentration by a turbidimetric immunoinhibition method. In the reaction, hemoglobin A1c antibodies combine with hemoglobin A1c from the sample to form soluble antigen-antibody complexes. Polyhaptens from the reagent then bind with the excess antibodies and the resulting agglutinated complex is measured turbidimetrically. The system automatically proportions the appropriate sample and reagent volumes into the cuvette. The ratio used is one part sample to 28 parts reagent. The system monitors the change in absorbance at 340 nanometers. This change in absorbance is inversely proportional to the concentration of hemoglobin A1c in the sample and is used by the systems to calculate and express hemoglobin A1c concentration as a ratio of total hemoglobin.

AI/ML Overview

This 510(k) premarket notification describes the UniCel DxC SYNCHRON Systems Hemoglobin A1c- (HbA1c-) Reagent, which is intended for the quantitative determination of hemoglobin A1c concentration in human whole blood. The submission compares the modified device to a predicate device and presents performance study results to demonstrate substantial equivalence.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

Area of Study	Test Protocols	Acceptance Criteria	Reported Device Performance (Pass/Fail)
Method Comparison	CLSI EP9A	Slope 1.0 ± 0.05, Intercept < ± 0.50, R ≥ 0.97	Pass
Analytic Sensitivity	CLSI EP17A	Total Hemoglobin (Hb-): LoD ≤ 6 g/dL (3.72 mmol/L) Hemoglobin A1c (A1c-): LoD ≤ 0.3 g/dL (0.19 mmol/L)	Pass
Linearity	CLSI EP6A	Recovery mean: - within ±6% bias for Hb- - within ±6% bias %HbA1c- - within ±6% bias A1c- ≥0.4 g/dL - within ±15% bias for A1c- < 0.4 g/dL	Pass
Precision	CLSI EP5A2	Within-run: - < 0.4 g/dL A1c-: HbA1c %CV ≤ 5.0 %CV - ≥ 0.4 g/dL A1c-: HbA1c %CV ≤4.0%CV Total: - ≥ 0.4 g/dL A1c-: HbA1c %CV ≤7.5%CV - < 0.4 g/dL A1c-: HbA1c %CV ≤4.0 %CV	Pass
Reference Interval	CLSI C28-A3	90% of samples fall within reference range (4 - 6 %HbA1c NGSP)	Pass
Interferences	CLSI EP7-A2	No Significant Interference (within ± 6% mathematical)	Pass
Specificity	CLSI EP7-A2	Recovery within ±10% mathematical	Pass
Anticoagulants	Development procedures	Slope 1.0 ± 0.05, Intercept < ± 0.75, r ≥ 0.97	Pass
Stability	Development procedures	Recovery of test samples is within ± 6%	Pass

2. Sample Size Used for the Test Set and Data Provenance

The document does not explicitly state the specific sample sizes used for each individual test (e.g., Method Comparison, Linearity, Precision). It references CLSI (Clinical and Laboratory Standards Institute) protocols, which typically outline recommended sample sizes. However, the exact numbers used in this specific study are not provided.

The data provenance is not explicitly mentioned (e.g., country of origin). The studies appear to be part of the development and verification process for a commercial medical device, likely conducted internally or with contracted labs. The document does not specify if the data is retrospective or prospective, but given the context of design verification and validation, it is highly likely to be prospective data generated during the development process.

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

This information is not applicable to this type of device and study. The UniCel DxC SYNCHRON Systems Hemoglobin A1c- (HbA1c-) Reagent is an in-vitro diagnostic device that quantitatively measures a biomarker (HbA1c) in whole blood. The "ground truth" for such devices is established through analytical methods and reference standards, not through expert consensus or interpretation of images/cases.

4. Adjudication Method for the Test Set

Not applicable. As described above, this is an analytical device, and ground truth is not established through expert adjudication of cases.

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

Not applicable. This is an in-vitro diagnostic device, not an AI-assisted diagnostic tool that involves human readers interpreting cases.

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

This refers to the performance of the device's analytical system as a standalone unit, which is the primary focus of all the listed performance studies. The studies assess the accuracy, precision, linearity, sensitivity, etc., of the reagent and instrument system in determining HbA1c concentration. Therefore, all the listed studies can be considered "standalone" in the sense that they evaluate the device's technical performance without human intervention in the HbA1c measurement process itself beyond standard laboratory procedures.

7. The Type of Ground Truth Used

The ground truth for this device is based on analytical reference methods and established standards. For example:

Method Comparison: Likely compares the new device's results against a previously validated or reference method (the predicate device in this case, or IFCC reference method for calibrator traceability).
Analytic Sensitivity, Linearity, Precision: Ground truth is derived from known concentrations of analytes, reference materials, and statistical methods to assess the device's ability to accurately and consistently measure those concentrations.
Calibrator Traceability: Explicitly states "maintaining traceability to IFCC reference method." This indicates that the ground truth for calibration is linked to internationally recognized reference standards for HbA1c.

8. The Sample Size for the Training Set

The document submitted is a 510(k) summary for a reagent, not a machine learning or AI model. Therefore, there is no "training set" in the context of data used to train an algorithm. The development of the reagent and its associated instrument parameters would involve extensive testing and optimization, but this is a different concept than a machine learning training set.

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

Not applicable, as there is no "training set" for an AI algorithm in this context. The "ground truth" for the development and optimization of the reagent and system (analogous to how a training set might inform an algorithm) would be established through established chemical and biochemical principles, analytical testing, and comparison to reference measurement procedures and materials, as described in point 7.

Summary

{0}------------------------------------------------

K121492

SEP 1 1 2012

510(k) SUMMARY

1.0 Submitted By:

Annette Hellie Staff Regulatory Affairs Specialist Beckman Coulter, Inc. 250 S. Kraemer Blvd., A2.SW.09 Brea. California 92821 Telephone: (714) 961-4517

2.0 Date Submitted:

September 7, 2012

3.0 Device Name(s):

3.1 Proprietary Names

UniCel® DxC SYNCHRON® Systems Hemoglobin A1c- (HbA1c-) Reagent

3.2 Classification Name

Glycosylated hemoglobin assay 21 CFR § 864.7470 [LCP] Calibrator for Hemoglobin or hematocrit measurement 21 CFR § 864.8165 IKRZI

4.0 Predicate Device:

Candidate(s)	Predicate	Manufacturer	DocketNumber
UniCel DxCHemoglobin A1c(HbA1c-) Reagent	SYNCHRON SystemsHemoglobin A1c(HbA1c) Reagent	BeckmanCoulter, Inc	K010748

5.0 Description:

{1}------------------------------------------------

reagent. The system monitors the change in absorbance at 410 nanometers. This change in absorbance is directly proportional to the concentration of total hemoglobin in the sample and is used by the system to calculate and express total hemoglobin concentration.

6.0 Indications for Use:

Measurement of hemoglobin A1c measures long-term alvcemic control in patients with diabetes mellitus.

{2}------------------------------------------------

7.0 Comparison to Predicate(s):

The following table shows similarities and differences between the predicate identified in Section 4.0 of this summary. Each modification was evaluated against the criteria for a Special 510(k) to insure that the particular change does not: (1) affect the intended use or (2) alter the fundamental scientific technology of the device.

Similarities
DxC HbA1c-Reagent	Intended Use (clarification added)
	Reagent components
	• Antibody Reagent
	• Polyhapten Reagent
	• Hemoglobin Reagent
	Calibrator formulation
	Calibrator traceability
	Acceptable Anticoagulants
	Specimen Stability
	Analytical Range
	Technology
	Methodology
	Kit configuration
Differences
DxC HbA1c-Reagent	Reagent and processoptimization	The formulation and manufacturing process wereimproved. The reagent to sample ratio was refined.
	%HbA1c (NGSP)analytic range	Accepted calculated range reduced from 2 - 20% to4 – 17%
	Sensitivity	Changed format to report out as LOD and LOB
	Reporting units	IFCC /IUPAC committee updated theirrecommendations on HbA1c units andnomenclature in 2007. HbA1c- is reported inNGSP% units and mmol/mol IFCC units.
	Stability	Claims have been updated
	Cal level 1	Changed from zero to non-zero level

8.0 Summary of Changes, Risk Analysis, Design Verification and Design Validation activities:

The UniCel DxC SYNCHRON Systems Hemoglobin A1c- reagent formulation and manufacturing process have been enhanced by the OEM manufacturer. The reagent to sample ratio and other DxC instrument parameters has been refined. The Calibrator level 1 was changed to a non-zero concentration utilizing the same matrix and manufacturing process as levels 2-5. Calibrator value-assignment process has been updated while maintaining traceability to IFCC reference method. New specifications and data were generated in support of these changes.

{3}------------------------------------------------

Risk Management Process for HbA1c-

. A Risk Management Plan was created to describe the various risk assessments required for the device modification and its components.
A design risk assessment (Failure Modes & Effects Analysis or FMEA) was . developed to identify potential risks on instrument parameter optimization. calibrator value assignment and system interaction associated with the device modification.
A process FMEA was developed to identify potential risks related to . manufacturing processes.
. A risk assessment on two software tolls for internal data analysis was developed to identify potential risks on the software's intended use.
. All risk assessments require that testing and reports (design verification, design validation and process validation) are complete before potential risks are mitigated.
. All safety-related risks (those that could potentially affect patient, bystander such as instrument operator, manufacturing personnel and field service engineer) from the various risk assessments are required to be transferred to a System Risk Assessment (SRA).
A Comprehensive Risk Management Review meeting is required before a Risk . Management Report is written.

Area of Study	Test Protocols	Acceptance Criteria	Pass/Fail
MethodComparison	CLSI EP9A	Slope 1.0 ± 0.05Intercept < ± 0.50R ≥ 0.97	Pass
AnalyticSensitivity	CLSI EP17A	Total Hemoglobin (Hb-)LoD ≤ 6 g/dL (3.72 mmol/L)Hemoglobin A1c (A1c-)LoD ≤ 0.3 g/dL (0.19 mmol/L)	Pass
Linearity	CLSI EP6A	Recovery mean within (target)±6% bias for Hb-±6% bias %HbA1c-±6% bias A1c- ≥0.4 g/dL±15% bias for A1c- < 0.4 g/dL	Pass
Precision	CLSI EP5A2	Within-run< 0.4 g/dL A1c-HbA1c %CV ≤ 5.0 %CV≥ 0.4 g/dL A1c-HbA1c %CV ≤4.0%CVTotal	Pass

Summary of Performance Studies

{4}------------------------------------------------

Area of Study	Test Protocols	Acceptance Criteria	Pass/Fail
		≥ 0.4 g/dL A1c-HbA1c %CV ≤7.5%CV
		< 0.4 g/dL A1c-HbA1c %CV ≤4.0 %CV
ReferenceInterval	CLSI C28-A3	90% of samples fall withinreference range (4 - 6 %HbA1cNGSP)	Pass
Interferences	CLSI EP7-A2	No Significant Interference (within ±6% mathematical)	Pass
Specificity	CLSI EP7-A2	Recovery within ±10%mathematical	Pass
Anticoagulants	Developmentprocedures	Slope 1.0 ± 0.05Intercept <± 0.75r ≥ 0.97	Pass
Stability	Developmentprocedures	Recovery of test samples is within ±6%	Pass

Conclusion:

The UniCel DxC Systems Hemoglobin A1c- (HbA1c-) reagent is substantially equivalent to the predicate device, SYNCHRON Systems Hemoglobin A1c (HbA1c) reagent (K010748) for the quantitative determination of hemoglobin A1c concentration in human whole blood.

This 510(k) summary is being submitted in accordance with the requirements of the Safe Medical Device Act of 1990 and the implementing regulation 21 CFR 807.92.

{5}------------------------------------------------

Image /page/5/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features a circular design with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter. Inside the circle is a stylized image of a caduceus, a symbol often associated with medicine and healthcare.

10903 New Hampshire Avenue Silver Spring, MD 20993

Beckman Coulter, Inc. c/o Annette Hellie 250 S. Kraemer Boulevard M/S A2.SW.09 Brea, CA 92821

SEP 1 1 2012

K121492 Re:

Trade Name: UniCel DxC Synchron® Systems Hemoglobin A1c (HbAlc-) Reagent Regulation Number: 21 CFR §864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Codes: LCP, KRZ Dated: August 14, 2012 Received: August 15, 2012

Dear Ms. Hellie:

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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

{6}------------------------------------------------

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please If you desire specific at Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, comacs the office of in Viaco Diage: Misbranding by reference to premarket notification" (21 prease note the regalation enames regarding postmarket surveillance, please contact CDRH3 Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) Onlice of Survillano and Diomours of (on of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/Medical

Devices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance ...

You may obtain other general information on your responsibilities under the Act from the Tou may other belief general meethanal and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm

Sincerely yours,

N. H. Liu, Ph.D.

Couriney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

{7}------------------------------------------------

510(k) Number (if known): K121492

Device Name: UniCel DxC SYNCHRON® Systems Hemoglobin A1c- Reagent

Indications for Use:

The Hemoglobin A1c- reagent, when used in conjunction with UniCel® DxC 600/800 SYNCHRON® Systems, UniCel® DxC SYNCHRON® Systems HbA1c- Calibrators and SYNCHRON® and AU® Systems Hemolyzing Reagent, is intended for the quantitative determination of hemoglobin A1c concentration in human whole blood.

Measurement of hemoglobin A1c measures long-term glycemic control in patients with diabetes mellitus.

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)

Rallw Luno

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K121492

Page 1 of _

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).