UNICEL DXC SYNCHRON SYSTEMS HEMOGLOBIN ALC-(HBA1C-) REAGENT

K121492 · Beckman Coulter, Inc. · LCP · Sep 11, 2012 · Hematology

Device Facts

• Record ID: K121492
• Device Name: UNICEL DXC SYNCHRON SYSTEMS HEMOGLOBIN ALC-(HBA1C-) REAGENT
• Applicant: Beckman Coulter, Inc.
• Product Code: LCP · Hematology
• Decision Date: Sep 11, 2012
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 864.7470
• Device Class: Class 2

Intended 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.

Device Story

The UniCel DxC SYNCHRON Systems HbA1c- Reagent is an in vitro diagnostic assay for clinical laboratory use. It processes human whole blood samples to measure hemoglobin A1c concentration as a ratio of total hemoglobin. The system uses two distinct reagents: an Hb- reagent for total hemoglobin via colorimetric measurement (absorbance at 410 nm) and an A1c- reagent for HbA1c via turbidimetric immunoinhibition (absorbance at 340 nm). In the A1c- reaction, HbA1c antibodies bind to sample HbA1c; polyhaptens then bind excess antibodies, creating agglutinated complexes measured turbidimetrically. The system automatically proportions samples and reagents into cuvettes. Results are calculated by the system and expressed as a ratio, providing clinicians with a quantitative metric for long-term glycemic control in diabetic patients.

Clinical Evidence

Bench testing only. Verification and validation activities were performed based on risk analysis to confirm that the modified reagent system met predetermined acceptance criteria. No clinical trial data was required or presented for this reagent modification.

Technological Characteristics

In vitro diagnostic reagent system for HbA1c quantification. Modifications include reagent re-formulation (buffer changes), adjusted reagent/sample volumes, and updated stability specifications. Measuring range: 4 to 17%. Reporting units: NGSP% and IFCC mmol/mol. Calibrator level 1 adjusted to non-zero concentration. System operates via established laboratory instrumentation (Synchron® Systems).

Indications for Use

Indicated for the quantitative determination of hemoglobin A1c in human whole blood to measure long-term glycemic control in patients with diabetes mellitus.

Regulatory Classification

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.

Predicate Devices

• Synchron® Systems Hemoglobin A1c Reagent (k010748)

Submission Summary (Full Text)

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# 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: [phone]

#### 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 | Docket<br>Number |
|--------------------------------------------------|-------------------------------------------------------|-------------------------|------------------|
| UniCel DxC<br>Hemoglobin A1c<br>(HbA1c-) Reagent | SYNCHRON Systems<br>Hemoglobin A1c<br>(HbA1c) Reagent | Beckman<br>Coulter, Inc | K010748 |

#### 5.0 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

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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.

#### 6.0 Indications for Use:

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.

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#### 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-<br>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-<br>Reagent | Reagent and process<br>optimization | The formulation and manufacturing process were<br>improved. The reagent to sample ratio was refined. |
| | %HbA1c (NGSP)<br>analytic range | Accepted calculated range reduced from 2 - 20% to<br>4 – 17% |
| | Sensitivity | Changed format to report out as LOD and LOB |
| | Reporting units | IFCC /IUPAC committee updated their<br>recommendations on HbA1c units and<br>nomenclature in 2007. HbA1c- is reported in<br>NGSP% 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.

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## 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 |
|-------------------------|----------------|-----------------------------------------------------------------------------------------------------------------------------------|-----------|
| Method<br>Comparison | CLSI EP9A | Slope 1.0 ± 0.05<br>Intercept < ± 0.50<br>R ≥ 0.97 | Pass |
| Analytic<br>Sensitivity | CLSI EP17A | Total Hemoglobin (Hb-)<br>LoD ≤ 6 g/dL (3.72 mmol/L)<br>Hemoglobin A1c (A1c-)<br>LoD ≤ 0.3 g/dL (0.19 mmol/L) | Pass |
| Linearity | CLSI EP6A | Recovery mean within (target)<br>±6% bias for Hb-<br>±6% bias %HbA1c-<br>±6% bias A1c- ≥0.4 g/dL<br>±15% bias for A1c- < 0.4 g/dL | Pass |
| Precision | CLSI EP5A2 | Within-run<br>< 0.4 g/dL A1c-<br>HbA1c %CV ≤ 5.0 %CV<br>≥ 0.4 g/dL A1c-<br>HbA1c %CV ≤4.0%CV<br>Total | Pass |

# Summary of Performance Studies

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

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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).

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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 [phone]. 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 [phone] or [phone] 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

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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

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