TINA-QUANT HBA1C GEN.2

K110313 · Roche Diagnostics · LCP · Dec 23, 2011 · Hematology

Device Facts

• Record ID: K110313
• Device Name: TINA-QUANT HBA1C GEN.2
• Applicant: Roche Diagnostics
• Product Code: LCP · Hematology
• Decision Date: Dec 23, 2011
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 864.7470
• Device Class: Class 2

Indications for Use

The Tina-Quant hemoglobin A1c Gen.2 assay is an in vitro diagnostic reagent system intended for quantitative determination of mmol/mol hemoglobin A1c (IFCC) and % hemoglobin A1c (DCCT/NGSP) in hemolysate or whole blood on Roche clinical chemistry analyzers. HbA1c determinations are useful for monitoring of long-term blood glucose control in individuals with diabetes mellitus.

Device Story

The Tina-quant HbA1c Gen.2 assay is an in vitro diagnostic reagent system used on Roche clinical chemistry analyzers to measure HbA1c levels in anticoagulated whole blood or hemolysate. The system utilizes a turbidimetric inhibition immunoassay (TINIA); antigen-antibody complexes form, and excess antibody aggregates with polyhapten to create insoluble complexes. Hemoglobin is measured bichromatically after conversion to a colored derivative. The instrument calculates the % HbA1c from the HbA1c/Hb ratio. The assay is intended for use by healthcare professionals in clinical settings to monitor long-term blood glucose control in diabetic patients. Results assist clinicians in assessing glycemic management.

Clinical Evidence

Bench testing only. Precision studies (n=90 low, n=25 medium, n=19 high) compared candidate anticoagulants against K2-EDTA predicate, showing comparable SD and CV. Matrix comparison (n=132) using Passing/Bablock regression confirmed equivalence across anticoagulants. Method comparison between whole blood and hemolysate applications showed high correlation (r > 0.99). LoB (2.3%) and LoD (2.5%) established per CLSI EP17-A.

Technological Characteristics

Turbidimetric inhibition immunoassay (TINIA) for HbA1c; bichromatic photometry for total hemoglobin. Uses sheep-derived polyclonal anti-HbA1c antibodies. Compatible with Roche Integra 400/400 plus and 800/800 CTS analyzers. Calibration via Logit/log 5 mode. Reagent stability: 2-8°C unopened; 10-15°C (Integra 400) or 8°C (Integra 800) on-board.

Indications for Use

Indicated for monitoring long-term blood glucose control in individuals with diabetes mellitus. Used for quantitative determination of HbA1c in hemolysate or whole blood samples.

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

• Tina-quant Hemoglobin A1c Gen.2 (K072714)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY ONLY TEMPLATE

A. 510(k) Number:
k110313

B. Purpose for Submission:
Addition of three additional anticoagulants (Na-heparin, NaF/K-Oxalate, and NaF/Na₂-EDTA) for use with a previously cleared device (k072714) and replacement of Lower Detection Limit (LDL) claims with Limit of Blank (LOB) and Limit of Detection (LOD) claim.

C. Measurand:
Glycosylated Hemoglobin (HgbA1C)

D. Type of Test:
Quantitative turbidimetric inhibition immunoassay

E. Applicant:
Roche Diagnostics Corporation

F. Proprietary and Established Names:
Tina-quant Hemoglobin A1c Gen.2 assay

G. Regulatory Information:
| Product Code | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| LCP | Class II | 21 CFR 864.7470 | Chemistry 75 |

H. Intended Use:
1. Intended use(s):
See indications for use below.
2. Indication(s) for use:

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The Tina-Quant hemoglobin A1c Gen.2 assay is an in vitro diagnostic reagent system intended for quantitative determination of mmol/mol hemoglobin A1c (IFCC) and % hemoglobin A1c (DCCT/NGSP) in hemolysate or whole blood on Roche clinical chemistry analyzers. HbA1c determinations are useful for monitoring of long-term blood glucose control in individuals with diabetes mellitus.

3. Special conditions for use statement(s):

Prescription use only.

There are two application methods: Whole Blood and Hemolysate. Hemolysate should be prepared and stored for analysis if whole blood cannot be analyzed within 8 hours of collection.

4. Special instrument requirements:

Performance was evaluated on the Roche Integra 800 Analyzer

I. Device Description:

The Roche Tina-quant Hemoglobin A1c Gen. 2 consists of two working reagents (R1 and R2) and an Hemolyzing reagent. The R1 reagent consists of antibody reagent, MES buffer: 0.025 mol/L; TRIS buffer: 0.015 mol/L, ph6.2; HbA1c antibody (bovine serum): ≥0.5 mg/ml; stabilizers; preservatives (liquid). R2 reagent (Polyhapten reagent) consists of MES buffer: 0.025 mol/L; TRIS buffer: 0.015 mol/L, ph 6.2, HbA1c polyhapton: ≥8 μg/mL; stabilizers; preservatives (liquid)

The Roche Tina-quant Hemoglobin A1c Gen. 2 consists of two application types: The Whole Blood application uses an automated on-board sample pretreatment with hemolyzing reagent. The Hemolysate application consists of a manual pretreatment step which is performed using the hemolyzing reagent before the sample is placed on the analyzer.

J. Substantial Equivalence Information:

1. Predicate Device name(s):

Roche Tina-quant Hemoglobin A1c Gen.2 test system

2. Predicate 510(k) number(s)

k072714

3. Comparison with predicate

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| Similarities and Differences | | |
| --- | --- | --- |
| Item | Candidate Device (k110313) | Predicate Device (k072714) |
| Intended Use | In vitro test for the quantitative determination of hemoglobin A1c in hemolysate and whole blood on Roche clinical chemistry analyzers. | Same |
| Sample Types | Li-Heparin, K2-EDTA, K3-EDTA, KF/Na_{2}-EDTA, Na-Heparin, NaF/K-Oxalate, NaF/Na_{2}-EDTA | Li-heparin, K2-EDTA, K3-EDTA, KF/Na_{2}-EDTA |
| Calibrator | Cfas HbA1c | Same |
| Instrument Platform | Roche Integra analyzers | Same |
| Calibration Mode | Logit/log 5 | Same |
| Controls | HbA1c Control N or PreciControl HbA1c norm; HbA1C Control P or PreciControl HbA1c path | Same |
| Measuring Range | Integra 400/400 plus Hb: 4-35 g/dL HbA1c: 4.3-19.5% Integra 800 Hb: 4-35 g/dL HbA1c: 4.3-24.8% | Same |
| Antibody | Polyclonal anti-HbA1c from sheep blood | Same |

K. Standard/Guidance Document Referenced (if applicable):

CLSI EP17-A, Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline

L. Test Principle:

Anticoagulated whole blood is hemolyzed prior to determination of HbA1c by a turbidimetric inhibition immunoassay (TINIA). Liberated hemoglobin (Hb) in the hemolyzed sample is converted to a derivative having a characteristic absorption spectrum and measured biochromatically. The instrument calculates the $\% \mathrm{HbA1c}$ from the $\mathrm{HbA1c / Hb}$ ratio according to a user selected protocol.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

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This tube type precision study was performed along with the matrix comparison study on the Roche Integra 800 analyzer with $\mathrm{K}_2$ -EDTA, Na-heparin, NaF/K-Oxalate, and NaF/Na $_2$ -EDTA. K2-EDTA was used as the reference anticoagulant since it was originally cleared in k072714. Duplicate samples from the matrix studies were calculated for average SD for 3 partitioned bins covering the ranges tested. The average SD and CV in each of the 3 bins for all tube types evaluated were summarized in the table below.

Precision Comparison with Full Tubes

| K2-EDTA (predicate) | n | Mean (% A1c) | SD | %CV |
| --- | --- | --- | --- | --- |
| Low Level | 90 | 5.64 | 0.35 | 6.2 |
| Medium Level | 25 | 9.42 | 0.43 | 4.5 |
| High Level | 19 | 13.81 | 0.71 | 5.1 |
| Na-Heparin (candidate) | n | Mean (% A1c) | SD | %CV |
| Low Level | 90 | 5.64 | 0.35 | 6.2 |
| Medium Level | 25 | 9.40 | 0.39 | 4.2 |
| High Level | 19 | 13.80 | 0.77 | 5.6 |
| NaF/K-Oxalate (candidate) | n | Mean (% A1c) | SD | %CV |
| Low Level | 90 | 5.65 | 0.35 | 6.2 |
| Medium Level | 25 | 9.44 | 0.42 | 4.5 |
| High Level | 19 | 13.80 | 0.70 | 5.1 |
| NaF/Na2-EDTA (candidate) | n | Mean (% A1c) | SD | %CV |
| Low Level | 90 | 5.64 | 0.35 | 6.1 |
| Medium Level | 25 | 9.44 | 0.41 | 4.3 |
| High Level | 19 | 13.79 | 0.74 | 5.4 |

Precision Comparison with Half Full Tubes

| K2-EDTA (predicate) | n | Mean (% A1c) | SD | %CV |
| --- | --- | --- | --- | --- |
| Low Level | 90 | 5.65 | 0.34 | 6.0 |
| Medium Level | 25 | 9.42 | 0.43 | 4.5 |
| High Level | 19 | 13.77 | 0.69 | 5.0 |
| Na-Heparin (candidate) | n | Mean (% A1c) | SD | %CV |
| Low Level | 90 | 5.66 | 0.35 | 6.1 |
| Medium Level | 25 | 9.39 | 0.42 | 4.5 |
| High Level | 19 | 13.77 | 0.71 | 5.2 |
| NaF/K-Oxalate (candidate) | n | Mean (% A1c) | SD | %CV |
| Low Level | 90 | 5.68 | 0.35 | 6.2 |
| Medium Level | 25 | 9.42 | 0.42 | 4.5 |
| High Level | 19 | 13.83 | 0.71 | 5.1 |
| NaF/Na2-EDTA (candidate) | n | Mean (% A1c) | SD | %CV |
| Low Level | 89 | 5.66 | 5.44 | 6.1 |
| Medium Level | 25 | 9.44 | 0.41 | 4.3 |
| High Level | 19 | 13.83 | 0.71 | 5.1 |

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| Medium Level | 25 | 9.44 | 0.40 | 4.3 |
| --- | --- | --- | --- | --- |
| High Level | 19 | 13.77 | 0.73 | 5.3 |

b. Linearity/assay reportable range:

Previously established in k072714

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

Previously established in k072714

Stability studies were conducted using all three candidate anticoagulants, Na-heparin, NaF/K-Oxalate, and NaF/Na₂-EDTA using the hemolysate and whole blood applications. The hemolysate is stable for 4 hours at 15-25°C, 24 hours at 2-8°C and 6 months at (-15) – (-25) °C when using Na-heparin, NaF/K-Oxalate, and NaF/Na₂-EDTA. Whole Blood samples should be analyzed within 8 hours of collection. The labeling indicates hemolysate should be prepared and stored for analysis if whole blood cannot be analyzed within 8 hours of collection. Frozen stability of HbA1c has not been determined for samples treated with anticoagulants Na-heparin, NaF/K-Oxalate, and NaF/Na₂-EDTA.

d. Detection limit:

The Limit of Blank (LoB) and Limit of Detection (LoD) were determined by assaying an analyte free sample (blank) and five low HbA1c samples according to CLSI guideline EP17A. Each sample was assayed twice a day for three days on two Roche Integra 800 Analyzers. The detection limits are summarized in the table below.

| Platform/Method | LoB (%A1c) | LoD (%A1c) |
| --- | --- | --- |
| Roche Integra 800 analyzer | 2.3% | 2.5% |

The assay has a reportable range of 4.3-24.8% on the Roche Integra 800 analyzer.

e. Analytical specificity:

Previously established in k072714

Interference studies for Na-heparin, NaF/K-Oxalate, and NaF/Na₂-EDTA were not performed. See previously cleared interference data in k072714.

f. Assay cut-off:

Not applicable.

2. Comparison studies:

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a. Method comparison with predicate device:

Previously established in k072714

b. Matrix comparison:

A matrix comparison study was performed using Na-heparin, NaF/K-Oxalate, and $\mathrm{NaF / Na_2}$ -EDTA. K2-EDTA was used as the reference anticoagulant. 132 total samples were analyzed for HbA1c. Each single set of samples were analyzed on the Roche Integra 800 analyzer and values obtained. Samples ranged from $4.97 - 15.97\%$ HbA1c. The results using Passing/Bablock linear regression analysis are as follows:

| Full Tubes | | |
| --- | --- | --- |
| Na-Heparin | NaF/K-Oxalate | NaF/Na2-EDTA |
| y=1.004x-0.026 | y=1.005x-0.010 | y=1.001x-0.011 |
| Half-Full Tubes | | |
| --- | --- | --- |
| Na-Heparin | NaF/K-Oxalate | NaF/Na2-EDTA |
| y=0.998x+0.006 | y=0.994x +0.051 | y=1.010x-0.057 |

An additional comparison study was performed to evaluate the two application methods (whole blood versus hemolysate). 30 whole blood samples were collected in Na-Heparin, NaF/K-Oxalate, and NaF/ $\mathrm{Na}_2$ -EDTA. Each whole blood sample was hemolyzed manually per labeling instructions and then placed on the Integra analyzer for the automated hemolysate application. The results using simple regression analysis are as follows:

Hemolysate Application vs. Whole Blood Application

| | Slope | Intercept | r | Sample range |
| --- | --- | --- | --- | --- |
| Na-Heparin | 1.0091 | 0.0590% | 0.9994 | 5.14 – 13.15% |
| NaF/K-Oxalate | 1.0122 | 0.0457% | 0.9980 | 5.18 – 12.75% |
| and NaF/ Na2-EDTA | 1.0025 | 0.1135% | 0.9994 | 5.17 – 13.0% |

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable.

b. Clinical specificity:

Not applicable.

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c. Other clinical supportive data (when a. and b. are not applicable):

Not applicable.

4. Clinical cut-off:

Not applicable.

5. Expected values/Reference range:

The expected values according to the literature cited are:

Protocol 1 (acc. to IFCC): 29-42 mmol/mol HbA1c*

Protocol 2 (acc. to DCCT/NGSP): 4.8-5.9% HbA1c*

*Junge, W, Wilke B, Halabi A et al. Determination of reference levels in adults for hemoglobin A1c (HbA1c). Poster presentation EUROMEDLAB, Barcelona 2003

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.