(237 days)
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 is intended for in vitro diagnostic use for the quantitative measurement of % hemoglobin A Ic (HbA 1c) (DCCT/NGSP) and mmol/mo hemoglobin A1c (IFCC) in whole blood specimens. This test is to be used as an aid in diagnosis of diabetes and as an aid in identifying patients who may be at risk for developing diabetes.
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 is an automated High Performance Liquid Chromatography (HPLC) system that separates and reports stable A 1c (sA1c) percentage in whole blood. The operational portion of the G8 is composed of a sampling unit, liquid pump, degasser, column, detector, microprocessors, sample loader, floppy disk drive unit, operation panel and a printer. The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 uses non-porous ion- exchange high performance liquid chromatography (HPLC) for rapid, accurate and precise separation of the stable form of HbA Ic from other hemoglobin fractions. The G8 uses a cation exchange column and separates the usual hemoglobin components in the blood into six fractions, A 1a, A 1b, F, LA 1c, sA Ic, and A0. The separation is done by eluting the hemoglobins from the column with a stepwise elution of three elution buffers containing different salt concentrations. The result report includes a sample ID, date, percentage and retention time of each fraction, sA1c percentage and total A1 percentage (A1a + A1b + sA1c), along with a chromatogram of the elution pattern of the hemoglobin fractions. If a sample contains a hemoglobin variant, the column elutes the material depending upon its charge.
Here's a breakdown of the acceptance criteria and the study details for the Tosoh Automated Glycohemoglobin Analyzer HLC-723G8, based on the provided 510(k) summary:
Acceptance Criteria and Device Performance
| Criterion | Acceptance Criteria (Stated or Implied) | Reported Device Performance |
|---|---|---|
| Linearity / Reportable Range | Previously established for 4.0% - 16.9% HbA1c (from predicate device comparison table) | 4.0% - 16.9% HbA1c |
| Interference | Variance greater than assigned value x 1.00 ± 5% for potential interferents. No interference from HbA2, HbS, HbC, HbD. Flag for HbE. | No Significant Interference Observed at Specified Concentrations: |
| Acetylated Hb: 50 mg/dL | ||
| Albumin: 5000 mg/dL | ||
| Aldehyde Hb: 25 mg/dL | ||
| Ascorbic Acid: 25 mg/dL | ||
| Carbamylated Hb: 25 mg/dL | ||
| Bilirubin C: 21 mg/dL | ||
| Labile Hb: 1000 mg/dL | ||
| Lipemia: 1000 mg/dL | ||
| Rheumatoid Factor: 550 IU/mL | ||
| Bilirubin F: 18 mg/dL | ||
| Hemoglobin Variant Interference: | ||
| HbS: No interference (at ~6% and ≥8% HbA1c levels) | ||
| HbC: No interference (at ~6% and ≥8% HbA1c levels) | ||
| HbE: Yes, interference. A flag is displayed, and %HbA1c result is not reported. | ||
| HbD: No interference (at ~6% and ≥8% HbA1c levels) | ||
| HbF: No interference (at ~6% and ≥8% HbA1c levels) | ||
| HbA2: No interference (at ~6% and ≥8% HbA1c levels) | ||
| Precision | Not explicitly stated as a numerical criterion for this device, but predicate device states "equal to or less than 1.5% for concentrations in the range of 5.3% to 12.1% HbA1c" for between-analyzer and between-lot. For this device, "0.7 - 1.8% (total precision) and 0.3 - 0.9% (within run, precision)" is mentioned in the comparison table as the performance of the new device. | Within-run Precision (CV%): Ranges from 0.18% (12% D1) to 1.00% (5% A2). |
| Total Precision (CV%): Ranges from 0.68% (6.5% B1) to 1.83% (5% A1). | ||
| Correlation (Method Comparison) | r ≥ 0.991; Y ≈ 1.0x + 0.0y (implied from predicate, which showed Y = 1.015x + 0.015) | Compared to Primus ultra2: |
| Slope (Deming): 0.996 (0.971 to 1.021) | ||
| Intercept (Deming): 0.073 (-0.110 to 0.255) | ||
| Correlation Coefficient (R): 0.991 | ||
| Bias: 0.047 (0.657%) | ||
| Total Error (TE) | %TE of ≤6% is acceptable. Goal at 6% for (TE)95 (e.g., 0.30 at 5.0% Decision Level, 0.72 at 12.0% Decision Level) | %TE (at 5%, 6.5%, 8%, 12%): 5.8%, 2.8%, 3.0%, 3.1% respectively (for the first method of calculation) |
| (TE)95 (at 5%, 6.5%, 8%, 12%): 0.23, 0.13, 0.20, 0.34 respectively (for the second method of calculation) |
Study Details for the HLC-723G8
The provided document describes the performance characteristics and studies conducted for the Tosoh Automated Glycohemoglobin Analyzer HLC-723G8.
-
Sample size used for the test set and the data provenance:
- Interference Studies:
- Various numbers of samples for each potential interferent, tested at two HbA1c levels (e.g., Acetylated Hb, Albumin, etc., were tested at certain concentrations, some up to 1000 mg/dL to 5000 mg/dL).
- Hemoglobin Variant Interference: 10 samples for each variant (HbS, HbC, HbE, HbD, HbF, HbA2), tested at two HbA1c levels (approximately 6% and ≥8%).
- Data Provenance: Not explicitly stated, but clinical samples are implied as "known concentrations of HbA1c" were spiked. The samples are likely clinical specimens from an unspecified region, retrospectively used for these studies.
- Precision Study: Four concentrations of unaltered EDTA whole blood specimens. Tested with 3 lots and 3 instruments.
- Each specimen/reagent combination had 2 replicates in a single run, 2 times a day for 20 nonconsecutive days, totaling 40 runs and 80 determinants per data set. This implies a large number of measurements, but the exact number of unique patient blood specimens for the "four concentrations" is not specified.
- Data Provenance: Unaltered EDTA whole blood specimens. Likely clinical samples, but country of origin/retrospective/prospective is not specified.
- Correlation (Method Comparison) Study:
- Sample Size: 120 unaltered EDTA whole blood specimens.
- Data Provenance: "Frozen specimens were utilized for this study." Implies retrospective samples, but country of origin is not specified.
- Sample Distribution: The 120 samples covered a range of HbA1c levels:
- ≤ 5%: 5 samples (4.2%)
- 5 – 6%: 15 samples (12.5%)
- 6 – 6.5%: 30 samples (25.0%)
- 6.5 – 7%: 30 samples (25.0%)
- 7 – 8%: 20 samples (16.7%)
- 8 – 9%: 10 samples (8.3%)
-
9%: 10 samples (8.3%)
- Interference Studies:
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- For this in vitro diagnostic device, "ground truth" is established by a reference method/device, not human experts.
- Interference Study: Ground truth was based on "known concentrations of HbA1c" (likely measured by a standardized reference method) and evaluated against a "variance greater than the assigned value x 1.00 ± 5%".
- Hemoglobin Variant Interference Study: Ground truth was established by "reference values" for %HbA1c and IFCC mmol/mol, likely from a reference method.
- Correlation Study: The comparative method was the Primus ultra2, analyzed by a "secondary NGSP reference laboratory." The Primus ultra2 is an established HPLC system for HbA1c. The qualification of individuals operating this reference laboratory is not specified, but its designation as an "NGSP reference laboratory" implies adherence to high standards for HbA1c measurement.
-
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- Not applicable in this context. Adjudication by multiple human experts is typically used for subjective assessments (e.g., image interpretation). For quantitative diagnostic devices, performance is typically assessed against a 'gold standard' reference method.
-
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 automated in vitro diagnostic device, not an AI-assisted human reader system.
-
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, this is a standalone device. The entire submission describes the algorithm-only performance of the Automated Glycohemoglobin Analyzer HLC-723G8. It is designed to quantitatively measure HbA1c without human intervention in the measurement process itself, beyond sample loading and general operation.
-
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The ground truth for performance evaluation was based on reference methods and certified standards.
- For correlation/comparison, the Primus ultra2 (analyzed by an NGSP reference laboratory) served as the comparative method.
- The device's assigned HbA1c values are certified via the National Glycohemoglobin Standardization Program (NGSP) and are traceable to both the International Federation of Clinical Chemistry (IFCC) and the Diabetes Control and Complications Trial (DCCT). This indicates that the ground truth is based on established and internationally recognized standardization programs and reference measurement procedures for HbA1c.
- The ground truth for performance evaluation was based on reference methods and certified standards.
-
The sample size for the training set:
- The document does not explicitly mention a "training set" in the context of machine learning or AI. This is a traditional HPLC system. Its development likely involved internal optimization and validation studies, but these are not described as distinct "training" and "test" sets in the way an AI/ML algorithm would. The linearity of the assay was "previously established" under a prior 510(k) (K071132).
-
How the ground truth for the training set was established:
- As a traditional HPLC system, there isn't a "training set" in the common understanding of AI/ML. The device's calibration and method development would rely on known standards and reference materials, traceable to NGSP/IFCC, to ensure accurate and reproducible measurements. The "ground truth" for developing such a system would involve calibrated reference materials with known HbA1c concentrations.
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K13/570
510(k) Summary
JAN 2 3 2014
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Tosoh Bioscience, Inc.'s Automated Glycohemoglobin Analyzer HLC-723G8
Submitter:
Contact Person:
: : : :
Device Name: Classification Name:
Predicate Device:
Tosoh Bioscience, Inc 3600 Gantz Road Grove City, OH 43123
Robert L. Wick Regulatory Specialist 6000 Shoreline Ct., Ste. 101 South San Francisco, CA 94080 . Phone: 650-636-8117 Fax: 650-636-8121 : . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Email: Robert.Wick@Tosoh.com
Automated Glycohemoglobin Analyzer HLC-723G8 Hemoglobin A1c Test System Class II PDJ 21 CFR 862.1373 : ・・・・・
K121291 Roche Diagnostics Corporation COBAS INTEGRA 800 Tina-quant HbA1cDx Gen.2 assay
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510(k) Summary
Automated Glycohemoglobin Analyzer HLC-723G8
According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence.
Device Description:
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 is an automated High Performance Liquid Chromatography (HPLC) system that separates and reports stable A 1c (sA1c) percentage in whole blood. The operational portion of the G8 is composed of a sampling unit, liquid pump, degasser, column, detector, microprocessors, sample loader, floppy disk drive unit, operation panel and a printer.
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 uses non-porous ion- exchange high performance liquid chromatography (HPLC) for rapid, accurate and precise separation of the stable form of HbA Ic from other hemoglobin fractions. The G8 uses a cation exchange column and separates the usual hemoglobin components in the blood into six fractions, A 1a, A 1b, F, LA 1c, sA Ic, and A0. The separation is done by eluting the hemoglobins from the column with a stepwise elution of three elution buffers containing different salt concentrations. The result report includes a sample ID, date, percentage and retention time of each fraction, sA1c percentage and total A1 percentage (A1a + A1b + sA1c), along with a chromatogram of the elution pattern of the hemoglobin fractions. If a sample contains a hemoglobin variant, the column elutes the material depending upon its charge.
New Device Intended Use:
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 is intended for in vitro diagnostic use for the quantitative measurement of % hemoglobin A Ic (HbA 1c) (DCCT/NGSP) and mmol/mo hemoglobin A1c (IFCC) in whole blood specimens. This test is to be used as an aid in diagnosis of diabetes and as an aid in identifying patients who may be at risk for developing diabetes.
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Substantial Equivalence:
Comparison between the Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 and the COBAS INTEGRA 800 Tina-quant HbA1cDx Gen.2 assay
Similarities
| Parameter | Tosoh AutomatedGlycohemoglobin AnalyzerHLC-723G8 (k)071132(k)131580 | COBAS INTEGRA 800Tina-quantHbA1cDx Gen.2 assay(k)121291 |
|---|---|---|
| Intended Use | The Tosoh AutomatedGlycohemoglobin AnalyzerHLC-723G8 is intended for invitro diagnostic use for themeasurement of hemoglobinA1c (HbA1c) in whole bloodspecimens. Hemoglobin A1cmeasurements are used in theclinical management ofdiabetes to assess the long-term efficacy of diabeticcontrol. This test is to be usedas an aid in diagnosis ofdiabetes and identifyingpatients who may be at risk fordeveloping diabetes. | This test is to be used as an aidin diagnosis of diabetes and asan aid in identifying patientswho may be at risk fordeveloping diabetes TheCOBAS INTEGRA 800 Tina-quant HbA1cDx Gen.2 assayis an in vitro diagnosticsreagent system intended forquantitative determination ofmmol/mol hemoglobin A1c(IFCC) and % hemoglobinA1c (DCCT/NGSP) inhemolysate or whole blood onthe Roche COBAS INTEGRA800 clinical chemistryanalyzer |
| Specimen TypeMatrix | Human Whole BloodEDTA Whole Blood | Human Whole BloodEDTA, Li-Heparin, NaHeparin, NaF/K- Oxalate |
| Standardization | Certified via the NationalGlycohemoglobinStandardizationProgram (NGSP) | Certified via the NationalGlycohemoglobinStandardizationProgram (NGSP) |
| Linearity | Linearity was previouslyevaluated for this assay underK071132. The reportablerange is 4.0% - 16.9%. | Linearity was previouslyevaluated for this assay underK072714. The reportablerange is 4.2-20.1% |
| Interference | Substances were evaluated attwo HbA1c levels (6.5% and≥8% HbA1c)LipemiaConjugated BilirubinUnconjugated bilirubinRheumatoid FactorGlucoseTotal ProteinAscorbic Acid | Substances were evaluated attwo HbA1c levels (~6.5 and~8.9% HbA1c)LipemiaConjugated BilirubinUnconjugated bilirubinRheumatoid FactorGlucoseTotal ProteinAscorbic Acid |
| Acetaldehyde | ||
| Precision | HbA1c concentration values ofapproximately 5%, 6.5%, 8%and 12% | HbA1c concentration values ofapproximately 5%, 6.5%, 8%and 10% |
| Precision was determined tobe 0.7 - 1.8% (total precision)and 0.3 - 0.9% (within run,precision). | The between-analyzer andbetween-lot precision wasequal to or less than 1.5% forconcentrations in the range of5.3% to 12.1% HbA1c | |
| Hemoglobin VariantInterference | HbA2, HbS, HbC, HbD, doesnot interfere with the assay. | HbA2, HbS, HbC, HbD, doesnot interfere with the assay. |
| Bias | Concentration and Bias: | Concentration and Bias: |
| 6.0% -0.847% | 5.2% 1.21% | |
| 6.5% -0.753% | 6.5% 1.29% | |
| 7.0% -0.673% | 8.0% 1.34% | |
| Total Error - allowable bias6% | Concentration and Total Error | Concentration and Total Error |
| 5.0 5.8% | 5.2 4.2% | |
| 6.5 2.8% | 6.5 4.1% | |
| 8.0 3.0% | 8.0 4.1% | |
| 12.0 3.1% |
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Differences
:
·
| Parameter | Tosoh AutomatedGlycohemoglobin AnalyzerHLC-723G8 (k)071132 | COBAS INTEGRA 800Tina-quantHbA1cDx Gen.2 assay(k)121291 |
|---|---|---|
| Assay Principle | Ion-exchange HPLC | Quantitative turbidimetricinhibition immunoassay |
| Detection Method | Visible wavelength detector | Absorption spectrum andmeasured biochromatically. |
| Method Comparison | The method comparison studywas conducted utilizing theAutomated GlycohemoglobinAnalyzer HLC-723G8 and thePrimus model ultra2.r = 0.991(Y = 0.996x + 0.073) | The method comparison studywas conducted using utilizingthe Roche COBAS INTEGRA800 Tina-quant HbA1cDxGen.2 assay and the TosohAutomated GlycohemoglobinAnalyzer HLC-723G8.r = None Listed(Y = 1.015x + 0.015) |
| Hemoglobin VariantInterference | HbE does interfere with theassay. |
Automated Glycohemoglobin Analyzer HLC-723G8
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PERFORMANCE CHARACTERISTICS
Interference:
This interference study was developed according to the CLSI guideline Interference Testing in Clinical Chemistry (EP7-A2).
Interference studies were conducted on known concentrations of HbA l . They were spiked with increasing amounts of the substances below. Interference was determined as a variance greater than the assigned value x 1.00 ± 5%.
| PotentialInterferent | Range tested | %A1cConcentrations | Concentration in whichno significantinterference wasobserved |
|---|---|---|---|
| Acetylated Hb | 10 - 50 mg/dL | 6.5 and 9.5 | 50 mg/dL |
| Albumin | 500 - 5000 mg/dL | 6.6 and 14.7 | 5000 mg/dL |
| Aldehyde Hb | 5.0 - 25 mg/dL | 6.3 and 12.6 | 25 mg/dL |
| Ascorbic Acid | 3.0 - 25 mg/dL | 6.4 and 10.8 | 25 mg/dL |
| Carbamylated Hb | 5.0 - 25 mg/dL | 6.5 and 9.8 | 25 mg/dL |
| Bilirubin C | 2.0 - 21 mg/dL | 6.5 and 14.3 | 21 mg/dL |
| Labile Hb | 200 – 1000 mg/dL | 6.4 and 10.3 | 1000 mg/dL |
| Lipemia | 100 - 1000 mg/dL | 6.4 and 14.1 | 1000 mg/dL |
| Rheumatoid Factor | 110 - 550 IU/mL | 6.3 and 12.6 | 550 IU/mL |
| Bilirubin F | 2.0 - 18 mg/dL | 6.5 and 14.3 | 18 mg/dL |
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| Hemoglobin Variant Interference study | ||
|---|---|---|
| HemoglobinVariant | Number ofSamples atapproximately6% and ≥8% | %HbA1creferencevalues | IFCCmmol/ml | % Variant | Interference |
|---|---|---|---|---|---|
| HbS | 10 | 6.2 | 44 | 36.42 | No |
| 10 | 9.8 | 78.1 | 29.49 | No | |
| HbC | 10 | 6.7 | 47 | 36.54 | No |
| 10 | 8.0 | 59.4 | 35.06 | No | |
| HbE* | 10 | 6.9 | N/A* | N/A* | Yes |
| 10 | 9.8 | N/A* | N/A* | Yes | |
| HbD | 10 | 6.0 | 43.1 | 36.23 | No |
| 10 | 8.5 | 66.9 | 35.70 | No | |
| HbF | 10 | 7.0 | 56.5 | 24.38 | No |
| 10 | 8.7 | 74 | 7.43 | No | |
| HbA2 | 10 | 6.59 | 47.1 | 13.9 | No |
| 10 | 8.05 | 62.9 | 12.7 | No |
*The G8 has known HbE interference. When a sample is suspected to contain HbE, a flag will be displayed. The %HbA Ic result will not be reported from the analyzer.
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 has known Hemoglobin E (HbE) interference. When a sample is suspected to contain HbE a flag will be displayed. The HbA1c result will not be reported from the analyzer.
The percent relative bias from the reference method at low and high concentrations of %HbA I c in each sample is:
| Hb Variant | Percent Relative Bias from Reference Methodat Low and High Concentrations of %HbA1cSamples | |
|---|---|---|
| ~6.5 %HbA1c | ≥8 %HbA1c | |
| S | 0 | -5 |
| C | 5 | -5 |
| E | *Flag | *Flag |
| D | 1 | -3 |
| A2 | -2 | -2 |
| F | 5 | 2 |
Precision:
The precision study was developed with reference to the CLSI protocol entitled: Evaluation of Precision Performance of Quantitative Measurement Methods (EP5-A2).
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Precision was assessed by assaying four concentrations of unaltered EDTA whole blood specimens with each using 3 lots and 3 instruments. Estimates of total and within-run precision were obtained from measurements of 2 replicates in a single run, 2 times a day for 20 nonconsecutive days for each specimen/reagent combination. This equaled a total of 40 runs and 80 determinants for each data set. There were three (3) data sets at HbA Ic concentrations of approximately 5%, 6.5%, 8% and 12% for each specimen.
Within-run Precision
Intra-assay (within run) Precision
| Mean | StandardDeviation | Coefficient ofVariation | |
|---|---|---|---|
| Sample | (%) | (%) | (%) |
| EDTA Whole Blood 5% A1 | 4.98 | 0.04 | 0.86 |
| EDTA Whole Blood 5% A2 | 5.00 | 0.05 | 1.00 |
| EDTA Whole Blood 5% A3 | 4.93 | 0.03 | 0.68 |
| EDTA Whole Blood 6.5% B1 | 6.50 | 0.02 | 0.29 |
| EDTA Whole Blood 6.5% B2 | 6.51 | 0.02 | 0.35 |
| EDTA Whole Blood 6.5% B3 | 6.44 | 0.03 | 0.44 |
| EDTA Whole Blood 8% C1 | 7.89 | 0.02 | 0.26 |
| EDTA Whole Blood 8% C2 | 7.90 | 0.03 | 0.32 |
| EDTA Whole Blood 8% C3 | 7.81 | 0.03 | 0.34 |
| EDTA Whole Blood 12% D1 | 11.90 | 0.02 | 0.18 |
| EDTA Whole Blood 12% D2 | 11.89 | 0.03 | 0.23 |
| EDTA Whole Blood 12% D3 | 11.79 | 0.03 | 0.27 |
Total Precision
.
.
| Mean | StandardDeviation | Coefficient ofVariation | |
|---|---|---|---|
| Sample | (%) | (%) | (%) |
| EDTA Whole Blood 5% A1 | 4.98 | 0.09 | 1.83 |
| EDTA Whole Blood 5% A2 | 5.00 | 0.09 | 1.79 |
| EDTA Whole Blood 5% A3 | 4.93 | 0.08 | 1.69 |
| EDTA Whole Blood 6.5% B1 | 6.50 | 0.04 | 0.68 |
| EDTA Whole Blood 6.5% B2 | 6.51 | 0.07 | 1.14 |
| EDTA Whole Blood 6.5% B3 | 6.44 | 0.07 | 1.10 |
| EDTA Whole Blood 8% C1 | 7.89 | 0.08 | 0.98 |
| EDTA Whole Blood 8% C2 | 7.90 | 0.07 | 0.89 |
| EDTA Whole Blood 8% C3 | 7.81 | 0.07 | 0.86 |
| EDTA Whole Blood 12% D1 | 11.90 | 0.16 | 1.31 |
| EDTA Whole Blood 12% D2 | 11.89 | 0.19 | 1.58 |
| EDTA Whole Blood 12% D3 | 11.79 | 0.13 | 1.14 |
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Correlation:
The methods comparison study was conducted with reference to the CLSI protocol entitled: Method Comparison and Bias Estimation Using Patient Samples; Approved Guideline (EP9-A2-IR).
Comparative testing was conducted between samples which were analyzed on the Automated Glycohemoglobin Analyzer HLC-723G8 (candidate method) and Primus ultra2 (comparative method) analyzed by a secondary NGSP reference laboratory.
A total of 120 unaltered EDTA whole blood specimens were assayed in singleton. Frozen specimens were utilized for this study. The sample distribution is as follows:
| Hemoglobin A1c level | Number of samplestested at each A1cLevel | %samples tested |
|---|---|---|
| ≤ 5% | 5 | 4.2% |
| 5 – 6% | 15 | 12.5% |
| 6 – 6.5% | 30 | 25.0% |
| 6.5 – 7% | 30 | 25.0% |
| 7 – 8% | 20 | 16.7% |
| 8 – 9% | 10 | 8.3 |
| > 9% | 10 | 8.3% |
| Total samples | 120 | 100% |
| Regression Analysis | ||
|---|---|---|
| Deming | Regular | |
| Slope: | 0.996 (0.971 to 1.021) | 0.987 (0.962 to 1.012) |
| Intercept: | 0.073 (-0.110 to 0.255) | 0.139 (-0.043 to 0.321) |
| Corr Coef (R): | 0.991 | |
| Bias: | 0.047 (0.657 %) | |
| Points(Plotted/Total): | 120/120 | |
| Result Ranges: | 4.50% to 16.5% |
Total Error Near the Cutoff
Using the results of bias estimation (%Bias) in the method comparison study and precision estimates in the precision study, Total Error (TE) at four concentrations: (5.0%, 6.5%, 8.0% and 12.0) was calculated as follows: %TE =|%Bias| + 1.96 %CV(1+%Bias). The results are presented in the tables below. %TE of ≤6% is acceptable.
| Decision Level % | % Bias | 1%CV | %TE |
|---|---|---|---|
| 1.08 | 0 .1.04 | W.V | |
| ﻟﻠﺘﻌﻠﻴﻘﺎﺕ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤ | 0 75N.I. | 0.68 | data o O |
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| 8.0 | 0.54 | 0.98 | 3.0 |
|---|---|---|---|
| 12.0 | 0.24 | 1.31 | 3.1 |
Using the calculation: (TE)95 = Bias + 1.96*SD the results are shown in the following table:
| Decision Level % | Bias | SD | (TE)95 | Goal at 6% |
|---|---|---|---|---|
| 5.0 | 0.054 | 0.09 | 0.23 | 0.30 |
| 6.5 | 0.049 | 0.04 | 0.13 | 0.39 |
| 8.0 | 0.043 | 0.08 | 0.20 | 0.48 |
| 12.0 | 0.029 | 0.16 | 0.34 | 0.72 |
Image /page/8/Figure/4 description: This image is a scatter plot with the title "Scatter Plot". The x-axis is labeled "Ultra 2 (%)" and ranges from 5 to 15. The y-axis is labeled "G8 (%)" and ranges from 5 to 15. The plot shows a cluster of points that follow a linear trend, along with a legend indicating "Deming Regr", "1:1 Line", and "Med Dec Pt".
Standards:
| Number | FDARecognitionNumber | RevisionDate | Title |
|---|---|---|---|
| EP5-A2 | 7-110 | 10/31/2005 | Evaluation of Precision Performance ofQuantitative Measurement Methods: ApprovedGuideline- Second Edition |
| EP09-A2-IR | 7-92 | 03/08/2004 | Method Comparison and Bias Estimation UsingPatient Samples; Approved Guideline-SecondEdition |
| EP7-A2 | 7-127 | 05/21/2007 | Interference Testing in Clinical Chemistry;Approved Guideline - Second Edition |
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Linearity and Detection Limit:
Linearity was previously established for this assay under K071132. The reportable range for this device is 4.0-16.9% HbAlc.
Calibrator and Controls:
Calibrators (Tosoh A 1c Calibrator Set) and Controls (Canterbury Scientific Hemoglobin A 1c) are recommended for use with this device. The calibrators and controls were previously cleared under 510(k) numbers K071132 and K021484 respectively.
Traceability
The assigned HbA1c values of the Tosoh Automated Glycohemoglobin Analyzer are certified with The National Glycohemoglobin Standardization Program (NGSP). The NGSP certification expires in one year. See NGSP website for current certification at http://www.ngsp.org.
· The final reportable result is traceable to both the International Federation if Clinical Chemistry (IFCC) and the Diabetes Control and Complications Trial (DCCT). The International Federation of Clinical Chemistry (IFCC) units of mmol/mol are calculated using the Master Equation NGSP (%) =0.09148 x IFCC (mmol/mol) + 2.52. HbA 1c results are provided to the customers using two different units: NGSP equivalent units (%) and IFCC equivalent units (mmol/mol).
Conclusion:
The Tosoh Bioscience, Inc. Automated Glycohemoglobin Analyzer HLC-723G8 is substantially equivalent to the Roche Diagnostics Corporation, COBAS INTEGRA 800 Tina-quant HbA 1cDx Gen.2 assay (K121291) for in vitro diagnostic use for the measurement of hemoglobin Alc (HbA1c) in whole blood specimens and to be used as an aid in diagnosis of diabetes and identifying patients who may be at risk for developing diabetes.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
January 23, 2014
TOSOH BIOSCIENCE. INC. C/O ROBERT WICK 6000 SHORELINE COURT SUITE 101 SOUTH SAN FRANCISCO CA 94080
Re: K131580
Trade/Device Name: Automated Glycohemoglobin Analyzer HLC-723G8 Regulation Number: 21 CFR 862.1373 Regulation Name: Hemoglobin A1c Test System Regulatory Class: II Product Code: PDJ Dated: December 20, 2013 Received: December 20, 2013
Dear Mr. Wick:
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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to 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 Parts 801 and 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) 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-Mr. Wick
if you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportalProblem/defiult.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 Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Courtney H.Lias-S
Courtney H. Lias, Ph.D. Director Division of Chemistry. and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
510(k) Number (if known) K131580
Device Name
Automated Glycohemoglobin Analyzer HLC-723G8
Indications for Use (Describe)
The Tosoh Automated Glycohemoglobin Analyzer HLC-723G8 is intended for in vitro diagnostic use for the quantitative measurement of % hemoglobin Alc (HbA Ic) (DCCT/NGSP) and mmol/mo hemoglobin A Ic (IFCC) in whole blood specimens. This test is to be used as an aid in diagnosis of diabetes and as an aid in identifying patients who may be at risk for developing diabetes.
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.
FOR FDA USE ONLY ....
Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
Stayce Beck
FORM FDA 3881 (1/14)
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.
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§ 862.1373 Hemoglobin A1c test system.
(a)
Identification. A hemoglobin A1c test system is a device used to measure the percentage concentration of hemoglobin A1c in blood. Measurement of hemoglobin A1c is used as an aid in the diagnosis of diabetes mellitus and as an aid in the identification of patients at risk for developing diabetes mellitus.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The device must have initial and annual standardization verification by a certifying glycohemoglobin standardization organization deemed acceptable by FDA.
(2) The premarket notification submission must include performance testing to evaluate precision, accuracy, linearity, and interference, including the following:
(i) Performance testing of device precision must, at a minimum, use blood samples with concentrations near 5.0 percent, 6.5 percent, 8.0 percent, and 12 percent hemoglobin A1c. This testing must evaluate precision over a minimum of 20 days using at least three lots of the device and three instruments, as applicable.
(ii) Performance testing of device accuracy must include a minimum of 120 blood samples that span the measuring interval of the device and compare results of the new device to results of a standardized test method. Results must demonstrate little or no bias versus the standardized method.
(iii) Total error of the new device must be evaluated using single measurements by the new device compared to results of the standardized test method, and this evaluation must demonstrate a total error less than or equal to 6 percent.
(iv) Performance testing must demonstrate that there is little to no interference from common hemoglobin variants, including Hemoglobin C, Hemoglobin D, Hemoglobin E, Hemoglobin A2, and Hemoglobin S.
(3) When assay interference from Hemoglobin F or interference with other hemoglobin variants with low frequency in the population is observed, a warning statement must be placed in a black box and must appear in all labeling material for these devices describing the interference and any affected populations.