(433 days)
cobas c 501, cobas e 501
No
The description details a standard in vitro diagnostic immunoassay and analyzer, with no mention of AI/ML in the device description, intended use, or performance studies. The calculations are based on established protocols (IFCC, NGSP).
No
This device is for in vitro diagnostic (IVD) use, specifically to aid in the diagnosis of diabetes, by measuring HbA1c levels. It is not used to treat or prevent a disease.
Yes
The product's intended use explicitly states, "This test is to be used as an aid in diagnosis of diabetes..." which directly indicates its role as a diagnostic device.
No
The device description clearly outlines a reagent system and its use on a physical clinical chemistry analyzer (Roche/Hitachi cobas c 501). The process involves handling whole blood samples, on-board hemolysis, and measurement using a turbidimetric inhibition immunoassay, all of which are hardware-dependent processes.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the assay is an "in vitro diagnostics reagent system intended for quantitative determination of mmol/mol hemoglobin Alc (IFCC) and % hemoglobin A1c (DCCT/NGSP) in whole blood". This directly aligns with the definition of an in vitro diagnostic device, which is used to examine specimens taken from the human body to provide information for diagnosis, monitoring, or screening.
- Device Description: The description details how the test is performed on whole blood samples, which are specimens taken from the human body.
- Performance Studies: The document describes various performance studies (precision, method comparison, interference, linearity, etc.) that are typical for validating an IVD device.
The entire document describes a test that is performed in vitro (outside the body) on a biological specimen (whole blood) to provide diagnostic information.
N/A
Intended Use / Indications for Use
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 cobas c 501 Tina-quant HbA1cDx Gen.3 assay is an in vitro diagnostics reagent system intended for quantitative determination of mmol/mol hemoglobin Alc (IFCC) and % hemoglobin A1c (DCCT/NGSP) in whole blood on the Roche/Hitachi cobas c 501 clinical chemistry analyzer.
Product codes
PDJ
Device Description
Whole blood samples are placed on the analyzer. The anticoagulated whole blood is hemolyzed on board the analyzer prior to determination of HbA1c by this turbidimetric inhibition immunoassay. Liberated hemoglobin in the hemolyzed sample is converted to a derivative having a characteristic absorption spectrum and measured bichromatically. The instrument first measures hemoglobin (Hb) and glycohemoglobin (HbA1c) in terms of either g/dL or mmol/L, then calculates the % HbA1c from the HbA1c/Hb ratio according to a user-selected protocol, either IFCC or NGSP protocols.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
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Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision:
Precision was evaluated according to CLSI EP5-A2. It included evaluation of three reagent lots, three cobas c 501 analyzers, four native samples and two control samples, two aliquots per sample run in singlicate, two runs per day for 21 days. Results are in terms of % HbA Ic.
Method Comparison:
A method comparison was performed to compare sample results from the candidate method using one reagent lot on one cobas e 501 analyzer to sample results from Tosoh HPLC, the secondary NGSP reference laboratory method. Samples were tested in singlicate and measured over three days. 141 variant-free samples ranged from 4.7 to 12.2% HbA1c.
Total Error:
The bias component from the method comparison study and the precision component from the reproducibility study are used to calculate the total error at three concentrations near the cutoff.
Endogenous Interference:
Six endogenous substances were evaluated for potential interference of the assay. These substances were spiked into whole blood sample pools. A separate preparation occurred for each substance. Two HbA1c levels, one near the medical decision level and one above it, were tested for each endogenous substance. Thus twelve dilution series were created. Each sample in each dilution series was tested ten-fold for % HbA1c on a single cobas c 501 analyzer, using a single reagent lot.
Drug Interference:
Sixteen drugs were evaluated for potential interference of the assay. These drugs were spiked into whole blood samples at two concentrations, Concentration 1 is ~5 times the maximum daily dose and Concentration 2 is the maximum daily dose. A separate preparation occurred for each drug. Two HbA1c levels, one near the medical decision level and one above it, were tested for each drug. Thus, 64 samples were prepared. Also, an HbA1c sample with no drug served at the reference sample. Each sample was tested ten-fold for % HbAIc on a single cobas c 501 analyzer, using a single reagent lot. Results show that no significant interference was observed.
Cross-Reactivity with Hemoglobin Derivatives:
Six hemoglobin derivatives were evaluated for potential interference of the assay. Two HbA1c levels, one near the medical decision level and one above it, were represented in whole blood sample pools. For each HbA1c level, two whole blood pools were prepared for each derivative, one with none and one with a high concentration of derivative. From the pools, a serial dilution was prepared to yield varying concentrations of the derivative for both HbA 1c levels. Each sample was tested ten-fold for % HbA1c on a single cobas c 501 analyzer, using a single reagent lot. There is no significant cross-reactivity with these hemoglobin derivatives at physiologically occurring concentrations.
Hemoglobin Variants Interference:
A hemoglobin variant interference study was performed using a total of 116 samples that contain one of six common hemoglobin variants (S, C, E, D, F, A2). Testing was performed on the candidate device and with an NGSP reference method that is known to be free from the hemoglobin interference being tested.
Lower Limits of Detection:
LoB (Limit of Blank) and LoD (Limit of Detection) were determined according to CLSI EP 17-A. LoB was determined using one analyte-free sample tested in five replicates on two cobas c 501 analyzers. LoD was determined using five low-analyte samples tested in singlicate on two cobas c 501 analyzers. Both LoB and LoD were evaluated for Hb and HbA 1c (g/dL). The tests were performed in two runs per day for three days per reagent batch with a total of three reagent batches.
Linearity:
Linearity was performed according to CLSI EP6-A for this submission and for 510(k) K102914. For this submission, a dilution series was prepared using a high analyte concentration sample pool and an analyte-free pool. The pools were mixed in different ratios to yield a 20-level dilution series with varying concentrations of Hb and HbA1c. Values were measured in triplicate for each level. The median values were compared to the theoretical values and regressed.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
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Predicate Device(s)
Reference Device(s)
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Predetermined Change Control Plan (PCCP) - All Relevant Information
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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.
0
AUG 8 2013
| Introduction | Roche Diagnostics hereby submits this 510(k) to provide FDA with notification of intent to market the cobas c 501 Tina-quant HbA1cDx Gen.3 assay with a new intended use that includes the device as an aid in the diagnosis of diabetes and as an aid in identifying patients who may be at risk of developing diabetes. This submission presents data to support this new intended use. | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Submitter | Susan Hollandbeck from Roche Diagnostics, U.S. Regulatory Affairs | ||||||||||
| Date prepared | The submission was originally prepared on May 31, 2012. | ||||||||||
| Device name | Proprietary name:cobas c 501 Tina-quant Hemoglobin A1cDx Gen.3 assayCommon names:HbA1cDx Gen.3 and TQ HbA1cDx Gen.3Classification name:Hemoglobin A1c Test SystemProduct codes:PDJC.F.R. Section:862.1373 | Proprietary name: | cobas c 501 Tina-quant Hemoglobin A1cDx Gen.3 assay | Common names: | HbA1cDx Gen.3 and TQ HbA1cDx Gen.3 | Classification name: | Hemoglobin A1c Test System | Product codes: | PDJ | C.F.R. Section: | 862.1373 |
| Proprietary name: | cobas c 501 Tina-quant Hemoglobin A1cDx Gen.3 assay | ||||||||||
| Common names: | HbA1cDx Gen.3 and TQ HbA1cDx Gen.3 | ||||||||||
| Classification name: | Hemoglobin A1c Test System | ||||||||||
| Product codes: | PDJ | ||||||||||
| C.F.R. Section: | 862.1373 | ||||||||||
| Device description | Whole blood samples are placed on the analyzer. The anticoagulated whole blood is hemolyzed on board the analyzer prior to determination of HbA1c by this turbidimetric inhibition immunoassay. Liberated hemoglobin in the hemolyzed sample is converted to a derivative having a characteristic absorption spectrum and measured bichromatically. The instrument first measures hemoglobin (Hb) and glycohemoglobin (HbA1c) in terms of either g/dL or mmol/L, then calculates the % HbA1c from the HbA1c/Hb ratio according to a user-selected protocol, either IFCC or NGSP protocols. | ||||||||||
| Predicate device | The cobas c Tina-quant HbA1cDx Gen.3 assay is substantially equivalent to the COBAS INTEGRA 800 Tina-quant HbA1cDx Gen.2 assay that was cleared in 510(k) K121291. |
Continued on next page:
1
| Intended use | 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 cobas c
501Tina-quant HbA1cDx Gen.3 assay is an in vitro diagnostics reagent
system intended for quantitative determination of mmol/mol hemoglobin Alc
(IFCC) and % hemoglobin A1c (DCCT/NGSP) in whole blood on the |
|--------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Roche/Hitachi cobas c 501 clinical chemistry analyzer. |
| Comparison to predicate | The table compares the features of the candidate device, cobas c Tina-quant HbA1cDx Gen.3 assay, to the predicate device, COBAS INTEGRA 800 HbA1cDx Gen.2 that was cleared in 510(k) K121291. |
|---|---|
| ------------------------- | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
| Feature | Candidate Device | Predicate Device | |
|---|---|---|---|
| Anticoagulated venous or capillary | |||
| blood | Same | ||
| Sample Types | Acceptable anticoagulants | ||
| . Li-Heparin | |||
| . K2-EDTA | |||
| . K3-EDTA | |||
| . KF/Na2-EDTA | |||
| . Na-Heparin | |||
| . NaF/K-Oxalate | |||
| . NaF/Na2-EDTA | |||
| Instrument Platform | cobas c 501 | COBAS INTEGRA 800 | |
| Calibrator | C.f.a.s. HbA1c | Same | |
| Calibration Frequency | Each lot, every 29 days, and as | ||
| required following quality control | |||
| procedures | Same | ||
| Calibration Mode | Hb determination uses a linear | ||
| mode. | |||
| HbAlc determination uses a | |||
| spline mode. | Logit/Log 5 | ||
| Controls | PreciControl HbA1c norm and path | Same |
Comparison Table
2
| Comparison to | The table compares the features of the candidate device, cobas c Tina- |
|---|---|
| predicate (continued) | quant HbA1cDx Gen.3 assay, to the predicate device, COBAS |
| INTEGRA 800 HbA1cDx Gen.2 that was cleared in 510(k) K121291. |
| Feature | Candidate Device | Predicate Device |
|---|---|---|
| Reporting Units | For the components, Hb and HbA1c: | |
| mmol/L and g/dL | Components: | |
| g/dL | ||
| For the ratio: | ||
| % HbA1c (DCCT/NGSP) and | ||
| mmol/mol HbA1c (IFCC) | Ratio: | |
| Same | ||
| Determination of HbA1c | HbA1c determination is based on the | |
| turbidimetric inhibition immunoassay | ||
| for hemolyzed whole blood. | ||
| Glycohemoglobin in the sample reacts | ||
| with anti-HbA1c to form soluble | ||
| antigen-antibody complexes. | ||
| Polyhaptens react with excess anti- | ||
| HbA1c to form an insoluble antibody- | ||
| polyhapten complex which can be | ||
| measured turbidimetrically. | Same | |
| Determination of Hb | Liberated hemoglobin in the | |
| hemolyzed sample is converted to a | ||
| derivative having a characteristic | ||
| absorption spectrum which is | ||
| measured bichromatically. | Same | |
| Sample Pretreatment | Automated on-board sample | |
| pretreatment with hemolyzing reagent | Same | |
| Measuring Range | Hb | |
| 2.48 - 24.8 mmol/L | ||
| (4 - 40 g/dL) | Hb | |
| 4 - 35 g/dL | ||
| HbA1c | ||
| 0.186 – 1.61 mmol/L | ||
| (0.3 - 2.6 g/dL) | HbA1c | |
| 0.3 - 3.4 g/dL | ||
| Ratio | ||
| 4.2 - 20.1 % HbA1c | ||
| 23 – 196 mmol/mol HbA1c | Ratio | |
| 4.3 - 24.8 % HbA1c | ||
| 23 - 258 mmol/mol HbA1c | ||
| Note: This measuring range was | ||
| established in 510(k) K102914 for the | ||
| COBAS INTEGRA Tina-quant | ||
| HbA1c Gen.3 assay. | ||
| Feature | Candidate Device | Predicate Device |
| Antibody | Polyclonal anti-HbA1c from sheep blood | Same |
| Reagent Stability | Unopened | |
| 2-8 °C until expiration date on cobas c pack label | ||
| On-board in use | ||
| Refrigerated on the analyzer for 4 weeks | Same | |
| Analytical Sensitivity | Hb | |
| LoB = 0.31 mmol/L (0.50 g/dL) | ||
| LoD = 0.62 mmol/L (1.00 g/dL) | Hb | |
| LoB = 0.50 g/dL | ||
| LoD = 1.00 g/dL | ||
| HbA1c | ||
| LoB = 0.12 mmol/L (0.19 g/dL) | ||
| LoD = 0.18 mmol/L (0.29 g/dL) | HbA1c | |
| LoB = 0.19 g/dL | ||
| LoD = 0.29 g/dL | ||
| Analytical Specificity | Hb fractions | |
| At physiological concentrations, no cross reactions were found with | ||
| · HbA0, | ||
| · HbA1a, | ||
| · HbA1b, | ||
| · acetylated hemoglobin, | ||
| · carbamylated hemoglobin, | ||
| · glycated albumin, and | ||
| · labile HbA1c. | Same | |
| Hb variants | ||
| This device has significant negative interference with samples containing elevated levels of HbF. The bias exceeds -7% when HbF content exceeds +7%. The negative bias with HbF is independent of % HbA1c, but is directly proportional in magnitude to the % HbF content. | ||
| HbS, HbC, HbD, HbA2, and HbE do not significantly interfere | Same | |
| Comparison to | The table compares the features of the candidate device, cobas c Tina-quant | |
| predicate | HbA1cDx Gen.3 assay, to the predicate device, COBAS INTEGRA 800 | |
| (continued) | HbA1cDx Gen.2 that was cleared in 510(k) K121291. |
Comparison Table (continued)
3
The table compares the features of the candidate device, cobas c Tina-quant Comparison to predicate HbA1cDx Gen.3 assay, to the predicate device, COBAS INTEGRA 800 (continued) HbA1cDx Gen.2 that was cleared in 510(k) K121291.
and the control of the comments of the comments of the comments of the comments of the comments of the comments of the comments of the comments of the comments of the comment
Comparison Table (continued)
4
| Comparison Table (continued) | ||
|---|---|---|
| Feature | Candidate Device | Predicate Device |
| Endogenous | ||
| Interferences | Icterus | |
| No significant interference up to 60 | ||
| mg/dL. | Icterus | |
| Same | ||
| Lipemia | ||
| No significant interference up to an | ||
| Intralipid concentration of 600 mg/dL. | Lipemia | |
| No significant interference up to an | ||
| Intralipid concentration of 800 mg/dL. | ||
| Glycemia | ||
| No significant interference up to 1000 | ||
| mg/dL. | Glycemia | |
| Same | ||
| Rheumatoid factors | ||
| No significant interference up to 750 | ||
| IU/mL. | Rheumatoid factors | |
| Same | ||
| Total Protein | ||
| Up to 21 g/dL of additional protein | ||
| spiked into the sample does not | ||
| interfere. | Total Protein | |
| Same | ||
| Drugs | ||
| No interference was found at | ||
| therapeutic concentrations using a | ||
| common drug panel of 16 drugs. | Drugs | |
| Same | ||
| Expected | ||
| Values | Protocol 1 (IFCC) | |
| 20 - 42 mmol/mol HbA1c | ||
| Protocol 2 (DCCT/NGSP) | ||
| 4.0 - 6.0 % HbA1c | Same |
Comparison Table (continued)
5
The following discusses the precision of the device. Analytical performance
Precision
Precision was evaluated according to CLSI EP5-A2. It included evaluation of three reagent lots, three cobas c 501 analyzers, four native samples and two control samples, two aliquots per sample run in singlicate, two runs per day for 21 days. Results are in terms of % HbA Ic.
| c 501 - Analyzer 1 Precision | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Mean | Repeatability | Between- | ||||||||
| run | Between- | |||||||||
| day | Between- | |||||||||
| lot | Total | |||||||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Human Sample 1 | ||||||||||
| (5.0 %HbA1c) | 0.056 | 1.1 | 0.022 | 0.4 | 0.047 | 0.9 | 0.067 | 1.3 | 0.102 | 2.0 |
| Human Sample 2 | ||||||||||
| (6.4 %HbA1c) | 0.062 | 1.0 | 0.035 | 0.5 | 0.051 | 0.8 | 0.095 | 1.5 | 0.129 | 2.0 |
| Human Sample 3 | ||||||||||
| (7.9 %HbA1c) | 0.078 | 1.0 | 0.051 | 0.7 | 0.087 | 1.1 | 0.053 | 0.7 | 0.139 | 1.8 |
| Human Sample 4 | ||||||||||
| (11.3 %HbA1c) | 0.116 | 1.0 | 0.000 | 0.0 | 0.084 | 0.7 | 0.239 | 2.1 | 0.278 | 2.5 |
| PreciControl HbAIc norm | ||||||||||
| (5.2 %HbAlc) | 0.062 | 1.2 | 0.034 | 0.7 | 0.050 | 1.0 | 0.077 | 1.5 | 0.115 | 2.2 |
| PreciControl HbAlc path | ||||||||||
| (9.4 %HbA1c) | 0.085 | 0.9 | 0.022 | 0.2 | 0.060 | 0.6 | 0.177 | 1.9 | 0.206 | 2.2 |
| c 501 - Analyzer 2 Precision | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Mean | Repeatability | Between-run | Between-day | Between-lot | Total | |||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |
| Human Sample 1 | ||||||||||
| (5.1 %HbA1c) | 0.054 | 1.1 | 0.051 | 1.0 | 0.024 | 0.5 | 0.028 | 0.5 | 0.083 | 1.6 |
| Human Sample 2 | ||||||||||
| (6.4 %HbA1c) | 0.072 | 1.1 | 0.055 | 0.9 | 0.032 | 0.5 | 0.043 | 0.7 | 0.105 | 1.6 |
| Human Sample 3 | ||||||||||
| (8.1 %HbA1c) | 0.081 | 1.0 | 0.060 | 0.7 | 0.083 | 1.0 | 0.021 | 0.3 | 0.133 | 1.6 |
| Human Sample 4 | ||||||||||
| (11.4 %HbA1c) | 0.107 | 0.9 | 0.077 | 0.7 | 0.076 | 0.7 | 0.175 | 1.5 | 0.232 | 2.0 |
| PreciControl HbA1c norm | ||||||||||
| (5.2 %HbA1c) | 0.065 | 1.2 | 0.054 | 1.0 | 0.014 | 0.3 | 0.029 | 0.6 | 0.090 | 1.7 |
| PreciControl HbA1c path | ||||||||||
| (9.6 %HbA1c) | 0.096 | 1.0 | 0.047 | 0.5 | 0.038 | 0.4 | 0.078 | 0.8 | 0.138 | 1.4 |
6
Analytical performance (continued) The following discusses the precision of the device.
| Precision results are in terms of % HbA 1c. | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| c 501 - Analyzer 3 Precision | |||||||||||||
| Repeatability | Between- | Between- | Between- | ||||||||||
| Mean | run | day | lot | Total | |||||||||
| %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | |||||
| Human Sample I | |||||||||||||
| (5.0 %HbAlc) | 0.062 | 1.2 | 0.026 | 0.5 | 0.020 | 0.4 | 0.075 | 1.5 | 0.103 | 2.0 | |||
| Human Sample 2 | |||||||||||||
| (6.4 %HbAlc) | 0.076 | 1.2 | 0.021 | 0.3 | 0.034 | 0:5 | 0.037 | 0.6 | 0.094 | 1.5 | |||
| Human Sample 3 | |||||||||||||
| (8.0 %HbAlc) | 0.100 | 1.2 | 0.055 | 0.7 | 0.027 | 0.3 | 0.073 | 0.9 | 0.138 | 1.7 | |||
| Human Sample 4 | |||||||||||||
| (11.3 %HbA1c) | 0.112 | 1.0 | 0.097 | 0.9 | 0.040 | 0.4 | 0.036 | 0.3 | 0.157 | 1.4 | |||
| PreciControl HbA1c norm | |||||||||||||
| (5.2 %HbAlc) | 0.076 | 1.5 | 0.000 | 0.0 | 0.029 | 0.6 | 0.133 | 2.6 | 0.156 | 3.0 | |||
| PreciControl HbA1c path | |||||||||||||
| (9.5 %HbAlc) | 0.121 | 1.3 | 0.044 | 0.5 | 0.000 | 0.0 | 0.116 | 1.2 | 0.174 | 1.8 | |||
| Reproducibility - Roche/Hitachi cobas c 501 | |||||||||||||
| Between- | Between- | ||||||||||||
| Between- | Between- | ||||||||||||
| Mean | Repeatability | run | day | lot | instrument | Total | |||||||
| SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | ||
| Human Sample 1 | |||||||||||||
| (5.1 %HbAlc) | 0.058 | 1.1 | 0.036 | 0.7 | 0.032 | 0.6 | 0.060 | 1.2 | 0.000 | 0.0 | 0.096 | 1.9 | |
| Human Sample 2 | |||||||||||||
| (6.4 %HbA1c) | 0.070 | 1.1 | 0.040 | 0.6 | 0.040 | 0.6 | 0.064 | 1.0 | 0.000 | 0.0 | 0.110 | 1.7 | |
| Human Sample 3 | |||||||||||||
| (8.0 %HbAlc) | 0.087 | 1.1 | 0.056 | 0.7 | 0.071 | 0.9 | 0.053 | 0.7 | 0.100 | 1.3 | 0.169 | 2.1 | |
| Human Sample 4 | |||||||||||||
| (11.3 %HbAlc) | 0.112 | 1.0 | 0.067 | 0.6 | 0.069 | 0.6 | 0.172 | 1.5 | 0.000 | 0.0 | 0.227 | 2.0 | |
| PreciControl | |||||||||||||
| HbAlc norm | |||||||||||||
| (5.2 %HbAIc) | 0.068 | 1.3 | 0.035 | 0.7 | 0.034 | 0.7 | 0.090 | 1.7 | 0.000 | 0.0 | 0.123 | 2.4 | |
| PreciControl | |||||||||||||
| HbAlc path | |||||||||||||
| (9.5 %HbAlc) | 0.102 | 1.1 | 0.039 | 0.4 | 0.040 | 0.4 | 0.130 | 1.4 | 0.079 | 0.8 | 0.192 | 2.0 |
7
Analytical performance The following discusses the method comparison and total error. (continued)
Method Comparison
A method comparison was performed to compare sample results from the candidate method using one reagent lot on one cobas e 501 analyzer to sample results from Tosoh HPLC, the secondary NGSP reference laboratory method. Samples were tested in singlicate and measured over three days. 141 variant-free samples ranged from 4.7 to 12.2% HbA1c. The distribution of samples tested appears below.
Sample Distribution
| % HbA1c | # sample tested | % samples tested |
|---|---|---|
| 9% | 12 | 8.5% |
| Total | 141 | 100% |
Total Error
The bias component from the method comparison study and the precision component from the reproducibility study are used to calculate the total error at three concentrations near the cutoff.
Total Error
| Decision Level (% HbA1c) | %Bias | %CV | %TE |
|---|---|---|---|
| 5.2 | -1.98% | 2.07% | 6.0% |
| 6.5 | -1.45% | 1.7% | 4.7% |
| 8.0 | -1.06% | 2.1% | 5.1% |
8
The following discusses the endogenous interference. Analytical performance (continued)
Endogenous Interference
Six endogenous substances were evaluated for potential interference of the assay. These substances were spiked into whole blood sample pools. A separate preparation occurred for each substance. Two HbA1c levels, one near the medical decision level and one above it, were tested for each endogenous substance. Thus twelve dilution series were created.
Each sample in each dilution series was tested ten-fold for % HbA1c on a single cobas c 501 analyzer, using a single reagent lot.
The median value for each set of ten was calculated. The reference sample is the sample Level 0 in the dilution series; it contains no interferent. The initial value is the measured result for the reference sample. The results for all remaining samples in the dilution series are compared to the initial value. This comparison is evaluated as a percent deviation. Interference is significant when it exceeds 7% deviation from the initial value.
| Endogenous Interference Summary | ||
|---|---|---|
| endogenous substance | range tested | highest level tested with |
| no significant interference | ||
| Lipemia (Intralipid) | 0-2000 mg/dL | 600 mg/dL |
| Unconjugated Bilirubin | 0-66 mg/dL | 60mg/dL |
| Conjugated Bilirubin | 0-66 mg/dL | 60 mg/dL |
| Glucose | 0-2000 mg/dL | 1000 mg/dL |
| Rheumatoid Factor | 0-1200 IU/mL | 750 IU/mL |
| Total Protein | 0-24.5 g/dL | 21 g/dL |
Endogenous Interference Summary
9
Analytical performance The following discusses the drug interference. (continued)
Drug Interference
Sixteen drugs were evaluated for potential interference of the assay. These drugs were spiked into whole blood samples at two concentrations, Concentration 1 is ~5 times the maximum daily dose and Concentration 2 is the maximum daily dose. A separate preparation occurred for each drug. Two HbA1c levels, one near the medical decision level and one above it, were tested for each drug. Thus, 64 samples were prepared. Also, an HbA1c sample with no drug served at the reference sample.
Each sample was tested ten-fold for % HbAIc on a single cobas c 501 analyzer, using a single reagent lot.
The median value for each set of ten was calculated and compared to the initial value. Percent recovery was calculated. Interference is significant when it exceeds 7% deviation from the initial value. Results show that no significant interference was observed with the following drugs up to the stated concentrations.
| drug | highest level tested with no significant interference |
|---|---|
| Acetylcystein | 150 mg/dL |
| Ampicillin-Na | 1000 mg/dL |
| Ascorbic acid | 300 mg/dL |
| Cefoxitin | 2500 mg/dL |
| Heparin | 5000 U/L |
| Levodopa | 20 mg/dL |
| Methyldopa | 20 mg/dL |
| Metronidazole | 200 mg/dL |
| Doxycyclin | 50 mg/dL |
| Acetylsalicylic Acid | 1000 mg/dL |
| Rifampicin | 60 mg/L |
| Cyclosporine | 5 mg/L |
| Acetaminophen | 200 mg/L |
| Ibuprofen | 500 mg/L |
| Theophylline | 100 mg/L |
| Phenylbutazone | 400 mg/L |
Drug Interference Summary
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Analytical performance (continued)
The following discusses cross-reactivity with hemoglobin derivatives.
Cross-Reactivity with Hemoglobin Derivatives
Six hemoglobin derivatives were evaluated for potential interference of the assay. Two HbA1c levels, one near the medical decision level and one above it, were represented in whole blood sample pools. For each HbA1c level, two whole blood pools were prepared for each derivative, one with none and one with a high concentration of derivative. From the pools, a serial dilution was prepared to yield varying concentrations of the derivative for both HbA 1c levels.
Each sample was tested ten-fold for % HbA1c on a single cobas c 501 analyzer, using a single reagent lot.
The median value for each set of ten was calculated. The reference sample is the sample Level 0 in the dilution series; it contains no interferent. The initial value is the measured result for the reference sample. The results for all remaining samples in the dilution series are compared to the initial value. This comparison is evaluated as a percent deviation. Interference is significant when it exceeds 7% deviation from the initial value.
| endogenous substance | range tested | highest level tested with
no significant interference |
|----------------------|--------------|----------------------------------------------------------|
| HbA0 | 0-120 g/dL | 120 g/dL |
| HbAla+b | 0-0.64 g/dL | 0.48 g/dL |
| Acetylated Hb | 0-2.0 g/dL | 2.0 g/dL |
| Carbamylated Hb | 0-1.0 g/dL | 1.0 g/dL |
| Labile HbAlc | 0-100 mg/dL | 100 mg/dL |
| Glycated Albumin | 0-10 g/dL | 10 g/dL |
Cross-Reactivity with Hemoglobin Derivatives Summary
There is no significant cross-reactivity with these hemoglobin derivatives at physiologically occurring concentrations.
11
Analytical performance The following discusses the interference with hemoglobin variants. (continued)
Hemoglobin Variants Interference
A hemoglobin variant interference study was performed using a total of 116 samples that contain one of six common hemoglobin variants. This table summarizes the sample profile.
| Hemoglobin | Quantity
of Samples | Range of
% Content of Variant | Range of
Concentration in % HbA1c |
|------------|------------------------|----------------------------------|--------------------------------------|
| S | 20 | 31 - 42% S | 4.60 - 13.0 |
| C | 19 | 33 - 44% C | 4.68 - 13.0 |
| E | 20 | 27 – 33% E | 5.00 - 9.68 |
| D | 20 | 34 – 42% D | 4.79 - 9.78 |
| F | 20 | 2 – 28% F | 5.83 - 10.1 |
| A2 | 17 | 4 – 7% A2 | 4.90 - 8.56 |
| Total | 116 | | |
Representation of Hemoglobin Variants
Testing was performed on the candidate device and with an NGSP reference method that is known to be free from the hemoglobin interference being tested. This table categorizes results for the variants as they are impacted by % HbA1c concentration. The results reflect bias between actual sample results. Interference > 7% deviation from the reference method is significant.
| Hb Variant | 6.0 % HbA1c | 9.0 % HbA1c |
|---|---|---|
| C | -3.07 | -0.35 |
| S | 2.17 | 3.42 |
| E | -1.58 | 3.46 |
| D | -2.30 | 3.35 |
| A2 | -5.73 | -4.12 |
| F | Bias exceeds -7% | |
| when HbF content exceeds + 7%.¹ |
Hemoglobin Variant Study Results St
A negative bias with HbF is independent of % HbA1c but is directly proportional in magnitude to the % HbF content.
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Analytical performance The following discusses the lower limits of detection and linearity. (continued)
Lower Limits of Detection
LoB (Limit of Blank) and LoD (Limit of Detection) were determined according to CLSI EP 17-A.
LoB was determined using one analyte-free sample tested in five replicates on two cobas c 501 analyzers. LoD was determined using five low-analyte samples tested in singlicate on two cobas c 501 analyzers. Both LoB and LoD were evaluated for Hb and HbA 1c (g/dL). The tests were performed in two runs per day for three days per reagent batch with a total of three reagent batches.
LoB and LoD
| Hb (g/dL) | HbA1c (g/dL) | |||
|---|---|---|---|---|
| Reagent Batch | LoB | LoD | LoB | LoD |
| 1 | 0.0380 | 0.0948 | 0.0097 | 0.0239 |
| 2 | 0.0210 | 0.0594 | 0.0079 | 0.0197 |
| 3 | 0.0445 | 0.1133 | 0.0163 | 0.0315 |
Linearity
Linearity was performed according to CLSI EP6-A for this submission and for 510(k) K102914. For this submission, a dilution series was prepared using a high analyte concentration sample pool and an analyte-free pool. The pools were mixed in different ratios to vield a 20-level dilution series with varying concentrations of Hb and HbA1c. Values were measured in triplicate for each level. The median values were compared to the theoretical values and regressed.
The linearity results from this study and from the one included in 510(k) K102914 support the claimed reportable range.
Linearity Summary
| Unit of Measure | Linear Range | |
|---|---|---|
| Glycohemoglobin | mmol/L HbA1c | 0.186-1.61 |
| g/dL HbA1c | 0.30-02.6 | |
| Hemoglobin | mmol/L Hb | 2.48-24.8 |
| g/dL Hb | 4-40 | |
| Ratio | % HbA1c (DCCT/NGSP) | 4.2-20.1 |
| mmol/mol HbA1c (IFCC) | 23-196 |
Conclusion- based on the performance characteristics stated above, this device is substantially equivalent to the predicate device.
13
DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/13/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized symbol that resembles an abstract human figure.
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-Gt Silver Spring, MD 20993-002
August 8, 2013
Roche Diagnostics c/o Ms. Susan Hollandbeck Regulatory Affairs Consultant 9115 Hague Road INDIANAPOLIS IN 46256
Re: K121610
Trade/Device Name: cobas c 501 Tina-quant HbA1cDx Gen.3 Assay Regulation Number: 21 CFR §862.1373 Regulation Name: Hemoglobin A1c Test System Regulatory Class: Class II Product Code: PDJ Dated: July 26, 2013 Received: July 29, 2013
Dear Ms. Hollandbeck:
We have reviewed your Section 510(k) premarket notification of intent to market the device we have roviewed your betermined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use stated in the enorosaly to regally the enactment date of the Medical Device Amendments, or to conninered prior been reclassified in accordance with the provisions of the Federal Food, Drug, devices that have boon require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Trou may, therefore, marisions 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 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 or any I with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (2) CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
14
Page 2 - Susan Hollandbeck
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and n you dealle openite as not office of In Vitro Diagnostics and Radiological Health at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket 9 150. Theo, prodot note not 102.97). 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/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 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/cdrh/industry/support/index.html.
Sincerely yours,
Carol C. Benson -S for
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
15
Indications for Use
510(k) Number (if known): K121610
Device Name: cobas c 501 Tina-quant HbA1cDx Gen.3
Indications for Use:
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 cobas c 501 Tina-quant HbA1cDx Gen.3 assay is an in vitro diagnostics reagent system intended for quantitative determination of mmol/mol hemoglobin Alc (IFCC) and % hemoglobin Alc (DCCT/NGSP) in whole blood on the Roche/Hitachi cobas c 501 clinical chemistry analyzer.
Prescription Use _X (21 CFR Part 801 Subpart D)
And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostics and Radiological Health (OIR)
Katherine Serrano -S
Division Sign-Off
Office of In Vitro Diagnostics and Radiological Health
510(k) K121610
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