(511 days)
The LabonaCheck™ A1c is intended for the quantitative measurement of glycated hemoglobin in venous whole blood and capillary fingerstick samples. This device is intended for multiple patient, professional use. Measurement of percent glycated hemoglobin (HbA 1c) is effective in monitoring long-term glucose control in individuals with diabetes mellitus by using the LabonaCheck™ A1c. Only auto-disabling, single use lancing devices should be used with this system.
The system consists of HbA1c Analyzer (MH 200) and HbA1c Test kit. The LabonaCheck™ AIc HbAic Analyzer measures the coloured responses of the LabonaCheck™ A1c HbA1c Test Kit by spectral reflectance.
The LabonaCheck™ A1c device is intended for the quantitative measurement of glycated hemoglobin (HbA1c) in venous whole blood and capillary fingerstick samples for professional use. The provided document details several performance characteristic studies.
Here's an analysis of the acceptance criteria and study data:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state formal acceptance criteria in a dedicated section with pass/fail thresholds for all studies. However, the manufacturer's conclusions and noted percentage differences are used to infer an implied acceptance criterion where applicable.
| Performance Characteristic | Implied Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Precision/Reproducibility | Not explicitly stated, but typical expectations for HbA1c CV% are generally below 3-5% for clinical utility. | Internal Study (Within-run, Day-to-day, and Total Precision): - Reference A1c 4.3% (Mean 4.4%): Total Precision CV 3.0% - Reference A1c 6.2% (Mean 6.1%): Total Precision CV 2.6% - Reference A1c 8.9% (Mean 9.1%): Total Precision CV 1.9% - Reference A1c 11.7% (Mean 11.6%): Total Precision CV 2.2% - Reference A1c 14.3% (Mean 14.2%): Total Precision CV 1.6% External Study (Point-of-Care Sites): - Interval 1 (approx 4.8% HbA1c): Overall CV% between 2.9% - 3.5% (across operators and sites) - Interval 2 (approx 8.8% HbA1c): Overall CV% between 2.7% - 3.6% (across operators and sites) - Interval 3 (approx 13.2% HbA1c): Overall CV% between 2.7% - 3.5% (across operators and sites) |
| Linearity/Assay Measuring Range | The study aims to support linearity from 4% to 15%. % Recovery between real and expected values should be close to 100%. (Implied successful if sponsor claims support for the range). | Supported linearity from 4% to 15%. - Expected 3.2% (Real 3.5%): 108% Recovery - Expected 5.6% (Real 5.8%): 103% Recovery - Expected 8.0% (Real 8.1%): 101% Recovery - Expected 10.4% (Real 10.5%): 101% Recovery - Expected 12.7% (Real 12.9%): 102% Recovery - Expected 15.1% (Real 15.4%): 102% Recovery - Expected 17.5% (Real 17.5%): 100% Recovery |
| Detection Limit | A reportable range of 4% to 15% A1c. | LoB Mean: 3.10%, LoD Mean: 4.12%. This suggests the lower end of the reportable range (4%) is supported. |
| Analytical Specificity (Interference) | Recovery within ±10% of control results for interfering substances. (For Hemoglobin F: average bias within ±10% up to 22.7% HbF. For variants C, D, E, S, Carbamylated Hb, and Rheumatoid factor: within ±10% of reference difference). For Hemoglobin concentration: within 10% difference. | Known Substances: All tested substances (Ascorbic acid, Bilirubin, Glucose, Hemoglobin (up to 20g/dL), Lipid, Albumin, K3EDTA, Heparin, Sodium fluoride, Sodium citrate, Acetaminophen, Metformin, Acetylsalicylic acid, Glybenclamide, Ibuprofen) showed no significant interference (implied within ±10%). Hemoglobin Variants: - HbF: Average bias within ±10% up to 22.7%. The device is affected by HbF > 20%. - HbC, D, E, S: Satisfied acceptance criteria (within ±10% of reference difference). Other interfering factors: - Carbamylated Hemoglobin & Rheumatoid Factor: Satisfied acceptance criteria (within ±10% of reference difference). Hemoglobin Concentration: Satisfied acceptance criteria (within 10% difference) for concentrations ranging from 8.7g/dL to 21.0g/dL. The claimed functional range is 10.0g/dL - 20.0g/dL. |
| Incubation Time Study | Reference difference within 5% when R1 reagent and whole blood sample incubated for 2 to 3 minutes. (Implied acceptance met if results within 5%). | When R1 reagent and whole blood sample incubated for 2 to 3 minutes, reference difference was within 5%. (Acceptance criteria satisfied). |
| Method Comparison (Accuracy) w/ Predicate Device | Not explicitly stated but typical metrics for point-of-care devices include a certain percentage of results within ±X% or correlation coefficient/slope/intercept criteria. For this submission, comparison to predicate and reference devices is key. For the difference % to predicate, 90% or more within 10% is often an acceptance. | LabonaCheck™A1c vs. Tosoh G7: 100% (50/50) within ±10% difference. Slope 1.0552, Intercept -0.4360, Correlation 0.9708. NycoCard vs. Tosoh G7: 96% (48/50) within ±10% difference. Slope 1.0613, Intercept -0.3304, Correlation 0.9695. LabonaCheck™A1c vs. NycoCard: 96% (48/50) within ±10% difference. Slope 0.9873, Intercept -0.0516, Correlation 0.9873. |
| Point-of-Care Study (Accuracy) | Slope (0.9-1.1), Intercept (less than 1%), Correlation coefficient results of three POC sites satisfied the acceptance criteria. | Venous Blood Samples (All sites combined): Slope 1.0005 (95% CI 0.9796 |
| Matrix Comparison | Not explicitly stated, but the sponsor concluded that the stated anticoagulants can be used, implying satisfactory performance based on the linear regression analysis. | K3EDTA vs. Sodium Heparin (combined results): Slope 0.9682 (95% CI 0.9279 |
2. Sample Size Used for the Test Set and Data Provenance
- Precision Studies (Internal): The internal study details whole blood samples, tested per day using two meters and two lots of reagents. The table shows 5 reference A1c levels. The specific number of distinct patient samples is not explicitly stated, but rather "whole blood samples" were used, with replicates for statistical analysis, implying a controlled, prospective study design. Provenance is internal (CERAGEM Medisys Inc.).
- Precision Studies (External): 3 intervals of HbA1c EDTA blood were analyzed. The specific number of distinct patient samples is not stated directly, but it specifies "three intervals of HbA1c EDTA blood." This was a multi-site prospective study conducted at three Point-of-Care (POC) sites. Provenance is external (three POC sites).
- Linearity/Assay Measuring Range: 7 mixed control solutions were used. This is likely a prospective, controlled study using prepared samples. The provenance is internal to the manufacturer.
- Detection Limit: A zero sample (blank) and five low HbA1c samples (n=60, Ns=60 for each, assayed twice a day in replicates of ten for three days). This is prospective, controlled study. Provenance is internal to the manufacturer.
- Analytical Specificity (Interference):
- Common Substances: Whole blood sample pools (3 intervals) were spiked with interfering substances. This is a controlled, prospective study. Provenance is internal to the manufacturer.
- Hemoglobin Variants (F, C, D, E, S): Samples provided by the National Glycohemoglobin Standardization Program (NGSP). This implies retrospective use of well-characterized samples from the NGSP program. Provenance: NGSP (likely international, given their role in standardization).
- Carbamylated Hemoglobin & Rheumatoid Factor: 10 samples (whole blood and spiked samples). This is a controlled, prospective study. Provenance is internal to the manufacturer.
- Hemoglobin Study: 50 whole blood samples. This is a prospective study using patient samples. Provenance is internal to the manufacturer.
- Incubation Time Study: Whole blood samples of 3 HbA1c concentrations (Low, Medium, High). This is a controlled, prospective study. Provenance is internal to the manufacturer.
- Method Comparison w/ Predicate Device: 50 EDTA venous whole blood patient samples (25 at each of two POC sites). Samples spanned 4.2-14.5% A1c. This is a prospective study using patient samples. Provenance is two Point-of-Care (POC) sites.
- Point-of-Care Study (Accuracy):
- Venous Blood: 120 EDTA venous whole blood samples (40 at each of three POC sites). Samples spanned 4.5-14.6% A1c. This is a prospective study using patient samples. Provenance is three Point-of-Care (POC) sites.
- Capillary Blood: 120 capillary blood samples (40 at each of three POC sites). Samples spanned 4.2-14.8% A1c. This is a prospective study using patient samples. Provenance is three Point-of-Care (POC) sites.
- Matrix Comparison: Venous whole blood samples (K3EDTA, Sodium heparin, NaF) collected from 40 donors. Samples spanned 4.5-14.1% A1c. This is a prospective study using patient samples. Provenance is internal to the manufacturer.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
The studies primarily involve quantitative measurements for HbA1c.
- For accuracy studies (Method Comparison, POC Study, Matrix Comparison), the ground truth was established by a reference method, Tosoh G7, and the predicate device, NycoCard® HbA1c, not by human experts interpreting results. The Tosoh G7 is likely an NGSP-certified laboratory method, considered a gold standard for HbA1c. The NycoCard® HbA1c is a legally marketed predicate device.
- For Precision studies, there isn't a "ground truth" in the sense of expert interpretation; rather, the "reference A1c (%)" values are used as targets for reproducibility.
- While operators (6 intended users across 3 sites for external precision and POC studies) performed the tests, they were not establishing ground truth, but rather generating test results to be compared against established reference values. The specific qualifications of these operators are not detailed beyond "intended users."
4. Adjudication Method for the Test Set
Not applicable. This device provides a quantitative measurement of a biomarker (HbA1c). The "ground truth" is established by laboratory reference methods (Tosoh G7, NGSP certified methods) or comparison to a predicate device, not by expert consensus or adjudication of qualitative interpretations.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was Done
No, an MRMC comparative effectiveness study was not explicitly done. The studies mentioned involve multiple operators or sites (e.g., 6 operators at 3 POC sites), but this is primarily to assess reproducibility and accuracy in a real-world setting, not to measure the human diagnostic improvement with vs. without AI assistance. The device is a standalone quantitative analyzer, not an AI-assisted diagnostic aid for human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was Done
Yes, the core of the submission provides standalone performance of the LabonaCheck™ A1c device. The studies evaluate the device's accuracy, precision, linearity, detection limits, and interference characteristics directly, comparing its results against reference methods or a predicate device. Human involvement is as operators performing the test, not as interpreters whose performance is being augmented by an algorithm.
7. The Type of Ground Truth Used
The ground truth used for these studies is primarily reference method data and, in some cases, predicate device data.
- For accuracy and method comparison studies, the Tosoh G7 (a laboratory reference method, likely NGSP-certified) served as the primary reference for establishing "true" HbA1c values.
- For interference studies of hemoglobin variants, NGSP-provided samples were used, with comparisons made against NGSP data (results of Primus - the predicate manufacturer).
- For precision and linearity, controlled samples with known or targeted HbA1c concentrations were used.
8. The Sample Size for the Training Set
This submission describes a medical device (HbA1c analyzer and test kit) that performs a chemical assay for quantitative measurement. It is not an AI/ML algorithm that requires a "training set" in the conventional sense of machine learning. Therefore, a training set sample size is not applicable to this type of device.
9. How the Ground Truth for the Training Set Was Established
As stated above, this is not applicable as the device is not an AI/ML algorithm requiring a training set. The device operates based on a boronate affinity assay, a chemical method.
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K IIIII28
SEP
13 2012
510(k) Summary
In accordance with the requirements of 21 CFR.807.92, the following information about 510(k) safety and effectiveness is being submitted.
-
- Submitter
CERAGEMS
- Submitter
MEDISYS
CERAGEM Medisys Inc.
#103-703, SK Ventium, 522 Dangjeong-dong, Gunpo-si, Gyeonggi-do, 435-776, Republic of Korea Phone : (+82) 070-4172-6805 Fax : (+82) 31-455-8822
-
- Date Prepared
August 24, 2012
- Date Prepared
-
- Device Name
Common name : LabonaCheck ™ Alc
- Device Name
Classification : Class II
(Regulation: 21 CFR 864.7470 )
Product Code : LCP (Assay, Glycosylated Hemoglobin)
-
- Predicate Device
The LabonaCheck™ Alc is substantially equivalent to NycoCard® HbAIc described as below.
- Predicate Device
(1) Trade Name: NycoCard® HbA1c Glycated Hemogiobin Assay
- (2) Applicant: Primus Corporation
- (3) 510(K) Number: K993131
- (4) Regulatory Class: II
- (5)-Product-Code:-LCP_
-
- Device Description
The system consists of HbA1c Analyzer (MH 200) and HbA1c Test kit.
The LabonaCheck™ AIc HbAic Analyzer measures the coloured responses of the LabonaCheck™ A1c HbA1c Test Kit by spectral reflectance.
5-1
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6. Intended Use
CERAGEM
MEDISYS
-
- Intended use(s): See indications for use.
-
- Indication(s) for use
The LabonaCheck™ Alc consists of LabonaCheck™ Alc HbAlc analyzer and LabonaCheck™ A1c HbA1c Test kit, is for in-vitro diagnostic use only. LabonaCheck TMAIc HbA1c Analyzer is designed to analyze the LabonaCheck™ A1c HbA1c Test Kit.
The LabonaCheck™ AIc is intended for the quantitative measurement of glycated hemoglobin in venous whole blood and capillary fingerstick samples. This device is intended for multiple patient, professional use. Measurement of percent glycated hemoglobin (HbA1c) is effective in monitoring long-term glucose control in individuals with diabetes mellitus by using the LabonaCheck™ Alc. Only auto-disabling, single use lancing devices should be used with this system.
| Comparison | ||
|---|---|---|
| Item | Device | Predicate |
| Device Name | LabonaCheck™ A1c | NycoCard® HbA1c |
| Similarities | ||
| Intended Use | The LabonaCheck A1c is an in-vitro diagnostic test for quantitative measurement of glycated hemoglobin (HbA1c) in venous whole blood and capillary fingerstick samples. | The NycoCard HbA1c is a rapid in vitro test for measurement of glycated hemoglobin in human blood. |
| Detection Method | Boronate affinity assay | Boronate affinity assay |
| Analytes | Glycated hemoglobin (HbA1c) | Glycated hemoglobin (HbA1c) |
| Sample Volume | 5 uL | 5 uL |
| Test Time | 3 minutes | 3 minutes |
-
- Comparison to Predicate Device
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Image /page/2/Picture/0 description: The image shows the logo for CERAGEM MEDISYS. The word "CERAGEM" is in bold, uppercase letters, and the word "MEDISYS" is in smaller, uppercase letters below it. To the right of the words is a geometric design.
| Measuring range | 4 ~ 15% | 4 ~ 15% |
|---|---|---|
| Storage Condition(Humidity range)(Test kit) | 2 | 2~8°C(Below 70%) |
| Warranty(Analyzer) | 1 year | 1 year |
| Differences | ||
| Power (Battery) | CR2032 | NiMH |
| Storage Condition(Humidity range) | HbA1c Analyzer 10 | Reader II 2 |
Conclusion
As the comparison table, the LabonaCheck™ Alc has same intended use, detection method, analytes, same volume, test time, measuring range, storage condition , humidity range (test kit), warranty (analyzer).
To sum up with the similarities, the LabonaCheck™ Alc is similar with the predicate device because most of the specifications deciding the characteristic of the device same.
In conclusion, despite of the difference such as power (battery) and etc., the LabonaCheck™ Alc is substantially equivalent to NycoCard® HbA1c.
8. Performance characteristics
A. Analytical Performance
a. Precision/Reproducibility
Precision studies were conducted internally by the manufacturer and externally at three POC -sites.Precision.studies_were.modeled_from_the NCCLS_guideline_EP5-A2.
Internal study performed at CERAGEM Medisys Inc.
Within-run, day to day and total precision were determined for whole blood samples. Test samples were analyzed per day of each sample using two meter and reagents of two lots.
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Image /page/3/Picture/1 description: The image shows the logo for CERAGEM MEDISYS. The word "CERAGEM" is in bold, block letters, with "MEDISYS" in a smaller font below it. To the right of the text is a geometric design that appears to be a stylized representation of a medical device or technology.
Within-run, day to day and total precision, expressed as Coefficient of Variation (CV) and standard deviation (STD).
| Interval | Reference A1c (%) | Mean(%) | STD | C.V(%) | STD | C.V(%) | STD | C.V(%) |
|---|---|---|---|---|---|---|---|---|
| Within run | Day to day run | Total Precision | ||||||
| 1 | 4.3 | 4.4 | 0.1 | 3.0 | 0.1 | 2.8 | 0.1 | 3.0 |
| 2 | 6.2 | 6.1 | 0.1 | 2.2 | 0.1 | 2.0 | 0.2 | 2.6 |
| 3 | 8.9 | 9.1 | 0.2 | 2.2 | 0.1 | 1.5 | 0.2 | 1.9 |
| 4 | 11.7 | 11.6 | 0.2 | 2.1 | 0.2 | 1.3 | 0.3 | 2.2 |
| 5 | 14.3 | 14.2 | 0.2 | 1.6 | 0.2 | 1.7 | 0.2 | 1.6 |
External study
An external precision study was performed in three point-of-care sites with six operators (two at each site). Three intervals of HbA Ic EDTA blood were analyzed. The results obtained on the A I c for site 1,2,3 are shown in the table below.
| Interval | POC Site 1 | POC Site 1 | POC Site2 | POC Site2 | POC Site3 | POC Site3 | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OP1 | OP2 | OP5 | OP6 | OP3 | OP4 | OP1 | OP2 | OP5 | OP6 | OP3 | OP4 | ||
| Mean | 4.8 | 4.8 | 4.9 | 4.9 | 4.8 | 5.0 | 4.9 | 4.9 | 4.9 | 4.9 | 4.9 | 4.9 | |
| STD | 0.14 | 0.15 | 0.16 | 0.16 | 0.14 | 0.16 | 0.14 | 0.16 | 0.16 | 0.15 | 0.17 | 0.15 | |
| C.V (%) | 2.9 | 3.2 | 3.3 | 3.3 | 2.9 | 3.2 | 2.9 | 3.3 | 3.3 | 3.1 | 3.5 | 3.1 | |
| I | Mean | 4.8 | 4.9 | 4.9 | 4.9 | 4.9 | 4.9 | ||||||
| STD | 0.15 | 0.16 | 0.17 | 0.15 | 0.16 | 0.16 | |||||||
| C.V (%) | 3.0 | 3.2 | 3.4 | 3.1 | 3.2 | 3.3 | |||||||
| Mean | 4.8 | 4.9 | 4.9 | ||||||||||
| STD | 0.16 | 0.16 | 0.16 | ||||||||||
| C.V (%) | 3.2 | 3.4 | 3.3 | ||||||||||
| 2 | Mean | 8.9 | 8.7 | 8.8 | 8.8 | 8.8 | 8.9 | 8.8 | 8.8 | 8.8 | 8.6 | 8.8 | 8.8 |
| STD | 0.25 | 0.29 | 0.29 | 0.28 | 0.29 | 0.26 | 0.26 | 0.23 | 0.28 | 0.26 | 0.32 | 0.28 | |
| C.V (%) | 2.8 | 3.3 | 3.3 | 3.2 | 3.3 | 2.9 | 2.9 | 2.7 | 3.2 | 3.0 | 3.6 | 3.1 | |
| Mean | 8.8 | 8.8 | 8.9 | 8.8 | 8.7 | 8.8 | |||||||
| STD | 0.28 | 0.29 | 0.29 | 0.25 | 0.28 | 0.30 | |||||||
| C.V (%) | 3.2 | 3.2 | 3.2 | 2.8 | 3.2 | 3.4 |
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Image /page/4/Picture/0 description: The image shows the logo for CERAGEM MEDISYS. The word "CERAGEM" is in bold, uppercase letters. Below it, the word "MEDISYS" is in smaller, uppercase letters. To the right of the words is a geometric design.
| Mean | 8.8 | 8.8 | 8.7 | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| STD | 0.28 | 0.27 | 0.29 | ||||||||||
| C.V (%) | 3.2 | 3.0 | 3.3 | ||||||||||
| Mean | 13.1 | 13.3 | 13.1 | 13.3 | 13.3 | 13.1 | 13.3 | 13.1 | 13.5 | 13.2 | 13.5 | 13.2 | |
| STD | 0.42 | 0.42 | 0.43 | 0.44 | 0.36 | 0.43 | 0.37 | 0.41 | 0.44 | 0.46 | 0.45 | 0.44 | |
| C.V (%) | 3.2 | 3.1 | 3.3 | 3.3 | 2.7 | 3.3 | 2.8 | 3.1 | 3.2 | 3.5 | 3.3 | 3.4 | |
| 3 | Mean | 13.2 | 13.2 | 13.2 | 13.2 | 13.3 | 13.3 | ||||||
| STD | 0.44 | 0.44 | 0.41 | 0.41 | 0.47 | 0.46 | |||||||
| C.V (%) | 3.3 | 3.3 | 3.1 | 3.1 | 3.5 | 3.4 | |||||||
| Mean | 13.2 | 13.2 | 13.3 | ||||||||||
| STD | 0.43 | 0.41 | 0.46 | ||||||||||
| C.V (%) | 3.3 | 3.1 | 3.5 |
b. Linearity/Assay Measuring Range
A linearity study across the entire clamed measuring range (4~15%) was evaluated using low (3.2% HbA1c) and high (17.5% HbA1c) control solutions. The low and high control solutions were mixed together in ratios to make five intermediate levels. The control solutions were mixed well and divided into two aliquots. One aliquot was used to perform on the LabonaCheck™ Alc analyzer and the second aliquot was analyzed on the reference HbAlc analyzer. Real value was compared to the theoretical values based upon the dilution factor. The % recovery was calculated with the following formula: Recovery = Real value / Expected % x 100. The percent recovery between the real values verses the expected values are shown in the table below :
| SampleNo. | Expected (%) | Real Value (%) | Difference (%) | % Recovery |
|---|---|---|---|---|
| 1 | 3.2 | 3.5 | 0.3 | 108 |
| 2 | 5.6 | 5.8 | 0.2 | 103 |
| 3 | 8.0 | 8.1 | 0.1 | 101 |
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Image /page/5/Picture/1 description: The image shows the logo for CERAGEM MEDISYS. The text "CERAGEM" is in bold, uppercase letters on the top line. Below that, the text "MEDISYS" is in smaller, uppercase letters. To the right of the text is a geometric design.
| 4 | 10.4 | 10.5 | 0.1 | 101 |
|---|---|---|---|---|
| 5 | 12.7 | 12.9 | 0.2 | 102 |
| 6 | 15.1 | 15.4 | 0.3 | 102 |
| 7 | 17.5 | 17.5 | 0 | 100 |
The results of the study support the sponsor's claimed that LabonaCheck™ Alc is linear from 4% to 15%.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
The LabonaCheck™ Alc device has been certified by the National Glycohemoglobin Standardization Program (NGSP). NGSP certifications are renewed annually. Current NGSP certifications are found on the web at http://www.ngsp.org/prog/index.html
d. Detection Limit
The !imit of Blank (LoB) and Limit of Detection (LoD) were determined by assaying a zero sample (blank) and five low HbAlc samples according to CLSI guideline EP17-A. A zero sample was Negative or very low concentration sample that is commutable with patient specimen. Each sample was assayed twice a day in replicates of ten (n=60) for three days on the LabonaCheck™ A1c.The detection limits were summarized in the table below :
(Ng=60, Ns=60)
| Blank(%) | Low concentration (%) | |
|---|---|---|
| Mean % | 3.10 | 4.12 |
| SD | 0.080 | 0.092 |
This assay has reportable range of 4% to 15% A1c.
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ERAGEM MEDISYS
e. Analytical Specificity
Interference Study: Interference testing was performed using a protocol based on NCCLS EP7-A. Studies were performed to assess common or known substances that could interfere with the LabonaCheck™ AIc. The interfering substances were evaluated in Interval 1 (4.66.6), Interval 2 (7.69.6), and Interval 3 (9.8~12.8). Three intervals of whole blood sample pools were spiked with interfering substance. The sponsor states that recovery within 10% of the control results was considered to be non-significant. The following compounds, at the levels indicated, were shown to have no significant interference on the LabonaCheck™ A1c test results : Ascorbic acid: 6mg/dL, Bilirubin (Conjugated): Smg/dL, Bilirubin (Unconjugated): 5mg/dL, Glucose: 1200mg/dL, Hemoglobin: 20g/dL, Lipid (Triglyceride): 500mg/dL, Albumin: 5g/dL, K3EDTA: 300 mg/dL, Heparin: 8000 U/dL, Sodium fluoride: 1000 mg/dL, Sodium citrate: 3.20%, Acetaminophen: 30 mg/dL, Metformin: 4 mg/dL, Acetylsalicylic acid: 1000mg/dL, Glybenclamide: 5 mg/dL, Ibuprofen: 40 mg/dL.
To evaluate the effect of Hemoglobin variants (F), Sponsor performed the testing using samples (HbF: 22.3~27.8%) provided by the NGSP. When sponsor compared between test result of candidate device and result of reference device, the average bias caused by the hemoglobin F sample were within ± 10% up to 22.7%. Therefore, sponsor claimed the test results of candidate device is affected by blood sample containing HbF (>20%).
To evaluate the effect of Hemoglobin variants (C, D, E, and S), Sponsor performed the testing using samples provided by the NGSP known to contain variants C, D, E, and, S on the LabonaCheck™ A1c. The results of LabonaCheck™ A1c were compared to NGSP's data (results of Primus). The sponsor's acceptance criteria was within ±10% of reference difference to be considered as no significant interference. Interference testing about Hemoglobin C, D, E, and S satisfied acceptance criteria.
NGSP has hemoglobin variants interference information for method at http://www.ngsp.org/prog/index.html
To evaluate the effect of Carbamylated hemoglobin and Rheumatoid factor, Sponsor
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Image /page/7/Picture/1 description: The image contains the logo for CERAGEM MEDISYS. The text "CERAGEM" is in a bold, sans-serif font, with "MEDISYS" in a smaller font size directly below it. To the right of the text is a stylized graphic element, possibly representing a medical device or technology.
performed the testing using 10 samples on the LabonaCheck™ A1c and reference device (Tosoh G7). The sponsor's acceptance criteria was within ±10% of reference difference to be considered as no significant interference. Interference testing about Carbamylated hemoglobin and Rheumatoid factor satisfied acceptance criteria.
r
| Carbamylated hemoglobin | Rheumatiod factor | |
|---|---|---|
| Control sample | Whole blood sample | Whole blood sample |
| Test sample 1(Low) | Whole blood sample +$2.5 \text{ mmol/L of sodium cyanate}$ | Whole blood sample +$100 \text{ IU/mL of rheumatoid factor}$ |
| Test sample 2(High) | Whole blood sample +$5 \text{ mmol/L of sodium cyanate}$ | Whole blood sample +$300 \text{ IU/mL of rheumatoid factor}$ |
Hemoglobin Study: The hemoglobin study was performed with 50 whole blood samples. We selected samples ranged from 4.6 to 22g/dL over a wide range of HbAIc concentrations. According to the results, LabonaCheckTM A1c satisfied the acceptance criteria (within 10% difference) at hemoglobin concentrations ranged from 8.7g/dL to 21.0g/dL. Sponsor claimed that the hemoglobin range for HbA1c measurement of the LabonaCheckTMA1c is 10.0g/dL -20.0g/dL. Lower than 10.0g/dL or higher than 20.0g/dL of hemoglobin concentration will lead to inaccurate result.
Image /page/7/Figure/5 description: The image shows a scatter plot titled "Effect of Hemoglobin concentration". The x-axis represents Hb Concentration in g/dL, ranging from 0.0 to 25.0. The y-axis represents the % Difference, ranging from -30.0% to 30.0%. The scatter plot shows the relationship between hemoglobin concentration and percentage difference, with data points clustered around the center.
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MEDISYS Incubation time study: The purpose of this testing is to evaluate incubation time between HbAlc in whole blood and R1 reagent have an effect on the LabonaCheck™ A1c. Each meter were performed 3 measurements using whole blood samples of 3 HbAlc concentrations (Low, Medium, High) for incubation times. According to test result, when R1 reagent and the whole blood sample incubated for 2 to 3 minutes, reference difference was
within 5%. Incubated samples for 2 minutes to 3minutes were satisfied acceptance criteria.
f. Assay cut-off
CERAGEM
Not applicable.
B. Comparison studies
a. Method comparison with predicate device
Accuracy: A method comparison study was performed with performed with 50 EDTA venous whole blood patient samples in two point of care sites (two at each site). The testing was performed by comparing the venous whole blood results of 50 samples (25 at each site) that spanned the claimed assay range to the results obtained by the predicate device, NycoCard® HbA1c. Samples ranged from 4.2-14.5 as measured by the reference device. The difference % are as follows:
| Difference betweenLabonaCheck™A1c andTosoh G7 | Difference betweenNycoCard and Tosoh G7 | Difference betweenLabonaCheck™A1c andNycoCard | |
|---|---|---|---|
| within± 10% | 100%(50/50) | 96%(48/50) | 96%(48/50) |
.The .linear_regression.and.correlation.coefficient.are.as follow:
| Slope | Intercept | Correlation coefficient | |
|---|---|---|---|
| LabonaCheck vs Tosoh G7 | 1.0552 | -0.4360 | 0.9708 |
| NycoCard vs Tosoh G7 | 1.0613 | -0.3304 | 0.9695 |
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| CERAGEMMEDISYS | CERAGEM Medisys Inc.www.ceragemmedisys.com | ||||
|---|---|---|---|---|---|
| LabonaCheck vs NycoCard | 0.9873 | -0.0516 | 0.9873 |
b. Point-of-Care study
Accuracy (using venous blood samples): POC study was performed with 120 EDTA venous whole blood samples in three point of care sites by 6 intended users (two at each site) on one meters. Total of 120 measurements are obtained (40 results of testing at each site) samples ranged from 4.5-14.6 as measured by the reference device. The linear regressions are as follows:
| Slope | Intercept | Correlation coefficient | |
|---|---|---|---|
| (95% confidence interval) | |||
| Site 1 | 1.0225(0.9850~1.0600) | -0.2129(-0.5291~-0.1034) | 0.9877 |
| Site 2 | 0.9868(0.9466~1.0271) | 0.0516(-0.2768~-0.3801) | 0.9848 |
| Site 3 | 0.9915(0.9565~1.0265) | 0.0756(-0.2172~-0.3683) | 0.9886 |
| All site combined | 1.0005(0.9796~1.0215) | -0.0292(-0.2036~-0.1451) | 0.9870 |
Accuracy (using capillary blood samples): POC study was performed with 120 capillary blood samples in three point of care sites on two meters. Total of 120 measurements are obtained (40 result of testing at each site) samples ranged from 4.2 %to 14.8 % as measured by the reference device. The linear regressions are as follows:
| Slope | Intercept | Correlation coefficient | |
|---|---|---|---|
| (95% confidence interval) | |||
| Site 1 | 1.0020 | 0.1670 | 0.9861 |
| (0.9629~1.0411) | (-0.4805~0.1465) | ||
| Site 2 | 0.9576 | 0.5119 | 0.9848 |
| (0.9185~0.9967) | (0.1959~0.8280) |
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| CERAGEMMEDISYS | CERAGEM Medisys Inc.www.ceragemmedisys.com | |||
|---|---|---|---|---|
| 0.9524 | 0.5584 | 0.9880 | ||
| Site 3 | (0.9180~0.9869) | (0.2773~0.8396) | ||
| All sitecombined | Site 1+2+3 | 0.9692 | 0.4230 | 0.9859 |
| (0.9481~0.9903) | (0.2523~0.5937) |
According to the above results, the slope (0.9-1.1), intercept (less than 1%), correlation coefficient results of three POC sites satisfied the acceptance criteria.
c. Matrix comparison
Venous whole blood samples (K3EDTA, Sodium heparin, NaF) collected from 40 donors were assayed on the LabonaCheck™ Alc and compared to the reference device (Tosoh G7). Samples ranged from 4.5-14.1%. The results of the studies are presented below:
(1) Linear regression analysis
| Slope | Intercept | Correlation coefficient | ||
|---|---|---|---|---|
| (95% confidence interval) | ||||
| Result 1 | 0.9661 | 0.2442 | 0.9685 | |
| K3EDTAvsSodium Heparin | (0.9088~1.0234) | (-0.2949-0.7833) | ||
| Result 2 | 0.9721 | 0.3790 | 0.9681 | |
| (0.9140~1.0301) | (-0.1587-0.9166) | |||
| Result 1+2 | 0.9682 | 0.3190 | 0.9670 | |
| (0.9279~1.0085) | (-0.0570-0.6951) | |||
| Result 1 | 0.9486 | 0.3807 | 0.9579 | |
| (0.8834-1.0139) | (-0.2332-0.9946) | |||
| K3EDTAvsNaF | 0.9498 | 0.4832 | ||
| Result 2 | (0.8834~1.0162) | (-0.1318-1.0983) | 0.9567 | |
| 0.9487 | 0.4364 | |||
| Result 1+2 | (0.9033-0.9941) | (0.0127-0.8602) | 0.9569 |
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Alc: The sponsor concluded that the following anticoagulants can be used with their Alc device: K3EDTA, Sodium heparin, NaF.
C. Safety and Reliability
Equipment temperature exposure limits: Repeatability precision using three levels of control solutions was evaluated before and after challenge with temperature change. The testing degrees of high temperature limits were 30±2℃, and testing degrees of low temperature limits were 4±2℃.
There is no significant difference or tendency between the each test result measured on the each condition, 4℃ and 30℃, on LabonaCheck™ Alc.
Equipment Humidity exposure limits: The humidity test was evaluated using three levels of control solutions. The testing degrees of high humidity were 80%RH±5 %, and the testing degrees of normal humidity limits were 40%RH±5 %, and the testing degrees of fow humidity were 10%RH±5 %. There is no significant difference or tendency on the each test result at 10%RH, 40%RH, and 80%RH.
D. Clinical studies
- Clinical sensitivity (1) Not Applicable
- (2) Clinical specificity: Not Applicable
- Other clinical supportable data(when a and b are not applicable) (3) Not Applicable
- E .- Clinical-cut-off:
Not Applicable
F. Appendix
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Image /page/12/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of two main elements: the department's name arranged in a circular fashion around the left side and a stylized symbol on the right. The symbol is a modern, abstract representation of a human figure, possibly suggesting care and support.
10903 New Hampshire Avenue Silver Spring, MD 20993
CERAGEM International c/o Raymond Chung 3699 Wilshire Blvd., Suite 930 Los Angeles, CA 90010
SEP 1 3 2012
Re: k11128 Trade Name: LabonaCheck™ Alc Regulation Number: 21 CFR §864.7470 Regulation Name: Quantitative, Hemoglobin Alc Test System Regulatory Class: Class II Product Codes: LCP Dated: September 4, 2012 Received: September 10, 2012
Dear Raymond Chung:
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).
{13}------------------------------------------------
Page 2
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please If you desire speeding and your stic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (2) proase note the regarding postmarket surveillance, please contact CDRH 's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) Office of but vemance and garding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/Medical
Devices/Safety/ReportalProblem/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 of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.html
Sincerely yours,
N. K. Jain, Ph.D.
Countney 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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Indication for Use
510(k) Number (if known): K111128
Device Name: LabonaCheck™ A1c
Indication For Use:
The LabonaCheck™ A1c is intended for the quantitative measurement of glycated hemoglobin in venous whole blood and capillary fingerstick samples. This device is intended for multiple patient, professional use. Measurement of percent glycated hemoglobin (HbA 1c) is effective in monitoring long-term glucose control in individuals with diabetes mellitus by using the LabonaCheck™ A1c. Only auto-disabling, single use lancing devices should be used with this system.
Prescription Use 4 (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 Diagnostic Device Evaluation and Safety (OVD)
Kattar Lussier
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K 11112 B
§ 864.7470 Glycosylated hemoglobin assay.
(a)
Identification. A glycosylated hemoglobin assay is a device used to measure the glycosylated hemoglobins (A1a , A1b , and A1c ) in a patient's blood by a column chromatographic procedure. Measurement of glycosylated hemoglobin is used to assess the level of control of a patient's diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient.(b)
Classification. Class II (performance standards).