The Hipro® Glycosylated Hemoglobin (HbA1c) Test System comprised of the Hipro Glycosylated hemoglobin (HbA1c) test kit and the HP-AFS/1 automatic immunoassay analyzer is used as an aid in diagnosis of diabetes mellitus, as an aid to identify patients who may be at risk for developing diabetes mellitus, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus. It is an in vitro diagnostics reagent system intended for quantitative determination of % hemoglobin A1c (DCCT/NGSP) in venous whole blood.
Device Story
The Hipro® Glycosylated Hemoglobin (HbA1c) Test System is an in vitro diagnostic system consisting of a test kit and the HP-AFS/1 automatic immunoassay analyzer. The system processes venous whole blood samples collected in K2-EDTA tubes. The test kit utilizes a nephelometry immunoassay method; reagents R1 (glycine buffer and latex) and R2 (glycine buffer, goat anti-mouse IgG, and mouse anti-human HbA1c monoclonal antibody) react with the sample. The HP-AFS/1 analyzer measures the reaction using light absorption, scattered light, and fluorescence modules. The system quantifies % HbA1c (DCCT/NGSP). It is intended for professional use in clinical settings. Healthcare providers use the quantitative results to assess long-term glycemic control, aiding in diabetes diagnosis and management. The system provides standardized results traceable to the NGSP.
Clinical Evidence
No clinical trials performed. Bench testing only. Method comparison study (n=120) against Bio-Rad D-100 showed high correlation (R=0.9972). Precision studies (n=3 analyzers, 20 days) showed total CVs ranging from 1.2% to 3.2%. Interference testing confirmed no significant impact from common endogenous/exogenous substances or hemoglobin variants (HbS, HbC, HbD, HbE, HbA2), excluding HbF.
Technological Characteristics
System components: Hipro HbA1c test kit (latex-enhanced nephelometry immunoassay) and HP-AFS/1 automatic immunoassay analyzer. Analyzer modules: light absorption, scattered light, and fluorescence. Specimen: venous whole blood (K2-EDTA). Measurement range: 4.3-14% HbA1c. Traceability: NGSP certified. Connectivity: includes data transmission interface.
Indications for Use
Indicated for use as an aid in the diagnosis of diabetes mellitus, identification of patients at risk for developing diabetes mellitus, and monitoring of long-term blood glucose control in individuals with diabetes mellitus. Intended for use with venous whole blood samples.
Regulatory Classification
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.
Special Controls
(b) Classification. Class II (special controls). Hemoglobin A1c test systems must comply with the following special controls: 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%, 6.5%, 8.0% and 12% hemoglobin A1c. This testing must evaluate precision over a minimum of 20 days using at least 3 lots of the device and 3 instruments, as applicable. ii) Performance testing of device accuracy must include a minimum of 120 blood samples that span the measuring interval of the new device and compare results of the new device to results of the 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%. 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.
*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.
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FDA
U.S. FOOD & DRUG
ADMINISTRATION
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY AND INSTRUMENT
## I Background Information:
A 510(k) Number
K220999
B Applicant
Shijiazhuang Hipro Biotechnology Co., Ltd.
C Proprietary and Established Names
Hipro® Glycosylated Hemoglobin (HbA1c) Test System
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| PDJ | Class II | 21 CFR 862.1373 - Hemoglobin A1c Test System | CH - Clinical Chemistry |
| LCP | Class II | 21 CFR 864.7470 - Glycosylated hemoglobin assay | HE - Hematology |
## II Submission/Device Overview:
A Purpose for Submission:
New device
B Measurand:
Whole Blood Glycosylated Hemoglobin (HbA1c)
C Type of Test:
Quantitative Nephelometric Immunoassay
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
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K220999 - Page 2 of 11
## III Intended Use/Indications for Use:
### A Intended Use(s):
See Indications for Use below.
### B Indication(s) for Use:
The Hipro® Glycosylated Hemoglobin (HbA1c) Test System comprised of the Hipro Glycosylated hemoglobin (HbA1c) test kit and the HP-AFS/1 automatic immunoassay analyzer is used as an aid in diagnosis of diabetes mellitus, as an aid to identify patients who may be at risk for developing diabetes mellitus, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus. It is an in vitro diagnostics reagent system intended for quantitative determination of % hemoglobin A1c (DCCT/NGSP) in venous whole blood.
### C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
- The device should not be used to diagnose Diabetes Mellitus in patients with iron deficiency and hemolytic anemia, various hemoglobinopathies, thalassemia, hereditary spherocytosis, malignancies and severe chronic hepatic and renal disease.
- The device should not be used in pregnant patients, patients with heterozygous sickle cell trait, hemolytic diseases and recent significant or chronic blood loss.
- The device should not be used in the diagnosis of gestational diabetes.
- In cases of rapidly evolving type 1 diabetes the increase of HbA1c values might be delayed compared to the acute increase in glucose concentrations. In these conditions diabetes mellitus must be diagnosed based on plasma glucose concentration and/or the typical clinical symptoms.
- This device has significant interference with fetal hemoglobin (HbF). HbA1c results are invalid for patients with abnormal amounts of HbF including those with known Hereditary Persistence of Fetal Hemoglobin.
### D Special Instrument Requirements:
The HP-AFS/1 automatic immunoassay analyzer
## IV Device/System Characteristics:
### A Device Description:
The Hipro® glycosylated hemoglobin (HbA1c) test system consists of the Hipro Glycosylated hemoglobin (HbA1c) test kit and the HP-AFS/1 automatic immunoassay analyzer. The Hipro Glycosylated hemoglobin (HbA1c) test kit further consists of two reagents R1 and R2. The Reagent 1 (R1) contains latex in a glycine buffer, and the Reagent 2 (R2) contains Goat anti-mouse IgG and mouse anti-human HbA1c monoclonal antibody.
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K220999 - Page 3 of 11
## B Principle of Operation:
The antigen-antibody reaction is used to directly determine the percentage of glycosylated hemoglobin (HbA1c) in total hemoglobin (Hb). The total hemoglobin and glycosylated hemoglobin in the sample have the same non-specific adsorption with latex to form a solid phase. When the specific HbA1c monoclonal antibody is added, a latex-HbA1c-mouse anti-human HbA1c monoclonal antibody complex is formed to cause agglutination due to the goat anti-mouse immunoglobulin G (IgG) antibody. The amount of agglutination is proportional to the amount of HbA1c solidified on the latex surface. The percentage of HbA1c in the sample to the total Hb can be obtained from the measured rate of change of the scattered light intensity at specific wavelength compared with the standard curve of the percentage concentration of HbA1c.
## C Instrument Description Information:
1. Instrument Name:
The HP-AFS/1 automatic immunoassay analyzer
2. Specimen Identification:
Sample identification number can either be entered manually or scanned on barcode.
3. Specimen Sampling and Handling:
Human venous whole blood should be collected in K2 EDTA tubes and can be stored at 2°C-8°C for 10 days before use.
4. Calibration:
Calibration information is provided for each new lot of the test kit through the QR code on the label of R1.
5. Quality Control:
The sponsor recommends multi-level controls being tested in each HbA1c run using Liquidchek Diabetes Control (K123798) from Bio-Rad as the quality control material of the device. Each laboratory should establish its own control ranges and routinely use quality control materials in every HbA1c run.
## V Substantial Equivalence Information:
### A Predicate Device Name(s):
D-100 HbA1c, D-100 HbA1c Calibrator Pack
### B Predicate 510(k) Number(s):
K151321
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K220999 - Page 4 of 11
# C Comparison with Predicate(s):
| Device & Predicate Device(s): | K220999 | K151321 |
| --- | --- | --- |
| Trade Name | Hipro Glycosylated Hemoglobin (HbA1c) Test System | D-100 HbA1c |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | An in vitro diagnostics device intended for the quantitative determination of hemoglobin A1c in whole blood as an aid in diagnosis of diabetes, as an aid in identifying patients who may be at risk for developing diabetes mellitus, and for the monitoring of long-term blood glucose control in individuals with diabetes mellitus. | Same |
| Traceability | The assigned HbA1c value of the Glycosylated hemoglobin (HbA1c) test kit is certified with the National Glycohemoglobin Standardization Program (NGSP). | Same |
| General Device Characteristic Differences | | |
| Methodology | Nephelometry Immunoassay Method | Ion-exchange HPLC |
| Measuring range | 4.3-14% HbA1c | 3.5- 20 % HbA1c |
# VI Standards/Guidance Documents Referenced:
- 21 CFR 862.1373 – Special controls for Hemoglobin A1c test system
- CLSI EP05-A3: Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline – Third Edition
- CLSI EP06-A2: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline– Second Edition
- CLSI EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline – Second Edition
- CLSI EP09-A3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline – Third Edition
- CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline – Second Edition
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VII Performance Characteristics (if/when applicable):
A. Analytical Performance:
1. Precision/Reproducibility:
Precision studies were conducted with the Hipro Glycosylated Hemoglobin (HbA1c) Test System using four K2 EDTA venous whole blood samples containing approximately 5.2%, 6.4%, 8.0%, and 12.3% HbA1c concentrations (P1, P2, P3 and P4 respectively) and two control samples containing approximately 6% and 11% HbA1c concentrations (QC1 and QC2 respectively). Samples were analyzed on three HP-AFS/1 Automatic Immunoassay Analyzer instruments using three lots of reagents on each instrument. Each sample was analyzed in two runs per day, two replicates per run, for 20 days. The results are shown below:
Precision for Analyzer 1
| Sample | Repeatability | | Between-Run | | Between-Day | | Between-Lot | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| P1 | 0.107 | 2.0% | 0.032 | 0.6% | 0.000 | 0.0% | 0.000 | 0.0% | 0.111 | 2.1% |
| P2 | 0.179 | 2.8% | 0.000 | 0.0% | 0.000 | 0.0% | 0.029 | 0.5% | 0.182 | 2.8% |
| P3 | 0.162 | 2.0% | 0.000 | 0.0% | 0.000 | 0.0% | 0.020 | 0.2% | 0.163 | 2.0% |
| P4 | 0.145 | 1.2% | 0.051 | 0.4% | 0.000 | 0.0% | 0.017 | 0.1% | 0.155 | 1.2% |
| QC1 | 0.176 | 2.9% | 0.000 | 0.0% | 0.000 | 0.0% | 0.020 | 0.3% | 0.177 | 2.9% |
| QC2 | 0.189 | 1.7% | 0.000 | 0.0% | 0.000 | 0.0% | 0.038 | 0.3% | 0.193 | 1.8% |
Precision for Analyzer 2
| Sample | Repeatability | | Between-Run | | Between-Day | | Between-Lot | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| P1 | 0.109 | 2.1% | 0.000 | 0.0% | 0.014 | 0.3% | 0.000 | 0.0% | 0.110 | 2.1% |
| P2 | 0.171 | 2.7% | 0.000 | 0.0% | 0.013 | 0.2% | 0.000 | 0.0% | 0.170 | 2.7% |
| P3 | 0.145 | 1.8% | 0.000 | 0.0% | 0.036 | 0.4% | 0.000 | 0.0% | 0.150 | 1.9% |
| P4 | 0.181 | 1.4% | 0.026 | 0.2% | 0.000 | 0.0% | 0.000 | 0.0% | 0.183 | 1.5% |
| QC1 | 0.177 | 2.9% | 0.000 | 0.0% | 0.020 | 0.3% | 0.027 | 0.5% | 0.180 | 3.0% |
| QC2 | 0.176 | 1.6% | 0.000 | 0.0% | 0.056 | 0.5% | 0.000 | 0.0% | 0.185 | 1.7% |
K220999 - Page 5 of 11
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Precision for Analyzer 3
| Sample | Repeatability | | Between-Run | | Between-Day | | Between-Lot | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| P1 | 0.093 | 1.8% | 0.000 | 0.0% | 0.011 | 0.2% | 0.000 | 0.0% | 0.094 | 1.8% |
| P2 | 0.163 | 2.6% | 0.000 | 0.0% | 0.033 | 0.5% | 0.000 | 0.0% | 0.166 | 2.6% |
| P3 | 0.243 | 3.0% | 0.000 | 0.0% | 0.000 | 0.0% | 0.022 | 0.3% | 0.244 | 3.0% |
| P4 | 0.145 | 1.2% | 0.000 | 0.0% | 0.063 | 0.5% | 0.050 | 0.4% | 0.166 | 1.3% |
| QC1 | 0.192 | 3.2% | 0.000 | 0.0% | 0.000 | 0.0% | 0.000 | 0.0% | 0.192 | 3.2% |
| QC2 | 0.147 | 1.3% | 0.000 | 0.0% | 0.039 | 0.4% | 0.036 | 0.3% | 0.156 | 1.4% |
All Analyzers Combined
| Sample | Repeatability | | Between-Run | | Between-Day | | Between-Lot | | Between-Analyzer | | Total | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| P1 | 0.10 | 2.0 | 0.01 | 0.3 | 0.0 | 0.0 | 0.00 | 0.0 | 0.01 | 0.2 | 0.10 | 2.0 |
| P2 | 0.17 | 2.7 | 0.00 | 0.0 | 0.0 | 0.0 | 0.01 | 0.2 | 0.06 | 1.0 | 0.17 | 2.7 |
| P3 | 0.19 | 2.3 | 0.00 | 0.0 | 0.00 | 0.0 | 0.02 | 0.2 | 0.03 | 0.4 | 0.19 | 2.4 |
| P4 | 0.16 | 1.3 | 0.01 | 0.1 | 0.03 | 0.2 | 0.03 | 0.2 | 0.09 | 0.7 | 0.19 | 1.5 |
| QC1 | 0.18 | 3.0 | 0.00 | 0.0 | 0.00 | 0.0 | 0.02 | 0.3 | 0.01 | 0.1 | 0.18 | 3.0 |
| QC2 | 0.17 | 1.6 | 0.00 | 0.0 | 0.03 | 0.3 | 0.03 | 0.3 | 0.00 | 0.0 | 0.18 | 1.6 |
2. Linearity:
Linearity was evaluated for the Hipro Glycosylated Hemoglobin (HbA1c) Test System using a dilution series consisting of 9 levels of HbA1c prepared by mixing high and low HbA1c whole blood pools in K2 EDTA. The expected sample concentrations were 4.3%, 5.5%, 6.4%, 7.4%, 8.4%, 10.2%, 11.4%, 12.6% and 13.8% HbA1c. Three replicates were tested at each concentration. The measured values were compared to the expected values. The linear regression is the following:
$$
Y = 1.0225X - 0.1524, R^2 = 0.999
$$
3. Analytical Specificity/Interference:
Endogenous and Exogenous Substances:
Interference studies were performed to assess the impact of endogenous and exogenous substances on the performance of the Hipro Glycosylated Hemoglobin (HbA1c) Test System. Pooled whole blood at two HbA1c levels (~6.6 and ~8.7% HbA1c) in K2 EDTA spiked with potential interferent was analyzed and compared to the same whole blood pool without interferent (control). The highest concentrations at which no significant interference (a difference of no more than ±7% from the control sample as defined by the sponsor) was observed are summarized below:
K220999 - Page 6 of 11
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| Interferent | Highest Concentration with No Significant Interference (mg/dL) |
| --- | --- |
| Lipemia | 600 |
| Unconjugated Bilirubin | 60 |
| Conjugated Bilirubin | 60 |
| Glucose | 9,000 |
| Rheumatoid Factor | 100 IU/mL |
| Total Protein | 15,000 |
| Acetaminophen | 20 |
| Acetylsalicylic acid | 100 |
| Ampicillin-Na | 100 |
| Ascorbic acid | 30 |
| Cefoxitin | 250 |
| Cyclosporin | 1.66 |
| Doxycycline | 5 |
| Heparin | 5000 U/L |
| Ibuprofen | 50 |
| Levodopa | 2 |
| Methyldopa | 2 |
| Metronidazole | 20 |
| N-Acetylcysteine | 166 |
| Phenylbutazone | 40 |
| Rifampicin | 6 |
| Theophylline | 10 |
## Cross Reactivity with Hemoglobin Derivatives:
Potential interference from HbA0, Labile HbA1c, Carbamylated Hb, Acetylated Hb, Glycated Albumin, and HbA1a+b were evaluated. Two HbA1c concentrations of pooled whole blood (~6.6% and ~8.7%) were spiked with the prepared potential interferent. The %HbA1c values were compared to the same control sample with no potential interferent present. The highest concentrations at which no significant interference (a difference of no more than ±7% from the control sample as defined by the sponsor) was observed are summarize below:
| Hemoglobin Derivatives | Highest Concentration Level Tested with No Significant Interference |
| --- | --- |
| Hb A0 | 150 g/dL |
| HbA1a+b | 1 g/dL |
| Labile HbA1c | 1 g/dL |
| Carbamylated Hb | 1.5 g/dL |
| Acetylated Hb | 1.5 g/dL |
| Glycated Albumin | 10 g/dL |
K220999 - Page 7 of 11
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# Hemoglobin Variant Interference:
A hemoglobin variant study was performed using K2 EDTA venous whole blood samples known to contain hemoglobin variants HbS, HbC, HbE, HbD, HbA2, and HbF. The samples containing the hemoglobin variants were tested using the Hipro Glycosylated Hemoglobin (HbA1c) Test System and using the comparator method (Bio-Rad VARIANT II TURBO Hemoglobin Testing System), which has been demonstrated to be free from interference by these hemoglobin variants. The following table summarizes the tested samples:
| Hemoglobin Variant | Number of Samples | Variant Concentration Range (%) | Range of %HbA1c Concentration |
| --- | --- | --- | --- |
| HbS | 20 | 16.8%-76.9% | 5.1-9.4 |
| HbC | 20 | 25%-66.6% | 4.7-9.7 |
| HbD | 20 | 12.9%-41.1% | 5.2-10.2 |
| HbE | 20 | 13.8%-30.5% | 5.1-12.2 |
| HbA2 | 20 | 3.1%-6.4% | 4.7-9.7 |
| HbF | 20 | 1.3%-40.5% | 4.4-8.4 |
Hemoglobin Variant Results Summary
| Hemoglobin Variants | Relative Bias Observed
Relative to the Comparator Method | | | |
| --- | --- | --- | --- | --- |
| | At ~6.5 % HbA1c | | At ~9.0% HbA1c | |
| | Relative bias, % | Range of relative bias, % | Relative bias, % | Range of relative bias, % |
| HbS | 1.69 | -3.08~6.15 | 1.20 | 1.08~1.35 |
| HbC | -0.17 | -3.77~3.77 | 2.27 | -1.15~4.11 |
| HbD | 1.67 | -1.79~5.08 | 2.10 | 1.16~3.03 |
| HbE | 1.58 | -1.67~5.36 | 1.38 | 0.00~4.17 |
| HbA2 | 1.57 | -1.79~5.00 | -0.51 | -1.02~0.00 |
| HbF | Specimens containing HbF (>8%) may yield inaccurate HbA1c with higher variability | | | |
The results show that there is no significant interference for HbS, HbC, HbE, HbD, and HbA2 at the concentrations stated in the table above.
The sponsor has included the following prominent boxed warning in the labeling: This device has significant negative interference with fetal hemoglobin (HbF). HbA1c results are invalid for patients with abnormal amounts of HbF including those with known Hereditary Persistence of Fetal Hemoglobin.
4. Assay Reportable Range:
The reportable range for this device is 4.3-14.0% HbA1c.
K220999 - Page 8 of 11
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5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
The assigned HbA1c values of the Hipro glycosylated hemoglobin (HbA1c) test kit are certified by the National Glycohemoglobin Standardization Program (NGSP). The NGSP certification expires in one year. See the NGSP website for current certification at http://www.ngsp.org.
6. Detection Limit:
The claimed measuring range for the HbA1c values of the Hipro glycosylated hemoglobin (HbA1c) test kit is 4.3 to 14%.
7. Assay Cut-Off:
Not applicable.
8. Accuracy (Instrument):
Not applicable. See method comparison study below.
9. Carry-Over:
Not applicable.
B. Comparison Studies:
1. Method Comparison with Predicate Device:
Method comparison testing was performed using 120 human whole blood samples in K2 EDTA with values spanning the assay measurement range of HbA1c. The candidate device results were compared to those from testing performed at a secondary NGSP reference laboratory on the Bio-Rad D-100 HbA1c Test as the comparator method. The distribution of samples spanning the measuring interval is as follows:
| % HbA1c | N | % of sample tested |
| --- | --- | --- |
| ≤ 5% | 9 | 7.5 |
| 5.0 – 6.0% | 11 | 9.2 |
| 6.0 – 6.5% | 25 | 20.8 |
| 6.5 – 7.0% | 36 | 30 |
| 7.0 – 8.0% | 10 | 8.3 |
| 8.0 – 9.0% | 10 | 8.3 |
| > 9.0% | 19 | 15.8 |
| Total | 120 | 100 |
Regression analyses were performed for the candidate device versus the comparator method. Summary of regression results are as follows:
K220999 - Page 9 of 11
{9}
| Method | Slope | 95% CI | y-intercept | 95% CI | R |
| --- | --- | --- | --- | --- | --- |
| Linear | 1.089 | 0.9952, 1.0226 | -0.0727 | -0.1775, 0.0321 | 0.9972 |
| Deming | 0.9884 | 0.9722, 1.0044 | 0.0926 | -0.0188, 0.2040 | 0.9972 |
| Passing-Bablok | 1.000 | 1.000, 1.0256 | 0.0000 | -0.1782, 0.0000 | 0.9830 |
Bias Estimation:
| %HbA1c | Bias | %Bias |
| --- | --- | --- |
| 5.23% | -0.0262 | -0.5% |
| 6.34% | -0.0163 | -0.26% |
| 8.03% | -0.0012 | -0.02% |
| 12.53% | 0.0388 | 0.31% |
## Total Error:
The bias estimation values determined in the method comparison study and the precision determined in the precision study were used to determine the total error at each of the HbA1c levels listed in the tables below. Total error was calculated by the following equation:
$$
\% \mathrm{TE} = \left| \% \mathrm{Bias} \right| + (1.96 \times \% \mathrm{CV}) \times (1 + \% \mathrm{Bias} / 100)
$$
| HbA1c Concentration, % | %Bias | %CV | %TE |
| --- | --- | --- | --- |
| 5.23 | -0.5% | 2.0 | 4.4 |
| 6.34 | -0.26% | 2.7 | 5.5 |
| 8.03 | -0.02% | 2.4 | 4.7 |
| 12.53 | 0.31% | 1.5 | 3.3 |
2. Matrix Comparison:
Not applicable.
## C Clinical Studies:
1. Clinical Sensitivity:
Not applicable
2. Clinical Specificity:
Not applicable
3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable
K220999 - Page 10 of 11
{10}
# D Clinical Cut-Off:
Not applicable.
# E Expected Values/Reference Range:
The following HbA1c ranges recommended by the American Diabetes Association (ADA) $^{1-3}$ may be used as an aid in the diagnosis of diabetes mellitus:
| HbA1c% (NGSP) | Suggested Diagnosis |
| --- | --- |
| Less than 5.7 | Non-Diabetic |
| 5.7 to 6.4 | Pre-Diabetic |
| 6.5 or higher | Diabetic |
The expected HbA1c range for non-diabetic adults is $4.0 - 6.0\%$
1. Hemoglobin A1C, Emily Eyth; Roopa Naik. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan. 2023 Mar 13.
2. American Diabetes Association. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019 Jan;42(Suppl 1):S61-S70.
3. American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2010, 33 (Suppl. 1), S62-S69.
4. HbA1c: A Review of Analytical and Clinical Aspects, Cas Weykamp, Ph.D., Ann Lab Med 2013;33:393-400.
# VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.
# IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
K220999 - Page 11 of 11
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Part 1 — Search, results, and everyday workflows 16 min
Part 2 — Embeddings: the galaxy map 3 min
1. Search: exact and fuzzy
Type a phrase like "coronary artery calcification" into the search box. You get two kinds of results. Exact results match the literal phrase — prefix searches work ("coronary artery calcificati") but suffix searches do not. Fuzzy results match on the meaning and intent of your phrase rather than the exact words, and are sorted by relevance score. Hover over the Exact or Fuzzy badge on any row to see exactly why it matched.
Use the checkboxes above the results to narrow: SaMD keeps only software-only devices, AI / ML keeps only devices with AI.
Exact vs. fuzzy search: what's the difference?
Exact matches on the literal phrase (prefix search works, suffix does not). Fuzzy matches on the meaning and intent of the phrase rather than the exact words. Hover over the badge on any row to see why it matched.
You search "coronary artery calcification" and want only software devices with AI. What two filters do you apply?
Narrow by SaMD (software-only devices), then narrow by AI/ML (devices with AI).
2. The results table
Scroll right in the results table. The intended use is extracted for you — no need to open the PDF. The device story gives a high-level snapshot of what the device does and how it's used. The AI Performance sub-table shows each output name, acceptance criteria, observed values, and development/test dataset descriptions — the same format Innolitics uses for regulatory strategy outputs, and the fastest high-level fingerprint of an AI device. It is AI-generated but has been very reliable in practice.
Where do you find a device's intended use without opening the PDF?
Scroll right in the search results table. The intended use column is extracted for you; no need to dig into the 510(k) summary PDF.
What does the AI Performance sub-table show, and why is it useful?
Output name, acceptance criteria, observed values, development dataset description, and test dataset description. It's the same format we use for regulatory strategy output and Fast 510(k) input, and the fastest high-level fingerprint of an AI device. AI-generated but reliable in practice.
3. Judging fuzzy relevance
Fuzzy results trail off in relevance as you scroll. Use three signals to decide how far down to go: the fuzzy badge explanations, the intended use column, and whether your target output (e.g., Cobb angle) still appears in the AI Performance sub-table. Once it stops appearing, you're past the relevant zone. A top hit with a low score (~0.4) and a stretched explanation is a hint the closest predicates are far away — the project may be headed for De Novo. Note the fuzzy search is a pattern match: it doesn't handle negation ("not") well, and hardware devices can appear — filter by SaMD/AI ML to cut them.
How do you judge how far down fuzzy search results to go?
Use the relevancy signals: the fuzzy badge explanations, the intended use column, and whether the target output (e.g., Cobb angle) still appears in the AI Performance sub-table. Once it stops appearing, results are trailing off in relevancy.
4. Device detail page: chat and citations
Click a device name to open its detail page: device facts on the left, a chat window on the right. Ask something like "Describe the training data". The answer carries little citation bubbles — click one to jump to the highlighted passage in the source PDF, so you can verify every AI answer against the document. There's also a Download PDF button for sharing.
How do you verify an AI chat answer on the device detail page?
Click the citation bubbles to jump to the relevant highlight in the source document.
Reading rule for every project: how many summaries do you read in full?
At least the three most relevant 510(k) or De Novo summaries, in full. After that, use targeted chat questions to confirm your memory quickly. The tool supports this professional habit — it doesn't replace it.
5. Side-by-side comparison
Select multiple rows in the results table (aim for under ~10), then open the PDF Viewer tab. Ask one question — it goes to all selected devices in parallel, each with citations. This is the fastest way to compare and contrast devices: training data, PCCP scope, how they handled adding new scanners, and so on.
What does the side-by-side PDF viewer mode do?
Select multiple devices, open the PDF viewer tab, and ask one question (e.g., "Describe the training data"). It queries all selected devices simultaneously with citations, so you can compare and contrast quickly.
6. Collections
With rows selected, go to the Collections tab and create a labeled collection (e.g., "Cobb Angle Project"). Reload that selection any time — before a client call, pull up the collection and ask questions across all of its devices at once.
How do you save a set of selected devices for later use?
Select the rows, go to the Collections tab, and create a labeled collection (e.g., "Cobb Angle Project"). You can reload the selection anytime and carry it into the PDF viewer and other tabs that support selections.
7. Product codes and the regulations tree
Click a product code in the results to jump to it in the regulations tree — identification text, sibling product codes, and devices you can open in a PDF viewer on the right. Click a regulation number to see its identification, special controls, and related product codes. You can also search by product code or regulation number at the top of the tree. Always read the special controls if any exist for your device — it broadens your search and sharpens pre-kickoff research.
What can you do from the regulations tree view?
Browse product codes and regulation numbers, read the identification text and special controls, browse sibling product codes, open device PDFs on the right, and search by product code or regulation number at the top of the tree.
8. Chart view
Click Show Chart and segment by regulation number (or product code) to see which regulations dominate your result set. Clicking a regulation takes you into the regulations tree. Great for spotting that most matches are, say, hardware laparoscopic devices — a cue to go back and filter.
How do you see which regulations dominate a search result set?
Click "Show Chart" and segment by Regulation Number. Clicking a regulation takes you to the regulations tree.
9. The predicate graph
Open the Predicates tab for a family-tree view of predicate relationships. Click a node to trace its parents and children; selections from search carry over pre-selected. Commonly predicated devices are worth reading — a lot of people predicated them for a reason. The visual lineage is also handy on client calls, e.g. to show how a predicate family evolved and justify why your predicate still holds.
In the predicate graph, why are commonly predicated devices worth reading?
A lot of people predicated them for a reason. Clicking a node traces parents and children, and selections from search carry over pre-selected.
10. Embeddings: the galaxy map
The Embeddings tab plots every matching document in a 2-D "galaxy map" where semantically similar devices cluster together. Hover or click clusters to explore, and let AI label the clusters for you. Embeddings beat product codes for grouping: two devices can carry different product codes (LLZ vs. QIH) yet do the same thing — the embedding captures the meaning of the intended use and device story. This is also exactly how retrieval-augmented generation (RAG) works under the hood, and it makes a great visual on client calls.
Try it yourself
Head to the search page and work through a few of these AI/ML fuzzy searches to build intuition: perivascular fat on CT · aortic valve calcification opportunistic screening on noncontrast CT · breast cancer prediction on digital pathology slides · autism detection · gestational age prediction · a hearing aid that can also detect a pulse · foundation model based analysis of ECG · large language models · penetration test. Watch how the relevance scores, intended use, and AI Performance tables tell you when results stop being meaningful.
