(434 days)
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No
The device description and performance studies focus on standard enzymatic and absorbance-based chemical analysis methods, with no mention of AI or ML algorithms for data processing or interpretation.
No
Explanation: This device is an in vitro diagnostic (IVD) device used for measuring Hemoglobin A1c levels, which aids in the diagnosis and monitoring of diabetes. It does not exert a therapeutic effect on the patient.
Yes
The device is described as aiding in the diagnosis of diabetes mellitus and identifying patients at risk for developing the disease, which falls under the definition of a diagnostic device.
No
The device description explicitly states that the assay consists of two separate concentration measurements (glycated hemoglobin and total hemoglobin) and utilizes an enzymatic method and absorbance measurement. It also includes Hemoglobin A1c Calibrators and Hemoglobin A1c Controls, which are physical components. This indicates it is a reagent/assay kit used on a laboratory instrument, not a software-only device.
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 used for "quantitative in vitro measurement" of hemoglobin A1c in human whole blood and hemolysate. It also mentions its use as an aid in the diagnosis and monitoring of diabetes mellitus.
- Device Description: The description details the components of the assay (reagents, calibrators, controls) and the method used to measure HbA1c and total hemoglobin, which are all typical characteristics of an in vitro diagnostic device.
- Performance Studies: The document includes detailed descriptions of performance studies conducted on the device, such as precision, linearity, interference, and method comparison studies. These types of studies are required for the regulatory approval of IVD devices to demonstrate their analytical performance.
- Predicate Device: The mention of a "Predicate Device(s)" with a K number (K130255) and name (ARCHITECT Hemoglobin A1c Reagents, Calibrators, and Controls) indicates that this device is being compared to a previously cleared IVD device, which is a standard part of the regulatory process for new IVDs.
All of these elements strongly indicate that this device is intended for in vitro diagnostic use.
N/A
Intended Use / Indications for Use
The Hemoglobin A1c assay is used in clinical laboratories for the quantitative in vitro measurement of percent hemoglobin A1c (NGSP) or HbA1c fraction mmol/mol (IFCC) in human whole blood and hemolysate on the ARCHITECT c 4000 System.
Hemoglobin A1c measurements are used as an aid in the 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.
The Hemoglobin A1c Calibrators are for use in the calibration of the Hemoglobin A1c assay on the ARCHITECT c 4000 System.
The Hemoglobin A1c Controls are used for the estimation of test precision and the detection of systematic analytical deviations of the Hemoglobin A1c assay on the ARCHITECT c 4000 System.
Product codes
PDJ, LCP, JIT, JJX
Device Description
The Hemoglobin A1c Reagent Kit contains:
- Reagent 1 (R1): 1 x 52 mL
- Reagent 2 (R2): 1 x 20 mL
- Diluent (A1cDIL): 2 x 35 mL
Estimated tests per kit: 300
The Hemoglobin A1c Calibrator Kit contains:
- Calibrator 1 (Cal 1): 1 x 1.6 mL (after reconstitution)
- Calibrator 2 (Cal 2): 1 x 1.6 mL (after reconstitution)
A1c Calibrators (lyophilized) contain hemoglobin and glycated hemoglobin from human whole blood. Prior to lyophilization, the calibrator matrix is an MES-buffered solution. Preservative: Ofloxacin.
The value-assigned A1c Calibrator values are within the following hemoglobin A1c ranges: - Calibrator 1: 4.59% to 6.02% HbA1c
- Calibrator 2: 10.52% to 13.37% HbA1c
The Hemoglobin A1c Control Kit contains:
- Low Control (Control L): 1 x 1 mL (after reconstitution)
- High Control (Control H): 1 x 1 mL (after reconstitution)
A1c Controls (lyophilized) contain hemoglobin and glycated hemoglobin from human whole blood. Prior to lyophilization, the control matrix is an MES-buffered solution. Preservative: Ofloxacin.
The value-assigned A1c Control values are within the following hemoglobin A1c ranges: - Low Control: 4.59% to 6.02% HbA1c
- High Control: 9.42% to 11.07% HbA1c
Principles of the Procedure:
The Hemoglobin A1c assay consists of two separate concentration measurements: glycated hemoglobin (HbA1c) and total hemoglobin (THb). The two concentrations are used to determine the percent HbA1c (NGSP units) or the hemoglobin fraction in mmol/mol (IFCC units).
The individual concentration values of HbA1c and THb generated by the Hemoglobin A1c assay are used only for calculating the percent hemoglobin A1c or HbA1c fraction, and must not be used individually for diagnostic purposes.
The anticoagulated whole blood specimen is lysed automatically on the system for the Whole Blood application or may be lysed manually using the Hemoglobin A1c Diluent (A1cDIL) for the Hemolysate application.
Glycated Hemoglobin (HbA1c):
The Hemoglobin A1c assay utilizes an enzymatic method that specifically measures N-terminal fructosyl dipeptides of the ß-chain of HbA1c.
- In the pretreatment process, the erythrocytes are lysed and the hemoglobin is transformed to methemoglobin by reaction with sodium nitrite.
- With the addition of Reagent 1 (R1) to the sample, the glycosylated N-terminal dipeptide (fructosyl-VH) of the ß-chain of hemoglobin is cleaved by the action of protease. The hemoglobin is transformed to stable methemoglobin azide by the action of sodium azide and the concentration of the hemoglobin is determined by measuring absorbance.
- Addition of Reagent 2 (R2) starts a reaction and fructosyl peptide oxidase (FPOX) is allowed to react with fructosyl-VH. The HbA1c concentration is measured by determining the resultant hydrogen peroxide.
Total Hemoglobin (THb):
The hemoglobin is oxidized to stable methemoglobin azide by the action of sodium nitrite and sodium azide and the concentration of the hemoglobin is determined by measuring absorbance (sample + R1).
Hemoglobin A1c Calculations:
The final result is expressed as %HbA1c (NGSP) or mmol/mol HbA1c (IFCC) and is automatically calculated by the system from the HbA1c/THb ratio as follows:
mmol/mol HbA1c IFCC: HbA1c (mmol/mol) = (HbA1c/THb) x 1000
%HbA1c DCCT/NGSP: HbA1c (%) = IFCC x 0.09148 + 2.152
Methodology: Enzymatic
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
Used in clinical laboratories.
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
-
Within-Laboratory Precision (20-Day)
- Study Type: Precision study based on CLSI document EP5-A2.
- Sample Size: Not explicitly stated as a single number, but involved 3 levels of human whole blood controls and human whole blood panels.
- Data Source: Internal testing.
- Key Results:
- NGSP (Whole Blood): Total imprecision (SD or %CV) ranged from 0.02 to 0.04 SD for Control Level 1, 0.3 to 0.4 %CV for Control Level 2, 0.4 to 0.5 %CV for Control Level 3 (Note: Control Level 3 data not included in draft insert due to concentration being above upper limit of measuring interval), 0.02 to 0.03 SD for panel near 4.0 %HbA1c, 0.3 to 0.4 %CV for panel 6.0-7.0 %HbA1c, 0.3 %CV for panel 8.0-10.0 %HbA1c.
- NGSP (Hemolysate): Total imprecision (SD or %CV) ranged from 0.01 to 0.02 SD for Low Control, 0.2 to 0.3 %CV for High Control, 0.3 to 0.5 %CV for Control Level 3, 0.01 to 0.03 SD for panel near 4.0 %HbA1c, 0.3 to 0.5 %CV for panel 6.0-7.0 %HbA1c, 0.3 to 0.4 %CV for panel 8.0-10.0 %HbA1c.
-
Limit of Blank (LoB) and Detection (LoD)
- Study Type: LoB/LoD study based on CLSI document EP17-A.
- Sample Size: Zero-level samples (minimum 3 replicates), low-level samples (minimum 2 replicates).
- Data Source: Internal testing using 2 lots of Hemoglobin A1c Reagents, 2 lots of Hemoglobin A1c Calibrators, and 1 lot of commercially available controls on 2 ARCHITECT c 4000 instruments.
- Key Results: LoB = 2.51 %HbA1c (3.89 mmol/mol), LoD = 2.52 %HbA1c (4.05 mmol/mol).
-
Interferences: Endogenous Substances
- Study Type: Interference study based on CLSI document EP7-A2.
- Sample Size: Test and reference samples tested in a minimum of 12 replicates.
- Data Source: Internal testing using 1 lot of Hemoglobin A1c Reagents and Calibrators and 1 lot of commercially available controls on 1 ARCHITECT c 4000 instrument.
- Key Results: No significant interference (difference within ± 5% for samples ≥ 5.7 %HbA1c) observed for Ascorbic Acid (3.0 mg/dL), Conjugated Bilirubin (20.0 mg/dL), Glucose (1000 mg/dL), Triglycerides (3000 mg/dL), Total Protein (22 g/dL), Unconjugated Bilirubin (15.0 mg/dL), Urea (667 mg/dL), Vitamin E (8.6 mg/dL).
-
Interferences: Hemoglobin Variants
- Study Type: Interference study based on CLSI document EP7-A2.
- Sample Size: Not explicitly stated for each variant, but ranges of samples for HbC (n=43), HbD (n=40), HbE (n=50), HbS (n=31), HbA2 (n=24), HbF (n=28) were tested.
- Data Source: Internal testing using 1 lot of Hemoglobin A1c Reagents and Calibrators, controls, on 1 ARCHITECT c 4000 instrument.
- Key Results: No significant interference observed for HbC, HbD, HbE, HbS, and HbA2 variants. Significant interference with Fetal Hemoglobin (HbF): "Difference exceeds -5% when the amount of HbF in the sample exceeds 5%". A negative % difference with HbF is proportional in magnitude to the % HbF present in the sample (e.g., 20.4% HbF resulted in -20.0% difference).
-
Interferences: Drugs
- Study Type: Interference study based on CLSI document EP7-A2.
- Sample Size: Minimum of 12 replicates.
- Data Source: Internal testing using 1 lot of Hemoglobin A1c Reagents and Calibrators and 1 lot of commercially available controls on 1 ARCHITECT c 4000 instrument.
- Key Results: No significant interference (difference within ± 5% for samples ≥ 5.7 %HbA1c) observed for various drugs at specified high test levels.
-
Interferences: Rheumatoid Factor
- Study Type: Interference study based on CLSI document EP7-A2.
- Sample Size: Minimum of 12 replicates.
- Data Source: Internal testing using 1 lot of Hemoglobin A1c Reagents and Calibrators and 1 lot of commercially available controls on ARCHITECT c 4000 instrument.
- Key Results: Not susceptible to interference effects from RF less than or equal to 200 IU/mL (difference within ± 5% for samples ≥ 5.7 %HbA1c).
-
Interferences: Hemoglobin Derivatives
- Study Type: Interference study based on CLSI document EP7-A2.
- Sample Size: Minimum of 12 replicates.
- Data Source: Internal testing using 1 lot of Hemoglobin A1c Reagents and Calibrators and 1 lot of commercially available controls on 1 ARCHITECT c 4000 instrument.
- Key Results: Not susceptible to interference effects from acetylated hemoglobin, carbamylated hemoglobin, or labile hemoglobin (difference within ± 5% for samples ≥ 5.7 %HbA1c).
-
Matrix Comparison
- Study Type: Matrix comparison study.
- Sample Size: Specimens collected from a minimum of 43 different donors.
- Data Source: Internal testing using 1 lot of Hemoglobin A1c Reagents and Calibrators and 1 lot of commercially available controls on 1 ARCHITECT c 4000 instrument.
- Key Results: Results support the use of Dipotassium EDTA (plastic), Lithium heparin (plastic), Sodium heparin (plastic), Sodium Fluoride/Disodium EDTA (plastic), Tripotassium EDTA (plastic) blood collection tube types.
-
Linearity
- Study Type: Linearity study based on CLSI document EP6-A.
- Sample Size: 9 samples (commercially available linearity sets and additional prepared samples), each tested in a minimum of 2 replicates.
- Data Source: Internal testing using 1 lot of Hemoglobin A1c Reagents and Calibrators and 1 lot of commercially available controls on 1 ARCHITECT c 4000 instrument.
- Key Results:
- NGSP: No deviation from linearity for samples ranging from 2.8 to 18.1 %HbA1c. Correlation Coefficient: 0.9996, Intercept: -0.40, Slope: 0.9709, r2: 0.999.
- IFCC: No deviation from linearity for samples ranging from 15.31 to 174.68 mmol/mol. Correlation Coefficient: 0.9997, Intercept: -6.17, Slope: 0.9831, r2: 0.999.
-
Method Comparison and Predicted Bias (vs. NGSP secondary reference laboratory method)
- Study Type: Method comparison study based on CLSI document EP9-A2-IR.
- Sample Size: Minimum of 120 human whole blood specimens. Tested in replicates of 2.
- Data Source: Internal testing on 2 ARCHITECT c 4000 instruments and an NGSP secondary reference laboratory method (Tosoh HPLC analyzer).
- Key Results:
- NGSP:
- Method Comparison: Hemolysate application: Deming regression slope 1.00, r-value 0.996. Whole Blood application: Deming regression slope 1.01, r-value 0.995.
- Predicted Bias: Hemolysate application: ranged from -2.4% to -0.7% at 5%, 6.5%, and 12 %HbA1c. Whole Blood application: ranged from -3.0% to -0.6% at 5%, 6.5%, and 12 %HbA1c.
- ATD Zone: Hemolysate application: 100.0% (128/128) observations in ATD zone, lower limit of 95% CI 97.1%. Whole Blood application: 100.0% (128/128) observations in ATD zone, lower limit of 95% CI 97.1%.
- IFCC:
- Method Comparison: Hemolysate application: Deming regression slope 0.98, r-value 0.996. Whole Blood application: Deming regression slope 1.00, r-value 0.996.
- Predicted Bias: Hemolysate application: ranged from -4.3% to -0.5% at 31.13, 47.53, 63.93, and 107.65 mmol/mol. Whole Blood application: ranged from -5.1% to -0.1% at 31.13, 47.53, 63.93, and 107.65 mmol/mol.
- ATD Zone: Hemolysate application: 96.9% (124/128) observations in ATD zone, lower limit of 95% CI 92.2%. Whole Blood application: 96.9% (124/128) observations in ATD zone, lower limit of 95% CI 92.2%.
- NGSP:
-
Total Error Near the Cutoff
- Study Type: Calculation based on bias and precision estimates.
- Key Results:
- Hemolysate (NGSP): % TE at 5.0% HbA1c (3.4%), 6.5% HbA1c (3.3%), 8.0% HbA1c (2.8%), 12.0% HbA1c (2.5%).
- Whole Blood (NGSP): % TE at 5.0% HbA1c (3.6%), 6.5% HbA1c (3.1%), 8.0% HbA1c (2.5%), 12.0% HbA1c (1.9%).
-
Method Comparison to Predicate Device
- Study Type: Method comparison study based on CLSI document EP9-A2-IR.
- Sample Size: Minimum of 120 human whole blood specimens. Tested in replicates of 2.
- Data Source: Internal testing on 2 ARCHITECT c 4000 and 2 ARCHITECT c 8000 instruments.
- Key Results:
- NGSP (First Replicate vs. First Replicate): Hemolysate application: Deming regression slope 0.99, r-value 0.999. Whole Blood application: Deming regression slope 1.00, r-value 0.999.
- NGSP (Mean vs. Mean): Hemolysate application: Deming regression slope 0.99, r-value 0.999. Whole Blood application: Deming regression slope 0.99, r-value 0.999.
- IFCC (First Replicate vs. First Replicate): Hemolysate application: Deming regression slope 0.99, r-value 1.000. Whole Blood application: Deming regression slope 1.00, r-value 1.000.
- IFCC (Mean vs. Mean): Hemolysate application: Deming regression slope 0.99, r-value 1.000. Whole Blood application: Deming regression slope 0.99, r-value 0.999.
-
Automated Lyse (Whole Blood Application) versus Manual Lyse Methods (Hemolysate Application)
- Study Type: Evaluation of performance.
- Key Results: Performance met study evaluation criteria, demonstrating acceptable automated and manual lyse methods across Within-Laboratory Precision and Method Comparison studies.
Key Metrics
- Precision: Standard Deviation (SD), Coefficient of Variation (%CV).
- Accuracy/Agreement: Deming regression slope, correlation coefficient (r-value), Predicted Bias (%), Total Error (TE).
- Measurement Range: Limit of Blank (LoB), Limit of Detection (LoD), Measuring Interval.
- Interference: Percentage difference (within ± 5%).
- Method Comparison: Percentage of observations in ATD Zone (Agreement with Total Analytical Error Distribution), lower limit of 95% CI.
- Linearity: Correlation coefficient, Intercept, Slope, r2.
Predicate Device(s)
Reference Device(s)
Not Found
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.
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Image /page/0/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized graphic of three human profiles facing to the right, stacked on top of each other. The profiles are rendered in a dark color, creating a sense of depth and unity. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the graphic.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
May 22, 2015
ABBOTT LABORATORIES JUDITH WALLACH DIAGNOSTICS DIVISION, DEPT. 09V6 AP8 100 ABBOTT PARK ROAD. ABBOTT PARK IL 60064
Re: K140654
Trade/Device Name: Hemoglobin A1c Assay. Hemoglobin A1c Calibrators, Hemoglobin A1c Controls Regulation Number: 21 CFR 862.1373 Regulation Name: Glycosylated hemoglogbin assay Regulatory Class: II Product Code: PDJ, LCP, JIT, JJX Dated: May 4, 2015 Received: May 5, 2015
Dear Ms. Judith Wallach:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food. Drug. and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the
1
electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/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 Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Courtney H. Lias -S
Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K140654
Device Name Hemoglobin A1c Assay Hemoglobin A1c Calibrators Hemoglobin A1c Controls
Indications for Use (Describe)
The Hemoglobin Alc assay is used in clinical laboratories for the quantitative in vitro measurement of percent hemoglobin A 1c (NGSP) or HbA1c fraction mmol/mol (IFCC) in human whole blood and hemolysate on the ARCHITECT c 4000 System.
Hemoglobin A1c measurements are used as an aid in the 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.
The Hemoglobin Alc Calibrators are for use in the callbration of the Hemoglobin A1c assay on the ARCHITECT e 4000 System.
The Hemoglobin A 1c Controls are used for the estimation of test precision of systematic analytical deviations of the Hemoglobin A1c assay on the ARCHITECT c 4000 System.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
X Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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Section 5: 510(k) Summary
This summary of the 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
1. Applicant Name
Judith Wallach, ADD, Regulatory Affairs Project Manager Abbott Laboratories Diagnostics Division Dept. 9V6, AP8 100 Abbott Park Road Abbott Park, IL 60064 Telephone Number: (224) 667-1132 Fax Number: (224) 667-4836 E-Mail: judith.r.wallach@abbott.com Date Summary prepared: March 13, 2014 Revised May 4, 2015
Grace LeMieux, ADD, Regulatory Affairs Director Phone (224) 668-0409 Fax (224) 668-4836 E-mail grace.lemieux@abbott.com
2. Device Name
Hemoglobin A1c Assay Hemoglobin A1c Calibrators Hemoglobin A1c Controls
Reagents
Classification Name: Assay, Glycosylated Hemoglobin Regulation Description: Glycosylated hemoglobin assay Trade Name: Hemoglobin A1c Common Name: HbA1c Governing Regulation: 862.1373 Device Classification: Class II Product Code: PDJ, LCP Panel Classification: Chemistry
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Calibrators
Classification Name: Calibrator, Secondary Regulation Description: Calibrator Trade Name: Hemoglobin A1c Calibrators (1 and 2) Common Name: Calibrator Governing Regulation: 862.1150 Device Classification: Class II Product Code: JIT Panel Classification: Clinical Chemistry
Controls
Classification Name: Single (Specified) Analyte Controls (assayed and unassayed) Regulation Description: Quality control material (assayed and unassayed) Trade Name: Hemoglobin A1c Controls (Low and High) Common Name: Control Governing Regulation: 862.1660 Device Classification: Class II Product Code: JJX Panel Classification: Clinical Chemistry
3. Predicate Device
ARCHITECT Hemoglobin A1c Reagents, Calibrators, and Controls (K130255)
Note: The candidate device consists of the same reagents as the predicate device, and utilizes the same calibrators and controls. The candidate device is intended for use on the ARCHITECT c 4000 System. The predicate device (K130255) was cleared for use on the ARCHITECT c 8000 System.
4. Description of Device
Reagents Description
The Hemoglobin A1c Reagent Kit contains:
| Component | Number of Bottles x Volume |
|---|---|
| Reagent 1 (R1) | 1 x 52 mL |
| Reagent 2 (R2) | 1 x 20 mL |
| Diluent (A1cDIL) | 2 x 35 mL |
Estimated tests per kit: 300
Calculation is based on the minimum fill volume per kit.
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| Reagent | Reactive Ingredients | Concentration |
|---|---|---|
| Reagent 1 | 10-(carboxymethylaminocarbonyl)- | |
| 3,7-bis(dimethylamino) | ||
| phenothiazine sodium salt | 0.000817% | |
| Protease (Bacterial) | E. coli , recombinant) | |
| Diluent | Sodium nitrite | > 0.05 to 10 mmol/L of Cyanate |
- Labile Hemoglobin with $\geq$ 1000 mg/dL of Glucose
The test and reference samples were tested in a minimum of 12 replicates using 1 lot of Hemoglobin A1c Reagents and Calibrators and 1 lot of commercially available controls on 1 ARCHITECT c 4000 instrument. The results were reported in both NGSP and IFCC units.
The Hemoglobin A1c assay had a difference within $\pm$ 5% for samples $\geq$ 5.7 %HbA1c. The Hemoglobin A1c assay is not susceptible to interference effects from acetylated hemoglobin, carbamylated hemoglobin, or labile hemoglobin.
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Matrix Comparison
A matrix comparison study was performed to evaluate the blood collection tube types that are suitable for use with the Hemoglobin A1c assay. Specimens with concentration values spanning the measuring interval of the assay were collected from a minimum of 43 different donors in the control tube type (dipotassium EDTA, plastic) and the blood collection tubes under evaluation. The blood collection tubes collected from one individual constituted one sample set.
Each sample was tested in a minimum of 2 replicates using 1 lot of Hemoglobin A1c Reagents and Calibrators and 1 lot of commercially available controls on 1 ARCHITECT c 4000 instrument.
The results support the use of the following blood collection tube types with the Hemoglobin A1c assay:
- Dipotassium EDTA, plastic
- Lithium heparin, plastic
- Sodium heparin, plastic
- Sodium Fluoride/Disodium EDTA, plastic
- Tripotassium EDTA, plastic
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Linearity
A linearity study was performed based on guidance from the CLSI document EP6-A.
Commercially available linearity sets, comprised of Levels 1, 2, 3, and 4, were obtained. Five additional samples were prepared by combining the 4 levels of the commercially available linearity sets in specific ratios. The 9 samples were tested using the Hemoglobin A1c assay. The 9 samples were tested in a minimum of 2 replicates using 1 lot of Hemoglobin A1c Reagents and Calibrators and 1 lot of commercially available controls on 1 ARCHITECT c 4000 instrument. All samples were tested as a set within a single run. The results were reported in both NGSP and IFCC units.
NGSP:
There was no deviation from linearity for samples ranging from 2.8 to 18.1 %HbA1c. The linearity regression analysis results in NGSP units are provided in the table below:
| Correlation
| Coefficient | Intercept | Slope | r2 |
|---|---|---|---|
| 0.9996 | -0.40 | 0.9709 | 0.999 |
IFCC:
There was no deviation from linearity for samples ranging from 15.31 to 174.68 mmol/mol. The linearity regression analysis results in IFCC units are provided in the table below:
| Correlation
| Coefficient | Intercept | Slope | r2 |
|---|---|---|---|
| 0.9997 | -6.17 | 0.9831 | 0.999 |
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Method Comparison and Predicted Bias
To demonstrate the assay effectiveness as an aid in the diagnosis of diabetes mellitus, 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, a method comparison study was performed using an NGSP secondary reference laboratory method (Tosoh HPLC analyzer) as the comparator (reference) method.
The study was performed based on guidance from the CLSI document EP9-A2-IR. A minimum of 120 human whole blood specimens were evaluated with the Hemoglobin A1c assay and the reference method.
For the Hemoglobin A1c assay, the specimens were tested internally in replicates of 2 using 2 lots each of Hemoglobin A1c Reagents and Calibrators, 1 lot of Hemoglobin A 1c Controls (for the hemolysate application), and 1 lot of commercially available controls (for the whole blood application) on 2 ARCHITECT c 4000 instruments.
The specimens were also tested with an NGSP secondary reference laboratory method in replicates of 2. The specimens were tested over a minimum of 5 days. The results were reported in both NGSP and IFCC units.
NGSP:
Method Comparison
- · For the Hemolysate application, the Deming regression slope was 1.00 and the correlation coefficient (r-value) was 0.996 for samples across the measuring interval when comparing the Hemoglobin A1c to the reference method.
- · For the Whole Blood application, the Deming regression slope was 1.01 and the correlation coefficient (r-value) was 0.995 for samples across the measuring interval when comparing the Hemoglobin A1c to the reference method.
Predicted Bias
The predicted bias from the regression ranged from -2.4% to -0.7% for the Hemolysate application and -3.0% to -0.6% for the Whole Blood application at 5%, 6.5%, and 12 %HbA1c.
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ATD Zone
- · For the Hemolysate application, the percentage of observations in the ATD zone was 100.0 (128/128) and the lower limit of the two-sided 95% CI was 97.1%.
- · For the Whole Blood application, the percentage of observations in the ATD zone 100.0 (128/128) and the lower limit of the two-sided 95% CI was 97.1%.
IFCC:
Method Comparison
- · For the Hemolysate application, the Deming regression slope was 0.98 and the correlation coefficient (r-value) was 0.996 for samples across the measuring interval when comparing the Hemoglobin A1c to the reference method.
- · For the Whole Blood application, the Deming regression slope was 1.00 and the correlation coefficient (r-value) was 0.996 for samples across the measuring interval when comparing the Hemoglobin A1c to the reference method.
Predicted Bias
The predicted bias from the regression ranged from -4.3% to -0.5% for the Hemolysate application and -5.1% to -0.1% for the Whole Blood application at 31.13, 47.53, 63.93, and 107.65 mmol/mol.
ATD Zone
- · For the Hemolysate application, the percentage of observations in the ATD zone was 96.9 (124/128) and the lower limit of the two-sided 95% CI was 92.2%.
- · For the Whole Blood application, the percentage of observations in the ATD zone was 96.9 (124/128) and the lower limit of the two-sided 95% CI was 92.2%.
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Total Error Near the Cutoff
Using the results of bias estimation (% Bias) in the method comparison study and precision estimates in the reproducibility study, the Total Error (TE) at four %HbA1c levels (approximately 5.0%, 6.5%, 8.0%, and 12.0%) was calculated as follows:
$$\text{\textbullet TE} = |\text{\textbullet Bias}| + 1.96 \ge \text{\textbullet CV} \ge (1 + \text{\textbullet Bias})^2$$
The results are presented in the tables below.
| % Total Error Summary - Hemolysate (NGSP) | |||||
|---|---|---|---|---|---|
| -- | -- | -- | -- | ------------------------------------------- | -- |
| % HbA1c Level | Average % Bias | % CV | % TE |
|---|---|---|---|
| 5.0 | -2.2 | 0.6 | 3.4 |
| 6.5 | -1.6 | 0.9 | 3.3 |
| 8.0 | -1.3 | 0.8 | 2.8 |
| 12.0 | -0.8 | 0.9 | 2.5 |
% Total Error Summary – Whole Blood (NGSP)
| % HbA1c Level | Average % Bias | % CV | % TE |
|---|---|---|---|
| 5.0 | -2.5 | 0.6 | 3.6 |
| 6.5 | -1.8 | 0.7 | 3.1 |
| 8.0 | -1.3 | 0.6 | 2.5 |
| 12.0 | -0.7 | 0.6 | 1.9 |
Measuring Interval
The measuring interval of the Hemoglobin A1c assay is 4.0 to 14.0 %HbA1c (20.22 to 129.51 mmol/mol HbA1c). The limits of the measuring interval were demonstrated through the results of the Within-Laboratory Precision, Tube Type, Linearity, and Method Comparison studies.
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Method Comparison to Predicate Device
The study was performed based on guidance from the CLSI document EP9-A2-IR.
A minimum of 120 human whole blood specimens were evaluated with the Hemoglobin A1c assay. The specimens were tested in replicates of 2 using 1 lot each of Hemoglobin A1c Reagents, Calibrators, and Controls (for the hemolysate application), and 1 lot of commercially available controls (for the whole blood application) on 2 ARCHITECT c 4000 and 2 ARCHITECT c 8000 instruments. The results were reported in both NGSP and IFCC units.
NGSP:
First Replicate versus First Replicate Regression Analysis
- · For the Hemolysate application, the Deming regression slope was 0.99 and the correlation coefficient (r-value) was 0.999.
- · For the Whole Blood application, the Deming regression slope was 1.00 and the correlation coefficient (r-value) was 0.999.
Mean versus Mean Regression Analysis
- · For the Hemolysate application, the Deming regression slope was 0.99 and the correlation coefficient (r-value) was 0.999.
- · For the Whole Blood application, the Deming regression slope was 0.99 and the correlation coefficient (r-value) was 0.999.
IFCC:
First Replicate versus First Replicate Regression Analysis
- · For the Hemolysate application, the Deming regression slope was 0.99 and the correlation coefficient (r-value) was 1.000.
- · For the Whole Blood application, the Deming regression slope was 1.00 and the correlation coefficient (r-value) was 1.000.
Mean versus Mean Regression Analysis
- · For the Hemolysate application, the Deming regression slope was 0.99 and the correlation coefficient (r-value) was 1.000.
- · For the Whole Blood application, the Deming regression slope was 0.99 and the correlation coefficient (r-value) was 0.999.
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Automated Lyse (Whole Blood Application) versus Manual Lyse Methods (Hemolysate Application)
Whole blood specimens are lysed automatically on the ARCHITECT c 4000 instrument with the Whole Blood application or may be lysed manually using the Hemoglobin A1c Diluent with the Hemolysate application. The performance of the Hemoglobin A1c automated lyse method versus the manual lyse method was evaluated by testing whole blood specimens using both applications (i.e., Whole Blood and Hemolysate) in the Within-Laboratory Precision and the Method Comparison studies. The results from these studies met the study evaluation criteria and therefore demonstrated acceptable automated and manual lyse methods.
8. Conclusion
The data presented in this premarket notification demonstrates that the Hemoglobin A 1c assay performs substantially equivalent to the predicate device, the ARCHITECT Hemoglobin A1c assay (K130255). Correlation was demonstrated by comparison to a National Glycohemoglobin Standard Program (NGSP) secondary reference laboratory method and by comparison to the predicate device (Hemoglobin A1c on the ARCHITECT c 8000 System).