(260 days)
The Alinity c Glucose Reagent Kit is used for the quantitation of glucose in human serum, plasma, urine, or cerebrospinal fluid (CSF) on the Alinity c analyzer. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.
The Alinity c System is a fully automated, random/continuous access, clinical chemistry analyzer intended for the in vitro determination of analytes in body fluids.
The Alinity c Glucose Reagent Kit contains Reagent 1 with ATP •2Na, NAD, G-6-PDH, and Hexokinase as reactive ingredients, and sodium azide as a preservative. The kit is available in two sizes: 400 tests per cartridge (10 cartridges per kit, 4000 tests per kit) and 1100 tests per cartridge (10 cartridges per kit, 11,000 tests per kit). The reagent container is made of black polypropylene with a black high density polyethylene closure.
The Alinity c Multiconstituent Calibrator Kit contains Cal 1 and Cal 2, prepared from a human-based matrix containing multiple analytes, including glucose, with sodium azide as a preservative. The calibrators are standardized for glucose using NIST SRM 965 and the ID-GC/MS reference method.
The Alinity c System is a fully automated chemistry analyzer allowing random and continuous access, as well as priority and automated retest processing using photometric and potentiometric detection technology. It uses photometric detection technology to measure sample absorbance for the quantification of analyte concentration. The system features robotic sample handling, continuous reagent access, continuous bulk solution access, and priority sample loading on all carrier positions.
This document describes the analytical performance of the Alinity c Glucose Reagent Kit and the Alinity c System for measuring glucose in human serum, plasma, urine, or cerebrospinal fluid (CSF). The studies evaluate various performance characteristics against predefined acceptance criteria to demonstrate substantial equivalence to predicate devices.
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Precision | ||
| Serum Samples | Within-laboratory imprecision (within-run, between-run, between-day) ≤ 5 %CV for samples targeted between 80 to 281 mg/dL. | For Control Level 2 (128 mg/dL): Lot 1 - 0.8% CV (within-run), 1.0% CV (within-laboratory); Lot 2 - 0.7% CV (within-run), 1.0% CV (within-laboratory). For Panel B (106 mg/dL): 0.8% CV (within-run), 0.9% CV (within-laboratory). All reported values for samples within the specified range (80-281 mg/dL) are well within the 5% CV criterion. Alinity c Glucose assay demonstrated acceptable precision. |
| Urine Samples | Within-laboratory imprecision (within-run, between-run, between-day) ≤ 6 %CV for samples targeted between 30 to 306 mg/dL. | For Control Level 1 (38 mg/dL): Lot 1 - 1.0% CV (within-run), 1.3% CV (within-laboratory); Lot 2 - 0.9% CV (within-run), 1.4% CV (within-laboratory). For Panel B (60 mg/dL): 1.6% CV (within-run), 2.1% CV (within-laboratory). For Panel C (110 mg/dL): 2.2% CV (within-run), 2.8% CV (within-laboratory). All reported values for samples within the specified range (30-306 mg/dL) are well within the 6% CV criterion. Alinity c Glucose assay demonstrated acceptable precision. |
| CSF Samples | Within-laboratory imprecision (within-run, between-run, between-day) ≤ 5 %CV for samples targeted between 29 to 60 mg/dL. | For Control Level 1 (60 mg/dL): Lot 1 - 0.9% CV (within-run), 1.1% CV (within-laboratory); Lot 2 - 0.7% CV (within-run), 1.0% CV (within-laboratory). For Control Level 2 (30-31 mg/dL): Lot 1 - 0.9% CV (within-run), 1.1% CV (within-laboratory); Lot 2 - 1.1% CV (within-run), 1.3% CV (within-laboratory). For Panel B (57 mg/dL): 0.8% CV (within-run), 0.9% CV (within-laboratory). All reported values for samples within the specified range (29-60 mg/dL) are well within the 5% CV criterion. Alinity c Glucose assay demonstrated acceptable precision. |
| Accuracy | Not explicitly stated as a single numerical acceptance criterion for each NIST level, but the performance is presented through mean, SD, %CV, bias, and %bias. The overall "Total Error" is also reported. | NIST level 1 (Target: 33.08): Mean 33 mg/dL, 0.2% Bias, 2.3% Total Error. NIST level 2 (Target: 75.56): Mean 76 mg/dL, 1.2% Bias, 2.5% Total Error. NIST level 3 (Target: 118.5): Mean 120 mg/dL, 1.1% Bias, 2.1% Total Error. NIST level 4 (Target: 294.5): Mean 306 mg/dL, 3.8% Bias, 4.7% Total Error. |
| Limit of Quantitation (LoQ) | Lowest concentration at which a maximum allowable precision of 20 %CV was met. | Serum/Plasma LoQ: 2.25 mg/dL. Urine/CSF LoQ: 0.86 mg/dL. |
| Linearity | Meet the limits of acceptable performance for linearity (part of Measuring Interval definition). | Serum/Plasma: Mean observed linear range 0 to 828 mg/dL. Urine: Mean observed linear range 0 to 843 mg/dL. CSF: Mean observed linear range 0 to 887 mg/dL. |
| Measuring Interval | Defined as the range of values which meets the limits of acceptable performance for linearity, imprecision, and bias. | Serum/Plasma: 5 mg/dL to 800 mg/dL. Urine/CSF: 1 mg/dL to 800 mg/dL. |
| Interference | Serum/Plasma: Bias of >6% or >1 mg/dL was considered significant interference. Urine: Bias of >10% or >1 mg/dL was considered significant interference. | The Alinity c Glucose assay (serum application) is not susceptible to interference from Unconjugated Bilirubin (≤ 30 mg/dL), Conjugated Bilirubin (≤ 60 mg/dL), Hemoglobin (≤ 2,000 mg/dL), Triglycerides (≤ 2,000 mg/dL), Ascorbic Acid (≤ 6 mg/dL), Acetaminophen (≤ 20 mg/dL), Ibuprofen (≤ 50 mg/dL), Acetylcysteine (≤ 167 mg/dL), Acetylsalicylic Acid (≤ 66 mg/dL), Sodium Salicylate (≤ 70 mg/dL). The Alinity c Glucose assay (urine application) is not susceptible to interference from Protein (≤ 50 mg/dL), Ascorbate (≤ 200 mg/dL), 8.5 N Acetic Acid (< 6.25 mL/dL), Boric Acid (≤ 250 mg/dL), 6 N Hydrochloric Acid (< 2.5 mL/dL), 6 N Nitric Acid (< 5.0 mL/dL), Sodium Oxalate (≤ 60 mg/dL), Sodium Carbonate (≤ 1.25 g/dL), Sodium Fluoride (≤ 400 mg/dL), Acetaminophen (≤ 20 mg/dL), Ibuprofen (≤ 50 mg/dL), Acetylcysteine (< 167 mg/dL). |
| Method Comparison | Acceptable correlation and agreement with the predicate device. | Serum (N=98): Correlation Coefficient 1.00, Intercept -1.78, Slope 1.00 (mg/dL) / Intercept -0.09, Slope 1.00 (mmol/L). Urine (N=118): Correlation Coefficient 1.00, Intercept 0.24, Slope 0.99 (mg/dL) / Intercept 0.01, Slope 0.99 (mmol/L). CSF (N=90): Correlation Coefficient 1.00, Intercept 0.50, Slope 1.00 (mg/dL) / Intercept 0.03, Slope 1.00 (mmol/L). The results were deemed acceptable. |
| Auto Dilution | Difference in measured concentration within ± 10% when comparing auto-diluted samples on the Alinity c analyzer to auto-diluted samples on the ARCHITECT c 8000 System. | Mean % difference -0.4% (range: -5.1% to 2.6%). Demonstrated acceptable performance. |
| Tube Type Equivalency | Acceptable for specified tube types. | Serum, Serum separator, dipotassium EDTA, lithium heparin, sodium heparin, sodium fluoride/potassium oxalate tubes were determined acceptable. |
2. Sample sizes and data provenance for the test set:
- Precision (20-Day Within-Laboratory):
- Serum Samples: 260-264 replicates for control levels, 523-528 replicates for panel samples (across reagent lots and instrument combinations).
- Urine Samples: 260-264 replicates for control levels, 525-528 replicates for panel samples (across reagent lots and instrument combinations).
- CSF Samples: 263-264 replicates for control levels, 526-528 replicates for panel samples (across reagent lots and instrument combinations).
- Data Provenance: Not explicitly stated, but typically these are prospective studies conducted in a controlled laboratory setting (likely within the manufacturer's R&D facilities or a collaborating lab).
- Accuracy (NIST Standards):
- 22 replicates for each of the 4 NIST levels.
- Data Provenance: Conducted in a controlled laboratory setting.
- Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ):
- LoB: n ≥ 60 replicates of zero-analyte samples.
- LoD & LoQ: n ≥ 60 replicates of low-analyte level samples.
- Data Provenance: Conducted in a controlled laboratory setting.
- Linearity:
- Sample sets used to cover the linear range. Specific 'n' for each sample type not individually quantified beyond "sample set."
- Data Provenance: Conducted in a controlled laboratory setting.
- Interference:
- Specific numbers of samples or replicates for interference studies are not provided, but the evaluation was conducted based on CLSI document EP07-A2.
- Data Provenance: Conducted in a controlled laboratory setting.
- Method Comparison:
- Serum: 98 samples.
- Urine: 118 samples.
- CSF: 90 samples.
- Data Provenance: Human serum, urine, and CSF specimens. Not explicitly stated if retrospective or prospective, or country of origin, but generally for device clearance, these are often prospective collections or carefully selected archived samples from diverse populations to ensure representativeness.
- Auto Dilution:
- Glucose serum specimens. Specific 'n' not provided beyond being a set of specimens.
- Data Provenance: Not explicitly stated, likely laboratory-prepared or clinical samples.
- Tube Type Equivalency:
- Minimum of 40 donors.
- Data Provenance: Samples collected from human donors.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
This document describes the analytical performance of an in vitro diagnostic (IVD) device for measuring glucose. For such devices, "ground truth" is typically established by:
- Reference Methods: Such as NIST (National Institute of Standards and Technology) certified reference materials (e.g., SRM 965 Glucose in Human Serum) and reference methods (e.g., ID-GC/MS - Isotope Dilution-Gas Chromatography Mass Spectrophotometry). These are highly accurate, traceable methods, and do not involve human "experts" in the diagnostic interpretation sense.
- Predicate Devices: The ARCHITECT c System and its associated Glucose assay (K060383) serve as the comparator (or "ground truth" surrogate) for method comparison studies.
- Clinical Laboratory Standards: The performance is evaluated against established clinical laboratory standards and guidelines (e.g., CLSI documents EP05-A2, EP17-A2, EP06-A, EP07-A2, EP09-A3). These standards define acceptable performance metrics.
Therefore, for this type of IVD device, there isn't a team of experts (like radiologists or pathologists) establishing a visual interpretation ground truth. The 'ground truth' is analytical, based on certified reference materials and established reference methods.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
Not applicable. Adjudication methods like 2+1 or 3+1 are typically used in studies involving subjective interpretation of medical images or clinical cases by multiple human readers (e.g., radiologists, pathologists) to establish a consensus ground truth. For an automated quantitative assay like a glucose test, the "ground truth" is objective and measured via reference methods or predicate devices, as described above.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, if so, what was the effect size of how much human readers improve with AI vs without AI assistance:
Not applicable. An MRMC study is relevant for AI-powered diagnostic imaging or interpretation tools where human readers' performance is compared with and without AI assistance across multiple cases. This document is for a fully automated in vitro diagnostic (IVD) chemistry analyzer and reagent kit, which does not involve human "readers" interpreting results in the same way.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, the studies presented here are for the standalone performance of the Alinity c Glucose Reagent Kit and the Alinity c System. The device measures glucose levels automatically, and the performance characteristics (precision, accuracy, linearity, interference, method comparison) are evaluated for the device itself. There is no "human-in-the-loop" aspect to the actual measurement process of the device as an IVD analyzer.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
The ground truth used is primarily reference measurements derived from:
- Certified Reference Materials: Specifically, NIST SRM 965 (Glucose in Human Serum), analyzed by a reference method (ID-GC/MS - Isotope Dilution-Gas Chromatography Mass Spectrophotometry) for accuracy studies.
- Comparator (Predicate) Device: The predicate Glucose assay (K060383) run on the ARCHITECT c System for method comparison studies. This serves as the comparative standard of care.
- Clinical Laboratory Standards (CLSI guidelines): These provide the framework and accepted ranges for evaluating various analytical performance characteristics (e.g., precision, linearity, LoQ).
8. The sample size for the training set:
The document does not explicitly mention a "training set" in the context of machine learning. This is an IVD device, and its analytical performance is validated against established laboratory standards and predicate devices. The development of such a device involves extensive R&D, calibration, and optimization using various samples, but these are not typically referred to as "training sets" in the same way as for AI/ML algorithms. The reported studies are for performance validation (test set).
9. How the ground truth for the training set was established:
Not applicable, as a "training set" as defined for AI/ML models is not directly addressed or implied for this type of IVD device. The development process would rely on precise chemical and enzymatic reactions, spectrophotometric detection principles, and calibration against reference materials to ensure accurate measurements across the analytical range.
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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 is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized image of three human profiles facing to the right, stacked on top of each other.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
October 19, 2017
ABBOTT LABORATORIES NOAH LERMER, PH.D. REGULATORY AFFAIRS DIRECTOR DEPT. 9AA, BLDG CP01-3, 100 ABBOTT PARK ROAD ABBOTT PARK, IL 60064
Re: K170316
Trade/Device Name: Alinity c Glucose Reagent Kit Alinity c System Regulation Number: 21 CFR 862.1345 Regulation Name: Glucose test system Regulatory Class: II Product Code: CFR, JJE Dated: September 06, 2017 Received: September 07, 2017
Dear Dr. Noah Lermer:
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
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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,
Stayce Beck -A
For: Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K170316
Device Name Alinity c Glucose Reagent Kit
Indications for Use (Describe)
The Alinity c Glucose Reagent Kit is used for the quantitation of glucose in human serum, plasma, urine, or cerebrospinal fluid (CSF) on the Alinity c analyzer. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CER 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
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Indications for Use
510(k) Number (if known) K170316
Device Name Alinity c System
Indications for Use (Describe)
The Alinity c System is a fully autom/continuous access, clinical chemistry analyzer intended for the in viro determination of analytes in body fluids.
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)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
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K170613 510(k) Summary (Summary of Safety and Effectiveness)
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.
I. Applicant Name
Abbott Laboratories Dept. 09AA, Bldg CP1 100 Abbott Park Road Abbott Park, IL 60064
Primary contact person for all communications:
Noah Lermer, PhD ADD, Director, Regulatory Affairs Phone: (224)-668-7613 Fax: (224) 667-4836 Email: Noah.Lermer@abbott.com
Secondary contact person for all communications:
Amy Ghering, PhD ADD, Associate Director, Regulatory Affairs Phone: (224) 668-6934 Fax: (224) 667-4836 Email: Amy.Ghering@abbott.com
Date Summary Prepared: January 31, 2017.
Date Summary Revised: October 19, 2017
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II. Device Name
Alinity c Glucose Reagent Kit Alinity c System
Alinity c Glucose Reagent Kit
Device Classification: Class II Classification Name: Hexokinase, glucose Governing Regulation: CFR 862.1345 Product Code: CFR
Alinity c System
Device Classification: Class I Classification Name: Discrete photometric chemistry analyzer for clinical use Governing Regulation: CFR 862.2160 Product Code: JJE
III. Predicate Device
Reagent Glucose (K060383)
Instrument
AEROSET/ARCHITECT c System family members (K980367)
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IV. Description of Device
A. Alinity c Glucose Reagent Kit
Kit Contents
Volumes (mL) listed in the table below indicate the volume per cartridge.
| Ref | 07P5520 | 07P5530 |
|---|---|---|
| Tests per cartridge | 400 | 1100 |
| Number of cartridges per kit | 10 | 10 |
| Tests per kit | 4000 | 11,000 |
| Reagent 1 (R1) | 26.5 mL | 66.4 mL |
| Reagent | Reactive Ingredients | Concentration |
|---|---|---|
| Reagent 1 | ATP •2Na | 9.0 mg/mL |
| NAD | 5.0 mg/mL | |
| G-6-PDH | 3000 U/L | |
| Hexokinase | 15,000 U/L |
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B. Alinity c Multiconstituent Calibrator Kit
The Alinity c Multiconstituent Calibrator contains:
| Number of Bottles × Volume | ||
|---|---|---|
| Component | 08P6001 | |
| Cal 1 | 3 × 2.9 mL | |
| Cal 2 | 3 × 2.9 mL |
The Alinity c Multiconstituent calibrators are prepared from a human-based matrix containing multiple analytes, including glucose. Sodium azide is present as a preservative.
The Alinity c Multiconstituent calibrators are prepared and standardized, for glucose, as described in the table below:
| Analyte | Reference Material | Reference Method |
|---|---|---|
| Glucose | NIST SRM 965 | ID-GC/MS |
NIST- National Institute of Standards and Technology SRM- Standard Reference Materials
ID-GC/MS- Isotope Dilution- Gas Chromatography Mass Spectrophotometry
C. Alinity c System
The Alinity c System is a fully automated chemistry analyzer allowing random and continuous access, as well as priority and automated retest processing using photometric and potentiometric detection technology. The Alinity c System uses photometric detection technology to measure sample absorbance for the quantification of analyte concentration.
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D. Principles of the Procedure
Glucose is phosphorylated by hexokinase (HK) in the presence of adenosine triphosphate (ATP) and magnesium ions to produce glucose-6-phosphate (G-6-P) and adenosine diphosphate (ADP). Glucose-6-phosphate dehydrogenase (G-6-PDH) specifically oxidizes G-6-P to 6-phosphogluconate with the concurrent reduction of nicotinamide adenine dinucleotide (NAD) to nicotinamide adenine dinucleotide reduced (NADH). One micromole of NADH is produced for each micromole of glucose consumed. The NADH produced absorbs light at 340 nm and can be detected spectrophotometrically as an increased absorbance.
Methodology: Enzymatic (Hexokinase/ G-6-PDH)
V. Intended Use of the Device
The Alinity c Glucose Reagent Kit is used for the quantitation of glucose in human serum, plasma, urine, or cerebrospinal fluid (CSF) on the Alinity c analyzer. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.
The Alinity c System is a fully automated, random/continuous access, clinical chemistry analyzer intended for the in vitro determination of analytes in body fluids.
VI. Comparison of Technological Characteristics
The Alinity c Glucose Reagent Kit is used for the quantitative analysis of glucose in human serum/plasma, urine or cerebrospinal fluid on the Alinity c analyzer.
The similarities and differences of the candidate assay (Alinity c Glucose Reagent Kit, LN 07P55) to the predicate assay (Glucose assay, LN 3L82) are presented in Table 1 starting on page 7 and Table 2 starting on page 8, respectively.
The similarities and differences between the Alinity c System and the AEROSET/ARCHITECT c System (K980367) are presented in Table 3 on page 9 and Table 4 on page 10, respectively.
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Table 1: Reagent Similarities
| Characteristics | Candidate AssayAlinity c Glucose Reagent Kit(LN 07P55) | Predicate Assay (K060383)Glucose(LN 3L82) |
|---|---|---|
| Technical Characteristics | ||
| Reagent Formulation | R1: Active ingredients: ATP• 2Na (9.0 mg/mL), NAD(5.0 mg/mL), G-6-PDH (3000 U/L), Hexokinase (15 000 U/L),Preservative: sodium azide (0.05%). | Same |
| Analyte Measured | Glucose | Same |
| Intended Use | The Alinity c Glucose assay is used for the quantitation ofglucose in human serum, plasma, urine, or cerebrospinal fluid(CSF). | Same |
| Indications for Use | A glucose test system is a device intended to measure glucosequantitatively in blood and other body fluids. Glucosemeasurements are used in the diagnosis and treatment ofcarbohydrate metabolism disorders including diabetes mellitus,neonatal hypoglycemia, and idiopathic hypoglycemia, and ofpancreatic islet cell carcinoma. | Same |
| Assay Principle | Glucose is phosphorylated by hexokinase (HK) in the presenceof adenosine triphosphate (ATP) and magnesium ions toproduce glucose-6-phosphate (G-6-P) and adenosinediphosphate (ADP). Glucose-6-phosphate dehydrogenase(G-6-PDH) specifically oxidizes G-6-P to 6-phosphogluconatewith the concurrent reduction of nicotinamide adeninedinucleotide (NAD) to nicotinamide adenine dinucleotidereduced (NADH). One micromole of NADH is produced foreach micromole of glucose consumed. The NADH producedabsorbs light at 340 nm and can be detectedspectrophotometrically as an increased absorbance. | Same |
| Detection of Analyte | End-point colorimetric. | Same |
| Specimen Type | Human serum, plasma, urine, or CSF. | Same |
| Candidate AssayAlinity c Glucose Reagent Kit(LN 07P55) | Predicate Assay (K060383)Glucose(LN 3L82) | |
| Characteristics | ||
| Performance Characteristics | ||
| Assay Range | Serum/Plasma5 to 800 mg/dL (0.28 to 44.40 mmol/L).Urine/ CSF1 to 800 mg/dL (0.06 to 44.40 mmol/L). | Same |
| Measuring Interval | Serum/ PlasmaThe measuring interval of the serum/plasma application is 5 to800 mg/dL (0.28 to 44.40 mmol/L).Urine/ CSFThe measuring interval of the urine/CSF application is 1 to800 mg/dL (0.06 to 44.40 mmol/L). | Same |
| Tube Types | SerumSerum tubes (with or without gel barrier).PlasmaCollection tubesAcceptable anticoagulants are: Lithium heparin (with or withoutgel barrier), Sodium heparin, Sodium fluoride/ potassiumoxalate, EDTA. | Same |
| Use of Calibrators | Yes | Same |
| Use of Controls | Yes; Commercially available controls | Same |
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r
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| Characteristics | Alinity c Glucose Reagent Kit(LN 07P55) | Predicate Assay (K060383)Glucose(LN 3L82) |
|---|---|---|
| Reagent Container | Polypropylene | High Density Polyethylene |
| Black color | White colorant | |
| Closure Material | High Density Polyethylene | F217 cap liner |
| Black color | Polyethylene Foam between Low-Density Polyethylene liners | |
| Green color |
Table 2: Reagent Differences
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| Characteristics | Candidate DeviceAlinity c System | Predicate DeviceAEROSET/ARCHITECT c System (K980367) |
|---|---|---|
| Intended Use/Indication for Use | The Alinity c System is a fully automated, random/continuousaccess, clinical chemistry analyzer intended for the in vitrodetermination of analytes in body fluids. | Same |
| Detection Technology | Potentiometric/Photometric | Same |
| Sample Handling | Robotic sample handler (RSH). Transport system that has random and continuous access to samples. Autoretest CapabilityPriority and batch sample loading | Same |
| Reagent Handling | The on-board storage area cooler provides evaporation control.Continuous Reagent Access. | Same |
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Table 4: Instrument Differences
| Characteristics | Alinity c System | AEROSET / ARCHITECT c System |
|---|---|---|
| Calibrator / Control Automation | Direct aspiration from the calibrator/control bottles | No. |
| Reagent Access | Continuous Reagent Access. | Scheduled Reagent Access. |
| Bulk Solutions Replenishment | Continuous Bulk Solution Access. | Scheduled Bulk Solution Access. |
| Priority Sample Loading | All carrier positions are available to have a priority sample loadingdesignation. | Select positions available for priority loading. |
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VII. Summary of Nonclinical Performance
Within-Laboratory Precision (20-Day)
Alinity Glucose Reagent Kit- Serum Samples
Precision was performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP05-A2.
A summary of results is presented below:
| Sample | ControlLot | n | Mean(mg/dL) | Within-Run(Repeatability) | Within-Laboratorya | ||
|---|---|---|---|---|---|---|---|
| SD | %CV | SD(Rangeb) | %CV(Rangeb) | ||||
| Control Level 1 | 1 | 264 | 55 | 0.6 | 1.1 | 0.7(0.5-0.8) | 1.2(1.0-1.4) |
| 2 | 264 | 55 | 0.5 | 0.9 | 0.6(0.5-0.7) | 1.1(0.9-1.2) | |
| Control Level 2 | 1 | 264 | 128 | 1.1 | 0.8 | 1.3(1.1-1.4) | 1.0(0.9-1.1) |
| 2 | 263 | 128 | 0.9 | 0.7 | 1.3(1.1-1.4) | 1.0(0.9-1.1) | |
| Control Level 3 | 1 | 264 | 315 | 2.2 | 0.7 | 2.8(2.5-3.1) | 0.9(0.8-1.0) |
| 2 | 260 | 311 | 2.1 | 0.7 | 2.5(2.1-2.9) | 0.8(0.7-0.9) | |
| Panel A | N/A | 527 | 7 | 0.1 | 1.9 | 0.1(0.0-0.2) | 1.9(0.0-2.8) |
| Panel B | N/A | 528 | 106 | 0.8 | 0.8 | 1.0(0.8-1.2) | 0.9(0.7-1.2) |
| Panel C | N/A | 523 | 728 | 5.6 | 0.8 | 5.9(4.4-7.6) | 0.8(0.6-1.1) |
4 Includes within-run, between-run, and between-day variability.
b Minimum and maximum SD or %CV for each reagent lot and instrument combination.
The precision of the Alinity c Glucose assay was considered acceptable if the within-laboratory imprecision (within-run, between-run, and between-day) was ≤ 5 %CV for serum samples targeted between 80 to 281 mg/dL.
The Alinity c Glucose assay demonstrated acceptable precision.
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Alinity Glucose Reagent Kit- Urine Samples
Precision was performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP05-A2.
A summary of results is presented below:
| Within-Run(Repeatability) | Within-Laboratorya | ||||||
|---|---|---|---|---|---|---|---|
| Sample | ControlLot | n | Mean(mg/dL) | SD | %CV | SD(Rangeb) | %CV(Rangeb) |
| Control Level 1 | 1 | 264 | 38 | 0.4 | 1.0 | 0.5(0.5-0.5) | 1.3(1.3-1.3) |
| 2 | 263 | 38 | 0.3 | 0.9 | 0.6(0.5-0.6) | 1.4(1.4-1.5) | |
| Control Level 2 | 1 | 260 | 359 | 2.9 | 0.8 | 3.4(2.9-4.0) | 1.0(0.8-1.1) |
| 2 | 264 | 353 | 2.4 | 0.7 | 3.0(2.5-3.3) | 0.8(0.7-0.9) | |
| Panel A | N/A | 527 | 3 | 0.1 | 3.8 | 0.1(0.0-0.2) | 3.8(0.0-6.4) |
| Panel B | N/A | 526 | 60 | 1.0 | 1.6 | 1.2(1.1-1.5) | 2.1(1.8-2.5) |
| Panel C | N/A | 528 | 110 | 2.4 | 2.2 | 3.1(2.5-4.2) | 2.8(2.3-3.8) |
| Panel D | N/A | 525 | 712 | 6.2 | 0.9 | 8.1(7.4-8.7) | 1.1(1.0-1.2) |
4 Includes within-run, between-run, and between-day variability.
b Minimum and maximum SD or %CV for each reagent lot and instrument combination.
The precision of the Alinity c Glucose assay was considered acceptable if the within-laboratory imprecision (within-run, between-run, and between-day) was ≤ 6 %CV for urine samples targeted between 30 to 306 mg/dL.
The Alinity c Glucose assay demonstrated acceptable precision.
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Alinity Glucose Reagent Kit- Cerebrospinal Fluid (CSF) Samples
Precision was performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP05-A2.
A summary of results is presented below:
| Within-Run(Repeatability) | Within-Laboratorya | ||||||
|---|---|---|---|---|---|---|---|
| Sample | ControlLot | n | Mean(mg/dL) | SD | %CV | SD(Rangeb) | %CV(Rangeb) |
| Control Level 1 | 1 | 264 | 60 | 0.5 | 0.9 | 0.6(0.6-0.7) | 1.1(1.0-1.1) |
| 2 | 264 | 61 | 0.5 | 0.7 | 0.6(0.6-0.6) | 1.0(1.0-1.0) | |
| Control Level 2 | 1 | 264 | 30 | 0.3 | 0.9 | 0.3(0.3-0.4) | 1.1(0.9-1.2) |
| 2 | 263 | 31 | 0.4 | 1.1 | 0.4(0.2-0.5) | 1.3(0.8-1.6) | |
| Panel A | N/A | 527 | 3 | 0.1 | 4.8 | 0.1(0.1-0.2) | 4.8(2.9-7.5) |
| Panel B | N/A | 528 | 57 | 0.4 | 0.8 | 0.5(0.4-0.6) | 0.9(0.8-1.0) |
| Panel C | N/A | 527 | 107 | 0.7 | 0.7 | 0.8(0.7-1.0) | 0.8(0.6-1.0) |
| Panel D | N/A | 526 | 700 | 3.8 | 0.5 | 4.8(4.3-5.3) | 0.7(0.6-0.8) |
4 Includes within-run, between-run, and between-day variability.
b Minimum and maximum SD or %CV for each reagent lot and instrument combination.
The precision of the Alinity c Glucose assay was considered acceptable if the within-laboratory imprecision (within-run, between-run, and between-day) was ≤ 5 %CV for CSF samples targeted between 29 to 60 mg/dL.
The Alinity c Glucose assay demonstrated acceptable precision.
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Accuracy
Alinity c Glucose Reagent Kit-Serum
A minimum of 1 level of a NIST standard (SRM 965b, Glucose in Human Serum) at or near the medical decision point of the Alinity c Glucose serum assay was tested.
The results are summarized in the table below.
| Sample Set | Target(mg/dL) | N | Mean(mg/dL) | SD | %CV | Bias | %Bias | TotalError(mg/dL) | % TotalError |
|---|---|---|---|---|---|---|---|---|---|
| NIST level 1 | 33.08 | 22 | 33 | 0.4 | 1.1 | 0 | 0.2 | 0.8 | 2.3 |
| NIST level 2 | 75.56 | 22 | 76 | 0.5 | 0.7 | 1 | 1.2 | 1.9 | 2.5 |
| NIST level 3 | 118.5 | 22 | 120 | 0.6 | 0.5 | 1 | 1.1 | 2.5 | 2.1 |
| NIST level 4 | 294.5 | 22 | 306 | 1.4 | 0.5 | 11 | 3.8 | 14.0 | 4.7 |
Limit of Blank, Limit of Detection, and Limit of Quantitation
Alinity c Glucose Reagent Kit-Serum/Plasma, Urine/CSF Samples
The LoB, LoD, and LoQ study was performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP17-A2.
The results are summarized in the table below:
| Serum/Plasma(mg/dL) | Urine/CSF(mg/dL) | |
|---|---|---|
| LoBa | 0.33 | 0.23 |
| LoDb | 0.55 | 0.40 |
| LoQc | 2.25 | 0.86 |
a The LoB represents the 95th percentile from n ≥ 60 replicates of zero-analyte samples.
b The LoD represents the lowest concentration at which the analyte can be detected with 95% probability based on n ≥ 60 replicates of low-analyte level samples.
C The LoQ was determined from n ≥ 60 replicates of low-analyte level samples and is defined as the lowest concentration at which a maximum allowable precision of 20 %CV was met.
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Linearity
Alinity c Glucose Reagent Kit- Serum/Plasma, Urine/CSF Samples
Linearity was determined based on guidance from Clinical and Laboratory Standards Institute (CLSI) document EP06-A.
Serum/Plasma: The mean observed linear range concentrations ranged from 0 to 828 mg/dL for the sample set.
Urine: The mean observed linear range concentrations ranged from 0 to 843 mg/dL for the sample set.
CSF: The mean observed linear range concentrations ranged from 0 to 887 mg/dL for the sample set.
Measuring Interval
The measuring interval of the Alinity c Glucose Serum/ Plasma application is 5 mg/dL to 800 mg/dL. The measuring interval of the Alinity c Glucose Urine/Cerebrospinal (CSF) application is 1 mg/dL to 800 mg/dL.
The measuring interval is defined as the range of values which meets the limits of acceptable performance for linearity, imprecision, and bias. The inputs to the measuring interval include imprecision, limit of quantification and linearity.
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Interference
Alinity c Glucose Reagent Kit– Serum Samples
Potential interference was evaluated based on guidance from the Clinical Laboratory and Standards Institute (CLSI) document EP07-A2.
For serum/plasma, a bias of >6% or >1 mg/dL was considered significant interference.
The Alinity c Glucose assay using the serum application is not susceptible to interference effects from the following interferents at the interferent levels listed in the table below:
| Interferent | Interferent Level |
|---|---|
| Unconjugated Bilirubin | $\u2264$ 30 mg/dL |
| Conjugated Bilirubin | $\u2264$ 60 mg/dL |
| Hemoglobin | $\u2264$ 2,000 mg/dL |
| Triglycerides | $\u2264$ 2,000 mg/dL |
| Ascorbic Acid | $\u2264$ 6 mg/dL |
| Acetaminophen | $\u2264$ 20 mg/dL |
| Ibuprofen | $\u2264$ 50 mg/dL |
| Acetylcysteine | $\u2264$ 167 mg/dL |
| Acetylsalicylic Acid | $\u2264$ 66 mg/dL |
| Sodium Salicylate | $\u2264$ 70 mg/dL |
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Alinity c Glucose Reagent Kit– Urine Samples
Potential interference was evaluated based on guidance from the Clinical Laboratory and Standards Institute (CLSI) document EP07-A2.
For urine, a bias of >10% or >1 mg/dL was considered significant interference.
The Alinity c Glucose assay using the urine application is not susceptible to interference effects from the following interferents at the interferent levels listed in the table below:
| Interferent | Interferent Level |
|---|---|
| Protein | ≤ 50 mg/dL |
| Ascorbate | ≤ 200 mg/dL |
| 8.5 N Acetic Acid | < 6.25 mL/dL |
| Boric Acid | ≤ 250 mg/dL |
| 6 N Hydrochloric Acid | < 2.5 mL/dL |
| 6 N Nitric Acid | < 5.0 mL/dL |
| Sodium Oxalate | ≤ 60 mg/dL |
| Sodium Carbonate | ≤ 1.25 g/dL |
| Sodium Fluoride | ≤ 400 mg/dL |
| Acetaminophen | ≤ 20 mg/dL |
| Ibuprofen | ≤ 50 mg/dL |
| Acetylcysteine | < 167 mg/dL |
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Method Comparison
Alinity c Glucose Reagent Kit- Serum, Urine and CSF Samples
The method comparison study was performed based on guidance from the Clinical and Laboratory Standards Institute (CLSI) document EP09-A3.
Human serum, urine, and CSF specimens that spanned the measuring interval of the assay were evaluated for serum, urine and CSF testing, respectively.
Representative results analyzed using the Passing-Bablok regression method are summarized in the table below:
| Sample | Correlation | Concentration | |||||
|---|---|---|---|---|---|---|---|
| Type | Units | N | Coefficient | Intercept | Slope | Range | |
| Alinity c Glucose vs.ARCHITECT Glucose | Serum | mg/dL | 98 | 1.00 | -1.78 | 1.00 | 8 - 791 |
| mmol/L | 98 | 1.00 | -0.09 | 1.00 | 0.44 - 43.87 | ||
| Urine | mg/dL | 118 | 1.00 | 0.24 | 0.99 | 4 - 785 | |
| mmol/L | 118 | 1.00 | 0.01 | 0.99 | 0.22 - 43.57 | ||
| CSF | mg/dL | 90 | 1.00 | 0.50 | 1.00 | 4 - 740 | |
| mmol/L | 90 | 1.00 | 0.03 | 1.00 | 0.22 - 41.07 |
The method comparison study results of the investigational method, Alinity c Glucose, versus the comparator method, Glucose assay on the ARCHITECT c System, are acceptable for serum, urine and CSF samples.
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Auto Dilution
Glucose serum specimens were tested using the 1:5 auto dilution protocol on the ARCHITECT c8000 instrument and the Alinity c analyzer
The performance of the Alinity c Glucose auto dilution protocol was considered acceptable if the difference in measured concentration was within ± 10% when comparing auto-diluted samples on the Alinity c analyzer to auto-diluted samples on the ARCHITECT c 8000 System.
The Alinity c Glucose assay auto dilution protocol demonstrated acceptable performance. The mean % difference was -0.4% (range: - 5.1% to 2.6%).
Tube Type Equivalency
Tube type equivalency was performed to evaluate whether specific blood collection tube types are suitable for use with the Alinity c Glucose assay using the serum application.
Samples were collected from a minimum of 40 donors and evaluated across tube types.
The following blood collection tube types were determined to be acceptable for use with the Alinity c Glucose assay:
- Serum .
- Serum separator ●
- dipotassium EDTA
- . lithium heparin
- sodium heparin
- . sodium fluoride/potassium oxalate
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VIII. Conclusion Drawn from Nonclinical Laboratory Studies
The results presented in this 510(k) premarket notification demonstrate that the Alinity c Glucose test system that includes the Alinity c System and the Alinity c Glucose Reagent Kit is substantially equivalent to each respective predicate device (Glucose Assay, K060383: AEROSET/ARCHITECT family K980367).
The similarities and differences between the candidate assay (Alinity c Glucose Reagent Kit, List No. 07P55) and the predicate assay (Glucose Assay, K060383), and the candidate instrument and predicate instrument are presented in the tables starting on page 7. Any differences between the candidate assay and the predicate assay, and the candidate instrument and the predicate instrument shown in the tables do not affect the safety and effectiveness of the candidate assay and instrument.
§ 862.1345 Glucose test system.
(a)
Identification. A glucose test system is a device intended to measure glucose quantitatively in blood and other body fluids. Glucose measurements are used in the diagnosis and treatment of carbohydrate metabolism disorders including diabetes mellitus, neonatal hypoglycemia, and idiopathic hypoglycemia, and of pancreatic islet cell carcinoma.(b)
Classification. Class II (special controls). The device, when it is solely intended for use as a drink to test glucose tolerance, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.