(399 days)
Not Found
No
The device description details a standard chemical reaction-based assay for measuring creatinine concentration, and there is no mention of AI, ML, or related concepts in the provided text.
No
Explanation: This device is an in vitro diagnostic (IVD) assay used for the quantitative measurement of creatinine, which aids in diagnosis and monitoring. It does not directly treat or prevent a disease, nor does it restore, modify, or replace functions of the body.
Yes
The device is used for the "quantitation of creatinine in human serum, plasma, or urine" and is intended "as an aid in the diagnosis and treatment of renal diseases". This function directly supports medical diagnosis.
No
The device description clearly states it is an "automated clinical chemistry assay" that involves a chemical reaction and absorbance measurement, indicating it is a hardware-based laboratory test, not software only.
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 the quantitation of creatinine in human serum, plasma, or urine. It also mentions its use as an aid in the diagnosis and treatment of renal diseases, monitoring renal dialysis, and as a calculation basis for other urine analytes. These are all activities performed in vitro (outside the body) on biological samples to provide information for diagnostic purposes.
- Device Description: The description details a chemical reaction that occurs with the sample in vitro to measure creatinine levels.
- Performance Studies: The performance studies describe testing conducted on biological samples (serum, plasma, urine) to evaluate the assay's performance, which is characteristic of IVD testing.
The definition of an IVD is a medical device that is used to examine specimens taken from the human body, such as blood, urine, or tissue, to provide information for diagnostic, monitoring, or compatibility purposes. This device clearly fits that description.
N/A
Intended Use / Indications for Use
The Creatinine2 assay is used for the quantitation of creatinine in human serum, plasma, or urine on the ARCHITECT c System.
The Creatinine2 assay is to be used as an aid in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
Product codes (comma separated list FDA assigned to the subject device)
CGX
Device Description
The Creatinine2 assay is an automated clinical chemistry assay. At an alkaline pH, creatinine in the sample reacts with picric acid to form a creatinine-picrate complex that absorbs at 500 nm. The rate of increase in absorbance is directly proportional to the concentration of creatinine in the sample.
Methodology: Kinetic Alkaline Picrate
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
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Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Summary of Nonclinical Performance
Reportable Interval
Serum/Plasma
Analytical Measuring Interval (AMI): 0.09 - 37.34 mg/dL
Reportable Interval: 0.04 - 37.34 mg/dL
Urine
Analytical Measuring Interval (AMI): 2.54 - 740 mg/dL
Reportable Interval: 1.24 - 740 mg/dL
Within-Laboratory Precision
Serum/Plasma
Study performed based on CLSI EP05-A3. Testing used 3 lots of Creatinine2 reagent, 3 lots of Consolidated Chemistry Calibrator, 1 lot of commercial controls, and 3 instruments. Two controls and 3 human serum panels were tested in duplicate, twice per day for 20 days on 3 reagent lot/calibrator lot/instrument combinations.
Controls and panels demonstrated acceptable precision. E.g., Control Level 1: Mean 1.42 mg/dL, Within-Run %CV 1.0, Within-Laboratory %CV 3.5. Panel C: Mean 36.36 mg/dL, Within-Run %CV 0.4, Within-Laboratory %CV 2.1.
Urine
Study performed based on CLSI EP05-A3. Testing used 3 lots of Creatinine2 reagent, 3 lots of Consolidated Chemistry Calibrator, 1 lot of commercial controls, and 3 instruments. Two controls and 3 human urine panels were tested in duplicate, twice per day for 20 days on 3 reagent lot/calibrator lot/instrument combinations.
Controls and panels demonstrated acceptable precision. E.g., Control Level 1: Mean 57.77 mg/dL, Within-Run %CV 0.9, Within-Laboratory %CV 2.1. Panel C: Mean 701.12 mg/dL, Within-Run %CV 0.5, Within-Laboratory %CV 1.8.
Accuracy
Serum/Plasma
Study performed to estimate bias relative to NIST SRM 967a. Testing used 3 lots of Creatinine2 reagent, 2 lots of Consolidated Chemistry Calibrator, and 1 instrument. Bias ranged from -4.1% to 0.4% across all instruments, calibrator and reagent lots.
Urine
Study performed to estimate bias relative to NIST SRM 914a. Testing used 3 concentrations of standard across 3 lots of Creatinine2 reagent, 2 lots of Consolidated Chemistry Calibrator, and 1 instrument. Bias ranged from -4.8% to 3.3% across all concentrations of standard, instruments, calibrator and reagent lots.
Lower Limits of Measurement
Study performed based on CLSI EP17-A2. Testing used 3 lots of Creatinine2 reagent kit on 2 instruments for a minimum of 3 days.
Serum/Plasma
LoB: 0.02 mg/dL
LoD: 0.04 mg/dL
LoQ: 0.09 mg/dL
Urine
LoB: 0.93 mg/dL
LoD: 1.24 mg/dL
LoQ: 2.54 mg/dL
Linearity
Study performed based on CLSI EP06-A. This assay demonstrated linearity across the analytical measuring interval of 0.09 to 37.34 mg/dL for the serum application, and 2.54 to 740 mg/dL for the urine application.
Potentially Interfering Endogenous and Exogenous Substances
Serum/Plasma - Potentially Interfering Endogenous Substances
Study performed based on CLSI EP07, 3rd ed. No significant interference (within ± 10%) observed for Acetoacetate (20 mg/dL), Bilirubin - conjugated (20 mg/dL), Bilirubin - unconjugated (8 mg/dL), Glucose (250 mg/dL, 750 mg/dL), Hemoglobin (1000 mg/dL), Triglycerides (750 mg/dL, 1500 mg/dL), Total protein (5.4 g/dL to 8.4 g/dL, 11.0 g/dL).
Interference beyond ± 10% was observed for: Bilirubin - conjugated (40 mg/dL, -14% at 0.6 mg/dL analyte), Bilirubin - unconjugated (10 mg/dL, -11% at 0.6 mg/dL analyte), Glucose (1000 mg/dL, 42% at 0.6 mg/dL analyte; 13% at 2.0 mg/dL analyte), Total protein (6.8 g/dL, 17% at 0.6 mg/dL; 5.0 g/dL, -14% at 0.6 mg/dL; 9.1 g/dL, 12% at 0.6 mg/dL; 15.3 g/dL, 20% at 2.0 mg/dL), Triglycerides (1000 mg/dL, 11% at 0.6 mg/dL analyte).
Serum/Plasma - Potentially Interfering Exogenous Substances
Study performed based on CLSI EP07, 3rd ed. No significant interference (within ± 10%) observed for various substances including Acetaminophen, Ibuprofen, Ascorbic acid, Cyclosporine, Eltrombopag (at certain levels), Hydroxocobalamin (at certain levels), Methyldopa (at certain levels), etc.
Interference beyond ± 10% was observed for: Acetohexamide (1.5 mg/dL, 18% at 0.6 mg/dL analyte; 2 mg/dL, 10% at 2.0 mg/dL analyte), Cefoxitin (71 mg/L, 14% at 0.6 mg/dL analyte; 119 mg/L, 13% at 2.0 mg/dL analyte), Cephalothin (180 mg/dL, 193% at 0.6 mg/dL analyte; 56% at 2.0 mg/dL analyte), Eltrombopag (300 mg/L, 53% at 0.6 mg/dL analyte; 25 mg/L, -12% at 2.0 mg/dL analyte), Hydroxocobalamin (Cyanokit) (375 mg/L, 16% at 0.6 mg/dL analyte; 2259 mg/L, 19% at 2.0 mg/dL analyte), Methyldopa (200 mg/L, -17% at 0.6 mg/dL analyte).
Urine - Potentially Interfering Endogenous Substances
Study performed based on CLSI EP07, 3rd ed./CLSI EP37, 1st ed. No significant interference (within ± 10%) observed for Acetoacetate (480 mg/dL), Ascorbate (220 mg/dL), Glucose (1000 mg/dL), Protein (50 mg/dL), Urobilinogen (40 mg/dL).
Urine - Potentially Interfering Exogenous Substances
Study performed based on CLSI EP07, 3rd ed./CLSI EP37, 1st ed. No significant interference (within ± 10%) observed for various substances including Acetaminophen, Ibuprofen, Biotin, Cefoxitin (at certain levels), Levodopa (at certain levels), etc.
Interference beyond ± 10% was observed for: Cefoxitin (400 mg/dL, 26% at 15 mg/dL analyte), Levodopa (1000 mg/dL, 15% at 15 mg/dL analyte).
Method Comparison
Study performed based on CLSI EP09-A3 using Passing-Bablok regression. Compared Creatinine2 assay to Creatinine assay (List Number 3L81).
Serum: n=128, Correlation Coefficient 1.00, Intercept -0.01, Slope 0.96, Concentration Range 0.47 - 35.72 mg/dL.
Urine: n=129, Correlation Coefficient 1.00, Intercept -1.23, Slope 1.01, Concentration Range 6.65 - 727.61 mg/dL.
Tube Type
Study performed to evaluate suitability of blood collection tube types. Samples from a minimum of 40 donors were evaluated.
Acceptable for Serum: Serum tubes, Serum separator tubes.
Acceptable for Plasma: Dipotassium EDTA tubes, Lithium heparin tubes, Lithium heparin separator tubes, Sodium heparin tubes.
Summary of Clinical Performance
This section does not apply.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 862.1225 Creatinine test system.
(a)
Identification. A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.(b)
Classification. Class II.
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA text logo on the right. The text logo has the FDA acronym in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue.
March 22, 2022
Abbott Ireland Diagnostics Division Magdalena Suszko Associate Director Regulatory Affairs Lisnamuck, Longford Ireland
Re: K210452
Trade/Device Name: Creatinine2 Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine Test System Regulatory Class: Class II Product Code: CGX Dated: December 6, 2021 Received: December 8, 2021
Dear Magdalena Suszko:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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.
1
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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Marianela Perez-Torres, Ph.D. Deputy Director Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
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Indications for Use
510(k) Number (if known) K210452
Device Name Creatinine2
Indications for Use (Describe)
The Creatinine2 assay is used for the quantitation of creatinine in human serum, plasma, or urine on the ARCHITECT c System.
The Creatinine2 assay is to be used as an aid in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
| Type of Use (Select one or both, as applicable) | 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 (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. 510(k) Number
II. Applicant Name
Abbott Ireland Diagnostics Division Lisnamuck, Longford Longford, IE
Primary contact person for all communications:
Magdalena Suszko, Manager, Regulatory Affairs Abbott Diagnostics Division Phone (224) 667-9025 Fax (224) 667-4836
Secondary contact person for all communications:
Suzanne Cheang, Manager, Regulatory Affairs Abbott Diagnostics Division Phone (972) 518-6617 Fax (972) 518-7498
Date Summary Prepared: December 6, 2021
4
III. Device Name
Creatinine2
Reagents
Trade Name: Creatinine2 Device Classification: Class II Classification Name: Creatinine test system Governing Regulation Number: 21 CFR 862.1225 Product Code: CGX
IV. Predicate Device
Creatinine (K083809)
V. Description of Device
A. Principles of the Procedure
The Creatinine2 assay is an automated clinical chemistry assay. At an alkaline pH, creatinine in the sample reacts with picric acid to form a creatinine-picrate complex that absorbs at 500 nm. The rate of increase in absorbance is directly proportional to the concentration of creatinine in the sample.
Methodology: Kinetic Alkaline Picrate
5
B. Reagents
The configuration of the Creatinine2 reagent kit is described below.
| List Number | |
|---|---|
| 04S9520 | |
| Tests per cartridge set | 450 |
| Number of cartridge sets per kit | 8 |
| Tests per kit | 3600 |
| Reagent 1 (R1) | 53.9 mL |
| Reagent 2 (R2) | 21.4 mL |
Reagent 2
VI. Intended Use of the Device
The Creatinine2 assay is used for the quantitation of creatinine in human serum, plasma, or urine on the ARCHITECT c System.
The Creatinine2 assay is to be used as an aid in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.
VII. Comparison of Technological Characteristics
The Creatinine2 assay (subject device) is an automated clinical chemistry assay for the quantitation of creatinine in human serum, plasma, or urine on the ARCHITECT c System.
The similarities and differences between the subject device and the predicate device are presented in the following table.
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| Characteristics | Subject Device
Creatinine2 (List No. 04S95) | Predicate Device
Creatinine (K083809; List No.
3L81) |
|------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Platform | ARCHITECT c System | Same |
| Intended Use and
Indications for
Use | The Creatinine2 assay is used for the
quantitation of creatinine in human
serum, plasma, or urine on the
ARCHITECT
c System.
The Creatinine2 assay is to be used as an
aid in the diagnosis and treatment of
renal diseases, in monitoring renal
dialysis, and as a calculation basis for
measuring other urine analytes. | The Creatinine assay is used for the
quantitation of creatinine in human
serum, plasma, or urine. |
| Methodology | Kinetic Alkaline Picrate | Same |
| Specimen Type | Human serum, plasma, urine | Same |
| Assay Principle /
Principle of
Procedure | The Creatinine2 assay is an automated
clinical chemistry assay. At an alkaline
pH, creatinine in the sample reacts with
picric acid to form a creatinine-picrate
complex that absorbs at 500 nm. The
rate of increase in absorbance is directly
proportional to the concentration of
creatinine in the sample. | At an alkaline pH, creatinine in the
sample reacts with picrate to form a
creatinine-picrate complex. The rate of
increase in absorbance at 500 nm due to
the formation of this complex is directly
proportional to the concentration of
creatinine in the sample. |
| Standardization | NIST SRM 967 for serum/plasma
NIST SRM 914 for urine | Same |
| Use of
Calibrators | Yes | Same |
| Use of Controls | Yes | Same |
| Characteristics | Subject Device
Creatinine2 (List No. 04S95) | Predicate Device
Creatinine (K083809; List No.
3L81) |
| Assay Range | Serum/Plasma:
Analytical Measuring Interval:
0.09 – 37.34 mg/dL
Reportable Interval:
0.04 – 37.34 mg/dL
Urine:
Analytical Measuring Interval:
2.54 – 740 mg/dL
Reportable Interval:
1.24 – 740 mg/dL | Serum/Plasma:
Creatinine serum is linear from 0.20
to 37.00 mg/dL.
Urine:
Creatinine urine is linear from 5.00 to
740.00 mg/dL. |
| Precision | Serum/Plasma:
Samples with creatinine concentrations
between 0.25 and 36.36 mg/dL were
evaluated. The samples demonstrated
% coefficients of variation (%CV) ≤
3.5% and standard deviations (SD)
≤ 0.011 mg/dL.
Urine:
Samples with creatinine concentrations
between 5.25 and 701.12 mg/dL were
evaluated. The samples demonstrated
%CV ≤ 2.4% and SD ≤ 0.294 mg/dL. | Serum/Plasma:
Samples with creatinine
concentrations between 1.20 and 4.66
mg/dL demonstrated %CV values
ranging from 3.18 to 4.95%.
Urine:
Samples with creatinine
concentrations between 61.95 and
145.48 mg/dL demonstrated %CV
values ranging from 1.27 to 1.34%. |
| Lower Limits of
Measurement | Serum/Plasma:
Limit of Blank: 0.02 mg/dL
Limit of Detection: 0.04 mg/dL
Limit of Quantitation: 0.09 mg/dL
Urine:
Limit of Blank: 0.93 mg/dL
Limit of Detection: 1.24 mg/dL
Limit of Quantitation: 2.54 mg/dL | Serum/Plasma:
Limit of Detection: 0.05 mg/dL
Limit of Quantitation: 0.10 mg/dL
Urine:
Limit of Detection: 4.00 mg/dL
Limit of Quantitation: 5.00 mg/dL |
| Characteristics | Subject Device
Creatinine2 (List No. 04S95) | Predicate Device
Creatinine (K083809; List No. 3L81) |
| Tube Types | Serum:
- Serum tubes
- Serum separator tubes
Plasma: - Dipotassium EDTA tubes
- Lithium heparin tubes
- Lithium heparin separator tubes
- Sodium heparin tubes | Serum:
- Glass or plastic tubes with or
without gel barrier
Plasma: - Glass or plastic lithium heparin
tubes (with or without gel barrier) - Glass or plastic EDTA tubes
- Glass or plastic sodium heparin
tubes |
Comparison of Subject Device (Creatinine2) to Predicate Device (Creatinine)
NIST - National Institute of Standards and Technology SRM - Standard Reference Materials
7
Comparison of Subject Device (Creatinine2) to Predicate Device (Creatinine) (Continued)
8
Comparison of Subject Device (Creatinine2) to Predicate Device (Creatinine) (Continued)
9
VIII. Summary of Nonclinical Performance
A. Reportable Interval
Based on the limit of detection (LoD), limit of quantitation (LoQ), precision, and linearity, the ranges over which results can be reported are provided below according to the definitions from CLSI EP34, 1st ed. *
Serum/Plasma
| mg/dL | |
|---|---|
| Analytical Measuring Interval (AMI)a | 0.09 - 37.34 |
| Reportable Intervalb | 0.04 - 37.34 |
a AMI: The AMI extends from the LoQ to the upper limit of quantitation (ULoQ). This is determined by the range of values in mg/dL that demonstrated acceptable performance for linearity, imprecision, and bias.
b The reportable interval extends from the LoD to the upper limit of the AMI.
NOTE: The default Low Linearity value of the assay file corresponds to the analytical measuring interval. Samples with a creatinine value below LoQ are reported as "" Clinical and Laboratory Standards Institute (CLS). Establishing and Verifying an Extended Measuring Interval Through Speciment Dilution and Spiking. 1st ed. CLSI Document EP34. Wayne, PA: CLSI; 2018.
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B. Within-Laboratory Precision
Serum/Plasma
A study was performed based on guidance from CLSI EP05-A3. * Testing was conducted using 3 lots of the Creatinine2 reagent, 3 lots of the Consolidated Chemistry Calibrator, 1 lot of commercially available controls, and 3 instruments. Two controls and 3 human serum panels were tested in duplicate, twice per day on 20 days on 3 reagent lot/calibrator lot/instrument combinations, where a unique reagent lot and a unique calibrator lot is paired with 1 instrument. The performance from a representative combination is shown in the following table.
| | | | Within-Run
(Repeatability) | | Within-Laboratorya | |
|-----------------|----|-----------------|-------------------------------|-----|--------------------------|--------------------|
| Sample | n | Mean
(mg/dL) | SD | %CV | SD
(Rangeb) | %CV
(Rangeb) |
| Control Level 1 | 80 | 1.42 | 0.015 | 1.0 | 0.050
(0.016 - 0.050) | 3.5
(1.1 - 3.5) |
| Control Level 2 | 80 | 5.91 | 0.035 | 0.6 | 0.147
(0.047 - 0.147) | 2.5
(0.8 - 2.5) |
| Panel A | 80 | 0.25 | 0.008 | 3.1 | 0.011
(0.010 - 0.011) | 4.5
(3.9 - 4.5) |
| Panel B | 80 | 26.00 | 0.121 | 0.5 | 0.588
(0.185 - 0.588) | 2.3
(0.7 - 2.3) |
| Panel C | 80 | 36.36 | 0.130 | 0.4 | 0.777
(0.260 - 0.777) | 2.1
(0.7 - 2.1) |
ª Includes within-run, between-run, and between-day variability.
b Minimum and maximum SD or %CV across all reagent lot and instrument combinations.
- Clinical and Laboratory Standards Institute (CLSI). Evaluation of Quantitative Measurement Procedures; Approved Guideline-Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.
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Urine
A study was performed based on guidance from CLSI EP05-A3. * Testing was conducted using 3 lots of the Creatinine2 reagent, 3 lots of the Consolidated Chemistry Calibrator, 1 lot of commercially available controls, and 3 instruments. Two controls and 3 human urine panels were tested in duplicate, twice per day on 20 days on 3 reagent lot/calibrator lot/instrument combinations, where a unique reagent lot and a unique calibrator lot is paired with 1 instrument. The performance from a representative combination is shown in the following table.
| | | | Within-Run
(Repeatability) | | Within-Laboratoryª | |
|-----------------|----|-----------------|-------------------------------|-----|----------------------------|--------------------|
| Sample | n | Mean
(mg/dL) | SD | %CV | SD
(Rangeb) | %CV
(Rangeb) |
| Control Level 1 | 80 | 57.77 | 0.491 | 0.9 | 1.194
(0.781 - 1.194) | 2.1
(1.4 - 2.1) |
| Control Level 2 | 80 | 132.61 | 1.165 | 0.9 | 3.158
(1.860 - 3.158) | 2.4
(1.4 - 2.4) |
| Panel A | 80 | 5.37 | 0.233 | 4.3 | 0.294
(0.221 - 0.294) | 5.5
(4.2 - 5.5) |
| Panel B | 80 | 278.12 | 1.958 | 0.7 | 5.003
(2.671 - 5.003) | 1.8
(1.0 - 1.8) |
| Panel C | 80 | 701.12 | 3.303 | 0.5 | 12.844
(7.631 - 12.844) | 1.8
(1.1 - 1.8) |
ª Includes within-run, between-run, and between-day variability.
b Minimum and maximum SD or %CV across all reagent lot and instrument combinations.
- Clinical and Laboratory Standards Institute (CLSI). Evaluation of Quantitative Measurement Procedures; Approved Guideline-Third Edition. CLSI Document EP05-A3. Wayne, PA: CLSI; 2014.
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C. Accuracy
Serum/Plasma
A study was performed to estimate the bias of the Creatinine2 assay relative to material standardized to the Certified Reference Material NIST SRM 967a.
Testing was conducted using 3 lots of the Creatinine2 reagent, 2 lots of the Consolidated Chemistry Calibrator, and 1 instrument. The bias ranged from -4.1% to 0.4% across all instruments, calibrator and reagent lots.
Urine
A study was performed to estimate the bias of the Creatinine2 assay relative to material standardized to the Certified Reference Material NIST SRM 914a.
Testing was conducted using 3 concentrations of standard across 3 lots of the Creatinine2 reagent, 2 lots of the Consolidated Chemistry Calibrator, and 1 instrument. The bias ranged from -4.8% to 3.3% across all concentrations of standard, instruments, calibrator and reagent lots.
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D. Lower Limits of Measurement
A study was performed based on guidance from CLSI EP17-A2.8 Testing was conducted using 3 lots of the Creatinine2 reagent kit on each of 2 instruments over a minimum of 3 days. The maximum observed limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) values are summarized below.
| mg/dL | |
|---|---|
| LoBa | 0.02 |
| LoDb | 0.04 |
| LoQc | 0.09 |
Serum/Plasma
Urine
| mg/dL | |
|---|---|
| LoBa | 0.93 |
| LoDb | 1.24 |
| LoQc | 2.54 |
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 is defined as the lowest concentration at which a maximum allowable precision of 20% CV was met and was determined from n ≥ 60 replicates of low-analyte level samples.
E. Linearity
A study was performed based on guidance from CLSI EP06-A.** This assay demonstrated linearity across the analytical measuring interval of 0.09 to 37.34 mg/dL
for the serum application, and 2.54 to 740 mg/dL for the urine application.
9 Clinical and Laboratory Standards Institute (CLS). Evaluation of Detection Capability for Clinical Laboratory Measurent Procedures; Approved Guideline-Second Edition. CLSI Document EP17-A2. Wayne, PA: CLSI; 2012.
** Clinical and Laboratory Standards of the Linearity of the Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline. CLSI Document EP06-A. Wayne, PA: CLSI; 2003.
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F. Potentially Interfering Endogenous and Exogenous Substances
Serum/Plasma - Potentially Interfering Endogenous Substances
A study was performed based on guidance from CLSI EP07, 3rd ed. ** Each substance was tested at 2 levels of the analyte (approximately 0.6 mg/dL and 2.0 mg/dL).
No significant interference (interference within ± 10%) was observed at the following concentrations.
| Potentially Interfering Substance | Interferent Level | Analyte Level |
|---|---|---|
| Acetoacetate | 20 mg/dL | 0.6 mg/dL |
| 2.0 mg/dL | ||
| Bilirubin - conjugated | 20 mg/dL | |
| 40 mg/dL | 0.6 mg/dL | |
| 2.0 mg/dL | ||
| Bilirubin - unconjugated | 8 mg/dL | |
| 40 mg/dL | 0.6 mg/dL | |
| 2.0 mg/dL | ||
| Glucose | 250 mg/dL | |
| 750 mg/dL | 0.6 mg/dL | |
| 2.0 mg/dL | ||
| Hemoglobin | 1000 mg/dL | 0.6 mg/dL |
| 2.0 mg/dL | ||
| Triglycerides | 750 mg/dL | |
| 1500 mg/dL | 0.6 mg/dL | |
| 2.0 mg/dL | ||
| Total protein | 5.4 g/dL to 8.4 g/dL* | |
| 11.0 g/dL** | 0.6 mg/dL | |
| 2.0 mg/dL |
- Interference relative to a reference protein sample at 7.0 g/dL.
** Interference relative to a reference protein sample at 5.7 g/dL.
** Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.
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Interference beyond ± 10% [based on 95% Confidence Interval (CI)] was observed
| Potentially Interfering
Substance | Interferent Level | Analyte Level | % Interference
(95% CI) |
|--------------------------------------|---------------------------------------|-------------------------------------|-------------------------------------------------------|
| Bilirubin - conjugated | 40 mg/dL | 0.6 mg/dL | -14% (-16%, -13%) |
| Bilirubin - unconjugated | 10 mg/dL | 0.6 mg/dL | -11% (-12%, -9%) |
| Glucose | 1000 mg/dL | 0.6 mg/dL | 42% (41%, 44%) |
| Glucose | 1000 mg/dL | 2.0 mg/dL | 13% (13%, 14%) |
| Total protein | 6.8 g/dL | 0.6 mg/dL | 17% (15%, 18%) |
| Triglycerides | 1000 mg/dL | 0.6 mg/dL | 11% (9%, 12%) |
| Total protein | 5.0 g/dL*
9.1 g/dL*
15.3 g/dL** | 0.6 mg/dL
0.6 mg/dL
2.0 mg/dL | -14% (-15%, -14%)
12% (11%, 12%)
20% (19%, 21%) |
at the concentrations shown below for the following substances.
- Interference relative to a reference protein sample at 7.0 g/dL.
** Interference relative to a reference protein sample at 5.7 g/dL.
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Serum/Plasma - Potentially Interfering Exogenous Substances
A study was performed based on guidance from CLSI EP07, 3rd ed.++ Each substance was tested at 2 levels of the analyte (approximately 0.6 mg/dL and 2.0 mg/dL).
No significant interference (interference within ± 10%) was observed at the following concentrations.
| Potentially Interfering
Substance | Interferent
Level | Potentially Interfering
Substance | Interferent
Level |
|--------------------------------------|----------------------|-----------------------------------------|----------------------|
| Acetaminophen | 160 mg/L | Ibuprofen | 220 mg/L |
| Acetohexamide | 0.5 mg/dL | Levodopa | 8 mg/L |
| Acetylcysteine | 150 mg/L | Methyldopa | 100 mg/L |
| Acetylsalicylic acid | 30 mg/L | Metronidazole | 130 mg/L |
| Ampicillin-Na | 80 mg/L | Nitrofurantoin | 0.3 mg/dL |
| Ascorbic acid | 60 mg/L | Nitroglycerin | 0.015 mg/L |
| Azlocillin | 7 g/L | Norfenefrine | 4 mg/L |
| Biotin | 4250 ng/mL | Phenylbutazone | 330 mg/L |
| Ca-dobesilate | 60 mg/L | Rifampicin | 50 mg/L |
| Cefotaxime | 53 mg/dL | Sodium heparin | 4 U/mL |
| Cefoxitin | 47 mg/L | Sulbactam | 240 mg/L |
| Cephalothin | 11 mg/dL | Sulfamethoxazole | 40 mg/dL |
| Cyclosporine | 2 mg/L | Sulfapyridine | 30 mg/dL |
| Doxycycline | 20 mg/L | Sulfasalazine | 500 mg/L |
| Eltrombopag | 10 mg/L | Theophylline (1.3-
dimethylxanthine) | 60 mg/L |
| Hydroxocobalamin (Cyanokit) | 187 mg/L | Trimethoprim | 5 mg/dL |
** Clinical and Laboratory Standards Institute (CLSI). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.
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Interference beyond ± 10% [based on 95% Confidence Interval (CI)] was observed
| Potentially Interfering
Substance | Interferent Level | Analyte Level | % Interference
(95% CI) |
|--------------------------------------|-------------------|---------------|----------------------------|
| Acetohexamide | 1.5 mg/dL | 0.6 mg/dL | 18% (16%, 20%) |
| Acetohexamide | 2 mg/dL | 2.0 mg/dL | 10% (10%, 11%) |
| Cefoxitin | 71 mg/L | 0.6 mg/dL | 14% (12%, 16%) |
| Cefoxitin | 119 mg/L | 2.0 mg/dL | 13% (12%, 14%) |
| Cephalothin | 180 mg/dL | 0.6 mg/dL | 193% (190%, 196%) |
| Cephalothin | 180 mg/dL | 2.0 mg/dL | 56% (55%, 57%) |
| Eltrombopag | 300 mg/L | 0.6 mg/dL | 53% (51%, 55%) |
| Eltrombopag | 25 mg/L | 2.0 mg/dL | -12% (-12%, -11%) |
| Hydroxocobalamin
(Cyanokit) | 375 mg/L | 0.6 mg/dL | 16% (14%, 18%) |
| Hydroxocobalamin
(Cyanokit) | 2259 mg/L | 2.0 mg/dL | 19% (19%, 20%) |
| Methyldopa | 200 mg/L | 0.6 mg/dL | -17% (-18%, -15%) |
at the concentrations shown below for the following substances.
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Urine - Potentially Interfering Endogenous Substances
A study was performed based on guidance from CLSI EP07, 3rd ed§§ / CLSI EP37, 1st ed.*** Each substance was tested at 2 levels of the analyte (approximately 15 mg/dL and 400 mg/dL).
No significant interference (interference within ± 10%) was observed at the following concentrations.
| Potentially Interfering Substance | Interferent Level |
|---|---|
| Acetoacetate | 480 mg/dL |
| Ascorbate | 220 mg/dL |
| Glucose | 1000 mg/dL |
| Protein | 50 mg/dL |
| Urobilinogen | 40 mg/dL |
80 Clinical and Laboratory Standards Institute (CLS). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.
***Clinical and Laboratory Standards Institute (CLSI). Supplemental Tables for Interference Testing in Clinical Chemistry. Ist ed. CLSI supplement EP37. Wayne, PA: CLSI; 2018.
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Urine - Potentially Interfering Exogenous Substances
A study was performed based on guidance from CLSI EP07, 3rd ed*** / CLSI EP37, 1st ed. ## Each substance was tested at 2 levels of the analyte (approximately 15 mg/dL and 400 mg/dL).
No significant interference (interference within ± 10%) was observed at the following concentrations.
| Potentially Interfering
Substance | Interferent Level | Potentially Interfering
Substance | Interferent Level |
|--------------------------------------|-------------------|--------------------------------------|-------------------|
| Acetaminophen | 16 mg/dL | Ibuprofen | 22 mg/dL |
| Acetic acid (8.5N) | 6.25 mL/dL | Levodopa | 700 mg/L |
| Acetylcysteine | 15 mg/dL | Methyldopa | 20 mg/L |
| Biotin | 4250 ng/mL | Nitric acid (6N) | 5.0 mL/dL |
| Boric acid | 250 mg/dL | Nitrofurantoin | 150 mg/L |
| Cefoxitin | 100 mg/dL | Nitrofurazone | 3 mg/L |
| Cephalothin | 180 mg/dL | Sodium carbonate | 1.25 g/dL |
| Homogentisic acid | 3.5 g/L | Sodium fluoride | 400 mg/dL |
| Hydrochloric acid (6N) | 2.5 mL/dL | Sodium oxalate | 60 mg/dL |
| Hydroxocobalamin (Cyanokit) | 180 mg/L | | |
Interference beyond ± 10% [based on 95% Confidence Interval (CI)] was observed
at the concentrations shown below for the following substances.
| Potentially Interfering
Substance | Interferent Level | Analyte Level | % Interference
(95% CI) |
|--------------------------------------|-------------------|---------------|----------------------------|
| Cefoxitin | 400 mg/dL | 15 mg/dL | 26% (24%, 27%) |
| Levodopa | 1000 mg/dL | 15 mg/dL | 15% (13%, 16%) |
Interferences from medication or endogenous substances may affect results. $$$
"T" Clinical and Laboratory Standards Institute (CLS). Interference Testing in Clinical Chemistry. 3rd ed. CLSI Guideline EP07. Wayne, PA: CLSI; 2018.
#1* Clinical and Laboratory Standards Institute (CLSI). Supplemental Tables for Interference Testing in Clinical Chemistry. Ist ed. CLSI supplement EP37. Wayne, PA: CLSI; 2018.
$$$ Young DS. Effects of Drugs on Clinical Laboratory Tests. 5th ed. Washington, DC: AACC Press; 2000:182-206
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G. Method Comparison
A study was performed based on guidance from CLSI EP09-A3 **** using the Passing-Bablok regression method. The study compared the Creatinine2 assay to the Creatinine assay (List Number 3L81).
| Creatinine2 vs Creatinine on the ARCHITECT c System | ||||||
|---|---|---|---|---|---|---|
| n | Units | Correlation | ||||
| Coefficient | Intercept | Slope | Concentration | |||
| Range | ||||||
| Serum | 128 | mg/dL | 1.00 | -0.01 | 0.96 | 0.47 - 35.72 |
| Urine | 129 | mg/dL | 1.00 | -1.23 | 1.01 | 6.65 - 727.61 |
H. Tube Type
A study was performed to evaluate the suitability of specific blood collection tube types for use with the Creatinine2 assay. 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 Creatinine2 assay:
Serum
- Serum tubes .
- . Serum separator tubes
Plasma
- . Dipotassium EDTA tubes
- Lithium heparin tubes .
- Lithium heparin separator tubes .
- Sodium heparin tubes
**** Samples; Approved Guideline-Third Edition. CLSI Document EP09-A3. Wayne, PA: CLSI; 2013.
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IX. Summary of Clinical Performance
This section does not apply.
X. Conclusion Drawn from Nonclinical Laboratory Studies
The results presented in this 510(k) premarket notification demonstrate that the performance of the subject device, Creatinine2 (List No. 04S95), is substantially equivalent to the predicate device, Creatinine (List No. 3L81, K083809).
The similarities and differences between the subject device and predicate device are presented in Section 5-VII.
There is no known potential adverse effect to the operator when using this in vitro device according to the Creatinine2 reagent package insert instructions.