(399 days)
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 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.
The provided document describes the Abbott Creatinine2 assay, an in vitro diagnostic device, and its performance relative to a predicate device. The information needed to answer the request is primarily found in Section 5: 510(k) Summary (Summary of Safety and Effectiveness), specifically subsections VIII (Summary of Nonclinical Performance) and VII (Comparison of Technological Characteristics).
Here's the breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" as a separate, pre-defined column. Instead, it presents the results of various performance studies. The "Reported Device Performance" below is extracted directly from the study results presented in the document. The comparable predicate device values are included for context where available.
Creatinine2 Assay - Performance Summary
| Metric | Acceptance Criteria (Implied/Predicate Performance) | Reported Device Performance (Creatinine2) |
|---|---|---|
| Analytical Measuring Interval (AMI) | Serum/Plasma: 0.09 – 37.34 mg/dL Urine: 2.54 – 740 mg/dL | |
| Reportable Interval | Serum/Plasma: 0.04 – 37.34 mg/dL Urine: 1.24 – 740 mg/dL | |
| Precision (Within-Laboratory %CV) | Predicate (Serum/Plasma): 3.18 - 4.95% (at 1.20-4.66 mg/dL) Predicate (Urine): 1.27 - 1.34% (at 61.95-145.48 mg/dL) | Serum/Plasma: ≤ 4.5% (Panel A: 0.25 mg/dL), ≤ 2.3% (Panel B: 26.00 mg/dL), ≤ 2.1% (Panel C: 36.36 mg/dL) Urine: ≤ 5.5% (Panel A: 5.37 mg/dL), ≤ 1.8% (Panel B: 278.12 mg/dL), ≤ 1.8% (Panel C: 701.12 mg/dL) |
| Accuracy (Bias) | Serum/Plasma (vs. NIST SRM 967a): -4.1% to 0.4% bias Urine (vs. NIST SRM 914a): -4.8% to 3.3% bias | |
| Lower Limits of Measurement (LoB, LoD, LoQ) | Predicate (Serum/Plasma LoD): 0.05 mg/dL Predicate (Serum/Plasma LoQ): 0.10 mg/dL Predicate (Urine LoD): 4.00 mg/dL Predicate (Urine LoQ): 5.00 mg/dL | 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 | Predicate (Serum/Plasma): 0.20 – 37.00 mg/dL Predicate (Urine): 5.00 – 740.00 mg/dL | Serum: 0.09 to 37.34 mg/dL Urine: 2.54 to 740 mg/dL |
| Method Comparison (Correlation Coefficient) | Predicate: Not explicitly stated as a target, but K083809 (Abbott Creatinine) is the predicate and a correlation of 1.00 for both serum and urine suggests excellent agreement. | Serum: 1.00 (between Creatinine2 and predicate Creatinine) Urine: 1.00 (between Creatinine2 and predicate Creatinine) |
| Method Comparison (Intercept) | Serum: -0.01 Urine: -1.23 | |
| Method Comparison (Slope) | Serum: 0.96 Urine: 1.01 | |
| Interference (within ±10%) | No significant interference | Serum/Plasma Endogenous: No interference from listed substances at specified levels (e.g., Acetoacetate 20 mg/dL, Hemoglobin 1000 mg/dL) Serum/Plasma Exogenous: No interference from listed substances at specified levels (e.g., Acetaminophen 160 mg/L) Urine Endogenous: No interference from listed substances at specified levels (e.g., Acetoacetate 480 mg/dL) Urine Exogenous: No interference from listed substances at specified levels (e.g., Acetaminophen 16 mg/dL) |
2. Sample Size Used for the Test Set and Data Provenance
The document describes several nonclinical laboratory studies.
- Precision (Within-Laboratory): For both Serum/Plasma and Urine, the studies tested 80 replicates per sample type for each of the two controls and three human panels (5 samples total). This was done in duplicate, twice per day, on 20 days. The provenance of the human panels (e.g., country of origin, retrospective/prospective) is not specified, but they are referred to as "human serum panels" and "human urine panels." This data is ex vivo laboratory testing.
- Accuracy: No specific sample size of "patient samples" is given. The study was performed using "material standardized to the Certified Reference Material NIST SRM 967a" for serum/plasma and "material standardized to the Certified Reference Material NIST SRM 914a" for urine.
- Lower Limits of Measurement (LoB, LoD, LoQ): n ≥ 60 replicates for zero-analyte and low-analyte level samples for LoB/LoD, and for low-analyte level samples for LoQ.
- Linearity: The sample size for linearity is not explicitly stated in terms of number of unique samples, but it covers the analytical measuring interval by spiking and dilution.
- Method Comparison:
- Serum: 128 samples
- Urine: 129 samples
The provenance of these clinical samples (e.g., country of origin, retrospective or prospective) is not explicitly stated.
- Interference: "Each substance was tested at 2 levels of the analyte." No specific sample size (n) for the number of replicates per interference test is given beyond this, nor is the provenance of the base samples used.
- Tube Type: "Samples were collected from a minimum of 40 donors." The provenance is not explicitly stated.
The studies described are nonclinical laboratory studies, primarily involving analytical performance evaluation rather than clinical patient studies.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This information is not applicable (N/A) to this specific device (Creatinine2 assay). The device is an in vitro diagnostic for quantitative measurement of creatinine, not an imaging device or a device requiring expert interpretation of complex clinical data to establish ground truth for its performance evaluation (e.g., a diagnosis of a disease from imaging). The "ground truth" for its analytical accuracy is typically established against certified reference materials (NIST SRM 967a for serum/plasma and NIST SRM 914a for urine) or reference methods, not by human experts adjudicating cases for a test set.
4. Adjudication Method for the Test Set
This information is not applicable (N/A) for the same reasons as #3. Clinical adjudication by multiple experts (like 2+1, 3+1) is typically used for devices that rely on human interpretation of outputs (e.g., medical images, pathology slides) where consensus or expert opinion defines the ground truth for diagnostic accuracy. This device measures a biochemical analyte.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This type of study is relevant for medical devices where human readers or interpreters are part of the diagnostic workflow, such as imaging-based AI tools. The Creatinine2 assay is an automated clinical chemistry assay that directly measures creatinine levels in biological samples and does not involve human image interpretation or a "human-in-the-loop" effectiveness study as typically understood in the context of MRMC studies.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
The Creatinine2 assay is a standalone (algorithm only) device in the sense that it performs a quantitative measurement without a human-in-the-loop for interpreting the output of the device to arrive at the creatinine value. The performance metrics described (precision, accuracy, linearity, lower limits of measurement, interference, method comparison) are all tests of the device's performance directly, independent of human interpretation or assistance in generating the result.
7. The Type of Ground Truth Used
The ground truth for the performance evaluation of the Creatinine2 assay was primarily established using:
- Certified Reference Materials: NIST SRM 967a for serum/plasma and NIST SRM 914a for urine were used for accuracy studies.
- Predicate Device/Reference Method: The Creatinine assay (K083809; List No. 3L81) was used as a comparator for the method comparison study to assess substantial equivalence.
- Defined Standards/Controls: For precision and lower limits of measurement, studies used control materials and low-analyte level samples with known or established concentrations to determine repeatability, detection, and quantitation limits.
8. The Sample Size for the Training Set
This information is not applicable (N/A). The Creatinine2 assay is a chemical assay, not a machine learning or AI-based device that requires a "training set" in the computational sense. Its performance is based on the chemical reaction and analytical methods described.
9. How the Ground Truth for the Training Set Was Established
This information is not applicable (N/A) for the same reasons as #8.
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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.
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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
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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
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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 DeviceCreatinine2 (List No. 04S95) | Predicate DeviceCreatinine (K083809; List No.3L81) |
|---|---|---|
| Platform | ARCHITECT c System | Same |
| Intended Use andIndications forUse | The Creatinine2 assay is used for thequantitation of creatinine in humanserum, plasma, or urine on theARCHITECTc System.The Creatinine2 assay is to be used as anaid in the diagnosis and treatment ofrenal diseases, in monitoring renaldialysis, and as a calculation basis formeasuring other urine analytes. | The Creatinine assay is used for thequantitation of creatinine in humanserum, plasma, or urine. |
| Methodology | Kinetic Alkaline Picrate | Same |
| Specimen Type | Human serum, plasma, urine | Same |
| Assay Principle /Principle ofProcedure | The Creatinine2 assay is an automatedclinical chemistry assay. At an alkalinepH, creatinine in the sample reacts withpicric acid to form a creatinine-picratecomplex that absorbs at 500 nm. Therate of increase in absorbance is directlyproportional to the concentration ofcreatinine in the sample. | At an alkaline pH, creatinine in thesample reacts with picrate to form acreatinine-picrate complex. The rate ofincrease in absorbance at 500 nm due tothe formation of this complex is directlyproportional to the concentration ofcreatinine in the sample. |
| Standardization | NIST SRM 967 for serum/plasmaNIST SRM 914 for urine | Same |
| Use ofCalibrators | Yes | Same |
| Use of Controls | Yes | Same |
| Characteristics | Subject DeviceCreatinine2 (List No. 04S95) | Predicate DeviceCreatinine (K083809; List No.3L81) |
| Assay Range | Serum/Plasma:Analytical Measuring Interval:0.09 – 37.34 mg/dLReportable Interval:0.04 – 37.34 mg/dLUrine:Analytical Measuring Interval:2.54 – 740 mg/dLReportable Interval:1.24 – 740 mg/dL | Serum/Plasma:Creatinine serum is linear from 0.20to 37.00 mg/dL.Urine:Creatinine urine is linear from 5.00 to740.00 mg/dL. |
| Precision | Serum/Plasma:Samples with creatinine concentrationsbetween 0.25 and 36.36 mg/dL wereevaluated. The samples demonstrated% coefficients of variation (%CV) ≤3.5% and standard deviations (SD)≤ 0.011 mg/dL.Urine:Samples with creatinine concentrationsbetween 5.25 and 701.12 mg/dL wereevaluated. The samples demonstrated%CV ≤ 2.4% and SD ≤ 0.294 mg/dL. | Serum/Plasma:Samples with creatinineconcentrations between 1.20 and 4.66mg/dL demonstrated %CV valuesranging from 3.18 to 4.95%.Urine:Samples with creatinineconcentrations between 61.95 and145.48 mg/dL demonstrated %CVvalues ranging from 1.27 to 1.34%. |
| Lower Limits ofMeasurement | Serum/Plasma:Limit of Blank: 0.02 mg/dLLimit of Detection: 0.04 mg/dLLimit of Quantitation: 0.09 mg/dLUrine:Limit of Blank: 0.93 mg/dLLimit of Detection: 1.24 mg/dLLimit of Quantitation: 2.54 mg/dL | Serum/Plasma:Limit of Detection: 0.05 mg/dLLimit of Quantitation: 0.10 mg/dLUrine:Limit of Detection: 4.00 mg/dLLimit of Quantitation: 5.00 mg/dL |
| Characteristics | Subject DeviceCreatinine2 (List No. 04S95) | Predicate DeviceCreatinine (K083809; List No. 3L81) |
| Tube Types | Serum:- Serum tubes- Serum separator tubesPlasma:- Dipotassium EDTA tubes- Lithium heparin tubes- Lithium heparin separator tubes- Sodium heparin tubes | Serum:- Glass or plastic tubes with orwithout gel barrierPlasma:- Glass or plastic lithium heparintubes (with or without gel barrier)- Glass or plastic EDTA tubes- Glass or plastic sodium heparintubes |
Comparison of Subject Device (Creatinine2) to Predicate Device (Creatinine)
NIST - National Institute of Standards and Technology SRM - Standard Reference Materials
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Comparison of Subject Device (Creatinine2) to Predicate Device (Creatinine) (Continued)
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Comparison of Subject Device (Creatinine2) to Predicate Device (Creatinine) (Continued)
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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 "<0.09 mg/dL").
Urine
| mg/dL | |
|---|---|
| Analytical Measuring Interval (AMI)a | 2.54 - 740 |
| Reportable Intervalb | 1.24 - 740 |
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 "<2.54 mg/dL").
" 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/dL2.0 mg/dL |
| Bilirubin - conjugated | 20 mg/dL40 mg/dL | 0.6 mg/dL2.0 mg/dL |
| Bilirubin - unconjugated | 8 mg/dL40 mg/dL | 0.6 mg/dL2.0 mg/dL |
| Glucose | 250 mg/dL750 mg/dL | 0.6 mg/dL2.0 mg/dL |
| Hemoglobin | 1000 mg/dL | 0.6 mg/dL2.0 mg/dL |
| Triglycerides | 750 mg/dL1500 mg/dL | 0.6 mg/dL2.0 mg/dL |
| Total protein | 5.4 g/dL to 8.4 g/dL*11.0 g/dL** | 0.6 mg/dL2.0 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 InterferingSubstance | 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/dL0.6 mg/dL2.0 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 InterferingSubstance | InterferentLevel | Potentially InterferingSubstance | InterferentLevel |
|---|---|---|---|
| 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 InterferingSubstance | 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 InterferingSubstance | Interferent Level | Potentially InterferingSubstance | 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 InterferingSubstance | 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 | CorrelationCoefficient | Intercept | Slope | ConcentrationRange | |
| 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.
§ 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.