(141 days)
For in vitro diagnostic use in the quantitative determination of creatinine in human serum, plasma, and urine on the ADVIA Chemistry Systems. Such measurements are used in the diagnosis and treatment of renal diseases, and in monitoring renal dialysis.
The ADVIA Chemistry Enzymatic Creatinine_2 is used for the in vitro quantitative determination of creatinine in human serum, plasma and urine on the ADVIA® Chemistry Systems. The proposed labeling indicates the ADVIA Chemistry Enzymatic Creatinine 2 reagents can be used on the ADVIA Chemistry 1200 / 1650 / 1800 / 2400 Systems.
The principle of the method is based on the enzymatic method employing creatininase, creatinase, sarcosine oxidase, horseradish peroxidase and N-(3-sulfopropy))-3methoxy-5-methylaniline (HMMPS) as the color agent. When a sample is mixed with Reagent 1 and Reagent 2, creatinine in the sample is converted to creatine by the action of creatininase. The creatine formed is hydrolyzed by creatinase to produce sarcosine and urea. The sarcosine is then decomposed by sarcosine oxidase to form glycine, formaldehyde and hydrogen peroxide. In the presence of peroxidase (POD), the hydrogen peroxide formed yields a blue pigment by quantitative oxidative condensation with N-(3-sulfopropy)-3-methoxy-5-methylaniline (HMMPS) and 4aminoantipyrine. The creatinine concentration is obtained by measuring the absorbance of blue color. The increase in optical absorbance is determined as an endpoint assay, which is proportional to the concentration of creatinine in the sample.
Here's a summary of the acceptance criteria and study findings for the ADVIA® Chemistry Enzymatic Creatinine_2 (ECRE_2) device, based on the provided 510(k) submission:
1. Table of Acceptance Criteria and Reported Device Performance
The submission demonstrates substantial equivalence by testing various performance characteristics and comparing them to predicate devices. The "acceptance criteria" are implied by showing the new device's performance to be comparable to, and within an acceptable range of, the predicate devices.
| Performance Characteristic | Acceptance Criteria (Implied by Predicate Device Performance and Comparability) | Reported Device Performance (ADVIA Chemistry Enzymatic Creatinine_2) |
|---|---|---|
| Imprecision (Serum) | Comparable total CV (%) to predicate devices (ADVIA Chemistry Creatinine_2 and Enzymatic Creatinine) | ADVIA 1650: 0.6% - 1.1% (across creatinine levels 1.29-8.80 mg/dL) |
| ADVIA 2400: 0.8% - 1.4% (across creatinine levels 1.28-8.81 mg/dL) | ||
| ADVIA 1200: 0.9% - 1.1% (across creatinine levels 1.29-8.79 mg/dL) | ||
| Imprecision (Urine) | Comparable total CV (%) to predicate devices (ADVIA Chemistry Creatinine_2) | ADVIA 1650: 0.9% - 1.3% (across creatinine levels 41.56-130.59 mg/dL) |
| ADVIA 2400: 0.9% - 1.0% (across creatinine levels 41.13-131.33 mg/dL) | ||
| ADVIA 1200: 1.0% - 1.1% (across creatinine levels 42.34-133.09 mg/dL) | ||
| Method Comparison (Correlation) | Linear regression results (slope, intercept, correlation coefficient 'r') and Sy.x values demonstrating strong correlation and similar performance to predicate devices. | Serum (vs. predicate Creatinine_2): Slopes 1.017-1.026; Intercepts -0.04 to 0.03; Sy.x 0.07-0.13; r 1.000 |
| Serum (vs. predicate Enzymatic Creatinine): Slopes 0.933-0.957; Intercepts 0.01 to 0.11; Sy.x 0.07-0.14; r 1.000 | ||
| Urine (vs. predicate Creatinine_2): Slopes 1.019-1.042; Intercepts -0.99 to 2.47; Sy.x 1.80-2.99; r 0.999-1.000 | ||
| Interfering Substances (Hemoglobin, Lipids, Bilirubin) | Minimal percentage change in creatinine concentration due to interferent, comparable to acceptable clinical limits. | Hemoglobin (500-1000 mg/dL): -3.8% to 7.5% change |
| Lipids (Intralipid, 1000 mg/dL): -5.7% to 6.6% change | ||
| Bilirubin, free (22.5-30.0 mg/dL): -6.6% to -9.8% change | ||
| Bilirubin, conjugated (30.0 mg/dL): -2.7% to -6.0% change | ||
| Analytical Range (Serum/Plasma) | Defined operational range covering clinically relevant concentrations. | 0.1 - 30.0 mg/dL |
| Analytical Range (Urine) | Defined operational range covering clinically relevant concentrations. | 1.0 - 245 mg/dL |
2. Sample Size Used for the Test Set and Data Provenance
- Imprecision Study (Serum): Levels tested were 1.29 mg/dL through 8.80 mg/dL. The number of samples for each level or total sample size is not explicitly stated but implied to be sufficient for precision calculations (CV%).
- Imprecision Study (Urine): Levels tested were 41.56 mg/dL through 130.59 mg/dL. The number of samples for each level or total sample size is not explicitly stated.
- Method Comparison (Correlation):
- Serum: 60 samples (for comparison against Creatinine_2 predicate), 28 or 42 samples (for comparison against Enzymatic Creatinine predicate), depending on the system (ADVIA 1200, 1650, 2400).
- Urine: 44 to 49 samples (for comparison against Creatinine_2 predicate), depending on the system.
- Interfering Substances: Specific sample sizes are not explicitly stated for each interferent test but are implied to be sufficient to determine the effect at specific analyte and interferent concentrations.
- Data Provenance: The document does not specify the country of origin of the data or explicitly state whether the studies were retrospective or prospective. Given the nature of an in vitro diagnostic device validation, these are typically prospective studies using well-characterized samples or spiked samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This type of information (number and qualifications of experts) is generally not applicable or provided for in vitro diagnostic (IVD) device submissions like this one, especially for quantitative assays. The "ground truth" for creatinine measurements in this context is established by the direct measurement by the predicate devices or by well-established reference methods (e.g., ID-MS, HPLC candidate reference method as mentioned for standardization), not by human expert consensus or clinical interpretation of images.
4. Adjudication Method for the Test Set
Not applicable. As noted above, the "ground truth" for an IVD quantitative assay like creatinine is based on instrument measurements and reference methods, not subjective human assessment requiring adjudication.
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. This device is an in vitro diagnostic assay (a laboratory test) that directly measures creatinine levels, not an imaging device or an AI-assisted diagnostic tool that would involve human "readers" or clinical interpretations.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, this entire submission represents the "standalone" performance of the assay itself. The ADVIA Chemistry Enzymatic Creatinine_2 assay is an automated in vitro diagnostic test system. All the performance data (imprecision, method comparison, interference, analytical range) reflect the performance of the algorithm/reagent system as a standalone measurement tool. There is no human interpretation or "in-the-loop" component in the direct measurement of creatinine by the device itself.
7. The Type of Ground Truth Used
The ground truth for the comparison studies was established by:
- Predicate Devices: The measurements obtained from the legally marketed predicate devices: ADVIA Chemistry Creatinine_2 (Jaffe method) and ADVIA Chemistry Enzymatic Creatinine (Enzymatic Deiminase/GLDH method). The new device's performance was evaluated against these established methods.
- Standardization: The new device (ECRE_2) uses ID-MS (SRM 967) for standardization. The predicate devices used an HPLC candidate reference method. These reference methods serve as the ultimate "ground truth" for standardization and traceability of the creatinine measurements.
8. The Sample Size for the Training Set
The document does not explicitly delineate a "training set" in the context of deep learning or AI model development, as this is a chemical assay, not an AI algorithm in that sense. The "training" in this context would refer to the optimization and verification during the assay's development. The data presented here are validation data for the established final product.
9. How the Ground Truth for the Training Set Was Established
As explained above, there isn't a traditional "training set" in the AI sense for this chemical assay. The development of the assay (analogous to "training") would involve establishing the chemical reactions, optimizing reagent concentrations, and calibrating the system. The "ground truth" for this development/optimization would be based on:
- Known concentrations of creatinine standards.
- Traceability to recognized reference methods (like ID-MS and HPLC).
- Performance established by predicate devices.
§ 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.