(132 days)
The ACE Carbon Dioxide (CO2-LC) Reagent is intended for the quantitative determination of carbon dioxide concentration in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Bicarbonate/carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
The ACE Direct Bilirubin Reagent is intended for the quantitative determination of direct bilirubin concentration in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal destruction of red blood cells, is used in the diagnosis and treatment of liver, hemolytic, hematological and metabolic disorders, including hepatitis and gall bladder block. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
The ACE Total Bilirubin Reagent is intended for the quantitative determination of total bilirubin concentration in serum and lithium heparin plasma using the ACE, ACE Alera and ACE Axcel Clinical Chemistry System. Measurements of the levels of bilirubin, an organic compound formed during the normal and abnormal destruction of red blood cells, is used in the diagnosis and treatment of liver, hemolytic, hematological and metabolic disorders, including hepatitis and gall bladder block. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
The ACE Magnesium Reagent is intended for the quantitative determination of magnesium in serum and lithium heparin plasma using the ACE, ACE Alera and ACE Axcel Clinical Chemistry Systems. Magnesium measurements are used in the diagnosis and treatment of hypomagnesemia (abnormally low plasma levels of magnesium) and hypermagnesemia (abnormally high plasma levels of magnesium). This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
In the ACE Carbon Dioxide (CO2-LC) Reagent assay, serum carbon dioxide (in the form of bicarbonate) reacts with phosphoenolpyruvate in the presence of phosphoenolpyruvate carboxylase and magnesium to yield oxaloacetic acid and phosphate. In the presence of malate dehydrogenase, the reduced cofactor is oxidized by oxaloacetic acid. The reduced cofactor absorbs strongly at 408 nm whereas its oxidized form does not. The rate of decrease in absorbance, monitored bichromatically at 408 nm/692 nm, is proportional to the carbon dioxide content of the sample.
In the ACE Direct Bilirubin Reagent assay, sodium nitrite added to sulfanilic acid forms diazotized sulfanilic acid. Bilirubin glucuronide in serum reacts with diazotized sulfanilic acid to form azobilirubin, which absorbs strongly at 554 nm. The increase in absorbance, measured bichromatically at 554 nm/692 nm, one minute after sample addition, is directly proportional to the direct bilirubin concentration.
In the ACE Total Bilirubin Reagent assay, sodium nitrite, when added to sulfanilic acid, forms diazotized sulfanilic acid. Bilirubin in serum reacts with diazotized sulfanilic acid to form azobilirubin, which absorbs strongly at 554 nm. The inclusion of dimethyl sulfoxide (DMSO) in the reagent as an accelerator causes both direct and indirect bilirubin to react rapidly. The increase in absorbance, measured bichromatically at 554 nm/692 nm, is directly proportional to the total bilirubin concentration in the sample.
Magnesium ions in serum react with Xylidyl blue-1 in an alkaline medium to produce a red complex which is measured bichromatically at 525 nm/692 nm. The intensity of color produced is directly proportional to the magnesium concentration in the sample. EGTA prevents calcium interference by preferential chelation of calcium present in the sample. A surfactant system is included to remove protein interference.
The provided text describes several in vitro diagnostic reagents (ACE Carbon Dioxide (CO2-LC) Reagent, ACE Direct Bilirubin Reagent, ACE Total Bilirubin Reagent, and ACE Magnesium Reagent) and their associated performance data. There isn't information about an AI-powered device or software. Therefore, questions related to AI aspects like multi-reader multi-case studies, effect size of AI assistance, or standalone algorithm performance are not applicable.
The acceptance criteria are not explicitly stated as clear thresholds in the provided document; rather, the document presents detailed performance data (precision, linearity, interference, and method comparison) that demonstrates the device's capability to perform as intended and to be substantially equivalent to its predicate devices. The "reported device performance" is presented directly through tables and statistical analyses for each reagent.
Here's an attempt to structure the available information based on the request, interpreting "acceptance criteria" as the performance demonstrated to support substantial equivalence:
1. Table of Acceptance Criteria and Reported Device Performance
Since explicit "acceptance criteria" (i.e., predefined thresholds for performance metrics) are not provided in the document, the "Reported Device Performance" below represents the data presented that presumably met the internal criteria for demonstrating substantial equivalence. The document primarily focuses on precision, linearity, interference, and method comparison with predicate devices and between different systems (ACE, ACE Alera, ACE Axcel).
ACE Carbon Dioxide (CO2-LC) Reagent
| Metric | Acceptance Criteria (Inferred from study design and historical data, not explicitly stated values) | Reported Device Performance (Summary of results across systems/sites) |
|---|---|---|
| Precision (In-House) | (Implied to be comparable to or better than predicate and acceptable for clinical use) | Serum: |
| Low: ~1.1-2.5% CV (Within-Run), ~5.6-7.5% CV (Total) | ||
| Mid: ~1.2-1.5% CV (Within-Run), ~3.3-3.7% CV (Total) | ||
| High: ~0.6-2.8% CV (Within-Run), ~2.6-3.2% CV (Total) | ||
| Plasma: | ||
| Low: ~1.3-3.0% CV (Within-Run), ~3.8-6.1% CV (Total) | ||
| Mid: ~0.7-1.2% CV (Within-Run), ~5.0-5.5% CV (Total) | ||
| High: ~1.0% CV (Within-Run), ~2.3-2.5% CV (Total) | ||
| Precision (POL sites) | (Implied to be comparable to in-house and acceptable for clinical use) | ACE: |
| Low (Sample 1): ~1.6-3.3% CV (Within-Run), ~3.0-4.3% CV (Total) | ||
| Mid (Sample 2): ~1.7-3.1% CV (Within-Run), ~2.7-7.4% CV (Total) | ||
| High (Sample 3): ~1.8-2.4% CV (Within-Run), ~2.4-6.4% CV (Total) | ||
| ACE Alera: | ||
| Low (Sample 1): ~1.3-2.0% CV (Within-Run), ~3.0-6.7% CV (Total) | ||
| Mid (Sample 2): ~0.9-1.7% CV (Within-Run), ~2.4-3.9% CV (Total) | ||
| High (Sample 3): ~1.0-1.6% CV (Within-Run), ~3.1-5.8% CV (Total) | ||
| Method Comparison (Serum vs. Plasma) | (Slope near 1, intercept near 0, high correlation) | ACE: Slope: 1.031, Intercept: -1.03, Correlation: 0.9922 |
| ACE Alera: Slope: 1.000, Intercept: -0.09, Correlation: 0.9955 | ||
| ACE Axcel: Slope: 0.988, Intercept: -0.35, Correlation: 0.9889 | ||
| Method Comparison (POL vs. In-House) | (Slope near 1, intercept near 0, high correlation) | ACE (POL 1-3 vs. In-House ACE): Slopes: 0.963-0.984, Intercepts: -0.71-1.29, Correlations: 0.9530-0.9908 |
| ACE Alera (POL 1-3 vs. In-House ACE): Slopes: 0.972-0.987, Intercepts: 0.10-0.57, Correlations: 0.9767-0.9903 | ||
| Detection Limits (ACE Alera) | (Appropriate for clinical use) | LoB: 1.27 mEq/L, LoD: 1.97 mEq/L, LoQ: 3.03 mEq/L |
| Linearity (ACE Alera) | (Linearity up to/beyond desired measuring range) | Linear to: 50 mEq/L (Equation: y=1.006x + 0.01) |
| Interferences (ACE Alera) | (No significant interference from common interferents) | No significant interference at or below Icterus 58.8 mg/dL, Hemolysis 250 mg/dL, Lipemia 2388 mg/dL, Ascorbic Acid 6 mg/dL |
ACE Direct Bilirubin Reagent
| Metric | Acceptance Criteria (Inferred from study design and historical data, not explicitly stated values) | Reported Device Performance (Summary of results across systems/sites) |
|---|---|---|
| Precision (In-House) | (Implied to be comparable to or better than predicate and acceptable for clinical use) | Serum: |
| Low: ~12.5-24.5% CV (Within-Run), ~14.0-30.0% CV (Total) | ||
| Mid: ~0.9-1.6% CV (Within-Run), ~1.2-2.2% CV (Total) | ||
| High: ~0.6-1.5% CV (Within-Run), ~1.1-1.7% CV (Total) | ||
| Plasma: | ||
| Low: ~16.6-26.6% CV (Within-Run), ~19.7-35.4% CV (Total) | ||
| Mid: ~0.8-2.4% CV (Within-Run), ~1.1-2.8% CV (Total) | ||
| High: ~0.7-1.9% CV (Within-Run), ~1.1-2.3% CV (Total) | ||
| Precision (POL sites) | (Implied to be comparable to in-house and acceptable for clinical use) | ACE: |
| Low (Sample 1): ~2.9-4.2% CV (Within-Run), ~2.9-4.9% CV (Total) | ||
| Mid (Sample 2): ~1.0-1.8% CV (Within-Run), ~1.3-2.1% CV (Total) | ||
| High (Sample 3): ~1.3-2.3% CV (Within-Run), ~2.0-2.3% CV (Total) | ||
| ACE Alera: | ||
| Low (Sample 1): ~2.5-5.1% CV (Within-Run), ~2.5-5.4% CV (Total) | ||
| Mid (Sample 2): ~1.0-1.5% CV (Within-Run), ~1.0-1.9% CV (Total) | ||
| High (Sample 3): ~0.6-2.6% CV (Within-Run), ~1.3-2.6% CV (Total) | ||
| Method Comparison (Serum vs. Plasma) | (Slope near 1, intercept near 0, high correlation) | ACE: Slope: 1.021, Intercept: 0.00, Correlation: 0.9982 |
| ACE Alera: Slope: 1.005, Intercept: 0.01, Correlation: 0.9978 | ||
| ACE Axcel: Slope: 1.004, Intercept: 0.00, Correlation: 0.9983 | ||
| Method Comparison (POL vs. In-House) | (Slope near 1, intercept near 0, high correlation) | ACE (POL 1-3 vs. In-House ACE): Slopes: 1.003-1.022, Intercepts: 0.04-0.11, Correlations: 0.9984-0.9986 |
| ACE Alera (POL 1-3 vs. In-House ACE): Slopes: 0.969-0.995, Intercepts: 0.09-0.11, Correlations: 0.9984-0.9991 | ||
| Detection Limits (ACE Alera) | (Appropriate for clinical use) | LoB: 0.06 mg/dL, LoD: 0.08 mg/dL, LoQ: 0.12 mg/dL |
| Linearity (ACE Alera) | (Linearity up to/beyond desired measuring range) | Linear to: 14.0 mg/dL (Equation: y=1.015x + 0.16) |
| Interferences (ACE Alera) | (No significant interference from common interferents) | Not Applicable (Icterus), No significant interference at or below Hemolysis 62.5 mg/dL, Lipemia 782 mg/dL, Ascorbic Acid 6 mg/dL |
ACE Total Bilirubin Reagent
| Metric | Acceptance Criteria (Inferred from study design and historical data, not explicitly stated values) | Reported Device Performance (Summary of results across systems/sites) |
|---|---|---|
| Precision (In-House) | (Implied to be comparable to or better than predicate and acceptable for clinical use) | Serum: |
| Low: ~11.0-21.3% CV (Within-Run), ~13.9-21.3% CV (Total) | ||
| Mid: ~1.0-1.1% CV (Within-Run), ~1.0-1.1% CV (Total) | ||
| High: ~0.4-0.7% CV (Within-Run), ~0.5-0.8% CV (Total) | ||
| Plasma: | ||
| Low: ~20.3-23.7% CV (Within-Run), ~21.3-29.4% CV (Total) | ||
| Mid: ~0.5-1.0% CV (Within-Run), ~0.5-1.1% CV (Total) | ||
| High: ~0.5-0.6% CV (Within-Run), ~0.5-0.7% CV (Total) | ||
| Precision (POL sites) | (Implied to be comparable to in-house and acceptable for clinical use) | ACE: |
| Low (Sample 1): ~3.4-5.5% CV (Within-Run), ~3.7-5.8% CV (Total) | ||
| Mid (Sample 2): ~0.5-1.7% CV (Within-Run), ~1.3-3.7% CV (Total) | ||
| High (Sample 3): ~1.0-1.2% CV (Within-Run), ~1.2-2.1% CV (Total) | ||
| ACE Alera: | ||
| Low (Sample 1): ~4.2-4.9% CV (Within-Run), ~4.5-5.2% CV (Total) | ||
| Mid (Sample 2): ~0.7-2.0% CV (Within-Run), ~0.8-2.1% CV (Total) | ||
| High (Sample 3): ~0.5-1.4% CV (Within-Run), ~0.6-1.7% CV (Total) | ||
| Method Comparison (Serum vs. Plasma) | (Slope near 1, intercept near 0, high correlation) | ACE: Slope: 1.017, Intercept: 0.01, Correlation: 0.9996 |
| ACE Alera: Slope: 1.020, Intercept: 0.00, Correlation: 0.9993 | ||
| ACE Axcel: Slope: 1.008, Intercept: 0.00, Correlation: 0.9995 | ||
| Method Comparison (POL vs. In-House) | (Slope near 1, intercept near 0, high correlation) | ACE (POL 1-3 vs. In-House ACE): Slopes: 0.979-1.000, Intercepts: 0.00-0.04, Correlations: 0.9995-0.9998 |
| ACE Alera (POL 1-3 vs. In-House ACE): Slopes: 0.957-1.020, Intercepts: 0.01-0.07, Correlations: 0.9991-0.9998 | ||
| Detection Limits (ACE Alera) | (Appropriate for clinical use) | LoB: 0.11 mg/dL, LoD: 0.14 mg/dL, LoQ: 0.14 mg/dL |
| Linearity (ACE Alera) | (Linearity up to/beyond desired measuring range) | Linear to: 40.0 mg/dL (Equation: y=1.004x + 0.03) |
| Interferences (ACE Alera) | (No significant interference from common interferents) | Not Applicable (Icterus), No significant interference at or below Hemolysis 62.5 mg/dL, Lipemia 951 mg/dL, Ascorbic Acid 6 mg/dL |
ACE Magnesium Reagent
| Metric | Acceptance Criteria (Inferred from study design and historical data, not explicitly stated values) | Reported Device Performance (Summary of results across systems/sites) |
|---|---|---|
| Precision (In-House) | (Implied to be comparable to or better than predicate and acceptable for clinical use) | Serum: |
| Low: ~3.1-5.1% CV (Within-Run), ~4.3-5.9% CV (Total) | ||
| Mid: ~1.7-2.6% CV (Within-Run), ~1.8-3.0% CV (Total) | ||
| High: ~1.0-1.4% CV (Within-Run), ~1.6-1.7% CV (Total) | ||
| Plasma: | ||
| Low: ~2.4-4.7% CV (Within-Run), ~4.1-6.8% CV (Total) | ||
| Mid: ~2.4-2.8% CV (Within-Run), ~2.6-3.7% CV (Total) | ||
| High: ~0.9-1.6% CV (Within-Run), ~1.8-1.9% CV (Total) | ||
| Precision (POL sites) | (Implied to be comparable to in-house and acceptable for clinical use) | ACE: |
| Low (Sample 1): ~3.3-4.6% CV (Within-Run), ~5.0-6.3% CV (Total) | ||
| Mid (Sample 2): ~1.3-2.5% CV (Within-Run), ~2.8-3.5% CV (Total) | ||
| High (Sample 3): ~1.1-1.8% CV (Within-Run), ~1.4-3.1% CV (Total) | ||
| ACE Alera: | ||
| Low (Sample 1): ~3.0-6.0% CV (Within-Run), ~4.5-8.4% CV (Total) | ||
| Mid (Sample 2): ~2.0-2.9% CV (Within-Run), ~2.5-5.2% CV (Total) | ||
| High (Sample 3): ~0.9-1.9% CV (Within-Run), ~1.6-4.8% CV (Total) | ||
| Method Comparison (Serum vs. Plasma) | (Slope near 1, intercept near 0, high correlation) | ACE: Slope: 0.957, Intercept: 0.04, Correlation: 0.9765 |
| ACE Alera: Slope: 0.986, Intercept: 0.05, Correlation: 0.9817 | ||
| ACE Axcel: Slope: 0.986, Intercept: 0.025, Correlation: 0.9892 | ||
| Method Comparison (POL vs. In-House) | (Slope near 1, intercept near 0, high correlation) | ACE (POL 1-3 vs. In-House ACE): Slopes: 0.970-1.026, Intercepts: -0.04-0.16, Correlations: 0.9902-0.9927 |
| ACE Alera (POL 1-3 vs. In-House ACE): Slopes: 0.990-1.010, Intercepts: -0.11-0.00, Correlations: 0.9870-0.9930 | ||
| Detection Limits (ACE Alera) | (Appropriate for clinical use) | LoB: 0.26 mg/dL, LoD: 0.37 mg/dL, LoQ: 0.37 mg/dL |
| Linearity (ACE Alera) | (Linearity up to/beyond desired measuring range) | Linear to: 6.1 mg/dL (Equation: y=0.959x + 0.27) |
| Interferences (ACE Alera) | (No significant interference from common interferents) | No significant interference at or below Icterus 50 mg/dL, Hemolysis 500 mg/dL, Lipemia 620 mg/dL, Ascorbic Acid 6 mg/dL |
2. Sample Size Used for the Test Set and the Data Provenance
The document describes several types of studies:
-
In-House Precision:
- CO2-LC: Low, Mid, High serum and plasma samples were tested (number of replicates per sample and runs is implicitly part of SD/CV calculation, but not explicitly stated).
- Direct Bilirubin: Low, Mid, High serum and plasma samples.
- Total Bilirubin: Low, Mid, High serum and plasma samples.
- Magnesium: Low, Mid, High serum and plasma samples.
- Data Provenance: In-house (Alfa Wassermann Diagnostic Technologies, LLC, West Caldwell, NJ), prospective testing.
-
POL (Physician Office Laboratory) Precision: Studies conducted at 3 POL sites.
- CO2-LC: 3 samples at each of 3 POL sites and in-house.
- Direct Bilirubin: 3 samples at each of 3 POL sites and in-house.
- Total Bilirubin: 3 samples at each of 3 POL sites and in-house.
- Magnesium: 3 samples at each of 3 POL sites and in-house.
- Data Provenance: Not explicitly stated but inferred to be from POLs in the USA (prospective testing under typical POL conditions).
-
In-House Matrix Comparison (Serum vs. Plasma):
- CO2-LC: 53-54 pairs (serum/plasma) on ACE and ACE Alera; 51 pairs on ACE Axcel.
- Direct Bilirubin: 102 pairs on ACE; 101 pairs on ACE Alera; 56 pairs on ACE Axcel.
- Total Bilirubin: 102 pairs on ACE and ACE Alera; 56 pairs on ACE Axcel.
- Magnesium: 101 pairs on ACE and ACE Alera; 55 pairs on ACE Axcel.
- Data Provenance: In-house, retrospective (presumably collected for a range of values).
-
POL Method Comparison (In-House ACE vs. POL ACE/Alera):
- CO2-LC: 45-46 samples per POL site comparison.
- Direct Bilirubin: 49-51 samples per POL site comparison.
- Total Bilirubin: 48-50 samples per POL site comparison.
- Magnesium: 50-52 samples per POL site comparison.
- Data Provenance: Not explicitly stated but inferred to be from POLs in the USA (prospective testing under typical POL conditions) compared against in-house data.
-
Detection Limits (LoB, LoD, LoQ), Linearity, Interferences (ACE Alera):
- Sample sizes for detection limits and linearity: Not explicitly stated, typically involves multiple replicates at various concentrations.
- Sample sizes for interferences: Not explicitly stated, typically involves samples spiked with various concentrations of interferents.
- Data Provenance: In-house.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts
This information is not provided in the document. For in vitro diagnostic assays, the "ground truth" is typically the reference method or established clinical laboratory results obtained from a highly accurate and calibrated instrument or laboratory using validated methods, rather than human expert consensus for image or clinical interpretation. The document compares performance against other (presumably established) methods and predicate devices.
4. Adjudication Method for the Test Set
This concept (e.g., 2+1, 3+1 for resolving discrepancies) is not applicable to these types of in vitro diagnostic device studies. Performance is measured numerically and objectively.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. This is an in vitro diagnostic assay, not an AI-powered diagnostic imaging device.
6. Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Not applicable. This is not an AI algorithm. The performance data presented are for the reagent and instrument system.
7. The Type of Ground Truth Used
For precision studies, the "ground truth" is the true concentration of the analyte in the control material or patient sample, which is established by reference methods or manufacturing specifications of the control materials. For method comparison studies, the predicate device's results or an established in-house method are used as the comparative reference. The document states the intended use is for "quantitative determination" of analytes, implying comparison to a quantitative gold standard.
8. The Sample Size for the Training Set
Not applicable. This is not a machine learning device and therefore does not have a "training set" in that context. The development of reagents and the establishment of their performance characteristics do not involve machine learning training sets.
9. How the Ground Truth for the Training Set was Established
Not applicable, as there is no "training set" for these reagents in the context of AI/ML.
§ 862.1160 Bicarbonate/carbon dioxide test system.
(a)
Identification. A bicarbonate/carbon dioxide test system is a device intended to measure bicarbonate/carbon dioxide in plasma, serum, and whole blood. Bicarbonate/carbon dioxide measurements are used in the diagnosis and treatment of numerous potentially serious disorders associated with changes in body acid-base balance.(b)
Classification. Class II.