(88 days)
ACE Albumin Reagent is intended for the quantitative determination of albumin concentration in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Albumin measurements are used in the diagnosis and treatment of numerous diseases involving primarily the liver or kidneys. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
ACE Total Protein Reagent is intended for the quantitative determination of total protein concentration in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Total protein measurements are used in the diagnosis and treatment of a variety of diseases involving the liver, kidney, or bone marrow as well as other metabolic or nutritional disorders. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
ACE Calcium-Arsenazo Reagent is intended for the quantitative determination of calcium concentration in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Calcium measurements are used in the diagnosis and treatment of parathyroid disease, a variety of bone diseases, chronic renal disease and tetany (intermittent muscular contractions or spasms). This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
ACE Inorganic Phosphorus U.V. Reagent is intended for the quantitative determination of inorganic phosphorus concentration in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Measurements of inorganic phosphorus are used in the diagnosis and treatment of various disorders, including parathyroid gland and kidney diseases and vitamin D imbalance. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
In the ACE Albumin Reagent assay, Bromcresol green binds specifically to albumin to form a green colored complex, which is measured bichromatically at 629 nm/692 nm. The intensity of color produced is directly proportional to the albumin concentration in the sample.
In the ACE Total Protein Reagent assay, cupric ions react with the peptide bonds of proteins under alkaline conditions to form a violet colored complex, which is measured bichromatically at 544 nm/692 nm. The intensity of color produced is directly proportional to the total protein concentration in the sample.
In the ACE Calcium-Arsenazo Reagent assay, calcium reacts with Arsenazo III in an acidic solution to form a blue-purple colored complex, which is measured bichromatically at 647 nm/692 nm. The intensity of color produced is directly proportional to the calcium concentration in the sample.
In the ACE Inorganic Phosphorus U.V. Reagent assay, under acidic conditions, inorganic phosphorus in serum reacts with ammonium molybdate to form an unreduced phosphomolybdate complex, which absorbs strongly at 340 nm. The increase in absorbance, measured bichromatically at 340 nm/378 nm, is directly proportional to the amount of phosphorus in the sample.
Here's an analysis of the acceptance criteria and study information for the ACE Albumin Reagent, ACE Total Protein Reagent, ACE Calcium-Arsenazo Reagent, and ACE Inorganic Phosphorus U.V. Reagent, based on the provided text.
1. Table of Acceptance Criteria and Reported Device Performance
The provided documentation does not explicitly state formal "acceptance criteria" with specific thresholds for each performance metric. However, it presents detailed performance data, particularly precision (within-run and total %CV) and method comparison (regression analysis, correlation coefficient), comparing the new reagents on various ACE clinical chemistry systems (ACE, ACE Alera, ACE Axcel) against existing predicate devices and among themselves. The implied acceptance is that the new reagents perform comparably to, or as effectively as, the predicate devices and demonstrate acceptable precision and linearity for clinical use.
Below is a summary of the reported device performance based on the "In-House Precision" and "In-House Matrix Comparison" tables. Since explicit acceptance criteria are not given, the performance data itself is presented as the evidence of meeting implied clinical utility and equivalence to predicate devices.
ACE Albumin Reagent
| Metric | Acceptance Criteria (Implied) | Reported Performance (Range across ACE, Alera, Axcel systems) |
|---|---|---|
| Precision (%CV) | Clinically acceptable | Serum: Within-Run: 0.5-1.6%, Total: 0.6-1.8% |
| Plasma: Within-Run: 0.8-1.7%, Total: 1.1-1.7% | ||
| Matrix Comparison (Serum vs. Plasma) | Slope close to 1, Intercept close to 0, High Correlation | Slope: 0.956 - 1.002 |
| Intercept: -0.01 - 0.20 | ||
| Correlation: 0.9850 - 0.9905 | ||
| Linearity | Broad clinical range, r^2 close to 1 | Linear to 7.6 g/dL |
| y = 0.980x + 0.01, r^2 = 0.9982 | ||
| Detection Limits (ACE Alera) | Low enough for clinical utility | LoB: 0.08 g/dL, LoD: 0.09 g/dL, LoQ: 0.09 g/dL |
| Interferences (ACE Alera) | No significant interference at clinically relevant levels | Icterus: 60 mg/dL, Hemolysis: 250 mg/dL, Lipemia: 1000 mg/dL, Ascorbic Acid: 6 mg/dL |
ACE Total Protein Reagent
| Metric | Acceptance Criteria (Implied) | Reported Performance (Range across ACE, Alera, Axcel systems) |
|---|---|---|
| Precision (%CV) | Clinically acceptable | Serum: Within-Run: 0.7-1.3%, Total: 0.8-1.4% |
| Plasma: Within-Run: 0.5-1.3%, Total: 0.7-1.4% | ||
| Matrix Comparison (Serum vs. Plasma) | Slope close to 1, Intercept close to 0, High Correlation | Slope: 0.994 - 1.001 |
| Intercept: 0.12 - 0.34 | ||
| Correlation: 0.9798 - 0.9885 | ||
| Linearity | Broad clinical range, r^2 close to 1 | Linear to 15.1 g/dL |
| y=0.991x + 0.04, r^2 = 0.9979 | ||
| Detection Limits (ACE Alera) | Low enough for clinical utility | LoB: 0.08 g/dL, LoD: 0.13 g/dL, LoQ: 0.20 g/dL |
| Interferences (ACE Alera) | No significant interference at clinically relevant levels | Icterus: 56.8 mg/dL, Hemolysis: 250 mg/dL, Lipemia: 929 mg/dL, Ascorbic Acid: 6 mg/dL |
ACE Calcium-Arsenazo Reagent
| Metric | Acceptance Criteria (Implied) | Reported Performance (Range across ACE, Alera, Axcel systems) |
|---|---|---|
| Precision (%CV) | Clinically acceptable | Serum: Within-Run: 0.7-1.6%, Total: 0.9-2.7% |
| Plasma: Within-Run: 0.5-1.9%, Total: 1.1-2.0% | ||
| Matrix Comparison (Serum vs. Plasma) | Slope close to 1, Intercept close to 0, High Correlation | Slope: 0.978 - 1.008 |
| Intercept: -0.06 - 0.33 | ||
| Correlation: 0.9793 - 0.9911 | ||
| Linearity | Broad clinical range, r^2 close to 1 | Linear to 16.5 mg/dL |
| y=0.992x +0.27, r^2 = 0.9990 | ||
| Detection Limits (ACE Alera) | Low enough for clinical utility | LoB: 0.09 mg/dL, LoD: 0.11 mg/dL, LoQ: 0.23 mg/dL |
| Interferences (ACE Alera) | No significant interference at clinically relevant levels | Icterus: 58.8 mg/dL, Hemolysis: 1000 mg/dL, Lipemia: 1000 mg/dL, Ascorbic Acid: 6 mg/dL |
ACE Inorganic Phosphorus U.V. Reagent
| Metric | Acceptance Criteria (Implied) | Reported Performance (Range across ACE, Alera, Axcel systems) |
|---|---|---|
| Precision (%CV) | Clinically acceptable | Serum: Within-Run: 0.3-4.4%, Total: 0.5-5.0% |
| Plasma: Within-Run: 0.9-5.1%, Total: 0.9-6.1% | ||
| Matrix Comparison (Serum vs. Plasma) | Slope close to 1, Intercept close to 0, High Correlation | Slope: 0.999 - 1.049 |
| Intercept: -0.28 - 0.04 | ||
| Correlation: 0.9927 - 0.9950 | ||
| Linearity | Broad clinical range, r^2 close to 1 | Linear to 21 mg/dL |
| y=1.001x +0.03, r^2 = 0.9995 | ||
| Detection Limits (ACE Alera) | Low enough for clinical utility | LoB: 0.25 mg/dL, LoD: 0.35 mg/dL, LoQ: 0.35 mg/dL |
| Interferences (ACE Alera) | No significant interference at clinically relevant levels | Icterus: 11.5 mg/dL, Hemolysis: 250 mg/dL, Lipemia: 306 mg/dL, Ascorbic Acid: 6 mg/dL |
2. Sample Sizes Used for the Test Set and Data Provenance
The studies mentioned are "In-House Precision," "In-House Matrix Comparison: Serum vs. Plasma," "POL - Precision," and "POL – Method Comparison."
- In-House Precision (Serum vs. Plasma):
- Sample Size: Not explicitly stated for each "low, mid, high" concentration level, but implies multiple replicates for each level tested across the three systems (ACE, Alera, Axcel). For example, the ACE Alera precision table (pg. 16) shows 3 levels (low, mid, high) for serum, with reported mean, within-run SD, and total SD. Typically, precision studies involve running samples multiple times a day over several days.
- Data Provenance: "In-House" suggests it was conducted by Alfa Wassermann Diagnostic Technologies, LLC, likely at their own facilities. It is a prospective study as they are performing experiments to generate data.
- In-House Matrix Comparison: Serum vs. Plasma:
- Sample Size:
- Albumin: ACE: 55 pairs, ACE Alera: 56 pairs, ACE Axcel: 56 pairs
- Total Protein: ACE: 56 pairs, ACE Alera: 56 pairs, ACE Axcel: 81 pairs
- Calcium-Arsenazo: ACE: 56 pairs, ACE Alera: 56 pairs, ACE Axcel: 81 pairs
- Inorganic Phosphorus: ACE: 100 pairs, ACE Alera: 102 pairs, ACE Axcel: 56 pairs
- Data Provenance: "In-House" suggests it was conducted by Alfa Wassermann Diagnostic Technologies, LLC, likely at their own facilities. The comparison between serum and plasma samples implies these were collected from human subjects. This is a prospective study.
- Sample Size:
- POL (Physician Office Laboratory) - Precision:
- Sample Size: For each reagent and each system (ACE and ACE Alera), there are 3 "samples" (representing different concentration levels) tested at 3 different POL sites. Each sample/site combination has "Within-Run" and "Total" precision reported, implying multiple replicates for each measurement.
- Data Provenance: Conducted at "POL 1," "POL 2," and "POL 3" sites, indicating external collection and testing beyond the manufacturer's immediate facilities. This is a prospective study.
- POL (Physician Office Laboratory) - Method Comparison:
- Sample Size:
- Albumin: 50 samples for each POL site (x3 POLs)
- Total Protein: 51 samples for each POL site (x3 POLs)
- Calcium-Arsenazo: 50 samples for each POL site (x3 POLs)
- Inorganic Phosphorus: 50 samples for POL 1 & 3, 48 samples for POL 2
- Data Provenance: Comparisons between "ACE In-House (x)" and "ACE POL (y)" or "ACE In-House (x)" and "ACE Alera POL (y)". This indicates the data for these studies was collected at both in-house facilities and external Physician Office Laboratories. This is a prospective study design, comparing results from different testing environments.
- Sample Size:
- Detection Limits & Linearity (ACE Alera):
- Sample Size: Not specified for these specific studies, but typically involves a series of diluted and concentrated samples to define the measuring range.
- Data Provenance: In-House, prospective.
- Interference (ACE Alera):
- Sample Size: Not specified, but involves spiking samples with various interferents at different concentrations.
- Data Provenance: In-House, prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
For these types of in vitro diagnostic (IVD) assays, the "ground truth" is typically established by reference methods or validated comparative methods, often using certified calibrators and controls. The documentation does not mention the use of human experts to establish ground truth for the test set in the traditional sense of medical image interpretation (e.g., radiologists interpreting images). Instead, the studies rely on quantitative measurements and statistical comparisons with established methods (the predicate devices or in-house reference measurements) to demonstrate performance. Therefore, no information is provided on the number or qualifications of experts for ground truth establishment.
4. Adjudication Method for the Test Set
Not applicable. As described in point 3, the "ground truth" for these quantitative chemical assays is not established through expert consensus or adjudication in the way it would be for qualitative or interpretive diagnostic devices like medical imaging. Performance is evaluated by statistical comparison of numerical results.
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 consists of chemical reagents for laboratory measurement, not an AI-assisted diagnostic tool interpreted by human readers. Therefore, an MRMC comparative effectiveness study involving human readers and AI is not relevant to this submission.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was Done
The performance presented for these reagents is inherently "standalone" in the sense that it reflects the direct analytical performance of the assays on the specified automated clinical chemistry systems. The results are quantitative measurements produced by the device without human interpretation of raw data beyond reading the numerical output. The "without human-in-the-loop" aspect applies here as the device itself performs the measurement and outputs a numerical value of concentration. The method comparison studies demonstrate the standalone performance of the candidate devices compared to predicate devices.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth for these assays is established through reference methods and comparison to legally marketed predicate devices.
- For precision, the "ground truth" for each replicate is assumed to be the true concentration within the sample, and the study assesses the reproducibility of the device in measuring that concentration.
- For method comparison studies (e.g., In-House vs. POL, or ACE vs. ACE Alera), one method's results (often the predicate or an established in-house method) serve as the comparative 'truth' to evaluate the new method's agreement. The reference method would itself be calibrated against known standards.
- For linearity, samples of known, graded concentrations are used.
- For detection limits, the ground truth involves samples with very low, known concentrations.
These are established analytical chemistry principles rather than "expert consensus" or "pathology" in the diagnostic interpretation sense.
8. The Sample Size for the Training Set
The concept of a "training set" is primarily relevant for machine learning or AI algorithms which are iteratively developed and optimized using data. These reagents are chemical assays with a defined photometric measurement principle. While there is a development phase that involves optimizing reagent formulations and instrument parameters, there isn't a "training set" in the computational sense. The data presented here are from formal "verification and validation studies" to demonstrate performance characteristics (precision, linearity, accuracy/comparison, interference, detection limits).
9. How the Ground Truth for the Training Set Was Established
As noted in point 8, the concept of a "training set" is not directly applicable to these chemical reagents. The "ground truth" for establishing and validating the performance of such assays is based on:
- Reference materials/calibrators: Solutions with precisely known concentrations of the analyte (albumin, total protein, calcium, phosphorus) traceable to international standards.
- Validated comparison methods: Measurements made by existing, legally marketed predicate devices or other well-established and accurate laboratory methods.
- Controlled spiking experiments: Adding known amounts of substance to samples to assess recovery, linearity, and interference.
These methods establish the quantitative "truth" against which the performance of the new reagents is measured.
§ 862.1035 Albumin test system.
(a)
Identification. An albumin test system is a device intended to measure the albumin concentration in serum and plasma. Albumin measurements are used in the diagnosis and treatment of numerous diseases involving primarily the liver or kidneys.(b)
Classification. Class II.