(193 days)
The ACE Axcel Clinical Chemistry System is an automated, discrete, bench-top, random access analyzer that is intended for in vitro diagnostic use in the quantitative determination of constituents in blood and other fluids.
The ACE TIBC Reagent is intended for the quantitative determination of total iron-binding capacity in serum using the ACE Axcel Clinical Chemistry System. Iron-binding capacity measurements are used in the diagnosis and treatment of anemia. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
The ACE Serum Iron Reagent is intended for the quantitative determination of iron concentration in serum using the ACE Axcel Clinical Chemistry System. Iron (non-heme) measurements are used in the diagnosis and treatment of diseases such as iron deficiency anemia, hemochromatosis (a disease associated with widespread deposit in the tissues of two iron-containing pigments, hemosiderin and hemofuscin, and characterized by pigmentation of the skin), and chronic renal disease. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
The ACE Lipase Reagent is intended for the quantitative determination of lipase activity in serum using the ACE Axcel Clinical Chemistry System. Lipase measurements are used in diagnosis and treatment of diseases of the pancreas such as acute pancreatitis and obstruction of the pancreatic duct. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
The ACE Axcel Clinical Chemistry System consists of two major components, the chemistry instrument and an integrated Panel PC. The instrument accepts the physical patient samples, performs the appropriate optical or potentiometric measurements on those samples and communicates that data to an integral Panel PC. The Panel PC uses keyboard or touch screen input to manually enter a variety of data, control and accept data from the instrument, manage and maintain system information and generate reports relative to patient status and instrument performance. The Panel PC also allows remote download of patient requisitions and upload of patient results via a standard interface.
In the ACE Direct Total Iron-Binding Capacity (TIBC) Reagent assay, Direct TIBC Color Reagent, an acidic buffer containing an iron-binding dye and ferric chloride, is added to the serum sample. The low pH of Direct TIBC Color Reagent releases iron from transferrin. The iron then forms a colored complex with the dye. The colored complex at the end of the first step represents both the serum iron and excess iron already present in Direct TIBC Color Reagent. Direct TIBC Buffer, a neutral buffer, is then added, shifting the pH and resulting in a large increase in the affinity of transferrin for iron. The serum transferrin rapidly binds the iron by abstracting it from the dye-iron complex. The observed decrease in absorbance of the colored dye-iron complex is directly proportional to the total iron-binding capacity of the serum sample. The absorbance is measured at 647 nm.
In the ACE Serum Iron Reagent assay, transferrin-bound iron in serum is released at an acidic pH and reduced from ferric to ferrous ions. These ions react with ferrozine to form a violet colored complex, which is measured bichromatically at 554 nm/692 nm. The intensity of color produced is directly proportional to the serum iron concentration.
In the ACE Lipase Reagent Assay, serum lipase acts on a natural substrate, 1,2-diglyceride, to liberate 2-monoglyceride. This is hydrolyzed by monoglyceride lipase (a highly specific enzyme for monoglyceride) into glycerol and free fatty acid. Glycerol kinase acts on glycerol to form glycerol-3-phosphate, which is in turn acted on by glycerol-3-phosphate oxidase to generate hydrogen peroxide. Peroxidase converts the hydrogen peroxide, 4-Aminoantipyrine and TOOS (N-ethyl-N-(2-hydroxy-3-sulfopropyl)-m-toluidine) into a quinine dye. The rate of formation of the dye, determined bichromatically at an absorbance of 573 nm/692 nm, is proportional to the lipase activity in the sample.
Here's a breakdown of the acceptance criteria and study information for the ACE Direct Total Iron-Binding Capacity (TIBC) Reagent, ACE Serum Iron Reagent, and ACE Lipase Reagent, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Device/Parameter | Acceptance Criteria (Implied) | Reported Device Performance and Confidence Intervals |
|---|---|---|
| ACE Direct TIBC Reagent | ||
| Precision | Low within-run and total CV for various TIBC levels. | Lab Testing: |
- Within-run CV: 0.9% to 2.2%
- Total CV: 2.0% to 3.3%
POL Sites: - Within-run CV: 0.9% to 3.4%
- Total CV: 0.9% to 4.1% |
| Accuracy (Correlation to Predicate) | High correlation coefficient, low standard error, slope near 1, intercept near 0 when compared to predicate device. | Lab (109 samples): - Correlation Coefficient: 0.9950
- Standard Error Estimate: 9.1
- Confidence Interval Slope: 0.961 to 0.998
- Confidence Interval Intercept: -9.2 to 4.3
POL Sites: - Correlation Coefficients: 0.9902 to 0.9987
- Standard Error Estimates: 6.1 to 11.2
- Confidence Interval Slopes: 0.923 to 1.006
- Confidence Interval Intercepts: -8.2 to 19.4 |
| Detection Limit | Low enough to be clinically useful. | 42.21 µg/dL |
| ACE Serum Iron Reagent |
| Precision | Low within-run and total CV for various Serum Iron levels. | Lab Testing: - Within-run CV: 1.2% to 5.2%
- Total CV: 1.3% to 5.4%
POL Sites: - Within-run CV: 1.2% to 4.1%
- Total CV: 1.2% to 4.2% |
| Accuracy (Correlation to Predicate) | High correlation coefficient, low standard error, slope near 1, intercept near 0 when compared to predicate device. | Lab (130 samples): - Correlation Coefficient: 0.9995
- Standard Error Estimate: 3.3
- Confidence Interval Slope: 1.000 to 1.012
- Confidence Interval Intercept: -2.7 to -1.0
POL Sites: - Correlation Coefficients: 0.9992 to 0.9998
- Standard Error Estimates: 6.1 to 11.2
- Confidence Interval Slopes: 0.997 to 1.041
- Confidence Interval Intercepts: -2.7 to 9.2 |
| Detection Limit | Low enough to be clinically useful. | 5.08 µg/dL |
| ACE Lipase Reagent |
| Precision | Low within-run and total CV for various lipase levels. | Lab Testing: - Within-run CV: 1.1% to 6.5%
- Total CV: 6.0% to 10.7%
POL Sites: - Within-run CV: "to 7.3%" (lower bound not specified)
- Total CV: 1.9% to 7.3% |
| Accuracy (Correlation to Predicate) | High correlation coefficient, low standard error, slope near 1, intercept near 0 when compared to predicate device. | Lab (107 samples): - Correlation Coefficient: 0.9980
- Standard Error Estimate: 9.06
- Confidence Interval Slope: 0.970 to 0.994
- Confidence Interval Intercept: 1.97 to 5.97
POL Sites: - Correlation Coefficients: 0.9993 to 0.9997
- Standard Error Estimates: 4.44 to 7.89
- Confidence Interval Slopes: 1.002 to 1.047
- Confidence Interval Intercepts: -4.74 to 3.41 |
| Detection Limit | Low enough to be clinically useful. | 10.63 U/L |
Note: The acceptance criteria are "implied" because the document primarily presents the results of the performance data without explicitly stating the pre-defined target values or ranges that were aimed for. However, the context of a 510(k) submission requires demonstrating substantial equivalence, meaning the performance should be comparable to the predicate device. Therefore, the reported data, particularly the high correlation coefficients, slopes near 1, and intercepts near 0 for accuracy, indicate that these outcomes met whatever internal acceptance criteria were set for demonstrating equivalency. For precision, low CVs are generally accepted as good performance.
2. Sample Size Used for the Test Set and Data Provenance
-
ACE Direct Total Iron-Binding Capacity (TIBC) Reagent:
- Sample Size:
- Accuracy (correlation study): 109 samples
- Precision (lab): 4 TIBC levels tested for 22 days.
- Precision (POL sites): 3 separate POL sites, testing over 5 days (number of samples not specified, but likely multiple runs per site per day).
- Data Provenance: Not explicitly stated, but the testing occurred at "Physician Office Laboratory (POL) sites" and an unnamed central lab. It is not specified if the data is retrospective or prospective, nor the country of origin.
- Sample Size:
-
ACE Serum Iron Reagent:
- Sample Size:
- Accuracy (correlation study): 130 samples
- Precision (lab): 4 Serum Iron levels tested for 22 days.
- Precision (POL sites): 3 separate POL sites, testing over 5 days (number of samples not specified).
- Data Provenance: Not explicitly stated, but testing occurred at "Physician Office Laboratory (POL) sites" and an unnamed central lab. Retrospective or prospective nature and country of origin are not specified.
- Sample Size:
-
ACE Lipase Reagent:
- Sample Size:
- Accuracy (correlation study): 107 samples
- Precision (lab): 3 lipase levels tested for 22 days.
- Precision (POL sites): 3 separate POL sites, testing over 5 days (number of samples not specified).
- Data Provenance: Not explicitly stated, but testing occurred at "Physician Office Laboratory (POL) sites" and an unnamed central lab. Retrospective or prospective nature and country of origin are not specified.
- Sample Size:
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not provided in the given text. The ground truth for these types of in vitro diagnostic tests is typically established by measurements from a reference method or a predicate device. The text indicates that the "Alfa Wassermann ACE Clinical Chemistry System" was used as the comparator (predicate device) (referred to as 'x' in the regression analyses).
4. Adjudication Method for the Test Set
This information is not applicable and therefore, not provided. Adjudication methods (e.g., 2+1, 3+1) are typically used in studies involving subjective interpretation, such as by human readers of medical images, to resolve discrepancies in diagnoses. These clinical chemistry devices produce quantitative numerical results, which are then compared statistically to a reference method or predicate device, rather than adjudicated.
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
This information is not applicable as the described devices are in vitro diagnostic clinical chemistry reagents and an automated system (ACE Axcel Clinical Chemistry System), not AI-assisted imaging or diagnostic tools designed for human readers to interpret. Therefore, an MRMC study and effects on human reader performance are not relevant to this submission.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies described are standalone performance studies of the device and reagents. The ACE Axcel Clinical Chemistry System is an "automated, discrete, bench-top, random access analyzer." The performance data presented (precision, accuracy, detection limit) are measurements of the system's ability to quantitatively determine analytes directly, without a human interpretation step that would introduce a "human-in-the-loop" component in the result generation itself. The results quantify the device's inherent measurement capabilities.
7. The Type of Ground Truth Used
The ground truth for these studies was established by comparison to a legally marketed predicate device, the "Alfa Wassermann ACE Clinical Chemistry System" (specifically, the ACE Reagents K000781, K944911 run on the K931786 system). This is a common method for demonstrating substantial equivalence for in vitro diagnostic devices in 510(k) submissions. The new device's measurements (y) were correlated against the predicate device's measurements (x).
8. The Sample Size for the Training Set
This information is not provided and is generally not applicable in the context of these types of in vitro diagnostic submissions for clinical chemistry reagents and analyzers. The device described does not employ a machine learning algorithm that requires a "training set" in the conventional sense. The "training" of such a device primarily involves rigorous internal calibration procedures and validation during its development and manufacturing, which are distinct from the concept of a "training set" for AI/ML models.
9. How the Ground Truth for the Training Set Was Established
As explained in point 8, the concept of a "training set" requiring ground truth establishment in this manner is not applicable to this type of device and submission. The device's operational parameters are set through design, engineering, and calibration processes, not machine learning model training.
§ 862.1415 Iron-binding capacity test system.
(a)
Identification. An iron-binding capacity test system is a device intended to measure iron-binding capacity in serum. Iron-binding capacity measurements are used in the diagnosis and treatment of anemia.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9.