(78 days)
The ACE y-GT Reagent is intended for the quantitative determination of gamma-glutamyltransferase activity in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Gamma-glutamyltransferase measurements are used in the diagnosis and treatment of liver diseases such as alcoholic cirrhosis and primary and secondary liver tumors. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.
The ACE Lipase Reagent is intended for the quantitative determination of lipase activity in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. 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 and physician office laboratories. For in vitro diagnostic use only.
The ACE T4 Reagent is intended for the quantitative determination of total thyroxine (T4) in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Total thyroxine measurements are used in the diagnosis and treatment of thyroid diseases. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.
In the ACE γ-GT Reagent assay, γ-GT in serum or heparin plasma catalyzes the transfer of the γ-glutamyl group from L-γ-glutamyl-3-carboxy-4-nitroanilide to glycylglycine in the reagent. The product, 5-amino-2-nitrobenzoate, absorbs strongly at 408 nm. The rate of increase in absorbance, monitored bichromatically at 408 nm/486 nm, is directly proportional to the γ-GT activity in the sample.
In the ACE Lipase Reagent Assay, lipase in serum or heparin plasma 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.
The ACE T4 Assay is a homogeneous enzyme immunoassay using ready-to-use liquid ACE T4 Reagent. The assay uses 8-anilino-1-naphthalene sulfonic acid (ANS) to dissociate thyroxine from the plasma binding proteins. Using specific antibodies to thyroxine, this assay is based on the competition of glucose-6-phosphate dehydrogenase (G6PD) labeled thyroxine and the dissociated thyroxine in the sample for a fixed amount of specific antibody binding sites. In the absence of thyroxine from the sample, the thyroxine labeled G6PD in the second reagent is bound by the specific antibody in the first reagent, inhibiting the enzyme's activity. The enzyme G6PD catalyzes the oxidation of glucose-6-phosphate (G6P) with nicotinamide adenine dinucleotide (NADT) to form 6-phosphogluconate and reduced nicotinamide adenine dinucleotide (NADH). NADH strongly absorbs at 340 nm whereas NAD does not. The rate of conversion, determined by measuring the increase in absorbance bichromatically at 340 nm/505 nm during a fixed time interval, is directly proportional to the amount of thyroxine in the sample. The concentration of thyroxine is determined automatically by the ACE Clinical Chemistry Systems using a logarithmic calibration curve established with calibrators, which are provided separately.
The information provided describes the performance of the ACE γ-GT, ACE Lipase, and ACE T4 Reagents on the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. This is not an AI/ML device, however, I will address the other requested points to the best of my ability with the provided text.
Here's a breakdown of the acceptance criteria and study information, where applicable:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" in a separate table. However, it provides performance data for precision, matrix comparison (serum vs. plasma), detection limits, linearity, and interference. Based on the "Conclusions" section, the goal was to demonstrate "substantial equivalence" of the reagents for lithium heparin plasma samples (compared to serum) and the ACE Alera System (compared to the predicate ACE Clinical Chemistry System). The performance data presented are implicitly intended to support this substantial equivalence.
Implied Acceptance Criteria (based on predicate comparison and performance data) and Reported Performance:
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (Summary) |
|---|---|---|
| Precision | For In-House Precision (Serum vs. Plasma): Low, Mid, and High analyte concentrations should demonstrate acceptable within-run and total %CV on ACE, ACE Alera, and ACE Axcel systems, comparable to expected values for clinical chemistry assays. |
For POL Precision: Similar acceptable %CV values for low, mid, and high samples across different POL sites and in-house, on ACE and ACE Alera systems. | In-House Precision (Serum vs. Plasma):
- γ-GT: Total %CV generally 0.997, Slope 0.960-0.987, Intercept 1.5-4.0 across systems.
Lipase: Correlation > 0.994, Slope 0.980-1.024, Intercept -2.5 to -0.9 across systems (for ACE and ACE Alera, Axcel missing intercept CI).
T4: Correlation > 0.984, Slope 0.963-1.007, Intercept 0.01-0.35 across systems. |
| Method Comparison (POL) | When comparing results from POL sites to in-house results on the same instrument, correlation coefficients should be high (close to 1), slopes close to 1, and with small intercepts, indicating consistency across testing locations. | ACE System: - γ-GT: Correlation > 0.9997, Slope 0.964-0.976, Intercept -2.7 to 0.7.
- Lipase: Correlation > 0.9966, Slope 0.994-1.031, Intercept -5.3 to 0.0.
- T4: Correlation > 0.9908, Slope 1.010-1.019, Intercept -0.09 to -0.04.
ACE Alera System:
- γ-GT: Correlation > 0.9996, Slope 0.950-1.028, Intercept 1.9 to 2.9.
- Lipase: Correlation > 0.9960, Slope 0.992-1.028, Intercept -3.5 to 3.3.
- T4: Correlation > 0.9868, Slope 1.022-1.048, Intercept -0.31 to -0.10. |
| Detection Limits (ACE Alera) | Limits of Blank (LOB), Detection (LOD), and Quantitation (LOQ) should be clinically acceptable. | γ-GT: LOB 3 U/L, LOD 5 U/L, LOQ 7 U/L.
Lipase: LOB 7 U/L, LOD 11 U/L, LOQ 13 U/L.
T4: LOB 0.3 µg/dL, LOD 0.8 µg/dL, LOQ 1.3 µg/dL. |
| Linearity (ACE Alera) | The assay should be linear up to the stated measuring range, with a linear regression equation demonstrating good fit. | γ-GT: Linear to 950 U/L ($y = 1.036x + 0.8$).
Lipase: Linear to 700 U/L ($y = 0.971x + 0.2$).
T4: Linear to 19.6 µg/dL ($y = 1.057x - 0.09$). |
| Interferences (ACE Alera) | No significant interference from common exogenous or endogenous substances at physiologically relevant or elevated concentrations. | γ-GT: No significant interference at or below Icterus 14.2 mg/dL, Hemolysis 125 mg/dL, Lipemia 500 mg/dL, Ascorbic Acid 6 mg/dL.
Lipase: No significant interference below Icterus 12.5 mg/dL, Hemolysis 1000 mg/dL, Lipemia 803 mg/dL, Ascorbic Acid 6 mg/dL.
T4: No significant interference below Icterus 47.2 mg/dL, Hemolysis 1000 mg/dL, Lipemia 1000 mg/dL, Ascorbic Acid 6 mg/dL.
Heterophile (T4): HAMA 800 ng/mL, RF 516 IU/mL.
Cross-Reactivity (T4): 3,3',5,5'- Tetraiodothyroacetic Acid (18.4%), L-Thyroxine (91.6%), D-Thyroxine (68.0%) at 5 µg/dL. |
2. Sample Sizes Used for the Test Set and Data Provenance
The document does not explicitly use the term "test set" in the context of AI/ML, but rather describes clinical performance studies. The sample sizes for these studies are as follows:
- In-House Matrix Comparison (Serum vs. Plasma):
- ACE γ-GT Reagent: 100 pairs (ACE), 97 pairs (ACE Alera), 53 pairs (ACE Axcel)
- ACE Lipase Reagent: 42 pairs (ACE), 43 pairs (ACE Alera), 62 pairs (ACE Axcel)
- ACE T4 Reagent: 55 pairs (ACE), 55 pairs (ACE Alera), 55 pairs (ACE Axcel)
- Method Comparison (POL vs. In-House):
- ACE System: 50-54 samples per reagent per POL site (3 POL sites)
- ACE Alera System: 48-51 samples per reagent per POL site (3 POL sites)
- Precision (In-House and POL): The number of replicates per sample level (Low, Mid, High) is not explicitly stated, but precision studies typically involve multiple runs over several days.
- Detection Limits, Linearity, Interferences, Cross-Reactivity: Sample sizes for these specific experiments are not detailed but are generally conducted with a sufficient number of replicates and concentrations to statistically establish the parameters.
Data Provenance: The studies are described as "In-House" and "POL" (Physician Office Laboratory) studies. This indicates that the data was collected at the manufacturer's facility ("In-House") and potentially at various POL sites. The country of origin is not explicitly stated, but given the 510(k) submission to the FDA, it is likely the studies align with US regulatory requirements and are potentially from US-based labs. The studies are prospective in nature, as they involve newly generated data to demonstrate the performance of the devices.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This section is not applicable as the device is a clinical chemistry reagent and not an AI/ML device that generates interpretations requiring expert ground truth for image or diagnostic data. The "ground truth" in this context refers to the measured analyte concentrations obtained from established laboratory methods, calibrators, and reference materials.
4. Adjudication Method for the Test Set
This section is not applicable as the device is a clinical chemistry reagent. Adjudication methods like 2+1 or 3+1 are used in contexts like human reader studies for diagnostic imaging, where discordant interpretations need resolution by additional experts.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
This section is not applicable as the device is a clinical chemistry reagent. MRMC studies are designed to assess the performance of diagnostic devices or AI algorithms by multiple human readers across multiple cases, especially in imaging.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
This section is not applicable as the device is a clinical chemistry reagent. This term is relevant for AI/ML diagnostic tools. The "performance" of this device is inherently standalone in that the instrument processes samples and generates quantitative results without human intervention in the measurement process itself, beyond sample loading and general operation.
7. The Type of Ground Truth Used
The "ground truth" for the performance studies presented is based on quantitative chemical measurements of the specific analytes (gamma-glutamyltransferase, lipase, total thyroxine) in control materials, patient samples, and comparison with established reference methods or predicate devices. This includes:
- Known concentrations: For precision, linearity, detection limits, and interference studies, samples with known or spiked concentrations are used.
- Comparison to predicate device: For method comparison studies, the results from the new device/system are compared against the results from the legally marketed predicate device/system.
- Reference materials/calibrators: The accuracy and calibration of the assays depend on traceable reference materials and calibrators.
8. The Sample Size for the Training Set
This section is not applicable as the device is a clinical chemistry reagent and not an AI/ML device. There is no "training set" in the context of machine learning model development.
9. How the Ground Truth for the Training Set Was Established
This section is not applicable for the same reasons as #8.
§ 862.1700 Total thyroxine test system.
(a)
Identification. A total thyroxine test system is a device intended to measure total (free and protein bound) thyroxine (thyroid hormone) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of thyroid diseases.(b)
Classification. Class II (special 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.