(97 days)
The ACE Alkaline Phosphatase Reagent is intended for the quantitative determination of alkaline phosphatase activity in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Measurements of alkaline phosphatase are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.
The ACE Amylase Reagent is intended for the quantitative determination of α-amylase activity in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Amylase measurements are used primarily for the diagnosis and treatment of pancreatitis (inflammation of the pancreas). This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.
The ACE ALT Reagent is intended for the quantitative determination of alanine aminotransferase activity in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Alanine aminotransferase measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis) and heart diseases. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.
The ACE AST Reagent is intended for the quantitative determination of aspartate aminotransferase activity in serum and lithium heparin plasma using the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems. Measurements of aspartate aminotransferase are used in the diagnosis and treatment of certain types of liver and heart disease. This test is intended for use in clinical laboratories and physician office laboratories. For in vitro diagnostic use only.
In the ACE Alkaline Phosphatase Reagent assay, alkaline phosphatase catalyzes the hydrolysis of colorless p-nitrophenyl phosphate to p-nitrophenol and inorganic phosphate. In an alkaline solution (pH 10.5), p-nitrophenol is in the phenoxide form and has a strong absorbance at 408 nm. The rate of increase in absorbance, monitored bichromatically at 408 nm/486 nm, is directly proportional to the alkaline phosphatase activity in the sample.
In the ACE Amylase Reagent assay, α-amylase hydrolyzes the 2-chloro-p-nitrophenyl-α-D-maltotrioside substrate to release 2-chloro-p-nitrophenol and form 2-chloro-p-nitrophenyl-α-D-maltoside, maltotriose and glucose. The rate of increase in absorbance, monitored bichromatically at 408 nm/ 647 nm, is directly proportional to the α-amylase activity in the sample.
In the ACE ALT Reagent assay, alanine aminotransferase converts the L-alanine and α-ketoglutarate substrates in the reagent to L-glutamate and pyruvate, respectively. Lactate dehydrogenase (LDH) catalyzes the oxidation of the reduced cofactor to the cofactor. The rate of conversion of the reduced cofactor to the cofactor can be determined by monitoring the decrease in absorbance bichromatically at 340 nm/647 nm. This rate of conversion from the reduced cofactor to the cofactor is a function of the activity of ALT in the sample.
In the ACE AST Reagent assay, aspartate aminotransferase converts the L-aspartate and α-ketoglutarate in the reagent to oxaloacetate and L-glutamate, respectively. The oxaloacetate undergoes reduction, with concurrent oxidation of NADH to NAD+ in the malate dehydrogenase-catalyzed indicator reaction. NADH absorbs strongly at 340 nm, whereas NAD+ does not. Therefore, the rate of conversion of NADH to NAD+ can be determined by monitoring the decrease in absorbance bichromatically at 340 nm/647 nm. This rate of conversion from NADH to NAD+ is a function of the activity of AST in the sample. Lactate dehydrogenase is added to prevent interference from endogenous pyruvate, which is normally present in blood.
Here's an analysis of the provided information regarding the acceptance criteria and study for the ACE reagents:
Summary of Acceptance Criteria and Reported Device Performance
The acceptance criteria for these in vitro diagnostic reagents (ALP, Amylase, ALT, AST) appear to be primarily demonstrated through comparisons with predicate devices and comprehensive performance characteristics like precision, linearity, and interference. The documentation focuses on demonstrating that the new devices perform equivalently to the existing predicate devices and meet established performance expectations for clinical chemistry assays.
1. Table of Acceptance Criteria and Reported Device Performance
Since this document describes multiple reagents and doesn't explicitly state pass/fail acceptance values for each performance metric, I will summarize the demonstrated performance and what can be inferred as the "acceptance criteria" (i.e., that the results are comparable to established predicate device performance and within acceptable clinical ranges).
| Performance Metric | Acceptance Criteria (Inferred) | Reported Device Performance |
|---|---|---|
| Precision | Low total CV% (generally 0.98 or 0.99) with narrow confidence intervals, indicating interchangeability of sample types. | ALP: Slopes 0.983-1.017, Intercepts -6.5 to -8.3, Correlations 0.9952-0.9982. |
| Amylase: Slopes 0.977-0.994, Intercepts -1.76 to 1.7, Correlations 0.9994-0.9996. | ||
| ALT: Slopes 0.985-1.003, Intercepts -3.35 to -3.6, Correlations 0.9986-0.9994. | ||
| AST: Slopes 0.998-1.006, Intercepts 0.3 to 1.5, Correlations 0.9993-0.9998. | ||
| All indicate a strong agreement between serum and plasma samples. | ||
| Method Comparison (vs. In-House ACE and POL sites) | Slopes close to 1.0, intercepts close to 0, and correlation coefficients (R) close to 1.0 (e.g., >0.98 or 0.99) with narrow confidence intervals, indicating consistency across different instruments and sites. | In-House ACE vs. POL ACE: |
| • ALP: Slopes 0.977-0.989, Intercepts -9.5 to -2.8, Correlations 0.9987-0.9997. | ||
| • AMY: Slopes 0.970-0.974, Intercepts 1.5-3.9, Correlations 0.9995-0.9998. | ||
| • ALT: Slopes 0.982-1.021, Intercepts -4.7 to -2.3, Correlations 0.9978-0.9993. | ||
| • AST: Slopes 0.992-1.019, Intercepts -0.6 to 2.4, Correlations 0.9989-0.9994. | ||
| In-House ACE vs. POL Alera: | ||
| • ALP: Slopes 0.997-1.029, Intercepts -6.6 to -4.1, Correlations 0.9986-0.9992. | ||
| • AMY: Slopes 0.960-1.010, Intercepts 3.0-5.8, Correlations 0.9991-0.9995. | ||
| • ALT: Slopes 0.970-1.019, Intercepts -3.5 to 2.4, Correlations 0.9977-0.9986. | ||
| • AST: Slopes 1.004-1.040, Intercepts 0.5-1.8, Correlations 0.9992-0.9995. | ||
| All indicate strong agreement between different sites and initial in-house testing, demonstrating substantial equivalence. | ||
| Detection Limits (LoB, LoD, LoQ) | Values below the clinical reference ranges and suitable for detecting low levels of analytes. | ACE Alera (Approximate): |
| ALP: LoB 2.8, LoD 0.9, LoQ 4.8 | ||
| Amylase: LoB 0.2, LoD 3.3, LoQ 5.6 | ||
| ALT: LoB 1.6, LoD 4.8, LoQ 4.1 | ||
| AST: LoB 2.2, LoD 3.1, LoQ 3.3 | ||
| Linearity | Correlation coefficient (R^2) close to 1.0 (e.g., >0.99) over the specified measuring range, with slopes near 1 and intercepts near 0 for the regression equation. | ACE Alera: |
| ALP: Linear to 1400 U/L, R^2 = 0.9993 | ||
| Amylase: Linear to 1900 U/L, R^2 = 0.9974 | ||
| ALT: Linear to 480 U/L, R^2 = 0.9992 | ||
| AST: Linear to 450 U/L, R^2 = 0.9992 | ||
| Interferences | No significant interference at stated concentrations of common interferents (Icterus, Hemolysis, Lipemia, Ascorbic Acid). | The document lists the tested concentrations of interferents (e.g., Icterus up to 70.6 mg/dL for ALP, Hemolysis up to 500 mg/dL for ALT, Lipemia up to 1000 mg/dL for ALP/Amylase, Ascorbic Acid 6 mg/dL for all). The implication, by inclusion in the performance data without negative remarks, is that these levels did not cause unacceptable interference. |
2. Sample Size Used for the Test Set and Data Provenance
- Precision (Serum vs. Plasma):
- In-House: Each dataset (low, mid, high for serum and plasma) involved "n=20" (number of replicates, likely over multiple days, contributing to within-run and total precision calculations).
- POL Precision (ACE & Alera): For each analyte (ALP, AMY, ALT, AST) and each POL site (POL 1, POL 2, POL 3), there were 2 to 3 sample levels (Low, Mid, High), with a reported "n" for each (e.g., n=24 for ALT/AST in initial in-house, but the POL tables don't explicitly state the 'n' for each specific mean/SD/CV, implying a standard number of replicates as per precision studies).
- Matrix Comparison (Serum vs. Plasma):
- ALP: ACE (108 pairs), ACE Alera (108 pairs), ACE Axcel (62 pairs).
- Amylase: ACE (104 pairs), ACE Alera (101 pairs), ACE Axcel (52 pairs).
- ALT: ACE (54 pairs), ACE Alera (52 pairs), ACE Axcel (56 pairs).
- AST: The number of pairs for AST in the serum vs. plasma matrix comparison is not explicitly stated in the provided snippet. However, based on the pattern of other analytes, it would likely be similar (e.g., 50+ pairs).
- Method Comparison (In-House vs. POL Sites):
- ALP: 49-50 samples per site.
- Amylase: 51 samples per site.
- ALT: 44-49 samples per site.
- AST: 50 samples per site.
- Linearity: Not explicitly stated as an "n" for samples, but rather as "low level tested," "upper level tested," and "linear to" values, which typically involve preparing a dilution series from a high concentration sample.
- Data Provenance: The studies are labeled "In-House" and "POL" (Point of Care). This suggests:
- Country of Origin: Likely the USA, given the FDA 510(k) submission.
- Retrospective or Prospective: These types of performance studies for IVDs are typically prospective, with samples analyzed specifically for the study. The method comparison data often uses a mix of native patient samples and spiked samples to cover the measuring range.
3. Number of Experts Used to Establish Ground Truth and Their Qualifications
This document describes the performance of IVD reagents on clinical chemistry systems. The "ground truth" here is not subjective, human interpretation (like in imaging AI), but rather the quantitative measurement of analytes.
- Number of Experts: Not applicable in the context of IVD reagent performance. The "ground truth" is established by the analytical method itself, or by comparison to a recognized reference method or a legally marketed predicate device.
- Qualifications of Experts: Not applicable. The "experts" would be qualified laboratory professionals operating the instruments and performing the biochemical assays according to established protocols.
4. Adjudication Method for the Test Set
Not applicable. As described above, the "truth" for these quantitative measurements is derived directly from the biochemical reactions and instrument readings, not subjective human judgment requiring adjudication. The predicate device's established performance serves as a comparative benchmark.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No. This is a submission for in vitro diagnostic reagents, not an AI-assisted diagnostic device that involves human readers interpreting images or complex data. Therefore, an MRMC study is not relevant.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, in essence, the performance data presented is "standalone" in the context of the device's function. The ACE reagents, when used on the ACE, ACE Alera, and ACE Axcel Clinical Chemistry Systems, operate as an automated system to quantify the target analytes. The performance metrics (precision, linearity, method comparison, interferences) reflect the intrinsic analytical performance of the regent-analyzer combination without human intervention influencing the measurement itself. Human operators are involved in sample loading, quality control, and result review, but not in directly influencing the quantitative output in a way that would require a human-in-the-loop comparison for algorithm performance.
7. The Type of Ground Truth Used
The "ground truth" in this context is established by:
- Comparison to Predicate Devices: The primary method is demonstrating substantial equivalence to previously cleared devices (K113253, K931786, K930104, K113436, K113382). This means the new reagents provide results that are analytically comparable to those already accepted by the FDA.
- Expected Analytical Performance: Meeting industry-standard requirements for precision (low CV%), accuracy (linearity, inter-instrument/site agreement via regression analysis), and specificity (minimal interference).
- Expected Values/Ranges: The devices are expected to produce results that align with established "expected values" for healthy individuals.
8. The Sample Size for the Training Set
Not applicable. These are chemical reagents for quantitative diagnostic tests, not machine learning algorithms that require a "training set" in the conventional sense. The "training" for such systems involves analytical validation experiments to define reagent stability, reaction kinetics, and instrument parameters.
9. How the Ground Truth for the Training Set Was Established
Not applicable for the same reason as point 8. The "ground truth" for developing and validating these reagents is based on fundamental principles of analytical chemistry, biochemical reactions, and extensive internal testing to ensure the reagents perform as intended within the specified analytical parameters.
§ 862.1050 Alkaline phosphatase or isoenzymes test system.
(a)
Identification. An alkaline phosphatase or isoenzymes test system is a device intended to measure alkaline phosphatase or its isoenzymes (a group of enzymes with similar biological activity) in serum or plasma. Measurements of alkaline phosphatase or its isoenzymes are used in the diagnosis and treatment of liver, bone, parathyroid, and intestinal diseases.(b)
Classification. Class II.