(246 days)
The ACE ALT Reagent is intended for the quantitative determination of alanine aminotransferase activity in serum using the ACE Axcel Clinical Chemistry System. 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 or 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 using the ACE Axcel Clinical Chemistry System. 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 or physician office laboratories. For in vitro diagnostic use only.
The ACE γ-GT Reagent is intended for the quantitative determination of gamma-glutamyltransferase activity in serum using the ACE Axcel Clinical Chemistry System. 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 or physician office laboratories. For in vitro diagnostic use only.
In the ACE ALT Reagent assay, alanine aminotransferase in serum converts the L-alanine and α-ketoglutarate substrates in the reagent to L-glutamate and pyruvate. 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 in serum converts the L-aspartate and α-ketoglutarate in the reagent to oxalacetate and L-glutamate. The oxalacetate undergoes reduction with simultaneous 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 serum.
In the ACE γ-GT Reagent assay, γ-GT in serum 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.
This document describes the performance of the ACE ALT, AST, and γ-GT Reagents on the ACE Axcel Clinical Chemistry System. These reagents are intended for the quantitative determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (γ-GT) activity in serum, used in the diagnosis and treatment of certain liver and heart diseases.
Here's an analysis of the provided information:
1. Table of Acceptance Criteria and Reported Device Performance:
The document does not explicitly state "acceptance criteria" as distinct from the reported performance. Instead, it presents the results of precision and accuracy studies. The implication is that these results demonstrate acceptable performance for the device. For the purpose of this table, the reported performance values are presented with the understanding that they met the internal requirements of the manufacturer for regulatory submission.
| Metric | Acceptance Criteria (Implied) | ACE ALT Reagent | ACE AST Reagent | ACE γ-GT Reagent |
|---|---|---|---|---|
| Precision | Low CV% for within-run and total CV | Lab Setting (4 levels, 22 days): Within-run CV: 0.8% - 6.9%; Total CV: 1.1% - 6.9%. | ||
| POL Sites (3 sites, 5 days): Within-run CV: 0.8% - 8.7%; Total CV: 1.3% - 8.7%. | Lab Setting (4 levels, 22 days): Within-run CV: 0.9% - 7.1%; Total CV: 1.4% - 8.5%. | |||
| POL Sites (3 sites, 5 days): Within-run CV: 1.1% - 11.3%; Total CV: 1.2% - 11.3%. | Lab Setting (4 levels, 22 days): Within-run CV: 1.0% - 3.0%; Total CV: 1.1% - 6.1%. | |||
| POL Sites (3 sites, 5 days): Within-run CV: 0.7% - 12.4%; Total CV: 1.3% - 13.0%. | ||||
| Accuracy (Correlation to Predicate) | High correlation coefficient (near 1), low standard error, slope near 1, intercept near 0 | Correlation Study (102 samples, 4-472 U/L): Correlation coefficient: 0.9996; Standard error: 2.4; CI slope: 1.035 to 1.047; CI intercept: -0.3 to 0.9. | ||
| POL Sites: Correlation coefficients: 0.9997 to 0.9999; Standard error: 2.4 to 3.1; CI slopes: 1.009 to 1.035; CI intercepts: -1.1 to 2.4. | Correlation Study (117 samples, 8-440 U/L): Correlation coefficient: 0.9996; Standard error: 2.2; CI slope: 1.002 to 1.012; CI intercept: 1.9 to 2.8. | |||
| POL Sites: Correlation coefficients: 0.9996 to 0.9998; Standard error: 2.5 to 2.9; CI slopes: 1.005 to 1.038; CI intercepts: -1.4 to 2.1. | Correlation Study (128 samples, 7-902 U/L): Correlation coefficient: 0.9998; Standard error: 3.4; CI slope: 0.981 to 0.988; CI intercept: -0.6 to 0.8. | |||
| POL Sites: Correlation coefficients: 0.9992 to 0.9999; Standard error: 3.6 to 8.8; CI slopes: 0.967 to 1.053; CI intercepts: -1.7 to 4.8. | ||||
| Detection Limit | Low U/L value | 3.1 U/L | 1.5 U/L | 2.7 U/L |
2. Sample Sizes Used for the Test Set and Data Provenance:
-
ACE ALT Reagent:
- Precision: Not explicitly stated as a "test set" sample size for patient samples. Precision was assessed at four ALT levels over 22 days in a lab setting and at three Physician Office Laboratory (POL) sites over 5 days. These studies would typically involve repeated measurements of control materials or pooled patient samples.
- Accuracy: 102 samples for the main correlation study (ALT values from 4 to 472 U/L) and patient correlation studies conducted at three separate POL sites.
- Data Provenance: Not explicitly stated, but the mention of Physician Office Laboratory (POL) sites suggests data from clinical settings. It is implied to be prospective data collected for the study, rather than retrospective.
-
ACE AST Reagent:
- Precision: Similar to ALT, assessed at four AST levels over 22 days in a lab and at three POL sites over 5 days.
- Accuracy: 117 samples for the main correlation study (AST values from 8 to 440 U/L) and patient correlation studies conducted at three separate POL sites.
- Data Provenance: Not explicitly stated, but implies clinical settings and prospective data.
-
ACE γ-GT Reagent:
- Precision: Similar to ALT and AST, assessed at four γ-GT levels over 22 days in a lab and at three POL sites over 5 days.
- Accuracy: 128 samples for the main correlation study (γ-GT values from 7 to 902 U/L) and patient correlation studies conducted at three separate POL sites.
- Data Provenance: Not explicitly stated, but implies clinical settings and prospective data.
The country of origin for the data is not specified, but the manufacturer is based in the US.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
This information is not applicable as the device is an in vitro diagnostic (IVD) chemistry system that provides quantitative measurements of enzyme activity. The "ground truth" for IVD devices like this is typically established by comparing performance against a reference method or a legally marketed predicate device, rather than expert interpretation of images or clinical assessments.
For accuracy, the device's performance was compared to the Alfa Wassermann ACE Clinical Chemistry System (predicate device K931786).
4. Adjudication Method for the Test Set:
This information is not applicable. Adjudication methods (like 2+1 or 3+1) are typically used in studies where human experts interpret results or clinical cases, and a consensus needs to be reached. For quantitative IVD tests, the "ground truth" is the result obtained from a reference method or predicate device.
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. MRMC studies are relevant for medical imaging AI devices where human readers interpret images. This device is an in vitro diagnostic system for chemical analysis and does not involve human readers interpreting cases in the same way.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done:
Yes, the performance studies described (precision, accuracy, and detection limit) represent the standalone performance of the ACE ALT, AST, and γ-GT Reagents on the ACE Axcel Clinical Chemistry System. These are objective, quantitative measurements generated directly by the analytical system, without human interpretation in the "loop" of the measurement process itself.
7. The Type of Ground Truth Used:
The ground truth used for the accuracy studies was the measurements obtained from the predicate device, the Alfa Wassermann ACE Clinical Chemistry System (K931786). The new reagents on the ACE Axcel system (y) were compared against the existing reagents on the ACE system (x) using patient samples. This is a common method for demonstrating substantial equivalence for new IVD devices by showing good correlation with an already legally marketed device.
8. The Sample Size for the Training Set:
This information is not applicable. The device is an in vitro diagnostic reagent and system, not an AI/ML algorithm that requires a "training set" in the conventional sense of machine learning. The reagents and system are developed and optimized through traditional chemical and engineering processes, followed by validation studies as described.
9. How the Ground Truth for the Training Set was Established:
This information is not applicable for the same reason as point 8. There is no training set in the machine learning context for this type of device.
§ 862.1030 Alanine amino transferase (ALT/SGPT) test system.
(a)
Identification. An alanine amino transferase (ALT/SGPT) test system is a device intended to measure the activity of the enzyme alanine amino transferase (ALT) (also known as a serum glutamic pyruvic transaminase or SGPT) in serum and plasma. Alanine amino transferase measurements are used in the diagnosis and treatment of certain liver diseases (e.g., viral hepatitis and cirrhosis) and heart diseases.(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 § 862.9.