(28 days)
The ACE Cholesterol Reagent is intended for the quantitative determination of cholesterol concentration in serum and lithium heparin plasma using the ACE Axcel Clinical Chemistry System. Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood and lipid and lipoprotein metabolism disorders. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
The ACE HDL-C Reagent is intended for the quantitative determination of high density lipoprotein cholesterol (HDL-C) concentration in serum and lithium heparin plasma using the ACE Axcel Clinical Chemistry System. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
The ACE LDL-C Reagent is intended for the quantitative determination of low density lipoprotein cholesterol (LDL-C) concentration in serum and lithium heparin plasma using the ACE Axcel Clinical Chemistry System. Lipoprotein measurements are used in the diagnosis and treatment of lipid disorders (such as diabetes mellitus), atherosclerosis, and various liver and renal diseases. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
The ACE Triglycerides Reagent is intended for the quantitative determination of triglyceride concentration in serum and lithium heparin plasma using the ACE Axcel Clinical Chemistry System. Triglyceride measurements are used in the diagnosis and treatment of patients with diabetes mellitus, nephrosis, liver obstruction, other diseases involving lipid metabolism or various endocrine disorders. This test is intended for use in clinical laboratories or physician office laboratories. For in vitro diagnostic use only.
The ACE Cholesterol Reagent is composed of a single reagent bottle. The reagent contains 4-aminoantipyrine, p-hydroxybenzoic acid, cholesterol oxidase, cholesterol esterase and peroxidase.
The HDL-C Reagent assay utilizes two reagent bottles, the second containing a unique detergent. This detergent solubilizes only the HDL lipoprotein particles, thus releasing HDL cholesterol to react with the cholesterol esterase and cholesterol oxidase, in the presence of a chromogen to produce color. The detergent also inhibits the reaction of the cholesterol enzymes with LDL, VLDL and chylomicron lipoproteins by adsorbing to their surfaces. The amount of chromogen formed, determined by measuring the increase in absorbance bichromatically at 592/692 nm, is directly proportional to the HDL cholesterol concentration in the sample.
In the ACE LDL-C Reagent assay, detergent 1 solubilizes non-LDL lipoprotein particles (HDL, VLDL and chylomicrons) and releases cholesterol. The cholesterol is consumed by cholesterol esterase and cholesterol oxidase in a non-color forming reaction. In a second reaction, detergent 2 solublizes the remaining LDL particles and forms peroxide, via the enzymes cholesterol esterase and cholesterol oxidase. The peroxide, in the presence of peroxidase and two peroxidase substrates, 4-aminoantipyrine and DSBmT, results in a purple-red color. The amount of color formed, determined by measuring the increase in absorbance bichromatically at 544/692 nm, is directly proportional to the LDL cholesterol concentration in the sample.
In the ACE Triglycerides Reagent assay, triglycerides in serum are hydrolyzed by lipase to form glycerol and free fatty acids. In the presence of adenosine triphosphate (ATP) and glycerol kinase, the glycerol is converted to glycerol-1-phosphate and the ATP to adenosine diphosphate. Glycerol-1-phosphate is oxidized by glycerol phosphate oxidase to yield hydrogen peroxide. The hydrogen peroxide then acts to oxidatively couple p-chlorophenol and 4-aminoantipyrine in a reaction catalyzed by peroxidase, producing a red colored quinoneimine complex which absorbs strongly at 505 nm. The amount of chromogen formed, determined by measuring the increase in absorbance bichromatically at 505 nm/692 nm, is directly proportional to the triglycerides concentration in the sample.
The provided text describes a 510(k) submission for the ACE Axcel Clinical Chemistry System and its associated reagents for Cholesterol, HDL-C, LDL-C, and Triglycerides. The submission focuses on demonstrating substantial equivalence to a predicate device (K113262) by showing that the new device has "Same" intended use, instrument platform, basic principle, and reagent composition, with the only difference being the expanded sample type (serum and lithium heparin plasma for the candidate device vs. serum only for the predicate device).
The acceptance criteria are implicitly defined by the performance characteristics demonstrated in the study, which aim to show that the expanded sample type (lithium heparin plasma) does not negatively impact the accuracy and precision of the measurements compared to serum. The study largely relies on analytical performance data rather than clinical outcomes or expert consensus on interpretations.
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as numerical targets in the document; instead, the study intends to demonstrate comparable performance to the predicate device and acceptable analytical characteristics. The reported device performance for precision and matrix comparison is provided below, which implicitly became the "accepted" performance for the expanded sample type.
| Analyte | Metric / Acceptance Criteria (Implied: Acceptable analytical performance and comparability) | Reported Device Performance (Precision) | Reported Device Performance (Matrix Comparison: Serum vs. Plasma) |
|---|---|---|---|
| Cholesterol | Precision (SD, %CV) at various concentrations for serum and plasma | Serum: Low: 2.4, 1.6%; Mid: 3.6, 1.4%; High: 6.8, 1.3% | |
| Plasma: Low: 2.7, 2.1%; Mid: 4.1, 1.2%; High: 7.9, 1.4% | Slope: 0.987, Intercept: -1.9, Correlation: 0.9987 (54 pairs) | ||
| HDL-C | Precision (SD, %CV) at various concentrations for serum and plasma | Serum: Low: 2.0, 4.3%; Mid: 2.0, 2.6%; High: 2.4, 2.2% | |
| Plasma: Low: 1.3, 3.1%; Mid: 1.2, 1.7%; High: 2.7, 2.6% | Slope: 1.011, Intercept: -1.1, Correlation: 0.9981 (53 pairs) | ||
| LDL-C | Precision (SD, %CV) at various concentrations for serum and plasma | Serum: Low: 2.4, 2.6%; Mid: 3.7, 2.3%; High: 7.1, 2.1% | |
| Plasma: Low: 1.8, 2.3%; Mid: 5.6, 2.6%; High: 9.6, 2.6% | Slope: 1.006, Intercept: -1.6, Correlation: 0.9981 (54 pairs) | ||
| Triglycerides | Precision (SD, %CV) at various concentrations for serum and plasma | Serum: Low: 1.4, 2.1%; Mid: 3.4, 1.0%; High: 4.3, 0.7% | |
| Plasma: Low: 2.2, 3.2%; Mid: 3.5, 1.0%; High: 13.5, 2.3% | Slope: 0.992, Intercept: -3.6, Correlation: 0.9993 (55 pairs) |
2. Sample size used for the test set and the data provenance
- Precision/Reproducibility Study (Test Set):
- For each analyte (Cholesterol, HDL-C, LDL-C, Triglycerides), for both serum and plasma, 3 levels of samples were used.
- Each level was tested with 2 replicates, twice a day, on 5 separate days, yielding a total of 20 replicates per level (3 levels * 2 sample types * 20 replicates/level = 120 total measurements per analyte category, e.g., Cholesterol on Serum).
- Data Provenance: Not explicitly stated, but typically these studies are conducted in a laboratory setting, likely in the US (given the FDA submission). It is a prospective analytical study designed to evaluate device performance under controlled conditions.
- Matrix Comparison Study (Test Set):
- Cholesterol: 54 paired serum and lithium heparin plasma specimens.
- HDL-C: 53 paired serum and lithium heparin plasma specimens.
- LDL-C: 54 paired serum and lithium heparin plasma specimens.
- Triglycerides: 55 paired serum and lithium heparin plasma specimens.
- These specimens covered the assay's dynamic range.
- Data Provenance: Not explicitly stated, but likely from a clinical laboratory setting, potentially within the US. The samples are retrospective specimens collected for analytical comparison.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This type of submission for in vitro diagnostic reagents does not typically involve human experts establishing "ground truth" through interpretation. The "ground truth" for the test set is established by comparative measurements against a reference method or the predicate device, and by the inherent chemical/physical properties of the samples used in reproducibility studies. No information about experts or their qualifications is provided or relevant in this context.
4. Adjudication method for the test set
Not applicable. This is an analytical performance study for laboratory reagents, not a clinical study involving human interpretation that would require an adjudication method.
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 is not an AI/imaging device, nor does it involve human readers or case interpretations. It is an in vitro diagnostic reagent.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
This is an analytical device, and its performance is inherently standalone in terms of generating a quantitative result. The results are then interpreted by clinicians in the overall diagnostic process. The study evaluates the standalone performance of the reagents on the ACE Axcel Clinical Chemistry System.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The "ground truth" for this type of analytical validation is established by:
- Reference methods and/or the predicate device: For the matrix comparison, the serum measurements on the candidate device (which is substantially equivalent to the predicate) serve as the reference against plasma measurements. The predicate device's performance also implicitly serves as a benchmark for comparison.
- Known concentrations: For precision studies, samples are "clinically relevant decision levels" meaning they have known or well-characterized concentrations of the analytes. These concentrations are typically determined by highly accurate laboratory methods.
8. The sample size for the training set
Not applicable. This is not an AI or machine learning device that requires a training set. The reagents are chemical formulations, and the system is an automated analyzer.
9. How the ground truth for the training set was established
Not applicable, as there is no training set for this type of device.
§ 862.1175 Cholesterol (total) test system.
(a)
Identification. A cholesterol (total) test system is a device intended to measure cholesterol in plasma and serum. Cholesterol measurements are used in the diagnosis and treatment of disorders involving excess cholesterol in the blood and lipid and lipoprotein metabolism disorders.(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.