(506 days)
ACL TOP 970 CL: The ACL TOP 970 CL is a bench top, fully automated, random access analyzer designed specifically for in vitro diagnostic use by health care professionals in a clinical laboratory. The system provides results for both direct measurements and calculated parameters.
HemosIL CL Anti-Cardiolipin IgM: HemosIL CL Anti-Cardiolipin IgM is a fully automated chemiluminescent immunoassay for the semi-quantitative measurement of anti-cardiolipin (aCL) IgM antibodies in human 3.2% or 3.8% citrated plasma on the ACL TOP 970 CL in the laboratory setting by a healthcare professional, as an aid in the diagnosis of Antiphospholipid Syndrome (APS) when used in conjunction with other laboratory and clinical findings. For use with adult population. For prescription use only.
HemosIL CL Anti-ß2 Glycoprotein-I IgM: HemosIL CL Anti-B2 Glycoprotein-I IgM is a fully automated chemiluminescent immunoassay for the semi-quantitative measurement of anti-B2 Glycoprotein-I (anti-B2GPI) IgM antibodies in human 3.2% or 3.8% citrated plasma on the ACL TOP 970 CL in the laboratory setting by a healthcare professional, as an aid in the diagnosis of Antiphospholipid Syndrome (APS) when used in conjunction with other laboratory and clinical findings. For use with adult population. For prescription use only.
ACL TOP 970 CL Instrument: The ACL TOP 970 CL is an instrument that integrates new chemiluminescent test capability similar to the ACL AcuStar, K083518.
HemosIL CL Anti-Cardiolipin IgM: HemosIL CL Anti-Cardiolipin IgM is a chemiluminescent two-step immunoassay consisting of magnetic particles coated with cardiolipin and human purified ß2GPI, which capture, if present, the aCL antibodies from the sample. After incubation, magnetic separation, and a wash step, a tracer consisting of an isoluminol-labeled anti-human IgM antibody is added and may bind with the captured aCL IgM on the particles. After a second incubation, magnetic separation, and wash step, reagents that trigger the luminescent reaction are added, and the emitted light is measured as relative light units (RLU) by the ACL TOP 970 CL optical system. RLUs are directly proportional to the aCL IgM concentration in the sample.
HemosIL CL Anti-ß2 Glycoprotein-I IgM: HemosIL CL Anti-ß2 Glycoprotein-I IgM is a chemiluminescent two-step immunoassay consisting of magnetic particles coated with human purified ß2GPI, which capture, if present, the aß2GPI antibodies from the sample. After incubation, magnetic separation, and a wash step, a tracer consisting of an isoluminol-labeled anti-human IgM antibody is added and may bind with the captured aß2GPI IgM on the particles. After a second incubation, magnetic separation, and wash step, reagents that trigger the luminescent reaction are added, and the emitted light is measured as relative light units (RLUs) by the ACL TOP 970 CL optical system. RLUs are directly proportional to the aß2GPI IgM concentration in the sample.
The provided text describes the 510(k) summary for the ACL TOP 970 CL instrument and two associated immunoassays, HemosIL CL Anti-Cardiolipin IgM and HemosIL CL Anti-β2 Glycoprotein-I IgM. The studies presented focus on analytical performance and comparability to predicate devices, rather than AI model performance or human-in-the-loop studies. Therefore, many of the requested elements pertaining to AI-driven diagnostic devices (such as expert adjudication, MRMC studies, or training set details for AI) are not applicable or cannot be extracted from this document.
However, I can extract information related to the acceptance criteria for the analytical performance of the assays and how that performance was demonstrated.
Here's a breakdown of the available information:
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for these in vitro diagnostic devices are demonstrated through various analytical performance studies, focusing on precision, linearity, analytical sensitivity (LoD/LoQ), analytical specificity, and method comparison to predicate devices. The document does not explicitly state pre-defined acceptance thresholds for each parameter (e.g., minimum CV for precision, minimum slope for linearity). Instead, it presents the results of these studies, implying that the observed performance met internal or regulatory acceptance.
HemosIL CL Anti-Cardiolipin IgM
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Precision (Low Lot-to-Lot Variability) | Lot-to-Lot Variability (% CV): |
- Low Multi-Ab Control: 1.6%
- High Multi-Ab Control: 1.2%
- Plasma Samples A-E: 1.6% - 9.6% |
| Reproducibility (Low CV across sites/runs)| Reproducibility (% CV): - Low Multi-Ab Control: 7.0%
- High Multi-Ab Control: 7.4%
- Clinical Samples 1-4: 4.5% - 9.5% |
| Analytical Sensitivity (LoD/LoQ) | LoD: 1.0 U/mL
LoQ: 1.0 U/mL |
| Linearity Range | 2.7 - 500.0 U/mL |
| Analytical Specificity (No interference) | No interference for: Hemoglobin, Bilirubin, Triglycerides, Heparin (LMW/UF), Rheumatoid Factor, Acetylsalicylic acid, Atorvastatin, Warfarin, Prednisone, Acid Citric Dextrose, Hydroxychloroquine, Rituximab at specified concentrations. |
| Method Comparison (Strong correlation to predicate) | Slope (95% CI): 1.00 (0.98 - 1.01)
r: 1.00 |
| Diagnostic Performance (Sensitivity/Specificity vs. APS Classification - provided for context, not a direct "acceptance criterion" in the same way as analytical measures) | Sensitivity: 40.5% (33.8% - 47.6%)
Specificity: 91.9% (88.4% - 94.5%) |
HemosIL CL Anti-β2 Glycoprotein-I IgM
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Precision (Low Lot-to-Lot Variability) | Lot-to-Lot Variability (% CV): |
- Low Multi-Ab Control: 12.8%
- High Multi-Ab Control: 11.5%
- Plasma Samples A-E: 3.6% - 7.2% |
| Reproducibility (Low CV across sites/runs)| Reproducibility (% CV): - Low Multi-Ab Control: 8.3%
- High Multi-Ab Control: 7.7%
- Clinical Samples 1-4: 4.8% - 8.3% |
| Analytical Sensitivity (LoD/LoQ) | LoD: 2.0 U/mL
LoQ: 2.0 U/mL |
| Linearity Range | 1.9 - 400.0 U/mL |
| Analytical Specificity (No interference) | No interference for: Hemoglobin, Bilirubin, Triglycerides, Heparin (LMW/UF), Rheumatoid Factor, Acetylsalicylic acid, Atorvastatin, Warfarin, Prednisone, Acid Citric Dextrose, Hydroxychloroquine, Rituximab at specified concentrations. |
| Method Comparison (Strong correlation to predicate) | Slope (95% CI): 0.94 (0.92 – 0.96)
r: 0.99 |
| Diagnostic Performance (Sensitivity/Specificity vs. APS Classification - provided for context, not a direct "acceptance criterion" in the same way as analytical measures) | Sensitivity: 33.0% (26.7% - 39.9%)
Specificity: 94.6% (91.4% - 96.6%) |
2. Sample Sizes Used for the Test Set and Data Provenance
- Precision Study (Test Set):
- HemosIL CL Anti-Cardiolipin IgM & Anti-β2 Glycoprotein-I IgM: 5 plasma samples (3 positive, 2 negative) and 2 levels of controls. Each material was run in duplicate, twice per day over 20 days.
- Reproducibility Study (Test Set):
- HemosIL CL Anti-Cardiolipin IgM & Anti-β2 Glycoprotein-I IgM: 4 plasma samples (3 positive, 1 negative for Anti-Cardiolipin IgM; 3 positive for Anti-β2 Glycoprotein-I IgM) and 2 levels of controls. Each material tested in triplicate, twice a day for 5 days, totaling 30 replicates per level.
- Analytical Sensitivity (LoD/LoQ):
- Specific sample numbers for LoD/LoQ for new reagent lots are not detailed, but samples prepared by combining Ab-positive and normal donor plasma were used.
- Linearity:
- For each assay, samples were prepared by diluting a high antibody plasma sample with a negative antibody plasma sample to create required concentrations. Each level was measured in seven replicates.
- Normal Reference Range:
- 100 citrated plasma normal donor samples.
- Method Comparison:
- HemosIL CL Anti-Cardiolipin IgM: N = 131 samples.
- HemosIL CL Anti-β2 Glycoprotein-I IgM: N = 123 samples.
- APS Outcome Study (Diagnostic Performance):
- HemosIL CL Anti-Cardiolipin IgM: N = 500 samples.
- HemosIL CL Anti-β2 Glycoprotein-I IgM: N = 503 samples (indicated by the sum of Positive/Negative categories: 63+17+128+295=503).
Data Provenance: The document does not specify the country of origin for the data or whether the studies were retrospective or prospective, though typical clinical performance studies for diagnostic devices are usually prospective or utilize carefully curated samples. Reproducibility studies were conducted at "3 external sites."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
This information is not provided. For these in vitro diagnostic immunoassays, the "ground truth" for the analytical performance studies (precision, linearity, etc.) is the quantitative measurement itself, validated against established laboratory methods or reference materials. For the "APS Outcome Study," the ground truth is "APS disease classification per 2006 International Consensus Statement from Miyakis et al." This classification is typically based on a combination of clinical and laboratory findings, interpreted by clinicians, but the specific number and qualifications of experts involved in this classification for the study samples are not detailed.
4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set
Not applicable, as this is an in vitro diagnostic device measuring analyte concentrations, not an imaging AI relying on expert interpretations or adjudications. The diagnostic performance (sensitivity/specificity) is compared against pre-defined clinical classification criteria (Miyakis et al. 2006).
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 document describes an in vitro diagnostic device (immunoassay and analyzer), not an AI-driven imaging diagnostic device. There is no mention of human readers or AI assistance in diagnostic interpretation.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
The performance data provided (precision, linearity, sensitivity, specificity, method comparison) is the standalone performance of the device (instrument + assay). The device provides a semi-quantitative measurement of antibodies, which then aids in diagnosis when used "in conjunction with other laboratory and clinical findings." There is no "human-in-the-loop" component in the assay's direct operation or result generation as described beyond the healthcare professional performing the test.
7. The Type of Ground Truth Used
- Analytical Studies (Precision, Linearity, LoD/LoQ, Specificity): The ground truth is inherent to the nature of these highly controlled analytical tests. For example, for linearity, serially diluted samples with known concentrations are used. For interference, samples spiked with known interferents are used.
- Method Comparison: The ground truth is established by the measurements obtained from the predicate (reference) devices: HemosIL AcuStar Anti-Cardiolipin IgM (K092181) and HemosIL AcuStar Anti-β2 Glycoprotein-I IgM (K091556) on the ACL AcuStar (K083518).
- Normal Reference Range: Established by testing 100 samples from "normal donors."
- APS Outcome Study: "APS disease classification per 2006 International Consensus Statement from Miyakis et al." This is a consensus-based clinical classification criteria.
8. The Sample Size for the Training Set
Not applicable, as this is not an AI/machine learning device that requires a distinct training set. The "development" of the assays would involve internal R&D, but not a "training set" in the context of AI.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no training set mentioned for an AI model. For the development/validation of the immunoassay itself, the "ground truth" for calibrators and controls would be established through careful analytical procedures, often traceable to international standards or reference materials, under strict quality control.
§ 864.5425 Multipurpose system for in vitro coagulation studies.
(a)
Identification. A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.(b)
Classification. Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.