(120 days)
The STA® - Liquid Anti-Xa kits are intended for use with STA-R®, STA Compact® and STA Satellite® analyzers, for the quantitative determination of the plasma levels of unfractionated (UFH) and low molecular weight (LMWH) heparins by measuring their anti-Xa activity on antithrombin in a competitive assay using a synthetic chromogenic substrate.
The STA® - Multi Hep Calibrator is a set of calibrator plasmas intended for use with STA-R®, STA Compact®, and STA Satellite® analyzers, for the calibration of heparin (UFH and LMWH) activity assay by measuring the anti-Xa activity.
The STA® - Quality HNF/UFH kit is a set of two plasmas intended for the quality control of unfractionated heparin (UFH) activity assay by measuring the anti-Xa activity performed on STA-R®, STA Compact®, and STA Satellite® analyzers.
The STA® - Quality HBPM/LMWH kit is a set of two plasmas intended for the quality control of low molecular weight heparin (LMWH) activity assay by measuring the anti-Xa activity performed on STA-R®, STA Compact, and STA Satellite® analyzers.
The STA® - Liquid Anti-Xa is a chromogenic assay technique used for determination of the level of UFH and LMWH that have high affinity for antithrombin by measuring their anti-Xa activity. The method is a one-step reaction based on a similar principle: as soon as factor Xa is added to the plasma-substrate mixture, two reactions take place simultaneously, namely, hydrolysis of the substrate by factor Xa and inhibition of factor Xa by the heparin-antithrombin complex. After the necessary period of time for the competitive reaction to reach equilibrium, the quantity of paranitroaniline that is released is inversely proportional to the concentration of heparin present in the test medium.
The STA® - Multi Hep Calibrator reagents are lyophilized human plasmas at five different heparin concentrations. They are used to create the calibration curve on STA-R®, STA Compact®, and STA Satellite® analyzers performing the chromogenic method for heparin (UFH and LMWH) using STA® - Liquid Anti-Xa.
The STA® - Quality HNF/UFH reagents are lyophilized human plasmas at two different UFH concentrations. They are used for the quality control of UFH activity assay by measuring the anti-Xa activity using the chromogenic method STA® - Liquid Anti-Xa performed on STA-R®, STA Compact®, and STA Satellite® analyzers.
The STA® - Quality HBPM/LMWH reagents are lyophilized human plasmas at two different LMWH concentrations. They are used for the quality control of LMWH activity assay by measuring the anti-Xa activity using the chromogenic methods, STA® - Liquid Anti-Xa and STA® - Rotachrom® Heparin, performed on STA-R®, STA Compact, and STA Satellite® analyzers.
The provided document describes the 510(k) summary for several in vitro diagnostic devices for measuring heparin activity. The document focuses on demonstrating substantial equivalence to predicate devices through performance characteristics, rather than establishing acceptance criteria and proving them with a specific study with a defined ground truth, as would be common for AI/ML device submissions.
Therefore, many of the requested elements (e.g., test set sample size, data provenance, number of experts for ground truth, adjudication method, MRMC study, training set details) are not applicable or not explicitly detailed in this type of submission.
However, I can extract information related to performance characteristics that serve as "acceptance criteria" for the device, and the studies performed to demonstrate these.
1. Table of Acceptance Criteria and Reported Device Performance:
The document describes performance characteristics of the STA® - Liquid Anti-Xa device (and its associated calibrator and controls) through precision and detection limit/working range studies. The "acceptance criteria" are implied by the ranges and values obtained, showing performance similar or superior to predicate devices or within acceptable analytical limits for IVD assays.
| Performance Characteristic | Acceptance Criteria (Implied) | Reported Device Performance | Comments |
|---|---|---|---|
| Precision (Hybrid Calibration - 5-point UFH/LMWH) | Coefficient of Variation (CV%) values within acceptable analytical limits for heparin assays. Specific numerical criteria are not explicitly stated, but common industry standards for IVD precision apply. | UFH Samples: |
- Sample 1 (mean 0.21 IU/mL): Repeatability CV 6.2%, Within-lab CV 9.9%
- Sample 2 (mean 0.55 IU/mL): Repeatability CV 3.1%, Within-lab CV 6.6%
- Sample 3 (mean 0.97 IU/mL): Repeatability CV 3.4%, Within-lab CV 5.5%
LMWH Samples: - Sample 4 (mean 0.86 IU/mL): Repeatability CV 3.1%, Within-lab CV 4.8%
- Sample 5 (mean 1.48 IU/mL): Repeatability CV 3.0%, Within-lab CV 5.1%
- Sample 6 (mean 1.75 IU/mL): Repeatability CV 2.9%, Within-lab CV 5.0% | Performed according to CLSI guideline EP5-A2 over 22 days, 2 runs/day. |
| Precision (Dedicated Calibration - 3-point UFH) | CV% values within acceptable analytical limits. | UFH Samples: - Sample 1 (mean 0.22 IU/mL): Repeatability CV 5.6%, Within-lab CV 9.2%
- Sample 2 (mean 0.55 IU/mL): Repeatability CV 3.0%, Within-lab CV 6.1%
- Sample 3 (mean 0.97 IU/mL): Repeatability CV 3.5%, Within-lab CV 5.1% | Similar study design to hybrid calibration. |
| Precision (Dedicated Calibration - 3-point LMWH) | CV% values within acceptable analytical limits. | LMWH Samples: - Sample 4 (mean 0.86 IU/mL): Repeatability CV 3.2%, Within-lab CV 5.2%
- Sample 5 (mean 1.48 IU/mL): Repeatability CV 3.1%, Within-lab CV 5.3%
- Sample 6 (mean 1.75 IU/mL): Repeatability CV 2.8%, Within-lab CV 5.1% | Similar study design to hybrid calibration. |
| Detection Limit (UFH/LMWH 5-point calibration) | Detection threshold should be clinically relevant for heparin monitoring. | 0.10 IU/mL (UFH and LMWH) | Assessed according to CLSI guideline EP17-A. |
| Linearity Range (UFH/LMWH 5-point calibration) | Linearity range should cover the clinically relevant range for heparin monitoring. | UFH: up to 1.10 IU/mL; LMWH: up to 2.00 anti-Xa IU/mL | Assessed according to CLSI guideline EP6-A. |
| Detection Limit (UFH 3-point calibration) | Detection threshold should be clinically relevant. | 0.10 IU/mL | Assessed according to CLSI guideline EP17-A. |
| Linearity Range (UFH 3-point calibration) | Linearity range should cover the clinically relevant range. | up to 1.10 IU/mL | Assessed according to CLSI guideline EP6-A. |
| Detection Limit (LMWH 3-point calibration) | Detection threshold should be clinically relevant. | 0.10 anti-Xa IU/mL | Assessed according to CLSI guideline EP17-A. |
| Linearity Range (LMWH 3-point calibration) | Linearity range should cover the clinically relevant range. | up to 2.00 anti-Xa IU/mL | Assessed according to CLSI guideline EP6-A. |
| Interfering Substances | No significant interference from common endogenous substances at clinically relevant concentrations. | Insensitive to: hemoglobin (up to 1.5 g/l), conjugated bilirubin (up to 288 mg/l), unconjugated bilirubin (up to 138 mg/l), triglycerides (up to 6.9 g/l). | Performed according to CLSI guideline EP7-A2. |
2. Sample size used for the test set and the data provenance:
- Test set sample size: For precision studies, 6 heparin samples (3 UFH, 3 LMWH) were used for each calibration type (hybrid and dedicated). For the detection limit and linearity studies, specific sample numbers are not provided but are implicit in the CLSI guidelines (EP17-A and EP6-A) which typically involve multiple replicates across different concentrations. For interfering substances, the number of samples is not explicitly stated, but the study tested specific concentrations of key interferents.
- Data provenance: Not explicitly stated, but given this is an in vitro diagnostic device for global markets, the samples would likely be prepared laboratory controls and patient plasma samples (for linearity, detection limit, and interference studies), not geographically defined "countries of origin" in the same way as imaging data. The studies are prospective in the sense that they are designed experiments to validate performance.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable (N/A) in the context of this IVD device. The "ground truth" for these types of assays is established by the known concentrations of calibrators, controls, and spiked samples, or by reference methods, not by expert interpretation.
4. Adjudication method for the test set:
- N/A. Adjudication is not relevant for analytical performance studies of quantitative IVD assays.
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:
- No. This is an in vitro diagnostic device, not an AI/ML-driven interpretive device typically associated with MRMC studies.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, this is a standalone device. The performance characteristics (precision, detection limits, linearity, interference) are determined for the algorithm/device only. Human involvement is in operating the analyzer and interpreting the numerical results, but the analytical performance itself is inherent to the device.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For precision, linearity, and detection limit, the ground truth is established by the known concentrations of the calibrators and control plasmas, or by accepted reference methods for heparin activity (e.g., anti-Xa activity).
- For interfering substances, the ground truth is the addition of specific interfering agents at known concentrations to samples, and then assessing if the device's measurement of heparin is accurately maintained.
8. The sample size for the training set:
- Not applicable (N/A) in the AI/ML sense. This is a traditional IVD device using established chromogenic assay principles, not an AI/ML system that requires a "training set" to learn. The method relies on biochemical reactions and quantitative measurement.
9. How the ground truth for the training set was established:
- N/A for the same reason as point 8.
§ 864.7525 Heparin assay.
(a)
Identification. A heparin assay is a device used to determine the level of the anticoagulant heparin in the patient's circulation. These assays are quantitative clotting time procedures using the effect of heparin on activated coagulation factor X (Stuart factor) or procedures based on the neutralization of heparin by protamine sulfate (a protein that neutralizes heparin).(b)
Classification. Class II (performance standards).