(227 days)
Automated coagulation functional assay for the quantitative determination of free Protein S in human citrated plasma as an aid in the diagnosis of hereditary and acquired Protein S deficiency, on ACL TOP Family members.
The HemosIL Protein S Activity assay determines the functional activity of free Protein S by measuring the degree of prolongation of prothrombin time in the presence of the human recombinant factor, phospholipids, calcium ions, and activated Protein C. The protein S activity is correlated with the prolongation of the clotting time of a Protein S deficient plasma to which a diluted sample has been added.
The provided document describes the HemosIL® Protein S Activity Assay, a device designed for the quantitative determination of free Protein S in human citrated plasma, aiding in the diagnosis of hereditary and acquired Protein S deficiency. The submission is a 510(k) premarket notification, indicating the device is being compared to a legally marketed predicate device (HemosIL ProS Assay, K053499) to establish substantial equivalence.
Based on the provided text, here's an analysis of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state "acceptance criteria" for the performance metrics (precision and method comparison). Instead, it presents the results of internal and field-site studies and implies that these results demonstrate performance equivalent to the predicate device, thereby fulfilling the requirements for substantial equivalence.
However, we can infer performance ranges from the provided data:
| Metric | Acceptance Criteria (Inferred from Predicate Equivalence) | Reported Device Performance (HemosIL Protein S Activity Assay) |
|---|---|---|
| Precision | Not explicitly stated as acceptance criteria, but results are compared to established levels for similar assays. | Within-Run CV%: 1.6 - 3.8% (for various controls/samples) |
| Total CV%: 4.2 - 7.1% (for various controls/samples) | ||
| Method Comparison (In-House) | Not explicitly stated. Implied to show substantial equivalence to predicate. | Slope: 0.966 (for ACL TOP 700) |
| Y-intercept: 0.000 (for ACL TOP 700) | ||
| Method Comparison (Field Site) | Not explicitly stated. Implied to show substantial equivalence to predicate. | Slope: 0.955 - 1.010 (across various systems) |
| Y-intercept: Not explicitly stated/clear in presented data. |
2. Sample Sizes Used for the Test Set and Data Provenance
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Precision Study:
- Sample Size: "n=80/ instrument/ lot" for each sample level (Normal Control, Low Abnormal Control, High Abnormal Control, Internal Control 1, Internal Control 2, High Plasma Sample). This means for each of the 3 lots and 3 instruments, there were 80 data points for each sample type. This is a total of (80 data points/sample type * 6 sample types * 3 lots * 3 instruments) = 4320 data points for precision (if all combinations were tested for each sample type). However, the table only shows data from a "representative lot" on "ACL TOP".
- Data Provenance: The study was conducted "in accordance with CLSI EP05-A2" and utilized "3 lots of reagent on 3 representative members of the ACL TOP Family (ACL TOP, ACL TOP 500 CTS and ACL TOP 700)". This indicates the data is prospective and generated during internal validation, likely at the manufacturer's facility. Country of origin is not specified but the manufacturer is based in Bedford, MA, USA.
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Method Comparison - In-House:
- Sample Size: Not explicitly stated in the provided text. The table only shows results for "ACL TOP 700" but doesn't mention the number of samples used for the comparison between the new device and the predicate.
- Data Provenance: "An in-house comparison study was performed". This indicates prospective data generated internally, likely at the manufacturer's facility.
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Method Comparison - Field Sites:
- Sample Size: Not explicitly stated in the provided text. The table shows results from "Two field site studies" but doesn't mention the number of samples used.
- Data Provenance: "Two field site studies were performed". This indicates prospective data collected from external laboratories, likely in different geographical locations (though country of origin is not specified).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This information is not applicable and therefore, not provided. The device is an in vitro diagnostic assay that measures analyte concentration (Protein S activity). The "ground truth" for such assays is typically established by the reference method or by the predicate device's performance, not by expert consensus in clinical interpretation of images or symptoms. The studies involve comparing the new assay's results to the predicate device's quantitative results, or evaluating its precision against statistical guidelines.
4. Adjudication Method for the Test Set
This information is not applicable and therefore, not provided. Adjudication methods are typically used in studies involving subjective interpretation (e.g., image reading) where multiple experts might disagree. For an analytical assay, the comparison is quantitative and statistical, not based on adjudication of expert opinions.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
This information is not applicable and therefore, not provided. An MRMC study is relevant for diagnostic imaging devices where human readers interpret cases, and the effectiveness of AI assistance on their performance is evaluated. This device is an in-vitro diagnostic assay and does not involve human "readers" in the same context.
6. Standalone Performance
Yes, a standalone performance study was done for the algorithm (the assay). The entire document describes the standalone performance of the HemosIL Protein S Activity assay. It characterizes the assay's precision (within-run and total CV%) and its correlation with a legally marketed predicate device through method comparison studies. The performance reported in section "VII. Summary of Performance Data" are characteristics of the device itself (the "algorithm only" if the assay method is considered analogous to an algorithm).
7. Type of Ground Truth Used
The ground truth used for performance evaluation is derived from:
- Precision: Statistical measures of reproducibility, comparing the device's own measurements across repeated tests.
- Method Comparison: The results obtained from the predicate device (HemosIL ProS). The new device's performance is established by demonstrating substantial equivalence to the predicate device's quantitative results. This means the predicate device's measurements serve as the referent or "ground truth" for comparison to establish equivalence.
8. Sample Size for the Training Set
This information is not applicable and not provided. The HemosIL Protein S Activity assay is a reagent-based assay for laboratory testing, not an AI/ML algorithm that requires a "training set" in the conventional sense of machine learning. The "training" for such an assay involves the development and optimization of the reagents and methodology, which is a chemical and biological process, not a computational one with a distinct training dataset.
9. How the Ground Truth for the Training Set Was Established
This information is not applicable and not provided for the reasons stated in point 8.
§ 864.7290 Factor deficiency test.
(a)
Identification. A factor deficiency test is a device used to diagnose specific coagulation defects, to monitor certain types of therapy, to detect coagulation inhibitors, and to detect a carrier state (a person carrying both a recessive gene for a coagulation factor deficiency such as hemophilia and the corresponding normal gene).(b)
Classification. Class II (performance standards).