(27 days)
HemosIL Fibrinogen-C is intended for the quantitative determination of fibrinogen, based on the Clauss method, in human citrated plasma on IL Coagulation Systems. For in vitro diagnostic use.
The Fibrinogen-C kit uses an excess of thrombin to convert fibrinogen to fibrin in diluted plasma. At high thrombin and low fibrinogen concentration, the rate of reaction is a function of the fibrinogen concentration.
Here's a breakdown of the acceptance criteria and study information for the HemosIL Fibrinogen-C device, based on the provided text:
Acceptance Criteria and Device Performance for HemosIL Fibrinogen-C
The submission details modifications to the HemosIL Fibrinogen-C test parameters on the ACL TOP system. The study aims to demonstrate that these modified parameters are substantially equivalent to the previously marketed device.
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" as a separate set of pass/fail thresholds. Instead, it presents the performance of both the "Current Parameters" (predicate device) and the "Modified Parameters" (new device) for comparison, implying that similar or improved performance for the modified parameters constitutes acceptance.
| Performance Characteristic | Current Parameters (Predicate Device Performance) | Modified Parameters (Reported Device Performance) | Implied Acceptance Criteria (Goal) |
|---|---|---|---|
| Interference | No significant increase in interference compared to predicate. | ||
| Heparin | Up to 1 U/mL (no interference) | Up to 1 U/mL (no interference) | $\le$ 1 U/mL (no interference) |
| Hemoglobin | Up to 375 mg/dL (no interference) | Up to 375 mg/dL (no interference) | $\le$ 375 mg/dL (no interference) |
| Triglycerides | Up to 890 mg/dL (no interference) | Up to 750 mg/dL (no interference) | Comparable or better than predicate |
| Bilirubin | Up to 21 mg/dL (no interference) | Up to 21 mg/dL (no interference) | $\le$ 21 mg/dL (no interference) |
| Fibrinogen Degradation Products (FDP) | Up to 100 µg/mL (no interference) | New testing showed interference from FDP. Insert will indicate results "may be affected." | Acknowledge and communicate any interference. |
| Precision (Within Run CV) | Comparable or better precision than predicate. | ||
| Normal Control Level | 7.9% @ 365 mg/dL | 4.5% @ 303 mg/dL | $\le$ 7.9% (ideally lower) |
| Low Fibrinogen Control Level | 7.7% @ 93 mg/dL | 5.1% @ 107 mg/dL | $\le$ 7.7% (ideally lower) |
| Linearity | 80 - 700 mg/dL | 35 - 1000 mg/dL | Expanded to 35 - 1000 mg/dL |
Note on FDP Interference: For FDP, the acceptance criteria are not to maintain "no interference" but rather to accurately characterize and communicate any newly identified interference. The modified parameters identified interference at FDP levels where the current parameters showed none (up to 100 µg/mL), leading to an update in the product insert.
2. Sample Size Used for the Test Set and Data Provenance
The document does not specify the exact sample sizes used for the test sets contributing to the performance data (interference, precision, and linearity).
The document does not explicitly state the data provenance (e.g., country of origin of the data, retrospective or prospective). However, given that this is a 510(k) submission for a medical device in the US, it is implied that the studies were conducted under appropriate regulatory guidelines, likely in the US, and typically involve prospective testing for performance characteristics.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This type of in vitro diagnostic (IVD) device (fibrinogen determination) does not typically involve "experts establishing ground truth" in the same way imaging or clinical diagnostic devices might. Instead, the "ground truth" for performance studies of IVD assays is established by:
- Reference Methods: For accuracy and linearity, the "ground truth" would be established by comparing the device's measurements to a known, highly accurate reference method or gravimetric/volumetric preparation of analytes.
- Known Concentrations: For precision studies, specific control levels (Normal, Low Fibrinogen) with known target concentrations are used.
- Spiked Samples: For interference studies, potentially interfering substances are added to samples at known concentrations.
Therefore, no information on the number or qualifications of "experts" for ground truth establishment is provided, as it's not applicable in the traditional sense for this kind of device.
4. Adjudication Method for the Test Set
Adjudication methods (like 2+1 or 3+1) are typically used for subjective assessments, such as interpreting medical images or clinical outcomes, where human expert consensus is needed. For an IVD device like HemosIL Fibrinogen-C, which provides quantitative measurements, formal adjudication by experts is not applicable. The measurements are objective and evaluated against established analytical performance metrics.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. MRMC studies are used to evaluate the diagnostic performance of devices (often imaging-based AI) when interpreted by multiple human readers, often comparing performance with and without AI assistance. This device is an in vitro diagnostic assay that produces a quantitative result, not an interpretation requiring human readers in the MRMC sense.
6. Standalone Performance (Algorithm Only)
Yes, a standalone performance assessment was effectively done. The performance data presented (interference, precision, linearity) directly reflects the capabilities of the HemosIL Fibrinogen-C reagent and the ACL TOP system's analytical process, independent of human interpretation or intervention beyond standard laboratory procedures for operating the instrument and running the assay. The "algorithm" here refers to the optimized test parameters, incubation time, and math model.
7. Type of Ground Truth Used
The type of ground truth for these studies would be based on:
- Analytical Measurement Standards: For linearity and accuracy, traceable reference materials or highly characterized plasma samples with known fibrinogen concentrations.
- Known Fibrinogen Concentrations: For precision, commercially prepared control materials with assigned target values.
- Spiked Interferent Concentrations: For interference studies, specific concentrations of potentially interfering substances (Heparin, Hemoglobin, Triglycerides, Bilirubin, FDP) added to plasma samples.
The document does not explicitly state the specific reference methods or standards used, but these are standard practices for IVD validation.
8. Sample Size for the Training Set
The document does not explicitly mention a "training set" or its sample size. For an IVD like HemosIL Fibrinogen-C, the "training" analogous to an AI model would be the development and optimization of the assay parameters, calibration levels, incubation time, and math model. This ongoing development process happens internally, often involving numerous experiments, but these are generally not characterized as a distinct "training set" in regulatory submissions, which focus on the final validation data.
9. How the Ground Truth for the Training Set Was Established
As with the "test set" ground truth, for the optimization/development (analogous to "training") phase of an IVD, the ground truth would be established through a combination of:
- Analytical Chemistry Principles: Ensuring the Clauss method is accurately implemented.
- Reference Materials: Using validated reference materials for calibration and early performance checks.
- Methodology Development: Iteratively testing and refining parameters (e.g., thrombin concentration, reaction time, dilution protocols, mathematical models) to achieve desired analytical performance characteristics (sensitivity, specificity, linearity, precision) against known standards and characterized samples.
The specific details of this internal development process for establishing ground truth are not provided in this 510(k) summary, which focuses on the final validation results.
§ 864.7340 Fibrinogen determination system.
(a)
Identification. A fibrinogen determination system is a device that consists of the instruments, reagents, standards, and controls used to determine the fibrinogen levels in disseminated intravascular coagulation (nonlocalized clotting within the blood vessels) and primary fibrinolysis (the dissolution of fibrin in a blood clot).(b)
Classification. Class II (special controls). A control or fibrinogen standard intended for use with a fibrinogen determination system is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.