(163 days)
HemosIL Factor VIII deficient plasma is human plasma, depleted of Factor VIII, which is intended for the in vitro diagnostic quantitative determination of Factor VIII activity in citrated plasma, based on the activated partial thromboplastin time (APTT) assay, on the ACL TOP® Family analyzers. HemosIL Factor VIII deficient plasma is indicated for use on patients who are suspected of congenital or acquired deficiency based on the activated partial thromboplastin time (APTT) assay results.
The assay determines the functional activity of Factor VIII by measuring the degree of prolongation of activated partial thromboplastin time in the presence of a contact activator, thromboplastin, phospholipids and calcium ions. Factor VIII activity is correlated with the prolongation of the clotting time of the Factor VIII deficient plasma to which diluted patient sample has been added.
Here's a breakdown of the requested information based on the provided text, focusing on the acceptance criteria and the study that proves the device meets them:
Acceptance Criteria and Device Performance
1. Table of Acceptance Criteria and Reported Device Performance
The provided document primarily details performance characteristics rather than explicit "acceptance criteria" for regulatory approval in every instance. However, it implicitly defines satisfactory performance through comparisons to the predicate device and established linearity/precision targets. Due to the nature of the submission (Reagent formulation change), the primary acceptance criterion is demonstrating comparable performance to the predicate device.
| Performance Metric | Acceptance Criteria (Implicit/Explicit) | Reported Device Performance |
|---|---|---|
| Precision (CV%) | Within acceptable limits for diagnostic assays (not explicitly stated as a numerical target in this summary, but typical for CLSI EP05-A2). The predicate device's performance would serve as the benchmark. | Within Run CV%: 3.7 - 4.1% (ACL TOP 500 CTS) |
| Total CV%: 3.9 - 6.4% (ACL TOP 500 CTS) | ||
| (These values are for various control levels with SynthASil reagent and a representative instrument/lot). | ||
| Linearity (R², Slope, Intercept) | R² close to 1.0, slope close to 1.0, and intercept close to 0.0, indicating proportional response across the analytical range. | R²: 0.995 - 0.998 |
| Slope: 0.964 - 1.045 | ||
| Intercept: -1.621 - 2.261 | ||
| (Demonstrated linearity for activities up to 150% for both reagent lots and ACL TOP Family instruments). | ||
| Analytical Range | Defined operational range for Factor VIII activity. | 0.1 - 150% (with SynthASil) |
| 0.5 - 150% (with APTT-SP) | ||
| Interference | No significant interference from common interferents at specified concentrations (e.g., hemoglobin, triglycerides, bilirubin, FVIII inhibitors, Lupus anticoagulant antibodies). | No effect from hemoglobin up to 530 mg/dL, triglycerides up to 2000 mg/dL, bilirubin up to 150 mg/dL, Factor VIII inhibitors up to 0.1BU, and Lupus anticoagulant antibodies. |
| Method Comparison (In-House) | Slope: Close to 1.0 | |
| Correlation Coefficient (R): Close to 1.0 (indicating strong agreement with the predicate device). "Satisfy the product specifications for method comparison and demonstrate comparable performance." | With SynthASil: Slope: 1.064 (ACL TOP), 1.112 (ACL TOP 500 CTS); R: 0.9885 (ACL TOP), 0.9923 (ACL TOP 500 CTS) | |
| With APTT-SP: Slope: 0.893 (ACL TOP), 0.913 (ACL TOP 500 CTS); R: 0.9884 (ACL TOP), 0.9926 (ACL TOP 500 CTS) | ||
| Conclusion: Satisfies product specifications and demonstrates comparable performance. | ||
| Method Comparison (Field Site) | Slope: Close to 1.0 | |
| Correlation Coefficient (R): >0.98 | ||
| "Statistically similar performance to the predicate device." | Slope: 0.871 - 1.138 | |
| Correlation Coefficient (R): >0.9829 | ||
| Conclusion: Performance is statistically similar. | ||
| Stability/Shelf Life | Demonstrated shelf life under specified storage conditions. The claimed shelf life would need to be supported by stability data. | 12 months when stored at 2-8°C (based on accelerated stability, real-time ongoing). |
2. Sample Sizes Used for the Test Set and Data Provenance
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Precision Study:
- Sample Size: 80 replicates per instrument/lot per control level (e.g., 4 control levels x 3 lots x 3 instruments x 80 = 2880 individual measurements if all were run, but data is shown for one representative instrument/reagent/lot).
- Data Provenance: Not explicitly stated, but clinical laboratory samples (normal and abnormal types) were used. Implied to be prospective within the context of the study design (20 days, 2 runs/day, 2 replicates/run). Country of origin is not specified, but the applicant is US-based.
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Linearity Study:
- Sample Size: 4 replicates for each Factor VIII sample level.
- Data Provenance: Not explicitly stated, but generated in-house using prepared Factor VIII samples ranging from 150%. Implied prospective within the study.
-
Interference Study:
- Sample Size: Not specified, but involved testing samples spiked with various interferents.
- Data Provenance: Not specified, likely in-house laboratory testing, prospective.
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In-House Method Comparison Study:
- Sample Size: Not explicitly stated for the regression analysis. The table shows 'N' for the ACL TOP 500 CTS as 90 (likely 90 samples tested).
- Data Provenance: "In-House Study," likely prospective laboratory testing.
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Field Site Study:
- Sample Size:
- OUS site: n = 109
- US #1 site: n = 125
- US #2 site: n = 102
- Data Provenance: Conducted at "2 US sites and one OUS site." The document states "Both normal and abnormal samples were tested." Implied prospective testing at these sites.
- Sample Size:
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This device is an in vitro diagnostic reagent kit for quantitative determination of Factor VIII activity. The "ground truth" for Factor VIII activity in the test samples is typically established by assigned values from reference materials or by established laboratory methods using calibrated instruments, not by expert human interpretation like in imaging or pathology. The document mentions "assigned values" for the HemosIL Calibration plasma (for calibration curves) and "assigned values" for samples in the linearity study, but does not detail how these assignments were made in terms of human experts. It's a quantitative chemical assay, where "ground truth" is analytical, not based on expert consensus for a "reading."
4. Adjudication Method for the Test Set
Not applicable. This is a quantitative diagnostic assay, not a diagnostic imaging or pathology device where human interpretation and adjudication would be typically required for a "test set" in the sense of establishing truth for diagnostic accuracy. The performance is assessed against known or assigned values for Factor VIII activity.
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 device is a diagnostic reagent, not an AI-powered diagnostic aid for human readers. It functions as a standalone laboratory test.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes. This device (HemosIL Factor VIII deficient plasma) is a reagent used in an automated assay on ACL TOP Family analyzers. Its performance characteristics (precision, linearity, interference, method comparison) are evaluated as a standalone component of the in vitro diagnostic system, independent of direct human interpretive "reading" of the results in the same way an imaging device would be read. The "performance" described is the analytical performance of the reagent used with the specified instruments.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
For the analytical studies (precision, linearity, method comparison), the "ground truth" is based on:
- Reference materials/assigned values: HemosIL Calibration plasma values are assigned for Factor VIII Activity and used to calibrate the standard curve. In the linearity study, samples had "assigned values."
- Established methods: The predicate device itself serves as the "truth" for comparative purposes in the method comparison studies.
- Known concentrations: For interference studies, samples are spiked with known concentrations of interferents.
This is primarily an analytical ground truth derived from laboratory standards, calibrated materials, and established predicate device performance.
8. The Sample Size for the Training Set
Not applicable. This is an IVD reagent, not a machine learning or AI-based device that requires a "training set" in the context of algorithm development. The reagent itself does not learn or get "trained."
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" for this type of device.
§ 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).