(210 days)
HemosIL D-Dimer HS is an automated latex enhanced immunoassay for the quantitative determination of D-Dimer in human citrated plasma on the ACL TOP for use in conjunction with a clinical pretest probability (PTP) assessment model to exclude venous thromboembolism (VTE) in outpatients suspected of deep venous thrombosis (DVT) and pulmonary embolism (PE).
For in vitro diagnostic use.
The D-Dimer HS Latex Reagent is a suspension of polystyrene latex particles of uniform size coated with the F(ab')2 fragment of a monoclonal antibody highly specific for the D-Dimer domain included in fibrin soluble derivatives. The use of the F(ab')2 fragment allows a more specific D-Dimer detection avoiding the interference of some endogenous factors like the Rheumatoid Factor. When a plasma containing D-Dimer is mixed with the Latex Reagent and the Reaction Buffer included in the D-Dimer HS kit, the coated latex particles agglutinate. The degree of agglutination is directly proportional to the concentration of D-Dimer in the sample and is determined by measuring the decrease of the transmitted light caused by the aggregates (turbidimetric immunoassay).
This document is a 510(k) summary for the HemosIL D-Dimer HS device, which is an in vitro diagnostic (IVD) test. This specific submission (K160885) is a "Special 510(k)" to update the Limit of Detection (LoD) claim for the device.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Key Takeaway: The "device" in this context is an in vitro diagnostic assay (HemosIL D-Dimer HS) used to quantitatively determine D-Dimer levels in human plasma. The primary focus of this specific 510(k) submission is to update a performance claim, specifically the Limit of Detection (LoD), rather than introducing a new product or a significant change in intended use.
Given this, the questions provided in the prompt, which are commonly associated with AI/ML-driven medical imaging devices, need to be reinterpreted or noted as "not applicable" for this type of IVD 510(k) submission.
Acceptance Criteria and Reported Device Performance
The core acceptance criterion for this submission is the updated Limit of Detection (LoD). The device's performance is reported directly against this criterion.
1. Table of acceptance criteria and the reported device performance:
| Acceptance Criterion | Original Claim (Predicate) | Updated Claim (Proposed/Reported Performance) |
|---|---|---|
| Limit of Detection (LoD) | 21 ng/mL | 137 ng/mL |
Note: The submission states that the only change is to the LoD claim based on additional testing. All other performance claims (linearity, cut-off, etc.) remain the same as the predicate device.
Study Details (Reinterpreted for IVD Context)
Many of the points in the prompt are more relevant to AI/ML image analysis rather than an IVD assay. Where applicable, the information is provided. Where not applicable, it is noted.
2. Sample size used for the test set and the data provenance:
- Sample Size: The document states that the testing was "additional testing done to current CLSI EP17-A2 requirements" to establish the updated LoD. However, the specific number of samples (e.g., patient samples, spiked samples, replicates) used for this testing to calculate the LoD is not provided in this summary. CLSI EP17-A2 is a standard guideline for evaluation of detection capability for clinical laboratory measurement procedures. This guideline typically involves a statistically significant number of replicates (e.g., 20 or more) of blank/low-level samples across multiple runs.
- Data Provenance: The document does not specify the country of origin of the data or whether the study was retrospective or prospective. Given it's an in vitro diagnostic, samples would typically be analyzed fresh or from appropriately stored biobanks.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not Applicable in this context. For an IVD assay like D-Dimer, the "ground truth" for the test set is established by the known concentrations of calibrators and controls, or by reference methods/materials of traceable value (e.g., a known concentration of D-Dimer in a sample matrix). It does not involve human expert interpretation in the same way an imaging study would.
4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not Applicable. This concept is for diagnostic interpretation, typically by human readers, not for quantitative analytical performance of an IVD assay.
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 is an IVD assay, not an AI-assisted diagnostic imaging system. Its performance is measured analytically (e.g., precision, accuracy, LoD, linearity) against known values or reference methods, not against human reader performance.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, in the context of an IVD. The HemosIL D-Dimer HS device is an automated, standalone assay run on ACL TOP instruments. Its performance (e.g., LoD) is determined analytically by the instrument and reagents, independent of human interpretive input. Human operators load samples and reagents, and review results, but the analytical measurement itself is automated.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- For an analytical performance evaluation like Limit of Detection, the ground truth is established based on statistical analysis of replicate measurements of samples with very low (or zero) analyte concentration. This would involve:
- Defined Calibrators: Solutions with known, precise concentrations of D-Dimer.
- Controls: Materials with target D-Dimer concentrations used for quality control.
- Reference Materials/Methods: Comparison to a highly accurate reference method or certified reference materials, if available, though for LoD, it's more about statistical confidence in detecting low levels.
- Statistical Methods: LoD is determined using statistical approaches defined by guidelines like CLSI EP17-A2, which typically involves measuring blank samples and low-level samples and calculating the concentration at which detection is statistically reliable. This does not involve "expert consensus" in the clinical diagnostic sense.
8. The sample size for the training set:
- Not Applicable in the AI/ML sense. This is not an AI/ML algorithm that requires a "training set." The assay is a chemical and immunoturbidimetric reaction. The development of such an assay involves extensive R&D and optimization, but not typically a "training set" in the machine learning paradigm.
9. How the ground truth for the training set was established:
- Not Applicable. See point 8. The "ground truth" for developing the assay itself involves ensuring the reagents specifically bind to D-Dimer and that the turbidimetric measurement accurately correlates with its concentration. This is achieved through chemical and biological validation, not through annotated training data.
§ 864.7320 Fibrinogen/fibrin degradation products assay.
(a)
Identification. A fibrinogen/fibrin degradation products assay is a device used to detect and measure fibrinogen degradation products and fibrin degradation products (protein fragments produced by the enzymatic action of plasmin on fibrinogen and fibrin) as an aid in detecting the presence and degree of intravascular coagulation and fibrinolysis (the dissolution of the fibrin in a blood clot) and in monitoring therapy for disseminated intravascular coagulation (nonlocalized clotting in the blood vessels).(b)
Classification. Class II (performance standards).