(240 days)
VALIDATE® D-Dimer Calibration Verification / Linearity Test Kit solutions are an assayed quality control materials intended for in vitro diagnostic use in the quantitative determination of linearity, calibration verification and verification of reportable range for the following analyte: D-Dimer in a clinical laboratory setting by laboratory personnel. The product is intended for use with quantitative assays on the indicated analyzers specified in the labeling.
Each VALIDATE® D-Dimer Calibration Verification / Linearity Test Kit contains one analyte set of D-Dimer in a human plasma base matrix. The kit includes a set containing five liquid levels, 3.0 mL each. The set is provided to establish the relationship between theoretical and actual performance of the included analyte D-Dimer. Material of human origin used in the manufacture of this test kit was tested at the donor level using FDA approved methods and was found to be non-reactive for HBsAG and to antibodies to HCV and HIV-1/2.
The document describes the VALIDATE® D-Dimer Calibration Verification / Linearity Test Kit, an in vitro diagnostic device. Here's an analysis of its acceptance criteria and the study proving it:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are primarily focused on the precision/reproducibility and linearity of the device when used with specific instrumentation (IL TOP® instrument system).
| Aspect | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Precision | ≤ 10% CV for all kit levels on the IL TOP® instrument system | Achieved: All levels of the VALIDATE® D-Dimer kit met the acceptance criteria of ≤ 10% CV on the IL TOP® instrument system during the precision study. |
| Reproducibility | ≤ 10% CV for all kit levels on the IL TOP® instrument system | Achieved: All levels of the VALIDATE® D-Dimer kit met the acceptance criteria of ≤ 10% CV on the IL TOP® instrument system during the reproducibility study. |
| Stability (DOM) | 90 to 110% of DOM value for all levels | Achieved: Testing at specific intervals post manufacture showed all levels met the 90 to 110% of DOM value acceptance criteria. |
| Freeze-Thaw Vial Stability | 90 to 110% of control acceptance criteria after 6 freeze-thaw vial events (for a claim of 4 freeze-thaw events) | Achieved: All product levels tested within the 90 to 110% of control acceptance criteria limits after 6 freeze-thaw vial events. |
| Linearity | Product linearity performance demonstrated for the automated system | Achieved: Product linearity performance was demonstrated for the automated system (Instrumentation Laboratory TOP® instrument system). |
| Shelf Life | 9 months at -10 to -25°C | Established: Shelf life set at 9 months based on available real-time stability studies with three lots. Real-time studies are ongoing to support an extended claim. |
2. Sample Size Used for the Test Set and Data Provenance
- Precision Test Set:
- Sample Size: Eighty (80) replicates per kit level (for each of 5 levels). This means 5 levels * 80 replicates/level = 400 data points.
- Data Provenance: Not explicitly stated as retrospective or prospective, but the description of "tested over 20 days, 2 runs per day, 2 replicates per run" implies a prospective study. The data was generated using the VALIDATE® D-Dimer product, IL system HemosIL D-Dimer reagent, and TOP® instrument system.
- Reproducibility Test Set:
- Sample Size: Seventy-five (75) replicates per kit level (for each of 5 levels). This means 5 levels * 75 replicates/level = 375 data points.
- Data Provenance: Not explicitly stated as retrospective or prospective, but "tested over 5 days, with 1 run per day of Level 1-5, 5 replicates per run" implies a prospective study. Data was generated on three instruments, multi-site.
- Stability Test Set:
- Sample Size: Not explicitly stated, but includes "three lots" for both real-time shelf life and freeze-thaw studies.
- Data Provenance: Prospective ("study testing time points included date of manufacture (DOM), followed by testing at specific intervals post manufacture" and "Real time stability studies are ongoing").
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
Not applicable. This device is a calibration verification/linearity test kit, designed to verify the performance of an instrument, not to make a diagnostic interpretation requiring expert human judgment for a "ground truth" diagnosis. The "ground truth" in this context is the known, expected relationship (linearity and target recovery values) between the different levels of the kit, established by the manufacturer's formulation and scientific principles of dilution (EP6-A guidelines).
4. Adjudication Method for the Test Set
Not applicable, as human expert adjudication for diagnostic interpretation is not relevant for this type of device and its performance studies. The "adjudication" is based on predefined statistical acceptance criteria (e.g., %CV, % recovery range) applied to quantitative measurements.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study was not done. This type of study is typically performed for diagnostic devices where human readers interpret medical images or data, and AI assistance is evaluated for its impact on reader performance. This device is a quality control material for an automated instrument.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the performance studies (precision, reproducibility, linearity, stability) represent standalone performance of the device (test kit) when used with the specified automated instrument system. The device itself is not an "algorithm" in the typical sense of AI, but a reagent system. The studies demonstrate the performance of the kit on the instrument without human interpretive intervention beyond setting up the tests and reviewing the quantitative output.
7. The Type of Ground Truth Used
The ground truth used is based on:
- Known Concentration Relationships: The manufacturer states, "VALIDATE® D-Dimer Calibration Verification / Linearity Test Kits are manufactured such that an equal relationship exists among Levels 1 through 5; Level 1 being the lowest concentration and Level 5 being the highest." And, "Specific recovery targets for Levels 1 through 5 are determined by the upper and lower detection limits for D-Dimer. Intermediate Levels 2, 3, and 4 are subsequently prepared from Levels 1 and 5 by equal part dilutions following EP6-A guidelines."
- CLSI EP6-A guidelines: This clinical laboratory standard provides guidance on evaluating the linearity of quantitative measurement procedures, which is the basis for establishing the expected linear relationship.
- Established Target Ranges: For stability, acceptance criteria are defined as 90 to 110% of the date of manufacture (DOM) value, with DOM values themselves being established through rigorous testing.
8. The Sample Size for the Training Set
Not applicable. This device is a calibration verification/linearity test kit, not an AI or machine learning algorithm that requires a "training set." The product is manufactured to known specifications and then its performance is verified through testing.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" for this type of device. The ground truth for the device's inherent design and expected performance is established through controlled manufacturing processes, gravimetric/volumetric preparation, and adherence to accepted laboratory standards like CLSI EP6-A for linearity.
§ 864.5425 Multipurpose system for in vitro coagulation studies.
(a)
Identification. A multipurpose system for in vitro coagulation studies is a device consisting of one automated or semiautomated instrument and its associated reagents and controls. The system is used to perform a series of coagulation studies and coagulation factor assays.(b)
Classification. Class II (special controls). A control intended for use with a multipurpose system for in vitro coagulation studies is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 864.9.