(280 days)
DiaSys Procalcitonin FS assay is a particle enhanced immunoturbidimetric test intended for the quantitative in vitro determination of procalcitonin (PCT) in human serum and lithium heparin plasma on automated Abbott ARCHITECT c8000 analyzer.
Measurement of PCT in conjunction with other laboratory findings and clinical assessments aids in the risk assessment of critically ill patients on their first day of Intensive Care Unit (ICU) admission for progression to severe sepsis and septic shock.
The TruCal Procalcitonin Calibrator Set is intended for in vitro use for calibration of the DiaSys Procalcitonin FS assay.
TruLab Procalcitonin Bi-Level Controls are an assayed quality control material for monitoring the performance of quantitative in vitro determination of Procalcitonin (PCT) for the DiaSys Procalcitonin FS assay.
For in vitro diagnostic use only.
The DiaSys Procalcitonin FS assay is a particle enhanced turbidimetric immunoassay (PETIA) test for in vitro quantitative determination of procalcitonin (PCT) levels in human serum and lithium heparin plasma on automated photometric systems.
The test utilizes anti-human PCT polyclonal antibodies (goat) covalently bound to polystyrene particles.
PCT in the sample binds to the anti-PCT antibodies on the particles and causes agglutination. The degree of the turbidity caused by agglutination is optically measured at 660 nm by the automated photometric system and is proportional to the amount of PCT in the sample. DiaSys Procalcitonin FS Reagent specifies settings for an automated photometric analyzer, the Abbott ARCHITECT c8000.
The DiaSys TruCal Procalcitonin Calibrator Set is provided in 6 levels, traceable to a commercial assay for use in the calibration of the DiaSys Procalcitonin FS assay.
The DiaSys TruLab Procalcitonin Bi-Level Controls, Levels 1 (low) and 2 (high) are intended for use as quality control for the DiaSys Procalcitonin FS assay.
DiaSys PCT Calibrators and Bi-Level Controls are ready-to-use, stable, aqueous solutions containing recombinant human full-length PCT and biological additives from bovine origin.
Here's a breakdown of the acceptance criteria and study information for the DiaSys Procalcitonin FS assay, extracted and organized from the provided FDA 510(k) clearance letter:
Acceptance Criteria and Reported Device Performance
| Test | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Precision/Reproducibility | ||
| Total Precision (Serum) | CV ≤ 10% (0.2-1.0 ng/mL) | |
| CV ≤ 7% (1.0-3.0 ng/mL) | ||
| CV ≤ 5% (3.0-20 ng/mL) | Met: | |
| 0.2-1.0 ng/mL: 5.64% | ||
| 1.0-3.0 ng/mL: 2.34% | ||
| 3.0-20 ng/mL: 1.93% | ||
| Total Precision (Plasma) | CV ≤ 10% (0.2-1.0 ng/mL) | |
| CV ≤ 7% (1.0-3.0 ng/mL) | ||
| CV ≤ 5% (3.0-20 ng/mL) | Met: | |
| 0.2-1.0 ng/mL: 8.31% | ||
| 1.0-3.0 ng/mL: 3.24% | ||
| 3.0-20 ng/mL: 2.61% | ||
| Within-run Precision (Serum) | CV ≤ 10% (0.2 ng/mL range) | |
| CV ≤ 7% (1.0-3.0 ng/mL range) | ||
| CV ≤ 5% (3.0-20 ng/mL range) | Met (except for LoQ proximity): | |
| 0.252 ng/mL: 16.62% (Determined acceptable given proximity to LoQ) | ||
| 0.555 ng/mL: 3.89% | ||
| 2.02 ng/mL: 2.78% | ||
| 9.68 ng/mL: 2.24% | ||
| 18.8 ng/mL: 2.16% | ||
| Within-run Precision (Plasma) | CV ≤ 10% (0.2 ng/mL range) | |
| CV ≤ 7% (1.0-3.0 ng/mL range) | ||
| CV ≤ 5% (3.0-20 ng/mL range) | Met: | |
| 0.314 ng/mL: 8.00% | ||
| 0.475 ng/mL: 6.94% | ||
| 1.910 ng/mL: 2.93% | ||
| 9.851 ng/mL: 1.94% | ||
| 17.953 ng/mL: 1.96% | ||
| Linearity/Assay Reportable Range | Linearity 5 ng/mL: ± 10% | Met (Human serum and plasma evaluations) |
| Detection Limits | LoB ≤ 0.2 ng/mL | |
| LoQ ≤ 0.5 ng/mL | Met: | |
| Limit of Blank (LOB): 0.081 ng/mL | ||
| Limit of Quantitation (LOQ): 0.23 ng/mL (with %CV ≤ 20%) | ||
| Interference | No significant interference (shift in PCT concentration > ±15%) | Met: (No significant interference observed for substances tested at specified concentrations, including Ascorbic acid, Bilirubin, Lipemia, HAMA, Rheumatoid factor, Hemolysis, and various drugs. N-Terminus interferes.) |
| Stability (Reagent) | ||
| Real-time Stability | 24 months stability | Confirmed: 25 months stability from date of production. |
| In-use Stability | 24 months stability | Confirmed: At least 25 months stability after opening. |
| Specimen Stability | Within ± 15% of concentration at time zero | |
| Slope of regression line within ± 10% | Met: for 24 hours at 20-25°C, 5 days at 2-8°C, and 14 days at -20°C (for both serum and plasma, and measurements >10% over specified durations). | |
| Freeze-Thaw Cycle (2 cycles) | Within 15% of concentration at time zero | Met: for both serum and plasma samples after one and two freeze-thaw cycles. |
| Hook Effect (Prozone) | No hook/prozone effect | Confirmed: No hook/prozone effect up to 1000 ng/mL. |
| Method Comparison (Study 1, 2021) | Slope: 0.85 – 1.15 | |
| Intercept: ± 1.0 ng/mL | ||
| Correlation coefficient R: ≥ 0.95 | ||
| n ≥ 100 | Met: | |
| N = 120 | ||
| Slope = 1.08 | ||
| Intercept = 0.105 ng/mL | ||
| R = 0.991 | ||
| PCT Cutoff 0.5 ng/mL: NPA 93.9%, PPA 100% | ||
| PCT Cutoff 2.0 ng/mL: NPA 93.3%, PPA 97.8% | ||
| Method Comparison (Study 2, 2025) | Slope: 0.85 – 1.15 | |
| Intercept: ± 1.0 ng/mL | ||
| Correlation coefficient R: ≥ 0.95 | ||
| n ≥ 100 | Met: | |
| N = 210 | ||
| Slope = 0.940 | ||
| Intercept = 0.017 ng/mL | ||
| R = 0.965 | ||
| PCT Cutoff 0.5 ng/mL: NPA 98%, PPA 100% | ||
| PCT Cutoff 2.0 ng/mL: NPA 100%, PPA 94% | ||
| Matrix Comparison | Slope: 0.85 – 1.15 | |
| Intercept: ± 1.0 ng/mL | ||
| Correlation coefficient R ≥ 0.98 | ||
| n ≥ 20 | Met: (Human serum vs. lithium heparin plasma, for at least 20 native patient samples) |
Study Details:
-
Sample Size used for the test set and the data provenance:
- Precision/Reproducibility (Total Precision): 3 human serum samples, 3 human plasma samples.
- Precision/Reproducibility (Within-run Precision): 5 human serum samples, 5 human plasma samples.
- Linearity/Assay Reportable Range: Stock solutions assayed in quadruplicate.
- Detection Limits (LOB, LOD, LOQ): Evaluated in human serum and plasma.
- Interference: Human samples at approximate PCT concentrations of 0.5 and 2.0 ng/mL.
- Specimen Stability: 15 human samples (serum and lithium heparin plasma).
- Freeze-Thaw Cycle Stability: 15 human samples (serum and plasma).
- Method Comparison (Study 1): 120 native patient samples.
- Method Comparison (Study 2): 210 native patient samples.
- Matrix Comparison: At least 20 native patient samples (serum and lithium heparin plasma).
- Data Provenance: Not explicitly stated as retrospective or prospective, nor country of origin for patient/human samples. The nature of "native patient samples" generally implies retrospective analysis of collected clinical samples, but this is not definitively stated.
-
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable for this type of in vitro diagnostic device (analyte measurement). The "ground truth" for the test set samples is typically established by reference methods or established values/concentrations for controls/calibrators, rather than expert clinical consensus.
-
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable. This is an assay for quantitative measurement of an analyte. "Adjudication" typically refers to the process of multiple readers/experts reviewing images or clinical cases.
-
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:
- No. This is an in vitro diagnostic assay, not an AI-assisted diagnostic imaging or clinical decision support system. The comparison studies are against a predicate device (another PCT assay), not human readers.
-
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, the performance listed in the table effectively represents the standalone performance of the DiaSys Procalcitonin FS assay when run on the automated Abbott ARCHITECT c8000 analyzer, without human intervention in the result generation itself. The results are quantitative measurements of the Procalcitonin analyte.
-
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Analytical Performance: Ground truth is based on known concentrations of analytes in controls and calibrators, and comparative measurements against a legally marketed predicate device (VIDAS B.R.A.H.M.S. PCT ASSAY, K071146).
- Clinical Efficacy/Impact: The device aids in risk assessment of critically ill patients for progression to severe sepsis and septic shock, "in conjunction with other laboratory findings and clinical assessments." This implies that the actual clinical "ground truth" (e.g., diagnosis of severe sepsis or septic shock, patient outcome) relies on a broader clinical picture, not solely on the PCT measurement. The study primarily focuses on analytical equivalence, not a direct measure of clinical outcomeprediction compared to a gold standard outcome.
-
The sample size for the training set:
- The document primarily describes validation and verification studies for the device's analytical performance and equivalence to a predicate. It does not mention a "training set" in the context of machine learning or AI algorithm development, as this device appears to be a traditional IVD assay.
-
How the ground truth for the training set was established:
- Not applicable, as there is no apparent "training set" in the machine learning sense. The device is a chemical reagent-based assay.
§ 866.3215 Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis.
(a)
Identification. A device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis is identified as an in vitro device intended for the detection and qualitative and/or quantitative measurement of one or more non-microbial analytes in human clinical specimens to aid in the assessment of patients with suspected sepsis when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include the device's detailed Indications for Use statement describing what the device detects and measures, the results provided to the user, whether the measure is qualitative and/or quantitative, the clinical indications for which the test is to be used, and the specific population(s) for which the device use is intended.
(2) Premarket notification submissions must include detailed documentation of the device description, including (as applicable), all device components, software, ancillary reagents required but not provided, explanation of the device principle and methodology, and for molecular devices include detailed documentation of the primer/probe sequence, design, and rationale for sequence selection.
(3) Premarket notification submissions must include detailed documentation of applicable analytical studies, such as, analytical sensitivity (Limit of Detection, Limit of Blank, and Limit of Quantitation), precision, reproducibility, analytical measuring range, interference, cross-reactivity, and specimen stability.
(4) Premarket notification submissions must include detailed documentation of a prospective clinical study or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information:
(i) Results must demonstrate adequate device performance relative to a well-accepted comparator.
(ii) Clinical sample results must demonstrate consistency of device output throughout the device measuring range likely to be encountered in the Intended Use population.
(iii) Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the Indications for Use(s), and results of all statistical analyses.
(5) Premarket notification submissions must include evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics (
e.g., age, racial, ethnic, and gender distribution) similar to the Intended Use population.(6) As part of the risk management activities performed under 21 CFR 820.30 design controls, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument.
(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling, and a detailed explanation of the interpretation of the limitations of the samples (
e.g., collected on day of diagnosis) must be included in the device's 21 CFR 809.10(b)(10) compliant labeling.