(210 days)
The Access PCT assay is a paramagnetic, chemiluminescent immunoassay for in vitro quantitative determination of procalcitonin (PCT) levels in human serum and plasma (lithium heparin and EDTA) using the Access Immunoassay Systems. 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 Access PCT assay is a paramaqnetic, chemiluminescent immunoassay for in vitro quantitative determination of procalcitonin (PCT) levels in human serum and plasma (lithium heparin and EDTA) using the Access Immunoassay Systems. 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. A description of the reagent pack is provided below.
- R1a: Dynabeads* paramagnetic particles coated with mouse anti-. human Procalcitonin monoclonal antibody in a TRIS buffer with surfactant, protein (bovine), ≤ 0.1% sodium azide, and 0.1% ProClin**300
- R1b: 0.10 N Sodium Hydroxide ●
- R1c: MOPS Buffer with surfactant and protein (bovine, murine), ≤ ● 0.1 % sodium azide, and 0.1% ProClin 300
- R1d: Rat anti-Procalcitonin recombinant alkaline phosphatase . coniugate in a MOPS buffer with surfactant and protein (bovine, murine, recombinant).
≤ 0.1% sodium azide, and 0.1% ProClin 300
The device in question is the Access PCT Assay for the Dxl 9000 Access Immunoassay Analyzer, used for the in vitro quantitative determination of procalcitonin (PCT) levels. The study presented aims to demonstrate its substantial equivalence to the previously cleared Access PCT Assay on the Access 2 Immunoassay System (K192271).
Here's a breakdown of the acceptance criteria and study details:
1. Table of Acceptance Criteria and Reported Device Performance
| Test/Characteristic | Acceptance Criteria (New Device) | Reported Device Performance (New Device - Access PCT on Dxl 9000) |
|---|---|---|
| Method Comparison | ||
| (vs. Predicate Access PCT on Access 2) | R² ≥ 0.95 | R² ≥ 0.95 (Met) |
| Slope | 1.00 ± 0.10 | 1.00 ± 0.10 (Met) |
| Method Concordance (at 0.5 ng/mL cutoff) | Not explicitly stated | 100.0% |
| Method Concordance (at 2.0 ng/mL cutoff) | Not explicitly stated | 98.3% |
| Imprecision (Within Laboratory) | SD ≤ 0.012 ng/mL for PCT 0.150 ng/mL | Met |
| Limit of Blank (LoB) | ≤ 0.005 ng/mL | 0.002 ng/mL (Met) |
| Limit of Detection (LoD) | ≤ 0.01 ng/mL | 0.003 ng/mL (Met) |
| Limit of Quantitation (LoQ) | ≤ 0.02 ng/mL (20% CV) | 0.002 ng/mL (reported as 0.003 ng/mL to align with LoD per CLSI EP17-A2 recommendation, Met) |
2. Sample Size and Data Provenance
The document does not explicitly state the specific sample sizes used for each test (e.g., method comparison, imprecision, linearity). It also does not specify the country of origin of the data or whether the data was retrospective or prospective. It states "The study" for imprecision and linearity, suggesting a single study per characteristic. The "Method Comparison" and "Method Concordance" imply patient samples were used to compare results between the new device and the predicate.
3. Number of Experts and Qualifications for Ground Truth
Not applicable. This device is an in vitro diagnostic immunoassay measuring procalcitonin levels. Ground truth is established through analytical validation and comparison to an established predicate device, not through expert review of interpretations.
4. Adjudication Method
Not applicable. As this is an analytical performance study for an immunoassay, adjudication methods typically used for qualitative or imaging-based diagnostics by human readers are not relevant.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, an MRMC comparative effectiveness study was not done. This type of study is typically performed for AI-powered diagnostic tools where human interpretation is involved. The Access PCT assay is an automated immunoassay.
6. Standalone Performance (Algorithm Only without Human-in-the-Loop)
Yes, the studies described represent the standalone performance of the Access PCT assay on the Dxl 9000 Analyzer. The tests (method comparison, imprecision, linearity, LoB, LoD, LoQ) evaluate the analytical performance of the device itself, independent of human interpretation or interaction beyond standard laboratory procedures.
7. Type of Ground Truth Used
The ground truth or reference for comparison in this submission is the measurements obtained from the previously cleared Access PCT assay on the Access 2 Immunoassay System (K192271). For analytical precision, linearity, and limits of detection/quantitation, the "ground truth" is defined by established analytical methods and statistical calculations following guidelines like CLSI EP17-A2.
8. Sample Size for the Training Set
Not applicable. This device is an immunoassay, not an AI/Machine Learning algorithm that undergoes a "training" phase with a specific dataset. Its performance is based on the chemical and biological reactions designed within the assay.
9. How Ground Truth for the Training Set was Established
Not applicable, as there is no "training set" in the context of this immunoassay. The development of the assay involves optimization of reagents and protocols, but not in the sense of supervised learning from a labeled dataset. The reference for comparison is the predicate device's performance.
§ 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.