(207 days)
The Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) assay is an in vitro diagnostic test for the quantitative measurement of procalcitonin in human serum and plasma (lithium heparin, K2EDTA, and K3EDTA) using the Dimension® EXL™ integrated chemistry system with LOCI® Module.
The Dimension EXL LOCI® BRAHMS PCT assay is intended for use in conjunction with other laboratory findings and clinical assessments, as an aid 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.
• Assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsis or septic shock in the ICU or when obtained in the emergency department or other medical wards prior to ICU admission using percentage change in PCT levels over time.
· Decision making on antibiotic therapy for patients with suspected or confirmed lower respiratory tract infections (LRTI) - defined as community-acquired pneumonia (CAP), acute bronchitis, and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) - in an inpatient setting or an emergency department.
· Decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.
The Dimension EXL LOCI BRAHMS PCT assay is a homogeneous sandwich chemiluminescent immunoassay based on LOCI technology. The LOCI reagents include two synthetic bead reagents and one biotinylated anti-procalcitonin (anti-PCT) monoclonal antibody. The first bead reagent (Sensibeads) is coated with streptavidin and contains photosensitizer dye. The second bead reagent (Chemibeads) is coated with two anti-PCT monoclonal antibodies and contains chemiluminescent dye. Sample is incubated with biotinylated antibody and Chemibeads to form bead-PCT-biotinylated antibody sandwiches. Sensibeads are added and bind to the biotin to form bead-pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from Sensibeads which diffuses into the Chemibeads, triggering a chemiluminescent reaction. The resulting signal is measured at 612 nm and is a direct function of the procalcitonin (PCT) concentration in the sample.
The provided document describes the performance characteristics of the Dimension® EXL™ LOCI® BRAHMS Procalcitonin (PCT) assay and its equivalence to a predicate device.
Here's a breakdown of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance |
|---|---|---|
| Precision | Within-lab %CV: ≤ 10.0% for QC1, QC2, QC3, Serum 2, 3, 4, 5; ≤ 15.0% for Plasma, Serum 1. | Lot FB1218: QC1 (4.3%), QC2 (2.2%), QC3 (2.5%), Plasma (4.0%), Serum 1 (4.0%), Serum 2 (2.7%), Serum 3 (2.0%), Serum 4 (1.5%), Serum 5 (2.7%). All Pass. |
| Lot FC1218: QC1 (3.3%), QC2 (4.2%), QC3 (2.6%), Plasma (4.0%), Serum 1 (3.0%), Serum 2 (2.7%), Serum 3 (2.7%), Serum 4 (2.1%), Serum 5 (2.3%). All Pass. | ||
| Total %CV: ≤ 10.0% for QC1, QC2, QC3, Serum 2, 3, 4, 5; ≤ 15.0% for Plasma, Serum 1. | Lot FB1218: QC1 (7.1%), QC2 (3.5%), QC3 (3.2%), Plasma (6.0%), Serum 1 (5.0%), Serum 2 (4.1%), Serum 3 (2.7%), Serum 4 (3.0%), Serum 5 (5.5%). All Pass. | |
| Lot FC1218: QC1 (6.2%), QC2 (4.5%), QC3 (3.2%), Plasma (6.0%), Serum 1 (6.0%), Serum 2 (3.6%), Serum 3 (3.2%), Serum 4 (3.1%), Serum 5 (5.8%). All Pass. | ||
| Reproducibility | Total Reproducibility (CV%) for various PCT levels. (No explicit criteria mentioned in the document, but results are provided indicating good reproducibility). | MDP1 (0.10 ng/mL): 7.0%, MDP2 (0.25 ng/mL): 4.4%, MDP3 (0.48 ng/mL): 3.8%, MDP4 (1.95 ng/mL): 3.8%, MDP5 (8.94 ng/mL): 4.2%, MDP6 (41.01 ng/mL): 9.3%. |
| Detection Capability | LoB 10% interference at >1200 ng/mL. HAMA >10% interference at 32.5 mg/mL (HAMA 1) and 65.0 mg/mL (HAMA 1 and 2), Total Protein >10% interference at 15.0 g/dL. | Biotin: >10% interference at 1500 ng/mL (-19% bias at 1.88 ng/mL PCT) and 3510 ng/mL (-26% to -29% bias). HAMA 1: -10% to -12% bias at 65.0 mg/mL and -11% to -12% bias at 32.5 mg/mL. HAMA 2: -14% to -13% bias at 65.0 mg/mL and -11% bias at 32.5 mg/mL (at 2.19 ng/mL PCT). Total Protein: -18% bias at 15.0 g/dL. These led to specific labeling cautions. |
| Cross-Reactivity | No explicit criterion provided, only results of testing. | No significant cross-reactivity observed with Calcitonin (Human, Eel, Salmon), Katacalcin (Human), α-CGRP, and β-CGRP. For example, Human Calcitonin at 8 ng/mL showed 0.00% to -0.50% cross-reactivity. |
| Hook Effect | No hook effect for PCT concentrations up to 2000.00 ng/mL. | For patient specimens with PCT concentrations between 50.00 ng/mL and 2000.00 ng/mL the assay will report results as "Above Assay Range" (> 50.00 ng/mL). |
| Sample Carryover | No sample carryover from high to low samples. | Calculated to be 0.00 ng/mL. No sample carryover observed. |
| Method Comparison | Strong correlation (r), passing Deming/Passing-Bablok regression, high percentage agreement at clinical cutoffs with predicate device. | Measuring Interval (0.05-50.00 ng/mL): |
| Lot FB1218: r = 0.958, Slopes 1.07, Intercepts -0.01. | ||
| Lot FC1218: r = 0.963, Slopes 1.04, Intercepts 0.00 to -0.01. | ||
| Positive % agreement: 96.1-97.8%, Negative % agreement: 89.1-97.5%, Overall % agreement: 95.9-97.5% across various cut-offs (0.10, 0.25, 0.50, 2.00 ng/mL). | ||
| Extended Measuring Interval (0.05-1000.00 ng/mL): | ||
| Lot FB1218: r = 0.988, Slopes 1.08, Intercepts -0.01. | ||
| Lot FC1218: r = 0.991, Slopes 1.05, Intercepts 0.00 to -0.01. | ||
| Positive % agreement: 96.5-98.0%, Negative % agreement: 89.1-97.5%, Overall % agreement: 96.1-97.6% across various cut-offs. These results demonstrate substantial equivalence to the predicate device. | ||
| Matrix Comparison | No significant difference based on Passing-Bablok regression analysis between serum and plasma samples. | All specimen types (Serum (SST), Serum (RST), Lithium Heparin plasma, Sodium Heparin plasma, K2EDTA plasma, and K3EDTA plasma) showed high correlation coefficients (0.996-0.998) and regression equations close to y=x (slopes around 0.98-1.00, intercepts around 0.00-0.01 ng/mL) when compared to Serum (SST), indicating no significant difference. |
| Reference Interval Verification | Reference interval claim of |
§ 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.