(93 days)
The Lumipulse G B•R•A•H•M•S PCT is a Chemiluminescent Enzyme Immunoassay (CLEIA) for the quantitative determination of PCT (procalcitonin) in human serum and plasma (sodium heparin, sodium citrate or dipotassium EDTA) on the LUMIPULSE G System.
Used in conjunction with other laboratory findings and clinical assessments, Lumipulse G B.R.A.H.M.S PCT is intended for use 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.
· Aid in 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 a change in PCT level over time.
· Aid in 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.
· Aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.
Lumipulse G B.R.A.H.M.S PCT Calibrators set
Lumipulse G B R A H M S PCT Calibrators set is for in vitro diagnostic use in the calibration of Lumipulse G B.R.A.H.M.S.PCT on the LUMIPULSE G System.
Lumipulse G B+R•A•H•M•S PCT is an assay system, including a set of immunoassay reagents, for the quantitative measurement of PCT in specimens based on CLEIA technology by a two-step sandwich immunoassay method on the LUMIPULSE G1200 System.
Lumipulse G B.R.A.H.M.S PCT Immunoreaction Cartridges: | IRC 235058. The Lumipulse G B•R•A•H•M•S PCT Immunoreaction Cartridges consists of 3 x 14 tests. Each kit contains the following:
1.) Antibody-Coated Particle Solution (Liquid when used, 250 µL/Immunoreaction Cartridge) Contains 150 µg/mL anti-PCT monoclonal antibody (mouse) and anti-calcitonin monoclonal antibody (mouse) coated particles, protein stabilizers (bovine and mouse) and chemical stabilizers in 0.15 M sodium chloride/Tris buffer. This solution contains gelatin and turns into gel at 15°C or lower. Preservative: sodium azide.
2.) Enzyme-Labeled Antibody Solution (Liquid, 350 µL/Immunoreaction Cartridge) Contains 0.25 µg/mL alkaline phosphatase (ALP: calf)-labeled anti-katacalcin monoclonal antibody (mouse), protein stabilizers (bovine, calf and mouse) and chemical stabilizers in 0.1 M sodium chloride/MES buffer. Preservative: sodium azide.
Lumipulse G B+R+A+H+M+S PCT Calibrators set |CAL SET 234150, Lyophilized, 2 x 2 Concentrations
Each calibrator kit contains one bottle each of Calibrators 1 - 2, and Reconstituting Solution. The calibrator kit is packaged separately.
CAL 1 0 ng/mL PCT calibrator (2 x 0.5 mL/vial)
CAL 2 100 ng/mL PCT calibrator (2 x 0.5 mL/vial)
Contains procalcitonin in 0.15 M sodium chloride in Tris buffer with protein stabilizer (bovine). Preservative: ProClin 300.
RS Reconstituting Solution: Liquid, 1 x 10 mL Preservative: sodium azide.
These calibrators are lyophilized and have to be prepared by adding exactly 0.5 mL of Reconstituting Solution to each Iyophilized calibrator.
The provided document describes the Lumipulse G B.R.A.H.M.S PCT Immunoreaction Cartridges and its associated calibrator set. This is an in-vitro diagnostic device, not an AI/ML medical device. Therefore, the questions related to AI/ML device acceptance criteria, performance studies (sample sizes, expert usage, adjudication, MRMC studies, standalone performance), and ground truth establishment are not applicable.
However, based on the provided text, the device's analytical performance and comparison studies can be summarized as follows:
1. A table of acceptance criteria and the reported device performance (for Analytical Performance):
The document refers to CLSI protocols for acceptance criteria, specifically for precision, linearity, and analytical specificity. The acceptance criteria themselves are generally implied by meeting the guidelines or by specific thresholds mentioned in conjunction with the results.
| Performance Characteristic | Acceptance Criteria (Implied/Stated) | Reported Device Performance |
|---|---|---|
| Precision (20-day) | CV ≤ 10% | Controls: Total precision ranged from 3.3% to 4.7% CV. |
| Panels: Total precision ranged from 1.8% to 3.1% CV. | ||
| Overall: All results met the acceptance criteria of CV ≤ 10%. | ||
| Precision (Lot-to-Lot Reproducibility) | CV ≤ 10% | Controls: Total precision ≤ 5.3% CV. |
| Panels: Total precision ≤ 3.0% CV. | ||
| Overall: Total precision ranged from 1.8% to 5.3%. Between-lot precision ≤ 6.5%. All results met the targeted acceptance criteria of CV ≤ 10%. | ||
| Precision (Site-to-Site Reproducibility) | CV ≤ 10% | Controls: Total precision ≤ 4.9% CV. |
| Panels: Total precision ≤ 4.8% CV. | ||
| Overall: Total precision ranged from 2.9% to 4.9%. Between-site precision ≤ 4.7%. All results met the targeted acceptance criteria of CV ≤ 10%. | ||
| Linearity/Reportable Range | Consistent with CLSI EP6-A guidelines, demonstrating correlation with expected concentrations. | Linear in the range of 0.010 ng/mL to 104.260 ng/mL. |
| Regression formula: y = 0.008734 + 0.856577; R-squared: 0.9979. | ||
| No high dose effect observed for samples containing approximately 12,000 ng/mL of PCT. | ||
| Detection Limit (LoD/LoQ) | Consistent with CLSI EP17-A2 guidelines. | LoB = 0.0095 ng/mL. |
| LoD = 0.0114 ng/mL. | ||
| LoQ = 0.0114 ng/mL. | ||
| Modeling analysis: TE ≤ 11.4% at 0.25 ng/mL (% bias ≤ -5.7%, precision CV ≤ 2.8%); TE ≤ 14.1% at 0.10 ng/mL (% bias ≤ -9.2%, precision CV ≤ 2.5%). | ||
| Analytical Specificity (Interference) | Average interference ≤ 10% for each compound. | Tested endogenous and therapeutic compounds showed average interference ≤ 10%. |
| Analytical Specificity (Cross-Reactivity) | Consistent with CLSI EP7-A2 guidelines. | Human Calcitonin: -0.346% |
| Human Katacalcin: 0.076% | ||
| α-CGRP: 0.002% | ||
| β-CGRP: 0.001% | ||
| Salmon Calcitonin: -0.001% | ||
| Eel Calcitonin: -0.001% | ||
| Method Comparison (vs. predicate) | High correlation and acceptable agreement with the predicate device. | Correlation Coefficient (r): 0.9535 |
| Intercept (95% CI): -0.0044 (-0.0223 to 0.0135) | ||
| Slope (95% CI): 1.0199 (0.9633 to 1.0765) | ||
| Mean Difference: 0.185 ng/mL. | ||
| Conclusion: Lumipulse G B.R.A.H.M.S PCT assay is substantially equivalent to the performance of the B.R.A.H.M.S PCT sensitive KRYPTOR. | ||
| Matrix Comparison | Slope for each tube type (vs. control) with 95% CI within 0.9-1.1 and correlation coefficients ≥ 0.9. | Slopes for each tube type (SST, K2EDTA, Lithium Heparin, Sodium Heparin, and Sodium Citrate) when compared to the control (Red top serum) had 95% confidence intervals entirely within 0.9 to 1.1, and correlation coefficients were ≥ 0.9. |
2. Sample sizes used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective):
- Precision (20-day): n=80 for each sample (Control Levels 1-3, Panels 1-8). Data generated at Fujirebio Diagnostics, Inc. (FDI).
- Precision (Lot-to-Lot Reproducibility): n=120 for each sample (Control Levels 1-3, Panels 1-6).
- Precision (Site-to-Site Reproducibility): n=120 for each panel (Control Levels 1-3, Panels 1-6). Performed at "several sites" (implied, typical for site-to-site reproducibility; specific sites or countries not mentioned).
- Linearity/Reportable Range: High and low sample pools created using patient serum samples. Number of samples not specified, but the study was "consistent with the guidelines in the CLSI Protocol EP6-A."
- Detection Limit (LoB/LoD/LoQ): Seven low-level specimens were tested over 3 days using two LUMIPULSE G1200 Systems and two Lumipulse G PCT lots, giving 120 determinations per panel for LoD. Number of unique samples for LoQ not specified, but involved "modeling analysis."
- Analytical Specificity (Interference): Human serum specimen pools (approximately 0.25 and 2.0 ng/mL PCT) supplemented with potentially interfering compounds. Number of individual samples not specified.
- Analytical Specificity (Cross-Reactivity): Human serum specimens (approximately 0.1, 0.25, 0.5, 2.0 and 80 ng/mL PCT) supplemented with potentially cross-reacting compounds. Number of individual samples not specified.
- Method Comparison: n=207 lithium heparin specimens.
- Expected Values/Reference Range: Population of 213 self-reported healthy individuals.
Data Provenance: The document does not explicitly state the country of origin for all patient samples or whether studies were retrospective or prospective, beyond "human serum," "patient serum samples," or "self-reported healthy individuals." The precision studies were conducted at "FDI" (Fujirebio Diagnostics, Inc. in Malvern, PA, USA) and "across several sites."
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):
Not applicable. This is an immunoassay device for quantitative determination of Procalcitonin (PCT), where the "ground truth" is measured analytically by the device itself or compared to a predicate device. It does not involve human interpretation of images or other subjective data that would require expert consensus for ground truth.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
Not applicable. As described above, this device is a quantitative immunoassay and does not involve human adjudication methods for its analytical performance or comparison studies.
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 in-vitro diagnostic device, not an AI/ML device, and does not involve human readers interpreting cases.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Not applicable. This is an in-vitro diagnostic device, not an AI/ML device. The performance data presented are for the analytical device itself.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
For the analytical performance studies (precision, linearity, detection limits, specificity), the "ground truth" is typically defined by reference materials, spiked samples with known concentrations, or established analytical methods. For method comparison, the predicate device (B.R.A.H.M.S PCT sensitive KRYPTOR®) serves as the comparator. For establishing expected values, the measured PCT levels in a population of "self-reported healthy individuals" are used.
8. The sample size for the training set:
Not applicable in the context of AI/ML. For analytical performance, the samples used in the various studies (e.g., 20-day precision, lot-to-lot, site-to-site, linearity, detection limits, interference, cross-reactivity) are referred to as test samples or panels to evaluate the device's accuracy and reliability. There is no concept of a "training set" in the AI/ML sense for this type of IVD device.
9. How the ground truth for the training set was established:
Not applicable, as there is no "training set" in the AI/ML sense. The analytical performance is established through rigorous testing against reference materials and predicate devices following CLSI guidelines.
§ 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.