(88 days)
The LIAISON® B.R.A.H.M.S PCT® II GEN assay uses chemiluminescence immunoassay (CLIA) technology for the in vitro quantitative determination of Procalcitonin in human serum and lithium heparin plasma specimens. Used in conjunction with other laboratory findings and clinical assessments, LIAISON® B.R.A.H.M.S.PCT® II GEN is intended for use as follows:
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to aid in the risk assessment of critically ill patients on their first day of ICU admission for progression to severe sepsis and septic shock,
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to aid in assessing the cumulative 28-day risk of all-cause mortality for patients diagnosed with severe sepsic 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,
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to aid in decision making on antibiotic therapy for patients with suspected or confirmed lower respiratory tract infections (LRT) 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,
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to aid in decision making on antibiotic discontinuation for patients with suspected or confirmed sepsis.
The LIAISON® Control B.R.A.H.M.S PCT® II GEN (level 1 and level 2) are intended for use as assayed quality control samples to monitor the performance and reliability of the LIAISON® BRAHMS PCT® II GEN assay. The performance characteristics of LIAISON® BRAHMS PCT® II GEN controls have not been established with any other assay or instrument platform different from the LIAISON® Analyzer.
The LIAISON® B.R.A.H.M.S PCT® II GEN Verifiers (four levels) are assayed quality control materials intended in the quantitative verification of calibration and reportable range of the LIAISON® BRAHMS PCT® II GEN assay. The performance characteristics of LIAISON® BRAHMS PCT® II GEN calibration verifiers have not been established in connection with any other assay or instrument platforms different from the LIAISON® Analyzer.
The method for the quantitative determination of PCT is a sandwich chemiluminescence immunoassav. A specific monoclonal antibody is coated on the magnetic particles (solid phase); another monoclonal antibody (specific for a different epitope of the procalcitonin molecule) is linked to an isoluminol derivative (isoluminol-antibody conjugate).
During the first incubation, PCT present in calibrators, samples or controls binds to the antibody conjugate. Then the solid phase is added to the reaction. A sandwich is formed only in the presence of PCT molecules that bridge both antibodies. After the second incubation, the unbound material is removed with a wash cycle.
Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and hence the amount of isoluminolantibody conjugate, is measured by a photomultiplier as relative light units (RLU) and is indicative of PCT concentration present in calibrators, samples or controls.
Here's a breakdown of the acceptance criteria and study details for the LIAISON® BRAHMS PCT® II GEN assay, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Specific Metric (Criteria not explicitly stated as numerical targets, but implied by methodology and comparison to predicate) | Reported Device Performance |
|---|---|---|
| Analytical Performance | Limit of Blank (LoB) | 0.01 ng/mL |
| Limit of Detection (LoD) | 0.02 ng/mL | |
| Limit of Quantitation (LoQ) (Bias 100 ng/mL. |
* The origin of these samples (e.g., country) and whether they were retrospective or prospective is **not explicitly stated** in the provided text.
- Precision (Internal 20-day): 10 frozen serum panel samples, 2 levels of kit controls, and 4 levels of verifiers.
- The origin of the serum samples is not explicitly stated, but they were prepared by DiaSorin S.p.A.
- Precision (Multi-Site): 10 frozen serum panel samples, 2 lots of kit controls (2 levels each), and 2 lots of verifiers (4 levels each).
- The origin of the serum samples is not explicitly stated, but they were prepared by DiaSorin S.p.A.
- Sample Equivalence: 40 matched patient samples (serum and lithium heparin collection tubes). These were "spiked or diluted" to span the assay range.
- The origin of these samples is not explicitly stated.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
This device is an in vitro diagnostic (IVD) assay that measures a specific analyte (Procalcitonin) quantitatively. For such devices, "ground truth" is typically established by comparing the device's measurements against a recognized reference method or by using samples with known, carefully characterized concentrations of the analyte.
The document states:
- Method Comparison: "A quantitative method comparison study was performed... following CLSI EP09-A2." This implies comparison against a predicate device (VIDAS® B-R-A-H·M·S PCT™ (K162827)), which serves as the reference method.
- Analytical Performance (LoB, LoD, LoQ): "Following the method from CLSI EP17-A2." This refers to standard statistical methods for determining these analytical characteristics, not expert consensus on individual case diagnoses.
- Precision: Standard statistical methods for assessing reproducibility.
Therefore, for this type of device, the "ground truth" is established by:
- Reference measurement methods: The predicate device itself acts as the comparative reference.
- Analytical standards/spiked samples: For LoB, LoD, LoQ, and precision, samples with known or precisely defined analyte concentrations (e.g., purified calibrators, spiked samples, control materials) are used.
Thus, this document does not indicate the use of human "experts" to establish a diagnostic ground truth for individual cases in the way one might for an imaging AI device (e.g., radiologists reviewing images). The ground truth here is analytical and comparative to a well-established predicate.
4. Adjudication Method for the Test Set
Not applicable in the context of an IVD assay measuring an analyte. The comparative method is against an established reference method (the predicate device) or analytical standards, not through human adjudication of diagnostic interpretations.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC study was not done. This is an in vitro diagnostic device, not an imaging AI device that would assist human readers in interpretation. Its performance is measured analytically and comparatively against a predicate device.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are all standalone. The LIAISON® BRAHMS PCT® II GEN assay is an automated chemiluminescence immunoassay device. The results presented (LoB, LoD, LoQ, method comparison, precision, stability) reflect the direct output of the assay system without human interpretation or intervention in the measurement process itself. The indication for use states it is "Used in conjunction with other laboratory findings and clinical assessments," implying that clinicians will interpret the results, but the performance data presented is for the device operating independently.
7. The Type of Ground Truth Used
The ground truth used in the studies is primarily:
- Reference Method Comparison: The measurements obtained from the FDA-cleared predicate device (VIDAS® B-R-A-H·M·S PCT™) for the method comparison studies.
- Known Concentrations/Analytical Standards: For LoB, LoD, LoQ, accuracy, and precision, samples with known, manufactured, or precisely characterized concentrations of Procalcitonin (e.g., calibrators, controls, characterized panel samples) are used.
It is not pathology, outcomes data, or expert diagnostic consensus on patient cases for the performance studies presented here.
8. The Sample Size for the Training Set
The provided document describes performance verification studies for a medical device (an IVD assay). It does not pertain to an AI/Machine Learning device that undergoes "training." Therefore, there is no training set in the context of AI models. The device operates based on established chemical and immunological principles, not learned patterns from data.
9. How the Ground Truth for the Training Set Was Established
As there is no training set for this type of device, this question is not applicable.
§ 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.