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The BÜHLMANN fCAL turbo is an in vitro diagnostic assay intended for the quantitative measurement of fecal calprotectin, a neutrophilic protein that is a marker of intestinal mucosal inflammation, in human stool. The BÜHLMANN fCAL turbo aids in the diagnosis of inflammatory bowel disease (IBD), specifically Crohn's disease (CD) and ulcerative colitis (UC) and aids in the differentiation of IBD from irritable bowel syndrome (IBS) in conjunction with other laboratory and clinical findings.

The BÜHLMANN fCAL® turbo, a particle-enhanced turbidimetric immunoassay (PETIA), is performed using patient stool extracts collected without preservatives. Calprotectin within the sample extract mediates immunoparticle agglutination; sample turbidity is proportional to calprotectin concentration. The detected light absorbance allows quantification of calprotectin concentration via interpolation of an established calibration curve. The assay is validated for use on clinical chemistry analyzers such as the Roche cobas® c501/c502 platforms.

The BÜHLMANN fCAL® turbo Reagent Kit is to be used in conjunction with the BÜHLMANN fCAL® turbo Calibrator Kit and BÜHLMANN fCAL® turbo Control Kit, which are available separately.

The provided document describes the 510(k) premarket notification for the BÜHLMANN fCAL® turbo device, an in vitro diagnostic assay. It details the device's indications for use, its technological characteristics compared to a predicate device, and the performance data collected to demonstrate its safety and effectiveness.

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:

Acceptance Criteria and Device Performance

The core of the acceptance criteria for the BÜHLMANN fCAL® turbo, as a new device seeking substantial equivalence to a legally marketed predicate (BÜHLMANN fCAL® ELISA), is demonstrated through various performance studies. The primary goal is to show that, despite technological differences, the new device performs comparably to the predicate and is safe and effective for its stated indications.

The document implicitly defines acceptance criteria through the successful outcomes of its performance studies, demonstrating analytical parity and comparable clinical utility. Explicit numerical thresholds for acceptance are not always stated outright as "acceptance criteria" but are demonstrated by the presented results falling within acceptable ranges or showing strong correlation/agreement with the predicate.

Here's a table summarizing the key performance metrics presented, which serve as the de facto acceptance criteria and the device's reported performance:

Study Details Proving Device Meets Acceptance Criteria

1. Sample Size and Data Provenance:

   • Precision Studies (Single-site, Multi-site, Lot-to-Lot): For each sample (typically 8 different concentration levels), n=80 (Single-site) or n=75 (Multi-site, Lot-to-Lot) measurements were performed. This refers to the number of replicates / runs, not distinct clinical samples. These are analytical performance studies using spiked samples or controls.

   • Extraction Reproducibility Study: n=80 for each of the 10 samples (again, replicates/runs).

   • Linearity Study: Each dilution was tested in 4 replicates. Number of unique stool specimens used for creating dilution series is not explicitly stated but implied to be at least two (one high, one low).

   • Accuracy/Recovery Study: 7 clinical samples were spiked and tested.

   • Interfering Substances Study: Stool extracts with 4 different calprotectin concentrations were used for analytes/pharmaceuticals/supplements. Microorganism interference was tested at given cell counts, presumably across various stool extracts. The exact number of distinct stool samples used for interference testing is not specified.

   • Method Comparison Study: A total of 248 clinical study samples were tested. 220 had valid results within the linear measuring range for both devices.

   • Clinical Sensitivity/Specificity Study: 337 clinical samples were included for IBD vs. non-IBD analysis, and 265 clinical samples for IBD vs. IBS.

   • Expected Values/Reference Range Study: 141 apparently healthy normal adults provided stool samples.

   • Data Provenance: Not explicitly stated but typically for an FDA 510(k) submission, these studies would be conducted in the country of origin of the manufacturer (Switzerland, in this case) or in clinical sites compliant with GCLP/GCP, often with diverse patient populations to support generalizability (though not explicitly stated as multi-national for every study). The studies are inherently prospective in nature, as they involve newly generated data from specified experimental designs for device validation.

2. Number of Experts and Qualifications for Ground Truth of Test Set:

   • This section is not applicable for this type of in-vitro diagnostic device (IVD). The device measures a biomarker (fecal calprotectin). The "ground truth" for the test set is either:
     • Analytical True Value: For analytical studies (precision, linearity, accuracy, analytical sensitivity, interference), the ground truth is established by the known concentrations of spiked samples, reference materials, or highly accurate reference methods.
     • Clinical Diagnosis: For the method comparison and clinical sensitivity/specificity studies, the ground truth for "IBD," "IBS," and "non-IBD" is based on the clinical diagnosis of the patient from whom the stool sample was collected. This diagnosis is established by healthcare professionals (e.g., gastroenterologists) using a combination of clinical findings, endoscopy, histology, and other laboratory tests, not by a panel of independent "experts" adjudicating images or cases for the purpose of a study (which is common in AI/Imaging studies).

3. Adjudication Method for the Test Set:

   • Not applicable in the context of expert adjudication for diagnostic calls, as this is an IVD measuring a biomarker.
   • For the clinical ground truth, it's based on the established clinical diagnosis by treating physicians. There is no mention of a separate adjudication process (e.g., 2+1 or 3+1 reader consensus) for these clinical diagnoses for the purpose of this device study.

4. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:

   • No, an MRMC study was not done. This type of study is specifically relevant for image-based diagnostic aids where the output of the AI directly influences a human reader's interpretive performance. The BÜHLMANN fCAL® turbo is a laboratory-based immunoassay that quantifies a biomarker. Its output is a numerical concentration, not an image interpretation requiring multiple readers. The "comparative effectiveness" is demonstrated against the predicate device's performance, not how it assists human readers in interpreting complex visual information.

5. Standalone (Algorithm Only) Performance:

   • Yes, this entire submission effectively describes a standalone performance. The BÜHLMANN fCAL® turbo is an automated analyzer/reagent system that directly measures fecal calprotectin concentration from a stool sample extract. The reported results (e.g., precision, linearity, accuracy, clinical sensitivity/specificity) are the direct output of the device itself, without human-in-the-loop interpretation of its primary numerical output. The device "aids in the diagnosis" in conjunction with other findings, meaning the numerical output is used by clinicians, but the device itself functions as a standalone measurement tool.

6. Type of Ground Truth Used:

   • Analytical Ground Truth: For the analytical performance studies (Precision, Linearity, Accuracy, Analytical Sensitivity, Interfering Substances), the ground truth is established through known concentrations of reference materials, spiked samples, or comparison to established reference methods.
   • Clinical Ground Truth: For the Method Comparison and Clinical Sensitivity/Specificity studies, the ground truth for patient classification (IBD, IBS, non-IBD, normal) is based on clinical diagnosis, which would typically include outcomes data, endoscopic findings, histological results, and the overall clinical picture as determined by a treating physician. It is not expert consensus of independent reviewers explicitly for the study, nor is it pathology in the sense of a single definitive pathology report for every case, but rather a comprehensive clinical workup.

7. Sample Size for the Training Set:

   • Not applicable / Not explicitly stated as a separate "training set" in the context of traditional machine learning. This device is an in vitro diagnostic (IVD) immunoassay, not an AI/ML algorithm that is "trained" on a large dataset of patient samples in the same way a deep learning model for image analysis is. The "training" here refers to the internal development and calibration of the assay (e.g., establishing the standard curve, optimizing reagent concentrations), which is part of the product development process, not a distinct "training set" like in AI/ML validation studies. The analytical performance and clinical validation studies presented here are akin to a "test set" and "validation set" in AI/ML terminology, but the concept of a separate "training set" for the device itself (rather than the general scientific knowledge used in developing the immunoassay) is not present.

8. How Ground Truth for Training Set Was Established:

   • As noted above, the concept of a "training set" for this type of IVD device is different from AI/ML models. The ground truth for developing and calibrating the assay (which could be loosely considered "training") involves:
     • Reference materials with known concentrations of calprotectin.
     • Standard curves generated using defined calibrators.
     • Analytical methods and clinical literature informing the selection of antibodies, detection methods, and clinical cut-offs.
     • Internal validation and optimization processes during product development.

In summary, the document thoroughly details the analytical and clinical performance of the BÜHLMANN fCAL® turbo, demonstrating substantial equivalence to its predicate by meeting rigorous criteria in terms of precision, linearity, accuracy, analytical sensitivity, and demonstrating comparable clinical utility in differentiating IBD from other gastrointestinal conditions. The nature of the device (an immunoassay) means certain aspects typically found in AI/ML performance studies (like MRMC or reader adjudication) are not applicable.

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