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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 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 CALEX® Cap is a single use tube intended for the preparation of human stool samples to be used with the BUHLMANN fCAL® turbo.

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.

Sample extracts may be prepared using manual weighing extraction methods or the CALEX® Cap.

The CALEX® Cap is a single use tube filled with extraction buffer. The sampling pin houses a dosing tip which is used to obtain sufficient stool sample for the extraction process. The extraction method leads to stool specimen extracts which can be measured directly using the BÜHLMANN fCAL® turbo assay.

The document discusses the BÜHLMANN fCAL® turbo and CALEX® Cap devices, which are used for quantitative measurement of fecal calprotectin. The primary purpose of this submission is to extend the stability of CALEX® Cap extracts.

Here's a breakdown of the requested information based on the provided text:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state acceptance criteria in a quantitative table format. Instead, it refers to a "risk assessment" and a "stability study conducted in accordance with CLSI EP25 to support the shelf-life extension of the CALEX® Cap extracts." The conclusion states that "The stability study supports the claimed extension to CALEX® Cap extract shelf-life." This implies that the performance in the stability study met the internal acceptance criteria established based on the risk assessment and CLSI EP25 guidelines.

2. Sample size used for the test set and the data provenance

The document states, "an extract stability study was conducted in accordance with CLSI EP25." However, it does not provide details on the specific sample size, country of origin of the data, or whether the study was retrospective or prospective.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not provided in the document. The study mentioned is a stability study, not a clinical study involving human experts establishing ground truth for diagnostic accuracy.

4. Adjudication method for the test set

This information is not provided as the study is a stability study, not a diagnostic accuracy study requiring adjudication.

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

An MRMC study was not performed, nor is it applicable to this device. The BÜHLMANN fCAL® turbo is an in vitro diagnostic (IVD) assay for measuring a biomarker, not an AI-assisted diagnostic imaging or interpretation device.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

This question is not applicable in the context of an immunoassay device. The BÜHLMANN fCAL® turbo is a laboratory test, and its performance is evaluated based on its analytical accuracy and precision in quantifying fecal calprotectin. There is no "algorithm only" performance separate from the assay itself.

7. The type of ground truth used

For the stability study, the "ground truth" would be the known and stable concentration of calprotectin in the samples used, measured at multiple time points to assess the stability of the extract over time. This is not "expert consensus," "pathology," or "outcomes data" in the typical sense of a diagnostic accuracy study.

8. The sample size for the training set

This information is not provided and is not applicable in the context of this submission. The submission is about extending the shelf-life of an existing device, which involves stability testing, not the development of a new algorithm requiring a "training set."

9. How the ground truth for the training set was established

This information is not provided and is not applicable for the reasons mentioned above.

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The ALPCO Calprotectin Immunoturbidimetric Assay is an in-vitro diagnostic assay used for the quantitative measurement of human fecal calprotectin in human stool. The ALPCO Calprotectin Immunoturbidimetric Assay is intended for in-vitro diagnostic use as an aid in diagnosis of inflammatory bowel disease (IBD), specifically Crohn's disease (CD) and ulcerative colitis (UC), and as an aid in the differentiation of IBD from irritable bowel syndrome (IBS) in conjunction with other clinical and laboratory findings.

Not Found

I am sorry to inform you that the provided text does not contain detailed information about the acceptance criteria, specific study results, sample sizes for test and training sets, expert qualifications, or adjudication methods for the ALPCO Calprotectin Immunoturbidimetric Assay.

The text is primarily a 510(k) clearance letter from the FDA, confirming that the device is substantially equivalent to a legally marketed predicate device. It outlines the regulatory classification, general controls, and indications for use. While it states the intended use of the assay, it does not provide the specifics of the performance study that would establish achievement of acceptance criteria.

Therefore, I cannot generate the requested table and detailed description based on the provided input. To answer your questions, I would need a different document, likely a '510(k) Summary' or the full '510(k) Premarket Notification' submission, which typically contains the detailed performance data.

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The DiaSorin LIAISON® Calprotectin assay is an in vitro diagnostic chemiluminescent immunoassay (CLIA) intended for the quantitative measurement, in human stool, of fecal calprotectin, a neutrophilic protein that is a marker of mucosal inflammation. The LIAISON® Calprotectin assay can be used as an aid in the diagnosis of inflammatory bowel diseases (IBD), specifically Crohn's disease and ulcerative colitis, and as an aid in differentiation of IBD from irritable bowel syndrome (IBS). Test results are to be used in conjunction with information obtained from the patients' clinical evaluation and other diagnostic procedures.

The test has to be performed on the LIAISON® Analyzer Family.

The DiaSorin LIAISON® Q.S.E.T. Device Plus (Quantitative Stool Extraction and Test) is intended for use in the preparation of human stool specimens for testing in the LIAISON® Calprotectin assay.

The LIAISON® Calprotectin assay is a sandwich assay that uses 2 monoclonal antibodies for capture and detection of calprotectin. The LIAISON® Calprotectin assay must be run on the LIAISON® Analyzer family, a fully automated system with continuous loading.

Calprotectin is first extracted from human stool samples with LIAISON® Q.S.E.T. Buffer using either the weigh method, the LIAISON® Q.S.E.T. Device or the LIAISON® Q.S.E.T. Device Plus. The assay incubates extracted sample, calibrator, control, or calibration verifiers with assay buffer and paramagnetic particles coated with a monoclonal antibody that specifically recognizes the calprotectin heterocomplex. Following incubation, a wash cycle is performed to remove any unbound material. An isoluminol conjuqated monoclonal antibody that recognizes calprotectin is then added to the reaction and incubated. The unbound conjugate is removed with a second wash step. Starter reagents are then added and a flash chemiluminescent reaction is initiated. The light signal is measured by a photomultiplier as relative light units (RLU) and is proportional to the concentration of calprotectin present in the calibrators, controls or samples.

All assay steps and incubations are performed by the LIAISON® XL Analyzer. The analyzer software automatically calculates the concentration of calprotectin in the sample. This concentration is expressed in ug/g.

The Q.S.E.T. Device Plus differs from its predicate Q.S.E.T. Device in that it is provided ready to use, and comes prefilled with the same extract buffer as required for use with the Q.S.E.T. Device, eliminating the need for the user to prepare the buffer and add it to the device themselves. In addition, minor changes to the shape and design of the tube were made.

The provided text is related to the FDA 510(k) premarket notification for the DiaSorin LIAISON® Calprotectin assay and the LIAISON® Q.S.E.T. Device Plus. None of the information requested in your prompt (Acceptance criteria, Study proving device meets criteria, Sample size, data provenance, expert numbers, etc. for AI/clinical studies) is present in the document.

The document describes an in vitro diagnostic (IVD) chemiluminescent immunoassay (CLIA) for fecal calprotectin, intended as an aid in diagnosing Inflammatory Bowel Diseases (IBD) and differentiating it from Irritable Bowel Syndrome (IBS). It also details a device for stool sample preparation.

The performance data included in the document specifically refers to the analytical performance of the IVD device and its sample preparation component, such as:

• Precision/Reproducibility: This section details the reproducibility of the LIAISON® Q.S.E.T. Device Plus extraction using five (5) stool samples with 90 measurements per sample (6 replicates over 5 days by 3 operators). It also shows sampling reproducibility using 5 human stool specimens, sampled by 3 operators with 5 replicates per specimen per operator on 3 lots of devices, totaling 225 sampling events.
• Reagent Stability: Mentions stability of the LIAISON® Q.S.E.T. Device Plus at 2-8°C for 12 months.
• Specimen Stability: Provides stability data for stool specimens under various storage conditions (refrigerated, room temperature, frozen, freeze/thaw cycles) and for sample extracts.

Therefore, I cannot provide the requested information regarding acceptance criteria for an AI/clinical study, the study setup to prove meeting those criteria, sample sizes for test/training sets in an AI context, expert qualifications, adjudication methods, MRMC studies, or standalone algorithm performance, as these concepts are not applicable to the analytical validation described for this IVD device.

The document solely focuses on the analytical performance validation of an IVD immunoassay, not on clinical performance or AI/machine learning aspects.

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

The ALPCO Easy Stool Extraction Device is intended for use in the preparation of human stool specimens for testing in the ALPCO Calprotectin Chemiluminescence ELISA.

The ALPCO Calprotectin Chemiluminescence ELISA is performed on stool samples, collected without preservatives. After an extraction procedure of the stool sample, using either the manual weighing or Easy Extraction Device procedure, the test allows the selective measurement of calprotectin-antigen by sandwich ELISA. A monoclonal capture antibody (mAb) highly specific to the calprotectin heterodimeric and polymeric complexes, respectively, is coated onto the microtiter plate. Calibrators, controls and specimen extracts are incubated. After a washing step, a biotinylated secondary monoclonal detection antibody detects the calprotectin molecules bound to the antibody coated onto the plate. After incubation and a further washing step, a Streptavidin-Horseradish Peroxidase Enzyme conjugate binds to the available biotin on the immobilized secondary antibody. A chemiluminescent substrate is added and read when the substrate glows as a result of its oxidation with the enzyme. The signal is then read on a chemiluminescent plate reader.

Here's an analysis of the acceptance criteria and study detailed in the provided text for the ALPCO Calprotectin Chemiluminescence ELISA and ALPCO Easy Stool Extraction Device:

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" for all performance aspects in a unified table. However, based on the narrative, acceptance implies successful demonstration of performance within established guidelines (e.g., CLSI standards) and acceptable ranges. Here's a table summarizing the performance evaluation and implied acceptance:

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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 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 CALEX Cap is a single use tube intended for the preparation of human stool samples to be used with the BÜHLMANN fCAL turbo.

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.

Sample extracts may be prepared using manual weighing extraction methods or the CALEX® Cap.

The CALEX® Cap is a single use tilled with extraction buffer. The sampling pin houses a dosing tip which is used to obtain sufficient stool sample for the extraction process. The extraction method leads to stool specimen extracts which can be measured directly using the BÜHLMANN fCAL® turbo assay.

This document describes the validation of the BÜHLMANN fCAL® turbo and CALEX® Cap device, an in vitro diagnostic assay for measuring fecal calprotectin.

1. Table of Acceptance Criteria (Implied) and Reported Device Performance

The document doesn't explicitly list "acceptance criteria" in a separate table, but the performance data sections demonstrate that the device meets various analytical and clinical performance standards. The key performance metrics are presented as results from studies.

2. Sample Size and Data Provenance

• Test Set Sample Sizes:

  • Precision Studies: 80 replicates per sample for Single-Site and Extraction Reproducibility, 75 replicates per sample for Multi-Site and Lot-to-Lot precision.
  • Linearity: Not explicitly stated as a number of unique patient samples, but involves two dilution series with "various mixing ratios" and 4 replicates per dilution.
  • Accuracy/Recovery: 7 samples.
  • Interfering Substances: Stool specimen extracts with 4 approximate calprotectin concentrations; specific number of runs not explicitly stated.
  • Method Comparison (vs. predicate ELISA): 248 clinical study samples.
  • Extraction Method Comparison (CALEX® Cap vs. Manual): 241 clinical study samples.
  • Clinical Sensitivity/Specificity: 265 samples for IBD vs. IBS analysis, 337 samples for IBD vs. non-IBD analysis.
  • Expected Values/Reference Range: 141 apparently healthy normal adults.

• Data Provenance: The document does not explicitly state the country of origin for the clinical study data or whether it was retrospective or prospective. Given the submitter's location (Switzerland), it's possible some or all studies were conducted there or internationally. The term "clinical study samples" usually implies prospective collection, but it's not explicitly stated.

3. Number of Experts and Qualifications for Ground Truth

• This document is for an in vitro diagnostic (IVD) assay, specifically an immunological test system for fecal calprotectin. The "ground truth" for such devices often relies on established laboratory methods, clinical diagnoses based on a constellation of evidence (e.g., endoscopy, histology, imaging, other lab findings), or consensus among clinicians.
• No "experts" in the sense of human readers for images are mentioned or used for establishing ground truth. Instead, the device's performance is compared against:
  • Itself (for precision, linearity, recovery, sensitivity).
  • A legally marketed predicate device (for method comparison).
  • External clinical diagnoses (for clinical sensitivity/specificity).
• For clinical diagnosis (e.g., IBD, IBS, non-IBD), the ground truth is implicitly established by clinical findings, which would typically involve qualified physicians (e.g., gastroenterologists) and pathologists, but their specific number or qualifications are not detailed as this is standard for IVD test validation.

4. Adjudication Method for the Test Set

• Adjudication methods (like 2+1, 3+1) are typically used for studies involving human interpretation of complex data (e.g., medical images) where a consensus is needed to define the ground truth for equivocal cases.
• This is an IVD device, not an image-based AI system. Therefore, there is no "adjudication method" as described in the context of human reader studies. The "ground truth" for clinical sensitivity/specificity would be the established clinical diagnosis for each patient, determined by standard medical practice, not by expert adjudication of the test results themselves.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No MRMC study was done. MRMC studies are designed to compare the diagnostic performance of human readers, often with and without AI assistance, on a set of medical cases.
• This document describes the validation of an in vitro diagnostic (IVD) test kit, which is a laboratory assay. It does not involve human readers interpreting images or any AI assistance for human interpretation.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

• Yes, this entire submission effectively represents a standalone performance study of the BÜHLMANN fCAL® turbo and CALEX® Cap device.
• As an IVD assay, its core function is to produce quantitative results based on the chemical reaction. The performance data (precision, linearity, accuracy, analytical sensitivity, method comparison) demonstrate its intrinsic performance independent of human interpretation of its raw output. The subsequent clinical sensitivity and specificity studies evaluate the diagnostic accuracy of the device's numerical output against clinical diagnoses. There is no "human-in-the-loop" in the direct operation or result generation of the assay itself, apart from standard laboratory procedures and subsequent clinical interpretation of the numerical calprotectin values.

7. Type of Ground Truth Used

• Analytical Ground Truths:
  • Known concentrations: For linearity, analytical sensitivity (LoB, LoD, LoQ), accuracy/recovery, and interfering substances, the ground truth involves samples with known or spiked concentrations of calprotectin or interferents.
  • Reference Methods/Predicate Device: For method comparison, the predicate BÜHLMANN fCAL® ELISA assay serves as a comparative ground truth.
• Clinical Ground Truths:
  • Clinical Diagnosis: For clinical sensitivity and specificity, the ground truth for patients was their established clinical diagnosis (e.g., IBD, IBS, non-IBD). This diagnosis is typically based on an aggregation of clinical findings, endoscopic results, histological reports, and other laboratory tests, representing the best available clinical determination.
  • Healthy Normal Cohort: For expected values/reference range, the ground truth was a cohort of "apparently healthy normal adults" based on lack of symptoms or signs of gastrointestinal disease, implying a clinical assessment.

8. Sample Size for the Training Set

• This document describes the validation studies for a pre-market submission (510(k)) for an IVD device. For such devices, particularly those based on immunoassay technology, the concept of a "training set" like that used in machine learning (ML) is generally not applicable in the same way. The device's underlying immunoassay methodology is laboratory-based and its parameters are established through extensive analytical development rather than data-driven "training" in the ML sense.
• The document presents performance data from verification and validation studies, which are essentially "test sets" for the final device. There is no mention of a separate "training set" of patient data for model development as one would see with a deep learning algorithm. The analytical parameters and performance characteristics of the immunoassay are developed and optimized by the manufacturer.

9. How the Ground Truth for the Training Set Was Established

• As explained above, the concept of a distinct "training set" and associated ground truth establishment in the context of an ML algorithm is not directly applicable to this immunoassay device's validation as described in the 510(k) summary. The development of such assays relies on biochemical principles, calibration curves established with known standards, and analytical validation experiments performed on various matrices and samples. The "ground truth" for developing the assay itself would be the precisely measured values of known calprotectin standards.

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Calprest is a quantitative ELISA for detecting concentration of fecal calprest can be used as an in vitro diagnostic to aid in the diagnosis of Inflammatory Bowel Diseases (IBD, Crohn's disease and ulcerative colitis) and to differentiate IBD from Irritable Bowel Syndrome (IBS) in conjunction with other clinical and laboratory findings.

Calprest® is an enzyme-linked immunosorbent assay (ELISA) system with colorimetric detection based on the use of polyclonal antibody against calprotectin. Calprotectin present in the diluted sample is bound by the antibody adsorbed to the surface of the plastic well. The enzyme conjugated antibody binds to the captured antigen and subsequently the enzyme catalyzes the conversion of the substrate to a colored product. The intensity of the color is proportional to the amount of conjugate bound, and thus to the amount of captured calprotectin. Concentration of calprotectin in the samples is calculated using the provided standards.

EasyCal is a single-use device for stool sample pre-analytical processing that allows the extraction of calprotectin from the specific amount of collected fecal sample required to perform Eurospital's Calprest® and Calprest®NG assays.

The device consists of a tube, containing 2.8 ml of extraction solution, a stick shaped with seven grooves for collecting the sample. The upper end is made up by two components which can be removed by opposite rotations. The screw cap (white) connected to the shaped stick traps the sample excess and can be then removed by counter-clockwise rotation. Once the extraction procedure has been completed, the sample can be transferred to an automated ELISA instrumentation, placing it directly into the sample rack. EasyCal allows an easy, reliable and reproducible way to sample from primary containers and analyze the extract directly from the device, without the need to weight the stool sample.

The provided document describes the 510(k) premarket notification for the Calprest device with the EasyCal accessory, a fecal calprotectin immunological test system. This submission primarily focuses on demonstrating that the addition of the EasyCal pre-analytical processing accessory does not negatively impact the performance of the previously cleared Calprest assay.

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

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally implied by the requirement for the new device with EasyCal to be "comparable" and "perform equivalently" to the predicate device (Calprest with manual extraction). Specific quantitative acceptance criteria are not explicitly listed in a typical "table" format with pass/fail thresholds for each metric. Instead, the study results are presented, demonstrating agreement or reproducibility within expected analytical variations for laboratory tests.

Here's a breakdown of the reported performance demonstrating equivalence:

• Slope: 1.005 (95% CI: 0.9603 to 1.060)
• Y-intercept: -0.3639 (95% CI: -3.977 to 2.056)
• Correlation (r): 0.968
• Bias at 120 mg/kg: 0.2% (95% CI: -3.7% to 5.6%)
  Qualitative Agreement (with 120 mg/kg cutoff):
• Total Agreement: 97.0% (95% CI: 91.5 to 99.0%) (Borderline as positive) / 92.0% (95% CI: 85.0 to 95.9%) (Borderline as negative)
• Negative Agreement: 96.4% (82.3 to 99.4%) (Borderline as positive) / 94.2% (84.4 to 98.0%) (Borderline as negative)
• Positive Agreement: 97.2% (90.4 to 99.2%) (Borderline as positive) / 89.6% (77.8 to 95.5%) (Borderline as negative) |
  | Stool Sample Collection Weight | Consistency in amount of fecal material collected by EasyCal. | Mean stool sample weight collected by EasyCal: 56 mg. |
  | Reproducibility | Acceptable Coefficient of Variation (CV) and Standard Deviation (SD) across different operators, days, and within laboratory. | Within Laboratory CVs: Ranged from 5.9% to 15.9% across 7 samples with varying calprotectin concentrations. (Specific SDs reported for repeatability, between-day, within-operator, between-operator, and within-laboratory). Reproducibility was "confirmed." |
  | Sample Stability (Extracted Stool) | Maintenance of calprotectin concentration in extracted samples over time and freeze/thaw cycles. | All samples "met the acceptance criteria" for:
• Storage at 2-8°C: up to 21 days tested (recommendation states "up to 14 days").
• Storage at Room Temperature: up to 73 hours tested (recommendation states "up to 72h").
• Freeze/Thaw Cycles: up to 5 cycles tested (recommendation states "not to exceed 4 freeze-thaw cycles"). Percent recovery was calculated. |
  | EasyCal Device Stability | Maintenance of extraction buffer pH and volume, and no impact on Calprest performance over shelf life and at room temperature. | Shelf Life (Real time stability): pH values between 7.77 and 7.84, volume variation 99.4%-100.6%. All measures "met the acceptance criteria" up to 25 months. The device is stable for 24 months at 4°C and "does not affect Calprest®'s performances."
  Room Temperature Stability: All acceptance criteria were met for EasyCal stored at room temperature for 72h, confirming it "doesn't affect Calprest® performances." |

2. Sample Sizes Used for the Test Set and Data Provenance

• Method Comparison: 100 stool samples.
• Stool Sample Collection Performance: 5 different human stool samples, collected in replicates of five (total 25 collections per operator for each sample consistency implicitly).
• Reproducibility Study: 7 stool samples, tested in replicate of five, once a day, for five days (5x5x3 scheme), resulting in 75 data points per sample.
• Sample Stability and Handling: 8 stool samples.
• EasyCal Device Stability (Shelf life): Data on 3 lots of EasyCal devices. Separately, 12 samples extracted with 3 lots of devices stored at 2-8°C for up to 25 months and a freshly produced one.
• EasyCal Device Stability (Room Temperature): 6 stool samples extracted with 3 different lots of EasyCal.

Data Provenance: The document does not explicitly state the country of origin for the samples or if the data was retrospective or prospective. Given it's a 510(k) submission for an in vitro diagnostic device, it's highly likely these were laboratory studies using clinical samples collected prospectively for the purpose of validation, or samples obtained from biobanks.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications

This device is an in-vitro diagnostic (IVD) test for measuring fecal calprotectin concentration. The "ground truth" for such a device is typically the known concentration of an analyte or the established "true" diagnosis or condition based on comprehensive clinical assessment.

• For the analytical performance studies (method comparison, reproducibility, stability), the ground truth is implicitly the true calprotectin concentration within the samples. This is established by rigorous laboratory practices, reference methods, and quality control materials, not by human expert consensus on images or clinical cases.
• The document mentions "three independent operators" for the stool sample collection performance and "three different operators" for the reproducibility study. These are laboratory personnel performing the assays, not clinical experts establishing a medical "ground truth." Their qualifications are not specified beyond being "operators."

4. Adjudication Method for the Test Set

Not applicable in the typical sense for an IVD test validation like this one. Adjudication methods (like 2+1, 3+1) are common in studies evaluating diagnostic imaging or AI algorithms where subjective human interpretation of complex data (e.g., radiologic images) is involved in establishing ground truth. For an IVD, the assays produce quantitative results, and the comparison is statistical between methods, not between human interpretations of the raw data.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. These studies are specifically designed to evaluate the impact of AI on human reader performance, typically in the context of image interpretation (e.g., radiology). This submission is for an IVD kit, which measures a biomarker and does not involve human interpretation of complex images or clinical cases in the same way. The primary comparison is between two methods of sample preparation for the same quantitative assay, not between human readers with and without AI assistance.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, the studies presented are essentially "standalone" in the sense that they evaluate the analytical performance of the combined "Calprest with EasyCal" system. The system provides a quantitative output (calprotectin concentration). The performance metrics (method comparison, reproducibility, stability) evaluate the accuracy, precision, and reliability of this quantitative output directly, not how it assists a human in a diagnostic task. The "human-in-the-loop" here refers to the laboratory technician performing the test, and the studies confirm the consistency of the results regardless of operator or processing method (EasyCal vs. manual).

7. The Type of Ground Truth Used

The ground truth used for these studies is analytical truth regarding fecal calprotectin concentration in stool samples. This is established by:

• Using samples with a "different levels of calprotectin evenly distributed and covering the quantification range" (method comparison).
• Performing assays according to established protocols to obtain the most accurate measurement possible for each sample.
• Using established statistical methods (e.g., Passing-Bablok regression, CLSI guidelines) for comparing the new method to the predicate method.

It is not based on:

• Expert consensus (as in radiology reads).
• Pathology (though a clinical diagnosis might correlate with calprotectin levels, the ground truth for the analytical performance is the concentration itself).
• Outcomes data (as in long-term patient follow-up).

8. The Sample Size for the Training Set

The document does not explicitly mention a "training set" in the context of an AI/ML algorithm that requires labeled data for model training. This is a conventional IVD device, not an AI/ML diagnostic tool. The "studies" presented are analytical validation studies, demonstrating the performance of the device itself (measurement accuracy, precision, stability), not for training a predictive model.

9. How the Ground Truth for the Training Set Was Established

As there is no AI/ML "training set" in the context of this device, this question is not applicable. The device itself performs the measurement based on a biochemical reaction (ELISA), not a learned algorithm. The ground truth for the analytical validation (as described in point 7) is established through laboratory measurement and comparison to an existing validated method.

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CalprestNG is a quantitative ELISA for detecting concentration of fecal calprotectin. CalprestNG can in vitro diagnostic to aid in the diagnosis of Inflammatory Bowel Diseases (IBD, Crohn's disease and ulcerative colitis) and to differentiate IBD from Irritable Bowel Syndrome (IBS) in conjunction with other clinical and laboratory findings.

Calprest®NG is an enzyme-linked immunosorbent assay (ELISA) system with colorimetric detection based on the use of antibodies against calprotectin. Calprotectin present in the diluted sample is bound by the antibody adsorbed to the surface of the plastic well. The enzyme conjugated antibody binds to the captured antigen and subsequently the enzyme catalyzes the conversion of the substrate to a colored product. The intensity of the color is proportional to the amount of conjugate bound, and thus to the amount of captured calprotectin. Concentration of calprotectin in the samples is calculated using the provided standards.

EasyCal is a single-use device for stool sample pre-analytical processing that allows the extraction of calprotectin from the specific amount of collected fecal sample required to perform Eurospital's Calprest® and Calprest®NG assays.

The device consists of a tube, containing 2.8 ml of extraction solution, a stick shaped with seven grooves for collecting the sample. The upper end is made up by two components which can be removed by opposite rotations. The screw cap (white) connected to the shaped stick traps the sample excess and can be then removed by counter-clockwise rotation. Once the extraction procedure has been completed, the sample can be transferred to an automated ELISA instrumentation, placing it directly into the sample rack. EasyCal allows an easy, reliable and reproducible way to sample from primary containers and analyze the extract directly from the device, without the need to weight the stool sample.

The document describes the CalprestNG device, an ELISA (enzyme-linked immunosorbent assay) for detecting fecal calprotectin, and its new pre-analytical processing accessory, EasyCal. The submission is for K191592, establishing substantial equivalence to the predicate device CalprestNG (K160447), which used manual extraction. The core of the study is to demonstrate that using EasyCal for sample extraction yields comparable results to the manual extraction method.

Here's an analysis of the acceptance criteria and the study proving the device meets them:

1. A table of acceptance criteria and the reported device performance:

The document primarily focuses on demonstrating the comparability of CalprestNG with EasyCal to CalprestNG with manual extraction, rather than predefined quantitative acceptance criteria with specific ranges. Instead, the "acceptance criteria" are implied by showing the comparability of the new method to the predicate method.

However, we can infer the performance metrics tested and their results, which serve as evidence of acceptance.

Table 1. Method Comparison and Performance

• Slope (95% CI): 0.9778 (0.901 to 1.003)
• Y-intercept (95% CI): 0.8495 (-0.8360 to 3.978)
• Correlation (r): 0.954
• Bias at 120 mg/kg (95% CI): -1.5% (-9.0% to 1.5%) |
  | Qualitative Agreement | High agreement (Negative, Positive, and Total Agreement) when classifying samples based on a clinical cut-off. | Referencing 120 mg/kg cut-off (borderline as positive/negative based on interpretation):
• Borderline as positive:
  • Negative Agreement (95% CI): 96.2% (81.1 to 99.3%)
  • Positive Agreement (95% CI): 100.0% (95.1 to 100%)
  • Total Agreement (95% CI): 99.0% (94.6 to 99.8%)
• Borderline as negative:
  • Negative Agreement (95% CI): 100.0% (90.1 to 100%)
  • Positive Agreement (95% CI): 95.4% (87.3 to 98.4%)
  • Total Agreement (95% CI): 97.0% (91.5 to 99.0%) |
    | Stool Sample Collection Performance| Maintain consistent and appropriate sample weight. | Mean weight collected by EasyCal: 56 mg. (This is a specific internal metric, the acceptance criteria implicitly being that this weight is consistent and adequate for the assay). |
    | Extraction Reproducibility | Low coefficient of variation (CV%) for within-run, between-day, within-operator, between-operator, and within-laboratory precision.| CV% for 8 samples across quantification range (average or example values presented): Representative CVs range from 3.8% to 6.9% for repeatability, and overall within-laboratory CVs up to 18.3%. (Specific ranges were not given as 'criteria', but the detailed table data demonstrates the measured precision). The study concludes: "Reproducibility of results obtained with Calprest® with EasyCal is confirmed." |
    | Extracted Sample Stability | Extracted samples should remain stable at specific temperatures and after freeze/thaw cycles for defined durations. | Samples met acceptance criteria for:
• 2-8 °C up to 21 days (recommendation: up to 14 days)
• Room temperature up to 73 hours (recommendation: up to 72 hours)
• Up to 5 freeze/thaw cycles (recommendation: not to exceed 4 cycles) |
  | EasyCal Device Stability (Shelf Life)| pH and volume stability over time; no adverse effect on CalprestNG performance. | pH and Volume: Between 7.77 and 7.84 (mean 7.80) for pH; 99.4% to 100.6% (mean 100.0%) for volume variation up to 25 months. All met acceptance criteria.
  CalprestNG performance: All acceptance criteria met at 25 months. Device stable for 24 months at 4 °C and does not affect CalprestNG performance. |
  | EasyCal Device Stability (Room Temp.)| Maintain performance when stored at room temperature for specified duration. | All acceptance criteria were met. Device stable for 72 hours at room temperature and doesn't affect CalprestNG performances. |

2. Sample sizes used for the test set and the data provenance

• Method Comparison (Stool extraction method comparison: EasyCal vs manual extraction procedure):

  • Sample Size: One hundred (100) stool samples.
  • Data Provenance: Not explicitly stated, but clinical studies for such devices typically involve prospective collection or use of banked samples from clinical sites. The document implies these are "patient samples" (from CLSI EP09c reference). Country of origin is not specified.
  • Retrospective/Prospective: Not explicitly stated for this particular sample set, but device validation studies often use a mix. Given the "CLSI EP09c" reference, it points to a formal comparison study, which could be prospective collection for the purpose of the study.

• Reproducibility study: Extraction Reproducibility:

  • Sample Size: Eight (8) stool samples (tested in replicate of five, once a day, for five days, by three different operators). This results in 8 samples * 5 replicates * 5 days * 3 operators = 600 total test points.
  • Data Provenance: Not specified.
  • Retrospective/Prospective: Not specified.

• Stool sample collection performance of EasyCal:

  • Sample Size: Five (5) different human stool samples. Each collected in replicates of five by three independent operators (5 samples * 5 replicates * 3 operators = 75 total weight measurements).
  • Data Provenance: Not specified.
  • Retrospective/Prospective: Not specified.

• Samples stability and handling:

  • Sample Size: Eight (8) stool samples.
  • Data Provenance: Not specified.
  • Retrospective/Prospective: Not specified.

• EasyCal device stability (Shelf life and Room Temperature):

  • Sample Size: Three lots of EasyCal devices were used for pH/volume tests. Twelve (12) samples were extracted for performance validation with aged vs. fresh devices. Eight (8) stool samples were used for room temperature storage validation.
  • Data Provenance: Not specified.
  • Retrospective/Prospective: Real-time stability studies are inherently prospective observations over time.

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)

This device is an in vitro diagnostic (IVD) quantitative assay for fecal calprotectin. The "ground truth" for such devices is established through:

• Referenced methods: The manual extraction method of the predicate device (K160447) served as the reference or comparative "truth" for the EasyCal method. The study aimed to show equivalence to this established method.
• Known concentrations: For reproducibility and stability studies, often spiked samples or samples with predetermined concentrations are used, verified by validated analytical methods.
• Clinical correlation (indirect): The output of the assay (Calprotectin concentration) is correlated with clinical findings (IBD vs. IBS diagnosis). However, the direct clinical diagnostic "ground truth" (e.g., patient biopsy, endoscopy results) is not used within this specific analytical validation section to establish the "truth" for the quantitative assay itself. The clinical performance characteristics are stated to be "Same as approved in 510(k) submission # K160447," implying that clinical utility was established previously, and this submission focuses on analytical equivalence.

Therefore, human experts in the context of "ground truth establishment" for an image analysis or diagnostic interpretation task (like radiologists for imaging) are not directly applicable here. The "ground truth" is the precise measurement of calprotectin or the established manual extraction benchmark.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

Adjudication methods like 2+1 or 3+1 are typically used in studies where human readers/experts independently interpret complex data (e.g., medical images), and a consensus or adjudication process is needed to resolve discrepancies and establish a robust ground truth for classification tasks.

This study is an analytical performance study of a quantitative in vitro diagnostic (IVD) device. The "truth" is either the measured concentration by a reference method or the established manual extraction procedure. Therefore, no adjudication method involving multiple human readers/experts is pertinent or mentioned for establishing the "ground truth" of the test set in this context.

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

No MRMC comparative effectiveness study was done or is relevant here. This is a submission for an IVD device measuring a biomarker (fecal calprotectin), not an AI-assisted diagnostic imaging or interpretation tool for human readers. There are no "human readers" interpreting the output in a way that would be "improved with AI assistance." The technology is a laboratory assay.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

This is an analytical device, and its performance is inherently "standalone" in terms of its measurement capabilities. The CalprestNG ELISA, whether with manual or EasyCal extraction, provides a quantitative result for fecal calprotectin. There isn't an "algorithm" in the sense of AI or machine learning that processes images or complex data for interpretation. The "algorithm" is the biochemical assay itself, which delivers a numerical value.

The performance studies (method comparison, reproducibility) directly evaluate this standalone performance. The "human-in-the-loop" aspect relates to standard laboratory practices (performing the assay, pipetting, reading results from the instrument), but not an assistive AI.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

The "ground truth" for the test set in this analytical validation is established by:

• Reference Method Comparison: The results obtained via the CalprestNG assay with the manual extraction procedure (K160447 predicate device) served as the primary reference method to which the new EasyCal extraction method was compared for equivalence.
• Known samples/standards: For reproducibility and stability, samples with known or well-characterized concentrations of calprotectin (likely established using a highly accurate and precise method) are typically used.
• Internal standards and controls: The assay uses calibrators (0, 2.5, 12.5, 25, 50, 150 ng/ml) to quantify calprotectin concentration, which act as internal "ground truth" for the assay's operational range.

8. The sample size for the training set

This document describes the validation of an in vitro diagnostic assay kit, not a machine learning or AI model that requires a "training set" to learn from data. Therefore, the concept of a "training set" in the AI/ML sense is not applicable here. The assay is based on established biochemical principles (ELISA) and does not "learn" from data in the way an algorithm does.

9. How the ground truth for the training set was established

As explained above, there is no "training set" in the context of AI/ML for this device. The "ground truth" for the assay's core function is inherent in its biochemical design, the use of validated reagents, and the calibration curves established with known standards. The validation studies described in the document (method comparison, reproducibility, stability) assess the performance of the final manufactured product against predefined analytical metrics and comparison to a predicate device.

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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:

• 8 samples tested (S01-S08).
• Mean values ranged from 42.9 µg/g to 5405.6 µg/g.
• Within-run %CV ranged from 0.7% to 8.3%.
• Within-laboratory %CV ranged from 1.4% to 9.1%.
  Multi-Site Reproducibility Study:
• 8 samples tested (S01-S08).
• Mean values ranged from 47.2 µg/g to 5475.6 µg/g.
• Total Precision %CV ranged from 3.2% to 11.3%.
  Lot-to-Lot Precision Study:
• 8 samples tested (S1-S8).
• Mean values ranged from 45.2 µg/g to 5303.1 µg/g.
• Total Precision %CV ranged from 3.6% to 11.3%.
  Extraction Reproducibility Study:
• 10 samples tested (S1-S10).
• Mean values ranged from 47.7 µg/g to 3330.4 µg/g.
• Total Precision %CV for extraction ranged from 1.4% to 13.0%. |
  | Linearity/Analytical Measuring Range (R² close to 1, small intercept, slope close to 1) | Linearity Study:
• Two dilution series analyzed.
• Dilution Series 1: Covered 37.6 – 12,216.0 µg/g. Regression: Intercept=5.7 (95% C.I. 1.6, 16.9), Slope=1.057 (95% C.I. 1.044, 1.075), R²=0.9983.
• Dilution Series 2: Covered 33.5 – 13,339.5 µg/g. Regression: Intercept=3.8 (95% C.I. -0.4, 13.3), Slope=1.031 (95% C.I. 1.014, 1.042), R²=0.9984.
  Claimed Analytical Measuring Range: Direct: 30 - 2000 µg/g. With automatic dilution: 30 - 10,000 µg/g. (Supported by data) |
  | High Dose Hook Effect (No significant effect at high concentrations) | High Dose Hook Effect Study:
• No high dose hook effect observed up to 45,715 µg/g. |
  | Accuracy/Recovery (Total Recovery % close to 100%) | Accuracy/Recovery Study:
• 7 spiked samples (varied baselines).
• Total recovery ranged from 93.6% to 102.0%. |
  | Analytical Sensitivity (Low LoB, LoD, LoQ) | Analytical Sensitivity Studies:
• LoB (Limit of Blank) = 16.7 µg/g.
• LoD (Limit of Detection) = 23.7 µg/g.
• LoQ (Limit of Quantitation) = 30 µg/g.
  Supports claimed direct measuring range of 30 - 2000 µg/g, and 30 - 10,000 µg/g with automatic dilution. |
  | Interfering Substances (No significant interference) | Interfering Substances Study:
• Tested various analytes (e.g., Iron, Prednisone, Mesalamine, Vancomycin, antibiotics, vitamins, hemoglobin) and common enteropathological microorganisms (e.g., E. coli, Salmonella, Klebsiella, Shigella, Yersinia) at specified concentrations.
• Confirmed no interference. |
  | Method Comparison with Predicate (Strong correlation, low bias, high PPA/NPA) | Method Comparison Study:
• Statistical Comparison (Passing-Bablok):
  • Slope = 1.025 (95% CI: 0.990, 1.058) (close to 1).
  • Intercept = -4.5 µg/g (95% CI: -8.7, 0.3) (close to 0).
  • Bias at 80 µg/g = -3.1% (95% CI: -7.2%, 0.5%).
  • Bias at 160 µg/g = -0.3% (95% CI: -2.4%, 2.7%).
  • Correlation (r) = 0.972 (strong positive correlation).
• Clinical Agreement (PPA/NPA):
  • All subjects combined: PPA (lower cutoff) = 93.6% (88.5%, 96.9%), NPA (lower cutoff) = 91.3% (83.6%, 96.2%).
  • PPA (upper cutoff) = 93.9% (87.1%, 97.7%), NPA (upper cutoff) = 95.3% (90.6%, 98.1%).
    (High PPA/NPA values indicate good agreement with the predicate across various patient subgroups and diagnostic cutoffs). |
    | Clinical Sensitivity/Specificity (Clinically meaningful diagnostic performance for IBD vs. IBS/non-IBD) | Clinical Sensitivity/Specificity Study:
• IBD vs. IBS:
  • Borderline considered Positive: Sensitivity = 91.1%, Specificity = 76.2%.
  • Borderline considered Negative: Sensitivity = 80.0%, Specificity = 87.7%.
• IBD vs. Non-IBD:
  • Borderline considered Positive: Sensitivity = 91.1%, Specificity = 74.3%.
  • Borderline considered Negative: Sensitivity = 80.0%, Specificity = 85.1%.
    (Demonstrates ability to differentiate IBD from IBS and non-IBD conditions). |
    | Expected Values/Reference Range (Distribution in healthy population) | Expected Values/Reference Range Study:
• Tested 141 healthy normal adults.
• Distribution: 75.2% 160 µg/g.
  (Provides population data for interpretation). |

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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The DiaSorin LIAISON® Calprotectin assay is an in vitro diagnostic chemiluminescent immunoassay (CLIA) intended for the quantitative measurement, in human stool, of fecal calprotectin, a neutrophilic protein that is a marker of mucosal inflammation. The LIAISON® Calprotectin assay can be used as an aid in the diagnosis of inflammatory bowel diseases (IBD), specifically Crohn's disease and ulcerative colitis, and as an aid in differentiation of IBD from irritable bowel syndrome (IBS). Test results are to be used in conjunction with information obtained from the patients' clinical evaluation and other diagnostic procedures.

The test has to be performed on the LIAISON® XL Analyzer.

The DiaSorin LIAISON® O.S.E.T. Device (Quantitative Stool Extraction and Test) is intended for use in the preparation of human stool specimens for testing in the LIAISON® Calprotectin assay.

The LIAISON® Calprotectin assay is a sandwich assay that uses 2 monoclonal antibodies for capture and detection of calprotectin. The LIAISON® Calprotectin assay must be run on the LIAISON® XL Analyzer, a fully automated system with continuous loading.

Calprotectin is first extracted from human stool samples with LIAISON® Q.S.E.T. Buffer using either the weigh method or the LIAISON® Q.S.E.T. Device. The assay incubates extracted sample, calibrator, control, or calibration verifiers with assay buffer and paramagnetic particles coated with a monoclonal antibody that specifically recognizes the calprotectin heterocomplex. Following incubation, a wash cycle is performed to remove any unbound material. An isoluminol conjugated monoclonal antibody that recognizes calprotectin is then added to the reaction and incubated. The unbound conjugate is removed with a second wash step. Starter reagents are then added and a flash chemiluminescent reaction is initiated. The light signal is measured by a photomultiplier as relative light units (RLU) and is proportional to the concentration of calprotectin present in the calibrators, controls or samples.

All assay steps and incubations are performed by the LIAISON® XL Analyzer. The analyzer software automatically calculates the concentration of calprotectin in the sample. This concentration is expressed in ug/q.

Here's an analysis of the acceptance criteria and supporting studies for the DiaSorin LIAISON® Calprotectin assay, LIAISON® Q.S.E.T. Device, and associated controls/calibrators, based on the provided FDA 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

The FDA 510(k) summary doesn't explicitly state "acceptance criteria" as a separate section with pass/fail thresholds for each performance metric. Instead, the performance studies themselves demonstrate the device's capabilities. I've extracted key performance metrics and their reported results from the document. The implicit "acceptance criteria" here would be that these performance characteristics are adequate for the intended use and comparable to predicate devices, demonstrating substantial equivalence.

2. Sample Sizes Used for the Test Set and Data Provenance

• Method Comparison (LIAISON Calprotectin vs. Commercial Calprotectin Assay):
  • Sample Size: 164 stool samples.
  • Data Provenance: Not explicitly stated, but implies clinical samples spanning the assay range. It's retrospective in the sense that these samples were then tested on two devices.
• Comparative Clinical Studies (IBD vs. non-IBD, IBD vs. IBS):
  • Sample Size: 240 prospectively collected human stool specimens.
  • Data Provenance: Prospectively collected from subjects with signs and symptoms suggestive of IBD or IBS. Geographic origin is not specified.
• Expected Values (Reference Ranges):
  • Sample Size:
    • Apparently Healthy: 127 subjects (15 pediatric, 112 adult)
    • IBD: 102 subjects (19 pediatric, 333 adults - Note: The document states 19 pediatric and 333 adults for IBD/IBS subjects, but the IBD specific count is 102 total in the table, suggesting a subset. Clarification needed if this were a definitive study report.).
    • IBS: 67 subjects (subset of the 19 pediatric and 333 adults mentioned for IBD/IBS).
    • Other GI: 71 subjects.
  • Data Provenance: Stool samples from apparently healthy donors and subjects with physician-diagnosed IBS and IBD. Not explicitly stated if these were the same 240 samples from the clinical studies or an additional set.
• LIAISON® Q.S.E.T. Device Accuracy (Method Comparison of Extraction):
  • Sample Size: 128 human stool samples.
  • Data Provenance: Not explicitly stated, but human stool samples spanning the measuring range.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications

• Method Comparison (LIAISON Calprotectin vs. Commercial Calprotectin Assay): Ground truth was established by another commercial calprotectin assay, not human experts.
• Comparative Clinical Studies (IBD vs. non-IBD, IBD vs. IBS):
  • Ground Truth Establishment: "Diagnosis of IBD, IBS, or other GI disorder was determined based on the results of colonoscopy, as well as other clinical findings. IBD diagnosis was confirmed by histological assessment of biopsy."
  • Number of Experts/Qualifications: Not specified. This typically would involve gastroenterologists, pathologists (for histological assessment), and other clinicians. The document does not provide details on the number or their specific qualifications (e.g., years of experience, board certification).
• Expected Values: Ground truth was based on "physician diagnosed" health status (apparently healthy, IBS, IBD). Number of physicians or their qualifications are not specified.

4. Adjudication Method for the Test Set

• Adjudication method for clinical diagnosis (ground truth): The document states that IBD diagnosis was confirmed by histological assessment of biopsy in addition to colonoscopy and other clinical findings. This implies a comprehensive clinical evaluation, but it doesn't specify an explicit adjudication process like a 2+1 or 3+1 reader consensus for borderline cases or disagreements among diagnostic methods/experts. It's a "clinical diagnosis" approach.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study involving human readers with and without AI assistance was not done. This device is an in-vitro diagnostic (IVD) assay that directly measures a biomarker, not an imaging analysis tool or a decision support system for human readers. Therefore, the concept of human readers improving with AI assistance is not applicable in this context.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the studies presented (method comparison, clinical sensitivity/specificity, analytical performance) represent the standalone performance of the LIAISON® Calprotectin assay. It is an automated chemiluminescent immunoassay run on the LIAISON® XL Analyzer, directly providing quantitative results without human interpretation as part of the primary diagnostic output.

7. The Type of Ground Truth Used

• Clinical Studies:
  • Expert Consensus/Clinical Diagnosis: For IBD, IBS, and other GI disorders, the ground truth was "clinical diagnosis by colonoscopy, as well as other clinical findings," with "histological assessment of biopsy" confirming IBD. This is a form of expert consensus based on established clinical and pathological methods.
• Method Comparison:
  • Comparator Device: The ground truth was established by a "commercial calprotectin assay."
• Expected Values:
  • Physician Diagnosis: "Physician diagnosed" health status.

8. The Sample Size for the Training Set

The provided document describes a 510(k) premarket notification for an IVD kit, which typically involves analytical validation and clinical performance studies, not a "training set" in the context of machine learning model development. For IVDs, the kit components (reagents, calibrators, controls) are manufactured and their performance characteristics are validated extensively. The studies described are validation studies, not training studies. Therefore, there is no "training set" in the machine learning sense for this device. The development of the assay itself would have involved internal optimization and development work, but specific sample sizes for "training" are not typically reported in 510(k) submissions for such assays.

9. How the Ground Truth for the Training Set Was Established

As noted above, there is no "training set" in the machine learning sense. The ground truth for the validation studies (clinical and method comparison) are described in point 7.

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The Fecal Extraction Device is a single use tube containing extraction buffer intended for sampling and extracting human stool specimens and subsequent analysis with the QUANTA Flash Calprotectin assay.

The Fecal Extraction Device acquires the amount of stool necessary to perform the QUANTA Flash Calprotectin assay directly from the primary specimen container instead of weighing the sample. The device consists of a tube, containing 2.8 mL of extraction buffer, and a stick shaped with seven grooves for collecting the sample. The upper end of the device is made up of two parts which can be removed with two separate rotations: the white screw cap (connected to the plastic stick with grooves) is removed by twisting counter-clockwise. The red lower part (for retaining the excess material) is removed by twisting clockwise. Once having completed the extraction procedure, remove both the white and red upper parts. The tube containing the extracted sample can be placed directly into the BIO-FLASH instrument sample rack.

The Fecal Extraction Device is intended for sampling and extracting human stool specimens for subsequent analysis with the QUANTA Flash Calprotectin assay. The device underwent several validation studies to demonstrate its performance and substantial equivalence to the predicate device (QUANTA Flash Calprotectin using manual extraction).

1. Table of Acceptance Criteria and Reported Device Performance

Stool Extraction Method Comparison: Fecal Extraction Device vs. Manual Weighing Method

Device Validation (Amount of Fecal Material Collected)

Extraction Reproducibility

Sample Stability and Handling (Extracted Samples)

Fecal Extraction Device Stability (Shelf Life - Real Time Stability)

Stability at Room Temperature (Fecal Extraction Device)

2. Sample Sizes and Data Provenance

• Stool Extraction Method Comparison Test Set: 97 human stool samples.
• Device Validation (Fecal Material Collection): 5 different human stool samples, tested in replicates of five.
• Extraction Reproducibility: 8 samples, with 75 data points per sample (replicates of 5, once a day for 5 days, by 3 independent operators).
• Sample Stability and Handling: 7 human stool samples (n=1 indeterminate, n=2 around cut-off, n=4 positive).
• Fecal Extraction Device Functionality at Expiration: 15 human stool samples (n=11 negative, n=2 indeterminate, n=1 around cut-off, n=1 positive).
• Fecal Extraction Device Stability at Room Temperature: 6 human stool samples (lots 2 and 3: n=1 indeterminate, n=1 around cut-off, n=3 positive; lot 1: n=1 indeterminate, n=1 around cut-off, n=4 positive).

Data Provenance: The document does not explicitly state the country of origin for the human stool samples. Given "Inova Diagnostics, Inc." is located in "San Diego, CA, 92131", it can be inferred that the studies were likely conducted in the United States. The studies are described as analytical performance characteristics, implying they are laboratory-based investigations evaluating the device's technical specifications rather than clinical trials for diagnostic accuracy with patient outcomes. The term "human stool samples" suggests these are clinical specimens, but whether they are retrospective or prospectively collected for the purpose of the study is not specified, though typically such analytical studies would use prospectively collected or banked specimens.

3. Number of Experts and Qualifications

• No information is provided regarding the use of experts to establish a "ground truth" for the test sets in the typical sense of medical image interpretation or clinical diagnosis. The studies focus on analytical performance characteristics (e.g., comparison of extraction methods, precision, stability) where the "ground truth" is typically the measured value from a reference method or a known target value.
• For the reproducibility study, "three independent operators" were involved in performing extractions, but their specific qualifications beyond being "operators" are not detailed.

4. Adjudication Method

• No adjudication method is described as these studies focus on quantitative analytical performance rather than diagnostic interpretation where adjudication by multiple experts would be common. The "Stool Extraction method comparison" uses a statistical method (Passing-Bablok fit) to compare results from the new device against a manual weighing method. Replicates were used for precision studies, but not for settling disputes between reader interpretations.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No MRMC comparative effectiveness study was performed. The document describes a comparison between two extraction methods (Fecal Extraction Device vs. Manual weighing method) and various performance characteristics of the Fecal Extraction Device itself. This is an analytical device for sample preparation, not a diagnostic imaging or interpretative AI device that typically undergoes MRMC studies to assess human reader improvement with AI assistance.

6. Standalone (Algorithm Only) Performance

• The studies described are for the "Fecal Extraction Device," which is a physical device for sample preparation, not a standalone software algorithm or AI. Its performance is evaluated in conjunction with the QUANTA Flash Calprotectin assay. The comparison study directly assesses the performance of the extraction device alone against a reference extraction method.

7. Type of Ground Truth Used

• For the "Stool Extraction method comparison," the ground truth is implicitly the quantitative calprotectin concentration obtained using the "manual weighing method," which serves as the reference method.
• For "Device Validation" (fecal material collection), the ground truth is the measured weight of the collected fecal material, with an expected target range of 56 mg ± 10%.
• For "Reproducibility Studies," the ground truth is the mean calprotectin concentration values of the samples, against which the precision (SD and %CV) of repeated measurements is assessed.
• For "Stability Studies," the ground truth for extracted sample stability is the initial measurement (time zero/zero cycles) or the pH of fresh devices for device stability, against which recovered concentrations or pH values are compared over time/conditions.

8. Sample Size for the Training Set

• The document describes validation studies for a medical device (Fecal Extraction Device), not an AI or machine learning algorithm. Therefore, there is no concept of a "training set" in the context of the provided information.

9. How the Ground Truth for the Training Set was Established

• As there is no training set for an AI/ML algorithm involved, this question is not applicable.

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