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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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