(186 days)
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
| Acceptance Criteria | Reported Device Performance (Fecal Extraction Device vs. Manual Extraction, n=97) |
|---|---|
| Intercept of regression line ± 15% of cut-off (18 mg/kg) | -1.2 (-9.7 to 6.4) - Met (-2.7 to 2.7 mg/kg is ±15% of cutoff, and -1.2 is within this range) |
| Slope of regression line between 0.90 and 1.10 | 0.93 (0.82 to 1.06) - Met |
| Predicted Bias at cut-off ≤ 15% | -7.8 % (-16.0% to 0.6%) - Met |
| 95% CI of the bias: does not exceed medically significant difference, 20% of cut-off | -16.0% to 0.6% - Met (Not exceeding 20% of 18 mg/kg which is 3.6 mg/kg) |
| Correlation r > 0.95 | 0.975 - Met |
Device Validation (Amount of Fecal Material Collected)
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Weight collected by FED is 56 mg ±10% (50 to 62 mg) | Mean Sample Weight (95% CI): 56 (55 - 57) mg - Met |
Extraction Reproducibility
| Acceptance Criteria | Reported Device Performance (Within Laboratory (Total Imprecision) %CV or SD) |
|---|---|
| Within Laboratory (Total Imprecision) %CV: ≤ 15% | Sample CVs ranged from 10.2% to 25.4% (for Sample 1) and 13.3% (for Sample 8), with only Sample 1 exceeding 15%. This suggests a partial meet depending on the interpretation for lower concentrations. However, the document states "All acceptance criteria were met," so it implies Sample 1's SD criterion was met. |
| or SD: ≤ 7.5 mg/kg for negative samples | Sample 1 (mean 29.5 mg/kg) had an SD of 7.5 mg/kg. Sample 2 (mean 40.0 mg/kg) had an SD of 6.8 mg/kg. Sample 3 (mean 53.2 mg/kg) had an SD of 7.5 mg/kg. - Met (for samples near cut-off/negative range) |
Sample Stability and Handling (Extracted Samples)
| Acceptance Criteria | Reported Device Performance |
|---|---|
| 80-120% average recovery | All samples fulfilled the acceptance criteria at each time point for each condition. - Met (Recommended storage: up to 72 hours at room temperature, up to 14 days at 2-8°C, up to 4 freeze/thaw cycles.) |
Fecal Extraction Device Stability (Shelf Life - Real Time Stability)
| Acceptance Criteria | Reported Device Performance |
|---|---|
| pH between 7.70 and 7.90 | pH values for three lots over 24-26 months ranged from 7.77 to 7.82. - Met |
| 70-130% average recovery (functionality at expiration date) | All samples fulfilled the acceptance criteria. - Met (Supports 2-year expiration date.) |
Stability at Room Temperature (Fecal Extraction Device)
| Acceptance Criteria | Reported Device Performance |
|---|---|
| 80-120% average recovery | All results obtained using the three different lots of Fecal Extraction Device fulfilled the acceptance criteria. - Met (Supports storage at room temperature up to 72 hours.) |
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.
§ 866.5180 Fecal calprotectin immunological test system.
(a)
Identification. A fecal calprotectin immunological test system is anin vitro diagnostic device that consists of reagents used to quantitatively measure, by immunochemical techniques, fecal calprotectin in human stool specimens. The device is intended forin vitro diagnostic use 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.(b)
Classification. Class II (special controls). The special control for these devices is FDA's guidance document entitled “Class II Special Controls Guidance Document: Fecal Calprotectin Immunological Test Systems.” For the availability of this guidance document, see § 866.1(e).