(90 days)
Not Found
No
The device description and performance studies focus on a turbidimetric immunoassay and standard statistical analyses, with no mention of AI or ML algorithms.
No
This device is an in vitro diagnostic assay used for the quantitative measurement of fecal calprotectin, which aids in the diagnosis of inflammatory bowel disease (IBD). It is a diagnostic tool, not a therapeutic one.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device "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)". This indicates a diagnostic purpose.
No
The device is an in vitro diagnostic assay and associated sample preparation tube, which are physical components used to perform a laboratory test. It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the BÜHLMANN fCAL turbo is an "in vitro diagnostic assay intended for the quantitative measurement of fecal calprotectin... in human stool." It also states its purpose is to "aid in the diagnosis of inflammatory bowel disease (IBD)... and aid in the differentiation of IBD from irritable bowel syndrome (IBS) in conjunction with other laboratory and clinical findings." This clearly indicates the device is used to test samples taken from the human body outside of the body for diagnostic purposes.
- Device Description: The description details a laboratory-based assay (particle-enhanced turbidimetric immunoassay) performed on "patient stool extracts." This further confirms it's an in vitro test.
- Anatomical Site: The sample is "Human stool," which is a biological specimen taken from the body.
- Performance Studies: The document describes various performance studies (Precision, Linearity, Accuracy/Recovery, Analytical Sensitivity, Interfering Substances, Method Comparison, Clinical Sensitivity/Specificity) which are typical for evaluating the performance of an IVD.
- Key Metrics: The listed key metrics (Sensitivity, Specificity, PPV, NPV, etc.) are standard metrics used to evaluate the clinical performance of diagnostic tests.
- Predicate Device: The mention of a predicate device (K190784; BÜHLMANN fCAL® turbo) is common in regulatory submissions for IVDs, indicating a comparison to a previously cleared device.
All of these points align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
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.
Product codes (comma separated list FDA assigned to the subject device)
NXO
Device Description
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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Human stool
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision
The submission includes single-site repeatability study results, multi-site reproducibility study results, lot-to-lot precision study results, and extraction reproducibility study results (both manual weighing and CALEX® Cap). Sample sizes for these precision studies range from n=72 to n=80 per sample tested. The results are presented as mean in µg/g, standard deviation (SD), and coefficient of variation (%CV) for within-run, between-run, between-day, between-lot, between-site, and total precision.
Linearity
Study procedures were performed using two dilution series. For each dilution series, a stool specimen extract with a calprotectin concentration above the anticipated upper limit of the analytical measuring range was combined with a stool specimen extract with a calprotectin concentration below the anticipated lower limit of the analytical measuring range, in various mixing ratios covering the range; each dilution was tested in four (4) replicates.
Dilution Series 1: Measuring Range 37.6 – 12,216.0 µg/g, R2 = 0.9983.
Dilution Series 2: Measuring Range 33.5 - 13,339.5 µg/g, R2 = 0.9984.
Key results: Supports a direct analytical measuring range of 30 - 2000 µg/g and a measuring range with automatic dilution of 30 - 10,000 ug/g.
High Dose Hook Effect
No high dose hook effect at theoretical concentrations up to 45,715 ug/g.
Accuracy/Recovery
Performed on 7 samples with baseline results ranging from 44.10 µg/g to 1076.33 µg/g. Total recovery ranged from 93.6% to 102.0%.
Analytical Sensitivity
LoB = 16.7 µg/g
LoD = 23.7 µg/g
LoQ = 30 µg/g
Key results: Supports a claimed direct measuring range of 30 -2000 µg/g and a measuring range of 30 - 10,000 µg/g with automatic dilution.
Interfering Substances
Study procedures were performed using stool specimen extracts with approximate calprotectin concentrations of 30 µg/g, 100 µg/g, 300 µg/g, and 550 µg/g. Various analytes, pharmaceuticals, nutritional supplements, and enteropathological microorganisms did not interfere.
Method Comparison
Study type: Comparison of BÜHLMANN fCAL® turbo with the predicate device (BÜHLMANN fCAL® ELISA assay).
Sample size: 248 clinical study samples. 220 samples had valid results within the linear measuring range for both assays.
Key results: Passing-Bablok regression analysis shows a slope of 1.025 (95% CI: 0.990, 1.058), intercept of -4.5 µg/g (95% CI: -8.7, 0.3), and correlation (r) of 0.972.
Frequency counts of agreement between the two assays were also provided:
160 µg/g: fCAL turbo 92, ELISA 92
Extraction Method Comparison
Study type: Comparison of CALEX® Cap extraction method with manual weighing extraction method using BÜHLMANN fCAL® turbo.
Sample size: 241 clinical study samples. 202 samples had valid results within the linear measuring range for both extraction methods.
Key results: Passing-Bablok regression analysis shows a slope of 1.149 (95% CI: 1.100, 1.201), intercept of -8.3 µg/g (95% CI: -17.1, -2.0), and correlation (r) of 0.921.
Frequency counts of agreement between the two extraction methods were also provided:
160 µg/g: Manual weighing 122, CALEX Cap 122
Clinical Sensitivity/Specificity (Manual Weighing Extraction Method)
Study type: Performance of BÜHLMANN fCAL® turbo in differentiating IBD from IBS and IBD from non-IBD.
Sample size: 265 for IBD vs. IBS; 337 for IBD vs. non-IBD.
Key results for IBD vs. IBS (Borderline Values Considered Positive):
Sensitivity = 91.1%; 95% C.I. (85.0%, 95.3%)
Specificity = 76.2%; 95% C.I. (67.9%, 83.2%)
PPV = 79.9%; 95% C.I. (72.7%, 85.9%)
NPV = 89.2%; 95% C.I. (81.9%, 94.3%)
Key results for IBD vs. IBS (Borderline Values Considered Negative):
Sensitivity = 80.0%; 95% C.I. (72.3%, 86.4%)
Specificity = 87.7%; 95% C.I. (80.8%, 92.8%)
PPV = 87.1%; 95% C.I. (79.9%, 92.4%)
NPV = 80.9%; 95% C.I. (73.4%, 87.0%)
Key results for IBD vs. non-IBD (Borderline Values Considered Positive):
Sensitivity = 91.1%; 95% C.I. (85.0%, 95.3%)
Specificity = 74.3%; 95% C.I. (67.7%, 80.1%)
PPV = 70.3%; 95% C.I. (62.9%, 76.9%)
NPV = 92.6%; 95% C.I. (87.4%, 96.1%)
Key results for IBD vs. non-IBD (Borderline Values Considered Negative):
Sensitivity = 80.0%; 95% C.I. (72.3%, 86.4%)
Specificity = 85.1%; 95% C.I. (79.5%, 89.8%)
PPV = 78.3%; 95% C.I. (70.4%, 84.8%)
NPV = 86.4%; 95% C.I. (80.9%, 90.9%)
Expected Values/Reference Range
Study type: Determination of calprotectin levels in healthy adults.
Sample size: 141 apparently healthy normal adults (> 21 years of age) with no symptoms or signs of gastrointestinal disease.
Key results:
160 µg/g: 17 subjects (12.1%)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Clinical Sensitivity/Specificity (Manual Weighing Extraction Method) for IBD vs. IBS:
Borderline Values Considered Positive:
Sensitivity = 91.1%; 95% C.I. (85.0%, 95.3%)
Specificity = 76.2%; 95% C.I. (67.9%, 83.2%)
PPV = 79.9%; 95% C.I. (72.7%, 85.9%)
NPV = 89.2%; 95% C.I. (81.9%, 94.3%)
Borderline Values Considered Negative:
Sensitivity = 80.0%; 95% C.I. (72.3%, 86.4%)
Specificity = 87.7%; 95% C.I. (80.8%, 92.8%)
PPV = 87.1%; 95% C.I. (79.9%, 92.4%)
NPV = 80.9%; 95% C.I. (73.4%, 87.0%)
Clinical Sensitivity/Specificity (Manual Weighing Extraction Method) for IBD vs. non-IBD:
Borderline Values Considered Positive:
Sensitivity = 91.1%; 95% C.I. (85.0%, 95.3%)
Specificity = 74.3%; 95% C.I. (67.7%, 80.1%)
PPV = 70.3%; 95% C.I. (62.9%, 76.9%)
NPV = 92.6%; 95% C.I. (87.4%, 96.1%)
Borderline Values Considered Negative:
Sensitivity = 80.0%; 95% C.I. (72.3%, 86.4%)
Specificity = 85.1%; 95% C.I. (79.5%, 89.8%)
PPV = 78.3%; 95% C.I. (70.4%, 84.8%)
NPV = 86.4%; 95% C.I. (80.9%, 90.9%)
Method Comparison (BÜHLMANN fCAL® turbo vs. BÜHLMANN fCAL® ELISA assay):
PPA (lower cutoff) for All subjects: 146/156 = 93.6% [88.5%, 96.9%]
NPA (lower cutoff) for All subjects: 84/92 = 91.3% [83.6%, 96.2%]
PPA (upper cutoff) for All subjects: 92/98 = 93.9% [87.1%, 97.7%]
NPA (upper cutoff) for All subjects: 143/150 = 95.3% [90.6%, 98.1%]
Extraction Method Comparison (CALEX® Cap vs. Manual Weighing):
PPA (lower cutoff): 159/162 = 98.1% [94.7%, 99.6%]
NPA (lower cutoff): 71/79 = 89.9% [81.0%, 95.5%]
PPA (upper cutoff): 122/125 = 97.6% [93.1%, 99.5%]
NPA (upper cutoff): 112/116 = 96.6% [91.4%, 99.1%]
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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).
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food & Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
September 24, 2019
BÜHLMANN Laboratories AG Roshana Ahmed President Quaras, LLC 2101 Camino Rey Fullerton, California 92833
Re: K191718
Trade/Device Name: BÜHLMANN fCAL turbo and CALEX Cap Regulation Number: 21 CFR 866.5180 Regulation Name: Fecal calprotectin immunological test system Regulatory Class: Class II Product Code: NXO Dated: June 26, 2019 Received: June 26, 2019
Dear Roshana Ahmed:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
1
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
for
Douglas Jeffery, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Ouality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known)
Device Name BÜHLMANN fCAL turbo, CALEX Cap
Indications for Use (Describe)
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.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ☑ Prescription Use (Part 21 CFR 801 Subpart D) | ☐ Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
510(k) Summary
I. Submitter
BUHLMANN Laboratories AG Baselstrasse 55 Schönenbuch CH-4124 Switzerland Phone: +41 61 487 12 50
Contact Person: Laura Zurbrügg Date Prepared: September 11, 2019
II. Device
| Device Proprietary Names: | BÜHLMANN fCAL® turbo, CALEX® Cap |
|---|---|
| Common or Usual Name: | Fecal calprotectin immunological test system |
| Classification Name: | Calprotectin, Fecal |
| Regulation Number: | 21 CFR 866.5180 |
| Product Code: | NXO |
| Device Classification: | II |
III. Predicate Device
Substantial equivalence is claimed to the following device:
- BÜHLMANN fCAL® turbo, K190784, BÜHLMANN Laboratories AG
Device Description IV.
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.
4
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.
V. Indications for Use
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 CALEX® Cap is a single use tube intended for the preparation of human stool samples to be used with the BÜHLMANN fCAL® turbo.
VI. Comparison of Technological Characteristics
The subject and predicate device utilize the same exact assay, controls, and calibrators. The only difference between the two products is the provision of the CALEX® Cap as an alternative sample extraction method to manual weighing.
The tables below compare key technological features between the subject and predicate devices.
Technological comparison
Comparison of Assay
| | BÜHLMANN fCAL® turbo and
CALEX® Cap | BÜHLMANN fCAL® turbo
(K190784) |
|--------------------------------------------|----------------------------------------------------------------------------------|----------------------------------------------------------------------------------|
| Analyte | Human fecal calprotectin
(MRP8/14) | Human fecal calprotectin
(MRP8/14) |
| Assay format | Quantitative | Quantitative |
| Specimen type | Human stool | Human stool |
| Clinical Decision
Thresholds | Normal: 160 µg/g | Normal: 160 µg/g |
| Method | PETIA | PETIA |
| Automation | Automated | Automated |
| Solid phase | Polystyrene nanoparticles (beads) | Polystyrene nanoparticles (beads) |
| Detection method | Automated clinical chemistry analyzer read at 546 nm | Automated clinical chemistry analyzer read at 546 nm |
| Analyte-specific
antibody
components | Polyclonal antibodies against human calprotectin coated on polystyrene beads | Polyclonal antibodies against human calprotectin coated on polystyrene beads |
5
| | BÜHLMANN fCAL® turbo and
CALEX® Cap | BÜHLMANN fCAL® turbo
(K190784) |
|----------------------|----------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------|
| Measuring range | Direct measuring range:
30 - 2000 μg/g
Measuring range with automatic
dilution: 30 - 10,000 μg/g | Direct measuring range:
30 - 2000 μg/g
Measuring range with automatic
dilution: 30 – 10,000 μg/g |
| Extraction
Method | Manual Weighing (1:50 dilution in
Extraction Buffer)
CALEX® Cap (1:500 dilution in
Extraction Buffer) | Manual Weighing (1:50 dilution in
Extraction Buffer)
N/A |
Comparison of Calibrators
| BÜHLMANN fCAL® turbo | BÜHLMANN fCAL® turbo (K190784) | |
|---|---|---|
| Indications for Use | The BÜHLMANN fCAL® turbo | |
| Calibrator Kit is intended for use | ||
| with the BÜHLMANN fCAL® | ||
| turbo Reagent Kit for the | ||
| determination of fecal calprotectin | ||
| levels in extracted stool samples. | ||
| Comprised of six (6) calibrators, | ||
| each calibrator establishes a point | ||
| of reference for the working curve | ||
| that is used to calculate test results | ||
| from patient samples. | The BÜHLMANN fCAL® turbo | |
| Calibrator Kit is intended for use | ||
| with the BÜHLMANN fCAL® | ||
| turbo Reagent Kit for the | ||
| determination of fecal calprotectin | ||
| levels in extracted stool samples. | ||
| Comprised of six (6) calibrators, | ||
| each calibrator establishes a point | ||
| of reference for the working curve | ||
| that is used to calculate test results | ||
| from patient samples. | ||
| Method | BÜHLMANN fCAL® turbo | BÜHLMANN fCAL® turbo |
| Analyte | Native human calprotectin | |
| Source: human granulocyte extract | Native human calprotectin | |
| Source: human granulocyte extract | ||
| Calibrators | 6 levels: | |
| Target values: 0, 50, 200, 500, | ||
| 1000, 2000 µg/g | 6 levels: | |
| Target values: 0, 50, 200, 500, | ||
| 1000, 2000 µg/g | ||
| Conversion factor | N/A | N/A |
| Value assignment: | Calibrator values assigned using a | |
| value transfer protocol for each | ||
| calibrator lot. Values are indicated | ||
| in the QC datasheet. | Calibrator values assigned using a | |
| value transfer protocol for each | ||
| calibrator lot. Values are indicated | ||
| in the QC datasheet. | ||
| Configuration | Available as a separate | |
| BÜHLMANN fCAL® turbo | ||
| Calibrator Kit | Available as a separate | |
| BÜHLMANN fCAL® turbo | ||
| Calibrator Kit |
-----------------------------------This space intentionally left blank--------------------------------------------------------------------------------------------------------
6
| | BÜHLMANN fCAL® turbo | BÜHLMANN fCAL® turbo
(K190784) | |
|------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------|
| Indications for
Use | The BÜHLMANN fCAL® turbo
Control Kit, comprised of a high
and low control, is intended for use
with the BÜHLMANN fCAL®
turbo Reagent Kit, for quality
control, in the determination of
fecal calprotectin levels in extracted
stool samples. | The BÜHLMANN fCAL® turbo
Control Kit, comprised of a high
and low control, is intended for use
with the BÜHLMANN fCAL®
turbo Reagent Kit, for quality
control, in the determination of
fecal calprotectin levels in
extracted stool samples. | |
| | Method | BÜHLMANN fCAL® turbo | |
| | Analyte | Native human calprotectin | Native human calprotectin |
| | | Source: human granulocyte extract | Source: human granulocyte extract |
| | Levels | 2 (low and high) | 2 (low and high) |
| | Physio-chemical
characteristics | Ready to use | Ready to use |
| | Configuration | Available as a separate
BÜHLMANN fCAL® turbo Control
Kit | Available as a separate
BÜHLMANN fCAL® turbo
Control Kit |
Comparison of Controls
Discussion
As seen above, the only difference between the subject and predicate devices is the provision of the CALEX® Cap as an alternative sample extraction method. This technological difference does not create new questions of safety and effectiveness and the differences are addressed by the performance studies identified below.
Performance Data VII.
A. Clinical Thresholds
| Calprotectin Concentration | Interpretation | Follow-Up |
|---|---|---|
| 160 µg/g | Elevated | Retest as appropriate |
-------------------------This space intentionally left blank------------------------------------------------------------------------------------------------------------------
7
B. Precision
| ID | Mean
[µg/g] | n | Within-run
(Repeatability) | | Between-
run | | Between-
day | | Within-
laboratory | |
|-----|----------------|----|-------------------------------|------|-----------------|------|-----------------|------|-----------------------|------|
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| S01 | 42.9 | 80 | 3.6 | 8.3% | 1.2 | 2.7% | 1.1 | 2.5% | 3.9 | 9.1% |
| S02 | 98.4 | 80 | 2.5 | 2.6% | 1.8 | 1.8% | 2.2 | 2.2% | 3.7 | 3.8% |
| S03 | 166.5 | 80 | 4.3 | 2.6% | 0.8 | 0.5% | 1.9 | 1.2% | 4.8 | 2.9% |
| S04 | 267.6 | 80 | 3.9 | 1.4% | 2.5 | 0.9% | 1.8 | 0.7% | 5.0 | 1.9% |
| S05 | 642.0 | 80 | 20.1 | 3.1% | 14.9 | 2.3% | 0.0 | 0.0% | 25.1 | 3.9% |
| S06 | 1414.2 | 80 | 19.6 | 1.4% | 11.1 | 0.8% | 3.5 | 0.2% | 22.8 | 1.6% |
| S07 | 3251.4 | 80 | 40.8 | 1.3% | 21.4 | 0.7% | 19.7 | 0.6% | 50.1 | 1.5% |
| S08 | 5405.6 | 80 | 40.2 | 0.7% | 56.6 | 1.0% | 34.5 | 0.6% | 77.5 | 1.4% |
Single-Site Repeatability Study Results (Manual Weighing Extraction Method):
| Multi-Site Reproducibility Study Results (Manual Weighing Extraction Method): | ||||
|---|---|---|---|---|
| ID | Mean
[µg/g] | n | Within-run
(Repeatability) | | Between-
day | | Between-
site | | Total
Precision | |
|-----|----------------|----|-------------------------------|-----|-----------------|-----|------------------|-----|--------------------|-----|
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| S01 | 47.2 | 75 | 3.6 | 7.6 | 2.4 | 5.0 | 0.0 | 0.0 | 4.3 | 9.1 |
| S02 | 91.1 | 75 | 3.5 | 3.8 | 3.5 | 3.8 | 2.8 | 3.1 | 5.7 | 6.2 |
| S03 | 185.4 | 75 | 5.1 | 2.7 | 2.7 | 1.4 | 5.5 | 3.0 | 7.9 | 4.3 |
| S04 | 276.9 | 75 | 6.4 | 2.3 | 4.5 | 1.6 | 9.7 | 3.5 | 12.5 | 4.5 |
| S05 | 674.5 | 75 | 12.9 | 1.9 | 1.2 | 0.2 | 22.8 | 3.4 | 26.3 | 3.9 |
| S06 | 1519.6 | 75 | 25.3 | 1.7 | 17.8 | 1.2 | 62.3 | 4.1 | 69.6 | 4.6 |
| S07 | 3343.8 | 75 | 54.6 | 1.6 | 35.6 | 1.1 | 100.0 | 3.0 | 119.4 | 3.6 |
| S08 | 5475.6 | 75 | 72.1 | 1.3 | 35.8 | 0.7 | 154.2 | 2.8 | 173.9 | 3.2 |
8
| ID | Mean
[µg/g] | n | Within-Run
(Repeatability) | | Between-
Day | | Between-
Lot | | Total
Precision | |
|----|----------------|----|-------------------------------|------|-----------------|------|-----------------|------|--------------------|-------|
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| S1 | 45.2 | 75 | 3.22 | 7.1% | 1.36 | 3.0% | 3.70 | 8.2% | 5.09 | 11.3% |
| S2 | 86.4 | 75 | 3.69 | 4.3% | 1.19 | 1.4% | 5.66 | 6.6% | 6.86 | 7.9% |
| S3 | 175.8 | 75 | 5.04 | 2.9% | 0.29 | 0.2% | 9.90 | 5.6% | 11.11 | 6.3% |
| S4 | 263.9 | 75 | 7.55 | 2.9% | 0.00 | 0.0% | 9.98 | 3.8% | 12.52 | 4.7% |
| S5 | 647.4 | 75 | 15.47 | 2.4% | 0.00 | 0.0% | 15.28 | 2.4% | 21.74 | 3.4% |
| S6 | 1460.7 | 75 | 33.66 | 2.3% | 11.64 | 0.8% | 41.01 | 2.8% | 54.32 | 3.7% |
| S7 | 3234.5 | 75 | 71.23 | 2.2% | 8.90 | 0.3% | 130.29 | 4.0% | 148.76 | 4.6% |
| S8 | 5303.1 | 75 | 97.42 | 1.8% | 11.18 | 0.2% | 163.87 | 3.1% | 190.97 | 3.6% |
Lot-to-Lot Precision Study Results (Manual Weighing Extraction Method):
Extraction Reproducibility (Manual Weighing Extraction Method) Study Results:
| Sample | n | Mean
(µg/g) | Within-Run
(Repeatability) | | Between-
extraction | | Between-
day | | Between-
operator | | Total
Precision | |
|--------|----|----------------|-------------------------------|-----|------------------------|------|-----------------|------|----------------------|-----|--------------------|------|
| | | | SD
(µg/g) | %CV | SD
(µg/g) | %CV | SD
(µg/g) | %CV | SD
(µg/g) | %CV | SD
(µg/g) | %CV |
| S1 | 80 | 47.7 | 2.8 | 5.9 | 1.1 | 2.4 | 0.7 | 1.5 | 1.4 | 2.9 | 3.4 | 7.2 |
| S2 | 80 | 72.3 | 3.8 | 5.2 | 3.9 | 5.4 | 4.2 | 5.8 | 0.0 | 0.0 | 6.8 | 9.5 |
| S3 | 80 | 96.1 | 3.8 | 3.9 | 2.2 | 2.3 | 1.4 | 1.4 | 0.0 | 0.0 | 4.6 | 4.8 |
| S4 | 80 | 170.6 | 4.0 | 2.4 | 2.5 | 1.5 | 8.7 | 5.1 | 0.0 | 0.0 | 9.9 | 5.8 |
| S5 | 80 | 277.0 | 3.7 | 1.4 | 27.9 | 10.1 | 10.0 | 3.6 | 11.0 | 4.0 | 31.8 | 11.5 |
| S6 | 80 | 421.1 | 9.8 | 2.3 | 5.9 | 1.4 | 15.3 | 3.6 | 0.0 | 0.0 | 19.1 | 4.5 |
| S7 | 80 | 573.9 | 5.4 | 0.9 | 39.5 | 6.9 | 0.0 | 0.0 | 0.0 | 0.0 | 39.9 | 6.9 |
| S8 | 80 | 1387.4 | 39.1 | 2.8 | 75.1 | 5.4 | 159.9 | 11.5 | 0.0 | 0.0 | 180.9 | 13.0 |
| S9 | 80 | 3264.9 | 87.2 | 2.7 | 236.2 | 7.2 | 256.9 | 7.9 | 0.0 | 0.0 | 359.7 | 11.0 |
| S10 | 80 | 3330.4 | 89.8 | 2.7 | 92.4 | 2.8 | 75.7 | 2.3 | 0.0 | 0.0 | 149.4 | 4.5 |
------------------------------This space intentionally left blank--------------------------------------------------------
9
| Sample | n | Mean
(µg/g) | Within-Run
(Repeatability) | | Between-
extraction | | Between-
day | | Between-Lot | | Between-
operator | | Total
Precision | |
|--------|----|----------------|-------------------------------|-----|------------------------|------|-----------------|------|--------------|-----|----------------------|------|--------------------|------|
| | | | SD
(µg/g) | %CV | SD
(µg/g) | %CV | SD
(µg/g) | %CV | SD
(µg/g) | %CV | SD
(µg/g) | %CV | SD
(µg/g) | %CV |
| S1 | 72 | 42.7 | 3.2 | 7.5 | 4.6 | 10.8 | 0.0 | 0.0 | 2.7 | 6.3 | 0.0 | 0.0 | 6.2 | 14.5 |
| S2 | 72 | 71.5 | 3.9 | 5.4 | 6.9 | 9.6 | 9.4 | 13.1 | 0.0 | 0.0 | 0.0 | 0.0 | 12.2 | 17.1 |
| S3 | 72 | 111.3 | 3.3 | 2.9 | 14.2 | 12.7 | 0.0 | 0.0 | 6.8 | 6.1 | 7.8 | 7.0 | 17.9 | 16.1 |
| S4 | 72 | 119.8 | 2.9 | 2.4 | 7.2 | 6.0 | 5.8 | 4.8 | 0.0 | 0.0 | 0.0 | 0.0 | 9.7 | 8.1 |
| S5 | 72 | 213.0 | 3.2 | 1.5 | 27.9 | 13.1 | 0.0 | 0.0 | 0.0 | 0.0 | 9.0 | 4.2 | 29.5 | 13.8 |
| S6 | 72 | 297.2 | 3.7 | 1.2 | 24.5 | 8.2 | 13.5 | 4.6 | 18.0 | 6.1 | 12.3 | 4.1 | 35.6 | 12.0 |
| S7 | 72 | 561.2 | 5.5 | 1.0 | 18.6 | 3.3 | 66.1 | 11.8 | 0.0 | 0.0 | 0.0 | 0.0 | 68.9 | 12.3 |
| S8 | 72 | 610.0 | 4.7 | 0.8 | 74.3 | 12.2 | 28.2 | 4.6 | 0.0 | 0.0 | 0.0 | 0.0 | 79.6 | 13.1 |
| S9 | 72 | 940.4 | 12.2 | 1.3 | 152.7 | 16.2 | 34.8 | 3.7 | 0.0 | 0.0 | 97.5 | 10.4 | 184.9 | 19.7 |
| S10 | 72 | 1558.4 | 7.8 | 0.5 | 152.0 | 9.8 | 39.9 | 2.6 | 98.6 | 6.3 | 146.2 | 9.4 | 236.4 | 15.2 |
| S11 | 72 | 2041.6 | 27.2 | 1.3 | 150.3 | 7.4 | 133.8 | 6.6 | 88.9 | 4.4 | 10.5 | 0.5 | 221.9 | 10.9 |
| S12 | 72 | 3440.0 | 48.7 | 1.4 | 177.7 | 5.2 | 321.5 | 9.3 | 0.0 | 0.0 | 0.0 | 0.0 | 370.5 | 10.8 |
Extraction Reproducibility (CALEX® Cap) Study Results:
C. Linearity
Study procedures were performed using two dilution series. For each dilution series, a stool specimen extract with a calprotectin concentration above the anticipated upper limit of the analytical measuring range was combined with a stool specimen extract with a calprotectin concentration below the anticipated lower limit of the analytical measuring range, in various mixing ratios covering the range; each dilution was tested in four (4) replicates. Results of the linear regression analyses are presented in the table below.
| Dilution
Series | Measuring
Range [µg/g] | Linear regression parameters | Intercept
(95% C.I.) | Slope
(95% C.I.) | R2 |
|--------------------|---------------------------|------------------------------|-------------------------|---------------------|----|
| 1 | 37.6 – 12,216.0 | 5.7
(1.6, 16.9) | 1.057
(1.044, 1.075) | 0.9983 | |
| 2 | 33.5 - 13,339.5 | 3.8
(-0.4, 13.3) | 1.031
(1.014, 1.042) | 0.9984 | |
The data supports the following claims for analytical measuring range:
- Direct analytical measuring range: 30 - 2000 µg/g
- Measuring range with automatic dilution: 30 - 10,000 ug/g
10
D. High Dose Hook Effect
No high dose hook effect at theoretical concentrations up to 45,715 ug/g.
E. Accuracy/Recovery
| Sample No | 7226 | 7228 | 7238 | 7236 | 7244 | 7234 | 7246 |
|---|---|---|---|---|---|---|---|
| Baseline result [µg/g] | 44.10 | 65.45 | 116.43 | 138.48 | 230.88 | 510.78 | 1076.33 |
| Expected post-spike result [µg/g] | 101.04 | 122.39 | 173.37 | 195.42 | 458.65 | 738.55 | 1304.10 |
| Observed post-spike result [µg/g] | 94.55 | 114.53 | 170.23 | 186.93 | 453.10 | 753.18 | 1309.28 |
| Total recovery [%] | 93.6% | 93.6% | 98.2% | 95.7% | 98.8% | 102.0% | 100.4% |
F. Analytical Sensitivity
Results of the analytical sensitivity studies support a claimed direct measuring range of 30 -2000 µg/g and a measuring range of 30 - 10,000 µg/g with automatic dilution.
LoB = 16.7 µg/g LoD = 23.7 µg/g LoQ = 30 µg/g
Interfering Substances G.
Study procedures were performed using stool specimen extracts with the following approximate calprotectin concentrations: 30 µg/g, 100 µg/g, 300 µg/g, and 550 µg/g. The following analytes, pharmaceuticals, and nutritional supplements did not interfere with the BÜHLMANN fCAL® turbo:
| Trade name | Active component | Solvent | Concentration
mg/50 mg
stool |
|------------------|-------------------------|---------------------------------|------------------------------------|
| gyno-Tardyferon | Iron (II) sulfate | HCl/NaOH | 0.11 |
| Prednisone | Prednisone | DMSO | 0.31 |
| Imurek | Azathioprine | DMSO | 0.19 |
| Salofalk | Mesalamine; 5-ASA | DMSO | 5.21 |
| Agopton | Lansoprazole | Dimethylformamide | 0.18 |
| Asacol | Mesalamine; 5-ASA | DMSO | 2.50 |
| Vancocin | Vancomycin | H2Odd | 2.00 |
| Sulfamethoxazole | Sulfamethoxazole | DMSO | 1.60 |
| Trimethoprim | Trimethoprim lactate | DMSO/Exbuffer | 0.35 |
| Ciproxine | Ciprofloxacin | solvent from manufacturer/H2Odd | 1.25 |
| Vitamin E | DL-α Tocopherol Acetate | H2O + Tween | 0.30 |
| Bion 3 | Multivitamin | HCl/NaOH | 1.06 |
| Hemoglobin | Hemoglobin | H2Odd | 1.25 |
11
| Microorganism | Concentration
(cfu/mL) |
|-----------------------------------------------|---------------------------|
| Escherichia coli | 3.3 x 107 |
| Salmonella enterica subsp. enterica | 9.0 x 107 |
| Klebsiella pneumoniae subsp. pneumonia | 5.3 x 107 |
| Citrobacter freundii | 12.9 x 107 |
| Shigella flexneri | 5.0 x 107 |
| Yersinia enterocolitica subsp. enterocolitica | 9.8 x 107 |
The following enteropathological microorganisms did not interfere with the BÜHLMANN fCAL® turbo when added to stool extracts at the given cell counts:
H. Method Comparison
A total of 248 clinical study samples, prepared using the manual weighing extraction method, were tested using the BÜHLMANN fCAL® turbo and the predicate device (BÜHLMANN fCAL® ELISA assay); valid results within the linear measuring range for both assays were obtained for 220 of these samples. Results were analyzed by Passing-Bablok regression analysis.
| Slope
(95% CI) | Intercept (µg/g)
(95% CI) | Bias at 80 µg/g
(95% CI) | Bias at 160 µg/g
(95% CI) | Correlation
r |
|-------------------------|------------------------------|-----------------------------|------------------------------|------------------|
| 1.025
(0.990, 1.058) | -4.5
(-8.7, 0.3) | -3.1%
(-7.2%, 0.5%) | -0.3%
(-2.4%, 2.7%) | 0.972 |
Frequency counts of BÜHLMANN fCAL® turbo test results and corresponding BÜHLMANN fCAL® ELISA assay results within each of the diagnostic ranges of these tests are provided below.
| # in BÜHLMANN fCAL® ELISA assay range (µg/g) | |||||
|---|---|---|---|---|---|
| 160 | Total | ||||
| # in fCAL | |||||
| turbo range | |||||
| (µg/g) | 160 | 0 | 7 | 92 | 99 |
| Total | 92 | 58 | 98 | 248 |
Estimates of positive percent agreement (PPA) and negative percent agreement (NPA) between the BÜHLMANN fCAL® turbo results and corresponding BÜHLMANN fCAL® ELISA assay results, using both sets of assay cutoffs, with respect to IBD subjects, other GI subjects, normal subjects, and all subjects combined are shown in the table below.
12
| Subgroup | Metric | Estimate | 95% C.I. |
|---|---|---|---|
| IBD | PPA (lower cutoff) | 68/70 = 97.1% | [90.1%, 99.7%] |
| NPA (lower cutoff) | 6/7 = 85.7% | [42.1%, 99.6%] | |
| PPA (upper cutoff) | 52/56 = 92.9% | [82.7%, 98.0%] | |
| NPA (upper cutoff) | 19/21 = 90.5% | [69.6%, 98.8%] | |
| IBS | PPA (lower cutoff) | 28/32 = 87.5% | [71.0%, 96.5%] |
| NPA (lower cutoff) | 31/33 = 93.9% | [79.8%, 99.3%] | |
| PPA (upper cutoff) | 12/13 = 92.3% | [64.0%, 99.8%] | |
| NPA (upper cutoff) | 49/52 = 94.2% | [84.1%, 98.8%] | |
| Other GI | PPA (lower cutoff) | 20/21 = 95.2% | [76.2%, 99.9%] |
| NPA (lower cutoff) | 16/16 = 100% | [79.4%, 100%] | |
| PPA (upper cutoff) | 13/14 = 92.9% | [66.1%, 99.8%] | |
| NPA (upper cutoff) | 23/23 = 100% | [85.2%, 100%] | |
| Normal | PPA (lower cutoff) | 30/33 = 90.9% | [75.7%, 98.1%] |
| NPA (lower cutoff) | 31/36 = 86.1% | [70.5%, 95.3%] | |
| PPA (upper cutoff) | 15/15 = 100% | [78.2%, 100%] | |
| NPA (upper cutoff) | 52/54 = 96.3% | [87.3%, 99.5%] | |
| All subjects | PPA (lower cutoff) | 146/156 = 93.6% | [88.5%, 96.9%] |
| NPA (lower cutoff) | 84/92 = 91.3% | [83.6%, 96.2%] | |
| PPA (upper cutoff) | 92/98 = 93.9% | [87.1%, 97.7%] | |
| NPA (upper cutoff) | 143/150 = 95.3% | [90.6%, 98.1%] |
I. Extraction Method Comparison
A total of 241 clinical study samples were extracted using the CALEX® Cap and manual weighing extraction methods and tested using the BÜHLMANN fCAL® turbo. Valid results within the linear measuring range were obtained for 202 of these samples using both extraction methods.
Results were analyzed by Passing-Bablok regression analysis.
13
| Slope
(95% CI) | Intercept (µg/g)
(95% CI) | Bias at 80 µg/g
(95% CI) | Bias at 160 µg/g
(95% CI) | Correlation
r |
|-------------------|------------------------------|-----------------------------|------------------------------|-------------------------|
| 1.149 | -8.3 | 4.6% | 9.7% | 0.921 |
| (1.100, 1.201) | (-17.1, -2.0) | (-4.3%, 9.1%) | (4.2%, 13.8%) | |
Frequency counts of BÜHLMANN fCAL® turbo test results using the CALEX® Cap and manual weighing extraction methods within each of the BÜHLMANN fCAL® turbo diagnostic ranges are provided below.
| # of CALEX® Cap results | |||||
|---|---|---|---|---|---|
| 160 | Total | ||||
| # of manual | |||||
| weighing | |||||
| results | 160 | 0 | 3 | 122 | 125 |
| Total | 74 | 41 | 126 | 241 |
Estimates of positive percent agreement (PPA) and negative percent agreement (NPA) between the BÜHLMANN fCAL® turbo results using the CALEX® Cap extraction method and corresponding results using the manual weighing extraction method, using both sets of assay cutoffs are shown in the table below.
| Metric | Estimate | 95% C.I. |
|---|---|---|
| PPA (lower cutoff) | $159/162 = 98.1%$ | [94.7%, 99.6%] |
| NPA (lower cutoff) | $71/79 = 89.9%$ | [81.0%, 95.5%] |
| PPA (upper cutoff) | $122/125 = 97.6%$ | [93.1%, 99.5%] |
| NPA (upper cutoff) | $112/116 = 96.6%$ | [91.4%, 99.1%] |
------------------This space intentionally left blank-------------------------------------------------------------------------------------------------------------------------
14
Clinical Sensitivity/Specificity (Manual Weighing Extraction Method) J.
| IBD vs. | IBS: |
|---|---|
| --------- | ------ |
| Borderline Values
| Considered Positive | Clinical Diagnosis | Total | ||
|---|---|---|---|---|
| IBD | IBS | |||
| BÜHLMANN | ||||
| fCAL® turbo | Positive | 123 | 31 | 154 |
| Negative | 12 | 99 | 111 | |
| Total | 135 | 130 | 265 | |
| Sensitivity = 91.1%; 95% C.I. (85.0%, 95.3%) | ||||
| Specificity = 76.2%; 95% C.I. (67.9%, 83.2%) | ||||
| PPV = 79.9%; 95% C.I. (72.7%, 85.9%) | ||||
| NPV = 89.2%; 95% C.I. (81.9%, 94.3%) |
| Borderline Values
| Considered Negative | Clinical Diagnosis | Total | ||
|---|---|---|---|---|
| IBD | IBS | |||
| BÜHLMANN | Positive | 108 | 16 | 124 |
| fCAL® turbo | Negative | 27 | 114 | 141 |
| Total | 135 | 130 | 265 | |
| Sensitivity = 80.0%; 95% C.I. (72.3%, 86.4%) | ||||
| Specificity = 87.7%; 95% C.I. (80.8%, 92.8%) | ||||
| PPV = 87.1%; 95% C.I. (79.9%, 92.4%) | ||||
| NPV =80.9%; 95% C.I. (73.4%, 87.0%) |
IBD vs. non-IBD:
| Borderline Values
| Considered Positive | Clinical Diagnosis | Total | ||
|---|---|---|---|---|
| IBD | Non-IBD | |||
| BÜHLMANN | Positive | 123 | 52 | 175 |
| fCAL® turbo | Negative | 12 | 150 | 162 |
| Total | 135 | 202 | 337 | |
| Sensitivity = 91.1%; 95% C.I. (85.0%, 95.3%) | ||||
| Specificity = 74.3%; 95% C.I. (67.7%, 80.1%) | ||||
| PPV = 70.3%; 95% C.I. (62.9%, 76.9%) | ||||
| NPV = 92.6%; 95% C.I. (87.4%, 96.1%) |
----------------------------------This space intentionally left blank-------------------------------------------------------
15
| Borderline Values
| Considered Negative | Clinical Diagnosis | Total | ||
|---|---|---|---|---|
| BÜHLMANN | ||||
| fCAL® turbo | IBD | IBS | ||
| Positive | 108 | 30 | 138 | |
| Negative | 27 | 172 | 199 | |
| Total | 135 | 202 | 337 | |
| Sensitivity = 80.0%; 95% C.I. (72.3%, 86.4%) | ||||
| Specificity = 85.1%; 95% C.I. (79.5%, 89.8%) | ||||
| PPV = 78.3%; 95% C.I. (70.4%, 84.8%) | ||||
| NPV =86.4%; 95% C.I. (80.9%, 90.9%) |
K. Expected Values/Reference Range:
Stool samples, prepared using the manual weighing extraction method, were obtained from 141 apparently healthy normal adults (> 21 years of age) with no symptoms or signs of gastrointestinal disease and were. The test results were categorized by the assay cut-offs below.
| Calprotectin level by BÜHLMANN fCAL turbo | ||||
|---|---|---|---|---|
| 160 µg/g | Total | |||
| Number of | ||||
| subjects (%) | 106 (75.2%) | 18 (12.8%) | 17 (12.1%) | 141 (100%) |
VIII. Conclusion
The information provided above supports that the BÜHLMANN fCAL® turbo and CALEX® Cap are as safe and effective as the predicate device. Verification and validation studies support that the use of the CALEX® Cap to prepare stool sample extracts does not raise any new questions of safety and effectiveness. Therefore, it is concluded that the BÜHLMANN fCAL® turbo and CALEX® Cap are substantially equivalent to the predicate device.