(90 days)
No
The device description details a standard chemiluminescent immunoassay and automated analyzer, with no mention of AI or ML in the assay process, data analysis, or intended use. The software performs standard calculations based on RLU measurements.
No
This device is an in vitro diagnostic (IVD) chemiluminescent immunoassay used to measure fecal calprotectin in human stool. It is intended to aid in the diagnosis and differentiation of inflammatory bowel diseases (IBD) from irritable bowel syndrome (IBS), which is a diagnostic purpose, not a therapeutic one.
Yes
The opening statement of the "Intended Use / Indications for Use" section explicitly states that the DiaSorin LIAISON® Calprotectin assay is an "in vitro diagnostic chemiluminescent immunoassay." Additionally, it is intended to be "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)."
No
The device is an in vitro diagnostic assay that requires a specific hardware analyzer (LIAISON® XL Analyzer) and a stool extraction device (LIAISON® O.S.E.T. Device) to function. While it includes software for calculation, it is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The DiaSorin LIAISON® Calprotectin assay is an in vitro diagnostic chemiluminescent immunoassay (CLIA) intended for the quantitative measurement, in human stool, of fecal calprotectin..."
This statement directly identifies the device as an in vitro diagnostic.
N/A
Intended Use / Indications for Use
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.
Product codes (comma separated list FDA assigned to the subject device)
NXO, JJX
Device Description
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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Stool (Fecal)
Indicated Patient Age Range
Adult and pediatric from 3 years of age.
Intended User / Care Setting
Prescription Use (Part 21 CFR 801 Subpart D)
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)
METHOD COMPARISON
A total of 164 stool samples spanning the assay range were tested by the LIAISON® Calprotectin assay and a commercial calprotectin assay following CLSA EP09-A3. The results were analyzed by the method of Passing & Bablok, returning a slope of 0.97 (95% Cl: 0.91 to 1.00), an intercept of 1.50 ug/q (95% Cl: -2.26 to 6.46) and an R value by linear regression of 0.961.
COMPARATIVE CLINICAL STUDIES
Clinical specificity and clinical sensitivity of the LIAISON® Calprotectin assay was determined against the clinical diagnosis by testing a total of 240 prospectively collected human stool specimens from subjects with signs and symptoms suggestive of IBD or IBS. 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. The final diagnoses of the subjects were as follows: 102 IBD (85 adult and 17 pediatric), 67 IBS (65 adult and 2 pediatric), and 71 other gastrointestinal disorders other than IBD or IBS.
PRECISION/REPRODUCIBILITY
A twelve (12) day study was conducted at DiaSorin Inc. A panel of six (6) human stool samples containing concentrations of analyte prepared to span the measuring range of the assay were extracted by each of three (3) operators using the manual extraction method each day over 12 operating days and tested in two (2) replicates in two (2) runs per day using one (1) lot of LIAISON® Calprotectin reagent. CLSI quideline EP5-A3 was consulted in the preparation of the testing protocol.
A five (5) day study was conducted at two (2) external laboratories and at DiaSorin Inc. A panel of six (6) human stool samples containing concentrations of analyte prepared to span the measuring range of the assay were extracted each day at each site using the manual extraction method. Kit controls were also included in the study. Each site utilized at least two (2) operators to perform the extraction and testing. The samples were tested in six (6) replicates in one (1) run each day using one (1) lot of LIAISON® Calprotectin reagent. CLSI document EP15-A3 was consulted in the preparation of the testing protocol.
LIAISON® Q.S.E.T. DEVICE ACCURACY
One hundred twenty-eight (128) human stool samples spanning the measuring range of the LIAISON® Calprotectin assay were extracted using the LIAISON® Q.S.E.T. Device and the weigh method to determine if these extraction methods provide equivalent results. Each human stool extract was tested in singlicate in the same run using one (1) LIAISON® Calprotectin assay reagent lot. The results were analyzed by Passing-Bablok regression analysis of manual weigh method versus device method.
LIAISON® Q.S.E.T. SAMPLE COLLECTION REPRODUCIBILITY
LIAISON® Q.S.E.T. Device weight reproducibility was tested using seven (7) human stool samples ranging from 2 - 6 on the Bristol Stool Form Scale (BSFS) were sampled by three (3) operators with five (5) replicates per sample per operator. Samples on the Q.S.E.T. device were weighed against the empty Q.S.E.T device.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Method Comparison: Agreement with Comparator Assay
- Borderline considered Elevated (Abnormal):
- Positive Agreement: (124/128) 96.9% (95% CI: 92.2% - 99.1%)
- Negative Agreement: (32/36) 88.9% (95% CI: 73.9% - 96.9%)
- Borderline considered Normal:
- Positive Agreement: (90/92) 97.8% (95% CI: 92.4% - 99.7%)
- Negative Agreement: (68/72) 94.4% (95% CI: 86.3% - 98.5%)
Comparative Clinical Studies: IBD vs non-IBD comparison
- Borderline considered Elevated:
- Clinical Sensitivity: 100/102 (98.0%) (95% CI: 93.1 – 99.8%)
- Clinical Specificity: 95/138 (66.8%) (95% CI: 60.4 – 76.7%)
- Borderline considered Normal:
- Clinical Sensitivity: 90/102 (88.2%) (95% CI: 80.4 - 93.8%)
- Clinical Specificity: 125/138 (90.6%) (95% CI: 84.4 - 94.9%)
Comparative Clinical Studies: IBD vs IBS comparison
- Borderline as Elevated:
- Clinical Sensitivity: 100/102 (98.0%) (95% CI: 93.1 - 99.8%)
- Clinical Specificity: 44/67 (65.7%) (95% CI: 53.1 - 76.9%)
- Borderline as Normal:
- Clinical Sensitivity: 90/102 (88.2%) (95% CI: 80.4 - 93.8%)
- Clinical Specificity: 59/67 (88.1%) (95% CI: 77.8 - 94.7%)
LIAISON® Q.S.E.T. DEVICE ACCURACY: Percent agreement analysis between the two methods of extraction
- Borderline considered Elevated:
- Positive Agreement: (65/72) 90.3% (95% Confidence Interval: 81.0% - 96.0%)
- Negative Agreement: (53/56) 94.6% (95% Confidence Interval: 85.1% - 99.0%)
- Overall: (119/128) 93.0% (95% Confidence Interval: 87.1% - 96.7%)
- Borderline considered Normal:
- Positive Agreement: (36/42) 85.7% (95% Confidence Interval: 71.5% - 94.6%)
- Negative Agreement: (86/86) 100% (95% Confidence Interval: 95.8% - 100.0%)
- Overall: (122/128) 95.3% (95% Confidence Interval: 90.1% - 98.3%)
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.
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).
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there 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.
December 26, 2018
DiaSorin Inc. Sandra Zimniewicz Regulatory Affairs Specialist 1951 Northwestern Ave. Stillwater, Minnesota 55082-0285
Re: K182698
Trade/Device Name: LIAISON Calprotectin, LIAISON Calprotectin Control Set, LIAISON Calprotectin Calibration Verifiers, LIAISON Q.S.E.T. Buffer, LIAISON Q.S.E.T. Device Regulation Number: 21 CFR 866.5180 Regulation Name: Fecal calprotectin immunological test system Regulatory Class: Class II Product Code: NXO Dated: September 26, 2018 Received: September 27, 2018
Dear Sandra Zimniewicz:
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.
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
1
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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Douglas A. Jeffery -S
For
Lea Carrington Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K182698
Device Name LIAISON® Calprotectin LIAISON® Q.S.E.T. Device
Indications for Use (Describe)
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.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ------------------------------------------------- | -- |
X 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 5.0
| SUBMITTED BY: | Sandra Zimniewicz
Regulatory Affairs Specialist
DiaSorin Inc.
1951 Northwestern Avenue
P.O. Box 285
Stillwater, MN 55082-0285
Phone (651) 351-5711
Fax (651) 351-5669
Email: sandra.zimniewicz@diasorin.com |
|----------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| DATE PREPARED: | September 27, 2018 |
| NAME OF DEVICE: | |
| Trade Name: | LIAISON® Calprotectin
LIAISON® Calprotectin Control Set
LIAISON® Calprotectin Calibration Verifiers
LIAISON® Q.S.E.T. Buffer
LIAISON® Q.S.E.T. Device |
| Common Names/Descriptions: | Calprotectin assay, Calprotectin controls, and
Calprotectin calibration verifiers |
| Classification Names: | Fecal calprotectin immunological test system:
Class II, 21 CFR: 866.5180; Immunology (82) |
| | Single (Specified) analyte controls (assayed
and unassayed): Class I,
21 CFR 862.1660; Clinical Chemistry (75) |
| Product Code: | NXO
JJX |
| PREDICATE DEVICES : | PhiCal™ Test Fecal Calprotectin Immunoassay
DEN060001 |
DEVICE DESCRIPTION:
INTENDED USE:
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
4
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® Calprotectin Control Set is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Calprotectin assay. The performance characteristics of the LIAISON® Calprotectin Control Set have not been established for any other assay or instrument platforms different from the LIAISON® XL Analyzer.
The DiaSorin LIAISON® Calprotectin Calibration Verifiers are assayed quality control materials intended for in vitro diagnostic use in the quantitative verification of calibration and reportable range of the LIAISON® Calprotectin assay when performed on the LIAISON® XL Analyzer.
The LIAISON® Q.S.E.T. Buffer (Quantitative Stool Extraction and Test) is intended for use in the preparation of human stool specimens for testing in designated DiaSorin stool assays.
The DiaSorin LIAISON® Q.S.E.T. (Quantitative Stool Extraction and Test) is intended for use in the preparation of human stool specimens for testing in the LIAISON® Calprotectin assay.
INDICATIONS FOR USE
Same as intended use.
KIT DESCRIPTION:
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.
5
COMPARISON WITH PREDICATE
The LIAISON® Calprotectin, LIAISON® Calprotecin Controls and LIAISON® Calprotecin Calibratin Verifiers are prepackaged reagents for use on an automated clinical chemistry analyzer. The PhiCal™ Test consists of prepackaged reagents for non/semiautomated manual use. A comparison of the similarities and differences between the devices are provided in the following table:
| Table 1: Table of Similarities - LIAISON® Calprotectin | ||
|---|---|---|
| Characteristic | New Device | |
| DiaSorin | ||
| LIAISON® Calprotectin | Predicate Device | |
| PhiCal™ Test | ||
| Fecal Calprotectin | ||
| Immunoassay | ||
| (DEN060001) | ||
| Intended Use | 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 PhiCal™ test is a | |
| quantitative ELISA for | ||
| measuring, in human stool, | ||
| concentrations of fecal | ||
| calprotectin, a neutrophilic | ||
| protein that is a marker of | ||
| mucosal inflammation. The | ||
| The PhiCal ™ test can be | ||
| used as an in vitro diagnostic | ||
| aid in the diagnosis of | ||
| inflammatory bowel diseases | ||
| (IBD), Crohn's disease and | ||
| ulcerative colitis, and to | ||
| differentiate IBD from irritable | ||
| bowel syndrome. | ||
| Measured Analyte | Calprotectin | Same |
| Assay Type | Solid phase immunoassay | Same |
| Results | Quantitative | Same |
| Sample Type | Extracted Human Stool | Same |
| Amount of | ||
| Specimen required | ||
| for Manual | ||
| Extraction | $50 - 100$ mg | $80 - 120$ mg |
| LIAISON® | ||
| Q.S.E.T.Device | ||
| Stool | ||
| Sampling Quantity | $10.5$ mg $\pm 0.1$ mg | NA |
| Table 1 - Continued | ||
| Interpretation | 120 µg/g = Elevated | 120 µg/g = Abnormal |
| Kit Storage | 2-8°C | Same |
6
| Table 2: Table of Differences - LIAISON® Calprotectin | ||
|---|---|---|
| Characteristic | New Device | |
| DiaSorin | ||
| LIAISON® Calprotectin | Predicate Device | |
| PhiCal™ Test | ||
| Fecal Calprotectin | ||
| Immunoassay (DEN060001) | ||
| Operating Principle | Automated Chemiluminescent | |
| Immunoassay (CLIA) | Manual/Semi-automated ELISA | |
| Solid Phase | Magnetic particles coated mouse | |
| monoclonal antibodies to | ||
| calprotectin | Microwells coated with rabbit | |
| polyclonal antibody to | ||
| calprotectin | ||
| Conjugate | Mouse monoclonal antibody | |
| against calprotectin conjugated to | ||
| an isoluminol derivative | Alkaline phosphatase labelled | |
| rabbit IgG antibodies against | ||
| calprotectin | ||
| Analytical | ||
| Measuring Range | 5 - 800 µg/g | 15.6 - 250 µg/g |
| Extraction | ||
| Procedure | Weigh Method or | |
| LIAISON® Q.S.E.T. Device method | ||
| Extraction Buffer provided | ||
| separately | Weigh Method | |
| Extraction Buffer included with kit | ||
| Calibrators | 2 Levels, Lyophilized | 5 Levels, Liquid, Ready to Use |
| Table 3: Table of Similarities and Differences - LIAISON® Calprotectin Control Set | ||
|---|---|---|
| Characteristic | New Device | |
| DiaSorin | ||
| LIAISON® Calprotectin | Predicate Device | |
| PhiCal™ Test | ||
| Fecal Calprotectin | ||
| Immunoassay | ||
| (DEN060001) | ||
| Intended Use | The DiaSorin LIAISON® Calprotectin | |
| Control Set is intended for use as | ||
| assayed quality control samples to | ||
| monitor the performance of the | ||
| LIAISON® Calprotectin assay. The | ||
| performance characteristics of the | ||
| LIAISON® Calprotectin Control Set have | ||
| not been established for any other | ||
| assay or instrument platforms different | ||
| from the LIAISON® XL Analyzer. | No separate intended use, | |
| controls are included as part | ||
| of the kit. |
7
| Table 3 - Continued | ||
|---|---|---|
| Antigen | Recombinant Calprotectin | Same |
| Levels | 2 Levels (Low and High) | Same |
| Characteristics | Lyophilized | |
| Provided separately | Liquid, Ready to Use | |
| Included with kit | ||
| Storage | 2-8°C | Same |
| Table 4: Table of Similarities and Differences - LIAISON® Calprotectin Calibration
| Verfiers | ||
|---|---|---|
| Characteristic | New Device | |
| DiaSorin | ||
| LIAISON® Calprotectin | Predicate Device | |
| LIAISON® XL 1,25 | ||
| Dihydroxyvitamin D | ||
| Calibration Verifiers | ||
| (K141463) | ||
| Intended Use | The DiaSorin LIAISON® Calprotectin | |
| Calibration Verifiers are assayed quality | ||
| control materials intended for in vitro | ||
| diagnostic use in the quantitative | ||
| verification of calibration and reportable | ||
| range of the LIAISON® Calprotectin | ||
| assay when performed on the LIAISON® | ||
| XL Analyzer. | Assayed quality control | |
| materials intended the | ||
| quantitative verification of | ||
| calibration and reportable | ||
| range of the LIAISON® XL | ||
| 1,25 Dihydroxyvitamin D. | ||
| Storage | 2-8°C | Same |
| Levels | 4 Levels, Lyophilized | |
| Provided separately | Same |
| Table 5: Table of Similarities and Differences - LIAISON®Q.S.E.T. Buffer | ||
|---|---|---|
| Characteristic | New Device | |
| DiaSorin | ||
| LIAISON® Calprotectin | Predicate Device | |
| PhiCal™ Test | ||
| Fecal Calprotectin | ||
| Immunoassay | ||
| (DEN060001) | ||
| Intended Use | The LIAISON® Q.S.E.T. Buffer | |
| (Quantitative Stool Extraction and Test) | ||
| is intended for use in the preparation of | ||
| human stool specimens for testing in | ||
| designated DiaSorin stool assays. | No separate intended use, | |
| extraction buffer is included | ||
| as part of the kit. | ||
| Storage | 2-8°C | Same |
| Concentration | 5X (Requires dilution to 1X working | |
| concentration) | 2.5X (Requires dilution to 1X | |
| working concentration) | ||
| Characteristics | 3 bottles x 100 mL each | |
| Liquid | ||
| Provided separately, not included with kit | 2 bottles x 50 mL each | |
| Liquid | ||
| Included with kit | ||
| Stability of 1X | ||
| Solution | 8 weeks at 2-8°C | 7 days at 2-8°C |
8
PERFORMANCE DATA:
METHOD COMPARISON
A total of 164 stool samples spanning the assay range were tested by the LIAISON® Calprotectin assay and a commercial calprotectin assay following CLSA EP09-A3. The results were analyzed by the method of Passing & Bablok, returning a slope of 0.97 (95% Cl: 0.91 to 1.00), an intercept of 1.50 µg/q (95% Cl: -2.26 to 6.46) and an R value by linear regression of 0.961
An agreement analysis was also performed relative to the respective assay cut-off values for relevant medical decision points. Positive and negative agreement were calculated with borderline results considered as normal and as elevated/abnormaand. Results are summarized in the tables below.
| | Comparator Calprotectin Assay
Concentration | | | |
|----------------------------------------------|------------------------------------------------|-------------------------------|-------------------------|-------|
| LIAISON® Calprotectin Assay
Concentration | 120 µg/g
(Abnormal) | Total |
| 120 µg/g (Elevated) | 0 | 4 | 90 | 94 |
| Total | 36 | 36 | 92 | 164 |
| Borderline considered Elevated (Abnormal) | 95% Confidence Interval | ||
|---|---|---|---|
| Positive Agreement | (124/128) | 96.9% | (92.2% - 99.1%) |
| Negative Agreement | (32/36) | 88.9% | (73.9% - 96.9%) |
| Borderline considered Normal | 95% Confidence Interval | ||
| Positive Agreement | (90/92) | 97.8% | (92.4% - 99.7%) |
| Negative Agreement | (68/72) | 94.4% | (86.3% - 98.5%) |
COMPARATIVE CLINICAL STUDIES:
Clinical specificity and clinical sensitivity of the LIAISON® Calprotectin assay was determined against the clinical diagnosis by testing a total of 240 prospectively collected human stool specimens from subjects with signs and symptoms suggestive of IBD or IBS. 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. The final diagnoses of the subjects were as follows: 102 IBD (85 adult and 17 pediatric), 67 IBS (65 adult and 2 pediatric), and 71 other gastrointestinal disorders other than IBD or IBS
IBD vs non-IBD comparison:
Sensitivity and specificity were calculated for the LIAISON Calprotectin assay as an aid in the diagnosis of IBD in all subjects. Borderline results were calculated as both normal and elevated and 95% confidence intervals were reported.
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| | Calprotectin
(µg/g) | IBD | Non-IBD |
|------------|------------------------|-----|---------|
| Normal | 120 | 90 | 13 |
| | All | 102 | 138 |
| Borderline considered | Elevated | 95% Confidence Interval | |
|---|---|---|---|
| Clinical Sensitivity | 100/102 | 98.0% | 93.1 – 99.8% |
| Clinical Specificity | 95/138 | 66.8% | 60.4 – 76.7% |
| Borderline considered Normal | 95% Confidence Interval | ||
|---|---|---|---|
| Clinical Sensitivity | 90/102 | 88.2% | 80.4 - 93.8% |
| Clinical Specificity | 125/138 | 90.6% | 84.4 - 94.9% |
IBD vs IBS comparison:
Sensitivity and specificity were calculated for the LIAISON® Calprotectin assay to aid in the differentiation of IBD and IBS. Borderline results were calculated as both normal and elevated and 95% confidence intervals were reported.
| | Calprotectin
(µg/g) | IBD | IBS |
|------------|------------------------|-----|-----|
| Normal | 120 | 90 | 8 |
| All | | 102 | 67 |
| Borderline as Elevated | 95% Confidence Interval | ||
|---|---|---|---|
| Clinical Sensitivity | 100/102 | 98.0% | 93.1 - 99.8% |
| Clinical Specificity | 44/67 | 65.7% | 53.1 - 76.9% |
| Borderline as Normal | 95% Confidence Interval | ||
| Clinical Sensitivity | 90/102 | 88.2% | 80.4 - 93.8% |
| Clinical Specificity | 59/67 | 88.1% | 77.8 - 94.7% |
EXPECTED VAUES:
Stool samples from apparently healthy donors (15 subjects with ages ranging from 3-21 and 112 adults) and subjects with physician diagnosed IBS and IBD (19 subjects with ages ranging from 8-21 and 333 adults) were tested with the LIAISON® Calprotectin assay. Results were evaluated using the medical decision points of 50 µg/g and 120 µg/g which corresponds to the consensus threshold for distinguishing between IBD and IBS.
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| Diagnosis | Number of Subjects and percent in LIAISON® Calprotectin | |||
|---|---|---|---|---|
| Range (µg/g) | ||||
| 120 | ||||
| Elevated | Total | |||
| Apparently Healthy | 112 (88.2%) | 15 (11.8%) | 0 (0%) | 127 (100%) |
| IBD | 2 (2.0 %) | 10 (9.8%) | 90 (88.2%) | 102 (100%) |
| IBS | 44 (65.7%) | 15 (22.4%) | 8 (11.9%) | 67 (100%) |
| OTHER GI | 51 (71.8%) | 15 (21.1%) | 5 (7.1%) | 71 (100%) |
Test results are to be used in conjunction with information obtained from the patients' clinical evaluation and other diagnostic procedures.
PRECISION/REPRODUCIBILITY:
A twelve (12) day study was conducted at DiaSorin Inc. A panel of six (6) human stool samples containing concentrations of analyte prepared to span the measuring range of the assay were extracted by each of three (3) operators using the manual extraction method each day over 12 operating days and tested in two (2) replicates in two (2) runs per day using one (1) lot of LIAISON® Calprotectin reagent. CLSI quideline EP5-A3 was consulted in the preparation of the testing protocol.
| Sample ID
n | | Mea
n
µg/g | Within Run | | Between
Run | | Between Day | | Between
Operator | | Total | |
|----------------|-----|------------------|------------|------|----------------|------|-------------|-------|---------------------|------|-------|-------|
| | | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Sample #1 | 144 | 24.9 | 0.74 | 3.0% | 0.66 | 2.6% | 2.91 | 11.7% | 1.04 | 4.2% | 3.25 | 13.0% |
| Sample #2 | 144 | 39.9 | 0.88 | 2.2% | 0.76 | 1.9% | 3.44 | 8.6% | 0.00 | 0.0% | 3.63 | 9.1% |
| Sample #3 | 144 | 155 | 3.99 | 2.6% | 3.47 | 2.2% | 11.26 | 7.2% | 8.27 | 5.3% | 14.94 | 9.6% |
| Sample #4 | 144 | 253 | 6.97 | 2.8% | 8.18 | 3.2% | 20.17 | 8.0% | 2.87 | 1.1% | 23.03 | 9.1% |
| Sample #5 | 144 | 21.6 | 0.67 | 3.1% | 0.37 | 1.7% | 2.93 | 13.5% | 0.62 | 2.9% | 3.09 | 14.3% |
| Sample #6 | 144 | 639 | 15.86 | 2.5% | 25.31 | 4.0% | 39.21 | 6.1% | 21.03 | 3.3% | 53.59 | 8.4% |
A five (5) day study was conducted at two (2) external laboratories and at DiaSorin Inc. A panel of six (6) human stool samples containing concentrations of analyte prepared to span the measuring range of the assay were extracted each day at each site using the manual extraction method. Kit controls were also included in the study. Each site utilized at least two (2) operators to perform the extraction and testing. The samples were tested in six (6) replicates in one (1) run each day using one (1) lot of LIAISON® Calprotectin reagent. CLSI document EP15-A3 was consulted in the preparation of the testing protocol.
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| Sample ID | Mean
µg/g | Within Run | | Between Day | | Within Site | | Site to Site | | Total | |
|-----------|--------------|------------|------|-------------|-------|-------------|-------|--------------|-------|-------|-------|
| | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| Control 1 | 51.2 | 1.19 | 2.3% | 3.67 | 7.2% | 3.83 | 7.5% | 0.15 | 0.3% | 3.83 | 7.5% |
| Control 2 | 254 | 7.59 | 3.0% | 26.11 | 10.3% | 27.02 | 10.6% | 0.00 | 0.0% | 25.94 | 10.2% |
| Sample #1 | 25.9 | 0.68 | 2.6% | 2.16 | 8.3% | 2.25 | 8.7% | 0.00 | 0.0% | 2.17 | 8.4% |
| Sample #2 | 42.1 | 0.78 | 1.8% | 5.26 | 12.5% | 5.31 | 12.6% | 1.87 | 4.4% | 5.63 | 13.4% |
| Sample #3 | 173 | 4.65 | 2.7% | 20.47 | 11.9% | 20.91 | 12.1% | 20.55 | 11.9% | 29.32 | 17.0% |
| Sample #4 | 281 | 5.62 | 2.0% | 26.92 | 9.6% | 27.41 | 9.7% | 40.10 | 14.3% | 48.57 | 17.3% |
| Sample #5 | 23.4 | 0.60 | 2.6% | 2.62 | 11.2% | 2.68 | 11.5% | 0.000 | 0.0% | 2.45 | 10.5% |
| Sample #6 | 695 | 18.85 | 2.7% | 66.06 | 9.5% | 68.26 | 9.8% | 39.61 | 5.7% | 78.92 | 11.3% |
LIAISON® Q.S.E.T. Device Reproducibility
To study precision of the Calprotectin dose using the Q.S.E.T. device to extract the stool sample, eight (8) stool samples spanning the analytical measuring range (AMR) were extracted using the Q.S.E.T. Device and tested once (1) per day using five (5) replicates over five (5) days by three (3) operators, for a total of 75 measurements per Each Q.S.E.T. device extraction was performed daily by each operator samples. independently. The precision study was based on CLSI EP05-A3.
| Sample ID | Mean
µg/g | Repeatability | | Between Day | | Within
Operator | | Between
Operator | | Total | |
|-----------|--------------|---------------|------|-------------|-------|--------------------|-------|---------------------|-------|-------|-------|
| | | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | 21.9 | 0.636 | 2.9% | 3.179 | 14.5% | 3.232 | 14.8% | 0.945 | 4.3% | 3.052 | 13.9% |
| 2 | 26.2 | 0.807 | 3.1% | 1.951 | 7.4% | 2.085 | 7.9% | 1.843 | 7.0% | 2.643 | 10.1% |
| 3 | 38.6 | 1.428 | 3.7% | 4.727 | 12.2% | 4.903 | 12.7% | 1.335 | 3.5% | 4.621 | 12.0% |
| 4 | 166 | 6.137 | 3.7% | 9.110 | 5.5% | 10.69 | 6.5% | 8.141 | 4.9% | 12.81 | 7.7% |
| 5 | 297 | 11.29 | 3.8% | 28.62 | 9.6% | 30.42 | 10.2% | 6.594 | 2.2% | 28.37 | 9.6% |
| 6 | 505 | 18.59 | 3.7% | 59.39 | 11.8% | 61.77 | 12.2% | 34.35 | 6.8% | 65.49 | 13.0% |
| 7 | 2381 | 62.56 | 2.6% | 410.4 | 17.2% | 414.4 | 17.4% | 254.7 | 10.7% | 450.5 | 18.9% |
| 8 | 4140 | 126.8 | 3.1% | 309.2 | 7.5% | 330.1 | 8.0% | 228.9 | 5.5% | 377.1 | 9.1% |
TRACEABILITY/STANDARDIZATION
The LIAISON® Calprotectin calibrator concentrations (µg/g) are referenced to an inhouse standard preparation made from recombinant calprotectin.
Each Reagent Integral requires calibration. Calibration is performed using the two (2) calibrators included with each LIAISON® Calprotectin kit. The two point kit calibrators are used to establish specific working curves based on 10 point assay master curves stored on the analyzer.
LINEARITY
Linearity is demostrated for the analytical measuring range of 5 - 800 µg/g.
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ACCURACY/RECOVERY
The mean recovery results of 5 samples tested ranged from 98 to 108% with an overall mean recovery of 103%.
| Samples | Defined
Concentration
(µg/g) | Expected
Concentration
n (µg/g) | Observed
Concentration
(µg/g) | %
Recovery |
|---------------------|------------------------------------|---------------------------------------|-------------------------------------|---------------|
| High Sample 1 (HS1) | 493 | | | |
| 2 HS1 : 1 LS1 | | 399 | 405 | 101% |
| 1 HS1 : 1 LS1 | | 351 | 358 | 102% |
| 1 HS1 : 2 LS1 | | 303 | 320 | 106% |
| Low Sample 1 (LS1) | 209 | | | |
| High Sample 2 (HS2) | 599 | | | |
| 2 HS2 : 1 LS2 | | 410 | 418 | 102% |
| 1 HS2 : 1 LS2 | | 313 | 330 | 106% |
| 1 HS2 : 2 LS2 | | 216 | 226 | 105% |
| Low Sample 2 (LS2) | 26.8 | | | |
| High Sample 3 (HS3) | 408 | | | |
| 2 HS3 : 1 LS3 | | 281 | 292 | 104% |
| 1 HS3 : 1 LS3 | | 215 | 217 | 101% |
| 1 HS3 : 2 LS3 | | 149 | 146 | 98% |
| Low Sample 3 (LS3) | 21.6 | | | |
| High Sample 4 (HS4) | 724 | | | |
| 2 HS4 : 1 LS4 | | 523 | 537 | 103% |
| 1 HS4 : 1 LS4 | | 420 | 435 | 104% |
| 1 HS4 : 2 LS4 | | 317 | 344 | 108% |
| Low Sample 4 (LS4) | 117 | | | |
| High Sample 5 (HS5) | 413 | | | |
| 2 HS5 : 1 LS5 | | 308 | 315 | 102% |
| 1 HS5 : 1 LS5 | | 253 | 271 | 107% |
| 1 HS5 : 2 LS5 | | 199 | 199 | 100% |
| Low Sample 5 (LS5) | 93.6 | | | |
| | | | Mean Recovery | 103% |
ANALYTICAL SENSITIVITY
Limit of Blank (LoB) is 0.107 µg/g.
Limit of Detection (LoD) is 0.395 µg/g.
Limit of Quantitation (LoQ) is 0.400 µg/g.
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INTERFERING SUBSTANCES
Controlled studies of potentially interfering substances and microorganisms performed in a human stool sample extract at a calprotectin level of approximately 50 µg/g showed no interference (