(75 days)
Celikey is intended for the semiquantitative and qualitative measurement of anti-tissue transglutaminase (tTG) IgA antibodies in human serum and plasma. Celikey is based on recombinant human tissue transglutaminase as antigen and is useful as an aid in the clinical diagnosis of patients with celiac disease.
Celikey is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of IgA antibodies against Tissue transglutaminase in human serum or plasma.
The test kit contains microplate strips coated with purified human recombinant tTG antigen, calibrators, positive and negative controls, enzyme-labeled conjugate, substrate and substrate stop solution, sample diluent and wash buffer.
Acceptance Criteria and Device Performance Study for Celikey® Tissue Transglutaminase (human, recombinant) IgA Antibody Assay
This response details the acceptance criteria and the study performed to demonstrate the Celikey® Tissue Transglutaminase (tTG) IgA Antibody Assay meets these criteria, based on the provided 510(k) summary.
1. Table of Acceptance Criteria and Reported Device Performance
The provided document doesn't explicitly list specific quantitative "acceptance criteria" in a table format with numerical targets for sensitivity, specificity, or agreement with a gold standard. Instead, it focuses on demonstrating substantial equivalence to a predicate device (INOVA QUANTA Lite™ tTG) and that the assay performs "as expected from the medical literature."
Therefore, the acceptance criteria are implicitly based on the predicate device's performance and general expectations for diagnostic tests for celiac disease, expressed as data showing comparability and expected performance.
| Acceptance Criteria (Implicit from Substantial Equivalence and Expected Performance) | Reported Device Performance |
|---|---|
| Comparability with Predicate Device (INOVA QUANTA Lite™ tTG): | Data from comparison study analyzing positive, equivocal, and negative sera showed comparability. |
| Expected Performance for Clinically Defined Sera: | Results obtained for clinically defined sera were consistent with medical literature expectations. |
| Expected Performance for Endemic and Normal Population Subjects: | Results obtained for endemic population (likely celiac patients) and normal population subjects were consistent with medical literature expectations. |
| Qualitative and Semiquantitative Measurement Capabilities: | The device is intended for and performs semiquantitative and qualitative measurement of anti-tTG IgA antibodies. |
| Reliable Discrimination (Negative, Equivocal, Positive): | The device uses a set of six calibrators and classifies results as negative, equivocal, and positive. |
| Suitability for use with Serum and Plasma: | The device is intended for and performs with both serum and plasma. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: The document does not explicitly state the exact sample size for the test set used in the comparison study or for the clinically defined and normal population sera. It refers to a "data set including" these categories of results.
- Data Provenance: The document does not specify the country of origin of the data. It indicates the data includes:
- Results obtained within a comparison study analyzing positive, equivocal, and negative sera.
- Results obtained for clinically defined sera.
- Results obtained for endemic and any and any subjects (normal population).
- Retrospective or Prospective: Not explicitly stated, however, the description of "results obtained" typically suggests retrospective analysis of collected samples, but this cannot be definitively confirmed from the provided text.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not provide details on the number or qualifications of experts used to establish the ground truth for the test set. The ground truth for "clinically defined sera" would typically rely on clinical diagnosis by medical professionals, but this is not elaborated upon.
4. Adjudication Method for the Test Set
The document does not describe any specific adjudication method (e.g., 2+1, 3+1, none) used for the test set. The evaluation seems to rely on direct comparison of results between the new device and the predicate, and against expected outcomes for clinically defined samples.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This type of study typically involves human readers interpreting diagnostic images or data with and without AI assistance, which is not applicable to this in-vitro diagnostic device (immunoassay). The study performed was a laboratory equivalence study comparing the new device to a predicate device.
6. Standalone Performance Study
Yes, a standalone performance study was implicitly done. The "results obtained for clinically defined sera" and "results obtained for endemic and normal population subjects" constitute the standalone performance evaluation of the Celikey® assay itself, demonstrating its ability to distinguish between different clinical states, even if in comparison to the predicate and medical literature expectations. The device is an immunoassay that provides a quantitative or semi-quantitative result directly, without requiring human-in-the-loop interpretation for its primary output.
7. Type of Ground Truth Used
The type of ground truth used appears to be a combination of:
- Predicate Device Results: For the "comparison study analyzing positive, equivocal and negative sera," the predicate device's results likely served as a reference or a comparative ground truth.
- Clinical Diagnosis/Medical Literature: For the "clinically defined sera" and "endemic and normal population subjects," the ground truth was based on the clinical diagnosis of the patients (e.g., diagnosed celiac disease patients vs. healthy controls) and general medical understanding of tTG IgA antibody levels in these populations. This indirectly points to clinical outcomes as the ultimate ground truth, but the direct evidence for the study was likely established diagnoses.
8. Sample Size for the Training Set
The document does not provide any information regarding a training set or its sample size. Immunoassays like this do not typically involve a "training" phase in the same way machine learning algorithms do. The development of such assays involves optimizing reagents and protocols, but the concept of a "training set" with established ground truth for an algorithm is not applicable here.
9. How the Ground Truth for the Training Set Was Established
As no training set is mentioned or applicable in the context of this device's development as described, there is no information on how its ground truth was established.
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JUL 1 9 2004
510(K) SUMMARY OF SAFETY AND 9. EFFECTIVENESS
This summary of safety and effectiveness information is being submitted in Inis summary of sacty and Check . The Safety Medical Devices Act of 1990 (SMDA 1990) and 21 CFR Part 807.92.
| Assigned 510(k) Number: | K041174 |
|---|---|
| Date of Summary Preparation: | April 28, 2004 |
| Manufacturer: | Sweden Diagnostics (Germany) GmbHMunzinger Strasse 7D-79111 Freiburg, Germany |
| Company Contact Person: | Michael LinssManager, Compliance & QualitySweden Diagnostics (Germany) GmbHMunzinger Strasse 7D-79111 Freiburg, Germany+49-761-47805-310 (Phone)+49-761-47805-335 (Fax) |
| Device Name: | Celikey® Tissue Transglutaminase(human, recombinant) IgA Antibody Assay |
| Common Name: | Tissue transglutaminase autoantibodiesimmunological test system |
Classification
| Product Name | Product Code | Class | CFR |
|---|---|---|---|
| Celikey® tTG (human,recombinant)IgA Antibody Assay | MVM | II | 866.5660 |
Substantial Equivalence to
INOVA QUANTA Lite™ tTG
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Intended Use Statement
Celikey is intended for the semiquantitative and qualitative measurement of anti-tissue transglutaminase (tTG) IgA antibodies in human serum and plasma. Celikey is based on recombinant human tissue transglutaminase as antigen and is useful as an aid in the clinical diagnosis of patients with celiac disease.
General Description of the Device
Celikey is an indirect noncompetitive enzyme immunoassay for the semiquantitative and qualitative determination of IgA antibodies against Tissue transglutaminase in human serum or plasma.
The test kit contains microplate strips coated with purified human recombinant tTG antigen, calibrators, positive and negative controls, enzyme-labeled conjugate, substrate and substrate stop solution, sample diluent and wash buffer.
Celikey® tTG IgA Antibody Assay Test Principle
Celikey is an indirect noncompetitive enzyme immunoassay for the semiguantitative and qualitative determination of tTG (IgA) antibodies in human serum or plasma. The wells of a microplate are coated with recombinant human tTG antigen. Antibodies specific for tTG present in the patient sample bind to the antigen.
In a second step the enzyme labeled second antibody (conjugate) binds to the antigen-antibody complex which leads to the formation of an enzyme labeled conjugate-antibody-antigen complex. The enzyme labeled antigen-antibody complex converts the added substrate to form a colored solution.
The rate of color formation from the chromogen is a function of the amount of conjugate complexed with the bound antibody and thus is proportional to the initial concentration of the respective antibodies in the patient sample.
Device Comparison
Both assays (the predicate and the new device) are indirect noncompetitive enzyme immunoassays for the semi-quantitative and qualitative determination of IgA antibodies to tissue transglutaminase (endomysium) in human serum. Both assays recommend the same sample dilutions and use comparable detection systems.
In accordance to the relevant scientific literature both assays state in the Intended Use, that the measuring of the IgA antibodies against tissue transglutaminase provides aid in the diagnosis of patients with celiac disease.
A difference between both assays is that the predicate device is only recommended for use in serum specimen while the new device is, intended for use with serum and plasma.
The predicate device uses a purified antigen from guinea pig liver whereas the new device is based on a recombinant human tTG antigen.
The cut-off in the predicate device assay is evaluated by using a low and a high positive Standard and a grading of the results in negative, weak, moderate and
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strong positive. The new device uses a set of six Calibrators and classifies the results as negative, equivocal and positive.
Laboratory equivalence
The comparability of INOVA QUANTA Lite™ tTG and Celikey® tTG IgA The Comparasy is supported by a data set including
- · results obtained within a comparison study analyzing positive, equivocal and negative sera.
- · results obtained for clinically defined sera.
- · results obtained for emisears and any and any subjects (normal population).
The data show that the assay performs as expected from the medical literature.
In summary, all available data support that the new device is substantially In Sunmal y, an available data sapp on that the new device performs according to state-of-the-art expectations.
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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an abstract symbol resembling an eagle or bird in flight, composed of three curved lines.
JUL 1 9 2004
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Michael Linss, Ph.D. Manager, Compliance and Quality Sweden Diagnostics (Germany) GmbH Munzinger Strasse 7 D-79111 Freiburg i. Br., Germany
Re: K041174 Trade/Device Name: Celikey® Tissue Transglutaminase (human, recombinant) IgA Antibody Assay Regulation Number: 21 CFR § 866.5660 Regulation Name: Multiple Autoantibodies immunological test system Regulatory Class: II Product Code: MVM Dated: July 8, 2004 Received: July 12, 2004
Dear Dr. Linss:
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. 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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
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If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely yours,
Robert L. Becker Jr.
Robert L. Becker, Jr., M.D., Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
K041174 510(k) Number:
Device Name: Celikey® Tissue Transglutaminase (human, recombinaut) IgA Antibody Assay
Indications For Use:
Celikey is intended for the semiquantitative and qualitative measurement of anti-tissue transglutaminase (tTG) IgA antibodies in human serum and plasma. Celikey is based on recombinant human tissue transglutaminase as antigen and is useful as an aid in the clinical diagnosis of patients with celiac disease.
Prescription Use V (Per 21 CFR 801.109)
AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Marie chan
Division Sign-Off
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Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K041174
§ 866.5660 Multiple autoantibodies immunological test system.
(a)
Identification. A multiple autoantibodies immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoantibodies (antibodies produced against the body's own tissues) in serum and other body fluids. Measurement of multiple autoantibodies aids in the diagnosis of autoimmune disorders (disease produced when the body's own tissues are injured by autoantibodies).(b)
Classification. Class II (performance standards).