(173 days)
The Wieslab™ Cap PR3-ANCA is an enzyme-linked immunosorbent assay (ELISA) for detection and semi-quantitation of IgG antibodies to proteinase 3 (PR3) in human sera. The assay is used to detect antibodies in a single serum specimen. The results of the assay are to be used as an aid to the diagnosis of Wegener's granulomatosis. The assay is intended for use in patients with signs and symptoms consistent with WG. It is not intended for screening a healthy population. The analysis should be performed by trained laboratory professionals.
The Capture-PR3-ANCA test kit is an enzyme-linked immunosorbent assay (ELISA) for detection and semi-quantitation of IgG antibodies to proteinase 3 (PR3) in human sera. The assay is used to detect antibodies in a single serum specimen. The results of the assay are to be used as an aid to the diagnosis of Wegener's granulomatosis. The assay is intended for use in patients with signs and symptoms consistent with WG. It is not intended for screening a healthy population. The analysis should be performed by trained laboratory professionals.
The wells of the microtiter strips are coated with monoclonal antibody to proteinase 3 and subsequently proteinase 3. During the first incubation, specific antibodies in diluted serum, will bind to the antigen coating.
The wells are then washed to remove unbound antibodies and other components. A conjugate of alkaline phosphatase-labeled antibodies to human IgG binds to the antibodies in the wells in this second incubation.
After a further washing step, detection of specific antibodies is obtained by incubation with substrate solution. The amount of bound antibodies correlates to the color intensity and is measured in terms of absorbance (optical density (OD)). The absorbance is then calculated against a calibrator curve and the results are given in arbitrary units.
Here's an analysis of the provided text to fulfill your request:
Acceptance Criteria and Study Details for Capture PR-3 ANCA Test Kit
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state pre-defined acceptance criteria for the clinical sensitivity and specificity. However, based on the presented data and the regulatory context of a 510(k) submission, the performance of the predicate device serves as the implicit benchmark for substantial equivalence. The reported performance for the new device is as follows:
| Metric | Acceptance Criteria (Implied by Predicate) | Reported Device Performance |
|---|---|---|
| Clinical Sensitivity for WG (Wegener's granulomatosis) | High sensitivity for WG (consistent with predicate) | 96.0% (48/50) with 95% CI (86.3-99.5%) |
| Clinical Sensitivity for MP (Microscopic polyangiitis) | (Not explicitly defined, but shown for comparison) | 46.9% (15/32) with 95% CI (29.1-65.3%) |
| Clinical Specificity for Normal Blood Donors | High specificity (consistent with predicate) | 100% (120/120) with 95% CI (97.0-100%) |
| Clinical Specificity for SLE (Systemic Lupus Erythematosus) | High specificity (consistent with predicate) | 100% (44/44) with 95% CI (92.0-100%) |
| Clinical Specificity for RA (Rheumatoid Arthritis) | High specificity (consistent with predicate) | 100% (16/16) with 95% CI (79.4-100%) |
| Clinical Specificity for GBM (Glomerular Basement Membrane) | High specificity (consistent with predicate) | 89.7% (26/29) with 95% CI (72.7-97.8%) |
| Relative Sensitivity (compared to alternative ELISA) | High (consistent with predicate) | 100% (40/40) with 95% CI (91.2-100%) |
| Relative Specificity (compared to alternative ELISA) | High (consistent with predicate) | 98.5% (134/136) with 95% CI (94.8-99.8%) |
| Relative Accuracy (compared to alternative ELISA) | High (consistent with predicate) | 98.9% (174/176) with 95% CI (96.0-99.9%) |
| Batch to Batch CV% (PK sample) | Low variability | 13% |
| Batch to Batch CV% (K1 sample) | Low variability | 7% |
| Batch to Batch CV% (K3 sample) | Low variability | 11% |
| Inter-Assay CV% (PK sample) | Low variability | 6% |
| Inter-Assay CV% (K1 sample) | Low variability | 6% |
| Inter-Assay CV% (K2 sample) | Low variability | 7% |
| Inter-Assay CV% (K3 sample) | Low variability | 7% |
| Linearity (r value) | Close to 1 | 0.95, 0.94, 0.98 for three sera |
2. Sample Size Used for the Test Set and Data Provenance:
- Clinical Sensitivity and Specificity Study (Table 1):
- Sample Size: 295 frozen sera (120 blood donors, 50 WG, 34 MP, 45 SLE, 17 RA, 29 GBM).
- Data Provenance: Retrospective sera. Country of origin is not explicitly stated.
- Comparison to IIF-ANCA (Table 2):
- Sample Size: 78 frozen retrospective sera from systemic vasculitis.
- Data Provenance: Retrospective sera. Country of origin is not explicitly stated.
- Comparison to Alternative ELISA (Table 3):
- Sample Size: 180 frozen retrospective sera.
- Data Provenance: Retrospective sera. Country of origin is not explicitly stated.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
The document does not explicitly state the number of experts or their qualifications for establishing the ground truth. It mentions "clinical characterisation" for the samples in Table 1 and "IIF-ANCA" and an "alternative ELISA" as comparators in Tables 2 and 3, respectively. This suggests that the ground truth was based on established clinical diagnoses and/or results from other diagnostic methods, though the specific process and expert involvement are not detailed.
4. Adjudication Method for the Test Set:
The document does not describe any specific adjudication method (e.g., 2+1, 3+1). The ground truth appears to be based on pre-existing clinical characterization or results from predicate/alternative assays.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance:
This document describes an Enzyme-Linked Immunosorbent Assay (ELISA) kit, which is a laboratory diagnostic device, not an AI-powered image analysis or diagnostic tool involving human readers. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
The "Capture PR-3 ANCA Test Kit" is an in-vitro diagnostic ELISA kit. Its performance is inherently standalone in the sense that the assay itself generates a result (optical density, converted to arbitrary units) without a human "in-the-loop" during the measurement process. The interpretation of these results for diagnosis is then done by trained laboratory professionals. So, yes, it functions as a standalone diagnostic assay.
7. The Type of Ground Truth Used:
- Clinical Sensitivity and Specificity Study (Table 1): The ground truth was based on clinical characterization of the patients' conditions (e.g., diagnosed with Wegener's granulomatosis, systemic lupus erythematosus, etc., or healthy blood donors).
- Comparison to IIF-ANCA (Table 2): The ground truth was based on the results of IIF-ANCA (Indirect Immunofluorescence - Anti-Neutrophil Cytoplasmic Antibodies), a well-established method for detecting ANCA.
- Comparison to Alternative ELISA (Table 3): The ground truth was based on the results of an alternative PR3-ANCA ELISA kit (presumed to be the predicate device or a similar commercially available assay).
8. The Sample Size for the Training Set:
The document describes performance studies (validation) with test sets. There is no mention of a separate "training set" for an algorithm, as this device is a biochemical assay kit rather than a machine learning model. The assay's parameters (e.g., calibrator values) would have been established during its development and manufacturing, but this is not typically referred to as a "training set" in the context of IVD kits.
9. How the Ground Truth for the Training Set Was Established:
As there is no "training set" in the context of an algorithm or machine learning model for this ELISA kit, this question is not applicable. The assay's inherent design and calibration are based on biochemical principles and established standards, rather than data-driven ground truthing for model training.
{0}------------------------------------------------
K05/458
Summary of Safety and Effectiveness Information Capture PR-3 ANCA Test Kit
NOV 2 3 2005
- I. Euro-Diagnostica AB Per Albin Hanssons vag 41, Medeon SE-205 12 Malmo Sweden Contact person: Sten Gershagen Telephone: 46-40-321100 Date of preparation: May 4, 2005
II. Description of Device: The Capture-PR3-ANCA test kit is an enzyme-linked immunosorbent assay (ELISA) for detection and semi-quantitation of IgG antibodies to proteinase 3 (PR3) in human sera. The assay is used to detect antibodies in a single serum specimen. The results of the assay are to be used as an aid to the diagnosis of Wegener's granulomatosis. The assay is intended for use in patients with signs and symptoms consistent with WG. It is not intended for screening a healthy population. The analysis should be performed by trained laboratory professionals.
The wells of the microtiter strips are coated with monoclonal antibody to proteinase 3 and subsequently proteinase 3. During the first incubation, specific antibodies in diluted serum, will bind to the antigen coating.
The wells are then washed to remove unbound antibodies and other components. A conjugate of alkaline phosphatase-labeled antibodies to human IgG binds to the antibodies in the wells in this second incubation.
After a further washing step, detection of specific antibodies is obtained by incubation with substrate solution. The amount of bound antibodies correlates to the color intensity and is measured in terms of absorbance (optical density (OD)). The absorbance is then calculated against a calibrator curve and the results are given in arbitrary units.
III. Predicate Device
The Capture PR-3 ANCA test is substantially equivalent to the PR-3 ANCA ELISA Kit. Equivalence is demonstrated by the following comparative results:
{1}------------------------------------------------
| Control andDisease groups | Totalnumber | Negative< 20 units | Equivocal21-30 units | Positive> 30 units |
|---|---|---|---|---|
| Blood donors: | 120 | 120 | 0 | 0 |
| WG: | 50 | 2 | 0 | 48 |
| MP: | 34 | 17 | 2 | 15 |
| SLE: | 45 | 44 | 1 | 0 |
| RA: | 17 | 16 | 1 | 0 |
| GBM: | 29 | 26 | 0 | 3 |
Table 1. Clinical sensitivity and specificity. A total of 295 frozen retrospective sera with clinical characterisation were assayed. The following table summarises the results
WG = Wegener's granulomatosis, SLE = systemic lupus erythematosus MP = microscopic polyangiitis
RA = rheumatoid arthritis
GBM = glomerular basement membrane
Clinical sensitivity (Equivocal samples excluded from calculations)
95% CI = 86.3-99.5 % WG = 48/50 = 96.0 % 95% CI = 29.1-65.3 % MP == 15/32 = 46.9 %
Clinical specificity (Equivocal samples excluded from calculations)
95% CI = 72.7-97.8 % GBM = 26/29 = 89.7 % 95% CI = 92.0-100 % SLE = 44/44 = 100 % 95% CI = 79.4-100 % = 16/16 = 100 % RA Normal = 120/120 = 100 % 95% CI = 97.0-100 %
The 95% confidence interval (CI) was calculated using the exact method.
{2}------------------------------------------------
Table 2. Wielisa capture PR3-ANCA kit compared to IIF-ANCA. A total of 78 frozen retrospective sera from systemic vasculitis were assayed. The following table summarises the results.
| IIF-ANCA | Positive | Equivocal | Negative | Total | |
|---|---|---|---|---|---|
| c-ANCA | 52 | 0 | 1 | 53 | |
| p-ANCA | 1 | 1 | 13 | 15 | |
| Negative | 10 | 0 | 0 | 10 | |
| Total | 63 | 1 | 14 | 78 |
Table 3. Relative sensitivity and specificity of the Wielisa capture PR3-ANCA kit compared to an alternative ELISA. A total of 180 frozen retrospective sera were assayed. The following table summarises the results.
| Positive | Equivocal | Negative | Total | |
|---|---|---|---|---|
| Positive | 40 | 0 | 0 | 40 |
| AlternativeEquivocal | 2 | 0 | 0 | 2 |
| ELISANegative | 2 | 2 | 134 | 138 |
| Total | 44 | 2 | 134 | 180 |
Sera falling in the equivocal range were excluded from the following calculations.
| Relative sensitivity | = 40/40 = 100% | 95% CI = 91.2-100 % |
|---|---|---|
| Relative specificity | = 134/136 = 98.5 % | 95% CI = 94.8-99.8 % |
| Relative Accuracy | = 174/176 = 98.9 % | 95% CI = 96.0-99.9 % |
The 95% confidence interval (CI) was calculated using the exact method.
Table 4. Batch to batch variation was determined by testing three different samples in duplicate. Results were obtained for five different batches.
| Sample | Mean value | SD | CV % |
|---|---|---|---|
| PK | 76 units | 10 | 13 |
| K1 | 45 units | 3 | 7 |
| K3 | 88 units | 10 | 11 |
{3}------------------------------------------------
Table 5. Inter-assay precision was determined by testing four different samples in duplicate. Results were obtained for four different runs.
| Sample | Mean value | SD | CV % |
|---|---|---|---|
| PK | 85 units | 5 | 6 |
| K1 | 49 units | 3 | 6 |
| K2 | 77 units | 5 | 7 |
| K3 | 138 units | 9 | 7 |
Table 6. Intra-assay precision was determined by testing two samples in 24 wells.
| Sample | A-4-4-4-4Mean value | CITY1 | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------Acres of can and a compare77 01/0 | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ |
|---|---|---|---|---|
| (1 30 | 1000 - 1000 | |||
| 1 | D1 | 4 Aﺑ | ----------------------------------------------------------------------------------Annual Partic Participant Property Controller Collection Comers of Children Comers of Children Comments of Children Comments of Children Comments of Children Comments of Chil | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ |
Table 7. Linearity. The values were determined for serial two-fold dilutions of three positive sera. The I able 7 Elizarion the has 2 of dilution by standard linear regression. The data indicates that the assay has a linear relationship with serum dilution.
| Serum | neat | 1:2 | 1:4 | 1:8 | 1:16 | 1:32 | r |
|---|---|---|---|---|---|---|---|
| 1 | 394 | 297 | 188 | 74 | 37 | 16 | 0.95 |
| 2 | 334 | 269 | 106 | 48 | 0.94 | ||
| 3 | 324 | 219 | 100 | 36 | 22 | 8 | 0.98 |
{4}------------------------------------------------
Image /page/4/Picture/0 description: The image shows the text "DEPARTMENT OF HEALTH & HUMAN SERVICES" in all caps. The text is in a bold, serif font. The text is centered horizontally in the image. The background of the image is white.
Public Health Service
Eurodiagnostica · c/o Mr. William L. Boteler Jr. Immuno Probe, Inc. 1306 Bailes Lane, Suite F Frederick, MD 21701
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
NOV 2 3 2005
Re: K051458
Trade/Device Name: Wieslab™ Cap PR-3 ANCA Regulation Number: 21 CFR 866.5660 Regulation Name: Multiple autoantibodies immunological test system Regulatory Class: Class II Product Code: MOB Dated: June 1, 2005 Received: June 2, 2005
Dear Mr. Boteler:
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 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 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
Image /page/4/Picture/12 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States of America. The seal features a stylized eagle with its wings spread, symbolizing protection and service. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" are arranged in a circular pattern around the eagle, indicating the department's name and national affiliation. The seal is simple and monochromatic.
{5}------------------------------------------------
Page 2 -
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 (240) 276-0484. 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/industry/support/index.html
Sincerely yours,
loburtz Beckerh
Robert L. Becker, Jr., MD, PK Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
{6}------------------------------------------------
Page 1 of 1
510(k) Number: K051458
Device Name: Wieslab™ Cap PR3-ANCA
Indications For Use: The Wieslab™ Cap PR3-ANCA is an enzyme-linked immunosorbent assay (ELISA) for detection and semi-quantitation of IgG antibodies to proteinase 3 (PR3) in human sera. The assay is used to detect antibodies in a single serum specimen. The results of the assay are to be used as an aid to the diagnosis of Wegener's granulomatosis. The assay is intended for use in patients with signs and symptoms consistent with WG. It is not intended for screening a healthy population. The analysis should be performed by trained laboratory professionals.
PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED) スマーニュレア |
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use V (Per 21 CFR 801.109)
OR
Over-The Counter Use (Optional Format 1-2-96)
Maria Chan
Division Stop-On
of In Vitro Diagnostic
510(k) K051454
§ 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).