K Number

Device Name

WIESLAB CAP PR-3 ANCA

Manufacturer

EURODIAGNOSTICA

Date Cleared

2005-11-22

(173 days)

Product Code

MOB

Regulation Number

866.5660

Intended 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.

Device Description

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.

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Expedited Review

Predicate Devices

PR-3 ANCA ELISA Kit

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The description details a standard ELISA assay with optical density measurement and calculation against a calibrator curve, which does not involve AI/ML.

Therapeutic

No
This device is an in vitro diagnostic (IVD) test used to detect antibodies for the diagnosis of a condition, not to treat it.

Diagnostic

Yes

The intended use explicitly states that "The results of the assay are to be used as an aid to the diagnosis of Wegener's granulomatosis." This directly indicates its role in diagnosis.

SaMD (Software as a Medical Device)

The device is an ELISA test kit, which is a laboratory assay involving physical reagents and procedures, not solely software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use clearly states that the device is an "enzyme-linked immunosorbent assay (ELISA) for detection and semi-quantitation of IgG antibodies to proteinase 3 (PR3) in human sera." It also specifies that the results are to be used "as an aid to the diagnosis of Wegener's granulomatosis." This indicates that the device is used to examine specimens derived from the human body (serum) to provide information for diagnostic purposes.
Device Description: The device description further elaborates on the process of using the assay to detect antibodies in human serum, reinforcing its use with human biological samples.
Performance Studies: The inclusion of performance studies evaluating clinical sensitivity and specificity, as well as comparisons to other diagnostic methods (IIF-ANCA and an alternative ELISA), is typical for IVD devices. These studies demonstrate the device's ability to provide relevant diagnostic information.
Predicate Device: The mention of a "Predicate Device(s)" with the name "PR-3 ANCA ELISA Kit" strongly suggests that this device is being compared to or is a successor to a previously cleared IVD device.

All of these factors align with the definition and characteristics of an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

Product codes

MOB

Device Description

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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

trained laboratory professionals

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)

Clinical sensitivity and specificity: A total of 295 frozen retrospective sera with clinical characterisation were assayed.
Results:
WG = 48/50 = 96.0 % (95% CI = 86.3-99.5 %)
MP == 15/32 = 46.9 % (95% CI = 29.1-65.3 %)
GBM = 26/29 = 89.7 % (95% CI = 72.7-97.8 %)
SLE = 44/44 = 100 % (95% CI = 92.0-100 %)
RA = 16/16 = 100 % (95% CI = 79.4-100 %)
Normal = 120/120 = 100 % (95% CI = 97.0-100 %)

Wielisa capture PR3-ANCA kit compared to IIF-ANCA: A total of 78 frozen retrospective sera from systemic vasculitis were assayed.

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.
Results (Equivocal samples excluded):
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 %)

Batch to batch variation: determined by testing three different samples in duplicate. Results were obtained for five different batches.
Sample PK: Mean value 76 units, SD 10, CV % 13
Sample K1: Mean value 45 units, SD 3, CV % 7
Sample K3: Mean value 88 units, SD 10, CV % 11

Inter-assay precision: determined by testing four different samples in duplicate. Results were obtained for four different runs.
Sample PK: Mean value 85 units, SD 5, CV % 6
Sample K1: Mean value 49 units, SD 3, CV % 6
Sample K2: Mean value 77 units, SD 5, CV % 7
Sample K3: Mean value 138 units, SD 9, CV % 7

Intra-assay precision: determined by testing two samples in 24 wells.

Linearity: Values determined for serial two-fold dilutions of three positive sera. Data indicates a linear relationship with serum dilution.
Serum 1: r=0.95
Serum 2: r=0.94
Serum 3: r=0.98

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Clinical sensitivity (Equivocal samples excluded from calculations): 96.0 % for WG, 46.9 % for MP.
Clinical specificity (Equivocal samples excluded from calculations): 89.7 % for GBM, 100 % for SLE, 100 % for RA, 100 % for Normal.
Relative sensitivity: 100%
Relative specificity: 98.5 %
Relative Accuracy: 98.9 %

Predicate Device(s)

PR-3 ANCA ELISA Kit

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

Regulation Number and Section

§ 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).

Summary

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.

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:

| Control and
Disease groups | Total
number | Negative
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.

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.

	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
Alternative
Equivocal	2	0	0	2
ELISA
Negative	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

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-4-4-4-4
Mean value | CITY
1 | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Acres of can and a compare
77 01
/0 | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ |
|--------|-------------------------|-------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | (
1 30 | 1000 - 1000 | | |
| 1 | D
1 | 4 A
ﺑ | ----------------------------------------------------------------------------------
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

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.

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

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)

Over-The Counter Use (Optional Format 1-2-96)

Maria Chan
Division Stop-On

of In Vitro Diagnostic

510(k) K051454