The Wielisa Anti-GBM, ANCA Screening Test Kit is an enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of antibodies to glomerular basement membrane (GBM), Proteinase-3 (PR-3) and Myeloperoxidase (MPO) 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 reno-pulmonary syndromes and rapidly progressive glomerulonephritis, especially Goodpasture syndrome (GP), Wegener's granulomatosis (WG) and microcopic polyangiitis (MP). The assay is intended for use in patients with signs and symptoms consistent with GP, WG, and MP. It is not intended for screening a healthy population. A positive result should always be confirmed by a semi-quantitative assay.

Device Description

The Wielisa Anti-GBM, ANCA Screening Test Kit is an II. enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of antibodies to glomerular basement membrane (GBM), Proteinase-3 (PR-3) and Myeloperoxidase (MPO) 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 reno-pulmonary syndromes and rapidly progressive glomerulonephritis, especially Goodpasture syndrome (GP). Wegener's granulomatosis (WG) and microcopic polyangiitis (MP). The assay is intended for use in patients with signs and symptoms consistent with GP, WG, and MP. It is not intended for screening a healthy population. A positive result should always be confirmed by a semi-quantitative assay.

The wells of the microtiter strips are coated with purified proteinase 3 (Human Neutrophil source). MPO (Human Neutrophil source) and GBM (Bovine source) antigen. 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 coniugate of alkaline phosphatase-labeled (Goat) 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 and the results are given as a ratio to the negative control.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Wielisa Anti-GBM, ANCA Screening Test Kit, based on the provided text:

Device Description: The Wielisa Anti-GBM, ANCA Screening Test Kit is an enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of antibodies to glomerular basement membrane (GBM), Proteinase-3 (PR-3), and Myeloperoxidase (MPO) in human sera. It's used as an aid to diagnose reno-pulmonary syndromes and rapidly progressive glomerulonephritis (Goodpasture syndrome, Wegener's granulomatosis, and microscopic polyangiitis).

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the clinical sensitivity and specificity results. The device aims to achieve high sensitivity (correctly identifying positive cases) and high specificity (correctly identifying negative cases) for each antibody against various disease states and controls.

Metric (Antibody)	Target/Acceptance Criteria (Implicit)	Reported Device Performance
Clinical Sensitivity
PR3-ANCA (WG)	High	92.9% (95% CI: 84.9 – 100%)
PR3-ANCA (MP)	High	51.2% (95% CI: 35.6-66.8%)
MPO-ANCA (WG)	High	9.8% (95% CI: 4.9 – 19.0%)
MPO-ANCA (MP)	High	46.5% (95% CI: 31.3-61.7%)
Anti-GBM (GP)	High	100% (95% CI: 92.2 – 100%)
Clinical Specificity
PR3-ANCA (SLE)	High	100% (95% CI: 90.4 – 100%)
PR3-ANCA (RA)	High	100% (95% CI: 92.7 - 100%)
PR3-ANCA (NS)	High	100% (95% CI: 97.7 - 100%)
MPO-ANCA (SLE)	High	82.8% (95% CI: 68.7 - 96.8%)
MPO-ANCA (RA)	High	100% (95% CI: 92.6 - 100%)
MPO-ANCA (NS)	High	100% (95% CI: 97.6 - 100%)
Anti-GBM (SLE)	High	100% (95% CI: 90.4 -100%)
Anti-GBM (RA)	High	100% (95% CI: 92.7 - 100%)
Anti-GBM (NS)	High	100% (95% CI: 97.6 – 100%)
Relative Sensitivity (vs. Semi-quantitative ELISA)
PR3-ANCA	High	98.3% (95% CI: 95.0 - 100%)
MPO-ANCA	High	95.8% (95% CI: 87.7 - 100%)
Anti-GBM	High	100% (95% CI: 92.0 - 100%)
Relative Specificity (vs. Semi-quantitative ELISA)
PR3-ANCA	High	100% (95% CI: 98.0 - 100%)
MPO-ANCA	High	100% (95% CI: 98.4 - 100%)
Anti-GBM	High	100% (95% CI: 97.7 - 100%)
Precision	Low CV% (for intra-assay, inter-assay, batch-to-batch)	All reported CV% values are below 21%, indicating good precision.

2. Sample Size Used for the Test Set and Data Provenance

Clinical Sensitivity and Specificity Study:
- Sample Size: A total of 326 frozen serum samples.
- Data Provenance: Retrospective sera. The country of origin is not explicitly stated.
  - Blood donors (NS): 131 samples
  - Wegener's granulomatosis (WG): 42 samples
  - Microscopic polyangiitis (MP): 43 samples
  - Systemic lupus erythematosus (SLE): 31 samples
  - Rheumatoid arthritis (RA): 41 samples
  - Goodpasture syndrome (GP): 38 samples
Relative Sensitivity and Specificity Study (vs. Predicate Device):
- Sample Size:
  - 216 frozen retrospective sera for PR-3 and MPO comparison.
  - 169 frozen retrospective sera for anti-GBM comparison.
- Data Provenance: Retrospective sera. The country of origin is not explicitly stated.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

The text states that the sera had "clinical characterisation" for the clinical sensitivity and specificity study, and were compared against an "alternative semi-quantitative ELISA" for the relative sensitivity and specificity study. However, the number of experts, their qualifications, or the specific methodology (beyond "clinical characterization") used to establish the ground truth for these samples is not provided in the given text.

4. Adjudication Method for the Test Set

The adjudication method for establishing the ground truth is not provided in the given text.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done as this is an in-vitro diagnostic (IVD) device (ELISA kit) that produces quantitative or qualitative results, not interpretations by human readers that would be assisted by AI. Thus, there is no AI assistance or human reader involvement in the primary assay performance.

6. If a Standalone Study Was Done

Yes, the studies presented are standalone (algorithm only) performance studies for the ELISA kit. The "device performance" refers to the output of the ELISA kit itself, without human interpretation or intervention in the diagnostic process beyond performing the assay according to instructions. The device generates an optical density (OD) which is then calculated as a ratio, and categorized as negative, equivocal, or positive.

7. The Type of Ground Truth Used

Clinical Sensitivity and Specificity Study: "Clinical characterisation" was used as the ground truth for the disease groups (WG, MP, SLE, RA, GP) and blood donors. This implies diagnosis based on clinical evidence, potentially confirmed by other laboratory tests or pathology (though not specified).
Relative Sensitivity and Specificity Study: The ground truth was established by comparison to results from an "alternative semi-quantitative ELISA" for PR-3, MPO, and anti-GBM. This suggests that the predicate device or a similar established method served as the reference standard.

8. The Sample Size for the Training Set

The text does not provide any information about a training set. This is typical for ELISA kits, where the assay design, antigen selection, and analytical parameters are developed through R&D, rather than an explicit "machine learning training set." The studies described focus on validation of the final product.

9. How the Ground Truth for the Training Set Was Established

As no training set is mentioned or described, the method for establishing its ground truth is not applicable/provided.

Summary

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K981750

Summary of Safety and Effectiveness Information GBM, ANCA Screening ELISA Test Kit

Wieslab AB Ideon Research Park S-223 70 Lund Sweden Contact person: Dr. Jorgen Wieslander Telephone: 46-46-182840 Date of preparation: May 1, 1998

Description of Device: The Wielisa Anti-GBM, ANCA Screening Test Kit is an II. enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of antibodies to glomerular basement membrane (GBM), Proteinase-3 (PR-3) and Myeloperoxidase (MPO) 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 reno-pulmonary syndromes and rapidly progressive glomerulonephritis, especially Goodpasture syndrome (GP). Wegener's granulomatosis (WG) and microcopic polyangiitis (MP). The assay is intended for use in patients with signs and symptoms consistent with GP, WG, and MP. It is not intended for screening a healthy population. A positive result should always be confirmed by a semi-quantitative assay.

III. Predicate Device

The GBM, ANCA Screening test is substantially equivalent to the Wielisa PR-3 ANCA ELISA Kit , the Wielisa MPO ANCA ELISA Kit and the Wielisa anti-GBM ELISA Kit. Equivalence is demonstrated by the following comparative results:

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Control andDisease groups	Total	Negative <3			Equivocal 3-4			Positive >4
		GBM	PR3	MPO	GBM	PR3	MPO	GBM	PR3	MPO
Blood donors: (NS)	131	128	131	127	3	0	4	0	0	0
WG:	42	-	3	37	-	0	1	-	39	4
MP:	43	-	20	23	-	2	0	-	21	20
SLE:	31	31	31	24	0	0	2	0	0	5*
RA:	41	41	41	40	0	0	1	0	0	0
GP:	38	0	-	-	0	-	-	38	-	-

Table 1. Clinical sensitivity and specificity. A total of 326 frozen retrospective sera with clinical characterisation were assayed. The following table summarises the results

MP = microscopic polyangiitis RA = rheumatoid arthritis WG = Wegener's granulomatosis,

SLE = systemic lupus erythematosus GP = Goodpasture syndrome

All samples were positive in semi-quantitative MPO-ELISA.

Clinical sensitivity (Equivocal samples are not included in the calculation)

PR3-ANCA:	WG = 39/42 = 92.9 %	95% CI = 84.9 – 100%
	MP = 21/41 = 51.2 %	95% CI = 35.6-66.8%
MPO-ANCA:	WG = 4/41 = 9.8 %	95% CI = 4.9 – 19.0%
	MP = 20/43 = 46.5 %	95% CI = 31.3-61.7%
Anti-GBM:	GP = 38/38 = 100 %	95% CI = 92.2 – 100%

Clinical specificity (Equivocal samples are not included in the calculation)

PR3-ANCA:	SLE = 31/31 = 100 %RA = 41/41 = 100 %NS = 131/131 = 100 %	95% CI = 90.4 – 100%95% CI = 92.7 - 100%95% CI = 97.7 - 100%
MPO-ANCA:	SLE = 24/29 = 82.8 %RA = 40/40 = 100 %NS = 127/127 = 100 %	95% CI = 68.7 - 96.8%95% CI = 92.6 - 100%95% CI = 97.6 - 100%
Anti-GBM:	SLE = 31/31 = 100 %RA = 41/41 = 100 %NS = 128/128 = 100 %	95% CI = 90.4 -100%95% CI = 92.7 - 100%95% CI = 97.6 – 100%

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Table 2. Relative sensitivity and specificity of the Wielisa anti-GBM, ANCA screen kit compared to an alternative semi-quantitative ELISA. A total of 216 frozen retrospective sera were assayed on the Wielisa anti-GBM, ANCA screen kit and a semi-quantitative ELISA for PR-3 and MPO. Also, a total of 169 frozen retrospective sera were assayed on the Wielisa anti-GBM, ANCA screen kit and an semiquantitative ELISA for anti-GBM. The following table summarises the results.

Semi-quantitativeELISA	Negative <3			Equivocal			Positive >4
	GBM	PR3	MPO	GBM	PR3	MPO	GBM	PR3	MPO
MPO-ANCA	Positive	0	0	1	0	0	0	0	0	23
PR3-ANCA	Positive	0	1	0	0	0	0	0	59	0
Anti-GBM	Positive	0	-	-	0	-	-	37	-	-
	Negative	128	152	182	3	2	4	0	0	0
	Equivocal	0	1	4	0	0	1	1	1	1
	Total	128	154	187	3	2	5	38	60	24

Relative sensitivity (Equivocal samples are not included in the calculation)

Relative sensitivity PR3-ANCA = 59/60 = 98.3% 95% CI = 95.0 - 100% Relative sensitivity MPO-ANCA = 23/24 = 95.8% 95% CI = 87.7 - 100% Relative sensitivity anti-GBM = 37/37 = 100 % 95% CI = 92.0 - 100%

Relative specificity (Equivocal samples are not included in the calculation)

Relative specificity PR3-ANCA = 152/152 = 100 % 95% CI = 98.0 - 100% Relative specificity MPO-ANCA= 182/182 = 100 % 95% CI = 98.4 - 100% Relative specificity anti-GBM = 128/128 = 100 % 95% CI = 97,7 - 100%

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Table 3. Batch to batch variation was determined by testing three different samples. Results were obtained for 4 different batches.

PR3	Sample Mean SD CV% Sample Mean SD CV% Sample Mean SD CV%MPO	GBM	OD ratio
2	37.5 × 3.8 × 10 × 10 × 3 × 3 × 16.8 × × 2.2 × 13 × 13 × × 1 × 1 × ×		21.8
	24.3 23.6 3.6 15 15 15 6 1	31.5 1.5 1.9 1.9 6 6 2 4 4 29.0 29.0 2.2 2.2 4 4
8	35.5 % 2.4 % 777 % % 9 % 28.3 % % 1.5 % % 5 % % 7 % % 33.8 % % 2.4 % 7 %

Table 4. Inter-assay precision was determined by testing one sample. Results were obtained for six different runs.

Sample	MeanOD ratio	SD	CV %	SampleMPO	MeanOD ratio	SD	CV %	SampleGBM	MeanOD ratio	SD	CV %
PK	27.3	2.9	11	PK	17.3	3.8	21	PK	16.5	1.1	6
K5	12.1	1.2	10	K6	16.5	0.84	5	K4	3.6	0.25	7

Table 5. Intra-assay precision was determined by testing one sample in 22 wells.

SamplePR3	MeanOD	SD	CV %	SampleMPO	MeanOD	SD	CV %	SampleGBM	MeanOD	SD	CV%
PK	1.3	0.07	6	PK	1.8	0.06	3	PK	1.2	0.19	16
K5	1.3	0.06	5	K6	1.46	0.07	5	K4	0.6	0.03	6

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Image /page/4/Picture/2 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized abstract symbol resembling an eagle or bird in flight. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the symbol. The text is in all capital letters and is evenly spaced around the circle.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

JUL 22 1998

Weislab AB c/o William L. Boteler, Jr. IMMUNO PROBE, INC. 1306 Bailes Lane, Suite F Frederick, MD 21701

Re: K981750 Trade Name: Wielisa Anti-GBM, ANCA Screening Test Kit Regulatory Class: II Product Code: DBL, MOB Dated: May 3, 1998 Received: May 18, 1998

Dear Mr. Boteler:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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 (Premarket Approval) , 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 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General requlation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal Laws or Requlations.

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Page 2

Under the Clinical Laboratory Improvement Amendments of 1988 (CDIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.

This letter will allow you to begin marketing your device as described in your 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.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"

Sincerely yours,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Page 1 of 1

510(k) Number: Not known K98) 750

Device Name: Wielisa Anti-GBM, ANCA Screening Test Kit

Indications For Use: The Wielisa Anti-GBM, ANCA Screening Test Kit is an enzymelinked immunosorbent assay (ELISA) for the qualitative detection of antibodies to glomerular basement membrane (GBM), Proteinase-3 (PR-3) and Myeloperoxidase (MPO) 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 reno-pulmonary syndromes and rapidly progressive glomerulonephritis, especially Goodpasture syndrome (GP), Wegener's granulomatosis (WG) and microcopic polyangiitis (MP). The assay is intended for use in patients with signs and symptoms consistent with GP, WG, and MP. It is not intended for screening a healthy population. A positive result should always be confirmed by a semi-quantitative assay.

PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

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)

(Division Sign-Off)
Division of Clinical Laboratory Devices K981,750
510(k) Number

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).