MODIFICATION TO FIDIS VASCULITIS, MODEL MX007

K070458 · Biomedical Diagnostics (Bmd) SA · MOB · Dec 21, 2007 · Immunology

Device Facts

• Record ID: K070458
• Device Name: MODIFICATION TO FIDIS VASCULITIS, MODEL MX007
• Applicant: Biomedical Diagnostics (Bmd) SA
• Product Code: MOB · Immunology
• Decision Date: Dec 21, 2007
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5660
• Device Class: Class 2

Intended Use

The FIDIS™ VASCULITIS® kit is a semi-quantitative homogeneous fluorescent-based microparticles immunoassay using flow cytometry readings. The test system is used to detect in patient serum samples the presence of anti-neutrophil cytoplasm antibodies (ANCA) directed against Myeloperoxidase (MPO) and Serine Proteinase 3 (PR3); and anti-glomerular basement membrane (GBM) antibodies. The results of the FIDIS™ VASCULITIS® test are to be used in conjunction with the clinical findings and the other laboratory tests to aid in the diagnosis of various primary systemic small vessel vasculitis. The presence of anti-MPO and anti-PR3 antibodies associated primary systemic small vessel vasculitis: Wegener's granulomatosis, Churg Strauss syndromes, microscopic periarteritis and idiopathic crescentic glomerulonephritis; and the presence of anti-GBM antibodies is associated with Goodpasture's syndrome. FIDIS™ VASCULITIS® kit is used on the FIDIS Analyser, MLX-BOOSTER Software and FIDIS™ Washer. FIDIS™ VASCULITIS* kit could be used with CARIS™ system (diluting and dispensing device). This test is for in vitro diagnostic use.

Device Story

In vitro diagnostic kit; detects anti-MPO, anti-PR3, and anti-GBM antibodies in patient serum. Uses color-coded microspheres covalently coupled to specific antigens; multiplexed assay format. Patient serum incubated with microspheres; bound antibodies detected via phycoerythrin-labeled anti-human IgG conjugate. Benchtop flow cytometer (Luminex 100/200) uses red laser for microsphere identification and green laser for fluorescence quantification. MLX-BOOSTER software processes signals; calculates antibody titers via interpolation against calibration system. Used in clinical laboratories; operated by trained personnel. Results aid clinicians in diagnosing systemic small vessel vasculitis and Goodpasture's syndrome. Optional CARIS system automates sample dilution and dispensing.

Clinical Evidence

Comparative study on 219 clinical samples (135 positive, 84 negative) against predicate K053012. Results: MPO (97.18% positive agreement, 100% negative agreement), PR3 (95.92% positive, 99.41% negative), GBM (100% positive, 100% negative). Additional study on 117 samples compared manual vs. CARIS™ automated preparation, showing high agreement (98.29-100%). Precision studies (intra-assay and inter-assay) met acceptance criteria (CV% ≤15-20%).

Technological Characteristics

Multiplexed fluorescent-based microparticle immunoassay. Components: color-coded microspheres coupled to MPO, PR3, and GBM antigens; phycoerythrin-labeled anti-human IgG conjugate. Platform: flow cytometry (Luminex 100/200). Energy: laser-based excitation. Connectivity: PC-based software (MLX-BOOSTER). Sample matrix: serum. Format: 96-well microplate with filtering membrane.

Indications for Use

Indicated for the detection of anti-neutrophil cytoplasm antibodies (ANCA) against MPO and PR3, and anti-glomerular basement membrane (GBM) antibodies in patient serum to aid in the diagnosis of primary systemic small vessel vasculitis (Wegener's granulomatosis, Churg Strauss syndrome, microscopic periarteritis, idiopathic crescentic glomerulonephritis) and Goodpasture's syndrome. Prescription use only.

Regulatory Classification

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).

Predicate Devices

• FIDIS™ VASCULITIS (k053012)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image shows a logo for "biomedical diagnostics". The logo consists of the letters "bmd" in a stylized font, with the letters connected at the top. Below the letters is a horizontal line, and below that is the text "biomedical diagnostics" in a smaller font. The letters "bmd" are in a bold, sans-serif font, and the letters are connected at the top.

## Premarket Notification 510(k) Summary

## Assigned 510(k) Number: K070458

DEC 2 1 2007

| | 1) Submitted by : | | |
|--|----------------------|-----------------------------------|--|
| | Name: | Biomedical Diagnostics S.A (bmd) | |
| | Contact Person: | Christelle COURIVAUD | |
| | | Regulatory Affairs Manager | |
| | Address: | Actipole 25, 4-6 Bld de Beaubourg | |
| | | 77435 Marne-La-Vallée Cedex 2 | |
| | | FRANCE | |
| | Telephone: | 33 (0)1 64 62 10 12 | |
| | Fax: | 33 (0)1 64 62 09 66 | |
| | Establishment | | |
| | Registration Number: | 3003935253 | |

US Agent correspondent:

Hoppe Regulatory Consultants Ms P. Ann HOPPE 2335 Massey Lane Decatur GA 30033 USA Phone: [phone] E-mail: [e-mail]

### 2) Device Name

| Trade/Proprietary Name : | FIDIS™ VASCULITIS Assay kit |
|--------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Common/Usual Name : | MX007 - FIDIS™ VASCULITIS: Detection test for<br>autoantibodies directed against Myeloperoxidase (MPO),<br>Serine Proteinase 3 (PR3) and Glomerular Basement<br>Membrane (GBM) in human serum |
| Classification Names: | Test system, Antineutrophil Cytoplasmic Antibodies (ANCA)<br>Devices, Measure, Antibodies to Glomerular Basement<br>Membrane (GBM) |
| Trade/Proprietary Name : | FIDIS™ Analyzer |
| Classification Name: | Instrumentation for Chemical Multiplex Systems |
| Trade/Proprietary Name : | CARIST™ System |
| Classification Name: | Device, Microtiter diluting/Dispensing |

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### 3) Intended use

The FIDIS™ VASCULITIS* kit is a semi-quantitative homogeneous fluorescent-based microparticle immunoassay using flow cytometry. The test system is used to simultaneously detect the presence of anti-neutrophil cytoplasmic antibodies (ANCA) directed against Myeloperoxidase (MPO), Serine Proteinase 3 (PR3) and antibodies directed against glomerular basement membrane (GBM) in human serum samples.

The results of the FIDIS™ VASCULITIS* test are to be used in conjunction with the clinical findings and the other laboratory tests to aid in the diagnosis of various primary systemic small blood vessel vasculitides and glomerular basement membrane disease.

### Clinical utility:

The detection of ANCA is associated with primary systemic small blood vessel vasculitides: Wegener's granulomatosis, Churg Strauss syndromes, microscopic periarteritis and idiopathic crescentic glomerulonephritis; and the detection of anti-GBM antibodies is associated with Goodpasture's syndrome.

FIDIS™ VASCULITIS* kit uses serum only, and is to be run on the FIDIS™ Instrument and MLX-BOOSTER Software.

FIDIS™ VASCULITIS* kit may be used with the CARIS™ system (diluting and dispensing device).

### This test is for In vitro diagnostic use.

* Detection of the serologic markers for primary systemic small blood vessel vasculitides (ANCA) and for Goodpasture syndrome (GBM).

### 4) Materials supplied

| 1 x 96 wells microplate including a filtering membrane and a lid. | 1 plate |
|-------------------------------------------------------------------------------------------------------------------------------------------------|-----------|
| 1 vial (A) of 3 sets of color-coded microsphere beads coupled with<br>MPO, PR3 and GBM*, plus 1 set of internal standard beads.<br>Ready to use | 1 x 6mL |
| 1 vial (B) of sample dilution buffer (PBS-Tween) (white vial)<br>Ready to use | 2 x 115mL |
| 1 vial of calibrator** titered for the specificities to be measured.<br>Ready to use<br>Each titer is printed on the vial label | 1 x 1,5mL |

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| 1 vial of positive control** concentrate. This control has a standard<br>reactivity that provides evidence of the proper functioning of<br>reagents and correct assay performance.<br>To be diluted<br>Expected values are printed on the vial label. | 1 x 250 µL |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------|
| 1 vial of negative control** concentrate. To be diluted | 1 x 250μL |
| 1 vial of anti-human IgG coupled to phycoerythrin<br>Ready to use | 1 x 12mL |
| 1 vial (C) of washing buffer (PBS-Tween) (black vial)<br>Ready to use | 1 x 100mL |
| Package Insert | 1 |
| Microplate Assay Configuration Worksheet | 1 |
| Microplate sealing films | 6 |

* GBM antigen purified from type IV collagen.

** Calibrator and control titers are expressed in arbitrary units per mL (AU/mL).

# 5) Predicate Device

.

| 510K Number | Device Classification Name | Manufacturer Name |
|-------------|----------------------------|-------------------------------------|
| K053012 | FIDISTM VASCULITIS | Biomedical Diagnostics<br>S.A.(bmd) |

# 6) Comparison with the predicate

| | | Predicate Device<br>FIDISTM VASCULITIS<br>K053012 | Modified Device<br>FIDISTM VASCULITIS |
|---------|-------------------|-----------------------------------------------------------------------------------------|---------------------------------------------------------------------------------|
| | Intended use | Individual determination in human serum, of IgG antibodies against:<br>MPO, PR3 and GBM | Same |
| | Antigen | - MPO: purified antigen<br>- PR3: purified antigen<br>- GBM: purified antigen | Same |
| CUT-OFF | Negative | <20 AU/mL<br>for the 3 specificities | Same |
| | Equivocal | 20-25 AU/mL<br>for the 3 specificities | Same |
| | Positive | >25 AU/mL<br>for the 3 specificities | Same |
| | Material supplied | Microplate with caps | Microplate with sealing films (no change in function and provides flexible use) |
| | Sample dilution | PBS-Tween concentrated | Sample dilution buffer – same ingredients but ready to use |
| | Wash buffer | PBS-Tween concentrated | Washing buffer – same ingredients but ready to use |

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| | Predicate Device<br>FIDIST™ VASCULITIS<br>K053012 | Modified Device<br>FIDIST™ VASCULITIS |
|---------------------------------------|---------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------|
| Internal standard beads | No | Yes |
| Assay configuration | 1 "reagent-blank" well<br>1 "calibrator" well<br>1 "negative control" well<br>1 "positive control" well | 1 "reagent-blank" well<br>1 "negative control" well<br>1 "positive control" well<br>2 "calibrator" wells |
| | Diluted sample wells | Same |
| | A second calibrator well every 32 well<br>series | No |
| Incubation time | 2 x 30mn RT | Same |
| Assay protocol | Optional final wash step | Final wash step (not optional) |
| Software | MLX-Booster Version 1.35 | MLX-Booster Version 2.2 |
| Assay technology | Flow cytometric | Flow cytometric |
| Sample delivery | Manual pipetting | Same |
| Automated sample delivery<br>(option) | CARIS™ (pipettor) | Same |

## 7) Performance Characteristics

# 1. Analytical performance

- a. Precision
Precision of the assay was assessed in 16 samples for antibodies to each of the three analytes (MPO, PR3, GBM) and 3 negative samples. Precision was determined by calculating the within-run (intra-assay) and the between run (interassay).

- For within-run: 10 tests in a same run.
- For between-run: 5 runs, 3 tests per run.

| Sample<br>range | Acceptance<br>criteria for<br>within-run and<br>between-run | MPO, PR3 and GBM parameters<br>Within-run | | Between-run | |
|-----------------------|-------------------------------------------------------------|-------------------------------------------|----------------|----------------|----------------|
| | | Minimal %CV | Maximal %CV | Minimal %CV | Maximal %CV |
| Less than<br>10 AU/mL | Not calulated | Not calculated | Not calculated | Not calculated | Not calculated |
| 10 to 19<br>AU/mL | %CV≤20% | 5.3% | 11.3% | 11.2% | 19.6% |
| 20 to 400<br>AU/mL | %CV≤15% | 2.3% | 12.4% | 5.4% | 14.2% |

### Table 1: Summary of FIDIS™ Vasculitis precision results

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### b. Linearity/ assay reportable range

FIDIS™ VASCULITIS assay has been optimized to express the average binding capacity at the current dilution (1:200) by a flow cytometric reading determined as the median fluorescence value obtained from 200 microspheres per parameter.

Further dilution potentially gives rise to inaccurate results because the reaction conditions and the equilibrium of the immunological reaction may be modified.

### c. Interfering Substances

The study was conducted by testing 27 MPO, PR3, GBM negative samples characterized as positive for various potential interferences obtained from a routine laboratory.

| | Number of positive samples | | |
|---------------------------------------|----------------------------|-----|-----|
| | MPO | PR3 | GBM |
| Cryoglobulinemia N=2 | 0 | 0 | 0 |
| Complement N=8 | 0 | 0 | 0 |
| IgG monoclonal<br>immunoglobulins N=2 | 0 | 0 | 0 |
| IgM monoclonal<br>immunoglobulins N=3 | 0 | 0 | 0 |
| Rheumatoid factor N=7 | 0 | 1 | 0 |
| Citrated plasma N=3 | 0 | 0 | 0 |
| Hemolyzed sera N=2 | 0 | 0 | 0 |

Table 2: Summary of Interfering Substance results

N: number of samples tested

### d. Threshold values

Threshold values were estimated from the 2 selected populations:

- . 37 samples from blood donors
- I 28 samples selected for their potential biological interferences

The negative thresholds (20AU/mL) correspond to the 100% of negative MPO/GBM samples and 98.5% of negative PR3 samples for the populations studied.

#### Stability of the assay results after final wash step e.

This assay included 3 test series for 6 samples per analyte (MPO, PR3, GBM). Each series of tests was washed and read after different times:

- -T= 0 hour: the first series of tests was read immediately after the final wash step.
- । T= 4 hours: the second series of test was read after 4 hours of storage at room temperature away from direct sunlight.

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- T=18 hours: the last series was read after 18 hours of storage at room temperature away from direct sunlight.

| %CV acceptance<br>criteria | Parameter | Sample | Mean<br>(AU/mL) | %CV |
|----------------------------|-----------|-----------|-----------------|-----|
| CV%<15% | MPO | Sample 1 | 19 | 14% |
| | | Sample 2 | 32 | 6% |
| | | Sample 3 | 45 | 4% |
| | | Sample 4 | 92 | 4% |
| | | Sample 5 | 156 | 12% |
| | | Sample 6 | 260 | 8% |
| CV%<15% | PR3 | Sample 7 | 23 | 11% |
| | | Sample 8 | 29 | 3% |
| | | Sample 9 | 50 | 3% |
| | | Sample 10 | 106 | 10% |
| | | Sample 11 | 231 | 8% |
| | | Sample 12 | 834 | 6% |
| CV%<15% | GBM | Sample 13 | 78 | 5% |
| | | Sample 14 | 79 | 5% |
| | | Sample 15 | 108 | 6% |
| | | Sample 16 | 129 | 5% |
| | | Sample 17 | 150 | 7% |
| | | Sample 18 | 213 | 5% |

Table 3: Summary of Stability of the assay results after final wash step

- Based on the common laboratories practices, the time range recommended is "one hour for a plate when stored at room temperature away from direct sunlight".

### 2. Comparison study with predicate

ﺖ

bmd has compared the results obtained with modified FIDIS™ VASCULITIS versus the results obtained with predicate FIDIS™ VASCULITIS K053012.

The study was performed on 219 samples characterized with the predicate test and the result repartition is described below:

- 135 samples were positive for one or more parameters ANCA and/or - GBM.
- 84 negative samples including some samples evaluated for their potential biological interferences.

All equivocal samples with predicate and FIDIS™ VASCULITIS tests are considered negative for the comparison and the evaluation studies.

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#### > Table 4: MPO performances

| | | PREDICATE FIDIS™<br>VASCULITIS<br>K053012 | | |
|----------------------------------|----------|-------------------------------------------|---------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | | | Positive Negative | Total |
| MODIFIED<br>FIDIS™<br>VASCULITIS | Positive | 69 | 0 | રેત્વે છે. આ ગામમાં પ્રાથમિક શાળા, આંગણવાડી તેમ જ દૂધની ડેરી જેવી સવલતો પ્રાપ્ય થયેલી છે. આ ગામનાં લોકોનો મુખ્ય વ્યવસાય ખેતી, ખેતમજૂરી તેમ જ પશુપાલન છે. આ ગામમાં મુખ્યત્વે આ |
| | Negative | 2 | 148 | 1 20 |
| | Total | 71 | 148 | 219 |

#### → Table 5: PR3 performances

| | | PREDICATE FIDIS™<br>VASCULITIS<br>K053012 | | |
|-----------------------------------|----------|-------------------------------------------|----------|-------|
| | | Positive | Negative | Total |
| MODIFIED<br>FIDIST™<br>VASCULITIS | Positive | 47 | 1 | 48 |
| | Negative | 2 | 169 | 171 |
| | Total | 49 | 170 | 219 |

#### → Table 6: GBM performances

| | PREDICATE FIDIS™<br>VASCULITIS<br>K053012 | | | |
|----------------------------------|-------------------------------------------|----------|-------|-----|
| | Positive | Negative | Total | |
| MODIFIED<br>FIDIS™<br>VASCULITIS | Positive | 25 | 0 | 25 |
| | Negative | 0 | 194 | 194 |
| | Total | 25 | 194 | 219 |

There were 7 equivocal results with assay. the For purposes of calculation. these results were considered as negative.

- Positive percent agreement: -97.18% (69/71)
- -Negative percent agreement: 100% (148/148)
- -Overall agreement: 99.09% (217/219)

There were 11 equivocal results with assay. the For purposes of calculation, these results were considered as negative.

- Positive percent agreement: ・ 95.92% (47/49)
- -Negative percent agreement: 99.41% (169/170)
- Overall agreement: 98.63% (216/219)

There were 3 equivocal results with the assay. For purposes of calculation, these results were considered as negative.

- -Positive percent agreement: 100% (25/25)
- . Negative percent agreement: 100% (194/194)
- -Overali agreement: 100% (219/219)

#### Table 7: Summary of performance agreement results

| Antigenic<br>Specificity | Sample<br>number | Positive<br>percent<br>agreement | Negative<br>percent<br>agreement | Overall<br>agreement |
|--------------------------|------------------|----------------------------------|----------------------------------|----------------------|
| MPO | 219 | 97.18% | 100% | 99.09% |
| PR3 | 219 | 95.92% | 99.41% | 98.63% |
| GBM | 219 | 100% | 100% | 100% |

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In addition to the analysis above, the 95% one-sided lower confidence limit in percent of proportion agreement (95% LCL (%) was calculated using the Exact Binomial Test for proportions to determine how low this proportion could be with a 95% confidence.

Table 7a: Summary of performance agreements results - 95% LCL (%)

| Antigenic<br>Specificity | N | Positive Agreement | | | | Negative Agreement | | | | Overall Agreement | | | |
|--------------------------|-----|--------------------|----|--------|-------------|--------------------|-----|--------|-------------|-------------------|-----|--------|-------------|
| | | N₁ | R₁ | P₁ (%) | 95% LCL (%) | N₂ | R₂ | P₂ (%) | 95% LCL (%) | N | R | P (%) | 95% LCL (%) |
| MPO | 219 | 71 | 69 | 97.18 | 91.40 | 148 | 148 | 100.00 | 98.00 | 219 | 217 | 99.09 | 97.15 |
| PR3 | 219 | 49 | 47 | 95.92 | 87.70 | 170 | 169 | 99.41 | 97.24 | 219 | 216 | 98.63 | 96.50 |
| GBM | 219 | 25 | 25 | 100.00 | 88.71 | 194 | 194 | 100.00 | 98.47 | 219 | 219 | 100.00 | 98.64 |

N1 = No. of positives;R1 = No. of positive agreements; P1 = R1/N1

N2 = No. of negatives; R2 = No. of negative agreements; P2 = R2/N2

N = N; + N2; R = R1 + R2; P = R/N

All of results show that FIDISTM VASCULITIS system can be considered substantially equivalent to the predicate K053012 FIDISTM VASCULITIS system.

# 3. Performance data for modified FIDIS™ VASCULITIS with CARISTM (diluting/ dispensing Device)

- a. Precision
Internal study was conducted to evaluate the reproducibility of the use of CARISTM with modified FIDISTM VASCULITIS.

Precision of the assay was assessed in 16 samples for antibodies to each of the three parameters (MPO, PR3, GBM) and 3 negative samples. Precision was determined by calculating the within-run (intra-assay) and the between-run (interassay).

Precision was determined by calculating the within-run (intra-assay) and the between-run (inter-assay).

- For within-run: 10 times in a same run. -
- For between-run: 5 runs, 3 times per run.

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| Sample range | Acceptance<br>criteria for<br>within-run<br>and between-<br>run | Within-run<br>minimal CV%<br>for MPO, PR3<br>and GBM<br>parameters | Within-run<br>maximal<br>CV% for<br>MPO, PR3<br>and GBM<br>parameters | Between-run<br>minimal CV%<br>for MPO, PR3<br>and GBM<br>parameters | Between-run<br>maximal<br>CV% for<br>MPO, PR3<br>and GBM<br>parameters |
|----------------------|-----------------------------------------------------------------|--------------------------------------------------------------------|-----------------------------------------------------------------------|---------------------------------------------------------------------|------------------------------------------------------------------------|
| Less than10<br>AU/mL | Not calculated | Not calculated | Not calculated | Not calculated | Not calculated |
| 10 to 19<br>AU/mL | CV=20% | 4.9% | 6.9% | 6.9% | 13.6% |
| 20 to 400<br>AU/mL | CV=15% | 2.6% | 10.8% | 5.9% | 11.7% |

Table 8: Summary of CARIS™ precision results

### b. Comparison studies (manual versus automated assay preparation steps)

bmd has compared the results obtained with modified FIDISTM VASCULITIS for manual or automated (with CARISTM).assay preparation steps.

The study was performed on 117 samples characterized with the modified FIDISTM VASCULITIS with manual assay preparation step.

The result repartition is described below:

- 75 positive samples for one or more parameters ANCA and/or GBM. –
- 42 negative samples including some samples evaluated for their – potential biological interferences.

All equivocal samples are considered negative for the comparison and the evaluation studies.

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### ∞ Table 9: MPO performances

| MPO | | MODIFIED FIDIS™<br>VASCULITIS<br>Manual | | |
|------------------------------------------------|----------|-----------------------------------------|----------|-------|
| | | Positive | Negative | Total |
| MODIFIED<br>FIDIS™<br>VASCULITIS<br>With CARIS | Positive | 34 | 2 | 36 |
| | Negative | 0 | 81 | 81 |
| | Total | 34 | 83 | 117 |

There were 5 equivocal results with the assay. For purposes of calculation, these results were considered as negative.

- Positive percent agreement: 100% ー (34/34)
- Negative percent agreement: -97.59% (81/83)
- -Overall agreement: 98.29% (115/117)

#### → Table 10: PR3 performances

| | PR3 | MODIFIED FIDIS™<br>VASCULITIS<br>Manual | | |
|------------------------------------------------|----------|-----------------------------------------|----------|-------|
| | | Positive | Negative | Total |
| MODIFIED<br>FIDIS™<br>VASCULITIS<br>With CARIS | Positive | 25 | 2 | 27 |
| | Negative | 0 | 90 | 90 |
| | Total | 25 | 92 | 117 |

→ Table 11: GBM performances

| | GBM | MODIFIED FIDIS™<br>VASCULITIS<br>Manual | Positive | Negative | Total |
|------------------------------------------------|----------|-----------------------------------------|----------|----------|-------|
| MODIFIED<br>FIDIS™<br>VASCULITIS<br>With CARIS | Positive | 23 | 0 | 23 | |
| | Negative | 0 | 94 | 94 | |
| | Total | 23 | 94 | 117 | |

assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 100% -

There were 6 equivocal results with the

- · (25/25)
- Negative percent agreement: । 97.83% (90/92)
- -Overall agreement: 98.29% (115/117)

There were 3 equivocal results with the assay. For purposes of calculation, these results were considered as negative.

- Positive percent agreement: 100% י (23/23)
- Negative percent agreement: 100% । (94/94)
- Overall agreement: 100% (117/117)

### Table 12: Summary of performance agreements results obtained with CARIS™ versus manual

ﺘ

| Antigenic<br>Specificity | Sample<br>number | Positive<br>percent<br>agreement | Negative<br>percent<br>agreement | Overall<br>agreement |
|--------------------------|------------------|----------------------------------|----------------------------------|----------------------|
| | | proportion | proportion | proportion |
| MPO | 117 | 100% | 97.59% | 98.29% |
| PR3 | 117 | 100% | 97.83% | 98.29% |
| GBM | 117 | 100% | 100% | 100% |

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In addition to the analysis above, the 95% one-sided lower confidence limit in percent of proportion agreement (95% LCL (%) was calculated using the Exact Binomial Test for proportions to determine how low this proportion could be with a 95% confidence.

Table 12a: Summary of performance agreements results obtained with CARIS™ versus manual -- 95% LCL (%)

| Antigenic<br>Specificity | N | Positive Agreement | | | | Negative Agreement | | | | Overall Agreement | | | |
|--------------------------|-----|--------------------|----|--------|-------------|--------------------|----|--------|-------------|-------------------|-----|--------|-------------|
| | | N₁ | R₁ | P₁ (%) | 95% LCL (%) | N₂ | R₂ | P₂ (%) | 95% LCL (%) | N | R | P (%) | 95% LCL (%) |
| MPO | 117 | 34 | 34 | 100.00 | 91.57 | 83 | 81 | 97.59 | 92.61 | 117 | 115 | 98.29 | 94.72 |
| PR3 | 117 | 25 | 25 | 100.00 | 88.71 | 92 | 90 | 97.83 | 93.31 | 117 | 115 | 98.29 | 94.72 |
| GBM | 117 | 23 | 23 | 100.00 | 87.79 | 94 | 94 | 100.00 | 96.86 | 117 | 117 | 100.00 | 97.47 |

N1 = No. of positives; R1 = No. of positive agreements; P1 = R1/N1

N2 = No. of negatives; N = N1 + N2; R = R1 + R2; P = R/N

All of previous evaluation results indicate that manual and automated (with CARISTM) assay preparation steps are substantially equivalent.

### 8) Conclusions

In conclusion, all supporting data demonstrate that the FIDIS™ VASCULITIS system can be considered substantially equivalent to the predicate device.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/11/Picture/1 description: The image shows the logo for the Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" arranged around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread, symbolizing the department's mission to protect and promote the health and well-being of the nation.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 2 1 2007

Biomedical Diagnostics S.A. (BMD) c/o Ms. Christelle Courivaud Regulatory Affairs Manager Actipole 25, 4-6 Bld de Beaubourg 77435 Marne La Vallée cedex 2 France

Re: k070458

Trade/Device Name: FIDIS™ VASCULITIS* Assay Regulation Number: 21 CFR 866.5660 Regulation Name: Multiple autoantibodies immunological test system Regulatory Class: Class II Product Code: MOB, MVJ Dated: November 27, 2007 Received: November 30, 2007

Dear Ms. Courivaud:

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). This letter will allow you to

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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.

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 [phone]. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at 240-276-3464. 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 [phone] or [phone] or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Robert Barton

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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# Indication for Use

510(k) Number (if known): K070458

Device Name:

# FIDIS™ VASCULITIS*

#### Indication For Use:

The FIDIS™ VASCULITIS* kit is a semi-quantitative homogeneous fluorescent-based microparticle immunoassay using flow cytometry. The test system is used to simultaneously detect the presence of anti-neutrophil cytoplasmic antibodies (ANCA) directed against Myeloperoxidase (MPO), Serine Proteinase 3 (PR3) and antibodies directed against glomerular basement membrane (GBM) in human serum samples.

The results of the FIDIS™ VASCULITIS* test are to be used in conjunction with the clinical findings and the other laboratory tests to aid in the diagnosis of various primary systemic small blood vessel vasculitides and glomerular basement membrane disease.

#### Clinical utility:

The detection of ANCA is associated with primary systemic small blood vessel vasculitides: Wegener's granulomatosis, Churg Strauss syndromes, microscopic periarteritis and idiopathic crescentic glomerulonephritis; and the detection of anti-GBM antibodies is associated with Goodpasture's syndrome.

FIDIS™ VASCULITIS* kit uses serum only, and is to be run on the FIDIS™ Instrument and MLX-BOOSTER Software.

FIDIS™ VASCULITIS* kit may be used with the CARIS™ system (diluting and dispensing device).

#### This test is for In vitro Diagnostic Use.

* Detection of the serologic markers for primary systemic small blood vessel vasculitides (ANCA) and for Goodpasture syndrome (GBM).

X : Prescription Use (21 CFR Part 801 Subpart D)

And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)

Maria M Chan

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety 510K 2070958