FIDISTM CONNECTIVE 10, FIDISTM ANALYZER, CARIS

K102607 · Biomedical Diagnostics (Bmd) SA · LLL · Dec 3, 2010 · Immunology

Device Facts

• Record ID: K102607
• Device Name: FIDISTM CONNECTIVE 10, FIDISTM ANALYZER, CARIS
• Applicant: Biomedical Diagnostics (Bmd) SA
• Product Code: LLL · Immunology
• Decision Date: Dec 3, 2010
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5100
• Device Class: Class 2

Intended Use

The FIDIS™ CONNECTIVE 10* kit is a semi-quantitative homogenous fluorescent-based microparticles immunoassay using flow cytometry. The test system is used to simultaneously detect the presence of 10 autoantibody specificities: double stranded DNA (dsDNA), SS-A (60kDA and TRIM 21 (52kDA)), SS-B, Sm, Sm/RNP, Scl-70, Jo-1, ribosome and centromere in human serum. (*Antibodies to dsDNA, Sm, Sm/RNP, SS-A, SS-B, Scl-70, Jo-1, ribosomes and centromere can be reported using this assay). The results of the FIDIS™ Connective 10 are to be used in conjunction with the clinical findings and the laboratory tests to aid in the diagnosis of connective diseases (systemic lupus erythematosus (SLE), Sjogren's syndrome, mixed connective tissue disease (MCTD) scleroderma, Dermatomyositis and CREST syndrome). FIDISTM Connective 10 kit uses serum only and is to be run on the FIDIS instrument and MLX-BOOSTER Software. FIDISTM Connective 10 kit may be used with the CARIS system (diluting and dispensing device). This kit is for In vitro diagnostic use.

Device Story

Multiplexed immunoassay for detection of 10 autoantibodies in human serum; utilizes color-coded microspheres conjugated to specific antigens; flow cytometry-based detection. Sample incubated with microspheres; unbound antibodies washed; phycoerythrin-labeled anti-human IgG conjugate added; final wash; flow cytometer measures fluorescence intensity to identify analyte and quantify reaction. Operated on FIDIS 200 Analyzer (Luminex 200) with MLX-Booster software; optional CARIS system for automated dilution/dispensing. Output provides semi-quantitative results (AU/mL or IU/mL) used by clinicians alongside clinical findings to aid diagnosis of connective tissue diseases. Benefits include simultaneous screening for multiple autoantibodies, improving diagnostic efficiency.

Clinical Evidence

Bench testing only. Precision/reproducibility studies performed (intra-assay CV 1-15%, inter-assay CV 3-15%). Method comparison study (n=80) against predicate device showed high agreement across all 10 analytes (overall agreement 97.5-100%). Automated CARIS system comparison also showed high agreement (97.5-100%). No clinical sensitivity/specificity studies provided.

Technological Characteristics

Multiplex flow immunoassay using color-coded microspheres. Analyte detection via flow cytometry (red/infrared laser for identification, green laser for quantification). Includes internal anti-IgG standard bead. Software: MLX-BOOSTER™ (Version 2.2). Sample preparation: manual or automated (CARIS™). Assay configuration: 96-well microplate with filtering membrane. Reagents: lyophilized microspheres, buffers, calibrators, controls, and phycoerythrin-conjugated anti-human IgG.

Indications for Use

Indicated for the semi-quantitative detection of autoantibodies (dsDNA, SS-A 60kDa, TRIM 21/SS-A 52kDa, SS-B, Sm, Sm/RNP, Scl-70, Jo-1, ribosomes, CENP-B) in human serum to aid in the diagnosis of connective tissue diseases including SLE, Sjogren's syndrome, MCTD, scleroderma, dermatomyositis, and CREST syndrome.

Regulatory Classification

Identification

An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).

Predicate Devices

• FIDIS™ CONNECTIVE 10 (K071210)

Submission Summary (Full Text)

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K102607

DEC - 3 2010

Image /page/0/Picture/2 description: The image shows a logo with the letters "bmd" in a stylized font. Below the letters, the words "biomedical diagnostics" are written in a smaller, sans-serif font. The letters "bmd" are connected by a horizontal line, and there are small, rounded shapes underneath each letter.

# Premarket Notification 510(k) Summary FIDIS™ CONNECTIVE 10 Assay kit and Multiparameters quality control

3003935253

# Assigned 510(k) Number:

1) Submitted by : Name:

Contact Person:

Address:

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

US Agent correspondent:

P. Ann Hoppe, President Hoppe Regulatory Consultants LLC 103 South Cherry Street Falls Church VA 22046 703 532 1145 Office FAX [phone] E-mail: HoppeRegulatory(@cs.com

### 2) Device Name

Trade/Proprietary Name :

# FIDISTM CONNECTIVE 10 Assay kit

Classification Names:

Common/Usual Name :

Antinuclear Antibody Immunological Test System

MX006 - MX506 - FIDIS™ CONNECTIVE 10: Detection test for autoantibodies directed against dsDNA, .SS-A (60kDa and TRIM 21 (SS-A 52kDa), SS-B, Sm, Sm/RNP, Scl-70, Jo-1, ribosomes and centromere (CENP-B).

S.A au Capital de 2 755.46 Euros RCS Meaux: B 339 685 612 Siret: 339 685 612 00048-APE: 514N Nº TVA Intracommunautaire: FR 68 339 685 612

Registered Office .: Actipole 25 4-6 bd de Beaubourg 77435 Mame La Vallée cedex 2

Tel: [phone] Fax : [phone] Email: [e-mail] Internet : www.bmd-net.com

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Image /page/1/Picture/0 description: The image shows a logo for "biomedical diagnostics". The logo consists of the letters "bmd" in a stylized font, with a line underneath. Below the line, the words "biomedical diagnostics" are written in a smaller, sans-serif font. The letters "bmd" are connected and have a rounded appearance.

Trade/Proprietary Name :

Classification Name:

Instrumentation for Chemical Multiplex Systems

Trade/Proprietary Name :

Classification Name:

# CARISTM System

FIDISTM Analyzer

Device, Microtiter diluting/Dispensing

# 3). Legally marketed equivalent device

| 510K Number | Device Classification Name | Manufacturer Name |
|-------------|----------------------------|-------------------------------------|
| K071210 | FIDISTM CONNECTIVE 10 | Biomedical Diagnostics<br>S.A.(bmd) |

# 4) Device description

FIDIS™ CONNECTIVE 10 kit is a multiplex flow immunoassay, which allows simultaneous identification and detection of several antibodies.

FIDIS™ CONNECTIVE 10 is based on the use of distinct uniform size color-coded microsphere sets and a benchtop flow cytometer interfaced to digital signal processing hardware and software. A red diode laser beam in the flow cytometer recognizes each set of microspheres on the basis of its unique fluorescence intensity (red and infrared) thus identifying which parameter is being tested. At the same time, a green laser beam illuminates the external second molecule fluorescence to quantify the reaction related to the specific antigen.

Ten different fluorescently "colored" sets of microspheres are coated with antigens associated with various connective diseases (dsDNA, SS-A (60kDA and TRIM 21 (SS-A 52kDa}}, SS-B, Sm, Sm/RNP, Scl-70, Jo-1, ribosomes and centromere). An additional microsphere (Internal Bead standard) set is coated with anti-IgG to ensure that false negative results due to operational error are detected.

The eleven different sets of microspheres are mixed together. The mixture is lyophilized and constitutes the final microspheres reagent.

The test is performed using a 96 wells microplate with a filtering membrane at the bottom of the wells.

S.A au Capital de 2 755.46 Euros RCS Meaux: B 339 685 612 Siret: 339 685 612 00048-APE: 514N Nº TVA Intracommunautaire: FR 68 339 685 612

Registered Office : . Actipole 25 4-6 bd de Beaubourg 77435 Marne La Vallée cedex 2

Tel: [phone] Fax : [phone] Email: bind(@bmd-net.com Internet : www.bmd-net.com

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Image /page/2/Picture/0 description: The image shows a logo with the letters 'bmd' in a stylized font. Below the letters, there is a horizontal line with some curved shapes underneath. Underneath the line, the words 'biomedical diagnostics' are written in a smaller, sans-serif font.

In the first step, the sample is distributed in each well containing the reconstituted microspheres mixture, allowing any anti-dsDNA; anti-SS-A (60kDa and TRIM 21 (SS-A 52kDa)), anti-SS-B, anti-Sm, anti-Sm/RNP, anti-Scl-70, anti-Io-1, anti-ribosomes and anti-centromere antibodies present to bind to the immobilized antigens on the microspheres, as well as free IgG to bind to the anti-IgG microsphere.

> After incubation, a wash step using a filtration process removes the unbound antibodies.

<> A phycoerythrin anti-human IgG conjugate is then added that binds to the previously bound antibodies.

> A final wash step stops the reaction and eliminates the unbound conjugate.

<> The reaction is then measured directly by the flow cytometer, which distinguishes each set of microspheres by its fluorescence color while simultaneously measuring the average fluorescence emitted by the conjugate. ·

<> A calibration system allows the determination of the titer (AU/mL) of each sample by interpolation for each antigenic specificity.

## Kit components

| | | MX006 | MX506 |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------|------------|------------|
| 96 wells microplate with filtering membrane and lid. | MP | 1 plate | 5 plates |
| Vial (A) of color-coded microsphere set of 10 sensitized by dsDNA, SS-A 60 kDa, TRIM 21 (SS-A 52<br>kDa), SS-B, Sm, Sm/RNP, Scl-70, Jo-1, ribosomes and CENP-B antigen(s).<br>Lyophilized (to be reconstituted with the buffer named D) | MICROSPHERES | qs 6mL | 5 x qs 6mL |
| Vial (B1) of sample dilution buffer (white vial)<br>Ready to use | DIL SPE | 2 × 115mL | 10 x 115mL |
| Vial of calibrator*<br>Ready to use<br>Each titer is printed on the vial label | CAL | 1 x 1.5mL | 5 x 1.5mL |
| Vial of positive control concentrated. This control has a standard reactivity, which provides evidence<br>of the proper reagents activity and proper assay performance.<br>To be diluted<br>Expected values are printed on the vial label. | CONTROL + | 1 × 250 µL | 5 x 250µL |
| Vial of negative control concentrate<br>To be diluted | CONTROL - | 1 x 250µL | 5 x 250µL |
| Vial of anti-human IgG coupled to phycoerythrin<br>Ready to use | CONJ IgG | 1 x 12mL | 5 x 12mL |
| Vial (C1) of washing buffer (black vial)<br>Ready to use | BUF WASH | 1 × 100mL | 5 x 100mL |
| Vial (D) of reconstitution buffer for the microsphere set<br>Ready to use | BUF MICROSPHERES | 1 x 6mL | 5 x 6mL |

S.A au Capital de 2 755.46 Euros RCS Meaux: B 339 685 612 Siret: 339 685 612 00048-APE: 514N Nº TVA Intracommunautaire: FR 68 339 685 612

Registered Office : Activole 25 4-6 bd de Beaubourg 77435 Marne La Vallée cedex 2

Tel: [phone] Fax : [phone] Email; [e-mail] Internet : www.bmd-net.com

{3}------------------------------------------------

Image /page/3/Picture/0 description: The image shows a logo for "bmd biomedical diagnostics". The letters "bmd" are in a stylized, sans-serif font, with each letter connected to a horizontal line. Below the line, the words "biomedical diagnostics" are written in a smaller, sans-serif font. There are some small, rounded shapes between the letters and the line.

5) Intended use

# FIDISTM CONNECTIVE 10 Assay kit

The FIDIS™ CONNECTIVE 10* kit is a semi-quantitative homogeneous fluorescentbased microparticles immunoassay using flow cytometry. The test system is used to simultaneously detect the presence of 10 autoantibody specificities: double stranded DNA (dsDNA), SS-A (60kDa and TRIM 21 (SS-A 52kDa)), SS-B, Sm, Sm/RNP, Scl-70, Jo-1, ribosomes and centromere (CENP-B).

(*Antibodies to dsDNA, Sm, Sm/RNP, SS-A, SS-B, Scl-70, Jo-1, ribosomes and CENP-B can be reported using this assay).

# Clinical utility:

The results of the FIDIS™ CONNECTIVE 10 are to be used in conjunction with the clinical findings and the other laboratory tests to aid in the diagnosis of connective diseases (systemic lupus erythematosus (SLE), Sjogren's syndrome, mixed connective tissue disease (MCTD), scleroderma, dermatomyositis and CREST syndrome).

FIDIS™ CONNECTIVE 10 kit uses serum only, and is to be run on the FIDIS™ Instrument and MLX-BOOSTER™ Software.

FIDIS™ CONNECTIVE 10 kit may be used with the CARIS™ system (diluting and dispensing device).

This kit is for In vitro diagnostic use.

S.A au Capital de 2 755.46 Euros RCS Meaux: B 339 685 612 Siret: 339 685 612 00048-APE: 514N Nº TVA Intracommunautaire: FR 68 339 685 612

Registered Office : Actipole 25 4-6 bd de Beaubourg 77435 Marne La Vallée cedex 2

Tel: [phone] Fax : [phone] Email: [e-mail] Internet : www.bmd-net.com

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Image /page/4/Picture/0 description: The image shows a logo with the letters "bmd" in a stylized font. Below the letters is a horizontal line, and beneath that line is the text "biomedical diagnostics" in a smaller, sans-serif font. The logo appears to be for a biomedical diagnostics company.

# 6) Technological characteristics

The following table summarizes similarities and differences between the modified FIDIS™ CONNECTIVE 10 and the predicate device FIDIS™ CONNECTIVE 10 (K071210).

| Comparison with the predicate | | | |
|-----------------------------------------------------|-----------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | | Predicate Device<br>FIDIS™ CONNECTIVE 10<br>K071210 | Modified Device<br>FIDIS™ CONNECTIVE 10 |
| Intended use | | Individual determination in human serum of<br>IgG antibodies against:<br>dsDNA, SSA 60kDa, SSA 52kDa, SSB,<br>Sm, Sm/RNP, Sc170, Jo-1, Ribosome and<br>centromere | (Minor text change)<br>Individual determination in human serum of<br>IgG antibodies against:<br>dsDNA, SS-A 60kDa, TRIM 21 (SS-A<br>52kDa), SS-B, Sm, Sm/RNP, Scl-70, Jo-1,<br>Ribosomes and centromere |
| CUT-OFF | Negative | <30<br>for the 10 specificities | Same |
| | Equivocal | 30-40<br>for the 10 specificities | Same |
| | Positive | >40<br>for the 10 specificities | Same |
| Beads | | Vial of color-coded microsphere set<br>Lyophilized<br>(Sufficient quantity to obtain 6mL after<br>reconstitution) | Same |
| Sample dilution | | Sample dilution buffer ready to use (B) | (Minor text change)<br>Sample dilution buffer ready to use (B1) |
| Washing buffer | | Washing buffer ready to use (C) | (Minor text change)<br>Washing buffer ready to use (C1) |
| Internal standard<br>beads | | Yes | Same |
| Reconstitution buffer<br>for the<br>microsphere set | | Vial (D) of reconstitution buffer for the<br>microsphere set<br>Ready to use (6mL) | Same |
| Assay configuration | | 1 "reagent-blank" well<br>1 "negative control" well<br>1 "positive control" well<br>2 "calibrator" wells<br>Diluted sample wells | Same |
| Incubation time | | 2 x 30min. RT | Same |
| Assay protocol | | Final wash step | Same |
| Software | | MLX-Booster Version 2.2 | Same |
| Assay technology | | Flow cytometry | Same |
| Number of reading<br>microspheres per<br>parameter | | 200 | 100 |
| Reading time | | 60 seconds | 90 seconds |
| Microplate scaling<br>films | | 6 | No |
| Sample delivery | | Manual pipetting | Same |
| Automated sample<br>delivery (option) | | CARIS™ (pipettor) | Same |

S.A au Capital de 2 755.46 Euros RCS Meaux: B 339 685 612 Siret: 339 685 612 00048-APE: 514N Nº TVA Intracommunautaire: FR 68 339 685 612

Registered Office Actipole 25 4-6 bd de Beaubourg 77435 Marne La Vallée cedex 2

Fax : [phone] Email: [e-mail] Internet : www.bmd-net.com

{5}------------------------------------------------

# 7) Performance Characteristics

# 7.1. Precision study - Using Manual Pipetting

Precision of the assay was assessed in using 6 samples for each of 7 analytes (dsDNA, SS-A 60kDa & TRIM 21 (SS-A 52 kDa), SS-B, Sm, Sm/RNP, Jo-1 and CENP-B) and only in using 5 samples for Scl-70 and Ribosomes. Precision was determined by calculating the within-run (intra-assay) and the between-run (inter-assay).

- For within-run: 10 tests in a same run. ト
For between-run: 5 runs, 1 test per run. -

| | dsDNA, SS-A 60kDa & TRIM 21 (SS-A 52 kDa), SS-B, Sm, Sm/RNP, Scl-70, Jo-1, Ribosomes and Centromere analytes | | | |
|--------------------------|--------------------------------------------------------------------------------------------------------------|-------------|-------------|-------------|
| Sample range | Within-run | | Between-run | |
| | Minimal %CV | Maximal %CV | Minimal %CV | Maximal %CV |
| ≤ 29 AU/mL or IU/mL | 4% | 15% | 6% | 15% |
| 30 to 400 AU/mL or IU/mL | 1% | 10% | 3% | 15% |

#### Table 1: Summary of FIDIS™ CONNECTIVE 10 precision results using Manual Pipetting

# 7.2. Comparison study with predicate - Using Manual Pipetting

bmd has compared the results obtained with modified FIDIS™ CONNECTIVE 10 versus the results obtained with predicate FIDISTM CONNECTIVE 10 K071210.

The study was performed on 80 samples characterized with the predicate test and the result repartition is described below:

- 77 samples were positive for one or more parameters (see ● table 3)
- 3 negative samples.

S.A au Capital de 2 755.46 Euros RCS Meaux: B 339 685 612 Siret: 339 685 612 00048-APE: 514N Nº TVA Intracommunautaire: FR 68 339 685 612

Registered Office : Actipole 25 4-6 bd de Beaubourg 77435 Marne La Vallée cedex 2

Tel: [phone] Fax : [phone] Email: [e-mail] Internet : www.bmd-net.com

{6}------------------------------------------------

First set of measures based on included the equivocal results with the test negative a. · results.

#### Ə dsDNA

| | | PREDICATE FIDIS™<br>CONNECTIVE 10<br>K071210 | | |
|----------------------------------------|-------|----------------------------------------------|-----|-------|
| dsDNA | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10 | Pos | 16 | 1 | 17 |
| | Neg | 0 | 63 | 63 |
| | Total | 16 | 64 | 80 |
| SS-A 60kDa | | PREDICATE FIDIS™<br>CONNECTIVE 10<br>K071210 | | |
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE | Pos | 25 | 1 | 26 |
| | Neg | 0 | 54 | 54 |

There was 1 equivocal result with the assay. For purposes of calculation, this result was considered to be negative.

- Positive percent agreement: 100% (16/16)

- Negative percent agreement: 98.4% (63/64)

- Overall agreement: 98.8% (79/80)

# > TRIM 21 (SS-A 52kDa)

| TRIM 21 (SS-A<br>52kDa) | | PREDICATE FIDIS™<br>CONNECTIVE 10<br>K071210 | | |
|----------------------------------------|-------|----------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10 | Pos | 23 | 0 | 23 |
| | Neg | 1 | 56 | 57 |
| | Total | 24 | 56 | 80 |

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

- Positive percent agreement: 95.8% (23/24)

- Negative percent agreement: 100% (56/56)

- Overall agreement: 98.8% (79/80)

## → Sm

| Sm | | PREDICATE FIDIST™<br>CONNECTIVE 10<br>K071210 | | |
|-----------------------------------------|-------|-----------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIST™<br>CONNECTIVE<br>10 | Pos | 17 | 0 | 17 |
| | Neg | 0 | 63 | 63 |
| | Total | 17 | 63 | 80 |

There was 1 equivocal result with the assay. For purposes of calculation, this result was considered to be negative.

- Positive percent agreement: 100% (17/17)

- Negative percent agreement: 100% (63/63)
- Overall agreement: 100% (80/80)

S.A au Capital de 2 755.46 Euros RCS Meaux: B 339 685 612 Siret: 339 685 612 00048-APE: 514N

Nº TVA Intracommunautaire: FR 68 339 685 612

# <> SS-A 60kDa

| SS-A 60kDa | | CONNECTIVE 10<br>K071210 | | |
|----------------------------------------|-------|--------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10 | Pos | 25 | 1 | 26 |
| | Neg | 0 | 54 | 54 |
| | Total | 25 | 55 | 80 |

There were 4 equivocal results with the assay, For purposes of calculation, these results were considered to be negative.

- Positive percent agreement: 100% (25/25)

- Negative percent agreement: 98.2% (54/55)

- Overall agreement: 98.8% (79/80)

#### = SS-B

| SS-B | | PREDICATE FIDIS TM<br>CONNECTIVE 10<br>K071210 | | |
|---------------------------------------------|-------|---------------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS TM<br>CONNECTIVE<br>10 | Pos | 14 | 1 | 15 |
| | Neg | 0 | 65 | 65 |
| | Total | 14 | 66 | 80 |

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

- Positive percent agreement: 100% (14/14)

- Negative percent agreement: 98.5% (65/66)

- Overall agreement: 98.8% (79/80)

### <> Sm/RNP

| | PREDICATE FIDIST™<br>CONNECTIVE 10<br>K071210 | | | |
|-----------------------------------------|-----------------------------------------------|-----|-------|----|
| Sm/RNP | Pos | Neg | Total | |
| MODIFIED<br>FIDIST™<br>CONNECTIVE<br>10 | Pos | 19 | 1 | 20 |
| | Neg | 0 | 60 | 60 |
| | Total | 19 | 61 | 80 |

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

- Positive percent agreement: 100% (19/19)

- Negative percent agreement: 98.4% (60/61)
- Overall agreement: 98.8% (79/80)

Registered Office : Actipole 25 4-6 bd de Beaubourg 77435 Marne La Vallée cedex 2

Tel: [phone] Fax : [phone] Email: [e-mail] Internet : www.bmd-net.com

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Image /page/7/Picture/0 description: The image shows a logo for "bmd biomedical diagnostics". The logo consists of the letters "bmd" in a stylized font, with a line underneath. Below the line, the words "biomedical diagnostics" are written in a smaller, sans-serif font. The logo is simple and clean, and the use of the lowercase letters gives it a modern look.

#### => Scl-70

| Scl-70 | | PREDICATE FIDIS™<br>CONNECTIVE 10<br>K071210 | | |
|----------------------------------------|-------|----------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10 | Pos | 15 | 2 | 17 |
| | Neg | 0 | 63 | 63 |
| | Total | 15 | 65 | 80 |

There were 2 equivocal results with the assay. For purposes of calculation, these results were considered to be negative.

- Positive percent agreement: 100% (15/15)

- Negative percent agreement: 96.9% (63/65)

- Overall agreement: 97.5% (78/80)
## CENP-B

| CENP-B | | PREDICATE FIDIS™<br>CONNECTIVE 10<br>K071210 | | |
|----------------------------------------|-------|----------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10 | Pos | 7 | 1 | 8 |
| | Neg | 0 | 72 | 72 |
| | Total | 7 | 73 | 80 |

There was 1 equivocal result with the assay. For purposes of calculation, this result was considered to be negative.

- Positive percent agreement: 100% (7/7)

- Negative percent agreement: 98.6% (72/73)

- Overall agreement: 98.8% (79/80)

> Jo-1

| Jo-1 | | PREDICATE FIDIS™<br>CONNECTIVE 10<br>K071210 | | |
|----------------------------------------|-------|----------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10 | Pos | 10 | 0 | 10 |
| | Neg | 0 | 70 | 70 |
| | Total | 10 | 70 | 80 |

There were 2 equivocal results with the assay. For purposes of calculation, these results were considered to be negative.

- Positive percent agreement: 100% (10/10)

- Negative percent agreement: 100% (70/70)

- Overall agreement: 100% (80/80)

## ⇒ Ribosomes

| Ribosomes | | PREDICATE FIDIS™<br>CONNECTIVE 10<br>K071210 | | |
|----------------------------------------|-------|----------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10 | Pos | 6 | 0 | 6 |
| | Neg | 0 | 74 | 74 |
| | Total | 6 | 74 | 80 |

There was 1 equivocal result with the assay. For purposes of calculation, this result was considered to be negative.

- Positive percent agreement: 100% (6/6)

- Negative percent agreement: 100% (74/74)

- Overall agreement: 100% (80/80)

S.A au Capital de 2 755.46 Euros RCS Meaux: B 339 685 612 Siret: 339 685 612 00048-APE: 514N Nº TVA Intracommunautaire: FR 68 339 685 6!2

Registered Office : Actipole 25 4-6 bd de Beaubourg 77435 Marne La Vallée cedex 2

Tel: [phone] Fax : [phone] Email: bmd(@bmd-net.com Internet : www.bmd-net.com

{8}------------------------------------------------

b. Second set of measures based on included the equivocal results with the test positive results.

#### > dsDNA

| dsDNA | | PREDICATE FIDISTM<br>CONNECTIVE 10<br>K071210 | | |
|-----------------------------------------|-------|-----------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDISTM<br>CONNECTIVE<br>10 | Pos | 17 | 0 | 17 |
| | Neg | 0 | 63 | 63 |
| | Total | 17 | 63 | 80 |
| SS-A 60kDa | | PREDICATE FIDIS™<br>CONNECTIVE 10<br>K071210 | | |
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10 | Pos | 29 | 0 | 29 |
| | Neg | 0 | 51 | 51 |
| | Total | 29 | 51 | 80 |

=> SS-A 60kDa

There were 4 equivocal results with the assay. For purposes of

calculation, these results were considered to be negative.

- Positive percent agreement: 100% (29/29)

- Negative percent agreement: 100% (51/51)

- Overall agreement: 100% (80/80)

There was 1 equivocal result with the assay, For purposes of calculation, this result is considered to be positive.

- Positive percent agreement: 100% (17/17)

- Negative percent agreement: 100% (63/63)

- Overall agreement: 100% (80/80)

# <> TRIM 21 (SS-A 52kDa)

| TRIM 21<br>(SS-A 52kDa) | | PREDICATE FIDIS™<br>CONNECTIVE 10<br>K071210 | | |
|----------------------------------------|-------|----------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10 | Pos | 25 | 1 | 26 |
| | Neg | 0 | 54 | 54 |
| | Total | 25 | 55 | 80 |

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

· Positive percent agreement: 100% (25/25)

- Negative percent agreement: 98.2% (54/55)

- Overall agreement: 98.8% (79/80)

#### < Sm

| Sm | | PREDICATE FIDIST™<br>CONNECTIVE 10<br>K071210 | | |
|----------------------|-------|-----------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED | Pos | 18 | 0 | 16 |
| FIDIS™<br>CONNECTIVE | Neg | 0 | 62 | 64 |
| 10 | Total | 17 | 63 | 80 |

There was 1 equivocal result with the assay. For purposes of calculation, this result is considered to be positive.

- · Positive percent agreement: 100% (18/18)
- Negative percent agreement: 100% (62/62)
- Overall agreement: 100% (80/80)

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| 1 | | |
|---|--|--|
|---|--|--|

| SS-B | | PREDICATE FIDIS™<br>CONNECTIVE 10<br>K071210 | | |
|-----------------------------------------|-------|----------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIST™<br>CONNECTIVE<br>10 | Pos | 19 | 0 | 19 |
| | Neg | 0 | 61 | 61 |
| | Total | 19 | 61 | 80 |

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

- Positive percent agreement: 100% (19/19)

- Negative percent agreement: 100% (61/61)

- Overall agreement: 100% (80/80)

# <> Sm/RNP

| Sm/RNP | | PREDICATE FIDIS™<br>CONNECTIVE 10<br>K071210 | | |
|----------------------------------------|-------|----------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10 | Pos | 20 | 1 | 21 |
| | Neg | 1 | 58 | 59 |
| | Total | 21 | 59 | 80 |

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

- . Positive percent agreement: 95.2% (20/21)
- Negative percent agreement: 98.3% (58/59)
- Overall agreement: 97.5% (78/80)

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{9}------------------------------------------------

Image /page/9/Picture/0 description: The image shows a logo with the letters 'bmd' in a stylized font. Below the letters, the words 'biomedical diagnostics' are written in a smaller, sans-serif font. The logo has a simple, clean design and appears to represent a company or organization in the biomedical or diagnostics field.

| Scl-70 | | | PREDICATE FIDIS™<br>CONNECTIVE 10<br>K071210 | | |
|----------------------------|-------|-----|----------------------------------------------|-------|--|
| | | Pos | Neg | Total | |
| MODIFIED | Pos | 17 | 0 | 17 | |
| FIDIS™<br>CONNECTIVE<br>10 | Neg | 0 | 63 | 63 | |
| | Total | 17 | 63 | 80 | |

There were 2 equivocal results with the assay. For purposes of calculation, these results were considered to be negative.

- Positive percent agreement: 100% (17/17)

- Negative percent agreement: 100% (63/63)

- Overall agreement: 100% (80/80)
## ⇒ CENP-B

| CENP-B | | PREDICATE FIDIS™<br>CONNECTIVE 10<br>K071210 | | | |
|----------------------------------------|-------|----------------------------------------------|----------------------------------------------|-------|-------|
| | | Pos | Neg | Total | |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10 | Pos | 8 | 0 | 8 | |
| | Neg | 0 | 72 | 72 | |
| | Total | 8 | 72 | 80 | |
| Jo-1 | | | PREDICATE FIDIS™<br>CONNECTIVE 10<br>K071210 | | |
| | | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™ | Pos | 12 | 0 | 12 | |
| CONNECTIVE<br>10 | Neg | 0 | 68 | 68 | |
| | Total | 12 | 68 | 80 | |

There was 1 equivocal result with the assay. For purposes of calculation, this result was considered to be negative.

- Positive percent agreement: 100% (8/8)

- Negative percent agreement: 100% (72/72)

- Overall agreement: 100% (80/80)

⇒ Jo-1

There were 2 equivocal results with the assay. For purposes of calculation, these results were considered to be negative.

· Positive percent agreement: 100% (12/12)

· Negative percent agreement: 100% (68/68)

- Overall agreement: 100% (80/80)

#### ⇒ Ribosomes

| Ribosomes | | PREDICATE FIDIS™<br>CONNECTIVE 10<br>K071210 | | |
|----------------------------------------|-------|----------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10 | Pos | 7 | 0 | 7 |
| | Neg | 0 | 73 | 73 |
| | Total | 7 | 73 | 80 |

There was ! equivocal result with the assay. For purposes of calculation, this result was considered to be negative.

· Positive percent agreement: 100% (7/7)

· Negative percent agreement: 100% (73/73)

- Overall agreement: 100% (80/80)

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{10}------------------------------------------------

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ﺎ

| Antigenic<br>Specificity | Positive<br>percent<br>agreement | Negative<br>percent<br>agreement | Overall<br>agreement | EP12-A<br>Chap 9.2.2. | EP12-A<br>Chap 9.1.1.<br>95%CI<br>For positive<br>agreement | EP12-A<br>Chap 9.1.1.<br>95%CI<br>For negative<br>agreement |
|--------------------------------------------------------------------------------------------|----------------------------------|----------------------------------|----------------------|-----------------------|-------------------------------------------------------------|-------------------------------------------------------------|
| equivocal results included<br>with the test negative results | 100% | 98.4% | 98.8% | 87.8%-100% | NA | NA |
| dsDNA<br>equivocal results Included<br>with the test positive results | 100% | 100% | 100% | NA | 81.6%-100% | 94.3%-100 |
| equivocal results included<br>with the test negative results | 100% | 98.2% | 98.8% | 86.6%-100% | NA | NA |
| SSA 60 kDa<br>equivocal results included<br>with the test positive results | 100% | 100% | 100% | NA | 88.3%-100% | 93%-100% |
| TRIM 21<br>(SSA 52<br>kDa)<br>equivocal results included<br>with the test negative results | 95.8% | 100% | 98.8% | 86.7%-100% | NA | NA |
| equivocal results included<br>with the test positive results | 100% | 98.2% | 98.8% | 86.6%-100% | NA | NA |
| equivocal results included<br>with the test negative results | 100% | 98.5% | 98.8% | 88.2%-100% | NA | NA |
| SSB<br>equivocal results included<br>with the test positive results | 100% | 100% | 100% | NA | 83.2%-100% | 94.1%-100 |
| equivocal results included<br>with the test negative results | 100% | 100% | 100% | NA | 81.6%-100% | 94.3%-100% |
| Sm<br>equivocal results included<br>with the test positive results | 100% | 100% | 100% | NA | 82.4%-100% | 94.2%-100% |
| equivocal results included<br>with the test negative results | 100% | 98.4% | 98.8% | 87.3%-100% | NA | NA |
| Sm/RNP<br>equivocal results included<br>with the test positive results | 95.2% | 98.3% | 97.5% | 85.8%-100% | NA | NA |
| equivocal results included<br>with the test negative results | 100% | 96.9% | 97.5% | 86.8%-100% | NA | NA |
| Sc170<br>equivocal results included<br>with the test positive results | 100% | 100% | 100% | NA | 81.6%-100% | 94.3%-100% |
| equivocal results included<br>with the test negative results | 100% | 100% | 100% | NA | 72.3%-100% | 94.8%-100% |
| Jo1<br>equivocal results included<br>with the test positive results | 100% | 100% | 100% | NA | 75.8%-100% | 94.7%-100% |
| equivocal results Included<br>with the test negative results | 100% | 98.6% | 98.8% | 90.2%-100% | NA | NA |
| CENP-B<br>equivocal results Included<br>with the test positive results | 100% | 100% | 100% | NA | 67.6%-100% | 94.9%-100% |
| equivocal results Included<br>with the test negative results | 100% | 100% | 100% | NA | 61.0%-100% | 95.1%-100% |
| Ribosomes<br>equivocal results Included<br>with the test positive results | 100% | 100% | 100% | NA | 64.6%-100% | 95.0%-100% |

#### Table 2: Summary of performance agreement results

# All of results show that FIDISTM CONNECTIVE 10 considered substantially equivalent to the predicate K071210IS™ CONNECTIVE 10

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{11}------------------------------------------------

# 7.3.Performance data for modified FIDIS™ CONNECTIVE 10 with CARIS™ (diluting/ dispensing Device)

#### a. Precision study

Precision of the assay was assessed in using 6 samples for each of 7 analytes (dsDNA, SS-A 60kDa & TRIM 21 (SS-A 52 kDa), SS-B, Sm, Sm/RNP, Jo-1 and CENP-B) and only in using 5 samples for Scl-70 and Ribosomes. 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, 1 test per run.

| | dsDNA, SS-A 60kDa & TRIM 21 (SS-A 52 kDa), SS-B, Sm, Sm/RNP, Scl-70, Jo-1 Ribosomes and Centromere analytes | | | |
|-----------------------------|-------------------------------------------------------------------------------------------------------------|-------------|-------------|-------------|
| Sample range | Within-run | Between-run | | |
| | Minimal %CV | Maximal %CV | Minimal %CV | Maximal %CV |
| ≤ 29 AU/mL or<br>IU/mL | 8% | 13% | 6% | 15% |
| 30 to 400 AU/mL or<br>IU/mL | 3% | 10% | 2% | 15% |

### Table 3: Summary of CARISTM precision results

- b. Comparison studies (manual versus automated assay preparation steps)
bmd has compared the results obtained with modified FIDISTM CONNECTIVE 10 for manual or automated (with CARIS™).assay preparation steps.

The study was performed on 80 samples characterized with the predicate test and the result repartition is described below:

- 77 samples were positive for one or more parameters . (see table 10)
- 3 negative samples. .

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{12}------------------------------------------------

bmd
biomedical diagnostics

a. First set of measures based on included the equivocal results with the test negative results.

ď dsDNA

| | dsDNA | | | |
|---------------------------------|-------|------------------------------------------------|-----|-------|
| | | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | |
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™ | Pos | 16 | 1 | 17 |
| CONNECTIVE<br>10<br>With CARIS™ | Neg | 0 | 63 | 63 |
| | Total | 16 | 64 | 80 |

There was 1 equivocal result with the assay. For purposes of calculation, this result was considered to be negative.

- Positive percent agreement: 100% (16/16)

- Negative percent agreement: 98.4% (63/64)

- Overall agreement: 98.8% (79/80)

# => TRIM 21 (SS-A 52kDa)

| TRIM 21<br>(SS-A 52kDa) | | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | |
|-------------------------------------------------------|-------|------------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10<br>With CARIS™ | Pos | 23 | 1 | 24 |
| | Neg | 0 | 56 | 56 |
| | Total | 23 | 57 | 80 |

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

- Positive percent agreement: 100% (22/22)

- Negative percent agreement: 98.3% (57/58)

- Overall agreement: 98.8% (79/80)

#### Ə Sm

| Sm | | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | |
|-------------------------------------------------------|-------|------------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10<br>With CARIS™ | Pos | 16 | 1 | 17 |
| | Neg | 0 | 63 | 63 |
| | Total | 16 | 64 | 80 |
| SS-A 60kDa | | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | |
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10<br>With CARIS™ | Pos | 26 | 1 | 27 |
| | Neg | 0 | 53 | 53 |
| | Total | 26 | 54 | 80 |

There was 1 equivocal result with the assay. For purposes of calculation, this result was considered to be negative.

- Positive percent agreement: 100% (16/16)
- Negative percent agreement: 98.4% (63/64)

- Overall agreement: 98.8% (79/80)

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# < SS-A 60kDa

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

- Positive percent agreement: 100% (26/26)

- Negative percent agreement: 98.1% (53/54)

- Overall agreement: 98.8% (79/80)

#### => SS-B

| SS-B | | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | |
|-------------------------------------------------------|-------|------------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10<br>With CARIS™ | Pos | 15 | 0 | 15 |
| | Neg | 0 | 65 | 65 |
| | Total | 15 | 65 | 80 |

There were 4 equivocal results with the assay. For purposes of calculation, these results were considered to be negative.

· Positive percent agreement: 100% (15/15)

- Negative percent agreement: 100% (65/65)

- Overall agreement: 100% (80/80)

#### ⇒ Sm/RNP

| Sm/RNP | | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | |
|---------------------------------|-------|------------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™ | Pos | 20 | 0 | 20 |
| CONNECTIVE<br>10<br>With CARIS™ | Neg | 0 | 60 | 60 |
| | Total | 20 | 60 | 80 |

There was 1 equivocal result with the assay. For purposes of calculation, this result was considered to be negative.

- Positive percent agreement: 100% (20/20)

- Negative percent agreement: 100% (60/60)

- Overall agreement: 100% (80/80)
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{13}------------------------------------------------

#### <> Scl-70

| Scl-70 | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | | |
|-------------------------------------------------------|------------------------------------------------|-----|-------|----|
| | Pos | Neg | Total | |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10<br>With CARIS™ | Pos | 15 | 2 | 17 |
| | Neg | 0 | 63 | 63 |
| | Total | 15 | 65 | 80 |

There were 2 equivocal results with the assay. For purposes of calculation, these results were considered to be negative.

- **Positive percent agreement:** 100% (15/15)

- Positive percent agreement: 100% (15/15)
- Negative percent agreement: 96.9% (63/65)

- Overall agreement: 97.5% (78/80)
# → CENP-B

| CENP-B | | MODIFIED FIDIST™<br>CONNECTIVE 10<br>Manual Use | | |
|-------------------------------------------------------|-------|-------------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIST™ | Pos | 8 | 0 | 8 |
| CONNECTIVE<br>10<br>With CARIST™ | Neg | 0 | 72 | 72 |
| | Total | 8 | 72 | 80 |
| Jo-1 | | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | |
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10<br>With CARIS™ | Pos | 10 | 0 | 10 |
| | Neg | 0 | 70 | 70 |
| | Total | 10 | 70 | 80 |

There was I equivocal result with the assay. For purposes of calculation, this result was considered to be negative.

- Positive percent agreement: 100% (8/8)

- Negative percent agreement: 100% (72/72)

- Overall agreement: 100% (80/80)

# 다 Jo-1

There were 2 equivocal results with the assay. For purposes of calculation, these results were considered to be negative.

- Positive percent agreement: 100% (10/10)
- Negative percent agreement: 100% (70/70)

- **Negative percent agreement:** 100% (70/70)

- Overall agreement: 100% (80/80)

# ⇒ Ribosomes

| Ribosomes | | MODIFIED FIDIST™<br>CONNECTIVE 10<br>Manual Use | | |
|---------------------------------|-------|-------------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIST™ | Pos | 6 | 0 | 6 |
| CONNECTIVE<br>10<br>With CARIS™ | Neg | 0 | 74 | 74 |
| | Total | 6 | 74 | 80 |

There was 1 equivocal result with the assay. For purposes of calculation, this result was considered to be negative.

· Positive percent agreement: 100% (6/6)

- Negative percent agreement: 100% (74/74)

- Overall agreement: 100% (80/80)

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{14}------------------------------------------------

b. Second set of measures based on included the equivocal results with the test positive results.

> SS-A 60kDa

#### <> dsDNA

| dsDNA | | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | |
|-------------------------------------------------------------|-------|------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDISTM<br>CONNECTIVE Neg<br>10<br>With CARISTM | Pos | 17 | 0 | 17 |
| | | 0 | ર્ણ રેજે રહ્યું હતું. સ્વર્ગ સાચના હતું રેતા પાસની વિદ્યોગના વિદ્યોગના વિદ્યારે તે જે તે આ ગામનાં છે તે આ ગામનાં છે તે આ ગામનાં છે તે આ ગામનાં છે છે. આ ગામનાં પ્રાથમિક શાળા, | 63 |
| | Total | 17 | ર્ભ રેસ | 80 |

MODIFIED FIDISTM CONNECTIVE 10 SS-A 60kDa Manual Use

There was i equivocal result with the assay. For purposes of calculation, this result is considered to be positive.

- Positive percent agreement: 100% (17/17)

- Negative percent agreement: 100% (63/63)

- Overall agreement: 100% (80/80)

# → TRIM 21 (SS-A 52kDa)

| TRIM 21<br>(SS-A 52kDa) | | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | |
|-------------------------------------------------------|-------|------------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10<br>With CARIS™ | Pos | 26 | 0 | 26 |
| | Neg | 0 | 54 | 54 |
| | Total | 26 | 54 | 80 |

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

- Positive percent agreement: 100% (26/26)

- Negative percent agreement: 100% (54/54) ·

- Overall agreement: 100% (80/80)

#### < Sm

| Sm | | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | |
|-------------------------------------------------------|-------|------------------------------------------------|-----|-------|
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10<br>With CARIS™ | Pos | Pos | Neg | Total |
| | Neg | 17 | 0 | 17 |
| | Total | 0 | 63 | 63 |
| | | 17 | 63 | 80 |
| | | Pos | Neg | Total |
| MODIFIED<br>FIDISTM | Pos | 29 | 0 | 29 |
| CONNECTIVE | Neg | 0 | 51 | 51 |
| 10<br>With CARISTM | Total | 29 | 51 | 80 |

There was I equivocal result with the assay. For purposes of calculation, this result is considered to be positive.

- Positive percent agreement: 100% (17/17)

- Negative percent agreement: 100% (63/63)
- Overall agreement: 100% (80/80)

S.A au Capital de 2 755.46 Euros

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

- Positive percent agreement: 100% (29/29)

- Negative percent agreement: 100% (51/51)

- Overall agreement: 100% (80/80)

#### => SS-B

| SS-B | | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | |
|---------------------------------|-------|------------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDISTM | Pos | 17 | 2 | 19 |
| CONNECTIVE<br>10<br>With CARIS™ | Neg | 0 | 61 | 61 |
| | Total | 17 | 63 | 80 |

There were 4 equivocal results with the assay. For purposes of calculation, these results were considered to be negative.

- Positive percent agreement: 100% (17/17)

· Negative percent agreement: 96.8% (61/63)

- Overall agreement: 97.5% (78/80)

#### <> Sm/RNP

| Sm/RNP | | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | |
|---------------------------------|-------|------------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™ | Pos | 20 | 0 | 20 |
| CONNECTIVE<br>10<br>With CARIS™ | Neg | 1 | 59 | 60 |
| | Total | 21 | 59 | 80 |

There was 1 equivocal result with the assay. For purposes of calculation, this result is considered to be positive.

- Positive percent agreement: 95.2% (20/21)

- Negative percent agreement: 100% (59/59)
- Overall agreement: 98.8% (79/80)

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{15}------------------------------------------------

#### <> Scl-70

| Scl-70 | | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | |
|--------------------------------------------------------|-------|------------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10<br>With CARISTM | Pos | 17 | 0 | 17 |
| | Neg | 0 | 63 | 63 |
| | Total | 17 | 63 | 80 |

There were 2 equivocal results with the assay. For purposes of calculation, these results were considered to be negative.

- Positive percent agreement: 100% (17/17)

- Negative percent agreement: 100% (63/63)

- Overall agreement: 100% (80/80)

## → CENP-B

| CENP-B | | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | |
|-------------------------------------------------------|-------|------------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10<br>With CARIS™ | Pos | 8 | 1 | 9 |
| | Neg | 0 | 71 | 71 |
| | Total | 8 | 72 | 80 |

There was I equivocal result with the assay. For purposes of calculation, this result was considered to be negative.

- Positive percent agreement: 100% (8/8)

- Negative percent agreement: 98.6% (71/72)

- Overall agreement: 98.8% (79/80)

⇒ Jo-1

| Jo-1 | | MODIFIED FIDIS™<br>CONNECTIVE 10<br>Manual Use | | |
|-------------------------------------------------------|-------|------------------------------------------------|-----|-------|
| | | Pos | Neg | Total |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10<br>With CARIS™ | Pos | 12 | 0 | 12 |
| | Neg | 0 | 68 | 68 |
| | Total | 12 | 68 | 80 |

There were 2 equivocal results with the assay. For purposes of calculation, these results were considered to be negative.

. - Positive percent agreement: 100% (12/12)

- Negative percent agreement: 100% (68/68)

- Overall agreement: 100% (80/80)

# ⇒ Ribosomes

| Ribosomes | MODIFIED FIDIS™ CONNECTIVE 10 Manual Use | | | |
|----------------------------------------|------------------------------------------|-----|-------|----|
| | Pos | Neg | Total | |
| MODIFIED<br>FIDIS™<br>CONNECTIVE<br>10 | Pos | 7 | 0 | 7 |
| | Neg | 0 | 73 | 73 |
| | Total | 7 | 73 | 80 |

There was 1 equivocal result with the assay. For purposes of calculation, this result was considered to be negative.

- Positive percent agreement: 100% (7/7)

- Negative percent agreement: 100% (73/73)

- Overall agreement: 100% (80/80)

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| Antigenic<br>Specificity | | Positive<br>percent<br>agreement | Negative<br>percent<br>agreement | Overall<br>agreement | EP12-A<br>Chap 9.2.2. | EP12-A<br>Chap 9.1.1. | EP12-A<br>Chap 9.1.1. |
|----------------------------|--------------------------------------------------------------|----------------------------------|----------------------------------|----------------------|-----------------------|-------------------------------------|-------------------------------------|
| | | proportion | proportion | proportion | 95% CI | 95% CI<br>For positive<br>agreement | 95% CI<br>For negative<br>agreement |
| dsDNA | equivocal results…