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 test is for in vitro diagnostic use.

Device Description

The FIDIS™ CONNECTIVE 10* kit is a semi-quantitative homogeneous fluorescentbased microparticles immunoasay using flow cytometry. The test system is used to simultaneously detect the presence of 10 autoantibody specificities: double stranded DNA (dsDNA), SSA (60 kDa and 52 kDa), SSB, Sm, Sm/RNP, Scl70, Jo1, ribosome and centromere. The kit includes a 96 wells microplate, vials of color-coded microsphere beads coupled with antigens and internal standard beads, sample dilution buffer, calibrator, positive control, negative control, anti-human IgG coupled to phycoerythrin, washing buffer, reconstitution buffer, package insert, microplate assay configuration worksheet, and microplate sealing films. The test is run on the FIDIS™ Instrument and MLX-BOOSTER™ Software, and may be used with the CARIS™ system (diluting and dispensing device).

AI/ML Overview

The Biomedical Diagnostics S.A. (bmd) FIDIS™ CONNECTIVE 10* assay is a semi-quantitative homogeneous fluorescent-based microparticles immunoassay that uses flow cytometry to detect 10 autoantibody specificities. The device's performance was established through analytical performance studies and comparison studies against a predicate device (K053653 FIDIS™ CONNECTIVE 10* system) and manual assay preparation steps.

1. Table of Acceptance Criteria and Reported Device Performance

The document provides acceptance criteria mainly for precision and outlines performance through agreement studies.

Precision Acceptance Criteria and Reported Performance

Sample range	Acceptance criteria (CV%)	Within-run minimal CV%	Within-run maximal CV%	Between-run minimal CV%	Between-run maximal CV%
Less than 10 AU/mL or IU/mL	Not determined	5.9%	12.8%	7.4%	13.6%
10 to 29 AU/mL or IU/mL	CV ≤ 20%	2.5%	11.8%	8.2%	17.3%
29 to 800 AU/mL or IU/mL	CV ≤ 15%	2.1%	12.7%	4.5%	14.3%

Comparison Study with Predicate Device (K053653 FIDIS™ CONNECTIVE 10)*

The acceptance criteria for the comparison study are implicitly that the agreement (Positive Percent Agreement, Negative Percent Agreement, and Overall Agreement) should demonstrate substantial equivalence to the predicate device. While specific percentage targets are not explicitly stated as "acceptance criteria" in the table format, the observed agreement percentages with 95% LCLs are reported and deemed sufficient for substantial equivalence.

Antigenic Specificity	Positive Percent Agreement (PPA)	Negative Percent Agreement (NPA)	Overall Agreement (OA)	95% LCL PPA	95% LCL NPA	95% LCL OA
dsDNA	91.84%	98.51%	95.69%	82.29%	93.11%	91.15%
SSA 60 kDa	100%	98.57%	99.15%	93.95%	93.40%	96.04%
SSA 52 kDa	95.08%	96.97%	96.06%	87.78%	90.77%	91.90%
SSB	100%	97.14%	97.85%	87.79%	91.28%	93.39%
Sm	95.83%	97.33%	96.97%	81.71%	91.84%	92.35%
Sm/RNP	96.88%	97.44%	97.27%	86.02%	92.15%	93.10%
Scl70	96.43%	97.14%	96.94%	84.15%	91.28%	92.28%
Jo1	96.3%	100%	98.96%	83.60%	95.75%	95.15%
Centromere	83.33%	100%	95.83%	65.82%	95.92%	90.72%
Ribosome	100%	100%	100%	84.67%	95.75%	96.62%

Comparison Study: Manual vs. Automated (CARIS™) Assay Preparation

Similar to the predicate comparison, the acceptance criteria here are also implicit that agreement between manual and automated methods shows substantial equivalence.

Antigenic Specificity	Positive Percent Agreement (PPA)	Negative Percent Agreement (NPA)	Overall Agreement (OA)	95% LCL PPA	95% LCL NPA	95% LCL OA
dsDNA	100%	100%	100%	93.27%	95.75%	97.36%
SSA 60 kDa	100%	100%	100%	93.12%	95.69%	97.31%
SSA 52 kDa	100%	98.48%	98.48%	94.40%	93.01%	96.04%
SSB	100%	100%	100%	88.71%	95.63%	96.80%
Sm	100%	95.83%	96.88%	88.27%	89.58%	92.12%
Sm/RNP	100%	95.77%	97.09%	91.06%	89.44%	92.64%
Scl70	100%	100%	100%	90.19%	95.69%	96.96%
Jo1	100%	100%	100%	89.12%	95.75%	96.90%
Centromere	100%	94.52%	95.70%	86.09%	87.90%	90.43%
Ribosome	100%	100%	100%	68.77%	95.69%	96.13%

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

Precision Study Test Set:
- Within-run: 6 samples (5 for Jo1) tested 10 times in the same run.
- Between-run: 6 samples (5 for Jo1) tested 3 times per run, across 6 runs.
- The document does not specify the country of origin or whether the data was retrospective or prospective for the precision study samples.
Comparison Study with Predicate Device Test Set:
- Sample Size: 264 samples.
- Composition: 194 samples positive for one or more parameters, and 70 negative samples (including some with potential biological interferences).
- Data Provenance: The document states "obtained from routine laboratory" for interfering substances study (part of analytical performance) and implies a similar source for the comparison study, but the specific country of origin or retrospective/prospective nature isn't explicitly stated. However, given the manufacturer is based in France, it's plausible the samples originated from Europe.
Comparison Study with Automated (CARIS™) system Test Set:
- Sample Size: 264 samples.
- Composition: 194 samples positive for one or more parameters, and 70 negative samples (including some with potential biological interferences).
- Data Provenance: Same as above.

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

The document does not mention the use of human experts to establish ground truth for the test sets. Instead, the "ground truth" for the comparison studies is defined by the results obtained from the predicate device (K053653 FIDIS™ CONNECTIVE 10 system)* or the manual assay preparation steps of the modified device. For the analytical performance (e.g., precision, interfering substances), the "truth" is based on the inherent characteristics of the spiked or characterized samples.

4. Adjudication Method for the Test Set

This type of in-vitro diagnostic device study typically doesn't involve human adjudication in the traditional sense (e.g., for imaging studies). For the comparison studies, discrepancies were handled as follows:

"All equivocal samples with predicate and modified CONNECTIVE 10* assays are considered negative for the comparison and the evaluation studies."
For individual specificities, the number of equivocal results is noted (e.g., "There were 3 equivocal results with the assay. For purposes of calculation, these results were considered as negative."). This method effectively converts equivocal results into negative results for agreement calculations.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of AI vs. Without AI Assistance

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This device is an in-vitro diagnostic test system, not an AI-assisted diagnostic tool that human readers would interact with in the context of interpretation. The comparison is between different versions or methods of the assay itself, or against a predicate device.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

The device itself is a standalone in-vitro diagnostic test system. The performance studies evaluate the device's analytical characteristics and its agreement with a predicate device or different operational modes (manual vs. automated sample preparation). There isn't an "algorithm" in the sense of a standalone AI intended to perform diagnostic interpretation; rather, it's a test system that provides semi-quantitative results. The system operates without human interpretive intervention beyond running the assay and reading the numerical output.

7. The Type of Ground Truth Used

The ground truth for the comparison studies was:

The results generated by the predicate device (K053653 FIDIS™ CONNECTIVE 10 system)* when comparing the modified device to the predicate.
The results generated by the manual assay preparation steps when comparing the automated (CARIS™) assay preparation to manual preparation.

For the analytical precision and interfering substances studies, the ground truth was based on the known characteristics of the samples (e.g., characterized positive/negative samples, spiked samples, or samples with known interferences). There is no mention of pathology, expert consensus, or outcomes data being directly used as ground truth for these performance evaluations.

8. The Sample Size for the Training Set

The document does not specify a separate "training set" in the context of machine learning or algorithm development. The studies performed are for performance evaluation and comparison studies for a medical device. Therefore, no training set size is reported in the provided text.

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

As no training set is indicated, this question is not applicable. The device's operational characteristics and comparisons are the focus of performance evaluation, not machine learning model training.

Summary

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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 a horizontal line underneath. Below the line, the words "biomedical diagnostics" are written in a smaller, sans-serif font. The letters "bmd" are in a bold, sans-serif font, with the "o" being a perfect circle.

Premarket Notification 510(k) Summary

DEC 1 9 2007

Assigned 510(k) Number: K071210

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: 404 248 0002
	E-mail: Hoppe Regulatory@cs.com
2. Device Name
Trade/Proprietary Name :	FIDIS™ CONNECTIVE 10* assay
Common/Usual Name :	MX006 - FIDIS™ CONNECTIVE 10*: Detection test of 10autoantibody specificities: double stranded DNA (dsDNA),SSA 60kDa, SSA 52kDa, SSB, Sm, Sm/RNP, Scl70, Jo-1,Ribosome and Centromere.
Classification Name:	Antinuclear antibody immunological test system
Trade/Proprietary Name :	FIDIS™ Analyzer
Classification Name:	Instrumentation for Chemical Multiplex Systems
Trade/Proprietary Name :	CARIS™ System

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

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3. Intended use of the device

(*Antibodies to dsDNA, Sm, Sm/RNP, SSA, SSB, Scl-70, Jo-1, ribosome and centromere 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 test is for in vitro diagnostic use.

4. Materials supplied

1 x 96 wells microplate with filtering membrane and a lid.	1 plate
1 Vial (A) of 10 sets of color-coded microsphere beads coupled with dsDNA, SSA 60 kDa,SSA 52 kDa, SS-B, Sm, Sm/RNP, Scl-70, Jo-1, ribosomes, centromere antigen, plus 1 setof Internal standard beads.Lyophilized (to be diluted with the buffer named D)	Sufficient quantity toobtain 6mL afterreconstitution
1 Vial (B) of sample dilution buffer (white vial)Ready to use	2 x 115mL
1 Vial of calibrator titered for the specificities to be mesuredReady to useEach titer is printed on the vial label	1 x 1,5mL
1 Vial of positive control concentrate. This control has a standard reactivity, that providesevidence of the proper functioning of reagents and correct assay performance.To be dilutedExpected values are printed on the vial label.	1 × 250 µL
1 Vial of negative control* concentrateTo be diluted	1 x 250µL

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1 Vial of anti-human IgG coupled to phycoerythrinReady to use	1 x 12mL
1 Vial (C) of washing buffer (black vial)Ready to use	1 x 100mL
1 Vial (D) of reconstitution buffer for the microsphere setReady to use	1 x 6mL
Package insert	1
Microplate Assay Configuration Worksheet	1
Microplate sealing films	6

5. Predicate Device

510K Number	Device Classification Name	Manufacturer Name
K053653	FIDIST TM CONNECTIVE 10*	bmd

6. Comparison with the predicate

		Predicate DeviceFIDIST™ CONNECTIVE 10*K053653		Modified DeviceFIDIST™ CONNECTIVE 10*
Intended use		Individual determination in human serum ofIgG antibodies against:dsDNA, SSA 60kDa, SSA 52kDa, SSB,Sm, Sm/RNP, Scl70, Jo-1, Ribosome andCentromere		Same(minor text changes)
CUT-OFF	Negative	<30for the 10 specificities	- In IU/mL fordsDNA- In AU/mL forthe 9 otherspecificities	Same
	Equivocal	30-40for the 10 specificities		Same
	Positive	>40for the 10 specificities		Same
Material supplied		Microplate with caps		Microplate with sealing films
	Beads	Vial of color-coded microsphere setready to use (6mL)		Vial of color-coded microsphere setLyophilized (sq 6mL)
	Sample dilution	PBS-Tween concentrated		Sample dilution buffer ready to use
Washing buffer		PBS-Tween concentrated		Washing buffer ready to use
	Internal standardbeads	No		Yes

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	Predicate DeviceFIDIS™ CONNECTIVE 10K053653	Modified DeviceFIDIS™ CONNECTIVE 10
Assay configuration	1 "reagent-blank" well1 "calibrator" well1 "negative control" well1 "positive control" well	1 "reagent-blank" well1 "negative control" well1 "positive control" well2 "calibrator" wells
	Diluted sample wells	Same
	A second calibrator well every 48 well series	No
Incubation time	2 x 30mn RT	Same
Wash step	2 x 200μL	2 x 300μL
Assay protocol	Optional final wash step	Final wash step (not optional)
Software	Booster Version 1.35	Booster Version 2.2
Detection Method	Fluorescence(using Luminex 100)	Fluorescence(using Luminex 200)
Sample preparation	Manual preparation	Same
Automatic sample preparation (option)	CARIS™	Same

7. Performance Characteristics

1. Analytical performance

a. Precision

Precision of the assay was assessed in 53 samples. Precision was determined by calculating the within-run (intra-assay) and the between run (inter-assay).

· For within run: 6 samples (except for Jo1 only 5 samples were tested) 10 times in a same run.

· For between run: 6 samples (except for Jo1 only 5 samples were tested) in 6 runs, 3 times per run.

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Sample range	Acceptancecriteria forwithin-runandbetween-run	Within-runminimal CV%for the 10parameters	Within-runmaximalCV% for the10 parameters	Between-runminimal CV%for the 10parameters	Between-runmaximalCV% for the10 parameters
Less than 10AU/mL or IU/mL	Notdetermined	5.9%	12.8%	7.4%	13.6%
10 to 29 AU/mLor IU/mL	CV≤20%	2.5%	11.8%	8.2%	17.3%
29 to 800 AU/mLor IU/mL	CV≤15%	2.1%	12.7%	4.5%	14.3%

Table 1: Summary of FIDIS™ CONNECTIVE 10* precision results

b. Linearity/ assay reportable range

FIDISTM CONNECTIVE 10* assay has been optimized to express the average binding capacity at the current dilution (1/200) by a flow cytometric reading resulting of the median fluorescence value obtained from 200 microspheres per parameter.

Further dilutions potentially give rise to inaccurate results because the reaction conditions and the equilibrium of the immunological reaction would be modified.

c. Interfering Substances

The study was conducted by testing 30 negative samples (for dsDNA, SSA 60kDa, SSA 52kDa, SSB, Sm, Sm/RNP, Scl70, Jo-1, Ribosome and Centromere) characterized as positive for various potential interferences obtained from routine laboratory (listed in following table).

	Number of positive sample
	dsDNA	SSA60 kD	SSA52kD	SSB	Sm	Sm/RNP	Scl70	Jo1	Ribo
Cryoglobulinemia N*=2	0	0	0	0	0	0	0	0	0
Complement N*=7	2	1	0	1	1	1	0	0	0
IgG monoclonalimmunoglobulins N*=1	0	0	0	0	0	0	0	0	0
IgM monoclonalimmunoglobulins N*=5	0	0	0	0	0	0	0	0	0
Rheumatoid factor N*=8	1	2	2	1	0	1	0	0	0
Plasma N*=3	0	0	0	0	0	0	0	0	0
Hemolyzed sera N*=3	0	0	0	0	0	0	0	0	0
Anti-smooth muscleantibodies N*=1	0	0	0	0	0	0	0	0	0

Table 2: Potential interferences results

*N: number of samples tested

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d. Threshold values

Threshold values were estimated from the 2 selected populations:

50 samples from blood donors -
48 samples selected for their potential biological interferences -

The negative thresholds (30AU/mL or 30IU/mL) correspond to the 97.9% for dsDNA. SSA. Sm/RNP: 99.0% for centromere and ribosome, and 100% for SSB, Sm, Scl70 and Jo1 for the populations studied.

e. Stability of the assay results after final wash step

This assay included 3 test series with:

5 positive samples for SSA 52kDa, SSA 60kDa, SSB, Sm, Sm/RNP, - Sc170, dsDNA and Centromere;
4 positive samples for Jol;
-3 positive samples for Ribosome.

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.
ﺖ T= 4 hours: the second series of test was read after 4 hours of storage at room temperature away from direct sunlight.
T=18 hours: the last series was read after 18 hours of storage at room temperature away from direct sunlight.

%CV acceptance criteria	Parameter	Sample	Mean results Obtained after 18H (AU/mL)	%CV Obtained after 18H	Mean results Obtained after 4H (AU/mL)	%CV Obtained after 4H
%CV ≤ 15%	SSA 52	Sample 1	169	9	Not calculated	Not calculated
		Sample 2	85	5
		Sample 3	52	5
		Sample 4	130	5
		Sample 5	180	11
	SSA 60	Sample 6	49	7	Not calculated	Not calculated
		Sample 7	94	11
		Sample 8	68	4
		Sample 9	85	7
		Sample 10	95	13
Acceptance criteria	Parameter	Sample	Mean results Obtained after 18H (AU/ml)	%CV Obtained after 18H	Mean results Obtained after 4H (AU/ml)	%CV Obtained after 4H
%CV ≤15%	SSB	Sample 11	167	6	Not calculated	Not calculated
		Sample 12	59	5
		Sample 13	85	7
		Sample 14	121	11
	Sm	Sample 15	23	5	Not calculated	Not calculated
		Sample 16	33	7
		Sample 17	309	10
		Sample 18	50	7
		Sample 19	103	13
		Sample 20	147	3
	Sm/RNP	Sample 21	202	7	Not calculated	Not calculated
		Sample 22	82	11
		Sample 23	374	11
		Sample 24	59	9
%CV ≤15%	Scl70	Sample 25	116	13	Not calculated	Not calculated
		Sample 26	57	4
		Sample 27	55	5
		Sample 28	144	3
		Sample 29	308	4
	Jo1	Sample 30	188	7	Not calculated	Not calculated
		Sample 31	79	13
	Jo1	Sample 32	242	6	Not calculated	Not calculated
		Sample 33	59	7
		Sample 34	77	6
		Sample 35	91	16
	Centromere	Sample 36	82	11	78	11
		Sample 37	81	7	78	6
		Sample 38	22	9	21	5
		Sample 39	19	5	20	0
	Ribosome	Sample 40	40	13	Not calculated	Not calculated
		Sample 41	141	7
		Sample 42	71	6
	dsDNA	Sample 43	49	11	Not calculated	Not calculated
		Sample 44	123	9
		Sample 45	51	10
		Sample 46	184	3
		Sample 47	62	8

Table 4: Stability of the assay results after final wash step

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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

bmd has compared the results obtained with modified FIDIS™ CONNECTIVE 10* versus the results obtained with predicate FIDISTM CONNECTIVE 10* K053653 in manual use.

The study was performed on 264 samples characterized with the predicate test and the result repartition is described as below:

194 samples were positive for one or more parameters (see table 5). -
ー 70 negative samples including some samples evaluated for their potential biological interferences.

57
48
23
29
40
28
26
26
17
46

Table 5: Number of positive samples per parameter.

FIDIS™ All equivocal samples with predicate and modified CONNECTIVE 10* assays are considered negative for the comparison and the evaluation studies.

dsDNA					SSA 60kDa
N=116		Pos	Neg	Total	N=118
	Pos	45	1	46	Pos
	Neg	4	66	70	Neg
	Total	49	67	116	Total

Tables 6: Specificity performances

of calculation, these results were considered as negative. Positive percent agreement: 100% (48/48) Negative percent agreement: 98.57% (69/70) Overall agreement: 99.15% (117/118)

Pos

Neg

રેજે

There were 3 equivocal results with the assay. For purposes There were 2 equivocal results with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 91.84% (45/49) Negative percent agreement: 98.51% (66/67) Overall agreement: 95.69% (111/116)

2017

Total

118

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SSA 52kDa
N=127
	Pos	Neg	Total
Pos	58	2	60
Neg	3	64	67
Total	61	66	127

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

Positive percent agreement: 95.08% (58/61) Negative percent agreement: 96.97% (64/66)

Overall agreement: 96.06% (122/127)

Sm
N=99		Pos	Neg	Total
	Pos	23	2	25
	Neg	1	73	74
	Total	24	75	99

There were 6 equivocal results with the assay. For purposes of calculation, these results were considered as negative.

Positive percent agreement: 95.83% (23/24) Negative percent agreement: 97.33% (73/75) Overall agreement: 96.97% (96/99)

Scl70
N=98		Pos	Neg	Total
	Pos	27	2	29
	Neg	1	68	69
	Total	28	70	98
SS-B
N=93
		Pos	Neg	Total
	Pos	23	2	25
	Neg	0	68	68
	Total	23	70	93

There is 1 equivocal result with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 96.43% (27/28)

Negative percent agreement: 97.14% (68/70) Overall agreement: 96.94% (95/98)

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

Positive percent agreement: 100% (23/23) Negative percent agreement: 97.14% (68/70) Overall agreement: 97.85% (91/93)

Sm/RNP
N= 110
	Pos	Neg	Total
Pos	31	2	33
Neg	1	76	77
Total	32	78	110

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

Positive percent agreement: 96.88% (31/32) Negative percent agreement: 97.44% (76/78) Overall agreement: 97.27% (107/110)

Jo1
N=96
	Pos	Neg	Total
Pos	26	0	26
Neg	1	69	70
Total	27	69	96

There is 0 equivocal result with the assay.

Positive percent agreement: 96.30% (26/27) Negative percent agreement: 100% (69/69) Overall agreement: 98.96% (95/96)

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Centromere
N=96
		Pos	Neg	Total
	Pos	20	0	20
	Neg	4	72	76
	Total	24	72	96

Ribosome
N=87		Pos	Neg	Total
	Pos	18	0	18
	Neg	0	69	69
	Total	18	69	87

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

Positive percent agreement: 83.33% (20/24) Negative percent agreement: 100% (72/72)

・

Overall agreement:95.83% (92/96)

There is 1 equivocal result with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 100% (18/18) Negative percent agreement: 100% (69/69) Overall agreement: 100% (87/87)

AntigenicSpecificity	Samplenumber	Positivepercentagreementproportion	Negativepercentagreementproportion	Overallagreementproportion
dsDNA	116	91.84%	98.51%	95.69%
SSA 60 kDa	118	100%	98.57%	99.15%
SSA 52 kDa	127	95.08%	96.97%	96.06%
SSB	93	100%	97.14%	97.85%
Sm	99	95.83%	97.33%	96.97%
Sm/RNP	110	96.88%	97.44%	97.27%
Scl70	98	96.43%	97.14%	96.94%
Jo1	96	96.3%	100%	98.96%
Centromere	96	83.33%	100%	95.83%
Ribosome	87	100%	100%	100%

Table 7: Summary of performance agreement results

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.

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AntigenicSpecificity	Positive percent agreement				Negative percent agreement				Overall percent agreement
	N1	R1	P1(%)	95%LCL (%)	N2	R2	P2(%)	95%LCL (%)	N	R	P(%)	95%LCL (%)
dsDNA	49	45	91.84	82.29	67	66	98.51	93.11	116	111	95.69	91.15
SSA 60 kDa	48	48	100	93.95	70	69	98.57	93.40	118	117	99.15	96.04
SSA 52 kDa	61	58	95.08	87.78	66	64	96.97	90.77	127	122	96.06	91.90
SSB	23	23	100	87.79	70	68	97.14	91.28	93	91	97.85	93.39
Sm	24	23	95.83	81.71	75	73	97.33	91.84	99	96	96.97	92.35
Sm/RNP	32	31	96.88	86.02	78	76	97.44	92.15	110	107	97.27	93.10
Scl70	28	27	96.43	84.15	70	68	97.14	91.28	98	95	96.94	92.28
Jo1	27	26	96.3	83.60	69	69	100	95.75	96	95	98.96	95.15
Centromere	24	20	83.33	65.82	72	72	100	95.92	96	92	95.83	90.72
Ribosome	18	18	100	84.67	69	69	100	95.75	87	87	100	96.62

Table 8: Summary of agreements results - 95% LCL (%)

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 = N1 + N2; R = R1 + R2; P = R/N

All of results show that FIDIS™ CONNECTIVE 10* system can be considered substantially equivalent to the predicate K053653 FIDIS™ CONNECTIVE 10* system.

3. Comparison study with predicate a. Precision

Precision of the assay was assessed in 36 samples. Precision was determined by calculating the within-run (intra-assay) and the between run (inter-assay):

For within run: 4 samples 10 times in a same run. .
For between run: 4 samples in 6 runs, 3 times per run. .

Sample range	Acceptancecriteria forwithin-runandbetween-run	Within-runminimal CV%for the 10parameters	Within-runmaximalCV% for the10 parameters	Between-runminimal CV%for the 10parameters	Between-runmaximalCV% for the10 parameters
Less than 10AU/mL or IU/mL	Notdetermined	Not evaluated	Not evaluated	Not evaluated	Not evaluated
10 to 29 AU/mLor IU/mL	CV≤20%	3.8%	10.3%	7.3%	13.9%
29 to 800 AU/mLor IU/mL	CV≤15%	1.7%	10.8%	3.7%	12.5%

Table 9: Summary of CARISTM Precision results

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b. Comparison study (manual versus automated assay preparation steps)

bmd has compared the results obtained with the modified FIDISTM CONNECTIVE 10* for the manual or automated (with CARIS™) assay preparation steps.

The study was performed on 264 samples characterized with the predicate test and the result repartition is described as below:

194 samples were positive for one or more parameters (see Table 12) -
70 negative samples including some samples evaluated for their potential biological interferences.

Pathological sample number/parameter
SSA52	48
SSA60	40
SSB	22
Sm	26
Sm/RNP	33
Scl70	27
JOI	25
Centro	23
Ribo	6
dsDNA	42

Table 10: Number of the pathological population per parameter.

All equivocal samples with FIDIS™ CONNECTIVE 10* assays are considered negative for the comparison and the evaluation studies.

	Pos	Neg	Total
	Pos	43	0
Neg	0	69	69
Total	43	69	112

Tables 11: Agreement performances

	Pos	Neg	Total
Pos	42	0	42
Neg	0	68	68
Total	42	68	110

of calculation, these results were considered as negative. Positive percent agreement: 100% (43/43) Negative percent agreement: 100% (69/69) Overall agreement: 100% (112/112)

There were 4 equivocal results with the assay. For purposes There Were 1 equivocal results with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 100% (42/42) Negative percent agreement: 100% (68/68) Overall agreement: 100% (110/110)

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		Pos	Neg	Total
dsDNAN=112	Pos	43	0	43
	Neg	0	69	69
	Total	43	69	112

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

Positive percent agreement: 100% (43/43) Negative percent agreement: 100% (69/69) Overall agreement: 100% (112/112)

Tables 11: Agreement performances

SSA 60kDa

N=110

Pos

Neg

08	110

	Positive percent agreement: 100% (42/42)Negative percent agreement: 100% (68/68)	There were 1 equivocal results with the assay. For purposesof calculation, these results were considered as negative.

Pos

NUTTS

Total

Neg

Overall agreement: 100% (110/110)

SSA 52kDaN=118		MANUAL
		Pos	Neg	Total
CARISTY	Pos	52	1	53
	Neg	0	65	65
	Total	52	66	118

There were 2 equivocal results with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 100% (52/52)

Negative percent agreement: 98.48% (65/66)

Overall agreement: 99.15% (117/118)

Sm		MANUAL
N=96		Pos	Neg	Total
CARIST	Pos	24	3	27
	Neg	0	69	69
	Total	24	72	96

There were 5 equivocal results with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 100% (24/24) Negative percent agreement: 95.83% (69/72) Overall agreement: 96.88% (93/96)

Scl70
N=97		Pos	Neg	Total
CARIS	Pos	29	0	29
	Neg	0	68	68
	Total	29	68	97

There is 0 equivocal result with the assay. Positive percent agreement: 100% (29/29) Negative percent agreement: 100% (68/68) Overall agreement: 100% (97/97)

SSBN=92		MANUAL
		Pos	Neg	Total
	Pos	25	0	25
CARIST	Neg	0	67	67
	Total	25	67	92

There is 1 equivocal result with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 100% (25/25) Negative percent agreement: 100% (67/67) Overall agreement: 100% (92/92)

	Sm/RNP
N=103		MANUAL
		Pos	Neg	Total
CARIS	Pos	32	3	35
	Neg	0	68	68
	Total	32	71	103

There were 6 borderline results with the assay. For purposes of calculation, these results were considered as negative. Positive percent agreement: 100% (32/32) Negative percent agreement: 95.77% (68/71) Overall agreement: 97.09% (100/103)

Jo1N=95			MANUAL
		Pos	Neg	Total
CARIST	Pos	26	0	26
	Neg	0	69	69
	Total	26	69	95

There is 0 equivocal result with the assay. Positive percent agreement: 100% (26/26) Negative percent agreement: 100% (69/69) Overall agreement: 100% (95/95)

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Centromere		MANUAL
N=93		Pos	Neg	Total
	Pos	20	4	24
	Neg	0	69	69
	Total	20	73	93

Ribosome		MANUAL
N=76		Pos	Neg	Total
CARIS	Pos	8	0	8
	Neg	0	68	68
	Total	8	68	76

There were 6 equivocal results with the assay. For purpose There is 0 equivocal result with the assay. of calculation, these results were considered as negative.

Positive percent agreement: 100% (20/20)

Negative percent agreement: 94.52% (69/73)

Overall agreement: 95.70% (89/93)

e There is 0 equivocal result with the assay.

Positive percent agreement: 100% (8/8) Negative percent agreement: 100% (68/68) Overall agreement: 100% (76/76)

AntigenicSpecificity	Samplenumber	Positivepercentagreement	Negativepercentagreement	Overallagreement
		proportion	proportion	proportion
dsDNA	112	100%	100%	100%
SSA 60 kDa	110	100%	100%	100%
SSA 52 kDa	118	100%	98.48%	98.48%
SSB	92	100%	100%	100%
Sm	96	100%	95.83%	95.83%
Sm/RNP	13	100%	95.77%	95.77%
Scl70	97	100%	100%	100%
Jo1	95	100%	100%	100%
Centromere	93	100%	94.52%	94.52%
Ribosome	76	100%	100%	100%

Table 12: Summary of performance agreement results

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AntigenicSpecificity	Positive percent agreement			Negative percent agreement			Overall percent agreement
	N₁	R₁	P₁(%)	95% LCL (%)	N₂	R₂	P₂(%)	95% LCL (%)	N	R	P(%)	95% LCL (%)
dsDNA	43	43	100	93.27	69	69	100	95.75	112	112	100	97.36
SSA 60 kDa	42	42	100	93.12	68	68	100	95.69	110	110	100	97.31
SSA 52 kDa	52	52	100	94.40	66	65	98.48	93.01	118	117	99.15	96.04
SSB	25	25	100	88.71	67	67	100	95.63	92	92	100	96.80
Sm	24	24	100	88.27	72	69	95.83	89.58	96	93	96.88	92.12
Sm/RNP	32	32	100	91.06	71	68	95.77	89.44	103	100	97.09	92.64
Scl70	29	29	100	90.19	68	68	100	95.69	97	97	100	96.96
Jo1	26	26	100	89.12	69	69	100	95.75	95	95	100	96.90
Centromere	20	20	100	86.09	73	69	94.52	87.90	93	89	95.70	90.43
Ribosome	8	8	100	68.77	68	68	100	95.69	76	76	100	96.13

Table 13: Summary of performance agreements results - 95% LCL (%)

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 previous evaluation results indicate that manual and automated (with CARIS™) assay preparation steps are considered substantially equivalents.

8. Conclusions

In conclusion, all supporting data demonstrate that the FIDIS™ CONNECTIVE 10* system can be considered substantially equivalent to the predicate device.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/15/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the circle is an abstract symbol that resembles a stylized eagle or bird in flight.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 1 9 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: K071210

Trade/Device Name: FIDISTM CONNECTIVE 10* Assay Regulation Number: 21 CFR 866.5100 Regulation Name: Antinuclear antibody immunological test system Regulatory Class: Class II Product Code: LLL, LKS, LKO, LKP, LSW, LJM, MQA Dated: December 5, 2007 Received: December 7, 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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Page 2 -

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 (240) 276-0450. 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 (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Robert D. Becker

Robert L. Becker, Jr., M.D., Ph.Ø 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): K071210

Device Name:

FIDISTM CONNECTIVE 10*

Indication For Use:

The FIDIS™ CONNECTIVE 10* kit is a semi-quantitative homogeneous fluorescent-based microparticles immunoassay using flow cytometry. The test system is used to simulaneously detect the presence of 10 autoantibody specificities: double stranded DNA (dsDNAA), SSA (60 kDa and 52 kDa), SSB, Sm, Sm/RNP, Scl70, Jo1, ribosome and centromere,

(*Antibodies to dsDNA, Sm, Sm/RNP, SSA, SSB, Scl-70, Jo-1, ribosome and centromere 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 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 test is for in vitro diagnostic use.

Prescription Use __ X (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 Elan

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

Regulation Number and Section

§ 866.5100 Antinuclear antibody immunological test system.

(a)
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).(b)
Classification. Class II (performance standards).