K Number
K053653
Date Cleared
2006-03-13

(73 days)

Product Code
Regulation Number
866.5100
Predicate For
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The FIDIS™ CONNECTIVE 10* kit is a semi-quantitative homogeneous fluorescent based microparticles immunoassay using flow cytometry readings. It is designed for the simultaneous detection of autoantibody specificities: double stranded DNA (dsDNA), SSA (60 kDA and 52 kDA), SSB, Sm. Sm/RNP, Scl-70, Jo-1 ribosome and centromere in human serum. (* Antibodies to dsDNA, SSA, SSB, Sm, Sm/RNP, Scl-70, Jo-1, ribosome and centromere can be reported using this assay).

The test system is used to screen serum samples and detect the presence of antinuclear antibodies associated with connective diseases systemic lupus erythematosus (SLE), Sjogren's syndrome, mixed connective tissue disease (MCTD), scleroderma, dermatomyositis, and CREST syndrome, in conjunction with clinical findings and other laboratory tests.

Device Description

The assay kits consist of:

  • a mixture of color-coded microspheres sensitized respectively by dsDNA, SSA 60kDa, SSA 52kDa, SSB, Sm, Sm/RNP, Scl70, Jo-1, Ribosomes and Centromeres.
  • a ready to use anti-human IgG coupled to phycoerythrin,
  • a ready to use calibrator titered for each specificity,
  • a positive control IgG to be diluted.
  • a negative control to be diluted,
  • a 10X concentrated PBS-Tween.
    Rk: Calibrators, positive and negative controls are diluted human sera.

The FIDIS™ System is a fully integrated and automated system for immunodiagnostic testing.
FIDIS™ System comprised of FIDIS flow cytometer, XYP platform for automatic sampling into the analyser, the analyzer itself, a SD pump, some assay products and a MLX-BOOSTER software.

The FIDIS™ CONNECTIVE 10 kit resembles traditional EIA, but allows simultaneous detection and identification of several antibodies in a single well.

    1. Diluted patient sera and multiplexed bead suspension are thoroughly mixed in the 96 well microtiter plate. Antigen specific antibodies in the patient sera, if present, bind to the immobilised antigen on one or more of the bead sets. Any unbound material is removed by performing a wash step.
    1. Phycoerythrin-conjugated goat anti-human IgG is added to the plate and a further incubation performed. The conjugated anti-human igG binds to the antigen specific antibodies immobilised on the microsphere surface to form an antigen/antibody complex.
    1. The bead suspension is then analysed by the FIDIS™ Instrument and reactions are directly calculated in biological units using specific data software (MLX-BOOSTER).

The FIDIS™ Instrument is able to distinguish the specific color-code of each microsphere types and it could associate the microsphere type with the individual tested antigen.
The FIDIS™ Instrument can quantify the fluorescence of the antibody captured by each microsphere. Measurement of the fluorescent signal from the final reaction complex allows the quantification of the presence or absence of autoantibodies.

AI/ML Overview

Here's a summary of the acceptance criteria and the study details for the FIDIS™ CONNECTIVE 10 device, based on the provided text:

Premarket Notification 510(k) Summary for FIDIS™ CONNECTIVE 10 (K053653)

The document primarily focuses on establishing substantial equivalence to predicate devices, rather than defining specific numerical acceptance criteria for performance metrics like sensitivity and specificity. The acceptance criteria appear to be implicit in demonstrating comparability to the predicate devices across various sample types.

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric/TestAcceptance Criteria (Implicit from comparability claim)Reported Device Performance (Summary)
ComparabilitySubstantially equivalent to predicate devicesData set included: - Results from a comparison study analyzing positive, equivocal, and negative sera. - Results from samples of apparently healthy subjects (normal population). - Results from samples with potential biological cross-reactivity.
AccuracyNot explicitly stated as a separate numerical criterionImplied through substantial equivalence to predicate device results, which are presumed to be accurate. The device allows for the detection of 10 autoantibody specificities (dsDNA, SSA 60kDa, SSA 52kDa, SSB, Sm, Sm/RNP, Scl70, Jo-1, Ribosomes, and Centromeres) and its measurements are directly calculated in biological units using specific data software.
Precision/ReproducibilityNot explicitly stated as a separate numerical criterionNot explicitly detailed in the provided summary.
Clinical UtilityAbility to screen serum samples and detect the presence of anti-nuclear antibodies associated with connective diseases (SLE, Sjogren's syndrome, MCTD, Scleroderma, Dermatomyositis, CREST syndrome)The device is designed for this intended use and is presented as being able to screen serum samples and detect these autoantibodies. Its use is in conjunction with clinical findings and other laboratory tests.

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

The exact sample sizes for the test set (comparison study, healthy subjects, cross-reactivity samples) are not specified in this summary document.
The document does not explicitly state the country of origin for the data or whether it was retrospective or prospective.

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

The document does not provide information on the number of experts used or their qualifications for establishing ground truth.

4. Adjudication Method for the Test Set

The document does not specify any adjudication method (e.g., 2+1, 3+1, none) for the test set.

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

There is no indication that a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done. This device is an in-vitro diagnostic (IVD) test for autoantibody detection, not an imaging device requiring human reader interpretation in the same way.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Study Was Done

The device is a semi-quantitative homogeneous fluorescent-based microparticles immunoassay using flow cytometry readings. It is an automated system for immunodiagnostic testing. The "standalone" performance is inherent to its function as an IVD device, where the instrument performs the detection and quantification. The summary describes the assay steps culminating in analysis by the FIDIS™ Instrument which calculates results using specific software. Therefore, the reported performance is a standalone (algorithm/instrument only) performance.

7. The Type of Ground Truth Used

The ground truth for the comparison studies is implicitly based on the results obtained from legally marketed predicate devices. The summary states the comparison included "positive, equivocal and negative sera" and "samples from apparently healthy subject (normal population)" and "samples with potential biological cross reactivity." This suggests that the ground truth for these samples was likely established through existing clinical diagnoses and reference methods (including the predicate devices themselves) based on a combination of clinical findings, other laboratory tests, and potentially expert consensus on patient status.

8. The Sample Size for the Training Set

The document does not provide information on a separate "training set" or its sample size. For IVD devices, the characterization of reagents and assay parameters during development might be analogous to "training," but the summary does not detail this.

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

Since no separate training set is explicitly mentioned, there is no information on how its ground truth was established.

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Image /page/0/Picture/0 description: The image shows a logo for "bmd biomedical diagnostics". The letters "bmd" are stacked on top of the words "biomedical diagnostics". There are three black water droplets underneath the letters "b", "m", and "d".

MAR 1 3 2006

Premarket Notification 510(k) Summary

Assigned 510(k) Number: KOS 3653

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 TM CONNECTIVE 10
Common/Usual Name :MX006 - FIDISTM CONNECTIVE 10: Detection test of 10autoantibody specificities: double stranded DNA (dsDNA),SSA 60kDa, SSA 52kDa, SSB, Sm, Sm/RNP, Scl70, Jo-1,Ribosomes and Centromeres.
Classification Name:Immunology and Microbiology Devices

3. Predicate Devices

510K NumberDevice Classification NameManufacturer Name
K950031Varelisa dsDNA antibodiesSweden Diagnostics, GBMH
K944169Varelisa RO (SS-A) antibodiesSweden Diagnostics, GBMH
K944168Varelisa LA (SS-B) antibodiesSweden Diagnostics, GBMH
K042629Varelisa SM antibodiesSweden Diagnostics, GBMH
K993589Varelisa RNP antibodiesSweden Diagnostics, GBMH
K944173Varelisa JO1 antibodiesSweden Diagnostics, GBMH
K944172Varelisa SCL-70 antibodiesSweden Diagnostics, GBMH
K944171Varelisa CENTROMERE antibodiesSweden Diagnostics, GBMH
K981237QuantaLite RIBOSOME P ELISAINOVA Diagnostics, Inc

Page 1 of 3

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

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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 the letters connected and sitting on top of a horizontal line. There are three black droplets or blobs of liquid underneath the letters, appearing to be dripping from the letters above. Below the line, the words "biomedical diagnostics" are written in a smaller, sans-serif font.

4. Intended use of the device

The FIDIS™ CONNECTIVE 10* kit is a semi-quantitative homogeneous fluorescentbased microparticles immunoassays using flow cytometry readings. It is designed for the simultaneous detection of 10 autoantibody specificities: double stranded DNA (dsDNA), SSA 60kDa. SSA 52kDa. SSB, Sm, Sm/RNP, Scl70, Jo-1, Ribosomes and Centromeres.

(* antibodies to dsDNA, Sm, Sm/RNP, SS-A, SS-B, Scl70, Jo1, Ribosomes and Centromeres can be reported using this assay).

The test system is used to screen serum samples and detect the presence of anti-nuclear antibodies associated with connective diseases (systemic lupus erythematosus (SLE), Sjogren's syndrome, mixed connective tissues disease (MCTD) scleroderma, dermatomyositis, polymyositis and CREST syndrome).

5. Description of the Device

The assay kits consist of:

  • a mixture of color-coded microspheres sensitized respectively by dsDNA, SSA 60kDa, SSA 52kDa, SSB, Sm, Sm/RNP, Scl70, Jo-1, Ribosomes and Centromeres.

  • a ready to use anti-human IgG coupled to phycoerythrin,

  • a ready to use calibrator titered for each specificity,

  • a positive control IgG to be diluted.

  • a negative control to be diluted,

  • a 10X concentrated PBS-Tween.

Rk: Calibrators, positive and negative controls are diluted human sera.

6. Summary of the technological characteristics of the device compared to the predicate device

The FIDIS™ System is a fully integrated and automated system for immunodiagnostic testing.

FIDIS™ System comprised of FIDIS flow cytometer, XYP platform for automatic sampling into the analyser, the analyzer itself, a SD pump, some assay products and a MLX-BOOSTER software.

{2}------------------------------------------------

Image /page/2/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. There are some black dots under the letters. The words "biomedical diagnostics" are written in a smaller font below the line.

The FIDIS™ CONNECTIVE 10 kit resembles traditional EIA, but allows simultaneous detection and identification of several antibodies in a single well.

    1. Diluted patient sera and multiplexed bead suspension are thoroughly mixed in the 96 well microtiter plate. Antigen specific antibodies in the patient sera, if present, bind to the immobilised antigen on one or more of the bead sets. Any unbound material is removed by performing a wash step.
    1. Phycoerythrin-conjugated goat anti-human IgG is added to the plate and a further incubation performed. The conjugated anti-human igG binds to the antigen specific antibodies immobilised on the microsphere surface to form an antigen/antibody complex.
    1. The bead suspension is then analysed by the FIDIS™ Instrument and reactions are directly calculated in biological units using specific data software (MLX-BOOSTER).

The FIDIS™ Instrument is able to distinguish the specific color-code of each microsphere types and it could associate the microsphere type with the individual tested antigen.

The FIDIS™ Instrument can quantify the fluorescence of the antibody captured by each microsphere. Measurement of the fluorescent signal from the final reaction complex allows the quantification of the presence or absence of autoantibodies.

It's a simple (just two steps), quick (2 x 30 minutes for the two incubations) and multiple parameter test (10 specific antibodies per patient sample).

7. Testing

The comparability of predicate devices and new devices is supported by a data set including:

  • results obtained within a comparison study analysing positive, equivocal and । negative sera
  • results obtained for samples from apparently healthy subject (normal population) -
  • results obtained for samples from samples with potential biological cross reactivity

8. Conclusions

In conclusion, all available data support that the new devices, FIDIS™ CONNECTIVE 10 kit is substantially equivalent to the predicate devices.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Image /page/3/Picture/2 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized depiction of an eagle or bird-like figure with three curved lines representing its wings or body. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES (USA)" is arranged in a circular fashion around the bird-like figure.

Re:

MAR 1 3 2006

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Christelle Courivaud Regulatory Manager Biomedical Diagnostics Actipole 25 4-6 BLD De Beaubourg Marne La Vallee Cedex 2 France 77435

K053653 Trade/Device Name: FIDIS™ Connective 10 Regulation Number: 21 CFR § 866.5100 Regulation Name: Antinuclear antibody immunological test system Regulatory Class: II Product Code: LLL, LKJ, LKJ, LKO, LKP, LSW, LJM, MQA Dated: February 17, 2006 Received: February 28, 2006

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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

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Page 2 –

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0484. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html

Sincerely yours,

lobatz Beckerh

Robert L. Becker, Jr., MD, PK. Director Division of Immunology and Hematology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Image /page/5/Picture/0 description: The image shows a logo with the text "amg" in a stylized font. The letters are large and bold, with rounded shapes. Below the letters, there is a horizontal line, and below the line is the text "biomedical diagnostics" in a smaller, sans-serif font. The logo appears to be for a company in the biomedical diagnostics field.

510(k) Number: K053653

Device Name:

FIDISTM CONNECTIVE 10

Indications For Use:

The FIDIS™ CONNECTIVE 10* kit is a semi-quantitative homogeneous fluorescent based microparticles immunoassay using flow cytometry readings. It is designed for the simultaneous detection of autoantibody specificities: double stranded DNA (dsDNA), SSA (60 kDA and 52 kDA), SSB, Sm. Sm/RNP, Scl-70, Jo-1 ribosome and centromere in human serum. (* Antibodies to dsDNA, SSA, SSB, Sm, Sm/RNP, Scl-70, Jo-1, ribosome and centromere can be reported using this assay).

Clinical utility:

The test system is used to screen serum samples and detect the presence of antinuclear antibodies associated with connective diseases systemic lupus erythematosus (SLE), Sjogren's syndrome, mixed connective tissue disease (MCTD), scleroderma, dermatomyositis, and CREST syndrome, in conjunction with clinical findings and other laboratory tests.

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OR

Division Sign-Of

Concurrence of CDRH, Office of Device Evaluation (ODE)

Office of In Vitro Diagnostic Dev Evaluation and Safety

510(k) K053653

Prescription Use (Per 21 CFR 801.109)

Professional Use

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

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

§ 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).