K Number

Device Name

FIDIS CELIAC

Manufacturer

BIOMEDICAL DIAGNOSTICS S.A.

Date Cleared

2004-09-24

(158 days)

Product Code

MST MVM

Regulation Number

866.5750

Intended Use

The FIDIS™ Celiac kit is a semi-quantitative homogeneous fluorescent-based microparticles immunoassay using flow cytometry readings. Celian IgA is designed for the simultaneous detection of human IgA isotype antibodies directed against Gliadin and Tissue Transglutaminase Enzyme. Celiac IgG is designed for the detection of human IgG isotype antibodies directed against Gliadin. The presence of these antibodies can be used in conjunction with clinical findings to aid in the diagnosis of Celiac disease. The FIDIS™ Celiac kit is to be used on serum only. FIDIS™ Celiac kits are to be used on FIDIS™ Analyser, software and washer. For in vitro diagnostic use.

Device Description

FIDISTM Celiac is based on Luminex 100TM Technology. The Luminex technology (LabMAP™, Laboratory Multi-Analyte Profiling) is a unique system I ho handler tooning of microspheres, flow cytometer, high speed digital signal processor and an X-Y platform for reading 96-well microtiter plates facilitating automated sample acquisition. This combination allows the diagnostic of multiple biological analytes simultaneously. This multiplexed microsphere-based flow cytometric assay involves fluorescent polystyrene microspheres. The antigen-coated microspheres are mixed and incubated with sample containing the analytes to be detected. A fluorochrome-conjugated detection molecule is subsequently incubated for analyte quantification. The flow cytometer is equipped with a powerful digital signal processor and two lasers. A red "classification" laser, excites fluorescent molecules intrinsic embedded to the microspheres and a green "reporter" laser, excites the extrinsic fluochrome (Phycoerythrin or Alexa-532nm) bound to the microsphere surface. During the sample reading, the flow cytometer analyzes individual microsphere, first, by size, and, second, by fluorescence emissions. Digital signal processors and computers algorithms provide simultaneous real-time acquisition of classification and reporter fluorescence signals output from the microspheres. Upon excitation, the emitted fluorescent signal from the microspheres travels through the optics paths to the individual detectors. According to the fluorescence ratio detected by the red laser, each microsphere is classified into on the basis of its unique fluorescence intensity which allows identifying which analyte is being tested. At the same time, the green "reporter" laser beam excites the external second molecule fluorescence to quantify the specific reaction related to each analyte. Each antigen required for the assay is covalently coupled to an individual set of microspheres through its surface functional groups. The different antigen coupled microspheres are mixed together to constitute the final microspheres reagent. Celiac IgA allows the detection of antigliadin and anti-tissue transglutaminase IgA isotype antibodies. Celiac IgG allows the detection of anti-gliadin IgG isotype antibodies. The test is performed in a 96 wells blank microplate including a filtering membrane at the bottom of the wells. In the first step, the sample is distributed in duplicate for the 2 isotypes (IgA and IgG) selected in each well containing respectively the Celiac A microspheres mixture, for the IgA isotype and the Celiac G microspheres mixture for the IgG isotype. After incubation, a wash step through a filtration process will eliminate the unbound antibodies. A specific conjugate consisting of either anti-human IgA or IgG antibodies coupled to phycoerythrin, is added to the mixture. It will bind to the previously captured antibodies. The reaction is then directly measured by the flow cytometer, which categorizes each microspheres set according to its fluorescence colour the microspheres while simultaneously measuring the average fluorescence emitted by the conjugate. A calibration system allows expressing by interpolation the titer of the sample for each antibody specificity using a specific software developed by bmd. The mixed and antigen-coated microspheres are first incubated with the sample to be analyzed. After the washing step, a phycoerythrin (PE)-labelled secondary anti-human IgA conjugate is added for antibodies quantifications at the surface of each microsphere set. The microspheres are classified on the basis of their unique fluorescence intensity ratio that allows the identity of analyte being tested. Each dot in a white plot corresponds to an individual microsphere.

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Type

Center

Panel

Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

Street 2

City

State

Country Code

ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

K981929, K981929, K993612

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The description details standard flow cytometry and digital signal processing for data acquisition and analysis, but does not mention AI or ML algorithms for interpretation or decision making.

Therapeutic

No.
The device is an in vitro diagnostic (IVD) test designed to detect antibodies associated with Celiac disease for diagnostic purposes, not for treating or preventing a disease.

Diagnostic

Yes

Explanation: The "Intended Use / Indications for Use" section explicitly states, "The presence of these antibodies can be used in conjunction with clinical findings to aid in the diagnosis of Celiac disease." Additionally, the final line of this section states, "For in vitro diagnostic use." These statements clearly indicate the device's diagnostic purpose.

SaMD (Software as a Medical Device)

The device is an in vitro diagnostic (IVD) kit that includes reagents (microspheres, conjugates) and is used on a specific hardware analyzer (FIDIS™ Analyser) which incorporates flow cytometry and digital signal processing. While software is mentioned as part of the system, the core of the device is a physical immunoassay kit and associated hardware.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Explicit Statement: The "Intended Use / Indications for Use" section clearly states: "For in vitro diagnostic use."
Intended Use: The device is designed to detect specific antibodies in human serum to aid in the diagnosis of Celiac disease. This is a classic example of an in vitro diagnostic test, as it analyzes a biological sample (serum) outside of the body to provide information for diagnosis.
Device Description: The description details a laboratory-based assay using flow cytometry to analyze components of a biological sample (serum incubated with microspheres). This process is characteristic of in vitro diagnostic procedures.
Performance Studies: The inclusion of performance studies comparing the device to predicate devices and reporting metrics like sensitivity, specificity, and agreement further supports its classification as an IVD, as these studies are required for regulatory approval of IVDs.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The FIDIS™ Celiac kit is a semi-quantitative homogeneous fluorescent-based microparticles immunoassay using flow cytometry readings.

Celiac IgA is designed for the simultaneous detection of human IgA isotype antibodies directed against Gliadin and Tissue Transglutaminase Enzyme.

Celiac IgG is designed for the detection of human IgG isotype antibodies directed against Gliadin.

The presence of these antibodies can be used in conjunction with clinical findings to aid in the diagnosis of Celiac disease.

The FIDIS™ Celiac kit is to be used on serum only.

FIDIS™ Celiac kits are to be used on FIDIS™ Analyser, software and washer.

For in vitro diagnostic use.

Product codes (comma separated list FDA assigned to the subject device)

MST, MVM

Device Description

FIDIS™ Celiac is based on Luminex 100™ Technology.

The Luminex technology (LabMAP™, Laboratory Multi-Analyte Profiling) is a unique system I ho handler tooning of microspheres, flow cytometer, high speed digital signal processor and an X-Y platform for reading 96-well microtiter plates facilitating automated sample acquisition. This combination allows the diagnostic of multiple biological analytes simultaneously.

This multiplexed microsphere-based flow cytometric assay involves fluorescent polystyrene microspheres. The antigen-coated microspheres are mixed and incubated with sample containing the analytes to be detected. A fluorochrome-conjugated detection molecule is subsequently incubated for analyte quantification.

The flow cytometer is equipped with a powerful digital signal processor and two lasers. A red "classification" laser, excites fluorescent molecules intrinsic embedded to the microspheres and a green "reporter" laser, excites the extrinsic fluochrome (Phycoerythrin or Alexa-532nm) bound to the microsphere surface.

During the sample reading, the flow cytometer analyzes individual microsphere, first, by size, and, second, by fluorescence emissions. Digital signal processors and computers algorithms provide simultaneous real-time acquisition of classification and reporter fluorescence signals output from the microspheres. Upon excitation, the emitted fluorescent signal from the microspheres travels through the optics paths to the individual detectors. According to the fluorescence ratio detected by the red laser, each microsphere is classified into on the basis of its unique fluorescence intensity which allows identifying which analyte is being tested. At the same time, the green "reporter" laser beam excites the external second molecule fluorescence to quantify the specific reaction related to each analyte.

Each antigen required for the assay is covalently coupled to an individual set of microspheres through its surface functional groups. The different antigen coupled microspheres are mixed together to constitute the final microspheres reagent. Celiac IgA allows the detection of antigliadin and anti-tissue transglutaminase IgA isotype antibodies. Celiac IgG allows the detection of anti-gliadin IgG isotype antibodies.

The test is performed in a 96 wells blank microplate including a filtering membrane at the bottom of the wells. In the first step, the sample is distributed in duplicate for the 2 isotypes (IgA and IgG) selected in each well containing respectively the Celiac A microspheres mixture, for the IgA isotype and the Celiac G microspheres mixture for the IgG isotype. After incubation, a wash step through a filtration process will eliminate the unbound antibodies. A specific conjugate consisting of either anti-human IgA or IgG antibodies coupled to phycoerythrin, is added to the mixture. It will bind to the previously captured antibodies.

The reaction is then directly measured by the flow cytometer, which categorizes each microspheres set according to its fluorescence colour the microspheres while simultaneously measuring the average fluorescence emitted by the conjugate. A calibration system allows expressing by interpolation the titer of the sample for each antibody specificity using a specific software developed by bmd.

The mixed and antigen-coated microspheres are first incubated with the sample to be analyzed. After the washing step, a phycoerythrin (PE)-labelled secondary anti-human IgA conjugate is added for antibodies quantifications at the surface of each microsphere set.

The microspheres are classified on the basis of their unique fluorescence intensity ratio that allows the identity of analyte being tested. Each dot in a white plot corresponds to an individual microsphere.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Precision/Reproducibility:
Patient sera were analyzed on the FIDIS™ Celiac to evaluate both intra-assay and inter-assay reproducibility. Samples included low, moderate, and high positives for each analyte.

Within-run (10 tests in the same run):
- tTG IgA: Mean CV(%) ranged from 3.9 to 4.6
- Glia IgA: Mean CV(%) ranged from 2.3 to 5.5
- Glia IgG: Mean CV(%) ranged from 2.3 to 4.4
Between-run (5 tests in 5 different runs):
- tTG IgA: Mean CV(%) ranged from 3.7 to 7.0
- Glia IgA: Mean CV(%) ranged from 2.4 to 3.1
- Glia IgG: Mean CV(%) ranged from 4.6 to 7.2

Linearity: Autoantibodies are measured as an estimation of binding capacity. The assay is optimized for average binding capacity at a 1/200 dilution, measured by flow cytometry using the median fluorescence value from 400 microspheres per parameter. Linearity is sera-dependent, and there is no dilution effect.

Assay cut-off:

Negative: 20U/mL for the 3 specificities

Comparison with predicate devices: Study was performed on 182 samples (66 celiac disease, 55 blood donors, biological interferences). Borderline results were considered negative for calculation.

Gliadin IgA: Positive percent agreement: 77.5% (55/71); Negative percent agreement: 98.2% (109/111); Overall agreement: 90.1% (164/182)
tTG IgA: Positive percent agreement: 94.0% (44/47); Negative percent agreement: 100% (135/135); Overall agreement: 98.3% (179/182)
Gliadin IgG: Positive percent agreement: 90% (54/60); Negative percent agreement: 100% (122/122); Overall agreement: 96.7% (176/182)

Clinical studies:

Clinical sensitivity: Not applicable.
Clinical specificity:
- Gliadin IgG: 97% for FIDIS™ Celiac (compared to 94% for Bindazyme™) on 116 samples from blood donors and biological interferences.
- Gliadin IgA: 91% for FIDIS™ Celiac (compared to 81% for Bindazyme™) on 116 samples from blood donors and biological interferences.
- tTG IgA: 99% for FIDIS™ Celiac (compared to 99% for Bindazyme™) on 116 samples from blood donors and biological interferences.

Threshold values and normal range values: Estimated from 55 blood donor samples and 61 samples with potential biological interferences.

Negative threshold (

Regulation Number and Section

§ 866.5750 Radioallergosorbent (RAST) immunological test system.

(a)
Identification. A radioallergosorbent immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the allergen antibodies (antibodies which cause an allergic reaction) specific for a given allergen. Measurement of specific allergen antibodies may aid in the diagnosis of asthma, allergies, and other pulmonary disorders.(b)
Classification. Class II (special controls). The device, when intended to detect any of the allergens included in Table 1 in this paragraph, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9. Table 1—Class II Exempt Allergens Under § 866.5750—Radioallergosorbent (RAST) Immunological Test Systems
Allergen code Allergen product Source (taxonomical name) Grass Pollens g1 Sweet vernal grass Anthoxanthum odoratum. g3 Cocksfoot grass, Orchard grass Dactylis glomerata. g4 Meadow fescue Festuca elatior. g5 Rye-grass (perennial rye grass) Lolium perenne. g7 Common reed (common reed grass) Phragmites communis. g8 Meadow grass, Kentucky blue (June grass) Poa pratensis. g9 Redtop, Bentgrass Agrostis stolonifera ,Agrostis gigantea (Agrostis alba ). g11 Brome grass Bromus inermis. g12 Cultivated rye (cultivated rye grass) Secale cereale. g13 Velvet grass Holcus lanatus. g14 Cultivated oat (cultivated oat grass) Avena sativa. g15 Cultivated wheat (cultivated wheat grass) Triticum aestivum (Triticum spp.). g16 Meadow foxtail (meadow foxtail grass) Alopecurus pratensis. g17 Bahia grass Paspalum notatum. g24 Wheat grass, Western Agropyron smithii (Elymus smithii ). g30 Bluegrass, annual Poa annua. g70 Wild rye grass Elymus triticoides Elymus condensatus. g71 Canary grass Phalaris arundinacea. g201 Barley, cultivated Hordeum vulgare. g202 Maize, corn (cultivated corn) Zea mays. g203 Salt grass Distichlis spicata. g204 False oat-grass Arrhenatherum elatius. g216 Cyn d 1 Cynodon dactylon. g701 Phl p 1.0102, Phl p 5.0101 Phleum pratense. g702 Phl p 7.0101 Phleum pratense. g703 Phl p 12.0101 Phleum pratense. Weed Pollens w2 Western ragweed Ambrosia psilostachya. w4 False ragweed Ambrosia acanthicarpa (Franseria acanthicarpa ). w5 Wormwood Artemisia absinthium Artemisia annua. w6 Mugwort Artemisia vulgaris. w7 Marguerite, ox-eye daisy Chrysanthemum leucanthemum. w8 Dandelion Taraxacum vulgare ,Taraxacum officinale. w9 Plantain (English), Ribwort Plantago lanceolata. w10 Goosefoot, lamb's quarters Chenopodium album. w11 Saltwort (prickly), Russian thistle Salsola kali (Salsola pestifer ). w12 Goldenrod Solidago virgaurea (Solidago spp.). w13 Cocklebur, common Xanthium commune. w14 Common pigweed (rough pigweed) Amaranthus retroflexus. w15 Scale, Lenscale Atriplex lentiformis. w16 Rough marsh elder Iva ciliate ,Iva annua. w17 Firebush (Kochia) Kochia scoparia. w18 Sheep sorrel Rumex acetosella. w19 Wall pellitory Parietaria officinalis. w20 Nettle (Common stinging nettle) Urtica dioica. w21 Wall pellitory Parietaria judaica. w22 Japanese hop (careless weed) Humulus japonicas (Humulus scandens ). w23 Yellow dock, Yellow dockweed Rumex crispus. w24 Spiny pigweed Amaranthus spinosus. w27 Carnation Dianthus spp. w28 Rose Rosa rugosa. w33 Clover Trifolium pratense. w35 Mexican tea Chenopodium ambrosioides. w36 Rabbit bush Ambrosia deltoidea (Franseria deltoides ). w37 Salt bush, annual Atriplex wrightii. w39 Water hemp, Western Amaranthus rudis (Acnida tamariscina ). w41 Burrobrush Hymenoclea salsola. w42 Poverty weed Baccharis neglecta. w43 Common sagebrush Artemisia tridentata. w45 Alfalfa Medicago sativa. w46 Dog fennel Eupatorium capillifolium. w53 Geranium Geranium spp. w67 Groundsel bush Baccharis halimifolia. w69 Iodine bush Allenrolfea occidentalis. w70 Ragweed, slender Ambrosia confertiflora. w75 Wing scale (wingscale) Atriplex canescens. w82 Careless weed Amaranthus palmeri ,Amaranthus hybridus. w90 Japanese hop Humulus japonicas (Humulus scandens ). w203 Rape (rape pollen) Brassica napus. w204 Sunflower Helianthus annuus. w206 Camomile Matricaria chamomilla. w207 Lupin Lupinus spp. w210 Sugar-beet Beta vulgaris. w211 Par j 2.0101 Parietaria judaica. w231 Art v 1 Artemisia vulgaris (Mugwort). w232 Sal k 1 Salsola kali. w233 Art v 3 Artemisa vulgaris (LTP, Mugwort). w234 Pla l 1 Plantago lanceolata. w235 Che a 1.0101 Chenopodium album. w236 Mer a 1.0101 Mercurialis annua. a753 Art v 1 Artemisia vulgaris (Mugwort weed). Tree Pollens t1 Box-elder (Maple) Acer negundo ,Acer saccharum. t2 Gray alder, speckled alder (alder) Alnus incana. t4 Hazel, hazelnut Corylus avellana ,Corylus americana. t5 American beech (beech) Fagus grandifolia (Fagus americana ). t6 Mountain juniper, Mountain cedar Juniperus ashei (Juniperus sabinoides ). t8 Elm Ulmus americana. t9 Olive Olea europaea. t10 Walnut Juglans californica ,Juglans nigra. t11 Maple leaf sycamore, London plane, Plane tree Platanus acerifolia. t61 Sycamore Platanus occidentalis. t12 Willow Salix caprea ,Salix nigra. t14 Cottonwood (Eastern Cottonwood/Black Cottonwood) Populus deltoides. t15 White ash Fraxinus americana. t16 White pine Pinus strobus. t18 Eucalyptus, gum-tree Eucalyptus globulus (Eucalyptus spp.). t19/t26 Acacia Acacia longifolia (Acacia spp.). t20 Mesquite Prosopis glandulosa/ Prosopis juliflora. t21 Melaleuca, cajeput tree Melaleuca quinquenervia (Melaleuca leucadendron ). t22 Pecan, hickory Carya illinoinensis (Carya pecan ). t23 Italian/Mediterranean/funeral cypress Cupressus sempervirens. t24 Japanese cypress Chamaecyparis obtusa (Chamaecyparis spp.). t25 Ash Fraxinus excelsior. t27 Maple, red Acer rubrum. t29 Acacia Acacia spp. t30 Birch, white Betula populifolia. t32 Willow, black Salix nigra. t33 Ash, Arizona Fraxinus velutina. t35 Cedar, salt Tamarix gallica. t37 Bald cypress (white bald cypress) Taxodium distichum. t38 Elm, Chinese/Siberian Ulmus pumila. t40 Hazelnut tree Corylus americana. t41 White hickory Carya alba (Carya tomentosa ). t42 Oak, red Quercus rubra. t43 Loblolly pine Pinus taeda. t44 Hackberry Celtis occidentalis. t45 Cedar elm Ulmus crassifolia. t47 Juniper, one seed Juniperus monosperma. t48 Pine, lodgepole Pinus contorta. t49 Pine, ponderosa Pinus ponderosa. t50 Beech, European Fagus sylvatica. t51 Tree of Heaven Ailanthus altissima. t52 Western white pine Pinus monticola. t54 Russian olive Elaeagnus angustifolia. t55 Scotch broom Cytisus scoparius. t56 Bayberry Myrica cerifera. t57 Red cedar Juniperus virginiana. t60 Western juniper Juniperus occidentalis. t61 Sycamore Platanus occidentalis. t70 Mulberry (white mulberry) Morus alba. t71 Red mulberry Morus rubra. t72 Queen palm Arecastrum romanzoffiamon. t73 Australian pine Casuarina equisetifolia. t77 Oak mix (red, white, black) Quercus spp. t80 Japanese cypress Chamaecyparis obtusa. t81 Japanese alder Alnus japonica. t83 Mango tree Mangifera indica. t90 Walnut, black Juglans nigra. t96 Poplar, white (poplar) Populus alba. t103/t218 Virginia live oak (live oak) Quercus virginiana. t105 Pepper tree Schinus molle. t110 Orange tree Citrus sinensis. t201 Spruce, Norway spruce Picea abies (Picea excelsa ). t202 Alder, smooth Alnus incana spp.Rugosa (Alnus rugosa ). t203 Horse chestnut Aesculus hippocastanum. t205 Elder Sambucus nigra. t206 Chestnut Castanea sativa. t207 Douglas fir Pseudotsuga menziesii (Pseudotsuga taxifolia ). t208 Linden Tilia cordata. t209 Horn beam Carpinus betulus. t210 Privet Ligustrum vulgare. t211 Sweet gum Liquidambar styraciflua. t212 Cedar Libocedrus decurrens. t213 Pine Pinus radiata. t214 Date palm Phoenix canariensis. t215 Lilac Syringa vulgaris. t217 Pepper tree Schinus molle. t217 Red alder Alnus rubra. t218 Virginia live oak Quercus virginiana. t218 Bayberry (bayberry/sweet gale) Myrica gale. t219 Palo verde Cercidium floridum. t219 Red cedar Juniperus virginiana. t220 Bet v 4 Betula verrucosa (Birch). t221 Bet v 2.0101, Bet v 4 Betula verrucosa (Birch). t222 Cypress (Arizona cypress) Cupressus arizonica. t223 Oil palm Elaeis guineensis. t224 Ole e 1 Olea europaea. t225 Bet v 6 Betula verrucosa (Birch). t226 Cup a 1 Cupressus arizonica. t227 Ole e 7 Olea Europaea. t228 Aspen, quaking Populus tremuloides. t229 Eastern hemlock Tsuga canadensis. t230 Redwood (sequoia) Sequoia sempervirens. t232 Pussy willow Salix discolor. t240 Ole e 9.0101 Olea Europaea. t241 Pla a 1.0101 Platanus acerifolia. t242 Pla a 2 Platanus acerifolia. t243 Pla a 3.0101 Platanus acerifolia. t244 Cor a 1.0103 Corylus avellana. t245 Aln g 1.0101 Alnus glutinosa. t246 Cry j 1 Cryptomeria japonica. t280 Locust tree Robinia pseudoacacia. t401 Brazilian peppertree Schinus terebinthifolius. t402 Mastic tree Pistacia lentiscus. t404 Tree of heaven Ailanthus altissima. t406 Date palm Phoenix dactylifera. a482 Ole e 1 Olea europaea (Olive Oil). Mites d207 Blo t 5.0101 Blomia tropicalis. d208 Lep d 2.0101 Lepidoglyphus destructor. Microorganisms, Molds, Yeast m1 Penicillium chrysogenum (Penicillium notatum ) Penicillium chrysogenum (Penicillium notatum ). m2 Cladosporium herbarum (Hormodendrum ) Cladosporium herbarum (Hormodendrum ). m3 Aspergillus fumigatus Aspergillus fumigatus. m4 Mucor racemosus Mucor racemosus. m5 Candida albicans Candida albicans. m7 Botrytis cinerea Botrytis cinerea. m8 Drechslera halodes (Setomelanomma rostrata, Helminthosporium halodes, Helminthosporium interseminatum ) Drechslera halodes (Setomelanomma rostrata, Helminthosporium halodes. m9 Fusarium moniliforme (Fusarium proliferatum ) Fusarium moniliforme (Fusarium proliferatum ). m10 Stemphylium botryosum Stemphylium herbarum (Stemphylium botryosum ). m11 Rhizopus nigricans Rhizopus nigricans. m12 Aureobasidium pullulans Aureobasidium pullulans. m13 Phoma betae Phoma betae. m14 Epicoccum purpurascens Epicoccum purpurascens (Epicoccum nigrum ). m15 Trichoderma viride Trichoderma viride. m16 Curvularia lunata Curvularia lunata ,Curvularia specifera (K923044 ). m17 Cladosporium fulvum Cladosporium fulvum. m18 Fusarium culmorum Fusarium culmorum. m19 Aspergillus versicolor Aspergillus versicolor. m20 Mucor mucedo Mucor mucedo. m21 Aspergillus clavatus Aspergillus clavatus. m22 Micropolyspora faeni Saccharopolyspora rectivirgula (Micropolyspora faeni ). m23 Thermoactinomyces vulgaris Thermoactinomyces vulgaris. m24 Stachybotrys atra Stachybotrys chartarum (Stachybotrys atra ). m24 Paecilomyces spp Paecilomyces spp. m25 Aspergillus versicolor Aspergillus versicolor. m25 Penicillium brevicompactum Penicillium brevicompactum. m26 Cladosporium cladosporioides Cladosporium cladosporioides. m26 Penicillium citrinum Penicillium citrinum. m27 Penicillium spp Penicillium spp. m29 Aspergillus repens Aspergillus repens. m30 Penicillium roqueforti Penicillium roqueforti. m32 Cladosporium cladosporioides Cladosporium cladosporioides. m34 Serpula lacrymans Serpula lacrymans. m36 Aspergillus terreus Aspergillus terreus. m37 Trichophyton mentagrophytes Trichophyton mentagrophytes. m40 Aspergillus amstelodami Aspergillus amstelodami. m43 Saccharomyces Carlsberg Saccharomyces carlsbergensis. m44 Saccharomyces cerevisiae Saccharomyces cerevisiae. m45 Hormodendrum hordei Hormodendrum hordei. m46 Bipolaris spicifera Bipolaris spicifera. m47 Aspergillus nidulans Aspergillus nidulans. m48 Aspergillus oryzae Aspergillus oryzae. m49 Fusarium oxysporum Fusarium oxysporum. m50 Micropolyspora faeni Saccharopolyspora rectivirgula (Micropolyspora faeni ). m51 Thermoactinomyces vulgaris Thermoactinomyces vulgaris. m53 Microspora canis Microsporum canis (Microspora canis ). m54 Aspergillus flavus Aspergillus flavus. m63 Helminthosporium intersemin Helminthosporium intersemin. m66 Mucor plumbeus Mucor plumbeus. m67 Mycogone Mycogone perniciosa. m68 Nigrospora oryzae Nigrospora oryzae. m69 Rhodotorula Rhodotorula rubra (Rhodotorula mucilaginosa ). m70 Malassezia furfur (Pityrosporum orbiculare ) Malassezia furfur (Pityrosporum orbiculare ). m71 Spondylocladium Spondylocladium spp. m72 Epidermophyton Epidermophyton floccosum. m73 Epicoccum nigrum Epicoccum purpurascens (Epicoccum nigrum ). m80 Staphylococcal enterotoxin A (Sta a SEA ) Staphylococcus aureus. m80 Helminthosporium spp Helminthosporium spp. m81 Staphylococcal enterotoxin B (Sta a SEB ) Staphylococcus aureus. m88 Stemphylium solani Stemphylium solani. m93 Gliocladium fimbriatum Gliocladium fimbriatum. m94 Phycomyces blakesleeanus Phycomyces blakesleeanus. m201 Tilletia tritici (Ustilago nuda, Ustilago tritici ) (Barley smut) Tilletia tritici (Ustilago nuda, Ustilago tritici ). m202 Acremonium kiliense (Cephalosporium acremonium ) Acremonium kiliense (Cephalosporium acremonium ). m203 Trichosporon pullulans Trichosporon pullulans. m204 Ulocladium chartarum Ulocladium chartarum. m205 Trichophyton rubrum Trichophyton rubrum. m207 Aspergillus niger Aspergillus niger. m208 Chaetomium globosum Chaetomium globosum. m209 Penicillium frequentans Penicillium glabrum (Penicillium frequentans ). m209 Stachybotrys chartarum Stachybotrys chartarum (Stachybotrys atra ). m210 Trichophyton mentagrophytes var. goetzii Trichophyton mentagrophytes var. goetzii. m211 Trichophyton mentagrophytes var. interdigitale Trichophyton mentagrophytes var. interdigitale. m211 Oat smut Ustilago avenae. m212 Micropolyspora faeni Saccharopolyspora rectivirgula (Micropolyspora faeni ). m212 Geotrichum candidum Geotrichum candidum. m213 Bermuda grass smut Ustilago cynodontis. m214 Johnson grass smut Sphacelotheca cruenta. m215 Corn smut Ustilago maydis. m218 Asp f 1.0101 Aspergillus fumigatus. a3050 Asp r 1 Aspergillus restrictus. m219 Asp f 2 Aspergillus fumigatus. m220 Asp f 3.0101 Aspergillus fumigatus. m221 Asp f 4 Aspergillus fumigatus. m222 Asp f 6.0101 Aspergillus fumigatus. m223 Staphylococcal enterotoxin C (Sta a SEC ) Staphylococcus aureus. m224 Staphylococcal enterotoxin D (Sta a SED ) Staphylococcus aureus. m226 Staphylococcal enterotoxin TSST (Sta a TSST ) Staphylococcus aureus. m227 Malassezia spp. (Pityrosporum spp.) Malassezia spp. (Pityrosporum spp.). m228 Aspergillus flavus. m229 Alt a 1.0101 Alternaria alternata (Alternaria tenuis ). m230 Alt a 6.0101 Alternaria alternata (Alternaria tenuis ). m231 Cla h 8.0101 Cladosporium herbarum (Hormodendrum ). m300 Eurotium spp Eurotium spp. m304 Aspergillus oryzae Aspergillus oryzae. m305 Penicillium brevicompactum Penicillium brevicompactum. m309 Aspergillus terreus Aspergillus terreus. m310 Aspergillus nidulans Aspergillus nidulans. m311 Aspergillus flavus Aspergillus flavus. m312 Aspergillus clavatus Aspergillus clavatus. Epidermal & Animal e6 Guinea pig epithelium Cavia porcellus. e7 Pigeon droppings Columba palumbus ,Columba livia. e25 Chicken serum Gallus domesticus (Gallus gallus domesticus; Gallus spp.). e26 Parrot serum Psittacoidea spp. e62 Camel Camelus dromedaries. e70 Goose feathers Anser anser. e71 Mouse epithelium Mus musculus (Mus spp.). e73 Rat epithelium Rattus norvegicus. e74 Rat urine proteins Rattus norvegicus ,Rattus rattus. e75 Rat serum proteins Rattus norvegicus ,Rattus rattus. e76 Mouse serum proteins Mus musculus (Mus spp.). e77 Budgerigar droppings Melopsittacus undulatus. e78 Budgerigar feathers Melopsittacus undulatus. e79 Budgerigar serum proteins Melopsittacus undulatus. e80 Goat epithelium Capra hircus. e81 Sheep epithelium Ovis aries (Ovis spp.). e82 Rabbit epithelium Oryctolagus cuniculus (Oryctolagus spp.). e83 Swine epithelium Sus scrofa (Sus scrofa domesticus; Sus spp.). e84 Hamster epithelium Cricetus cricetus, Mesocricetus auratus, and Phodopus sungorus. e85 Chicken feathers Gallus domesticus (Gallus gallus domesticus; Gallus spp.). e86 Duck feathers Anas platyrhynchos. e87 Rat epithelium, serum proteins, and urine proteins Rattus norvegicus Rattus rattus. e88 Mouse epithelium, serum proteins, and urine proteins (mouse) Mus musculus (Mus spp.). e89 Turkey feathers Meleagris gallopavo. e90 Budgerigar serum proteins, feathers, and droppings Melopsittacus undulatus. e91 Pigeon serum proteins, feathers, and droppings Streptopelia roseogrisea ,Psittacidae spp. e92 Parrot serum proteins, feathers, and droppings Ara spp. e93 Pigeon serum proteins Streptopelia roseogrisea. e94 Fel d 1.0101 Felis domesticus. a345 Fel d 1 Felis domesticus. e98 Parrot droppings Psittacoidea spp. e101 Can f 1.0101 Canis familiaris (Canis domesticus ). a174 Can f 1 Canis familiaris (Canis domesticus ). e102 Can f 2.0101 Canis familiaris (Canis domesticus ). e196 Parakeet feathers Nymphicus hollandicus. e197 Parakeet droppings Nymphicus hollandicus. e198 Parakeet serum Nymphicus hollandicus. e199 Canary bird serum Serinus canarius. e200 Canary bird droppings Serinus canarius. e201 Canary bird feathers (Canary feathers) Serinus canarius. e202 Reindeer epithelium Rangifer tarandus. e203 Mink epithelium Mustela spp. e204 Bos d 6 Bos domesticus (Bos taurus; Bos spp.). e205 Horse, serum proteins Equus caballus (Equus spp.). e206 Rabbit, serum proteins Oryctolagus cuniculus (Oryctolagus spp.). e208 Chinchilla epithelium Chinchilla laniger. e209 Gerbil epithelium Meriones unguiculatus. e210 Fox epithelium Vulpes vulpes. e211 Rabbit, urine proteins Oryctolagus cuniculus (Oryctolagus spp.). e212 Swine, urine proteins Sus scrofa (Sus scrofa domesticus; Sus spp.). e213 Parrot feathers Ara spp. e214 Finch feathers Lonchura domestica. e215 Pigeon feathers Streptopelia roseogrisea (Streptopelia spp.),Columbia spp. e216 Deer epithelium Dama dama. e217 Ferret epithelium Mustela putorius. e218 Chicken droppings Gallus domesticus (Gallus gallus domesticus; Gallus spp.). e219 Chicken, serum proteins Gallus domesticus (Gallus gallus domesticus; Gallus spp.). e220 Fel d 2, Cat serum albumin Felis domesticus. e221 Can f 3 Canis familiaris (Canis domesticus ) (Dog serum albumin ). e222 Swine serum albumin (Sus s PSA) Sus scrofa (Sus scrofa domesticus; Sus spp.). e225 Lovebird feathers Psittacoidea agapomis. e226 Can f 5.0101 Canis familiaris. e227 Equ c 1.0101 Equus caballus. e228 Fel d 4.0101 Felis domesticus. e230 Equ c 3 Equus caballus. e231 Mus m 1 Mus musculus. Food f9 Rice Oryza sativa. f12 Pea (green pea) Pisum sativum. f15 White bean Phaseolus vulgaris. f19 Cayenne pepper Capsicum frutescens (Capsicum annum ). f21 Sugar cane Saccharum officinarum. f22 Raspberry Rubus idaeus. f26 Pork Sus scrofa (Sus scrofa domesticus; Sus spp.). f29 Watermelon Citrullus lanatus (Citrullus vulgaris ). f31 Carrot Daucus carota. f32 Oyster mushroom Pleurotus ostreatus. f33 Orange Citrus sinensis. f35 Potato Solanum tuberosum. f43 Mother's milk Homo sapiens. f44 Strawberry Fragaria vesca (Fragaria spp.). f45 Yeast, baker's Saccharomyces cerevisiae. f46 Pepper, Red Capsicum annuum. f47 Garlic Allium sativum. f48 Onion Allium cepa. f49 Apple Malus x domestica (Malus spp.). f51 Bamboo shoot Phyllostachys pubescens. f52 Cacao/chocolate Theobroma cacao. f54 Sweet potato Ipomoea batatas. f55 Common millet Panicum miliaceum. f56 Foxtail millet Setaria italica. f57 Japanese millet Echinochloa crus-galli. f58 Pacific squid Todarodes pacificus. f59 Octopus Octopus vulgaris (Octopus spp.). f63 Kefir NA. f67 Parmesan cheese NA. f81 Cheese, cheddar type NA. f82 Cheese, mold type NA. f83 Chicken Gallus domesticus (Gallus gallus domesticus; Gallus spp.). f86 Parsley Petroselinum crispum. f87 Melon Cucumis melo Cucumis melo + Citrullus lanatus. f88 Mutton (lamb) Ovis aries (Ovis spp.). f90 Malt Hordeum vulgare. f92 Banana Musa spp. f93 Cacao Theobroma cacao. f94 Pear Pyrus communis (Pyrus spp.). f97 Yam Dioscorea spp.Dioscorea opposita. f97 Chamomile tea Matricaria chamomilla. f98 Gliadin Triticum aestivum (Triticum spp.). f102 Cantaloupe Cucumis melo var. cantalupensis. f105 Chocolate Theobroma cacao. f109 Cottonseed Gossypium hirsutum. f110 Giant radish Raphanus sativus. f118 Zucchini Cucurbita pepo. f119 Radish Raphanus sativus. f120 Venison Capreolus capeolus. f121 Pinto bean Phaseolus vulgaris. f122 Cheese, American NA. f127 Black-eyed pea Vigna unguiculata. f131 Black Olive Olea europaea. f136 Red beet Beta vulgaris var. conditiva. f139 Goat's Cheese Capra aegagrus. f140 Bran NA. f141 Corn (vegetables) Zea mays. f152 Green bell pepper Capsicum annuum. f155 Brewer's yeast Saccharomyces carlsbergensis. f157 Duck Anas domesticus. f158 Goose Anser anser. f160 Camembert cheese NA. f162 Nectarine Prunus persica var. nucipersica. f163 Kohlrabi Brassica oleracea var. gongylodes. f65 Perch f166 Leek Allium porrum. f170 Cheese (Switzerland) (Swiss cheese) NA. f174 Fig Ficus carica. f177 Cranberry Vaccinium macrocarpon. f179 Raisin Vitis spp. f182 Lima bean Phaseolus lunatus. f198 Flaxseed (bruised grain) Linum usitatissimum. f199 Untreated native milk Bos domesticus (Bos taurus; Bos spp.). f208 Lemon Citrus limon. f209 Grapefruit Citrus paradisi. f210 Pineapple Ananas comosus. f211 Blackberry Rubus fruticosus. f212 Mushroom (champignon) Agaricus hortensis (Agaricus spp.). f213 Rabbit Oryctolagus cuniculus (Oryctolagus spp.). f214 Spinach Spinacia oleracea. f215 Lettuce Lactuca sativa. f216 Cabbage Brassica oleracea var. capitata. f217 Brussels sprouts Brassica oleracea var. gem. f218 Paprika, sweet pepper Capsicum annuum. f219 Fennel seed Foeniculum vulgare. f219 Sage Salvia officinalis. f220 Cinnamon Cinnamomum spp. f221 Coffee Coffea spp. f222 Tea Camellia sinensis. f223 Green olive Olea europaea. f225 Summer squash, pumpkin Cucurbita pepo. f225 Pumpkin Cucurbita maxima. f226 Pumpkin seed Cucurbita pepo. f227 Sugar-beet seed Beta vulgaris. f229 Safflower Seed Carthamus tinctorius. f231 Milk, boiled Bos domesticus (Bos taurus; Bos spp.). f234 Vanilla Vanilla planifolia. f237 Apricot Prunus armeniaca. f241 Gouda cheese NA. f242 Cherry Prunus avium. f244 Cucumber Cucumis sativus. f246 Guar, guar gum Cyamopsis tetragonoloba. f247 Honey NA. f248 Rosemary Rosmarinus officinalis. f254 Plaice Pleuronectes platessa. f255 Plum Prunus domestica ,Prunus americana. f258 Squid Loligo spp. f259 Grape Vitis vinifera (Vitis spp.). f260 Broccoli Brassica oleracea var. italica (Brassica oleracea var. cultivar ). f261 Asparagus Asparagus officinalis. f262 Aubergine, eggplant Solanum melongena. f263 Green pepper Piper nigrum ,Capsicum annuum. f264 Eel Anguilla anguilla. f265 Caraway Carum carvi. f265 Cumin Cuminum cyminum. f266 Mace Myristica fragrans. f267 Cardamon Elettaria cardamomum. f268 Clove Syzygium aromaticum. f269 Basil Ocimum basilicum. f270 Ginger Zingiber officinale. f271 Anise Pimpinella anisum. f272 Tarragon Artemisia dracunculus. f273 Thyme Thymus vulgaris. f274 Marjoram Origanum majorana. f275 Lovage Levisticum officinale. f276 Fennel, fresh Foeniculum vulgare. f277 Dill Anethum graveolens. f278 Bay leaf Laurus nobilis. f279 Chili pepper Capsicum frutescens. f280 Black pepper Piper nigrum. f281 Curry (Santa Maria) NA. f282 Nutmeg Myristica fragrans. f283 Oregano Origanum vulgare. f284 Turkey meat Meleagris gallopavo. f285 Elk/moose meat Alces spp. f286 Mare's milk Equus caballus (Equus spp.). f287 Red kidney bean Phaseolus vulgaris. f288 Blueberry Vaccinium myrtillus (Vaccinium spp.). f289 Date Phoenix dactylifera. f291 Cauliflower Brassica oleracea var. botrytis. f292 Guava Psidium guajava. f293 Papaya Carica papaya. f294 Passion fruit, Maracuja Passiflora edulis (Passiflora spp.). f295 Carambola Averrhoa carambola. f296 Carob Ceratonia siliqua. f297 Gum Arabic Acacia senegal (Acacia spp.). f298 Tragacanth Astragalus spp. f299 Sweet chestnut (chestnut) Castanea sativa. f300 Pinto bean Phaseolus spp. f301 Persimmon (kaki fruit, sharon) Diospyros kaki. f302 Mandarin (tangerine, clementine, satsumas) Citrus reticulata. f305 Fenugreek Trigonella foenum-graecum. f306 Lime Citrus aurantifolia. f307 Hake Merluccius merluccius. f308 Sardine (pilchard) Sardina pilchardus. f310 Blue vetch Lathyrus sativus. f311 Megrim Lepidorhombus whiffiagonis. f315 Green bean Phaseolus vulgaris. f316 Rape seed Brassica napus. f317 Coriander Coriandrum sativum. f318 Jack fruit Artocarpus heterophyllus. f319 Beetroot Beta vulgaris. f320 Crayfish Astacus astacus. f321 Horse meat Equus caballus (Equus spp.). f322 Red currant Ribes sylvestre. f324 Hop (fruit cone) Humulus lupulus. f325 Saffron Colchicum autumnale. f328 Fig Ficus carica. f329 Watermelon Citrullus lanatus. f330 Rose hip Rosa spp. f331 Saffron Crocus sativus. f332 Mint Mentha piperita. f333 Linseed Linum usitatissimum. f336 Jujube Ziziphus jujuba. f336 Wine vinegar Vitis vinifera (Vitis spp.). f337 Sole Solea solea. f337 English sole Parophrys vetulus. f338 Wine, white Vitis vinifera (Vitis spp.). f339 Allspice Pimenta dioica. f339 Wine, red Vitis vinifera (Vitis spp.). f341 Cranberry Vaccinium oxycoccus ,Vaccinium macrocarpon. f342 Olive (black, fresh) Olea europaea. f343 Raspberry Rubus idaeus. f344 Sage Salvia officinalis. f346 Chives Allium schoenoprasum. f347 Quinoa Chenopodium quinoa. f348 Litchi Litchi chinensis. f349 Chum salmon roe Oncorhynchus keta. f358 Artichoke Cynara scolymus. f360 Yogurt NA. f368 Black bass Micropterus dolomieu (Micropterus dolomieui ). f374 Karaya gum Sterculia urens. f375 Horseradish Armoracia rusticana. f377 Maple syrup NA. f379 Okra Abelmoschus esculentus. f382 Beet, sugar Beta vulgaris var. altissima. f401 Loquat Eriobotrya japonica. f402 Fig Ficus carica. f403 Brewer's yeast Saccharomyces cerevisiae. f405 Mint Mentha spp. f406 Arugula Eruca vesicaria. House Dust h1 Greer Labs., Inc NA. h2 Hollister-Stier Labs NA. h6 Japan NA. Venoms & Insects i7 Midge Chironomus yoshimatsui. i8 Moth Bombyx mori ,Heterocera spp. i47 Water flea Daphnia spp. i49 Deer fly Chrysops spp. i51 Black ant Camponotus pennsylvanicus. i54 Flea mix (dog/cat), common flea Ctenocephalides spp. i71 Mosquito Aedes communis ,Aedes spp.and Culex spp. i72 Green nimitti Cladotanytarsus lewisi. i73 Blood worm Chironomus thummi ,Chironomusri parius ,Chironomus spp. i75 European hornet Vespa crabro. i76 Berlin beetle Trogoderma angustum. i77 European paper wasp Polistes dominulus. i78 Fly Musca domestica. i80 Bumblebee Bombus pennsylvanicus. i201 Horse bot fly Gasterophilus intestinalis. i202 Grain weevil Sitophilus granarius. i203 Mediterranean flour moth Ephestia kuehniella (Anagasta kuehniella ). i204 Horse fly Tabanus spp. i205 Bumblebee Bombus terrestris. i208 Api m 1.0101 Apis mellifera. a45 Api m 1 Apis mellifera. i209 Ves v 5.0101 Vespula vulgaris. a670 Ves v 5 Vespula vulgaris. i210 Pol d 5.0101 Polistes dominulus. i211 Ves v 1.0101 Vespula vulgaris. i213 Api m 4 Apis mellifera. i214 Api m 2 Apis mellifera. i215 Api m 3 Apis mellifera. i216 Api m 5 Apis mellifera. i217 Api m 10 Apis mellifera. i220 Bla g 1.0101 Blattella germanica. i221 Bla g 2.0101 Blattella germanica. i222 Bla g 5.0101 Blattella germanica. i223 Bla g 7 Blattella germanica. a46 Api m 2 Apis mellifera. Miscellaneous o1 Cotton, crude fibers Gossypium spp. o3 Cotton (treated) Gossypium spp. o70 Seminal fluid Homo sapiens. o71 Staphylococcus aureus Staphylococcus aureus. o72 Pichia pastoris crude extract customer specific Pichia pastoris. o72 Sperm-sediment Homo sapiens. o73 Pichia pastoris crude extr. vector customer specific Pichia pastoris. o74 Pichia pastoris with vector customer specific Pichia pastoris. o201 Tobacco leaf, tobacco dust Nicotiana tabacum. o202 Artemia salina, fish feed Artemia salina. o203 Tetramin, fish feed NA. o207 Daphnia, fish feed Daphnia spp. o211 Mealworm Tenebrio molitor. o212 Streptavidin Streptomyces avidini. o213 MBP (maltose binding protein) Escherichia coli. o214 CCD; MUXF3 from bromelain Ananas comosus. o72 Enterotoxin A (Sta a SEA) Staphylococcus aureus. o73 Enterotoxin B (Sta a SEB) Staphylococcus aureus. Parasites p1 Ascaris Ascaris suum. p2 Echinococcus Echinococcus granulosus. p3 Schistosoma Schistosoma mansoni. p4 Anisakis (Herring Worm) Anisakis simplex (Anisakis spp.). p5 Toxocara canis Toxocara canis. p10 Ani s 3.0101 Anisakis simplex (Anisakis spp.). p11 Ani s 1 Anisakis simplex (Anisakis spp.). Occupational k4 Threshing dust NA. k5 Flax NA. k7 Hay Dust NA. k8 Hop (hops) Humulus lupulus. k12 Grain mill dust NA. k14 Kapok NA. k20 Sheep's wool (treated) (wool) Ovis aries (Ovis spp.). k21 Sheep's wool (Untreated) Ovis aries (Ovis spp.). k23 Straw Dust NA. k33 Oak NA. k70 Green coffee bean Coffea spp. k71 Castor bean Ricinus communis. k72 Ispaghula Plantago psyllium/Plantago ovata. k73 Silk waste NA. k74 Silk Bombyx mori. k75 Isocyanate TDI (Toluene diisocyanate) NA. k76 Isocyanate MDI (Diphenylmethane diisocyanate) NA. k77 Isocyanate HDI (Hexamethylen diisocyanate) NA. k78 Ethylene oxide NA. k79 Phthalic anhydride NA. k80 Formaldehyde/Formalin NA. k81 Ficus Ficus benjamina (Ficus spp.). k83 Cotton seed Gossypium hirsutum. k84 Sunflower seed Helianthus annuus. k85 Chloramin T NA. k86 Trimellitic anhydride, TMA NA. k87 Asp o 21, alpha-amylase Aspergillus oryzae. k89 Orris root Iris florentina. k99 HSA (Human Serum Albumin) (Hom s HSA) Homo sapiens. k201 Car p 1, Papain Carica papaya. k202 Ana c 2, Bromelain Ananas comosus. k204 Maxatase Bacillus licheniformis. k205 Alcalase Bacillus spp. k206 Savinase, Protease 1 (Bac l Subtilisin) Bacillus spp. k208 Gal d 4, Lysozyme Gallus domesticus (Gallus gallus domesticus; Gallus spp.). k209 Hexahydrophtalic anhydrid NA. k210 Maleic anhydride NA. k211 Methyltetrahydrophtalic anhydrid NA. k212 Abachi wood dust Triplochiton scleroxylon. k213 Pepsin (Sus s Pepsin) Sus scrofa (Sus scrofa domesticus; Sus spp.). k213 TCPA NA. k214 Bougainvillea Bougainvillea spp. k225 Horse radish peroxidase (Arm r HRP) Armoracia rusticana. k226 Ascorbate oxidase (Cuc p ascorbate oxidase) Cucurbita pepo. k301 Flour dust Triticum spp. k501 Savinase customer specific Proprietary knowledge of customer. k502 Lipolase customer specific Proprietary knowledge of customer. k503 Termamyl customer specific Proprietary knowledge of customer. k504 Clazinase customer specific Proprietary knowledge of customer.

Summary

SEP 2 4 2004

510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION

A. 510(K) NUMBER: K041002

B. ANALYTE:

Celiac IgA is designed for the simultaneous detection of human IgA isotype autoantibodies directed against Gliadin and Tissue Transglutaminase Enzyme.

Celiac IgG is designed for the detection of human IgG isotype autoantibodies directed against Gliadin.

C. TYPE OF TEST:

The FIDIS™ Celia kit is a quantitative homogeneous fluorescent-based microparticles immunoassay using flow cytometry readings.

D. APPLICANT:

Biomedical Diagnostics S.A (bmd) Actipole, 25-Bd de Beaubourg Bb 103 77423 Marne-La-Vallée Cedex 2 FRANCE.

PROPRIETARY AND ESTABLISHED NAMES: E.

FIDIS™ Celiac

F. REGULATORY INFORMATION:

1. Regulation section:
  21 CFR 866.5660 Multiple Autoantibodies Immunological Test System
1. Classification:
- Class II
1. Product Code: MST

MVM

1. Panel:
  Immunology and Microbiology Devices

G. INTENDED USE:

The FIDIS™ Celiac kit is a semi-quantitative homogeneous fluorescent-based micro particles immunoassay using flow cytometry readings.

Celiac IgA is designed for the simultaneous detection of human IgA isotype antibodies directed against Gliadin and Tissue Transglutaminase Enzyme.

Celiac IgG is designed for the detection of human IgG isotype antibodies directed against Gliadin.

The presence of these antibodies can be used in conjunction with clinical findings to aid in the diagnosis of Celiac disease.

The FIDIS™ Celiac kit is to be used on serum only.

FIDIS™ Celiac kits are to be used on FIDIS™ Analyser, software and washer.

For in vitro diagnostic use.

GENERAL DESCRIPTION OF THE DEVICE: H.

FIDISTM Celiac is based on Luminex 100TM Technology.

SUBSTANTIAL EQUIVALENCE INFORMATION: l.

Predicate device name(s): BINDAZYME™ ELISA Human Anti Gliadin IgG Kit BINDAZYME™ ELISA Human Anti Gliadin IgA Kit BINDAZYME™ ELISA Human Anti Tissue Transglutaminase IgA Kit

Predicate K number(s): K981929, K981929 and K993612

Comparison with predicate:

Item	Predicate devices	Current device
Intended use	Determination of IgG and IgA antibodies
against gliadin and of IgA antibodies
against tTG in human serum	Same
Antigens	Gliadin, tTG	Same
Washing	Yes	Same
Assay type	ELISA	fluorescent-based microparticles
immunoassay using flow cytometry
Assay format	Individual assays	Individual assay for IgG and
multiplexed assay for IgA
Solid phase	Microtiter plate	Colored-code microspheres sets
Reporter conjugate	HR peroxidase	Phycoerythrin
Substrate solution	TMB	None
Detection method	Colorimetry	Fluorescence
Reading	Spectrophotometer	Flow cytometer

TEST PRINCIPLE: J.

FIDIS™ Celiac is based on the use of distinct uniform size code-colored microspheres and a benchtopflow cytometer interfaced to a digital signal processing hardware and software. A red diode laser beam of the flow cytometer classifies each set of microspheres on the basis of its unique fluorescence intensity (red to orange), which allows identifying which analyte is being tested.

At the same time, a green laser beam illuminates the external second molecule fluorescence to quantify the specific reaction related to each analyte.

Each antigen required for the assay is covalently coupled to an individual set of microspheres through its surface functional groups. The different antigen coupled microspheres are mixed together to constitute the final microspheres reagent. Celiac IgA allows the detection of antigliadin and anti-tissue transglutaminase IgA isotype autoantibodies. Celiac IgG allows the detection of anti-gliadin IgG isotype autoantibodies.

The test is performed in a 96 wells blank microplate including a filtering membrane at the bottom of the wells. In the first step, the sample is distributed in duplicate for the 2 isotypes (IgA and

IgG) selected in each well containing respectively the Celiac A microspheres mixture, for the IgA is of serent the Celiac G microspheres mixture for the IgG isotype. If the sample tested contains one or more of the suspected antibodies, this (ese) antibody (ies) will bind to the corresponding one of more of the various categories of microspheres. After incubation, a wash step through a filtration process will eliminate the unbound antibodies.

A specific conjugate consisting of either anti-human IgA or IgG antibodies coupled to phycoerythrin, is added to the mixture. It will bind to the previously captured antibodies.

The reaction is then directly measured by the flow cytometer, which categorizes each microspheres set according to its fluorescence color the microspheres while simultaneously measuring the average fluorescence emitted by the conjugate. A calibration system allows expressing by interpolation the titer of the sample for each antigenic specificity.

PERFORMANCE CHARACTERISTICS: K.

1. Analytical performance:

Precision/Reproducibility: l . I

To evaluate both intra-assay and inter-assay reproducibility, patient sera were analyzed on the FIDIS™ Celiac. These samples were selected to include low, moderate and high positives for each analyte.

				Results of the low, moderate and high positive samples are summarized below.
--	--	--	--	------------------------------------------------------------------------------

| | Within-run
(10 tests in the same run) | | Between-run
(5 tests in 5 different runs) | |
|---------------------|------------------------------------------|--------|----------------------------------------------|--------|
| Antibody specifcity | Mean value | CV (%) | Mean value | CV (%) |
| tTG IgA | 41 | 3.9 | 42 | 3.7 |
| tTG IgA | 151 | 4.6 | 152 | 5.3 |
| tTG IgA | 318 | 4.0 | 323 | 7.0 |
| Glia IgA | 41 | 3.4 | 42 | 2.8 |
| Glia IgA | 71 | 2.3 | 72 | 2.4 |
| Glia IgA | 474 | 5.5 | 493 | 3.1 |
| Glia IgG | 69 | 2.3 | 70 | 5.6 |
| Glia IgG | 99 | 4.4 | 101 | 7.2 |
| Glia IgG | 151 | 3.5 | 155 | 4.6 |

1.2 Linearity:

Autoantibodies should not be measured in terms of their concentration in serum but as an estimation of the binding capacity between antibody and antigen. This capacity varies between samples and even within the same sample. The main variables characterising these are the nature of the target epitopes and the quantity of antibodies recognising each of these epitopes. For these reasons, the average binding capacity is the best compromise to represent the mean affinity and avidity of the antibody being studied. The result of this measurement is strongly influenced by the reaction conditions.

FIDIS™ Celiac assay has been optimised 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 400 microspheres per parameter.

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

For this reason linearity is sera dependent in all FIDIS tests and there is no dilution effect.

Traceability (controls, calibrators, or method): 1.3

For each assay, a positive control IgA, a positive control IgG and a negative control are included.

1.4 Assay cut-off:

	FIDIS™ Celiac
Negative	20U/mL for the 3 specificities

Comparison studies: 2.

Comparison with predicate devices: 2.1

The method comparison with predicate devices was performed on 182 samples:

66 samples related to Celiac Disease -
55 samples from blood donors -
biological interferences (cryoglobulinemia, selected from their potential samples (1 ﺴ hypergammaglobulinemia, IgG and IgM monoclonal immunoglobulins, complement, rheumatoid factor, hemolyzed sera, plasma and lipemic serum).

	Gliadin IgA
	Bindazyme™
	+	-
FIDIS™	+	55	2
	-	16	109

There were 9 borderline results with the assay. For purposes of calculation, these results were considered as negative.

Positive percent agreement:	77.5% (55/71)
Negative percent agreement:	98.2% (109/111)
Overall agreement:	90.1% (164/182)

tTG IgA
	BindazymeTM +	BindazymeTM -
FidisTM +	44	0
FidisTM -	3	135

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

Positive percent agreement:	94.0% (44/47)
Negative percent agreement:	100% (135/135)
Overall agreement:	98.3% (179/182)

Gliadin IgG
	BindazymeTM
	+	-
FIDISTM	+	54	0
	-	6	122

There were 8 borderline results with the assay. For purposes of calculation, these results were considered as negative.

Positive percent agreement:	90% (54/60)
Negative percent agreement:	100% (122/122)
Overall agreement:	96.7% (176/182)

Summary of results

| All samples (n=182) | Positive percent
agreement | Negative percent
agreement | Overall
agreement |
|---------------------|-------------------------------|-------------------------------|----------------------|
| Gliadin IgA | 77.5% | 98.2% | 90.1% |
| tTG IgA | 94.0% | 100% | 98.3% |
| Gliadin IgG | 90% | 100% | 96.7% |

2.2 Matrix comparison:

FIDIS™ Celiac and predicate devices use serum.

3. Clinical studies:

The clinical investigation of FIDIS™ Celiac in comparison with Bindazyme™ was studied on the same samples previously tested for the comparative study. Results are compiled below.

Clinical sensitivity: not applicable a.
Clinical specificity: b.

The clinical specificity of FIDIS™ Celiac in comparison with Bindazyme™ was studied on the same samples populations previously tested for the comparative study. Results are compiled below.

| Blood donors and
biological

interferences n=116	ELISA BindazymeTM			FIDISTM Celiac
	Pos	Neg	Clinical
specificity	Pos	Neg	Clinical
specificity
Gliadin IgG	7	109	94%	3	113	97%
Gliadin IgA	22	94	81%	10	106	91%
tTG IgA	1	115	99%	1	115	99%

4. Threshold values and normal range values:

They were estimated from the 2 populations previously used for the comparative study:

55 samples from blood donors -
61 samples selected from their potential biological interferences. -

The number of positive samples and the percentage of negative samples by FIDIS™ Celiac is given by the above table.

The negative threshold (