IMMUNOCAP ALLERGEN D202, ALLERGEN COMPONENT NDER P 1, HOUSE DUST MITE, IMMUNOCAP ALLERGEN D203, ALLERGEN

K101251 · Phadia AB · DHB · May 27, 2011 · Immunology

Device Facts

• Record ID: K101251
• Device Name: IMMUNOCAP ALLERGEN D202, ALLERGEN COMPONENT NDER P 1, HOUSE DUST MITE, IMMUNOCAP ALLERGEN D203, ALLERGEN
• Applicant: Phadia AB
• Product Code: DHB · Immunology
• Decision Date: May 27, 2011
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5750
• Device Class: Class 2

Indications for Use

ImmunoCAP Specific IgE is an in vitro quantitative assay for the measurement of allergen specific IgE in human serum or plasma. ImmunoCAP Specific IgE is to be used with instruments Phadia 100, Phadia 250, and Phadia 1000. It is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings, and is to be used in clinical laboratories.

Device Story

ImmunoCAP system is a fully integrated, automated fluoroenzymeimmunoassay platform for measuring allergen-specific IgE in human serum or plasma. The system utilizes individual allergen proteins (purified native or recombinant) covalently coupled to a solid-phase support within a plastic housing. Patient samples are incubated with the allergen-coated solid phase; specific IgE antibodies bind to the allergen. After washing, enzyme-labeled anti-IgE antibodies are added to form a complex. Following a second wash, a developing agent is added; the resulting fluorescence is measured to quantify IgE concentration. The system includes Phadia 100, 250, and 1000 instrument modules and associated data management software. Used in clinical laboratories, the output provides quantitative IgE levels to assist clinicians in diagnosing allergic disorders. The device benefits patients by enabling precise identification of specific allergen sensitivities, facilitating targeted clinical management.

Clinical Evidence

Clinical performance was evaluated by comparing results against clinical diagnosis (history of symptoms and/or positive skin prick test) in atopic patients and healthy non-atopic donors. Sensitivity varied by allergen (e.g., 98-100% for house dust mites/grass/ragweed, 40-70% for peanut components). Specificity was 100% across all 13 allergens. Analytical performance included precision (Total CV% typically <10%), linearity (R² ≥ 0.99), and LoD/LoB determination per CLSI EP17-A. Literature support was provided for allergens with lower clinical sensitivity to contextualize performance across different geographic populations.

Technological Characteristics

In vitro quantitative fluorescence immunoassay. Modular reagents; allergen covalently coupled to ImmunoCAP. Automated processing via Phadia 100, 250, or 1000 instruments. Measures fluorescence of eluate proportional to specific IgE concentration. Calibration curve used for quantification.

Indications for Use

Indicated for patients suspected of IgE-mediated allergic disorders; used as an aid in clinical diagnosis via measurement of allergen-specific IgE in human serum or plasma.

Regulatory Classification

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.

Special Controls

*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.

Predicate Devices

• ImmunoCAP Specific IgE (k051218)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
k101251

B. Purpose for Submission:
Addition of 13 new allergens to a cleared device

C. Measurand:
Thirteen new allergen-specific IgE: nDer p 1, rDer p 2, rDer 10, rFel d 1, nFel d 2, rAra h 1, rAra h 2, rAra h 3, rAra h 8, rAra h 9, nCyn d 1, rAlt a 1, and nAmb a 1

D. Type of Test:
Fluoroenzymeimmunoassay, Quantitative and Semi-quantitative

E. Applicant:
Phadia AB

F. Proprietary and Established Names:
ImmunoCAP Allergen d202, Allergen component nDer p 1, House dust mite
ImmunoCAP Allergen d203, Allergen component rDer p 2, House dust mite
ImmunoCAP Allergen d205, Allergen component rDer p 10, Tropomyosin, House dust mite
ImmunoCAP Allergen e94, Allergen component rFel d 1, Cat
ImmunoCAP Allergen e220, Allergen component nFel d 2, Cat serum albumin
ImmunoCAP Allergen f422, Allergen component rAra h 1, Peanut
ImmunoCAP Allergen f423, Allergen component rAra h 2, Peanut
ImmunoCAP Allergen f424, Allergen component rAra h 3, Peanut
ImmunoCAP Allergen f352, Allergen component rAra h 8, PR-10, Peanut
ImmunoCAP Allergen f427, Allergen component rAra h 9, LTP, Peanut
ImmunoCAP Allergen g216, Allergen component nCyn d 1, Bermuda grass
ImmunoCAP Allergen m229, Allergen component rAlt a 1, Alternaria alternata
ImmunoCAP Allergen w230, Allergen component nAmb a 1, Ragweed

G. Regulatory Information:
1. Regulation section:
21 CFR § 866.5750, Radioallergosorbent (RAST) immunological test system
2. Classification:
Class II
3. Product code:
DHB - System, Test, Radioallergosorbent (RAST), Immunological
4. Panel:
Immunology (82)

H. Intended Use:
1. Intended use(s):
ImmunoCAP Specific IgE is an in vitro quantitative assay for the measurement of allergen specific IgE in human serum or plasma. ImmunoCAP Specific IgE is to be used with instruments Phadia 100, Phadia 250, and Phadia 1000. It is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE mediated

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allergic disorders in conjunction with other clinical findings, and is to be used in clinical laboratories.

2. Indication(s) for use:
Same as intended use.

3. Special conditions for use statement(s):
For prescription use only

4. Special instrument requirements:
ImmunoCAP Specific IgE is to be used with the instrument Phadia 100 Phadia 250 and Phadia 1000

I. Device Description:
The ImmunoCAP system is a fully integrated and automated system for the determination of specific IgE in human blood serum or plasma. It is comprised of instrument Phadia 100, Phadia 250 and Phadia 1000 test system modules (comprising general, test and method specific reagents), as well as instrument and data management software. The ImmunoCAP reagents include ImmunoCAP specific IgE Conjugate, ImmunoCAP Specific IgE Curve Control, ImmunoCAP Specific IgE Calibrators, Specific IgE anti-IgE ImmunoCAP, Allergen ImmunoCAP carriers, ImmunoCAP development solution and stop solution.

Individual allergen tests (the method specific reagents) are individual proteins covalently coupled to a support in a plastic housing. Individual allergens are purified native proteins or recombinantly produced and purified proteins.

J. Substantial Equivalence Information:

1. Predicate device name(s):
ImmunoCAP Specific IgE

2. Predicate K number(s):
k051218

3. Comparison with predicate:
| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Indications for Use | ImmunoCAP Specific IgE is an in vitro quantitative assay for the measurement of allergen specific IgE in human serum or plasma. It is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings, and is to be used in clinical laboratories, as well as physician office laboratories. | Same |
| Number of calibrators | Six | Same |
| Sample matrix | Serum and Plasma | Same |
| Antibody | β-Galactosidase-anti-IgE (mouse monoclonal antibody) for all ImmunoCAP | Same |
| Basic principle | Fluoroenzymeimmunoassay | Same |

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| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Sample volume | 40 μl | Same |
| Process time | 2 hours 30 minutes for Phadia 100.1 hour 45 minutes for Phadia 250 and 1000. | Same |
| Incubation temperature | 37°C | Same |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Modification | Existing allergen tests consist of multiple proteins from the allergen source. The new devices are individual proteins from this mix. Some are purified native proteins and some are recombinantly produced and purified. Recombinant proteins are: rDer p 2, rDer 10, rFel d 1, rAra h 1, rAra h 2, rAra h 3, rAra h 8, rAra h 9, rAlt a 1 | Existing allergen tests are to whole allergens comprising multiple proteins from the allergen source |

# K. Standard/Guidance Document Referenced (if applicable):

CLSI I/LA20-A: Evaluation Methods and Analytical Performance Characteristics of Immunological Assays for Human Immunoglobulin E (IgE) Antibodies of Defined Allergen Specificities; Approved Guideline (1997) I/LA20-A.

CEN 13640: Stability Testing of in vitro Diagnostic Reagents.

CLSI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation.

Radioallergosorbent Test (RAST) Methods for Allergen-Specific Immunoglobulin E (IgE) 510(k)s; Final Guidance for Industry and FDA

# L. Test Principle:

The allergen of interest covalently coupled to the ImmunoCAP solid phase, reacts with the specific IgE in the patients plasma/serum sample. After washing away non specific IgE, enzyme labeled antibodies against IgE are added to form a complex. After incubation, unbound enzyme-anti-IgE is washed away and the bound complex is then incubated with the developing agent. After stopping the reaction, the fluorescence of the eluate is measured. The higher the response value, the more specific IgE present in the specimen. To evaluate the rest results, the response for the patient samples are transformed to concentrations with the use of a calibration curve.

# M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Within-Lot imprecision:

Imprecision of the individual allergen components were tested by using two

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plasma samples $(0.35 \pm 25\%)$ and $\geq 0.7 \mathrm{kU}_{\mathrm{A}} / \mathrm{l})$ tested four times per run, two runs per day, for ten days (a total of 80 replicates per allergen). The studies shown below were performed on a Phadia 250 instrument according to the ImmunoCAP Specific IgE, Directions for Use. In data not shown here, the applicant demonstrated similar assay precision on the Phadia 100 and Phadia 1000 instruments.

Allergen Group: House Dust Mite (Dermatophagoides pteronyssinus)

| Allergen | Component Number | Mean (kUA/l) | Between days CV% | Between runs within day CV% | Within run CV% | Total CV% |
| --- | --- | --- | --- | --- | --- | --- |
| nDer p 1 | d202 | 0.34 | 0.66 | 3.12 | 2.91 | 4.31 |
| | | 1.82 | 2.93 | 2.59 | 2.93 | 4.89 |
| rDer p 2 | d203 | 0.33 | 2.02 | 2.46 | 2.35 | 3.96 |
| | | 2.02 | 0.42 | 3.76 | 1.70 | 4.14 |
| rDer 10 | d205 | 0.36 | 1.99 | 3.24 | 2.90 | 4.78 |
| | | 2.36 | 1.86 | 4.67 | 2.23 | 5.50 |

Allergen Group: Cat (Felis catus)

| Allergen | Component Number | Mean (kUa/l) | Between days CV% | Between runs within day CV% | Within run CV% | Total CV% |
| --- | --- | --- | --- | --- | --- | --- |
| rFel d 1 | e94 | 0.33 | 0.00 | 2.89 | 3.21 | 4.32 |
| | | 2.58 | 0.00 | 6.53 | 1.98 | 6.82 |
| nFel d 2 | e220 | 0.36 | 0.85 | 2.77 | 2.22 | 3.66 |
| | | 2.14 | 1.85 | 1.91 | 2.24 | 3.48 |

Allergen Group: Peanut (Arachis hypogea)

| Allergen | Component Number | Mean (kUa/l) | Between days CV% | Between runs within day CV% | Within run CV% | Total CV% |
| --- | --- | --- | --- | --- | --- | --- |
| rAra h 1 | f422 | 0.35 | 0.66 | 3.82 | 1.90 | 4.32 |
| | | 1.96 | 5.43 | 3.82 | 1.65 | 6.84 |
| rAra h 2 | f423 | 0.31 | 3.83 | 4.03 | 10.05 | 11.49 |
| | | 2.82 | 2.62 | 6.48 | 7.04 | 9.92 |
| rAra h 3 | f424 | 0.36 | 1.49 | 2.76 | 6.04 | 6.80 |

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| Allergen | Component Number | Mean (kU_{A}/l) | Between days CV% | Between runs within day CV% | Within run CV% | Total CV% |
| --- | --- | --- | --- | --- | --- | --- |
| | | 3.47 | 1.49 | 3.10 | 3.17 | 4.68 |
| rAra h 8 | f352 | 0.37 | 0.67 | 1.65 | 2.11 | 2.76 |
| | | 2.55 | 0.00 | 3.49 | 3.97 | 5.29 |
| rAra h 9 | f427 | 0.33 | 1.80 | 2.82 | 1.99 | 3.90 |
| | | 2.35 | 6.03 | 5.02 | 2.38 | 8.20 |

Allergen Group: **Bermuda grass** (*Cynodon dactylon*)

| Allergen | Component Number | Mean (kU_{A}/l) | Between days CV% | Between runs within day CV% | Within run CV% | Total CV% |
| --- | --- | --- | --- | --- | --- | --- |
| rCyn d 1 | g216 | 0.35 | 1.93 | 1.88 | 2.25 | 3.51 |
| | | 2.07 | 0.00 | 3.02 | 2.23 | 3.75 |

Allergen Group: **Alternaria alternata**

| Allergen | Component Number | Mean (kU_{A}/l) | Between days CV% | Between runs within day CV% | Within run CV% | Total CV% |
| --- | --- | --- | --- | --- | --- | --- |
| rAlt a 1 | w230 | 0.37 | 3.10 | 2.35 | 1.82 | 4.29 |
| | | 2.32 | 2.16 | 2.60 | 2.27 | 4.07 |

Allergen Group: **Ragweed** (*Ambrosia artemisiifolia*)

| Allergen | Component Number | Mean (kU_{A}/l) | Between days CV% | Between runs within day CV% | Within run CV% | Total CV% |
| --- | --- | --- | --- | --- | --- | --- |
| nAmb a 1 | m229 | 0.35 | 1.58 | 3.05 | 1.89 | 3.92 |
| | | 2.36 | 2.22 | 2.75 | 1.88 | 4.00 |

## Lot-to-lot imprecision:

Three lots of each individual allergen were tested using two positive samples (0.35 ± 25% and ≥0.7 kU_A/L) and one negative sample (&lt; 0.1 kU_A/L). For each lot the samples were tested in 12 replicates in one assay run. Each lot represented a different preparation of the allergen from routine production.

Allergen Group: **House Dust Mite** (*Dermatophagoides pteronyssinus*)

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6

| Allergen
(Component number) | Lot | Sample | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | Positive 1 | | Positive 2 | | Negative |
| | | Mean (kU_{A}/l) | CV (%) | Mean (kU_{A}/l) | CV (%) | Mean (kU_{A}/l) |
| nDer p 1
(d202) | 1 | 2.49 | 4.1 | 0.39 | 3.4 | 0.00 |
| | 2 | 2.73 | 6.0 | 0.40 | 4.9 | 0.00 |
| | 3 | 2.35 | 8.8 | 0.37 | 3.4 | 0.00 |
| rDer p 2
(d203) | 1 | 2.10 | 2.6 | 0.35 | 2.5 | 0.00 |
| | 2 | 2.27 | 2.9 | 0.38 | 1.8 | 0.00 |
| | 3 | 2.11 | 1.5 | 0.35 | 2.6 | 0.00 |
| rDer 10
(d205) | 1 | 2.63 | 1.2 | 0.44 | 2.2 | 0.00 |
| | 2 | 2.47 | 2.2 | 0.42 | 2.6 | 0.00 |
| | 3 | 2.58 | 2.0 | 0.41 | 2.2 | 0.00 |

Allergen Group: Cat (Felis catus)

| Allergen
(Component number) | Lot | Sample | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | Positive 1 | | Positive 2 | | Negative |
| | | Mean (kU_{A}/l) | CV (%) | Mean (kU_{A}/l) | CV (%) | Mean (kU_{A}/l) |
| rFel d 1
(e94) | 1 | 3.10 | 1.7 | 0.40 | 3.3 | 0.00 |
| | 2 | 2.77 | 2.1 | 0.37 | 2.0 | 0.00 |
| | 3 | 3.07 | 2.7 | 0.40 | 1.8 | 0.00 |
| nFel d 2
(e220) | 1 | 2.16 | 1.9 | 0.33 | 2.0 | 0.00 |
| | 2 | 2.18 | 2.7 | 0.38 | 1.8 | 0.00 |
| | 3 | 2.15 | 1.5 | 0.37 | 2.8 | 0.00 |

Allergen Group: Peanut (Arachis hypogea)

| Allergen
(Component number) | Lot | Sample | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | Positive 1 | | Positive 2 | | Negative |
| | | Mean (kU_{A}/l) | CV (%) | Mean (kU_{A}/l) | CV (%) | Mean (kU_{A}/l) |
| rAra h 1
(f422) | 1 | 2.35 | 1.4 | 0.41 | 1.2 | 0.00 |
| | 2 | 2.29 | 2.2 | 0.39 | 1.7 | 0.00 |
| | 3 | 2.23 | 2.6 | 0.39 | 2.5 | 0.00 |
| rAra h 2
(f423) | 1 | 3.60 | 3.8 | 0.32 | 2.6 | 0.03 |
| | 2 | 3.27 | 4.5 | 0.29 | 3.5 | 0.03 |

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7

| Allergen
(Component number) | Lot | Sample | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | Positive 1 | | Positive 2 | | Negative |
| | | Mean (kU_{A}/l) | CV (%) | Mean (kU_{A}/l) | CV (%) | Mean (kU_{A}/l) |
| | 3 | 2.99 | 6.6 | 0.26 | 2.9 | 0.02 |
| rAra h 3
(f424) | 1 | 3.77 | 3.1 | 0.32 | 1.9 | 0.00 |
| | 2 | 3.81 | 1.8 | 0.34 | 2.6 | 0.00 |
| | 3 | 4.06 | 2.8 | 0.34 | 3.7 | 0.00 |
| rAra h 8
(f352) | 1 | 2.57 | 4.1 | 0.33 | 1.9 | 0.00 |
| | 2 | 2.44 | 5.1 | 0.32 | 2.3 | 0.00 |
| | 3 | 2.70 | 3.6 | 0.33 | 1.9 | 0.00 |
| rAra h 9
(f427) | 1 | 2.85 | 3.5 | 0.38 | 2.1 | 0.00 |
| | 2 | 3.00 | 3.7 | 0.39 | 1.9 | 0.00 |
| | 3 | 2.53 | 1.9 | 0.34 | 1.2 | 0.00 |

Allergen Group: Bermuda grass (Cynodon dactylon)

| Allergen
(Component number) | Lot | Sample | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | Positive 1 | | Positive 2 | | Negative |
| | | Mean (kU_{A}/l) | CV (%) | Mean (kU_{A}/l) | CV (%) | Mean (kU_{A}/l) |
| nCyn d 1
(g216) | 1 | 1.78 | 4.5 | 0.37 | 2.7 | 0.00 |
| | 2 | 2.19 | 2.1 | 0.39 | 3.4 | 0.00 |
| | 3 | 2.16 | 2.8 | 0.38 | 2.3 | 0.00 |

Allergen Group: Alternaria alternata

| Allergen
(Component number) | Lot | Sample | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | Positive 1 | | Positive 2 | | Negative |
| | | Mean (kU_{A}/l) | CV (%) | Mean (kU_{A}/l) | CV (%) | Mean (kU_{A}/l) |
| rAlt a 1
(w230) | 1 | 2.30 | 1.8 | 0.37 | 2.2 | 0.00 |
| | 2 | 2.28 | 2.2 | 0.37 | 2.1 | 0.00 |
| | 3 | 2.24 | 2.0 | 0.36 | 1.5 | 0.00 |

Allergen Group: Ragweed (Ambrosia artemisiifolia)

| Allergen
(Component number) | Lot | Sample | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | | Positive 1 | | Positive 2 | | Negative |
| | | Mean (kU_{A}/l) | CV (%) | Mean (kU_{A}/l) | CV (%) | Mean (kU_{A}/l) |

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b. Linearity/assay reportable range:

The linearity of the 13 individual allergens was assessed by diluting three positive plasma samples per allergen in negative plasma to provide at least five 2-fold consecutive dilutions. Undiluted and diluted samples were tested in four replicates in one assay run. The assay was performed according to the ImmunoCAP Specific IgE, Directions for Use using instrument Phadia 250. For each product one lot of ImmunoCAP Allergen Component was used. The ImmunoCAP Specific Total IgE working range is LoD – 100 kUA/l.

For each allergen, the replicates from all three samples were pooled and analyzed for linearity. Regression statistics for each allergen comparing the observed results to expected results are presented below:

| Allergen (Component Number) | Regression Equation | R2 | 95% CI Slope | 95% CI Intercept |
| --- | --- | --- | --- | --- |
| nDer p 1 (d202) | y = 0.99x + 0.04 | 0.99 | 0.97 – 1.00 | 0.04 – 0.02 |
| rDer p 2 (d203) | y = 1.00x | 1.00 | 0.99 – 1.01 | -0.01 – 0.01 |
| rDer 10 (d205) | y = 1.00x + 0.03 | 1.00 | 0.97 – 1.02 | 0.01 – 0.05 |
| Allergen (Component Number) | Regression Equation | R2 | 95% CI Slope | 95% CI Intercept |
| --- | --- | --- | --- | --- |
| rFel d 1 (e94) | y = 0.97x +0.03 | 0.99 | 0.95 – 0.98 | 0.02 – 0.04 |
| nFel d 2 (e220) | y = 0.94x + 0.08 | 0.99 | 0.93 – 0.96 | 0.06 – 0.09 |

Allergen Group: Peanut (Arachis hypogea)

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| Allergen (Component Number) | Regression Equation | R2 | 95% CI Slope | 95% CI Intercept |
| --- | --- | --- | --- | --- |
| rAra h 1 (f422) | y = 1.00x - 0.05 | 1.00 | 1.00 – 1.01 | -0.05 - -0.04 |
| rAra h 2 (f423) | y = 0.91x + b0.09 | 0.99 | 0.90 – 0.93 | 0.08 – 0.11 |
| rAra h 3 (f424) | y = 0.99x + 0.02 | 0.99 | 0.96 – 1..01 | 0 – 0.04 |
| rAra h 8 (f352) | y =1.00x | 1.00 | 0.99 – 1.01 | -0.01 – 0.01 |
| rAra h 9 (f427) | y = 1.01x – 0.03 | 1.00 | 1.00 – 1.03 | -0.04 - -0.02 |

Allergen Group: Bermuda grass, Alternaria alternata, and Ragweed

| Allergen (Component Number) | Regression Equation | R2 | 95% CI Slope | 95% CI Intercept |
| --- | --- | --- | --- | --- |
| nCyn d (g216) | y = 0.96 | 1.00 | 0.95 – 0.97 | 0.04 – 0.05 |
| rAlt a 1 (m229) | y = 0.96x | 0.99 | 0.96 – 0.99 | -0.01 – 0.01 |
| nAmb a 1 (w230) | y = 0.97x + 0.02 | 1.00 | 0.96 – 0.98 | 0.02 – 0.03 |

c. Traceability, Stability, Expected values (controls, calibrators, or methods): The IgE calibrators are traceable (via an unbroken chain of calibrations) to the $2^{\mathrm{nd}}$ International Reference Preparation (IRP) 75/502 of Human Serum Immunoglobulin E from World Health Organization (WHO).

Real-time stability study results were available for rFel d 1, nFel d 2, rAlt a 1, rAra h 1, rAra h 2, rAra h 3 and rAra h 8 PR-10 and support an unopened shelf-life of 24 months from the date of manufacture when stored at $2 - 8^{\circ}\mathrm{C}$ . For the real-time study, more than one lot of each component allergen was stored at $2 - 8^{\circ}\mathrm{C}$ . At different times a positive and a negative plasma sample were tested in three replicates in one assay; the results were compared to the results of the same samples tested at time $= 0$ .

Accelerated stability studies performed on allergen components nDer p 1, rDer p 2, rDer 10, nAmb a 1, nCyn d 1, and rAra h 9 LTP support an

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unopened shelf-life of 24 months from the date of manufacture when stored at $2 - 8^{\circ}\mathrm{C}$ . For the accelerated study, three lots of component allergens were stored at $30^{\circ}\mathrm{C}$ for eight weeks. The same lot stored at $2 - 8^{\circ}\mathrm{C}$ was used as reference. At four weeks and at eight weeks two positive and one negative control samples (stored human plasma) were tested in duplicate in each storage condition/lot combination. The results support the manufacture's claim of 24 months. Real-time stability studies are underway for these components and currently support a claim of 13 months.

The stability of the calibration curve, real time, and on-board stability of ImmunoCAP Specific IgE calibrator are detailed in k100999.

# d. Detection limit:

The Limit of Blank (LoB) and the Limit of Detection (LoD) were determined for each allergen component on the Phadia 250 in alignment with CLSI EP17-A. The LoB was based on single determinations of 100 negative samples (blank samples); the LoB was estimated as the $95\%$ percentile of the distribution. LoD was calculated according to the equation: $\mathrm{LoD} = \mathrm{LoB} + c_{\beta} \times \mathrm{SD}$ where SD, the standard deviation, was based on 20 determinations of 3 low positive samples, in total 60 determinations. In data not shown here, the applicant demonstrated that the Phadia 100 and the Phadia 1000 instruments had similar LoBs and LoDs for a subset of the allergens below.

| Allergen Group | Allergen component | LoB | LoD |
| --- | --- | --- | --- |
| House Dust Mite | d202 | 0.025 | 0.036 |
| | d203 | 0.000 | 0.010 |
| | d205 | 0.000 | 0.009 |
| Cat | e94 | 0.010 | 0.024 |
| | e220 | 0.002 | 0.020 |
| Peanut | f422 | 0.004 | 0.010 |
| | f423 | 0.008 | 0.066 |
| | f424 | 0.006 | 0.029 |
| | f352 | 0.008 | 0.020 |
| | f427 | 0.007 | 0.019 |
| Bermuda Grass | g216 | 0.016 | 0.030 |
| Alternaria alternata | w230 | 0.007 | 0.018 |

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| Allergen Group | Allergen component | LoB | LoD |
| --- | --- | --- | --- |
| Ragweed | m229 | 0.007 | 0.014 |

e. Analytical specificity:

Specificity of each allergen was verified through competitive inhibition studies planned in accordance with CLSI I/LA20-A. Inhibition studies should show an overall dose dependent decrease of free specific IgE antibodies available to bind to the ImmunoCAP Allergen. This dose dependent decrease indicates the presence of antibodies that recognize the allergen; no, or little, decrease in response indicates that there are no antibodies specific to the allergen. The specific inhibition demonstrates the presence of immunologically relevant and reactive allergen bound to the solid phase.

To establish the minimum theoretical response level for the sample (100% inhibition, "100%"), equal volumes of negative sample and buffer were premixed and tested with the assay. This should mimic the state where all IgE antibodies are bound by the added soluble inhibitor (allergen) so that no specific IgE antibodies are available to bind to the solid phase.

The maximum response level for the sample (0% inhibition, "0%"), is established by pre-mixing equal volumes of positive sample and buffer and testing with the assay.

Overall dose dependent inhibition of specific allergens was demonstrated by premixing 100 µl of positive sample with varying dilutions of allergen solution (inhibitor). As a control, three unrelated antigens were also tested at one concentration each in separate experiments.

The mixtures were incubated in a sample tube at room temperature for 1 hour before being analyzed with the ImmunoCAP Allergen Component according to the manufacturer's instructions. The testing was performed in duplicates in one assay run. Mean values were calculated.

The results of the studies (not shown) demonstrate that the allergens tested are inhibited by the relevant inhibitor extract in a concentration dependent fashion; all allergens were able to be inhibited by more than 50%. Most allergens could be inhibited more than 90% by the highest concentration of inhibitor (i.e. the least dilute dilution).

Additional inhibition studies were conducted to show that the specific allergens are not cross-reacting to unrelated allergens. Testing was performed using one positive sample with three unrelated allergen extracts.

f. Assay cut-off:

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Not applicable

2. Comparison studies:
a. Method comparison with predicate device:
Refer to clinical studies.
b. Matrix comparison:
Serum, heparin plasma, and EDTA plasma samples were collected from patients with clinical history of known specific allergies. These samples were tested with the ImmunoCap allergen components included in this submission. This resulted in a range of results (negative and positive) within each sample; for example, a sample was negative for f423 (peanut rAra h 2) but was strongly positive for e94 (cat rFel d 1). Recovery of the heparin plasma and EDTA plasma was acceptable in all positive (≥ 0.35 kU_A/L) samples. This study suggests that the three sample matrices are interchangeable.

3. Clinical studies:
a. Clinical sensitivity and Specificity:
The performance of all 13 individual allergen components was compared to a clinical diagnosis of allergy. Atopic samples were obtained from individuals with a clinical history of allergy-like symptoms upon exposure to an allergen as diagnosed by a physician and/or clinical symptoms and/or positive skin prick test to a specific allergen. Information about clinical symptoms and manifestations was available for all atopic samples. 100 negative samples (&lt;0.35 kU_A/L) from healthy non-atopic donors were also tested.

House dust mites:
ImmunoCAP Allergen d202, nDer p 1

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| nDer p 1(d202) | Positive | 56 | 0 | 56 |
| | Negative | 1 | 100 | 101 |
| | Total | 57 | 100 | 157 |

Sensitivity = 98% (95% CI: 90.7 - 99.7%)
Specificity = 100%

ImmunoCAP Allergen d203, rDer p 2

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| rDer p 2 (d203) | Positive | 53 | 0 | 53 |
| | Negative | 4 | 100 | 104 |
| | Total | 57 | 100 | 157 |

Sensitivity = 93% (95% CI: 83.3 - 97.2%)
Specificity = 100%

ImmunoCAP Allergen d205, rDer p 10, Tropomyosin

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13

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| rDer p 10 (d205) | Positive | 36 | 0 | 36 |
| | Negative | 36 | 100 | 136 |
| | Total | 72 | 100 | 172 |

Sensitivity =50% (95% CI: 38.8 – 61.3%
Specificity =100%

Cat:
ImmunoCAP Allergen e94, rFel d 1

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| rFel d 1 (e94) | Positive | 72 | 0 | 72 |
| | Negative | 1 | 100 | 101 |
| | Total | 73 | 100 | 173 |

Sensitivity =99% (95% CI: 92.6 – 99.8%)
Specificity =100%

ImmunoCAP Allergen e220, nFel d 2

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| nFel d 2 (e220) | Positive | 34 | 0 | 34 |
| | Negative | 39 | 100 | 139 |
| | Total | 73 | 100 | 173 |

Sensitivity =47% (95% CI: 35.6 – 57.9%)
Specificity =100%

Peanut:
ImmunoCAP Allergen f422, rAra h 1

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| rAra h 1 (f422) | Positive | 37 | 0 | 37 |
| | Negative | 56 | 100 | 156 |
| | Total | 93 | 100 | 193 |

Sensitivity =40% (95% CI: 30.4 – 50.0%)
Specificity =100%

ImmunoCAP Allergen f423, rAra h 2

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| rAra h 2 (f423) | Positive | 40 | 0 | 40 |
| | Negative | 53 | 100 | 153 |

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14

| | Total | 93 | 100 | 193 |
| --- | --- | --- | --- | --- |

Sensitivity =43% (95% CI: 33.4 – 53.2%)
Specificity =100%

ImmnuoCAP Allergen f424, rAra h 3

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| rAra h 3 (f424) | Positive | 37 | 0 | 37 |
| | Negative | 56 | 100 | 156 |
| | Total | 93 | 100 | 193 |

Sensitivity =40% (95% CI: 30.4 – 50.0%)
Specificity =100%

ImmunoCAP Allergen f352, rAra h 8, PR-10

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| rAra h 8 (f352) | Positive | 43 | 0 | 43 |
| | Negative | 50 | 100 | 150 |
| | Total | 93 | 100 | 193 |

Sensitivity =46% (95% CI: 33.4 – 53.2%)
Specificity =100%

ImmnuoCAP Allergen f427, rAra h 9, LTP

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| rAra h 9 (f427) | Positive | 52 | 0 | 52 |
| | Negative | 22 | 100 | 141 |
| | Total | 74 | 100 | 193 |

Sensitivity =70% 95% CI: 59.1 – 79.5%)
Specificity =100%

Bermuda grass:
ImmunoCAP Allergen g216, nCyn d 1

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| nCyn d 1 (g216) | Positive | 31 | 0 | 31 |
| | Negative | 0 | 100 | 100 |
| | Total | 31 | 100 | 131 |

Sensitivity =100%
Specificity =100%

Alternaria alternata:

{14}

ImmunoCAP Allergen m229, rAlt a 1

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| rAlt a 1 (m229) | Positive | 45 | 0 | 45 |
| | Negative | 0 | 100 | 100 |
| | Total | 45 | 100 | 145 |

Sensitivity =100%

Specificity =100%

# Ragweed:

ImmunoCAP Allergen w230, nAmb a 1

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| nAmb a 1 (w230) | Positive | 34 | 0 | 34 |
| | Negative | 0 | 100 | 100 |
| | Total | 34 | 100 | 134 |

Sensitivity =100%

Specificity =100%

All studies described above were performed on the Phadia 250 instrument system. The applicant provided studies to show that the Phadia 100 and Phadia 1000 instrument system performed similarly to the Phadia 250.

Literature support was provided on allergens with low prevalence and % sensitivity as shown below:

| Specific Allergen Clinical Sensitivity (%) | Allergen Name | Literature Cited | Prevalence Found | Clinical Sensitivity |
| --- | --- | --- | --- | --- |
| rDer p 10 d205 (50%) | d1 House dust mite | 1) Jaén A et al. European Community Respiratory Health Survey. Specific sensitization to common allergens and pulmonary function in the European Community Respiratory Health Survey. Clin Exp Allergy. 2002 Dec;32(12):1713-9. 2) Weghofer M et al. Variability of IgE reactivity profiles among European mite allergic patients. Eur J Clin Invest 2008;38 (12): 959-65. | 1) ECRHS 12687 subjects from 34 centres in 15 countries. Prevalence of sensitization to mite: Women; 16.8% Men; 23.5% | 2) Mite allergic patients from Austria (n=56) France N(55) Italy n=(67) Sweden (n=31) Der p 10 positive in 18%, 9%,10% and 18% respectively 3) 90 mite allergic patients in Colombia. Der p 10 positive |

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| Specific Allergen Clinical Sensitivity (%) | Allergen Name | Literature Cited | Prevalence Found | Clinical Sensitivity |
| --- | --- | --- | --- | --- |
| | | 3) Jiménez S. et al. IgE antibody responses to recombinant allergens of Blomia tropicalis and Dermatophagoides pteronyssinus in a tropical environment. Allergy and Clinical Immunology International Volume 19, Issue 6, November 2007, Pages 233-238
4) Boquete M. et al. Seafood hypersensitivity in mite sensitized individuals: is tropomyosin the only responsible allergen? Annals of Allergy, Asthma & Immunology, Volume 106, Issue 3, March 2011, Pages 223-229 | | 16.7%
4) 60 mite allergic patients in Spain; Der p 10 positive in 32% of 30 patients with both mite and seafood symptoms and in 0% of 30 patients with only mite symptoms |
| n Fel d 2 e220 (47%) | e1 Cat | 1) Spitzauer S. et al. IgE cross-reactivities against albumins in patients allergic to animals. J Allergy Clin Immunol 1995;96(6 Pt 1): 951-9
2) Hilger C. et al. Allergic cross-reactions between cat and pig serum albumin. Study at the protein and DNA levels. Allergy 1997;52(2):179-87
3) van Ree R. et al. Purified natural and recombinant Fel d 1 and cat albumin in in vitro diagnostics for cat allergy. J Allergy Clin Immunol 1999;104(6):1223-30
4) Cabanas, R., M. C. Lopez-Serrano, et al. "Importance of albumin in cross-reactivity among cat, dog and horse allergens." Journal of Investigational Allergology & Clinical Immunology 2000; 10(2): 71-77. | 1) ECRHS 12687 subjects from 34 centres in 15 countries. Prevalence of sensitization to cat: Women ; 9.3 % Men; 9.5% | 1) 200 animal allergic patients; Cat albumin (Fel d 2) positive in 26% of patients
2) 2 groups of cat allergic patients (n=39 and n=39) Fel d 2 positive in 14% and 23%
1 group (n=10) allergic both to cat and pork ; Fel d 2 positive in 100%
3) 509 cat sensitized patients ; Fel d 2 positive in 16.7%
4) 117 cat allergic patients; Fel d 2 positive in 22% |

16

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| Specific Allergen Clinical Sensitivity (%) | Allergen Name | Literature Cited | Prevalence Found | Clinical Sensitivity |
| --- | --- | --- | --- | --- |
| rAra h 1 f422 (40%) | f13 Peanut | 1) Branum AM, Lukacs SL. Food allergy among children in the United States Pediatrics. 2009 Dec;124(6):1549-55. Epub 2009 Nov 16.
2) Asarnoj A. et al. IgE to peanut allergen components: relation to peanut symptoms and pollen sensitization in 8-year-olds. Allergy 2010;65: 1189-1195
3) Codreanu et al. A Novel Immunoassay using recombinant allergens simplifies peanut allergy diagnosis. Int Arch Allergy Immunol 2011;154:216–226
4) Vereda A. et al. Peanut allergy: Clinical and immunologic differences among patients from 3 different geographic regions (J Allergy Clin Immunol 2011 in press on line; DOI: 10.1016/j.jaci.2010.09.010) | 1) NHANES: Prevalence of peanut sensitized children in USA estimated to 9% | 2) Peanut allergic children in Sweden (n=58); Positive to: Ara h 1; 48%
3) Peanut allergic patients in France (n=166) Positive to: Ara h 1;75%
4) Peanut Allergic patients from 3 countries Spain (n=50) USA (n=30), Sweden (n=35) Positive to : Ara h 1; 30%, 80%, 62,9% respectively |
| r Ar a h 2f423 (43%) | f13 Peanut | 1) Branum AM, Lukacs SL. Food allergy among children in the United States Pediatrics. 2009 Dec;124(6):1549-55. Epub 2009 Nov 16.
2) Asarnoj A. et al. IgE to peanut allergen components: relation to peanut symptoms and pollen sensitization in 8-year-olds. Allergy 2010;65: 1189-1195
3) Codreanu et al. A Novel Immunoassay using recombinant allergens simplifies peanut allergy diagnosis. Int Arch Allergy Immunol 2011;154:216–226 | 1) NHANES: Prevalence of peanut sensitized children in USA estimated to 9% | 2) Peanut allergic children in Sweden (n=58); Positive to: Ara h 2; 78%
3) Peanut allergic patients in France (n=166) Positive to: Ara h 2; 96%
4) Peanut Allergic patients from 3 countries Spain (n=50) USA (n=30), Sweden (n=35) |

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| Specific Allergen Clinical Sensitivity (%) | Allergen Name | Literature Cited | Prevalence Found | Clinical Sensitivity |
| --- | --- | --- | --- | --- |
| | | 4) Vereda A. et al. Peanut allergy: Clinical and immunologic differences among patients from 3 different geographic regions (J Allergy Clin Immunol 2011 in press on line ; DOI: 10.1016/j.jaci.2010.09.010) | | Positive to : Ara h 2; 42%, 90%, 74,3% respectively |
| rAra h 3 f424 (40%) | f13 Peanut | 1) Branum AM, Lukacs SL. Food allergy among children in the United States Pediatrics. 2009 Dec;124(6):1549-55. Epub 2009 Nov 16.
2) Asarnoj A. et al. IgE to peanut allergen components: relation to peanut symptoms and pollen sensitization in 8-year-olds. Allergy 2010;65: 1189-1195
3) Codreanu et al. A Novel Immunoassay using recombinant allergens simplifies peanut allergy diagnosis. Int Arch Allergy Immunol 2011;154:216–226
4) Vereda A. et al. Peanut allergy: Clinical and immunologic differences among patients from 3 different geographic regions (J Allergy Clin Immunol 2011 in press on line; DOI: 10.1016/j.jaci.2010.09.010) | 1) NHANES: Prevalence of peanut sensitized children in USA estimated to 9% | 2) Peanut allergic children in Sweden (n=58); Positive to: Ara h 3; 41%
3) Peanut allergic patients in France (n=166)
Positive to: Ara h 3; 61%
4) Peanut Allergic patients from 3 countries Spain (n=50)
USA (n=30), Sweden (n=35)
Positive to : Ara h 3: 16%,56,7%, 37,1% respectively |
| rAra h 8 f352 (46%) | f13 Peanut | 1) Branum AM, Lukacs SL. Food allergy among children in the United States Pediatrics. 2009 Dec;124(6):1549-55. Epub 2009 Nov 16.
2) Mittag D. et al. Ara h 8, a Bet v 1-homologous allergen from peanut, is a major allergen in | 1) NHANES: Prevalence of peanut sensitized children in USA estimated to 9% | 2) Peanut and birch allergic patients in Germany (n=20)
Positive to: Ara h 8; 85 %
3) Peanut allergic children in Sweden (n=58); |

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| Specific Allergen Clinical Sensitivity (%) | Allergen Name | Literature Cited | Prevalence Found | Clinical Sensitivity |
| --- | --- | --- | --- | --- |
| | | patients with combined birch pollen and peanut allergy.
J Allergy Clin Immunol 2004;114:1410-1417
3) Asarnoj A. et al. IgE to peanut allergen components: relation to peanut symptoms and pollen sensitization in 8-year-olds.
Allergy 2010;65: 1189-1195
4) Vereda A. et al. Peanut allergy: Clinical and immunologic differences among patients from 3 different geographic regions (J Allergy Clin Immunol 2011 in press on line; DOI: 10.1016/j.jaci.2010.09.010) | | Positive to:
Ara h 8; 14 %
4) Peanut Allergic patients from 3 countries Spain (n=50)
USA (n=30), Sweden (n=35)
Positive to :
Ara h 8: 2%, 19,1%, 65,7% |

b. Other clinical supportive data (when a. and b. are not applicable):<br/>
Not applicable

4. Clinical cut-off:<br/>
Not applicable

5. Expected values/Reference range:<br/>
The expected value is negative (&lt; 0.35 kU_A/L) for a specific allergen in a non-allergic person. The manufacturer recommends a cut-off of 0.35 kU_A/L. Each laboratory should establish its own expected range of values.

N. Proposed Labeling:<br/>
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:<br/>
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.