AUTOMATED IN VITRO QUANTITATIVE ASSAY FOR THE MEASUREMENT OF ALLERGEN SPECIFIC IGE ANTIBODIES

K121156 · Phadia AB · DHB · Mar 13, 2013 · Immunology

Device Facts

• Record ID: K121156
• Device Name: AUTOMATED IN VITRO QUANTITATIVE ASSAY FOR THE MEASUREMENT OF ALLERGEN SPECIFIC IGE ANTIBODIES
• Applicant: Phadia AB
• Product Code: DHB · Immunology
• Decision Date: Mar 13, 2013
• 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 (EDTA or Na-Heparin). 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 an automated fluoroenzyme immunoassay for detecting allergen-specific IgE in human serum or plasma. The device uses purified native allergens covalently coupled to a solid-phase support. Patient samples are incubated with the allergen; specific IgE binds to the solid phase. After washing, enzyme-labeled anti-IgE antibodies are added to form a complex. A developing agent is added, and fluorescence is measured; higher fluorescence indicates higher IgE concentration. The system includes Phadia 100, 250, or 1000 instruments and data management software. Used in clinical laboratories by trained personnel. Results assist clinicians in diagnosing IgE-mediated allergic disorders by confirming sensitization to specific allergens, supporting clinical decision-making alongside patient history and other findings.

Clinical Evidence

Clinical validation compared the four new allergen components against clinical diagnosis in 30+ atopic patients and 100 non-atopic healthy donors. Sensitivity and specificity were 100% for all four allergens (95% CIs ranging from 87.7% to 100%). Analytical performance included precision (total CV% 3.56%–13.28%), linearity (r²=1.00), and limit of detection (0.012–0.067 kUA/L). Inhibition studies confirmed immunological specificity. Matrix interchangeability (serum, EDTA, heparin plasma) was verified.

Technological Characteristics

Fluoroenzyme immunoassay; solid-phase allergen coupling. Instruments: Phadia 100, 250, 1000. Detection: β-Galactosidase-anti-human IgE (mouse monoclonal). Calibration: 6-point curve traceable to WHO 2nd IRP 75/502. Sample volume: 40 μL. Incubation: 37°C. Software: Integrated instrument and data management. Sterilization: Not applicable (reagents). Connectivity: Automated system.

Indications for Use

Indicated for the quantitative measurement of allergen-specific IgE in human serum or plasma to aid in the clinical diagnosis of IgE-mediated allergic disorders in patients suspected of having such disorders.

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

• UniCAP® Specific IgE Assay and UniCAP® Specific IgE Conjugate 100 and 400 (k051218)
• UniCAP® Specific IgE Assay (k962274)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
k121156

B. Purpose for Submission:
Addition of 4 new native allergens to a cleared device

C. Analyte:
Four new native allergen-specific IgE analytes: Cow’s milk whey, Chick pea, Cedar, Cupressus arizonica

D. Type of Test:
Fluoroenzyme immunoassay, Quantitative

E. Applicant:
Phadia AB

F. Proprietary and Established Names:
ImmunoCAP Specific IgE
ImmunoCAP Allergen f236, Cow’s milk whey
ImmunoCAP Allergen f309, Chick pea
ImmunoCAP Allergen t212, Cedar
ImmunoCAP Allergen t222, Cupressus arizonica

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 (EDTA or Na-Heparin). ImmunoCAP

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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.

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

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

4. Special instrument requirements:
For use on the instruments 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 serum, sodium heparin plasma or EDTA plasma sample. It is comprised of general, test and method specific reagents for Phadia 100, Phadia 250 and Phadia 1000 test system modules, as well as instrument and data management software.

The general 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. The method specific reagents consist of individual purified allergen (native) covalently coupled to a support in a plastic housing.

J. Substantial Equivalence Information:

1. Predicate device name and Predicate K number

UniCAP® Specific IgE Assay and UniCAP® Specific IgE Conjugate 100 and 400, (k051218)

UniCAP® Specific IgE Assay (k962274)

2. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | 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. | Same |

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| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Assay type | Quantitative | Same |
| Test method | Fluoroenzymeimmunoassay | Same |
| 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 |
| Detection antibody | β-Galactosidase-anti- human IgE (mouse monoclonal antibody) for all ImmunoCAP | Same |
| Number of calibrators | Six | Same |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Modification | Addition of new allergens: f236, Cow's milk whey f309, Chick pea t212, Cedar t222, Cupressus arizonica | Not included |
| Sample matrix | Serum and plasma (EDTA or sodium heparin) | Serum and plasma (sodium heparin) |
| Laboratory settings | Clinical laboratories | Clinical laboratories and physician office laboratories. |
| Instruments | Phadia 100, Phadia 250 and Phadia 1000 | UniCAP 100 |

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

CLSI EP5-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline - Second Edition.

CSLI EP17-A: Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline

CLSI I/LA20-A2: Analytical Performance Characteristics and Clinical Utility of Immunological Assays for Human Immunoglobulin E (IgE) Antibodies and Defined Allergy Specificities; Approved Guidelines - Second Edition.

CEN 13640: 2002 Stability Testing of in vitro Diagnostic Reagents

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FDA Guidance – 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 patient 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:

i) Within-Lot imprecision:

Imprecision of the individual allergen components was evaluated by using two positive plasma samples including a low range sample (0.35 ± 25%) and a high range sample (≥0.7 kU/L), each tested in 4 replicates in 1 assay run per day for a total of 20 operating days (a total of 80 replicates per sample). The assay was performed according to the ImmunoCAP Specific IgE Directions for Use using Phadia 250. Between-day and within-run coefficients of variance (%CV) were calculated for each component and each sample separately.

CV% values for individual allergen components

| ImmunoCAP Allergen | Positive Sample | n | Mean (kU/L) | Between Days CV% | Within-run CV% | Total CV% |
| --- | --- | --- | --- | --- | --- | --- |
| f236, Cow’s milk whey | 1 | 80 | 2.68 | 3.47 | 3.58 | 4.98 |
| | 2 | 80 | 0.34 | 4.65 | 3.16 | 5.62 |
| f309, Chick pea | 1 | 80 | 3.30 | 1.56 | 3.20 | 3.56 |
| | 2 | 80 | 0.36 | 1.58 | 3.93 | 4.23 |
| t212, Cedar | 1 | 80 | 2.15 | 4.47 | 5.47 | 7.07 |
| | 2 | 80 | 0.30 | 3.61 | 3.66 | 5.14 |
| t222, Cupressus arizonica | 1 | 80 | 2.17 | 7.58 | 10.91 | 13.28 |
| | 2 | 80 | 0.32 | 4.09 | 4.41 | 6.02 |

n = number of samples

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Pooled CV% values for individual allergens

| ImmunoCAP Allergen | N | Between Day CV% | Within-run CV% | Total CV% |
| --- | --- | --- | --- | --- |
| f236, Cow’s milk whey | 2 | 4.10 | 3.37 | 5.31 |
| f309, Chick pea | 2 | 1.57 | 3.58 | 3.91 |
| t212, Cedar | 2 | 4.06 | 4.65 | 6.18 |
| t222, Cupressus arizonica | 2 | 6.09 | 8.32 | 10.31 |

n = number of samples

ii) Lot-to-lot imprecision:

Three ImmunoCAP Allergen Component lots for each allergen were tested using two positive samples (0.35 ± 25% and ≥0.7 kU_A/l) and one negative sample (< 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. The assay was performed according to the ImmunoCAP Specific IgE, Directions for Use using Phadia 250. Mean concentration values, %CV and concentration quotients between lots were calculated for the positive samples.

| Lot | Positive 1 | | Positive 2 | | Negative | Concentration Quotient | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Mean (kU_A/L) | CV (%) | Mean (kU_A/L) | CV (%) | Mean (kU_A/L) | | Positive 1 | Positive 2 |
| ImmunoCAP Allergen f236, Allergen Component Cow’s milk whey | | | | | | | | |
| 1 | 1.95 | 2.7 | 0.33 | 1.8 | <0.1 | lot1/lot2 | 1.04 | 1.05 |
| 2 | 1.87 | 3.8 | 0.32 | 1.2 | <0.1 | lot1/lot3 | 0.99 | 1.02 |
| 3 | 1.96 | 2.5 | 0.33 | 2.2 | <0.1 | lot2/lot3 | 0.96 | 0.97 |
| ImmunoCAP Allergen f309, Allergen Component Chick pea | | | | | | | | |
| 1 | 1.89 | 5.8 | 0.27 | 3.6 | <0.1 | lot1/lot2 | 0.83 | 0.89 |
| 2 | 2.26 | 2.6 | 0.31 | 2.1 | <0.1 | lot1/lot3 | 0.84 | 0.93 |
| 3 | 2.23 | 2.7 | 0.29 | 5.4 | <0.1 | lot2/lot3 | 1.01 | 1.05 |
| ImmunoCAP Allergen t212, Allergen Component Cedar | | | | | | | | |
| 1 | 3.23 | 3.7 | 0.32 | 2.7 | <0.1 | lot1/lot2 | 0.91 | 0.94 |
| 2 | 3.57 | 2.1 | 0.34 | 2.1 | <0.1 | lot1/lot3 | 0.86 | 0.94 |
| 3 | 3.75 | 4.0 | 0.34 | 1.7 | <0.1 | lot2/lot3 | 0.95 | 1.01 |

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| Lot | Positive 1 | | Positive 2 | | Negative | Concentration Quotient | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Mean (kU_A/L) | CV (%) | Mean (kU_A/L) | CV (%) | Mean (kU_A/L) | | Positive 1 | Positive 2 |
| ImmunoCAP Allergen t222, Allergen Component Cupressus arizonica | | | | | | | | |
| 1 | 1.90 | 2.0 | 0.40 | 2.6 | <0.1 | lot1/lot2 | 1.03 | 1.04 |
| 2 | 2.81 | 5.3 | 0.39 | 1.6 | <0.1 | lot1/lot3 | 0.84 | 1.01 |
| 3 | 3.45 | 3.7 | 0.40 | 3.4 | <0.1 | lot2/lot3 | 0.81 | 0.97 |

b. Linearity/assay reportable range:

The linearity of the four individual allergens was assessed following the CLSI I/LA20-A2 guidelines. For each allergen component, three positive plasma samples were each diluted in negative plasma generating 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. ImmunoCAP Specific Total IgE working range is LoD to 100 kU_A/L.

For each allergen, results of 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:

| ImmunoCAP Allergen | Regression Equation | r² | 95% CI Slope | 95% CI Intercept | Highest level tested (kU_A/L) |
| --- | --- | --- | --- | --- | --- |
| f236, Cow's milk whey | y = 0.96x + 0.09 | 1.00 | 0.95 – 0.97 | 0.08 – 0.10 | 85.61 |
| f309, Chick pea | y = 0.95x + 0.07 | 1.00 | 0.94 – 0.95 | 0.06 – 0.08 | 52.51 |
| t212, Cedar | y = 0.96x + 0.08 | 1.00 | 0.95 – 0.97 | 0.07 – 0.08 | 39.42 |
| t222, Cupressus arizonica | y = 0.95x + 0.06 | 1.00 | 0.94 – 0.95 | 0.05 – 0.06 | 14.30 |

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

i) Traceability:

The IgE calibrators are traceable (via an unbroken chain of calibrations) to the 2nd International Reference Preparation (IRP) 75/502 of Human Serum Immunoglobulin E from World Health Organization (WHO).

ii) Kit Stability:

Real-time and Accelerated stability - The stability studies were performed in accordance with EN 13640 (Stability Testing of In Vitro Diagnostic Reagents) to demonstrate 24 month unopened shelf-life stability (from the date of manufacture

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when stored at recommended temperature $2 - 8^{\circ}\mathrm{C}$ ) of the ImmunoCAP Allergen f236 Cow's milk whey, f309 Chick pea, t212 Cedar and t222 Cupressus arizonica by an on-going real time stability study and accelerated stability study. For real-time stability study, three lots of ImmunoCAP Allergen Component were stored at recommended storage temperature $2 - 8^{\circ}\mathrm{C}$ . Two positive plasma samples and one negative plasma sample were tested at different occasions according to the ImmunoCAP Specific IgE, Directions for Use, using Phadia 250. The study is ongoing. For accelerated study, three lots of ImmunoCAP Allergen Components were stored at $30^{\circ}\mathrm{C}$ and tested after 4 and 8 weeks using two positive plasma samples and one negative plasma sample. The same lots stored at $2 - 8^{\circ}\mathrm{C}$ were used as reference. The results support the manufacture's claim of 24 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) and 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. The results are shown in the table below.

| ImmunoCAP Allergen | LoB | LoD |
| --- | --- | --- |
| f236, Cow's milk whey | 0.032 | 0.043 |
| f309, Chick pea | 0.018 | 0.029 |
| t212,Cedar | 0.000 | 0.012 |
| t222, Cupressus arizonica | 0.05 | 0.067 |

# d. Analytical specificity:

# i) Inhibition studies:

Immunological specificity of the allergen components was verified through competitive inhibition studies in accordance with CLSI I/LA20-A2. The specific IgE concentration for the positive samples is shown in the table below.

| ImmunoCAP Allergen | kUAl/L |
| --- | --- |
| f236, Cow's milk whey | 9.3 |
| f309, Chick pea | 12.5 |
| t212, Cedar | 12.0 |
| t222, Cupressus arizonica | 9.2 |

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The allergen solution was serially diluted with buffer to show an overall dose dependent inhibition. The unrelated allergen solutions are not further diluted. Equal volumes of a positive sample and varying dilutions of allergen solution (inhibitor) were premixed. The mixture was incubated in a sample tube at room temperature for 1 hour before being analyzed with the corresponding ImmunoCAP Allergen Component on ImmunoCAP instrument according to the manufacturer's instructions. The testing was performed in duplicates in one assay run. Mean values were calculated.

The inhibition test was evaluated with inhibition values in %, calculated according to the formula below:

$$
\left(\frac {1 - \left(\frac {t - b}{t - b}\right)}{t - b}\right) \times 10 = \%
$$

r = response [RU]
b = background response (100% inhibition) [RU]
t = total response (0% inhibition) [RU]
i = inhibition

Any negative inhibition %-values are shown as 0% inhibition.

The results of the inhibition with the allergen solution and the unrelated inhibitors indicate that the 4 new allergens contain the immunologically relevant allergen as shown below:

## ImmunoCAP Allergen f236, Allergen Component Cow's milk whey

The Cow's milk whey allergen Inhibition study showed that ≥ 50% inhibition was achieved with the related inhibitor (Cow's milk whey allergen) at a final inhibitor concentration of 480 ng/mL. The inhibition studies using four unrelated inhibitors, including three from unrelated groups (m36, e85, w204) and one from the related/same group (f83) did not show any significant inhibition at the highest inhibitor concentration of 1.4 mg/mL. The inhibition studies indicate that the ImmunoCAP Allergen f236, Cow's milk whey solid phase contains the immunologically relevant allergen.

## ImmunoCAP Allergen f309, Allergen Component Chick pea

The Chick pea allergen Inhibition study showed that about 50% inhibition was achieved with the related inhibitor (Chick pea allergen) at a final inhibitor concentration of ~0.31 mg/mL. The inhibition studies using four unrelated inhibitors, including three from unrelated groups (m36, g6, d201) and one from the related/same group (f83) did not show any significant inhibition at the highest inhibitor concentration of 4.0 mg/mL. The inhibition studies indicate that the ImmunoCAP Allergen f309, Chick pea solid phase contains the immunologically relevant allergen.

## ImmunoCAP Allergen t212, Allergen Component Cedar

The Cedar allergen Inhibition study showed that about 50% inhibition was achieved with the related inhibitor (Cedar allergen) at a final inhibitor concentration of ~27 μg/mL. The inhibition studies using three unrelated inhibitors from unrelated groups (m36, w204, g6) did not show any significant inhibition at the highest inhibitor

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concentration of 4.0 µg/mL. An unrelated allergen f222, Cupressus arizonica did show significant inhibition (&gt;15%) at a final concentration of 2.7 mg/mL. In contrast, another unrelated allergen t3, birch from the related/same group did not show any significant inhibition at a final concentration of 2.7 mg/mL.

## ImmunoCAP Allergen t222, Allergen Component Cupressus arizonica

The Cupressus arizonica allergen Inhibition study showed that about 50% inhibition was achieved at a final inhibitor concentration of ~8.7 µg/mL. The inhibition studies using three unrelated inhibitors from unrelated groups (m36, d74, w204) did not show any significant inhibition at the highest inhibitor concentration of 4.0 mg/mL. An unrelated allergen t212, Cedar from the related/same group did show significant inhibition (&gt;15%) at a final concentration of 2.7 mg/mL. In contrast, another unrelated allergen t3, birch from the related/same group did not show any significant inhibition at a final concentration of 0.87 mg/mL.

### ii) Interference:

#### a) Endogenous Substance Interference:

In order to show that icteric, hemolytic or lipemic samples do not adversely affects the results in ImmunoCAP Specific IgE assay using representative allergens, Bilirubin C [final concentration (fc) 20 mg/dL], Bilirubin F (fc 19 mg/dL), Hemoglobin (fc 489 mg/dL) and Chyle (fc 1,440 Formazine Turbidity Units) were spiked into 2 samples per allergen. The allergens tested were e228 rFel d 4 Cat, f351 rPen a 1 Tropomyosin Shrimp, f354 rBer e 1 Brazil nut, f420 rPru p 3 LTP Peach and w231 nArt v 1 Mugwort. The design of the studies was in general alignment with CLSI EP7-A2 Guideline. The results demonstrate that icteric, hemolytic or lipemic samples do not adversely affects the results in ImmunoCAP Specific IgE.

#### b) Exogenous Substance Interference:

Two literature references were provided supporting that commonly prescribed "allergy medications" do not interfere with ImmunoCAP Specific IgE. The references included (i) Robert G. Hamilton, Accuracy of US Food and Drug Administration-cleared IgE antibody assays in the presence of anti-IgE (omalizumab), J. Allergy Clin. Immunol. 2006; 759-766, and (ii) Linda Cox et al., Pearls and pitfalls of allergy diagnostic testing: report from the American College of Allergy, Asthma and Immunology/American Academy of Allergy, Asthma and Immunology Specific IgE Test Task Force, Annals of Allergy, Asthma &amp; Immunology, 2008; 101:580-592.

### f. Assay cut-off:

Limit of Quantitation for ImmunoCAP Specific IgE is 0.1 kUA/L. All results &gt;0.1 kUA/L are interpreted as being analytically positive.

## 2. Comparison studies:

### a. Method comparison with predicate device:

Refer to clinical studies.

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# b. Matrix comparison:

The "Proof of Principle" study that different matrix samples (heparin plasma, EDTA plasma and serum) are interchangeable for ImmunoCAP Allergen Components was provided in k101251. Serum, sodium heparin plasma, and EDTA plasma samples were collected from four patients with clinical history of known specific allergies and four nonatopic patients. The samples contained specific IgE antibodies for one or more of the allergen components tested. All sample matrices (heparin plasma, EDTA plasma and serum) from each patient were tested with ImmunoCAP Allergen Components in 2 replicates in one assay run. Mean concentration values for each sample matrix were calculated. Mean logarithmic ratios for 17 results were -0.022 (Plasma heparin/Serum) and 0.054 (Plasma EDTA/Serum). The results from the study show that samples of different matrices (heparin plasma, EDTA plasma and serum) are interchangeable for ImmunoCAP Allergen Components.

# 3. Clinical studies:

# a. Clinical Sensitivity and Specificity:

The performance of all 4 individual allergen components was compared to a clinical diagnosis of allergy. The objectives of this study were (i) to show the linkage between specific IgE antibodies to ImmunoCAP Allergen Component and the corresponding extract based ImmunoCAP Allergen, using clinical samples, and (ii) to demonstrate that samples from healthy, non-atopic donors with no reported clinical reaction to the allergen have undetectable or very low levels of specific IgE to the individual ImmunoCAP Allergen Component. At least 30 clinical serum samples from individuals with a clinical history of allergy-like symptoms upon exposure to the allergen, as diagnosed by a physician were used in the study. Information about clinical symptoms and manifestations was available for all clinical samples. 100 negative samples $(&lt; 0.35\mathrm{kU}_{\mathrm{A}} / \mathrm{L})$ from healthy non-atopic donors with no reported clinical reaction to the allergen were also tested.

ImmunoCAP Allergen f236, Cow's milk whey

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| f236, Cow's milk whey | Positive | 42 | 0 | 42 |
| | Negative | 0 | 100 | 100 |
| | Total | 42 | 100 | 142 |

Sensitivity $= 100\%$ (95% CI: 91.6 - 100%)
Specificity $= 100\%$ (95% CI: 96.4 - 100%)

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ImmunoCAP Allergen f309, Chick pea

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| f309, Chick pea | Positive | 64 | 0 | 64 |
| | Negative | 0 | 100 | 100 |
| | Total | 64 | 100 | 164 |

Sensitivity = 100% (95% CI: 94.4 - 100%)
Specificity = 100% (95% CI: 96.4 - 100%)

ImmunoCAP Allergen t212, Cedar

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| t212, Cedar | Positive | 30 | 0 | 28 |
| | Negative | 0 | 100 | 100 |
| | Total | 30 | 100 | 128 |

Sensitivity = 100% (95% CI: 87.7 - 100%)
Specificity = 100% (95% CI: 96.4 - 100%)

ImmunoCAP Allergen t222, Cupressus arizonica

| | Clinical Diagnosis | | | |
| --- | --- | --- | --- | --- |
| | | Atopic | Non-atopic | Total |
| t222, Cupressus arizonica | Positive | 63 | 0 | 63 |
| | Negative | 0 | 100 | 100 |
| | Total | 63 | 100 | 163 |

Sensitivity = 100% (95% CI: 94.3 - 100%)
Specificity = 100% (95% CI: 96.4 - 100%)

All negative samples showed undetectable level (&lt;0.1 kU_A/L) of allergen specific IgE. Studies described above were performed on the Phadia 1000 instrument system.

b. Other clinical supportive data (when a. is not applicable):
Not applicable.

4. Clinical cut-off:
Not applicable.

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5. Expected values/Reference range:

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

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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