ImmunoCAP Allergen o215, Component nGal-alpha-1,3-Gal(alpha-Gal) Thyroglobulin, bovine

K200279 · Phadia AB · DHB · May 1, 2020 · Immunology

Device Facts

• Record ID: K200279
• Device Name: ImmunoCAP Allergen o215, Component nGal-alpha-1,3-Gal(alpha-Gal) Thyroglobulin, bovine
• Applicant: Phadia AB
• Product Code: DHB · Immunology
• Decision Date: May 1, 2020
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5750
• Device Class: Class 2

Indications for Use

ImmunoCAP Allergen o215, Component nGal-alpha-1,3-Gal (alpha-Gal) Thyroglobulin, bovine, is intended for in vitro diagnostic use, in human serum or EDTA plasma, as an aid in the diagnosis of IgE mediated mammalian (red) meat hypersensitivity, due to alpha-Gal sensitization, and to be used in conjunction with other clinical findings. This test is not to be the sole criterion for diagnosing allergy to alpha-Gal. It is a quantitative test to be used in clinical laboratories. ImmunoCAP Allergen o215, alpha-Gal is to be used with the ImmunoCAP Specific IgE assay on the instrument Phadia 250.

Device Story

ImmunoCAP Allergen o215 is an in vitro diagnostic reagent used with the Phadia 250 instrument to quantify allergen-specific IgE antibodies in human serum or EDTA plasma. The device consists of purified bovine thyroglobulin (nGal-alpha-1,3-Gal) covalently coupled to a solid-phase carrier. During operation, patient samples are incubated with the allergen-coated carrier; specific IgE antibodies bind to the allergen. After washing, enzyme-labeled anti-IgE antibodies are added, forming a complex. A developing agent is added, and the resulting fluorescence is measured. The system software converts fluorescence intensity into concentration (kUA/L) using a calibration curve. Results assist clinicians in diagnosing red meat hypersensitivity in patients presenting with symptoms like urticaria or anaphylaxis. The test is intended for professional use in clinical laboratories.

Clinical Evidence

Retrospective clinical study of 310 subjects: 200 patients with red meat hypersensitivity (Group A) and 110 controls (60 atopic, 50 non-atopic). Primary endpoint was clinical sensitivity and specificity for alpha-Gal sensitization. Results: 195/200 positive in Group A (97.5% sensitivity; 95% CI: 94.3–99.2%). 100/110 negative in control groups (90.9% specificity; 95% CI: 83.9–95.6%). Bench testing included precision (within-run/between-run CVs), linearity (r²=1.00), and interference studies (bilirubin, chyle, hemoglobin, rheumatoid factor).

Technological Characteristics

Quantitative fluorescence immunoassay. Solid phase: ImmunoCAP with covalently coupled nGal-alpha-1,3-Gal (alpha-Gal) Thyroglobulin, bovine. Detection: enzyme-labeled anti-IgE antibodies. Instrument: Phadia 250. Software: Phadia Information Data Manager (IDM) or Phadia Prime. System is an automated in vitro diagnostic platform.

Indications for Use

Indicated for in vitro diagnostic use in human serum or EDTA plasma as an aid in diagnosing IgE-mediated mammalian (red) meat hypersensitivity due to alpha-Gal sensitization. For use in clinical laboratories in conjunction with other clinical findings. Not for use as the sole diagnostic criterion.

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 system, UniCAP Specific IgE Assay and UniCAP Specific IgE Conjugate 100 and Conjugate 400 (K051218)

Submission Summary (Full Text)

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FDA U.S. FOOD & DRUG ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

## I Background Information:

A 510(k) Number
K200279

B Applicant
Phadia AB

C Proprietary and Established Names
ImmunoCAP Allergen o215, Component nGal-alpha-1,3-Gal(alpha-Gal) Thyroglobulin, bovine

D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| DHB | Class II | 21 CFR 866.5750 - Radioallergosorbent(Rast) Immunological Test System | IM - Immunology |

## II Submission/Device Overview:

A Purpose for Submission:
Addition of an allergen to a cleared device

B Measurand:
Allergen-specific IgE for o215, Component nGal-alpha-1,3-Gal (alpha-Gal) Thyroglobulin, bovine

C Type of Test:
Fluoroenzyme immunoassay, Quantitative

Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov

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III Intended Use/Indications for Use:

A Intended Use(s):
See Indications for Use below.

B Indication(s) for Use:
ImmunoCAP Allergen o215, Component nGal-alpha-1,3-Gal (alpha-Gal) Thyroglobulin, bovine, is intended for in vitro diagnostic use, in human serum or EDTA plasma, as an aid in the diagnosis of IgE mediated mammalian (red) meat hypersensitivity, due to alpha-Gal sensitization, and to be used in conjunction with other clinical findings. This test is not to be the sole criterion for diagnosing allergy to alpha-Gal. It is a quantitative test to be used in clinical laboratories. ImmunoCAP Allergen o215, alpha-Gal is to be used with the ImmunoCAP Specific IgE assay on the instrument Phadia 250.

C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only

D Special Instrument Requirements:
For use on the Phadia 250 instrument

IV Device/System Characteristics:

A Device Description:
The ImmunoCAP system is a fully integrated and automated system for the determination of specific IgE in human blood serum or plasma samples. It is comprised of general, and test- and method-specific reagents for Phadia 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 allergens (native or recombinant) covalently coupled to a support in a plastic housing.

B Principle of Operation:
The allergen of interest, covalently coupled to ImmunoCAP solid phase, reacts with the specific IgE in the patient sample. After washing away nonspecific 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 a developing agent. After stopping the reaction, the fluorescence of the eluate is measured. The higher the response value, the more

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specific IgE is present in the specimen. The fluorescence results are converted to $\mathrm{kU_A / L^+}$ concentrations by the software with the use of a calibration curve.

V Substantial Equivalence Information:

A Predicate Device Name(s):

UniCAP system, UniCAP Specific IgE Assay and UniCAP Specific IgE Conjugate 100 and Conjugate 400

B Predicate 510(k) Number(s):

K051218

C Comparison with Predicate(s):

| Device & Predicate Device(s): | Device K200279 | Predicate K051218 |
| --- | --- | --- |
| Device Trade Name | ImmunoCAP Allergen o215, alpha-Gal | UniCAP Specific IgE |
| General Device Characteristic Similarities | | |
| Intended Use/Indications for Use | ImmunoCAP Allergen o215, Component nGal-alpha-1,3-Gal (alpha-Gal) Thyroglobulin, bovine, is intended for in vitro diagnostic use, in human serum or EDTA plasma, as an aid in the diagnosis of IgE mediated mammalian (red) meat hypersensitivity, due to alpha-Gal sensitization, and to be used in conjunction with other clinical findings. This test is not to be the sole criterion for diagnosing allergy to alpha-Gal. It is a quantitative test to be used in clinical laboratories. ImmunoCAP Allergen o215, alpha-Gal is to be used with the ImmunoCAP Specific IgE assay on the instrument Phadia 250. | UniCAP 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 |
| Type of Test | Quantitative | Same |
| Test Principle | Fluoroenzyme immunoassay | Same |
| Software | Phadia Information Data Manager or Phadia Prime | Same |
| Detection antibody | β-Galactosidase-anti-human IgE | Same |

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| | (mouse monoclonal antibody) | |
| --- | --- | --- |
| Number of calibrators | Six | Same |
| Sample Matrix | Human serum or plasma (EDTA) | Same |
| Sample volume | 40 μL | Same |
| Analytical Sensitivity (LoD/LoQ) | 0.1 kU_{A}/L | Same |

VI Standards/Guidance Documents Referenced:

CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline –Third Edition

CLSI EP06-A, Evaluation of Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline

CLSI EP07, 3rd Edition, Interference Testing in Clinical Chemistry

CLSI EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline – Second Edition

CLSI EP25-A: Evaluation of Stability of in vitro Diagnostic Reagents

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

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

All results presented below met the manufacturer’s pre-determined acceptance criteria.

1. Precision/Reproducibility:

i) Within-laboratory imprecision:

Imprecision of the ImmunoCAP Allergen o215, alpha-Gal was evaluated by testing three positive samples including a low-level sample near the medical decision point (0.35 ± 25% kU_A/L), each tested in four replicates in one 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 a Phadia 250 instrument. Between-run and within-run coefficients of variance (%CVs) were calculated for each sample separately. Results are shown in the table below:

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| Specimen | N | Mean (kU_{A}/L) | Within-Run (Repeatability) | | Between-Run (Repeatability) | | Total (Within-Laboratory) | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | SD | %CV | SD | %CV | SD | %CV |
| 1 | 80 | 0.18 | 0.02 | 9.2 | 0.02 | 8.9 | 0.02 | 12.8 |
| 2 | 80 | 0.42 | 0.02 | 5.1 | 0.02 | 5.1 | 0.03 | 7.3 |
| 3 | 80 | 3.03 | 0.07 | 2.4 | 0.11 | 2.4 | 0.13 | 4.4 |
| N=number of replicates | | | | | | | | |

ii) Lot-to-lot imprecision:

Three different lots of ImmunoCAP Allergen o215, alpha-Gal were tested using three positive samples and one negative plasma sample (< 0.1 kU_A/L). For each lot, the samples were tested in 12 replicates in one assay run. The assay was performed according to the ImmunoCAP Specific IgE, Directions for Use, using a Phadia 250 instrument. Negative samples results were all below 0.1 kU_A/L and only positive results are included in the table below. Mean concentration values and %CV (lowest mean concentration/ highest mean concentration between lots) were calculated for the positive samples and are presented in the tables below:

| Lot | Sample Panel | | | | | |
| --- | --- | --- | --- | --- | --- | --- |
| | Positive 1 | | Positive 2 | | Positive 3 | |
| | Mean (kU_A/L) | CV (%) | Mean (kU_A/L) | CV (%) | Mean (kU_A/L) | CV (%) |
| 1 | 0.42 | 6.3 | 2.52 | 3.2 | 16.5 | 3.4 |
| 2 | 0.39 | 7.3 | 2.60 | 3.4 | 17.0 | 1.7 |
| 3 | 0.38 | 9.0 | 2.54 | 3.0 | 16.4 | 3.4 |

2. Linearity:

The linearity of ImmunoCAP Allergen o215, alpha-Gal was assessed following CLSI guideline I/LA-20 3rd Edition. Three positive samples were each diluted to generate at least six 2-fold consecutive dilutions. Undiluted samples were tested in 12 replicates and diluted samples were tested in four replicates in one assay run on the Phadia 250 instrument according to the ImmunoCAP Specific IgE, Directions for Use using one lot of ImmunoCAP Allergen o215 reagent. Results of the replicates from all three samples were analyzed for linearity. Regression statistics comparing the observed results to expected results are presented below:

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| Sample | Concentration range tested (kU_{A}/L) | r^{2} | Slope (95% CI) | Intercept (95% CI) |
| --- | --- | --- | --- | --- |
| 1 | 0.11 – 14.9 | 1.00 | 1.00 (0.98 – 1.02) | -0.07 (-0.19 – 0.05) |
| 2 | 0.16 – 23.8 | 1.00 | 1.00 (0.95 – 1.03) | -0.10 (-0.49 – 0.29) |
| 3 | 0.15 – 47.3 | 1.00 | 0.99 (0.95 – 1.03) | -0.38 (-1.14 – 0.39) |
| 4 | 0.13 – 86.3 | 1.00 | 1.04 (1.03 – 1.05) | -0.06 (-0.07 – -0.05) |
| Pooled | 0.11 – 86.3 | 1.00 | 1.03 (1.03 – 1.04) | -0.05 (-0.06 – -0.04) |

The claimed assay range of ImmunoCAP Allergen o215, alpha-Gal is 0.1 to 86.3 kU$_{\mathrm{A}}$/L.

## 3. Analytical Specificity/Interference:

### i) Inhibition studies:

Immunological specificity of ImmunoCAP Allergen o215, alpha-Gal was verified by performing competitive inhibition studies in accordance with I/LA-20 3rd Edition. A positive sample with known concentration of IgE specific to allergen component o215 (4.8 kU$_{\mathrm{A}}$/L) was tested. Equal volumes of the positive sample and varying serial dilutions of the specific allergen component o215 in solution were premixed. The mixture was incubated in a sample tube at room temperature for two hours before being analyzed with ImmunoCAP Allergen o215, alpha-Gal on the Phadia 250 according to the ImmunoCAP Specific IgE, Directions for Use. The testing was performed in duplicate in one assay run. Mean values (in kU$_{\mathrm{A}}$/L) were calculated. The inhibition values in % were calculated according to the formula below:

$$
\left(1 - \left(\frac {r - b}{t - b}\right)\right) \times 100 = i \%
$$

r = concentration [kU$_{\mathrm{A}}$/L]

b = background concentration (100% inhibition) [kU$_{\mathrm{A}}$/L]

t = total concentration (0% inhibition) [kU$_{\mathrm{A}}$/L]

i = inhibition

Results from the dose-dependent inhibition study showed that >50% inhibition was achieved with the specific allergen component o215 in solution at a concentration of 6.5 pmol/μL.

To further evaluate the immunological specificity of ImmunoCAP Allergen o215, alpha-Gal, three allergens from different or unrelated allergen groups [nGal d 1 (ovomucoid), Pla l 1 (Plantain) and rPhl p 11 (grass pollen)] and one allergen from the same or related allergen group [cross-reactive carbohydrate determinants (CCD)] were tested at doses that are 10-fold or higher than the specific allergen component concentration that yielded

K200279 - Page 6 of 12

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>50% inhibition. None of the allergens tested show any significant inhibition. The inhibition studies indicate that the ImmunoCAP Allergen o215 solid phase contains the immunologically relevant allergen component.

## ii) Interference:

### a) Endogenous Substance Interference:

Interferences were assessed by testing two positive samples and one negative sample. Each sample was spiked with the interfering substances or substance-specific diluents and analyzed in four replicates in one assay run using the Phadia 250 according to the ImmunoCAP Specific IgE, Directions for Use. The data demonstrated that ImmunoCAP Allergen o215, alpha-Gal was not adversely affected by high levels of the following substances up to the concentrations listed in the table below:

| Interferent | No inhibition up to the tested concentrations |
| --- | --- |
| Bilirubin, unconjugated | 327.0 μmol/L |
| Bilirubin, conjugated | 363.0 μmol/L |
| Chyle | 1610.0 FTU (Formazine Turbidity Units) |
| Hemoglobin | 4.9 g/L |
| Rheumatoid factor | 550 IU/mL |

### b) Exogenous Substance Interference:

Two literature references were provided supporting the claim 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 & Immunology, 2008; 101:580-592.

## 4. Assay Reportable Range:

The claimed measuring range is from 0.1 to 86.3 kU_A/L.

## 5. 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 or the equivalent 3rd International Standard 11/234 of Human Serum Immunoglobulin E from World Health Organization (WHO).

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ii) Kit Stability:

A real-time stability study was performed using three lots of ImmunoCAP Allergen o215, alpha-Gal in accordance with CLSI EP25-A to demonstrate shelf-life stability (from the date of manufacture). The stability data support 24 months unopened shelf-life stability.

The studies to determine the stability of the calibration curve calibrators, real-time, and on-board stability of ImmunoCAP IgE calibrator are described in K100999.

6. Detection Limit:

The Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation (LoQ) were determined on the Phadia 250 in alignment with the CLSI guideline EP17-A2 using two lots of ImmunoCAP Allergen o215, alpha-Gal.

The LoB was determined by testing five blank samples in three runs with five replicates per run to yield a total of 75 replicates per lot for all samples. The LoB was estimated as the 95% percentile of the distribution and determined as 0 kUA/L and 0.013 kUA/L for the two lots of ImmunoCAP Allergen o215, alpha-Gal. The claimed LoB is 0.013 kUA/L.

The LoD was determined by testing five low positive samples in three runs with five replicates to yield a total of 75 replicates per lot for all samples. The LoD was calculated according to the equation: $$ \text{LoD} = \text{LoB} + c\beta \cdot \text{SDLoD} $$ where SDLoD is the pooled SD for the samples, and determined as 0.021 kUA/L and 0.025 kUA/L for the two lots of ImmunoCAP Allergen o215, alpha-Gal. The claimed LoD is 0.1 kUA/L.

The LoQ was estimated as the mean value of the sample which fulfills the specification for the total within-laboratory imprecision ≤ 20% CV. The LoQ was determined as 0.025 kUA/L and 0.034 kUA/L for the two lots of ImmunoCAP Allergen o215, alpha-Gal. The precision profile supports the LoQ claim of 0.1 kUA/L which is the lower limit of the measuring range claimed for ImmunoCAP Allergen o215, alpha-Gal.

7. Assay Cut-Off:

Limit of Quantitation for ImmunoCAP Specific IgE is 0.10 kUA/L. All results > 0.1 kUA/L are interpreted as being analytically positive.

B Comparison Studies:

1. Method Comparison with Predicate Device:

Refer to clinical studies.

2. Matrix Comparison:

To demonstrate that K₂-EDTA plasma samples yield results comparable with serum samples by the ImmunoCAP Allergen o215, alpha-Gal, a study was performed by using 40 serum/K2-

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EDTA plasma paired samples. None of the samples were contrived. Paired samples were each tested according to ImmunoCAP Specific IgE Directions for Use in one replicate in one assay run on one Phadia 250 instrument using one lot of ImmunoCAP Allergen o215, alpha-Gal. The Passing-Bablok regression analysis was performed, and the results are summarized in the following table:

| Comparison | N* | Sample Range (kU_{A}/L) | Slope (95% CI) | Intercept (95% CI) | Correlation Coefficient (r) |
| --- | --- | --- | --- | --- | --- |
| K_{2}-EDTA plasma vs. serum | 31 | 0.14–85.0 | 0.99 (0.97 – 1.00) | 0.001 (-0.002 – 0.03) | 1.00 |
| * Excludes five samples with results below the measuring range for both matrices and four samples with results above the measuring range for both matrices. | | | | | |

## C Clinical Studies:

### 1. Clinical Sensitivity and Specificity:

Serum samples from 200 patients presenting to the University of Virginia Allergy Clinic with urticaria, anaphylaxis, or other symptoms following intake of red meat, were evaluated retrospectively (Study Group A: Allergic to red meat). Sixty allergic individuals without known alpha-Gal mediated red meat hypersensitivity were included as atopic controls in the study. Of these, 30 presented known allergies to foods, including animal-derived foods other than red meat (Study Group B: Atopic controls/ Other foods), and 30 were allergic to airborne allergens (Study Group C: Atopic controls/ Inhalants). Additionally, samples from 50 individuals, with no history of allergic disease and no evidence of atopic sensitization (Study Group D: Non-atopic controls), were analyzed. A summary of the demographic data per study group is presented in the table below.

| | Study Group A (N=200) | Study Group B (N=30) | Study Group C (N=30) | Study Group D (N=50) |
| --- | --- | --- | --- | --- |
| | Allergic to red meat | *Atopic controls/ Other foods | ^Atopic controls/ Inhalants | Non-atopic controls |
| Gender | | | | |
| Male/Female | 87 / 113 | 18 / 12 | 11 / 19 | 25 / 25 |
| Ethnicity | | | | |
| Caucasian | 189 | 2 | 12 | 0 |
| African American | 3 | 1 | 1 | 0 |
| Asian | 4 | 1 | 0 | 0 |
| Hispanic | 1 | 0 | 0 | 0 |
| Other | 1 | 1 | 1 | 0 |
| Not recorded | 2 | 25 | 16 | 50 |
| Age at blood draw | | | | |
| Years Median [Q1–Q3]) | 53.0 [43.0–64.0] | 11.5 [7.2–21.8] | 32.5 [19.8–46.2] | 47.5 [39.2–54.8] |
| * Allergic to foods other than red meat
^ Allergic to inhalants but not red meat | | | | |

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Allergy-related case history of the subjects in Study Groups A–C including history of food reactions, history of tick bites, doctor’s diagnosis of asthma and history of wheeze over the past 5 years are summarized in the table below.

| | Study Group A
(N=200) | Study Group B
(N=30) | Study Group C
(N=30) |
| --- | --- | --- | --- |
| | Allergic to red meat | *Atopic controls/
Other foods | ^Atopic controls/
Inhalants |
| History of wheeze 5 years | | | |
| Yes/No/Unknown | 59 / 139 / 2 | 10 / 5 / 15 | 11 / 11 / 8 |
| Doctor's diagnosis of Asthma | | | |
| Yes/No/Unknown | 33 / 166 / 1 | 8 / 7 / 15 | 13 / 17 / 0 |
| History of food reaction | | | |
| Yes/No/Unknown# | 39 / 159 / 2 | 30 / 0 / 0 | 13 / 17 / 0 |
| History of tick or chigger bites | | | |
| Yes/No/Unknown | 197 / 2 / 1 | 1 / 4 / 25 | 11 / 3 / 16 |
| Total IgE levels (kU_{A}/L) | | | |
| Median [Q1–Q3] | 146 [66–265] | 516 [175–1039] | 144 [54–263] |
| * Allergic to foods other than red meat
^ Allergic to inhalants but not red meat
# Excluding reactions to red meat | | | |

The reactions to red meat and dairy products or other foods in Study Group A is summarized in the table below:

| Clinical Features | Positive Cases (Positive Rate) |
| --- | --- |
| Gastro intestinal (GI) symptoms to red meat | 125/9 (63%) |
| Skin symptoms to red meat | 184 (92%) |
| Anaphylaxis to red meat | 111 (56%) |
| Reactions to dairy products | 16 (8%) |
| Reactions to other food(s) | 39 (20%) |

Among the patients with a red meat hypersensitivity (Group A), 97.5% (195/200) were found to be sensitized to alpha-Gal as measured by ImmunoCAP Allergen o215, alpha-Gal. Consistent with the ubiquitous presence of alpha-Gal in non-primate mammals, more than 75% of these patients also had specific IgE to other animal allergens tested: 98% were sensitized to beef (f27), 78% to cat dander (e1), 86% to dog dander (e5), 94% to pork (f26) and 93% to cow’s milk (f2). Consistent with the absence of alpha-Gal in non-mammalian animals, only 5% and 18% were sensitized to chicken (f83) and egg white (f1), respectively. Among the atopic controls (Study Groups B and C), 16.7% were sensitized to alpha-Gal. None of the non-atopic controls in Study Group D showed sensitization either to alpha-Gal or beef.

In total, 195 of 200 patients with a red meat hypersensitivity had specific IgE antibodies to alpha-Gal, corresponding to a clinical sensitivity of 97.5%. Of the 110 control subjects (60 atopic and 50 non-atopic), 10 (five food allergic subjects and five inhalant allergic subjects) were

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sensitized to alpha-Gal. Clinical performance, sensitivity (Se) and specificity (Sp) was calculated based on the detection limit of 0.1 kU/L. The results are summarized in the following table:

| | Clinical Diagnosis of red meat hypersensitivity | | | |
| --- | --- | --- | --- | --- |
| | | Present | Absent | Total |
| ImmunoCAP Allergen Component o215 | Positive ≥ 0.1 kU/L | 195 | 10 | 205 |
| | Negative < 0.1 kU/L | 5 | 100 | 105 |
| | Total | 200 | 110 | 310 |
| Sensitivity = 97.5% (195/200) 95% CI: 94.3 – 99.2%
Specificity = 90.9% (100/110) 95% CI: 83.9 – 95.6% | | | | |

The performance of samples from atopic controls and non-atopic subjects is summarized below:

| Study Groups | N Total | N Negative (< 0.1 kU/L) | Specificity (%) (95% CI) |
| --- | --- | --- | --- |
| All atopic controls (Study Groups B and C) | 60 | 50 | 83.3 (72.0 – 90.7) |
| All atopic controls (Study Group B) | 30 | 25 | 83.3 (66.4 – 92.7) |
| All atopic controls (Study Group C) | 30 | 25 | 83.3 (66.4 – 92.7) |
| Non-atopic controls (Study Group D) | 50 | 0 | 100 (92.9 – 100) |
| Total number of samples | 200 | | |
| N=Number | | | |

The specificity obtained from the atopic controls (83.3%) agrees with previous random cohort studies indicating that 15% or more of the general U.S. population is sensitized to alpha-Gal 1-3.

## D Clinical Cut-Off:

Not applicable

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E Expected Values/Reference Range:

The expected value determined in healthy, non-sensitized, individuals is &lt; 0.1 kU/A/L. Each laboratory is recommended to establish its own expected range of values.

VIII Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

IX Conclusion:

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