IMMUNOCAP RAPID INHALANT PROFILE , IMMUNOCAP RAPID READER, IMMUNOCAP RAPID READER CHECK DEVICE, AND IMMUNOCAP RAPID QC1

K081830 · Phadia AB · DHB · Mar 16, 2009 · Immunology

Device Facts

• Record ID: K081830
• Device Name: IMMUNOCAP RAPID INHALANT PROFILE , IMMUNOCAP RAPID READER, IMMUNOCAP RAPID READER CHECK DEVICE, AND IMMUNOCAP RAPID QC1
• Applicant: Phadia AB
• Product Code: DHB · Immunology
• Decision Date: Mar 16, 2009
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5750
• Device Class: Class 2

Intended Use

ImmunoCAP® Rapid Inhalant Profile 1, part of the ImmunoCAP Rapid System, is an in vitro semi-quantitative assay for measurement of allergen specific IgE to ten inhalant allergens (house dust mite, cat, dog, mold, and pollen from common ragweed, Bermuda grass, timothy grass, oak, and elm) in heparinized human capillary whole blood, heparinized venous whole blood, or heparinized 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, licensed under CLIA to perform nonwaived assays.

Device Story

System uses lateral flow immunoassay to detect allergen-specific IgE in heparinized capillary/venous whole blood or plasma; 10 allergens coupled to strips; gold-labeled anti-IgE conjugate binds IgE; Reader instrument captures images of test/control windows via CCD camera; measures color saturation; converts to Color Units (CU); categorizes into Class 1, 2, or 3. Used in CLIA-licensed clinical laboratories; operated by laboratory personnel. Output provides semi-quantitative IgE levels to aid clinical diagnosis of allergic disorders; results interpreted by clinicians alongside other findings.

Clinical Evidence

Bench testing only. Method comparison study (n=245) compared Rapid IP1 to predicate ImmunoCAP Specific IgE. Overall agreement 90.6-94.7% across matrices. Precision studies (CLSI EP5-A2) showed total CVs 12-25%. Interference testing (hemoglobin, heparin, bilirubin, chyle, total IgE) showed no significant interference. LoD/LoB established per CLSI EP17-A.

Technological Characteristics

Lateral flow immunoassay; gold-labeled anti-human IgE (mouse monoclonal clone 390); semi-quantitative; ambient temperature operation; Reader uses CCD camera (1024x768), white LED illumination, and mini-PC. Sterilization not specified. Software-based image analysis converts color saturation to Color Units.

Indications for Use

Indicated for patients suspected of IgE mediated allergic disorders to ten inhalant allergens (house dust mite, cat, dog, mold, and pollen from common ragweed, Bermuda grass, timothy grass, oak, and elm). For professional use only.

Regulatory Classification

Identification

A radioallergosorbent immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the allergen antibodies (antibodies which cause an allergic reaction) specific for a given allergen. Measurement of specific allergen antibodies may aid in the diagnosis of asthma, allergies, and other pulmonary disorders.

Special Controls

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

Predicate Devices

• ImmunoCAP Specific IgE (k962274)

Submission Summary (Full Text)

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# 10(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
k081830

B. Purpose for Submission:
New Device

C. Measurand:
Allergen specific IgE (house dust mite, cat, dog, mold, and pollen from common ragweed, Bermuda grass, timothy grass, oak, and elm)

D. Type of Test:
Semi-quantitative lateral flow

E. Applicant:
Phadia AB

F. Proprietary and Established Names:
ImmunoCAP® Rapid System
ImmunoCAP® Rapid Inhalant Profile 1
ImmunoCAP® Rapid Reader
ImmunoCAP® Rapid Reader Check Device
ImmunoCAP® Rapid QC 1

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® Rapid Inhalant Profile 1, part of the ImmunoCAP Rapid System, is an in vitro semi-quantitative assay for measurement of allergen specific IgE to ten inhalant allergens (house dust mite, cat, dog, mold, and pollen from common ragweed, Bermuda grass, timothy grass, oak, and elm) in heparinized human capillary whole blood, heparinized venous whole blood, or heparinized 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, licensed under CLIA to perform nonwaived assays.
2. Indication(s) for use:
See intended use above
3. Special conditions for use statement(s):
For professional use only
4. Special instrument requirements:
ImmunoCAP® Rapid Reader

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2

# I. Device Description:

The ImmunoCAP® Rapid System is a combination of lateral flow immunoassay reagents and instrument/software for semi-quantitative determination of antibodies or antigens in human capillary whole blood, heparinized venous whole blood or heparinized plasma. It is comprised of the ImmunoCAP® Rapid Inhalant Profile 1 kit (Rapid IP1), ImmunoCAP® Rapid Reader (Rapid Reader), ImmunoCAP® Rapid Reader Check Device (Rapid Reader CD), and ImmunoCAP® Rapid QC1 (Rapid QC1). The Rapid IP1 kit consists of three individually foil wrapped lateral flow devices, each containing 10 allergens coupled with a conjugated gold-anti-IgE (mouse monoclonal) antibody, one 6mL vial Developer Solution, 3 pipettes, and 3 blood sampling devices containing lithium heparin. The Rapid Reader consists of the Rapid Reader instrument and associated software. The Rapid Reader CD and Rapid QC 1 consist of (1 vial each, 0.2 mL positive and negative human plasma controls). The configuration of the allergens on the Rapid IP1 is as follows:

| Allergen | Code | flow | Allergen | Code |
| --- | --- | --- | --- | --- |
| Cat | e1 | | Mold (A. alternata) | m6 |
| House dust mite (D. pteronyssinus) | d1 | | Timothy | g6 |
| Bermuda grass | g2 | | Elm | t8 |
| Common ragweed | w1 | | Dog | e5 |
| Oak | t7 | | House dust mite (D. farinae) | d2 |

# J. Substantial Equivalence Information:

1. Predicate device name(s): ImmunoCAP Specific IgE
2. Predicate 510(k) number(s): k962274
3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Method | Sandwich immunoassay | Same |
| Allergens | house dust mite, cat, dog, mold, and pollen from common ragweed, Bermuda grass, timothy grass, oak, and elm | Same |
| Analyte | Specific IgE | Same |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | ImmunoCAP® Rapid Inhalant Profile 1, part of the ImmunoCAP Rapid System, is an in vitro semi-quantitative assay for measurement of | ImmunoCAP Specific IgE Assay is an in vitro quantitative assay for the measurement of allergen specific IgE in human serum |

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| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| | allergen specific IgE to ten inhalant allergens (house dust mite, cat, dog, mold, and pollen from common ragweed, Bermuda grass, timothy grass, oak, and elm) in heparinized human capillary whole blood, heparinized venous whole blood, or heparinized 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, licensed under CLIA to perform nonwaived assays. | or plasma. ImmunoCAP Specific IgE Assay is to be used with the instrument ImmunoCAP 100. 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. |
| Matrix | Capillary whole blood (lithium heparin); Venous whole blood (lithium and sodium heparin); Plasma (sodium heparin), | Serum or Plasma (EDTA, lithium & sodium heparin) |
| Detection Method | Direct reading | Enzyme-substrate reaction |
| Technology | Lateral flow | Fluroenzyme immunoassay |
| Reaction times | Step 1: 5 minutes
Step 2: 15 minutes | Step 1: 30 minutes
Step 1: 24 minutes |
| Detection agent | Anti-human IgE conjugated to gold particles | Anti-human IgE conjugated to beta-galactosidase |
| Assay Environment | Ambient room conditions (18-32°C, Relative humidity: 15-85%) | Instrument controlled |
| Sample volume | 90 μL: Plasma
110 μL: whole blood (capillary or venous) | 40 μL: Plasma or serum |
| Results Interpretation | Class 1 (Absent or Low)
Class 2 (Moderate or High)
Class 3 (Very High) | Class 0-1
Class 2-3
Class 4-6 |

K. Standard/Guidance Document Referenced (if applicable):
Radioallergosorbent Test (RAST) Methods for Allergen-Specific Immunoglobulin E (IgE) 510(k)s; Final Guidance for Industry and FDA
Guidance for the Content of Premarket Submissions for Software Contained in Medical

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Devices - Guidance for Industry and FDA Staff

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

EP07-A2 Interference Testing in Clinical Chemistry; Approved Guideline

# L. Test Principle:

Rapid IP1 is a lateral flow immunoassay for the semi-quantitative measurement of allergen specific IgE antibodies in human whole blood (WB) or plasma. Ten different allergens are bound to the strips in the Test Windows in separate lines. IgE antibodies present in the patient sample, specific to any of the allergens in the test, bind to the relevant allergen lines on the strips. In a single step, a gold labeled anti-IgE conjugate is solubilized, migrates up the strips and forms a visible red complex with bound IgE antibodies while unbound IgE is washed away. The conjugate continues to migrate, forming visible red lines in the Control Windows. The Rapid Reader quantitatively measures the color saturation and converts the signal into Color Units (CU). The higher the concentration of IgE antibodies in the sample the stronger the color of the red lines, i.e. higher CU values. CU values are then categorized semi-quantitatively into Class 1, 2 or 3.

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

# 1. Analytical performance:

# a. Precision/Reproducibility:

ImmunoCAP Rapid IP1 is a unitized point-of care test thus no intra- or within assay run component exists. In the analyses and presentations, the within assay run component is therefore equalized with the between Assay Device component. All precision studies were carried out in accordance to CLSI EP5-A2. For studies using whole blood, total precision was used as the measure of precision. Variation between device, run, lot, and operator were not determined.

# Run-to-Run:

Six sensitized single donors and one pooled plasma sample covering the Class 2 and 3 for all the allergens were tested using 3 devices per sample for 20 occasions and 50 sensitized single venous whole blood donor samples covering Classes 1-3 were tested using 3 devices per sample for 4 occasions. A minimum of 4 hours occurred between occasions. For plasma samples, the total variation between Assay Devices, between occasions was estimated to have a CV of $13\%$ and the variation between Assay Devices was $12\%$ , and the variation between occasions $4\%$ . The total variation using venous whole blood from 50 donors assayed in 12 Assay Devices gave a CV of $16\%$ .

Table 1. Coefficients of variance (CV%) for plasma samples tested in 3 Assay Devices on 20 occasions and measured as Color Units.

| Allergen | CV% Between Occasions | CV% Between Assay Devices | CV% Total |
| --- | --- | --- | --- |
| e1 | 3.39 | 10.35 | 10.89 |
| d1 | 4.64 | 13.43 | 14.21 |
| g2 | 6.08 | 14.87 | 16.06 |
| w1 | 2.99 | 13.37 | 13.70 |
| t7 | 3.59 | 11.80 | 12.33 |

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Table 2. Coefficients of variance (CV%) for venous whole blood from 50 donors assayed in 12 Assay Devices and measured as Color Units.

| Allergen | Number of samples | CV% Between Occasions | CV% Between Assay Devices | CV% Total (Sum of components) | CV% Total (All observations) |
| --- | --- | --- | --- | --- | --- |
| e1 | 22 | 7.25 | 11.86 | 13.9 | 13.55 |
| d1 | 17 | 4.89 | 13.86 | 14.7 | 14.55 |
| g2 | 23 | 7.86 | 16.33 | 18.13 | 17.82 |
| w1 | 32 | 6.89 | 13.58 | 15.23 | 14.94 |
| t7 | 22 | 6.5 | 17.13 | 18.32 | 18.11 |
| m6 | 13 | 9.68 | 14.22 | 17.2 | 16.7 |
| g6 | 31 | 7.3 | 12.68 | 14.63 | 14.3 |
| t8 | 16 | 9.7 | 16.37 | 19.02 | 18.57 |
| e5 | 11 | 12.01 | 15.13 | 19.31 | 18.62 |
| d2 | 17 | 6.09 | 10.37 | 12.02 | 11.74 |
| Total | 204 | 7.68 | 14.19 | 16.14 | 15.8 |

# Lot-to-Lot:

Three manufactured lots were tested using three (3) sensitized single plasma donor and 2 pooled plasma samples, covering Classes 2 & 3 were tested using 8 devices per sample and 50 venous whole blood sample covering Classes 1-3 were tested with 3 devices per sample. For the plasma samples, the total variation between Assay Devices and between lots was estimated to have a CV of $14\%$ , the variation between Assay Devices was $12\%$ , and the variation between lots $7\%$ . The total variation for the venous whole blood samples was $18\%$ CV.

Table 3. Coefficients of variance (CV%) for plasma samples tested in 8 Assay Devices using 3 lots of Assay Devices and measured as Color Units.

| Allergen | CV% Between Lots | CV% Between Assay Devices | CV% Total |
| --- | --- | --- | --- |
| e1 | 7.30 | 12.23 | 14.24 |
| d1 | 4.60 | 10.42 | 11.40 |
| g2 | 8.94 | 13.08 | 15.85 |
| w1 | 8.04 | 10.88 | 13.53 |
| t7 | 7.56 | 12.68 | 14.76 |
| m6 | 4.95 | 17.07 | 17.78 |

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Table 4. Coefficients of variance (CV%) for venous whole blood from 50 donors assayed in 9 Assay Devices (3 Assay Devices from 3 lots) and measured as Color Units.

| Allergen | Number of samples | CV% Between Occasions | CV% Between Assay Devices | CV% Total (Sum of components) | CV% Total (All observations) |
| --- | --- | --- | --- | --- | --- |
| e1 | 22 | 12.17 | 11.47 | 16.73 | 15.58 |
| d1 | 17 | 11.56 | 13.40 | 17.69 | 16.72 |
| g2 | 23 | 16.95 | 16.12 | 23.39 | 21.80 |
| w1 | 32 | 12.67 | 12.09 | 17.51 | 16.33 |
| t7 | 21 | 14.80 | 14.00 | 20.37 | 18.98 |
| m6 | 13 | 13.11 | 13.43 | 18.77 | 17.59 |
| g6 | 31 | 12.70 | 12.06 | 17.51 | 16.32 |
| t8 | 16 | 17.62 | 15.78 | 23.65 | 21.95 |
| e5 | 11 | 11.92 | 17.21 | 20.93 | 20.07 |
| d2 | 17 | 10.04 | 10.22 | 14.32 | 13.42 |
| Total | 203 | 13.56 | 13.42 | 19.08 | 17.84 |

# Site-to-Site:

The site-to-site study was performed using 4 pooled samples from sensitized donors and a single negative sample and were tested using 4 devices per sample for 3 days. The total variation between Assay Devices and between sites was estimated to CV $16\%$ . The variation between Assay Devices was CV $15\%$ and the variation between sites CV $7\%$ .

Table 5. Coefficients of variance (CV%) for plasma samples from sensitized donors tested in 4 Assay Devices at 3 sites and measured as Color Units.

| Allergen | CV% Between Sites | CV% Between Assay Devices | CV% Total |
| --- | --- | --- | --- |
| e1 | 6.19 | 12.16 | 13.65 |
| d1 | 5.81 | 13.15 | 14.38 |
| g2 | 6.24 | 12.31 | 13.81 |
| w1 | 3.14 | 11.01 | 11.45 |
| t7 | 7.95 | 9.02 | 12.03 |
| m6 | 6.78 | 15.54 | 16.95 |
| g6 | 7.26 | 12.21 | 14.20 |

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| Allergen | CV% Between Sites | CV% Between Assay Devices | CV% Total |
| --- | --- | --- | --- |
| t8 | 10.30 | 18.54 | 21.21 |
| e5 | 7.93 | 23.66 | 24.95 |
| d2 | 5.29 | 11.89 | 13.01 |
| Total | 7.00 | 14.57 | 16.17 |

Operator-to-Operator:

Five venous whole blood samples were tested with five devices per sample with 5 different operators. The total variation between operators was $16\%$ .

Table 6. of variance (CV%) for venous whole blood samples from sensitized donors tested in 5 Assay Devices between 5 different operators and measured as Color Units.

| Allergen | Number of samples | CV% Between Occasions | CV% Between Assay Devices | CV% Total (Sum of components) | CV% Total (All observations) |
| --- | --- | --- | --- | --- | --- |
| e1 | 3 | 4.31 | 10.47 | 11.32 | 11.19 |
| d1 | 1 | 7.48 | 10.95 | 13.26 | 12.90 |
| g2 | 3 | 14.86 | 17.50 | 22.96 | 22.14 |
| w1 | 1 | 13.73 | 14.97 | 20.31 | 19.52 |
| t7 | 3 | 8.10 | 14.48 | 16.59 | 16.26 |
| m6 | 0 | - | - | - | - |
| g6 | 3 | 7.41 | 15.33 | 17.03 | 16.76 |
| t8 | 0 | - | - | - | - |
| e5 | 2 | 5.01 | 8.86 | 10.18 | 9.97 |
| d2 | 1 | 10.13 | 11.68 | 15.46 | 14.90 |
| Total | 17 | 9.32 | 13.76 | 16.62 | 16.18 |

b. Linearity/assay reportable range:

Measuring Range:

The semi-quantitative reportable range is subdivided into Class 1, 2 and 3 which correspond to levels of IgE antibodies spanning the range from Low (0.35 kUA/L) to Very High (100 kUA/L) as measured by ImmunoCAP Specific IgE (IC Specific IgE). A Class 1 result corresponds to absent or low levels, a Class 2 result corresponds to moderate to high levels and a Class 3 result corresponds to very high levels of IgE antibody when compared to IC Specific IgE. In Rapid IP1, the response value (RU) for the class borders between Class 1/2 and Class 2/3 have been established through comparison studies with the IC Specific IgE using samples with known IgE antibody levels.

Linearity:

Four plasma samples from different sensitized donors for each allergen were diluted 4-8 times with IgE negative plasma and tested using one device per sample. The allergen specific IgE antibody level was determined with the IC Specific IgE device.

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The linear regression data for each sample are shown in the table below.

Table 7. Linearity study results.

| Allergen | Sample | Slope Estimate | 95% CI | Intercept Estimate | 95% CI | R2 |
| --- | --- | --- | --- | --- | --- | --- |
| e1 | 1 | 1.10 | 0.83 – 1.37 | 0.27 | -0.01 – 0.54 | 0.98 |
| | 2 | 1.06 | 0.83 – 1.28 | 0.13 | -0.03 – 0.29 | 1.00 |
| | 3 | 1.14 | 0.58 – 1.69 | 0.06 | -0.40 – 0.52 | 0.93 |
| | 4 | 0.86 | 0.42 – 1.30 | -0.78 | -1.02 – -0.54 | 0.93 |
| d1 | 1 | 0.96 | 0.88 – 1.04 | -0.25 | -0.31 – -0.19 | 1.00 |
| | 2 | 0.85 | 0.75 – 0.94 | -0.22 | -0.29 – -0.15 | 0.99 |
| | 3 | 0.90 | 0.73 – 1.07 | -0.42 | -0.57 – -0.27 | 0.98 |
| | 4 | 0.92 | 0.84 – 1.01 | -0.35 | -0.40 – -0.30 | 1.00 |
| g2 | 1 | 0.78 | 0.45 – 1.11 | -0.75 | -0.98 – -0.53 | 0.95 |
| | 2 | 0.97 | 0.83 – 1.11 | -0.05 | -0.17 – 0.06 | 0.99 |
| | 3 | 0.83 | 0.60 – 1.06 | -0.65 | -0.82 – -0.48 | 0.98 |
| | 4 | 0.71 | 0.39 – 1.04 | -0.78 | -1.03 – -0.54 | 0.94 |
| w1 | 1 | 1.19 | 1.09 – 1.30 | -0.58 | -0.68 – -0.48 | 0.99 |
| | 2 | 1.09 | 0.92 – 1.25 | -0.62 | -0.74 – -0.51 | 0.99 |
| | 3 | 1.22 | 0.98 – 1.46 | -1.08 | -1.31 – -0.86 | 0.98 |
| | 4 | 1.13 | 0.96 – 1.30 | -0.47 | -0.58 – -0.37 | 0.99 |
| t7 | 1 | 1.02 | 0.90 – 1.15 | -0.56 | -0.66 – -0.47 | 0.99 |
| | 2 | 0.99 | 0.77 – 1.21 | -0.43 | -0.59 – -0.27 | 0.97 |
| | 3 | 1.03 | 0.66 – 1.41 | -1.45 | -1.82 – -1.09 | 0.94 |
| | 4 | 1.15 | 0.82 – 1.49 | -0.64 | -0.85 – -0.42 | 0.96 |
| m6 | 1 | 1.27 | 0.60 – 1.95 | -0.43 | -0.81 – -0.06 | 0.92 |
| | 2 | 1.17 | 0.89 – 1.45 | -0.58 | -0.71 – -0.46 | 0.97 |
| | 3 | 1.22 | 0.89 – 1.56 | -0.52 | -0.70 – -0.34 | 0.98 |
| | 4 | 1.16 | 0.89 – 1.42 | -1.13 | -1.42 – -0.84 | 0.98 |
| g6 | 1 | 0.91 | 0.74 – 1.07 | -0.45 | -0.65 – -0.26 | 0.99 |
| | 2 | 1.19 | 1.07 – 1.31 | -0.84 | -0.94 – -0.75 | 0.99 |
| | 3 | 1.07 | 0.59 – 1.55 | -0.80 | -1.13 – -0.48 | 0.94 |
| | 4 | 1.12 | 0.85 – 1.39 | -0.65 | -0.88 – -0.41 | 0.98 |
| t8 | 1 | 1.15 | 1.02 – 1.28 | -0.71 | -0.91 – -0.51 | 0.99 |
| | 2 | 1.06 | 0.86 – 1.25 | -0.22 | -0.38 – -0.06 | 0.99 |
| | 3 | 1.11 | 0.68 – 1.55 | -0.77 | -1.09 – -0.44 | 0.98 |
| | 4 | 1.11 | 0.90 – 1.33 | -0.82 | -0.99 – -0.65 | 0.99 |
| e5 | 1 | 1.08 | 0.93 – 1.24 | -0.06 | -0.20 – 0.08 | 0.99 |
| | 2 | 1.01 | 0.91 – 1.10 | -0.04 | -0.12 – 0.04 | 1.00 |
| | 3 | 0.93 | 0.73 – 1.14 | -0.39 | -0.53 – -0.25 | 0.99 |
| | 4 | 1.30 | 0.94 – 1.65 | -0.18 | -0.40 – 0.04 | 0.98 |
| d2 | 1 | 0.92 | 0.53 – 1.31 | -0.27 | -0.54 – 0.00 | 0.95 |
| | 2 | 0.96 | 0.39 – 1.53 | -0.09 | -0.65 – 0.46 | 0.91 |
| | 3 | 0.88 | 0.58 – 1.18 | -0.66 | -0.88 – -0.45 | 0.97 |
| | 4 | 0.93 | 0.69 – 1.16 | -0.27 | -0.44 – -0.10 | 0.98 |

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

1. Controls:
The ImmunoCAP Rapid QC1 positive and negative controls contain specific IgE antibodies to specified allergens with an assigned response value based on the IC Specific IgE assay values of the candidate raw materials prior to pooling. The final pool of materials is verified by the Rapid IP1. Specific class values for the positive QC1 control, allergens e1, m6, and e5 are Class 3, Class 2, and Class 2, respectively. The response value (RU) for the class borders between Class 1/2 and Class 2/3 have been established through comparison studies with the IC Specific IgE assay using samples with known IgE antibody levels.

2. Stability:
Two positive plasma pools covering all ten allergens and one negative plasma pool were tested with six assay devices per sample and are compared with baseline results. Three lots of Rapid IP1 kit, were placed in reference storage conditions, +2°C to +8°C, for real time stability testing. The testing was performed at start of study, reference condition at 0 months, and after 3, 6, 10, and 13 months. The study is planned to continue until test occasion 25 months. For Lot 1, an initial transport simulation was performed during 1 week. After initial testing at reference conditions, Lot 1 was stored at +32°C. During this week, Lot 1 was also stored at +2°C to +8°C for 18-24 hours at two occasions and at -20°C for 2-3 hours at one occasion. After this week, Lot 1 was returned to reference storage at +2°C to +8°C together with Lots 2 and 3.

d. Detection limit:
The Limit of Detection (LoD) and Limit of Blank (LoB) were determined using the capillary and venous heparinized whole blood samples obtained from the 245 donors from the Method Comparison study. Plasma was processed from the venous whole blood and the amount of specific IgE antibodies for each of the 10 allergens included in the Rapid IP1 was determined. All results with an allergen specific IgE antibody level lower than 0.1 kUA/L, i.e. an undetectable level of allergen specific IgE as determined by the IC Specific IgE, was considered as a blank sample for that allergen. The samples fulfilling this criterion were selected for this study. For each sample and allergen, fulfilling the criteria, the Color Units (CU) was recorded. The LoB and LoD were estimated according to CLSI EP17-A. The overall LoB was estimated to 0.16 CU and the LoD to 0.22 CU. The specification for the LoD was within Class I (<0.28 CU). The LoB was calculated according to the following formula: LoB = μB + 1.645σB and using the 95% percentile: LoB = PctB100- α

The LoD study, using only CU values, gave an estimated overall LoD of CU = 0.22. The Dilution Study (Linearity) gave an estimated level of detection of 0.58kUA/L with a corresponding CU of 0.20. The results for each allergen individually are shown below. Column "LoD Mean CU" is based on LoB using mean and standard deviation, and column "LoD 95% Percentile CU" is based on LoB using the 95% percentile.

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Table 8. Limit of Blank values for each individual allergen.

| Allergen | No. of Samples | Mean CU | SD (CU) | LoB Mean CU | LoB 95% Percentile CU |
| --- | --- | --- | --- | --- | --- |
| e1 | 179 | 0.079 | 0.025 | 0.119 | 0.123 |
| d1 | 206 | 0.117 | 0.034 | 0.173 | 0.169 |
| g2 | 172 | 0.080 | 0.030 | 0.130 | 0.130 |
| w1 | 137 | 0.069 | 0.026 | 0.111 | 0.112 |
| t7 | 13 | 0.104 | 0.039 | 0.169 | 0.183 |
| m6 | 121 | 0.092 | 0.053 | 0.178 | 0.195 |
| g6 | 148 | 0.083 | 0.022 | 0.118 | 0.117 |
| t8 | 210 | 0.078 | 0.033 | 0.131 | 0.122 |
| e5 | 147 | 0.108 | 0.037 | 0.168 | 0.156 |
| d2 | 207 | 0.124 | 0.046 | 0.200 | 0.178 |

Table 9. Limit of Detection values for each individual allergen.

| Allergen | LoD Mean CU | LoD 95% Percintile CU |
| --- | --- | --- |
| e1 | 0.150 | 0.155 |
| d1 | 0.228 | 0.223 |
| g2 | 0.190 | 0.191 |
| w1 | 0.165 | 0.167 |
| t7 | 0.237 | 0.256 |
| m6 | 0.251 | 0.274 |
| g6 | 0.161 | 0.159 |
| t8 | 0.187 | 0.174 |
| e5 | 0.235 | 0.218 |
| d2 | 0.246 | 0.219 |

# e. Analytical specificity:

Plasma and whole blood samples from sensitized and non-sensitized donors were spiked with potentially interfering substances and the studies were performed according CLSI EP-7A2. Samples were distributed in Classes 1, 2 and 3 as measured by ImmunoCAP Rapid IP1. The assay performance of the ImmunoCAP Rapid IP1 for samples both with and without measurable allergen specific IgE antibodies was verified for high levels of total IgE (1,000; 3,000; and $10,000\mathrm{kU / L}$ ). No interference of high levels of total IgE could be observed. The spiking studies regarding potentially interfering substances showed no interference in samples from sensitized and non-sensitized donors samples spiked with hemoglobin $(5.5\mathrm{g / L})$ , heparin (150 IE/mL), bilirubin $(340\mu \mathrm{mol / L})$ and Chyle $(1,800\mathrm{U / mL})$ .

The antibody used for detection in ImmunoCAP Rapid contains the monoclonal (mAb) anti-human IgE antibody clone 390. The specificity of this antibody for human IgE was studied using BIAcore technology. Interactions were studied using polyclonal rabbit anti-mouse-IgG, covalently linked to the reaction surface, to which

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the mAb anti-human IgE antibody clone 390 bound upon injection. Subsequent injections were done with purified human myeloma immunoglobulin (Ig) of the IgE, IgG1, IgG2, IgG3, IgG4, IgA, IgM or IgD isotypes. The interactions were studied as measurement of binding and release in comparison with buffer injections and were evaluated in the BIAcore program. As positive control human myeloma IgE (ND) was used and it was injected at the concentrations of 1/1, 1/10, 1/100 and 1/1000 as compared to the other Ig isotypes. No cross reactivity (< 0.1%) with other human immunoglobulin classes

## Interference of Total IgE:

Three sets of samples were tested. The first consisted of five sensitized and five non-sensitized single plasma donors, which were each spiked with 1,000 and 3,000 kU/L of IgE; the second set consisted of five sensitized and one non-sensitized single plasma donors, which were spiked to 10,000 kU/L of IgE; and the third set consisted of two sensitized and one non-sensitized single venous whole blood samples, which were spiked to 1,000 kU/L of IgE. Plasma samples were tested with one device per sample and three devices per sample were used for the venous whole blood. All samples were measured in Rapid Reader and the results compared to a non-spiked (neat) sample. The CU value for each plasma sample and the mean CU value for each whole blood sample and allergen were scored as Class 1, Class 2 or Class 3. Results obtained with spiked samples were compared with results obtained with non-spiked samples. The overall agreement was calculated for each spiking level and sample matrix. One plasma sample spiked at 3,000 kU/L and three plasma samples spiked at 10,000 kU/L were discordant when compared to the non-spiked controls. No discordant calls were observed with either plasma or venous whole blood samples spiked with 1,000 kU/L IgE.

## Interference of Hemoglobin:

Two sensitized and one non-sensitized samples each for plasma and venous whole blood were spiked with 5.5 g/L hemoglobin and compared to non-spiked samples using three devices per sample. One discordant sample (Class 3) was miscalled (Class 2) with the plasma samples and no discordant samples were seen with the venous whole blood when compared to non-spiked samples. The overall agreement for plasma samples was 97% and 100% for venous whole blood.

## Interference of Heparin

Two sensitized and one non-sensitized samples each for plasma and venous whole blood were spiked with 150 IE/mL heparin and compared to non-spiked samples using three devices per sample. No discordant samples were observed for either plasma or whole blood.

## Interference of Bilirubin

Two sensitized and one non-sensitized samples each for plasma and venous whole blood were spiked with 340 μmol/L bilirubin and compared to non-spiked samples using three devices per sample. One discordant sample (Class 1) was miscalled (Class 2) with the plasma samples and no discordant samples were seen with the venous whole blood when compared to non-spiked samples. The overall agreement

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for plasma samples was $97\%$ and $100\%$ for venous whole blood.

# Interference of Chyle

Three sensitized and one non-sensitized plasma samples and two sensitized and one non-sensitized venous whole blood samples were spiked with $1800\mathrm{U / mL}$ of Chyle and compared to non-spiked samples using three devices per sample. One discordant sample (Class 2) was miscalled (Class 3) with the plasma samples and no discordant samples were seen with the venous whole blood when compared to non-spiked samples. The overall agreement for plasma samples was $97.5\%$ and $100\%$ for venous whole blood.

# f. Assay cut-off:

Rapid IP1 gives results in one of three classes of IgE antibody levels, while IC Specific IgE assay reports in one of seven classes. Each of the Rapid IP1 classes, Class 1: absent or low, Class 2: moderate to high, Class 3: very high, encompasses 2 to 3 IC Specific IgE assay classes. As in the IC Specific IgE assay, higher class scores denote increasing levels of specific IgE antibody with the same descriptive terminology for IgE antibody levels. In the IC Specific IgE assay, $0.7\mathrm{kU}_{\mathrm{A}} / \mathrm{L}$ is used as the border between low and moderate and $17.5\mathrm{kU}_{\mathrm{A}} / \mathrm{L}$ is used as the border between high and very high. Rapid IP1 is a rapid, POC, semi quantitative assay with class borders approximated to 1 and $15\mathrm{kUA} / \mathrm{L}$ respectively. In Rapid IP1, the response value (CU) for the class borders between Class 1 and 2 and Class 2 and 3 have been established through comparison studies with the IC Specific IgE using samples with known IgE antibody levels. A comparison of the measuring range between the Rapid IP1 device, the IC Specific IgE assay, and other reporting methods are depicted in Figure 1, below.

Figure 1. The class scoring range for Rapid IP1 device and corresponding commonly used class scoring and the measuring range for the IC Specific IgE.

# 2. Comparison studies:

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# a. Method comparison with predicate device:

The comparison study included 245 donors. Heparinized capillary (lithium) and venous (sodium) whole blood were collected from all donors. Plasma was processed from the venous whole blood. All three sample types were used in the Rapid IP1, but plasma was only was used with the IC Specific IgE assay. A distribution of allergen levels as determined by the IC Specific IgE assay is depicted in Table 10, below.

Table 10. Distribution of analyte levels for the 245 donors.

| Allergen | e1 | d1 | g2 | w1 | t7 | m6 | g6 | t8 | e5 | d2 |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| <1 kUA/L | 144 | 164 | 152 | 100 | 142 | 188 | 101 | 187 | 171 | 165 |
| ≥1 -<15 kUA/L | 77 | 56 | 79 | 88 | 78 | 47 | 90 | 53 | 63 | 49 |
| ≥15 kUA/L | 24 | 25 | 14 | 57 | 25 | 10 | 54 | 5 | 11 | 31 |

When compared using a 3x3 format (Table A), the "exact" positive percent agreements (PPA) for Class 2 and Class 3 are indicated by the subscript. The 3x3 format was subsequently collapsed into a 2x2 format (Table B) to calculate the final positive percent (PPA), negative percent (NPA), and overall percent (OA) agreement calculations and is shown below. The NPA is identical between the 3x3 and the corresponding 2x2 comparison tables. The 3x3 tables were collapsed into a 2x2 table based on the following:

| IC Specific IgE | | | | |
| --- | --- | --- | --- | --- |
| Rapid IP1 | Class | 3 | 2 | 1 |
| | 3 | a | B | c |
| | 2 | d | e | f |
| | 1 | g | h | i |
| | | T1 | T2 | T3 |
| | (+) | (-) |
| --- | --- | --- |
| | a+b+d+e | c+f |
| | g+h | i |
| | T1+T2 | T3 |

Tables 11 and 13 below show the semi-quantitative comparison of the Rapid IP1 vs. IC Specific IgE for the different sample types.

| 11A. Plasma | IC Specific IgE | | | |
| --- | --- | --- | --- | --- |
| Rapid IP1 | Class | 3 | 2 | 1 |
| | 3 | 210 | 17 | 0 |
| | 2 | 46 | 627 | 94 |
| | 1 | 0 | 36 | 1420 |
| | Total | 256 | 680 | 1514 |

$\mathrm{PPA}_3 = 82.03\%$ (210/256)

$\mathrm{PPA}_2 = 92.2\%$ (627/680)

$\mathrm{PPA}_{2 + 3} = 89.4\%$ (837/936)

OA = 92.1% (2257/2450)

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11B. Plasma IC Specific IgE

| Rapid IP1 | (+) | (-) | Total |
| --- | --- | --- | --- |
| | (+) | 900 | 94 |
| | (-) | 36 | 1420 |
| | Total | 936 | 1514 |

PPA = 96.2% (900/936)

NPA = 93.8% (1420/1514)

OA = 94.7% (1320/2450)

12A. Venous WB IC Specific IgE

| Rapid IP1 | Class | 3 | 2 | 1 | Total |
| --- | --- | --- | --- | --- | --- |
| | 3 | 202 | 19 | 0 | 221 |
| | 2 | 54 | 613 | 97 | 764 |
| | 1 | 0 | 48 | 1417 | 1465 |
| | Total | 256 | 680 | 1514 | 2450 |

$\mathrm{PPA}_3 = 82.03\%$ (202/256)

$\mathrm{PPA}_2 = 92.2\%$ (613/680)

$\mathrm{PPA}_{2 + 3} = 89.4\%$ (815/936)

OA = 92.1% (2257/2450)

12B. Venous WB IC Specific IgE

| Rapid IP1 | (+) | (-) | Total |
| --- | --- | --- | --- |
| | (+) | 888 | 97 |
| | (-) | 48 | 1417 |
| | Total | 936 | 1514 |

PPA = 94.9% (888/936)

NPA = 93.6% (1417/1514)

OA = 94.1% (2305/2450)

13A. Capillary WB IC Specific IgE

| Rapid IP1 | Class | 3 | 2 | 1 | Total |
| --- | --- | --- | --- | --- | --- |
| | 3 | 199 | 18 | 0 | 217 |
| | 2 | 57 | 608 | 103 | 768 |
| | 1 | 0 | 53* | 1411 | 1464 |
| | Total | 256 | 679 | 1514 | 2449 |

*One missing result for capillary whole blood for one allergen due to a blood stain making the result unreadable.

$\mathrm{PPA}_3 = 77.7\%$ (199/256)

$\mathrm{PPA}_2 = 89.5\%$ (608/679)

$\mathrm{PPA}_{2 + 3} = 86.3\%$ (807/935)

OA = 90.6% (2218/2449)

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13B. Capillary WB IC Specific IgE

| Rapid IP1 | (+) | (-) |
| --- | --- | --- |
| | 882 | 103 |
| | 53* | 1411 |
| | 935 | 1514 |

985 1464 2449

$\mathrm{PPA} =$ 95.07% (882/935)

$\mathrm{NPA} =$ 93.2% (1411/1514)

OA = 93.6% (2293/2449)

For the discrepant results for each sample type and allergen, the number of samples at or near the class borders were determined and presented as shown in the example below. A sample falling at or near the border was defined as a sample within a distance of $\pm 2$ SD from the border. The SD used was for the IC Specific IgE assay $\mathrm{CV} = 10\%$ and for the Rapid IP1 $\mathrm{CV} = 17\%$ in Class 2 and Class 3, and $\mathrm{CV} = 30\%$ for samples in Class 1. The figures within the dotted lines are the number of samples at or near the border. The figures in the middle of the different squares are the remaining number samples. The $3\times 3$ tables were also compared to a plot of CU for the Rapid IP1 vs. the quantity of specific IgE as determined by the IC Specific IgE assay for each of the matrices.

Figure 2. Semi-quantitative evaluation with number of samples at or near Class borders for all allergens and CU plot for all allergens for each sample matrix type. A = Plasma, B = venous whole blood, and C = capillary whole blood.




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Figure3. Positive and Negative percent agreement comparisons between different


# b. Matrix comparison:

The matrix comparison study used blood samples from the Method Comparison study where lithium heparin capillary whole blood and sodium heparin venous whole blood samples were collected. Plasma was processed from the venous whole blood as described above in the "Method comparison to predicate device". The results for all allergens and matrices showed an overall agreement within Classes was $\geq 91\%$ . Capillary and venous whole blood and subsequent processed plasma samples were compared to results of the IC Specific IgE performed on the matched plasma samples and the results are shown in Table 14 and Figure 3, below.

Table 14. Percent Agreements between different matrices by allergen.

| Allergen | Number tests | Capillary vs. Venous whole blood | | | Capillary whole blood vs. Plasma | | | Venous whole blood vs. Plasma | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | PPA | NPA | OA | PPA | NPA | OA | PPA | NPA | OA |
| e1 | 245 | 96 | 98 | 97 | 92 | 99 | 96 | 93 | 100 | 96 |
| d1 | 245 | 91 | 99 | 96 | 94 | 97 | 96 | 93 | 96 | 95 |
| g2 | 245 | 96 | 99 | 98 | 94 | 98 | 96 | 94 | 97 | 96 |
| w1 | 245 | 90 | 97 | 94 | 91 | 95 | 93 | 95 | 96 | 95 |
| t7 | 245 (244*) | 91 | 96 | 94* | 90 | 98 | 94* | 93 | 99 | 96 |
| m6 | 245 | 92 | 99 | 97 | 93 | 99 | 98 | 93 | 100 | 98 |
| g6 | 245 | 94 | 96 | 95 | 95 | 96 | 95 | 94 | 97 | 95 |
| t8 | 245 | 96 | 97 | 97 | 99 | 95 | 96 | 99 | 97 | 97 |
| e5 | 245 | 94 | 96 | 95 | 97 | 97 | 97 | 95 | 98 | 97 |
| d2 | 245 | 94 | 100 | 98 | 94 | 98 | 97 | 100 | 98 | 99 |
| Total | 2450 (2449*) | | | 96 | | | 96 | | | 96 |

*One missing result for capillary whole blood for one allergen due to a blood stain thus making the result unreadable.

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matrices by allergen.



3. Clinical studies:

a. Clinical Sensitivity:

Not applicable.

b. Clinical specificity:

Not applicable.

4. Clinical cut-off:

Same as analytical cut-off.

5. Expected values/Reference range:

Matched heparinized capillary (lithium) and heparinized venous whole blood (sodium) samples were obtained from 101 healthy, self-reported, non-allergic donors. Plasma was obtained from the venous whole blood as described in the Method Comparison section, and all sample types were tested on the Rapid IP1 device using one device per sample per matrix. A distribution of color units for the three matrices is shown below.

Figure 5. Distribution of Color Units for 101 self reported, non-allergic donors for three different sample matrices
N. Instrument Name:

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ImmunoCAP® Rapid Reader

## O. System Descriptions:

### 1. Device Description:

ImmunoCAP Rapid Reader (Rapid Reader) is a stand alone instrument to be used with ImmunoCAP Rapid Assay Device. The user interface consists of a LCD display with a touch screen and a slot for insertion of the ImmunoCAP Rapid Assay Device.

### Assay Device docking system

The slot for the ImmunoCAP Rapid Assay Device has two switches for interaction with the Assay Device.

- One outer switch, to be able to take an image of the Assay Device ID area when inserted into the slot.
- One inner switch; to be able to take a series of images of the Test Window area of the device.

### Camera, optics and light source

The color camera has a CCD image sensor with 1024 x 768 pixel resolution, a firewire interface and I/O pins for external signals. The firewire interface delivers the power needed by the camera. A mirror is located between the camera lens and the Assay Device to give a longer optical path and lower optical distortion. Four white color spectrum LED's are placed behind two optical diffusers making the illumination of the Assay Device more even.

### Computer system, hard disk and power supply

The computer is a mini-PC (Intel) with 1.67GHz Core2 Duo processor, RAM (512MByte) and Hard drive (80GByte). The power supply (65W Input 100-240V ~ 1.6A 50-60 Hz) delivers power to the mini-PC and peripherals.

### Display and Touch screen

The display is a LCD panel with 640 x 480 resolution, a standard VGA resolution supported by GNU/Linux operating system. A Touch screen is placed on top of the LCD panel and connected to the mini-PC.

### Printer

The printer is a thermo label printer with automatic paper cutter and USB interface.

### 2. Principles of Operation:

The Reader is part of ImmunoCAP Rapid System, which is a combination of lateral flow immunoassay reagents and instrument/software for semi-quantitative determination of antibodies or antigens in human capillary whole blood, heparinized venous whole blood or heparinized plasma. The ImmunoCAP Rapid Reader quantitatively measures the color saturation and converts the signal into Color Units (CU). The higher the concentration of IgE antibodies in the sample the stronger the color of the red lines, i.e. higher CU values. CU values are then categorized semiquantitatively into Class 1, 2 or 3.

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The user performs the Rapid IP1 assay according to the instructions for use and inserts the Rapid IP1 device into the Rapid Reader as shown on the screen of the Reader. If the necessary control conditions are met, assay results will be displayed on the screen. Print the results, by pressing the Print button on the screen. If the Reader does not detect the blood sample or the assay control lines are missing, the Rapid Reader will not report any results. The Reader will display the results as Class 1, 2 or 3.

3. **Modes of Operation:**
Semi-automated

4. **Software:**
FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types:
Yes ☐ X ☐ or No ☐

5. **Specimen Identification:**
Manual input by user.

6. **Specimen Sampling and Handling:**
Samples should be obtained and handled according to the laboratory’s standard operating procedures and following the protocol described in the package insert for the Rapid IP1 device.

7. **Calibration:**
The ImmunoCAP Rapid Reader is calibrated at manufacturing and does not require any user calibration.

8. **Quality Control:**
The user is instructed to perform routine quality control at set schedules which includes cleaning and disinfecting the unit and components. A Reader Check using the Rapid Reader CD is requested by the Rapid Reader the first time the Reader is used during Start-up. Regular Checks will be required every 7 days. A valid Reader Check will reset the 7 day time frame. The operator will be reminded by the Reader at day 5 of the 7 day time frame. A Check button will then appear on the screen, see Figure below. The Reader must register a valid Check within the next 2 days. Note: The Reader will not score any Assay Devices after 7 days have passed, unless a new Check procedure with a valid result has been registered.

The Reader has several internal controls, which automatically check for proper light and optical conditions before reading the test results. If any of these checks fails the Reader will not score Assay Devices. Patient or external control results will not be displayed on the screen if the Reader fails to detect addition of whole blood sample or the development of the control lines in the Control Window of the Assay Device. If this occurs, the Reader flags the assay as invalid and no result will be shown.

P. **Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:**

**ImmunoCAP Rapid Reader Check Device Stability:**
The Rapid Reader CD consists of a plastic housing containing a color card with defined colored areas. The color cards are purchased from an external manufacturer, Scandinavian Colour Institute AB, Stockholm, Sweden. The stability of the color cards are warranted by the Scandinavian Colour Institute AB for a time of 5 years when stored dark in room

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temperature. The recommended use of Rapid Reader CD is to remove the Check Device from the foil bag, i.e. stored at reference storage condition, and perform a Reader check once a week. The Scandinavian Colour Institute AB also report an accelerated light stability study where color card samples were exposed to light of high illumination dose, approximately 10 times normal office light, at a temperature of +30°C for 3 months. The conclusion, made by The Scandinavian Colour Institute AB, is that the color cards are stable under these conditions for 50 days. The set stability time of 24 months is based on

- The stability of the color cards is of 5 years when stored dark at room temperature.
- The color cards are stable for 50 days when exposed to a dose of 209184 lx per day.
- According to the recommended use, the reader check device will be exposed to light only for approximately 25 hours (15 minutes at approximately 100 occasions).

## ImmunoCAP Rapid Reader Check Device Reproducibility Study:

Three lots of Rapid Reader CDs were measured 52 (lot 1) and 60 (lots 2-3) times each on one instrument. The total variation between Rapid Reader CDs and between lots was CV 0.68%. The variation between Rapid Reader CDs was CV 0.63% and the variation between lots CV 0.25%. The specifications set for between the CDs and between lots was CV &lt;0.7% and a total variation of CD ≤1%.

## Q. Proposed Labeling:

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

## R. Conclusion:

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

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