Allergen-Specific IgE Assay 12 Allergen Bundle

K193613 · Hitachi Chemical Diagnostics, Inc. · DHB · Oct 18, 2021 · Immunology

Device Facts

• Record ID: K193613
• Device Name: Allergen-Specific IgE Assay 12 Allergen Bundle
• Applicant: Hitachi Chemical Diagnostics, Inc.
• Product Code: DHB · Immunology
• Decision Date: Oct 18, 2021
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.5750
• Device Class: Class 2

Indications for Use

The OPTIGEN® Allergen-Specific IgE Assay 12 Allergen Bundle A is an in vitro test for use in the semi-quantitative determination of circulating allergen specific IgE concentrations in human serum. OPTIGEN® Allergen-Specific IgE assays are meant to be included in panel tests to be used with the AP3600™ instrument. Each assay is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE mediated allergenic disorders in conjunction with other clinical findings and are to be used in clinical laboratories. The OPTIGEN® 12 Allergen Bundle A includes Almond (f20), Bermuda Grass (g2), Cashew (f207), Crab (f23), Hazelnut (Food) (f17), Oak, White (f7), Salmon (f41), Sesame Seed (f10), Shrimp (f24), Tuna (f40), and Walnut (Food) (f256).

Device Story

The OPTIGEN® Allergen-Specific IgE Assay 12 Allergen Bundle A is an in vitro diagnostic test designed for use with the AP3600™ instrument. It processes human serum samples to measure concentrations of allergen-specific IgE antibodies. The device utilizes a panel-based approach to detect IgE reactivity to specific allergens, including various nuts, seafood, and grasses. Operated by laboratory professionals in a clinical setting, the assay provides semi-quantitative results that assist clinicians in diagnosing IgE-mediated allergic disorders. These results are intended to be interpreted alongside other clinical findings to inform patient management and treatment decisions.

Clinical Evidence

Bench testing only. Performance evaluated via precision (within-run, between-run, between-day, total), linearity, analytical specificity (inhibition studies), and interference testing. Method comparison study against ImmunoCAP (N=3397) showed 90.5% PPA, 92.6% NPA, and 91.9% TPA. No clinical prospective/retrospective studies performed.

Technological Characteristics

In vitro diagnostic immunoassay for semi-quantitative IgE detection. Designed for use with the AP3600™ instrument. Analyzes human serum samples for specific allergen reactivity.

Indications for Use

Indicated for the semi-quantitative determination of circulating allergen-specific IgE concentrations in human serum to aid in the clinical diagnosis of IgE-mediated allergenic disorders. For use in clinical laboratories by professional personnel.

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.

Submission Summary (Full Text)

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FDA

U.S. FOOD & DRUG

ADMINISTRATION

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K193613

B Applicant

Minaris Medical

C Proprietary and Established Names

OPTIGEN Allergen-Specific IgE Assay 12 Allergen Bundle A

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:

New device

B Measurand:

Allergen-specific IgE analytes: Almond (f20), Bermuda Grass (g2), Cashew (f202), Clam (f207), Crab (f23), Hazelnut (f17), White Oak (t7), Salmon (f41), Sesame Seed (f10), Shrimp (f24), Tuna (f40), and Walnut (f256)

Food and Drug Administration

10903 New Hampshire Avenue

Silver Spring, MD 20993-0002

www.fda.gov

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C Type of Test:

Chemiluminescence immunoassay, Semi-quantitative

III Intended Use/Indications for Use:

A Intended Use(s):

See Indications for Use below.

B Indication(s) for Use:

The OPTIGEN Allergen-Specific IgE Assay 12 Allergen Bundle A is an in vitro test for use in the semi-quantitative determination of circulating allergen specific IgE concentrations in human serum. OPTIGEN Allergen-Specific IgE assays are meant to be included in panel tests to be used with the AP3600 instrument. Each assay is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE mediated allergenic disorders in conjunction with other clinical findings and are to be used in clinical laboratories.

The OPTIGEN 12 Allergen Bundle A includes Almond (f20), Bermuda Grass (g2), Cashew (f202), Clam (f207), Crab (f23), Hazelnut (f17), White Oak (t7), Salmon (f41), Sesame Seed (f10), Shrimp (f24), Tuna (f40), and Walnut (f256).

C Special Conditions for Use Statement(s):

Rx - For Prescription Use Only

D Special Instrument Requirements:

OPTIGEN AP3600 Instrument

IV Device/System Characteristics:

A Device Description:

The OPTIGEN Allergen-Specific IgE Assay 12 Allergen Bundle A employs a test chamber (pette) to expose patient serum simultaneously to a number of allergens. The pette consists of three molded parts: the pette body, the coverslip and the partition. The coverslip contains discrete polystyrene wells, each with an allergen bound to it. Up to 36 different allergens can be tested in a single pette in addition to the Positive Procedural Control and Negative Blanking test wells. The allergens included in the OPTIGEN 12 Allergen Bundle A are Almond (f20), Bermuda Grass (g2), Cashew (f202), Clam (f207), Crab (f23), Hazelnut (f17), White Oak (t7), Salmon (f41), Sesame Seed (f10), Shrimp (f24), Tuna (f40), and Walnut (f256).

Reagents:

- Wash Buffer Concentrate, that when diluted, contains 0.01 M phosphate-buffered saline, 0.1% Tween 20, and 0.001% sodium azide as a preservative.

K193613 - Page 2 of 16

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- Antibody Reagent, a solution containing enzyme-labeled goat anti-human IgE, 0.01 M phosphate-buffered saline, pH 7.2, protein stabilizers, 0.1% Proclin as a preservative.
- Photoreagent I, a solution containing 7-15 mM 3-aminophthalhydrazide (luminol), 5-25 µM enhancer and 0.025 M borate buffer, pH 9.4.
- Photoreagent II, a solution containing 0.00125 M ethyl orange and 1.2 M hydrogen peroxide

## B Principle of Operation:

The AP3600 Instrument re-hydrates the pette and loads the patient serum sample into the pette. IgE antibodies in the patient sera bind to allergen-coated wells of the pette test chambers. After an incubation period, the instrument washes the pette with buffer solution to remove any unbound serum components and adds an enzyme-labeled anti-IgE antibody that binds to the IgE bound to the wells. After a second washing, the instrument fills the pette with a Photoreagent mixture which, when combined with the enzyme-labeled anti-IgE antibody gives off a chemically generated light (i.e. chemiluminescence). The amount of light emitted by each well is directly proportional to the amount of allergen-specific IgE in the patient's serum. A photomultiplier tube unit in the instrument measures the chemiluminescence light emitted and converts the light output into Luminometer Count (LMC) units. To calculate the patient's IgE response, the instrument automatically subtracts the emission level of the Negative Blanking Control from the emission level of each allergen. AP3600 Class Values are assigned from 0 to 6 based on the amount of light emitted by the individual allergens in the pette. The amounts of IgE associated with AP3600 Class values and instrument readings are listed in the following table.

| AP3600 Class Allergy Scoring System of the OPTIGEN Allergen-Specific IgE Assay | | |
| --- | --- | --- |
| AP3600 Class | LMC | Levels of allergen-Specific IgE Concentration |
| 0 | 0–500 | No antibodies detected |
| 1 | 501–1500 | Low levels of antibodies |
| 2 | 1501–7000 | Moderate levels of antibodies |
| 3 | 7001–36000 | High levels of antibodies |
| 4 | 36001–72000 | Very high levels of antibodies |
| 5 | 72001–150000 | |
| 6 | 150001–500000 | |

## V Substantial Equivalence Information:

### A Predicate Device Name(s):

ImmunoCAP Specific IgE (Modification from: Unicap Specific IgE)

### B Predicate 510(k) Number(s):

K051218

### C Comparison with Predicate(s):

K193613 - Page 3 of 16

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K193613 - Page 4 of 16
| Device & Predicate Device(s): | K193613 | K051218 |
| --- | --- | --- |
| Device Trade Name | OPTIGEN Allergen-Specific IgE
12 Allergen Bundle A | ImmunoCAP Specific IgE |
| **General Device Characteristic Similarities** | | |
| Intended Use/
Indications for Use | The OPTIGEN Allergen-Specific IgE Assay 12 Allergen Bundle A is an in vitro test for use in the semi-quantitative determination of circulating allergen specific IgE concentrations in human serum. OPTIGEN® Allergen-Specific IgE assays are meant to be included in panel tests to be used with the AP3600 instrument. Each assay is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE mediated allergenic disorders in conjunction with other clinical findings and are to be used in clinical laboratories.

The OPTIGEN 12 Allergen Bundle A includes Almond (f20), Bermuda Grass (g2), Cashew (f202), Clam (f207), Crab (f23), Hazelnut (f17), White Oak (t17), Salmon (f41), Sesame Seed (f10), Shrimp (f24), Tuna (f40), and Walnut (f256). | The ImmunoCAP Specific IgE is an in vitro quantitative assay for the measurement of allergen specific IgE in human serum or plasma (EDTA or Na-Heparin). ImmunoCAP Specific IgE is to be used with instruments Phadia 100, Phadia 250, and Phadia 1000. It is intended for in vitro diagnostic use as an aid in the clinical diagnosis of IgE mediated allergic disorders in conjunction with other clinical findings, and is to be used in clinical laboratories. |
| Sample Processing | Fully automated | Same |
| Antibody Reagent | Enzyme-labeled goat anti-human IgE | Same |
| Testing Environment | Clinical Laboratories | Same |
| **General Device Characteristic Differences** | | |
| System Configuration | AP3600 instrument+ pettes + consumables | Phadia 100, 250 or 1000 instrument + ImmunoCAP Specific IgE reagents |
| Methodology | Chemiluminescence immunoassay | Fluoroenzyme immunoassay |
| Assay Format | Semi-quantitative | Quantitative |
| Sample Type S | Serum | Serum and plasma (EDTA or sodium heparin) |

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| Device & Predicate Device(s): | K193613 | K051218 |
| --- | --- | --- |
| Minimum Sample Volume | 600 μL | 40–200 μL |
| Reagent Component | Fully integrated disposable pettes | Modular in concept and are available individually |
| Reported Unit | Luminometer Count (LMC) | kU_{A}/L |
| Class Allergy Scoring System | AP3600 Class Allergy Scoring System of the OPTIGEN Allergen-Specific IgE Assay: Class 0 to Class 6 | ASM (Alternate Scoring Method): Class 0/1 to Class 6 |

VI Standards/Guidance Documents Referenced:

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

CLSI I/LA20, 3rd Edition, Analytical Performance Characteristics, Quality Assurance, and Clinical Utility of Immunological Assays for Human Immunoglobulin E Antibodies of Defined Allergen Specificities

CLSI EP5-A3, Evaluation of Precision Performance of Quantitative Measurement Procedures; Approved Guideline – Third Edition.

CLSI EP12-A2, User Protocol for Evaluation of Qualitative Test Performance

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

CLSI EP37, 1st Edition, Supplemental Tables for Interference Testing in Clinical Chemistry

VII Performance Characteristics (if/when applicable):

A Analytical Performance:

1. Precision/Reproducibility:

The precision of the OPTIGEN 12 Allergen Bundle A on the AP3600 Automated Instrument was assessed with eight serum samples from single donors for each of the 12 allergens in the pette, with the exceptions of Sesame Seed (seven single-donor serum samples) and Tuna (six single-donor serum samples), in accordance with CLSI guideline EP05-A3. Each sample was tested by one operator in two replicates per run, two runs per day over the course of 20 days, using one reagent lot and one AP3600 Instrument, giving a total of 80 replicates per test sample. With the exceptions of Sesame Seed and Tuna, the levels of IgE in the test samples for OPTIGEN allergens represent the six AP 3600 Classes (Class 0 – Class 6) with the following ranges of values in LMC unit, from 501 to 750 and 1000 to 1500, for the Low Class I and High Class 1, respectively.

K193613 - Page 5 of 16

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The standard deviation (SD) and percent coefficients of variation (%CV) for within-run, between-run, between-day, and total within-laboratory imprecision are calculated for each OPTIGEN allergen at each Class level and summarized in the tables below.

| Within-Run | | | | | | | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| OPTIGEN 12
Allergen Bundle A | Samples by AP3600 Class | | | | | | | | | | | | | | | |
| | | Class 0 | | Low Class 1 | | High Class 1 | | Class 2 | | Class 3 | | Class 4 | | Class 5 | | Class 6 |
| # | Allergen | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD |
| 1 | Almond | 22 | 5.9 | 28 | 5.2 | 47 | 3.7 | 99 | 3.2 | 541 | 3.1 | 6331 | 12.0 | 2925 | 2.6 | 9649 |
| 2 | Bermuda Grass | 35 | 13.0 | 62 | 9.5 | 81 | 5.9 | 268 | 5.8 | 692 | 7.2 | 2454 | 3.9 | 4029 | 2.7 | 6137 |
| 3 | Cashew | 14 | 7.2 | 18 | 3.1 | 45 | 4.7 | 87 | 3.4 | 820 | 5.4 | 1216 | 2.0 | 4391 | 5.1 | 4653 |
| 4 | Clam | 18 | 4.2 | 15 | 2.7 | 33 | 3.6 | 208 | 5.9 | 273 | 3.5 | 1378 | 2.9 | 4100 | 4.4 | 7860 |
| 5 | Crab | 10 | 4.2 | 26 | 4.5 | 38 | 3.2 | 108 | 3.4 | 551 | 2.7 | 2943 | 5.3 | 1914 | 2.3 | 4912 |
| 6 | Hazelnut | 29 | 6.9 | 19 | 3.6 | 35 | 2.9 | 210 | 5.7 | 610 | 3.4 | 3127 | 4.4 | 3577 | 2.8 | 4380 |
| 7 | Oak, White | 11 | 7.6 | 33 | 6.3 | 66 | 5.8 | 78 | 2.9 | 2188 | 7.6 | 2841 | 5.6 | 5719 | 5.2 | 7100 |
| 8 | Salmon | 36 | 9.6 | 22 | 3.1 | 40 | 3.1 | 414 | 6.3 | 942 | 3.4 | 1699 | 3.6 | 2926 | 3.2 | 5658 |
| 9 | Sesame Seed* | 25 | 5.3 | 33 | 3.8 | 116 | 9.1 | 158 | 3.0 | 422 | 2.4 | 1400 | 2.4 | 2239 | 2.4 | - |
| 10 | Shrimp | 13 | 5.2 | 31 | 5.3 | 28 | 2.6 | 348 | 6.0 | 1124 | 3.9 | 2420 | 3.8 | 5673 | 3.8 | 8105 |
| 11 | Tuna# | 13 | 3.8 | 23 | 3.9 | 40 | 3.2 | 188 | 4.6 | 790 | 4.3 | 2472 | 4.6 | - | - | - |
| 12 | Walnut | 6 | 4.5 | 42 | 6.3 | 27 | 2.8 | 205 | 3.5 | 1046 | 3.7 | 2670 | 5.1 | 1406 | 1.4 | 9399 |
| *Sesame Seed was evaluated with samples containing IgE levels up to Class 5
#Tuna was evaluated with samples containing IgE levels up to Class 4 | | | | | | | | | | | | | | | | |
| Between-Run | | | | | | | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| OPTIGEN 12
Allergen Bundle A | Samples by AP3600 Class | | | | | | | | | | | | | | | |
| | | Class 0 | | Low Class 1 | | High Class 1 | | Class 2 | | Class 3 | | Class 4 | | Class 5 | | Class 6 |
| # | Allergen | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD |
| 1 | Almond | 43 | 11.6 | 96 | 17.9 | 150 | 12.1 | 276 | 9.0 | 1173 | 6.7 | 1403 | 2.7 | 21358 | 19.0 | 12931 |
| 2 | Bermuda Grass | 38 | 14.2 | 91 | 14.0 | 141 | 10.3 | 510 | 11.1 | 1007 | 10.5 | 11222 | 17.6 | 12709 | 8.6 | 17629 |
| 3 | Cashew | 28 | 14.4 | 99 | 17.0 | 81 | 8.5 | 245 | 9.6 | 2559 | 16.8 | 6796 | 11.4 | 15757 | 18.4 | 26462 |
| 4 | Clam | 7 | 1.6 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 |
| 5 | Crab | 4 | 1.7 | 17 | 2.8 | 30 | 2.6 | 151 | 4.8 | 0 | 0.0 | 1938 | 3.5 | 0 | 0.0 | 0 |
| 6 | Hazelnut | 73 | 17.1 | 67 | 12.9 | 148 | 12.2 | 580 | 15.6 | 2348 | 12.9 | 6178 | 8.6 | 17090 | 13.3 | 19886 |
| 7 | Oak, White | 17 | 11.8 | 76 | 14.5 | 144 | 12.5 | 441 | 16.4 | 3796 | 13.2 | 5465 | 10.8 | 13920 | 12.7 | 10614 |
| 8 | Salmon | 0 | 0.0 | 33 | 4.8 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1349 | 2.9 | 1811 | 2.0 | 0 |
| 9 | Sesame Seed* | 7 | 1.6 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | - |
| 10 | Shrimp | 6 | 2.3 | 0 | 0.0 | 12 | 1.1 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 3572 | 2.4 | 0 |
| 11 | Tuna# | 0 | 0.0 | 0 | 0.0 | 37 | 2.9 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | - | - | - |
| 12 | Walnut | 25 | 18.1 | 96 | 14.4 | 189 | 19.2 | 497 | 8.5 | 2217 | 7.8 | 4476 | 8.6 | 6997 | 6.8 | 26989 |
| *Sesame Seed was evaluated with samples containing IgE levels up to Class 5
#Tuna was evaluated with samples containing IgE levels up to Class 4 | | | | | | | | | | | | | | | | |

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Between-Day

| OPTIGEN 12 Allergen Bundle A | Samples by AP3600 Class | | | | | | | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Class 0 | | Low Class 1 | | High Class 1 | | Class 2 | | Class 3 | | Class 4 | | Class 5 | | Class 6 | |
| # | Allergen | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | Almond | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 7793 | 14.8 | 0 | 0.0 | 562 | 0.0 |
| 2 | Bermuda Grass | 18 | 6.7 | 0 | 0.0 | 41 | 2.9 | 0 | 0.0 | 336 | 3.5 | 3099 | 4.9 | 10558 | 7.2 | 8182 | 3.2 |
| 3 | Cashew | 0 | 0.0 | 28 | 4.8 | 69 | 7.3 | 56 | 2.2 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 20953 | 9.0 |
| 4 | Clam | 69 | 15.9 | 63 | 11.8 | 47 | 5.2 | 444 | 12.6 | 1392 | 18.1 | 3531 | 7.4 | 11383 | 12.1 | 8427 | 4.8 |
| 5 | Crab | 33 | 13.9 | 68 | 11.6 | 151 | 12.9 | 297 | 9.5 | 1173 | 5.8 | 6533 | 11.8 | 9494 | 11.3 | 10482 | 5.9 |
| 6 | Hazelnut | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 | 1419 | 2.0 | 0 | 0.0 | 11068 | 4.6 |
| 7 | Oak, White | 2 | 1.3 | 39 | 7.5 | 100 | 8.7 | 0 | 0.0 | 1788 | 6.2 | 6018 | 11.9 | 6833 | 6.3 | 2266 | 1.2 |
| 8 | Salmon | 49 | 12.9 | 82 | 11.8 | 144 | 11.4 | 363 | 5.5 | 2860 | 10.4 | 5507 | 11.8 | 2343 | 2.6 | 9552 | 3.8 |
| 9 | Sesame Seed* | 70 | 14.9 | 109 | 12.4 | 153 | 12.0 | 287 | 5.5 | 1710 | 9.8 | 9023 | 15.2 | 6648 | 7.2 | - | - |
| 10 | Shrimp | 32 | 12.6 | 80 | 13.6 | 225 | 21.1 | 653 | 11.2 | 3020 | 10.4 | 4810 | 7.5 | 10995 | 7.5 | 14299 | 6.2 |
| 11 | Tuna# | 43 | 13.1 | 53 | 9.0 | 85 | 6.7 | 373 | 9.1 | 1565 | 8.4 | 8362 | 15.7 | - | - | - | - |
| 12 | Walnut | 0 | 0.0 | 37 | 5.6 | 0 | 0.0 | 201 | 3.4 | 0 | 0.0 | 1141 | 2.2 | 6067 | 5.9 | 0 | 0.0 |
| *Sesame Seed was evaluated with samples containing IgE levels up to Class 5 #Tuna was evaluated with samples containing IgE levels up to Class 4 | | | | | | | | | | | | | | | | | |

Total (Within-Laboratory)

| OPTIGEN 12 Allergen Bundle A | Samples by AP3600 Class | | | | | | | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Class 0 | | Low Class 1 | | High Class 1 | | Class 2 | | Class 3 | | Class 4 | | Class 5 | | Class 6 | |
| # | Allergen | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV | SD | %CV |
| 1 | Almond | 48 | 13.0 | 100 | 18.6 | 157 | 12.6 | 293 | 9.6 | 1292 | 7.4 | 10138 | 19.2 | 21557 | 19.2 | 16144 | 10.1 |
| 2 | Bermuda Grass | 54 | 20.4 | 110 | 16.9 | 168 | 12.2 | 576 | 12.5 | 1267 | 13.2 | 11898 | 18.7 | 17007 | 11.5 | 20381 | 7.9 |
| 3 | Cashew | 32 | 16.1 | 104 | 17.9 | 115 | 12.2 | 266 | 10.5 | 2687 | 17.7 | 6904 | 11.6 | 16357 | 19.1 | 34072 | 14.7 |
| 4 | Clam | 72 | 16.5 | 65 | 12.1 | 57 | 6.4 | 490 | 13.9 | 1419 | 18.5 | 3790 | 7.9 | 12099 | 12.9 | 11523 | 6.6 |
| 5 | Crab | 35 | 14.6 | 75 | 12.8 | 159 | 13.5 | 351 | 11.2 | 1296 | 6.4 | 7423 | 13.4 | 9685 | 11.5 | 11576 | 6.5 |
| 6 | Hazelnut | 79 | 18.5 | 70 | 13.4 | 152 | 12.5 | 617 | 16.6 | 2426 | 13.3 | 7068 | 9.9 | 17460 | 13.6 | 23176 | 9.6 |
| 7 | Oak, White | 20 | 14.1 | 92 | 17.5 | 188 | 16.3 | 448 | 16.7 | 4732 | 16.4 | 8612 | 17.0 | 16528 | 15.1 | 12969 | 6.9 |
| 8 | Salmon | 61 | 16.1 | 91 | 13.1 | 150 | 11.8 | 551 | 8.4 | 3011 | 10.9 | 5919 | 12.7 | 4163 | 4.6 | 11102 | 4.5 |
| 9 | Sesame Seed* | 74 | 15.9 | 114 | 12.9 | 192 | 15.1 | 327 | 6.3 | 1761 | 10.0 | 9131 | 15.4 | 7015 | 7.6 | - | - |
| 10 | Shrimp | 36 | 13.8 | 86 | 14.6 | 227 | 21.3 | 740 | 12.7 | 3222 | 11.1 | 5384 | 8.4 | 12878 | 8.7 | 16437 | 7.1 |
| 11 | Tuna# | 45 | 13.7 | 58 | 9.8 | 101 | 7.9 | 417 | 10.2 | 1753 | 9.5 | 8720 | 16.4 | - | - | - | - |
| 12 | Walnut | 26 | 18.6 | 112 | 16.7 | 191 | 19.4 | 574 | 9.8 | 2451 | 8.6 | 5336 | 10.3 | 9367 | 9.1 | 28578 | 17.9 |
| *Sesame Seed was evaluated with samples containing IgE levels up to Class 5 #Tuna was evaluated with samples containing IgE levels up to Class 4 | | | | | | | | | | | | | | | | | |

# Lot-to-lot imprecision:

A study was performed in accordance with CLSI guideline EP5-A3. The OPTIGEN allergens were evaluated with three kit lots in replicates of five over five days. A total of 75 replicates were tested for each allergen at each level. The mean SD and $\% \mathrm{CV}$ of the responses were calculated per AP3600 class, and results are summarized below for within-run, between-run, between-lot and within-laboratory (total variance) precision.

K193613 - Page 7 of 16

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| | Samples by AP3600 Class | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | Class 0 | Low Class 1* | High Class 1 | Class 2 | Class 3 | Class 4 | Class 5* | Class 6*,# |
| Number of samples | 12 | 12 | 12 | 12 | 12 | 12 | 11 | 10 |
| LMC Class Average | 274.6 | 654.0 | 1220.4 | 4273.7 | 18460.7 | 56836.9 | 104344.6 | 206874.8 |
| Repeatability | | | | | | | | |
| • SD | 36.4 | 83.0 | 133.3 | 520.0 | 1951.1 | 6791.1 | 12773.8 | 20597.3 |
| • %CV | 13.3 | 12.7 | 10.9 | 12.2 | 10.6 | 11.9 | 12.2 | 10.0 |
| Between-Run | | | | | | | | |
| • SD | 20.2 | 51.7 | 44.0 | 99.2 | 572.1 | 1790.2 | 4213.9 | 6192.6 |
| • %CV | 7.3 | 7.9 | 3.6 | 2.3 | 3.1 | 3.1 | 4.0 | 3.0 |
| Between-Lot | | | | | | | | |
| • SD | 0.0 | 5.4 | 0.0 | 3.6 | 46.3 | 298.2 | 0.0 | 1360.7 |
| • %CV | 0.0 | 0.8 | 0.0 | 0.1 | 0.3 | 0.5 | 0.0 | 0.7 |
| Total | | | | | | | | |
| • SD | 42.7 | 103.5 | 143.4 | 539.0 | 2126.9 | 7342 | 13894.9 | 23157.8 |
| • %CV | 15.5 | 15.8 | 11.8 | 12.6 | 11.5 | 12.9 | 13.3 | 11.2 |
| # Samples contain allergen-specific IgEs near the transition boundary of undetectable (Class 0) to a low Class 1
^ None of the Class 5 and Class 6 samples contains IgE specific to Tuna
# None of the Class 6 samples contains IgE specific to Sesame Seed | | | | | | | | |

# 2. Linearity:

Linearity of the continuous LMC signal for each OPTIGEN allergen was evaluated according to the CLSI guideline I/LA20. For each allergen, a minimum of two pooled samples (one Class 0 and one Class 6) was used. The pair of high (Class 6) and low (Class 0) samples were mixed in different ratios to prepare 15 levels of IgE for each allergen across the six AP3600 classes. Each level was tested in three replicates with one lot of the OPTIGEN 12 Allergen Bundle A using one AP3600 Instrument. Bermuda Grass, Sesame Seed, Tuna and Walnut did not have clinically high positive samples to yield results with all six AP3600 classes. The results of the regression analysis and the claimed linear range for the allergens tested are summarized in the table below.

| OPTIGEN 12 Allergen Bundle A | Sample range tested | | Slope 95% CI | Intercept 95% CI | r² | Claimed linear range | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | LMC | | | | AP3600 Class | LMC | AP3600 Class |
| Almond | f20 | 0–172793 | 0-6 | 0.98 0.93–1.04 | 2470.5 -479.4–5420.4 | 0.992 | 76–172793 | 0–6 |
| Bermuda Grass* | g2 | 0–132413 | 0-5 | 1.01 0.95–1.07 | 2080.4 -717.3–4878.0 | 0.994 | 91–132413 | 0–5 |
| Cashew | f202 | 0–201390 | 0-6 | 1.08 0.92–1.23 | 9334.4 -2194.7–20863.5 | 0.958 | 78–201390 | 0–6 |
| Clam | f207 | 0–249654 | 0-6 | 1.03 0.89–1.18 | 9265.3 -4080.8–22611.3 | 0.972 | 180–249654 | 0–6 |
| Crab | f23 | 0–180332 | 0-6 | 1.05 0.96–1.14 | 4905.0 -533.7–10343.6 | 0.978 | 73–180332 | 0–6 |
| Hazelnut | f17 | 0–183935 | 0-6 | 1.08 0.94–1.21 | 7826.7 -178.9–15832.2 | 0.958 | 87–183935 | 0–6 |
| Oak, White | t7 | 0–171287 | 0-6 | 1.00 0.96 –1.04 | 1590.5 -715.2–3896.1 | 0.995 | 98-171287 | 0–6 |

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K193613 - Page 9 of 16

| OPTIGEN 12 Allergen Bundle A | Sample range tested | | Slope 95% CI | Intercept 95% CI | r² | Claimed linear range | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | LMC | | | | AP3600 Class | LMC | AP3600 Class |
| Salmon | f41 | 0–176707 | 0-6 | 1.05 0.93–1.17 | 6193.6 -1483.1–13870.4 | 0.974 | 93–176707 | 0–6 |
| Sesame Seed* | f10 | 0–106921 | 0-5 | 1.00 0.99–1.02 | 9.7 -520.7–540.0 | 0.999 | 95–106921 | 0–5 |
| Shrimp | f24 | 0–199150 | 0-6 | 1.07 0.94–1.21 | 9779.2 -605.0–16563.5 | 0.959 | 82–199150 | 0–6 |
| Tuna** | f40 | 0–53716 | 0-4 | 1.02 0.96–1.07 | 575.8 -479.5–1631.1 | 0.992 | 116–53716 | 0–4 |
| Walnut* | f256 | 0–130720 | 0-5 | 1.04 0.96–1.12 | 2763.0 -574.1–6100.1 | 0.984 | 100–130720 | 0–5 |
| * Bermuda Grass, Sesame Seed and Walnut have a reportable range up to Class 5. **Tuna has a reportable range up to Class 4. | | | | | | | | |

## 3. Analytical Specificity/Interference:

### Analytical Specificity:

The analytical specificity of each OPTIGEN allergen in the pette was evaluated by competitive inhibition testing with the homologous allergen extract and heterologous (unrelated) allergen extracts from similar or different allergen groups. The studies were conducted in accordance with I/LA-20 3rd Edition. For each OPTIGEN allergen, a Class 3 serum (pooled or single donor sample with LMC between 7001-36000) was incubated with increasing amounts of the corresponding (homologous) allergen extracts in solution. The required amounts of allergen extract to achieve $\geq 50\%$ inhibition of the LMC signal for each OPTIGEN allergen is showed in the table below.

| | | Class 3 Samples + Diluent* | Class 3 Samples + Homologous Allergen Extract in Solution | | |
| --- | --- | --- | --- | --- | --- |
| OPTIGEN 12 Allergen Bundle A | | LMC | LMC | % Inhibition Achieved | Required Concentration of Allergen Extract |
| Almond | f20 | 12563 | 3536 | 71.8 | 0.00625 mg/mL |
| Bermuda Grass | g2 | 12757 | 4615 | 63.8 | 0.0004 mg/mL |
| Cashew | f202 | 13392 | 1789 | 86.6 | 0.0000125 mg/mL |
| Clam | f207 | 13217 | 6653 | 50.0 | 0.003 mg/mL |
| Crab | f23 | 15986 | 4887 | 69.4 | 0.00075 mg/mL |
| Hazelnut | f17 | 8341 | 3598 | 56.8 | 0.0125 mg/mL |
| Oak, White | t7 | 9476 | 3469 | 63.4 | 0.04 mg/mL |
| Salmon | f41 | 24011 | 5949 | 75.2 | 0.00005 mg/mL |
| Sesame Seed | f10 | 9360 | 3993 | 57.3 | 0.0125 mg/mL |
| Shrimp | f24 | 21161 | 7555 | 64.3 | 0.00312 mg/mL |
| Tuna | f40 | 7350 | 3661 | 50.2 | 0.05 mg/mL |
| Walnut | f256 | 23220 | 11201 | 51.7 | 0.00005 mg/mL |
| *Saline is the diluent used for the allergen extracts | | | | | |

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For each OPTIGEN allergen, four unrelated allergens, one from the same allergen group and three from different allergen groups, were incubated with the Class 3 serum samples at a dose that is at least ten-fold higher than the concentration of the homologous allergen that yielded $\geq 50\%$ inhibition. Testing was performed in duplicate in one assay run and the mean values were calculated. Results are summarized in the tables below.

| Unrelated Allergens from the Same Group | | | |
| --- | --- | --- | --- |
| OPTIGEN 12 Allergen Bundle A | | Unrelated Allergen Extract (in solution) | % Inhibition |
| Almond | f20 | Milk, f2 | -7.5 |
| Bermuda Grass | g2 | Sweet vernal, g1 | 63.8 |
| | | Orchard, g3 | 67.9 |
| | | Perennial rye, g5 | 73.6 |
| | | Timothy, g6 | 79.1 |
| | | Cultivated rye, g12 | 60.0 |
| | | Bahia, g16 | 76.4 |
| Cashew | f202 | Milk, f2 | -20.3 |
| Clam | f207 | Tuna, f40 | 12.4 |
| Crab | f23 | Milk, f2 | -27.6 |
| Hazelnut | f17 | Milk, f2 | -88.7 |
| Oak, White | t7 | Mulberry, t71 | 18.0 |
| Salmon | f41 | Clam, f207 | 8.2 |
| Sesame Seed | f10 | Milk, f2 | -0.6 |
| Shrimp | f24 | Milk, f2 | -21.8 |
| Tuna | f40 | Milk, f2 | -41.8 |
| Walnut | f256 | Egg white, f1 | -11.4 |
| Unrelated Allergens from Different Groups | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| OPTIGEN 12 Allergen Bundle A | Allergen Group 1 | | Allergen Group 2 | | Allergen Group 3 | | |
| | | Unrelated Allergen Extract (in solution) | % Inhibition | Unrelated Allergen Extract (in solution) | % Inhibition | Unrelated Allergen Extract (in solution) | % Inhibition |
| Almond | f20 | Alternaria, m6 | -18.7 | Dog, e5 | -24.2 | House dust, h2 | -15.8 |
| Bermuda Grass | g2 | Mugwort, w6 | 4.9 | Dog, e5 | 0.5 | Milk, f2 | -1.2 |
| Cashew | f202 | Alternaria, m6 | -8.2 | Cat, e1 | -0.6 | Mite F, d2 | -3.5 |
| Clam | f207 | Black Willow, t32 | 3.2 | Dog, e5 | 0.5 | Aspergillus, m3 | 12.5 |
| Crab | f23 | Black Willow, t32 | -5.8 | Dog, e5 | 4.2 | Aspergillus, m3 | 6.6 |
| Hazelnut | f17 | Mite F, d2 | -34.2 | Dog, e5 | -17.4 | Aspergillus, m3 | -44.2 |
| Oak, White | t7 | Alternaria, m6 | -36.6 | Dog, e5 | -30.2 | Milk, f2 | -45.6 |
| Salmon | f41 | Oak, t7 | 2.9 | Bermuda, g2 | 0.6 | Aspergillus, m3 | -7.0 |
| Sesame Seed | f10 | Alternaria, m6 | -7.0 | Dog, e5 | -5.0 | House dust, h2 | 2.0 |
| Shrimp | f24 | Black Willow, t32 | -30.0 | Dog, e5 | -22.7 | Aspergillus, m3 | -16.9 |
| Tuna | f40 | Black Willow, t32 | -13.5 | Dog, e5 | -22.6 | Aspergillus, m3 | -161.5 |
| Walnut | f256 | Penicillium, m1 | -5.5 | Cat, e1 | -1.6 | House dust, h2 | -2.8 |

Two OPTIGEN allergens, Bermuda Grass, and White Oak, in the pette did not meet specification of less than $15\%$ inhibition with the unrelated allergen from the same group. The grass and tree allergens are known to have cross-reactivity within the same group of

K193613 - Page 10 of 16

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allergens. A study done by Bullimore et al.,¹ stated that each grass tested exhibited a greater than 55% similarity. Trees are also known to be cross-reactive to each other². The inhibition studies using four unrelated allergens from different groups did not show any significant inhibition.

## Interference:

To determine the effects of both endogenous and exogenous interfering substances on the 12 OPTIGEN allergens in the pette, three patient serum samples were tested for each OPTIGEN allergen: one in Class 0 (0–500 LMC), one in Class 1 (501–1500 LMC) and one with LMCs near the transition boundary of Class 0 and Class 1 (375–625 LMC). Each sample was spiked with the interferent substance (test sample) or with the corresponding buffer (control sample). The test samples in Class 0 and Class 1 and corresponding control samples were assayed in 20 replicates (for endogenous interfering substances) or 10 replicates (for exogenous interfering substances) on an AP3600 Instrument. The test samples near the transition boundary of Class 0 and Class 1 and the corresponding control samples were assayed in six replicates for both endogenous and exogenous interfering substances. The endogenous (hemoglobin, bilirubin and triglycerides) and exogenous (Astemizole, Cetirizine, Delsoratadine, Hydroxyzine and Promethazine) interfering substances were tested at the final concentrations recommended in the CLSI guideline EP07-03. Results show that the mean LMC for each test (spiked) serum remains within the definition of Class 0 (0–500 LMC) and Class 1 (501–1500 LMC) and that there was no change in Class for the test samples near the transition boundary of Class 0 and Class 1 for each allergen indicating that hemoglobin up to 500 mg/dL, bilirubin up to 20 mg/dL, triglycerides up to 2000 mg/dL, astemizole at 0.654 μmol/L, cetirizine at 11.2 μmol/L, delsoratadine at 0.281 μmol/L, hydroxyzine at 0.712 μmol/L, and promethazine at 1.04 μmol/L do not adversely impact the test results for each OPTIGEN allergen.

## Cross-reactivity:

There is no detectable cross-reactivity with human serum immunoglobulins IgA, IgM, IgG, or IgD at normal physiological levels.

## 4. Assay Reportable Range:

The OPTIGEN Allergen-Specific IgE Assay 12 Allergen Bundle A reports six AP3600 classes. For Bermuda Grass, Sesame Seed and Walnut, the reportable range is from Class 0 to Class 5. Tuna has a reportable range up to Class 4.

## 5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

Traceability:

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¹ Bullimore A., Batten T, Hewings S., von Weikersthal-Drachenber KJF and Skinner M. Cross-reactivity in Grasses: Biochemical Attributes Define Exemplar Relevance. WAO Journal 2012; 5:111–119

² Richard W. Weber, Patterns of pollen cross-allergenicity From the National Jewish Medical and Research Center August 2003 Volume 112, Issue 2, Pages 229–239

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The method has no absolute standard and has been arbitrarily assigned levels of classification.

# Kit stability:

A real-time stability study using three lots of the OPTIGEN 12 Allergen Bundle is on-going. A minimum of two positive and one negative human serum samples were tested in duplicate. Currently available data supports a shelf-life of 3 months from the date of manufacture when stored at the recommended storage temperature of $2 - 8^{\circ}\mathrm{C}$ .

# 6. Detection Limit:

The Limit of Blank (LoB) and Limit of Detection (LoD) were determined for each OPTIGEN allergen in the pette in alignment with CLSI guideline EP17-A2 using two lots of reagents. The LoB is based on 75 blank measurements (one blank sample tested in 25 replicates $\times$ one run/day $\times$ three days) using one AP3600 Instrument for each of the 12 OPTIGEN allergens on the pette. The LoD for each allergen was determined by running four or more low level "Class 1" sera. Each serum was assayed in duplicate per run with two runs per day over four different days on an AP3600 Instrument for each of two reagent lots yielding a total of more than 64 replicates per reagent lot. For each allergen, the criterion for use of a serum to calculate the LoB and LoD was that the mean LMC for the runs for that allergen had to be less than the cut-off between undetectable (Class 0: 0-500 LMC) and low positive (Class 1:501-1500 LMC). Results summarized in the table below show that the higher LoB value reported for the two lots is above 0 LMC for two of the 12 allergens and that the higher of the two LoD values reported is not uniform across allergens and instead was a range from 73 LMC to 180 LMC.

| | | LoB | | LoD | |
| --- | --- | --- | --- | --- | --- |
| OPTIGEN 12Allergen Bundle A | | Number ofblank tested | LMC | Number of low-level sera tested | LMC |
| Almond | f20 | 1 | 0 | 7 | 76 |
| Bermuda Grass | g2 | | 0 | 4 | 91 |
| Cashew | f202 | | 0 | 5 | 78 |
| Clam | f207 | | 100 | 8 | 180 |
| Crab | f23 | | 0 | 7 | 73 |
| Hazelnut | f17 | | 0 | 8 | 87 |
| Oak, White | t7 | | 0 | 6 | 98 |
| Salmon | f41 | | 0 | 4 | 93 |
| Sesame Seed | f10 | | 0 | 8 | 95 |
| Shrimp | f24 | | 0 | 4 | 82 |
| Tuna | f40 | | 2 | 4 | 116 |
| Walnut | f256 | | 0 | 8 | 100 |

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# 7. Assay Cut-Off:

The OPTIGEN Allergen Assay reports six AP3600 classes. Class cut-offs assigned based on the amount of light emitted by the individual OPTIGEN allergens in the pette and converted into LMC units are listed in the table below:

| AP3600 Class | LMC |
| --- | --- |
| 0 | 0-500 |
| 1 | 501-1500 |
| 2 | 1501-7000 |
| 3 | 7001-36000 |
| 4 | 36001-72000 |
| 5 | 72001-150000 |
| 6 | 150001-500000 |

# B Comparison Studies:

# 1. Method Comparison with Predicate Device:

A study was performed to compare results obtained with the OPTIGEN 12 Allergen Bundle A to the results obtained by the comparator method, Thermos Fisher ImmunoCAP Specific IgE. A total of 49-171 positive serum samples (with total IgE concentration $\geq 20$ IU/mL) and 165-237 negative serum samples (with total IgE concentration $< 20$ IU/mL) were assayed in singleton by both methods. The samples tested (N) represent all AP3600 classes, i.e., Class 0 to Class 6. The positive percentage agreement (PPA), negative percentage agreement (NPA), and total percentage agreement (TPA) for each OPTIGEN allergen in the pette are calculated and summarized in the table below.

| OPTIGEN 12 Allergen Bundle A | Positive Samples | | | Negative Samples | | | All Samples | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | N | PPA (%) | 95% CI | N | NPA (%) | 95% CI | N | TPA (%) | 95% CI |
| Almond | f20 | 81 | 97.5 (79/81) | 91.4–99.7 | 175 | 88.6 (155/175) | 82.9–92.9 | 256 | 91.4 (234/256) | 87.3–94.5 |
| Bermuda Grass | g2 | 111 | 94.6 (105/111) | 88.6–98.0 | 170 | 93.5 (159/170) | 88.7–96.7 | 281 | 94.0 (264/281) | 90.5–96.4 |
| Cashew | f202 | 49 | 100 (49/49) | 92.8–100.0 | 169 | 92.3 (156/169) | 87.2–95.8 | 218 | 94.0 (205/218) | 90.0–96.8 |
| Clam | f207 | 96 | 95.8 (92/96) | 89.7–98.9 | 207 | 87.0 (180/207) | 81.6–91.2 | 303 | 89.8 (272/303) | 89.8–92.9 |
| Crab | f23 | 148 | 85.1 (126/148) | 78.4–90.4 | 189 | 94.7 (179/189) | 90.5–97.4 | 337 | 90.5 (305/337) | 86.9–93.4 |
| Hazelnut | f17 | 72 | 95.8 (69/72) | 88.3–99.1 | 169 | 90.5 (153/169) | 85.1–94.5 | 241 | 92.1 (222/241) | 88.0–95.2 |
| Oak, White | t7 | 103 | 87.4 (90/103) | 79.4–93.1 | 177 | 96.6 (171/177) | 92.8–98.8 | 280 | 93.2 (261/280) | 89.6–95.9 |
| Salmon | f41 | 82 | 93.9 (77/82) | 86.3–98.0 | 199 | 92.0 (183/199) | 87.3–95.3 | 281 | 92.5 (260/281) | 88.8–95.3 |

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| OPTIGEN 12 Allergen Bundle A | Positive Samples | | | Negative Samples | | | All Samples | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | N | PPA (%) | 95% CI | N | NPA (%) | 95% CI | N | TPA (%) | 95% CI |
| Sesame Seed | f10 | 91 | 84.6 (77/91) | 75.5–91.3 | 165 | 96.4 (159/165) | 92.3–98.7 | 256 | 92.2 (236/256) | 88.2–95.2 |
| Shrimp | f24 | 171 | 84.8 (145/171) | 78.5–89.8 | 194 | 95.4 (185/194) | 91.4–97.9 | 365 | 90.4 (330/365) | 86.9–93.2 |
| Tuna | f40 | 76 | 90.8 (69/76) | 81.9–96.2 | 237 | 91.1 (216/237) | 86.8–94.4 | 313 | 91.1 (285/313) | 87.3–94.0 |
| Walnut | f256 | 89 | 89.9 (80/89) | 81.7–95.3 | 177 | 93.8 (166/177) | 89.2–96.9 | 266 | 92.5 (246/266) | 88.6–95.4 |

The PPA, NPA and TPA for all OPTIGEN allergens in the pette are summarized in the table below:

| | Comparator Method | | | |
| --- | --- | --- | --- | --- |
| | | Positive (Class 1 and above) | Negative (Class 0) | Total |
| OPTIGEN 12 Allergen Bundle Assayed on AP3600 | Positive (Class 1 and above) | 1058 | 166 | 1224 |
| | Negative (Class 0) | 111 | 2062 | 2173 |
| | Total | 1169 | 2228 | 3397 |
| PPA: 90.5% (1058/1169) 95% CI: 88.7 – 92.1% NPA: 92.6% (2062/2228) 95% CI: 91.4 – 93.6% TPA: 91.9% (3120/3397) 95% CI: 90.9 – 92.7% | | | | |

A comparison by each AP3600 class was also performed for all allergens and all serum samples tested by the two methods to determine the number of misclassifications. The results are summarized in the table below. For all AP3600 classes, the total number of disagreements between the two methods is 929 or $27.3\%$ (929/3397). The majority of disagreements (647/929 or $69.6\%$ ) were within one class. A total of 229 (229/929 or $24.7\%$ ) differed by two classes, 41 (41/929 or $4.4\%$ ) differed by three classes and 12 (12/929 or $1.3\%$ ) differed by four classes.

| | Comparator Method | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Class 0 | Class 1 | Class 2 | Class 3 | Class 4 | Class 5 | Class 6 | Total |
| OPTIGEN 12 Allergen Bundle A Assayed on AP3600 | Class 0 | 2062 | 47 | 47 | 17 | 0 | 0 | 0 | 2173 |
| | Class 1 | 86 | 36 | 48 | 16 | 0 | 0 | 0 | 186 |
| | Class 2 | 72 | 66 | 174 | 50 | 10 | 0 | 0 | 372 |
| | Class 3 | 8 | 16 | 198 | 153 | 15 | 1 | 0 | 391 |
| | Class 4 | 0 | 2 | 14 | 77 | 26 | 3 | 0 | 122 |
| | Class 5 | 0 | 1 | 2 | 34 | 36 | 8 | 1 | 82 |
| | Class 6 | 0 | 0 | 11 | 12 | 19 | 20 | 9 | 71 |
| | Total | 2228 | 168 | 494 | 359 | 106 | 32 | 10 | 3397 |

A comparison between OPTIGEN 12 Allergen Bundle A on AP3600 and the comparator method for non-Class 0 samples that differ by one AP 3600 class show strong correlation

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(78.0% –100%) for all classes except Class 4 (72.6%). There is no risk of misclassification as these samples are all positive.

| | OPTIGEN 12 Allergen Bundle A vs. Comparator Method | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | Positive (Class 1 and above) | | | | | | |
| | Class 1 | Class 2 | Class 3 | Class 4 | Class 5 | Class 6 | Class 1-6 |
| Within one class | 149/168 (88.7%) | 420/494 (85.0%) | 280/359 (78.0%) | 77/106 (72.6%) | 28/32 (88.0%) | 10/10 (100%) | 964/1169 (82.4%) |

The numbers of samples that differ by one AP3600 class for each allergen tested are summarized in the table below.

| OPTIGEN 12 Allergen Bundle A | | N | Within one class |
| --- | --- | --- | --- |
| Almond | f20 | 256 | 242 (94.5%) |
| Bermuda Grass | g2 | 281 | 273 (97.2%) |
| Cashew | f202 | 218 | 197 (90.4%) |
| Clam | f207 | 303 | 261 (86.1%) |
| Crab | f23 | 337 | 305 (90.5%) |
| Hazelnut | f17 | 241 | 222 (92.1%) |
| Oak, White | t7 | 280 | 263 (93.9%) |
| Salmon | f41 | 281 | 246 (87.5%) |
| Sesame Seed | f10 | 256 | 242 (94.5%) |
| Shrimp | f24 | 365 | 316 (86.6%) |
| Tuna | f40 | 313 | 297 (94.9%) |
| Walnut | f256 | 266 | 251 (94.4%) |
| Total | | 3397 | 3115 (91.7%) |

2. Matrix Comparison:

Not applicable. Serum is the only matrix for this assay.

C Clinical Studies:

1. Clinical Sensitivity:

Not applicable

2. Clinical Specificity:

Not applicable

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):

None

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D Clinical Cut-Off:

Not applicable

E Expected Values/Reference Range:

The expected values for the 12 OPTIGEN allergens in the pette were analyzed in accordance with CLSI guideline C28-A3c. A minimum of 120 samples that were negative for each allergen (i.e., the subjects were confirmed as allergen-negative from the approved commercial vendor) along with samples that were positive for an allergen but did not have a specific positive response were evaluated. The number of samples used for each OPTIGEN allergen ranges from 153 to 216. The study cohort demographics are as follows: 40.2% female / 59.8% male, between 19 to 71 years of age (average age is 38 years and 8 months), 62.3% Caucasian, 22.1% African American, 11.5% Hispanic, 2.5% Asian, <1% Pacific Islander, <1% Native Alaskan and <1% 'mixed' race. The mean, median, range and 97.5th percentile of the LMC values as well as the number and percentage of test positive results for each OPTIGEN allergen are summarized in the table below:

| OPTIGEN 12 Allergen Bundle A | | N | Mean (LMC) | Range (LMC) | 97.5th Percentile (LMC) | N (%) Test positive |
| --- | --- | --- | --- | --- | --- | --- |
| Almond | f20 | 155 | 9.7 | 0–413 | 311 | 20 (12.9) |
| Bermuda Grass | g2 | 159 | 7.5 | 0–393 | 327 | 11 (6.9) |
| Cashew | f202 | 156 | 5.1 | 0–412 | 122 | 13 (8.3) |
| Clam | f207 | 180 | 26.8 | 0–488 | 428 | 27 (15.0) |
| Crab | f23 | 179 | 12.8 | 0–442 | 412 | 10 (5.6) |
| Hazelnut | f17 | 153 | 10.3 | 0–474 | 363 | 16 (10.5) |
| Oak, White | t7 | 171 | 5.8 | 0–315 | 206 | 6 (3.5) |
| Salmon | f41 | 183 | 14.9 | 0–442 | 412 | 16 (8.7) |
| Sesame Seed | f10 | 159 | 0.6 | 0–95 | 0 | 6 (3.8) |
| Shrimp | f24 | 185 | 7.0 | 0–495 | 256 | 9 (4.8) |
| Tuna | f40 | 216 | 17.3 | 0–458 | 369 | 21 (9.7) |
| Walnut | f256 | 166 | 7.3 | 0–455 | 281 | 11 (6.6) |

It is the responsibility of each laboratory to establish its own reference ranges for the population of patients it serves, as expected values are affected by many different factors.

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.

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