(257 days)
The IMMULITE® 2000 3gAllergy™ Specific IgE Universal Kit is for in vitro diagnostic use with the IMMULITE® 2000 Analyzer — for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinical diagnosis of IgE-mediated allergic disorders. The test results are to be used in conjunction with clinical findings and other laboratory tests.
IMMULITE® 2000 3gAllergy™ Specific IgE Universal Kit assay is a solid-phase, two-step, chemiluminescent immunoassay that exploits liquid phase kinetics in a bead format. It represents a significant advance over conventional methods relying on allergens attached to a solid-phase support. The allergens are covalently bound to a soluble polymer/co-polymer matrix, which in turn is labeled with a ligand. The use of an amino acid co-polymer amplifies the amount of allergen that the matrix can support. This 510(k) submission is for clearance of seven additional specific molecular allergens shown in Table 1 to be used with the IMMULITE® 2000 3gAllergy™ Specific IgE Universal Kit on the IMMULITE® 2000 analyzer.
Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided 510(k) summary (K132801):
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by the performance test results provided and the statement that the device "meets the criteria for acceptable repeatability, within-lab, and lot-to-lot precision." The summary also states that the device's working range is 0.10 to 100 kU/L, and its detection limits are ≤0.10 kU/L.
| Performance Metric | Acceptance Criteria (Implied / Stated) | Reported Device Performance (Best Case / Range) |
|---|---|---|
| Non-Clinical Performance | ||
| Repeatability (%CV) | < 15% for all allergen lots (Positive samples) | rBet v 2: 1.65% (min) - 5.07% (max)rMal d 1: 3.33% (min) - 5.32% (max)rMal d 4: 1.65% (min) - 4.25% (max)rPru av 1: 2.43% (min) - 5.17% (max)rPru av 3: 2.82% (min) - 5.17% (max)rPru av 4: 2.45% (min) - 4.25% (max)nPru p 3: 2.44% (min) - 7.43% (max) |
| Within-Lab Precision (%CV) | < 15% for all allergen lots (Positive samples) | rBet v 2: 4.1% (min) - 7.3% (max)rMal d 1: 4.29% (min) - 9.36% (max)rMal d 4: 4.06% (min) - 7.3% (max)rPru av 1: 4.49% (min) - 14.31% (max) (with outliers) / 5.66% - 7.41% (without outliers)rPru av 3: 4.84% (min) - 12.8% (max) (with outliers) / 5.03% - 8.01% (without outliers)rPru av 4: 4.72% (min) - 17.5% (max) (with outliers) / 4.5% - 7.56% (without outliers)nPru p 3: 3.93% (min) - 80.67% (max) (with outliers) / 4.55% - 7.71% (without outliers) |
| Lot-to-Lot Precision (%CV) | < 20% for all seven allergens (Positive samples) | rBet v 2: 10.1% (Positive 2) - 12.5% (Positive 1)rMal d 1: 13.0% (Positive 1) - 15.7% (Positive 2)rMal d 4: 6.49% (Positive 1) - 8.94% (Positive 2)rPru av 1: 9.29% (Positive 1) - 13.7% (Positive 2)rPru av 3: 10.3% (Positive 1) - 11.6% (Positive 3)rPru av 4: 5.83% (Positive 1) - 15.7% (Positive 2)nPru p 3: 7.71% (Positive 2**) - 9.52% (Positive 3) (without outliers) |
| Negative Control | Remained negative (< 0.10 kU/L) | Maintained negative (<0.10 kU/L) throughout precision testing. |
| Limit of Blank (LoB) | ≤0.06 kU/L (specific value depends on allergen) | Range from 0.00 kU/L to 0.06 kU/L for various allergens and lots. Meets stated criteria. |
| Limit of Detection (LoD) | ≤0.10 kU/L for all specified allergens | Range from 0.03 kU/L to 0.09 kU/L for various allergens and lots. Meets stated criteria. |
| Specificity (Competitive Inhibition) | Relevant inhibitor extract causes concentration-dependent inhibition, with ≥50% inhibition at highest concentration. | Inhibition demonstrated, meeting 50% target for highest inhibitor concentration. |
| Specificity (Cross-Reactivity) | Irrelevant/related allergens should not generate inhibition >15%. | Irrelevant and related extracts did not generate inhibition >15% for the specified allergens. |
| Linearity | Demonstrated linearity within the working range (0.10-100 kU/L). Regression equation slope near 1, R-squared near 1. | R-squared values were high (e.g., 0.998 - 1.000 for most, one noted as 0.899). Slopes were generally close to 1 with confidence intervals including 1 (e.g., 0.953-1.053, 0.987-1.083). Range tested for linearity varied by allergen (e.g., 0.24 to 26.33 kU/L). |
| Clinical Performance | ||
| Sensitivity | Not explicitly stated as a separate acceptance criterion, but presented to show clinical effectiveness. | 46.8% (42.1% - 51.5% 95% CI) |
| Specificity | Not explicitly stated as a separate acceptance criterion, but presented to show clinical effectiveness. | 98.9% (98.1% - 99.4% 95% CI) |
| Agreement | Not explicitly stated as a separate acceptance criterion, but presented to show clinical effectiveness. | 84.0% (82% - 86% 95% CI) |
The acceptance criteria for precision (repeatability, within-lab, and lot-to-lot) were met for all allergens after addressing outliers as indicated by "No outliers used in calculation" footnotes for some positive samples.
2. Sample Size Used for the Test Set and Data Provenance
- Non-Clinical Performance (Precision):
- For each allergen lot and positive sample: 84 (2 runs/day x 20 days x 3 replicates, with some adjustments for outliers resulting in 80 or 79 valid data points).
- For lot-to-lot precision: 332-334 samples (across 4 lots of each allergen).
- For negative control: 84 samples (across multiple runs/days).
- Non-Clinical Performance (Detection Limits - LoB): 80 data points for each allergen lot (4 blank samples tested in replicates of two, with one run per day, over five days, using two instruments and three lots of allergen).
- Non-Clinical Performance (Detection Limits - LoD): At least 60 data points for each allergen lot (4 low positive samples tested in replicates of two, with one run per day, over five days, using two instruments and three lots of allergen).
- Clinical Performance:
- Total Samples: 1,146 human serum samples (162 positive by IMMULITE®, 984 negative by IMMULITE®; 327 clinically positive, 819 clinically normal).
- Data Provenance: The document does not specify the country of origin of the data. The data is retrospective, as it involves testing serum samples that were associated with "clinical documentation of presence of signs, symptoms and other diagnostic evidence of allergen sensitivity" or "clinically diagnosed atopic and non-atopic individuals."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number of experts or their specific qualifications (e.g., years of experience as a radiologist). However, the clinical ground truth for the clinical performance study was based on "clinical documentation of presence of signs, symptoms and other diagnostic evidence of allergen sensitivity." This implies that the diagnosis was established by medical professionals in a clinical setting.
4. Adjudication Method for the Test Set
The document does not describe a specific adjudication method (e.g., 2+1, 3+1, none) for the clinical diagnosis of the test set. It refers to "clinical documentation of presence of signs, symptoms and other diagnostic evidence of allergen sensitivity," suggesting standard clinical diagnostic practices were followed.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) assay designed for quantitative measurement of IgE. The performance validation focuses on analytical precision, detection limits, specificity, linearity and clinical agreement with existing clinical diagnoses, not on the improvement of human reader performance with or without AI assistance.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) Was Done
Yes, the studies described are standalone performance studies for the device (IMMULITE® 2000 3gAllergy™ Specific IgE Universal Kit) as an automated in vitro diagnostic test. The precision, detection limits, specificity, and linearity tests evaluate the algorithm/assay performance directly. The "clinical performance testing" evaluates the device's quantitative measurements against an established clinical diagnosis, which is a standalone assessment of the device's diagnostic utility. There is no human-in-the-loop component in the direct measurement process of this diagnostic kit.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
- Non-Clinical Tests: The ground truth for precision, detection limits, and linearity is based on known concentrations of analytes in controlled samples (e.g., positive samples, blank samples, diluted samples, calibrators).
- Specificity Tests: The ground truth for specificity (inhibition and cross-reactivity) is based on the known presence or absence of specific inhibitor extracts or irrelevant/related allergens.
- Clinical Performance: The ground truth for clinical performance was "clinical documentation of presence of signs, symptoms and other diagnostic evidence of allergen sensitivity" for "clinically diagnosed atopic and non-atopic individuals." This is a form of outcomes data or clinical diagnosis that relies on a combination of clinical findings and potentially other laboratory tests as determined by medical professionals.
8. The Sample Size for the Training Set
The document does not specify a separate "training set" sample size. This is common for IVD devices of this type, where method validation studies (like precision, linearity, detection limits) establish robust analytical performance using controlled samples, and then a separate clinical performance study assesses agreement with clinical diagnoses. The document focuses on performance testing rather than machine learning model training.
9. How the Ground Truth for the Training Set Was Established
As no specific "training set" for a machine learning model is mentioned, the method for establishing its ground truth is not applicable to this submission. The validation studies for this IVD device use reference materials and clinical diagnoses as their basis for ground truth.
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510(k) Summary
Introduction: According to the requirements of 21 CFR 807.92, the following information provides sufficient details to understand the basis for determination of substantial equivalence.
The assigned 510(k) Number : K132801
| 1. Date Prepared: | May 23rd, 2014 | |
|---|---|---|
| 2. | SubmitterMailing Address: | Siemens Healthcare Diagnostics Inc.511 Benedict AvenueTarrytown, NY 10591 |
| Contact Person:Phone Number:Fax Number:E-mail Address: | Ernest JosephSenior Manager, Regulatory Affairs(914)-524-2431(914)-524-2101ernest.joseph@siemens.com | |
| 3. Device NameProprietary Name:Device Common Name:Regulation Number:Classification:Classification Products Code:Panel: | IMMULITE® 2000 3gAllergy™ Specific IgE Universal KitRadioallergosorbent (RAST) Immunological Test System866.5750Class IIDHBImmunology (82) | |
| 4. Predicate Device Name | IMMULITE® 2000 3gAllergy™ Specific IgE Assay | |
| FDA clearance was previously obtained for the assay kit and 111specific allergens (K093987, K100910, K101572 and K112523). | ||
| 5. Device Description: | IMMULITE® 2000 3gAllergy™ Specific IgE Universal Kitassay is a solid-phase, two-step, chemiluminescentimmunoassay that exploits liquid phase kinetics in a beadformat. It represents a significant advance over conventionalmethods relying on allergens attached to a solid-phasesupport. The allergens are covalently bound to a solublepolymer/co-polymer matrix, which in turn is labeled with aligand. The use of an amino acid co-polymer amplifiesthe amount of allergen that the matrix can support.This 510(k) submission is for clearance of sevenadditional specific molecular allergens shown in Table 1 tobe used with the IMMULITE® 2000 3gAllergy™ SpecificIgE Universal Kit on the IMMULITE® 2000 analyzer. |
{1}------------------------------------------------
Table 1: Specific Molecular Allergens
- rBet v 2: Birch pollen (Betula verrucosa) 一
- ଧ rMal d 1: Apple (Malus domestica)
- గా rPru av 1: Cherry (Prunus avium)
- 4 rPru av3: Cherry (Prunus avium)
- ഗ rPru av 4: Cherry (Prunus avium)
- nPru p 3: Peach (Prunus persica) Q
- 7 rMal d 4: Apple (Malus domestica)
| 6. Intended Use:Indication for Use: | See Indications for Use Statement belowThe IMMULITE® 2000 3gAllergy™ Specific IgE UniversalKit is for in vitro diagnostic use with the IMMULITE® 2000Analyzer — for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinicaldiagnosis of IgE-mediated allergic disorders. The test results |
|---|---|
| Special Conditions forUse Statement(s): | are to be used in conjunction with clinical findings and otherlaboratory tests. |
| Special InstrumentRequirements: | For prescription use onlyIMMULITE® 2000 Systems |
Technological Characteristics and Substantial Equivalence Comparison with Predicate:
A comparison of the device features, intended use, and other information demonstrates that the IMMULITE 2000 3gAllergy™ Specific IgE Universal Kit is substantially equivalent to the predicate device summarized in Table 2.
| Table 2: Substantial Equivalence Comparison |
|---|
| --------------------------------------------- |
| Similarities | ||
|---|---|---|
| Description Item | Candidate Device : IMMULITE® 2000 3gAllergy™ Specific IgE Universal Kit | Predicate Device:(K112523) |
| Indication for Use | The IMMULITE® 2000 3gAllergy™ Specific IgE Universal Kit is for in vitro diagnostic use with the IMMULITE® 2000 Analyzer – for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinical diagnosis of IgE-mediated allergic disorders. The test results are to be used in conjunction with clinical findings and other laboratory tests. | Same |
| Number ofCalibrators | Eight | Same |
| Sample Matrix | Serum | Same |
| Antibody | Monoclonal murine anti-human IgE conjugated to alkaline phosphatase | Same |
| Basic Principle | Chemiluminescent Immunoassay | Same |
| Sample Volume | 50 μl | Same |
| Process Time | 65 minutes | Same |
| IncubationTemperature | 37°C | Same |
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| Differences | |||||
|---|---|---|---|---|---|
| Description Item | Candidate Device :IMMULITE® 2000 3gAllergy™Specific IgE Universal Kit | Predicate Device:(K112523) | |||
| AllergenSource | Allergenic proteins expressed byrecombinant techniques or purified fromnative sources. | Whole allergenextracts or Allergenicproteins purifiedfrom native sourcesonly. |
8. Non-Clinical Performance Testing
Performance testing has been carried out to demonstrate that this device meets the performance specifications for its intend use. The following tests were performed on the candidate device.
8.1 Precision
Precision studies were performed in accordance with Clinical Laboratory Standard Institute (CLSI) guidance: Evaluation of Precision Performance of Quantitative Methods; Approved Guideline-Second Edition. CLSI document EP5-A2 (ISBN 1-56238-542-9). CLSI, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2004 assaying each test sample in two runs per day on 20 different days. Analysis of variance was used to estimate the repeatability and within-lab precision.
Four allergen lots were tested using three positive samples and one negative control sample. Repeatability, within-lab, and lot-to-lot precision for the positive samples were evaluated by calculating the kU/L dose percent coefficients of variation (%CV) for each positive sample. Nonspecific binding (NSB) was monitored by testing the negative control sample. Precision outliers according to the >3.0 SD rule are attributed to sample specific issues and/or operator error. In these cases precision results will be included with and without outliers. Representative precision claims for each allergen tested are presented in Table 3.
Precision studies were conducted using instruments 13325 and 13474 for lots 110, 111, and 112 and instruments 13325 and 13476 for lot 201. Data for each instrument is presented below:
| Repeatability | Within-Lab | |||||
|---|---|---|---|---|---|---|
| Sample | N | Mean(kU/L) | SD(kU/L) | CV% | SD(kU/L) | CV% |
| Allergen = rBet v 2, Lot 110, I3325 | ||||||
| Positive 1 | 84 | 0.60 | 0.020 | 3.40 | 0.043 | 7.1 |
| Positive 2 | 84 | 1.62 | 0.053 | 3.30 | 0.096 | 5.9 |
| Positive 3 | 84 | 8.16 | 0.293 | 3.59 | 0.598 | 7.3 |
| Allergen = rBet v 2, Lot 110, I3474 | ||||||
| Positive 1 | 84 | 0.63 | 0.026 | 4.13 | 0.036 | 5.6 |
| Positive 2 | 84 | 1.70 | 0.057 | 3.33 | 0.097 | 5.6 |
| Positive 3 | 84 | 8.41 | 0.334 | 3.98 | 0.440 | 5.2 |
| Allergen = rBet v 2, Lot 111, I3325 | ||||||
| Positive 1 | 84 | 0.60 | 0.021 | 3.51 | 0.037 | 6.1 |
| Positive 2 | 84 | 1.62 | 0.057 | 3.52 | 0.102 | 6.3 |
| Positive 3 | 84 | 8.20 | 0.280 | 3.42 | 0.577 | 7.0 |
| Allergen = rBet v 2, Lot 111, I3474 | ||||||
| Positive 1 | 84 | 0.64 | 0.032 | 4.97 | 0.041 | 6.3 |
| Positive 2 | 84 | 1.71 | 0.052 | 3.03 | 0.089 | 5.2 |
| Positive 3 | 84 | 8.44 | 0.316 | 3.74 | 0.396 | 4.6 |
| Allergen = rBet v 2, Lot 112, I3325 | ||||||
| Positive 1 | 84 | 0.60 | 0.019 | 3.09 | 0.038 | 6.4 |
| Positive 2 | 84 | 1.62 | 0.058 | 3.57 | 0.104 | 6.4 |
| Positive 3 | 84 | 8.30 | 0.247 | 2.97 | 0.603 | 7.2 |
| Allergen = rBet v 2, Lot 112, I3474 | ||||||
| Positive 1 | 84 | 0.63 | 0.032 | 5.07 | 0.046 | 7.3 |
| Positive 2 | 84 | 1.71 | 0.065 | 3.80 | 0.102 | 5.9 |
| Positive 3 | 84 | 8.46 | 0.299 | 3.54 | 0.462 | 5.4 |
| Allergen = rBet v 2, Lot 201, I3325 | ||||||
| Positive 1 | 80 | 0.46 | 0.016 | 3.49 | 0.022 | 4.6 |
| Positive 2 | 80 | 1.34 | 0.046 | 3.41 | 0.058 | 4.3 |
| Positive 3 | 80 | 6.68 | 0.220 | 3.30 | 0.278 | 4.1 |
| Allergen = rBet v 2, Lot 201, I3476 | ||||||
| Positive 1 | 80 | 0.49 | 0.019 | 3.89 | 0.035 | 7.1 |
| Positive 2 | 80 | 1.43 | 0.047 | 3.30 | 0.075 | 5.2 |
| Positive 3 | 80 | 7.18 | 0.243 | 3.39 | 0.413 | 5.7 |
| Allergen = rMal d 1, Lot 110, I3325 | ||||||
| Positive 1 | 84 | 0.57 | 0.026 | 4.58 | 0.042 | 7.2 |
| Positive 2 | 84 | 2.78 | 0.115 | 4.14 | 0.200 | 7.1 |
| Positive 3 | 84 | 5.64 | 0.236 | 4.18 | 0.418 | 7.4 |
| Allergen = rMal d 1, Lot 110, I3474 | ||||||
| Positive 1 | 84 | 0.60 | 0.027 | 4.60 | 0.044 | 7.4 |
| Positive 2 | 84 | 2.97 | 0.158 | 5.32 | 0.206 | 6.9 |
| Positive 3 | 84 | 5.85 | 0.221 | 3.78 | 0.286 | 4.8 |
| Allergen = rMal d 1, Lot 111, I3474 | ||||||
| Positive 1 | 84 | 0.60 | 0.024 | 4.03 | 0.041 | 6.87 |
| Positive 2 | 84 | 2.94 | 0.112 | 3.79 | 0.172 | 5.84 |
| Positive 3 | 84 | 5.90 | 0.267 | 4.52 | 0.286 | 4.85 |
| Allergen = rMal d 1, Lot 112, I3325 | ||||||
| Positive 1 | 84 | 0.62 | 0.028 | 4.50 | 0.044 | 7.10 |
| Positive 2 | 84 | 2.45 | 0.096 | 3.90 | 0.177 | 7.20 |
| Positive 3 | 84 | 5.96 | 0.227 | 3.80 | 0.438 | 7.30 |
| Allergen = rMal d 1, Lot 112, I3474 | ||||||
| Positive 1 | 84 | 0.64 | 0.031 | 4.90 | 0.054 | 8.50 |
| Positive 2 | 84 | 2.59 | 0.106 | 4.10 | 0.201 | 7.80 |
| Positive 3 | 84 | 6.06 | 0.284 | 4.70 | 0.396 | 6.50 |
| Allergen = rMal d 1, Lot 201, I3325 | ||||||
| Positive 1 | 80 | 0.46 | 0.023 | 4.93 | 0.035 | 7.53 |
| Positive 2 | 80 | 1.97 | 0.068 | 3.44 | 0.085 | 4.29 |
| Positive 3 | 80 | 4.52 | 0.189 | 4.18 | 0.423 | 9.36 |
| Allergen = rMal d 1, Lot 201, I3476 | ||||||
| Positive 1 | 80 | 0.49 | 0.021 | 4.24 | 0.035 | 7.26 |
| Positive 2 | 80 | 2.16 | 0.101 | 4.69 | 0.189 | 8.76 |
| Positive 3 | 80 | 4.99 | 0.209 | 4.19 | 0.371 | 7.43 |
| Allergen = rMal d 4, Lot 110, I3325 | ||||||
| Positive 1 | 84 | 0.64 | 0.027 | 4.18 | 0.036 | 5.60 |
| Positive 2 | 84 | 1.67 | 0.063 | 3.78 | 0.105 | 6.29 |
| Positive 3 | 84 | 7.37 | 0.206 | 2.79 | 0.469 | 6.36 |
| Allergen = rMal d 4, Lot 110, I3474 | ||||||
| Positive 1 | 84 | 0.67 | 0.021 | 3.14 | 0.038 | 5.64 |
| Positive 2 | 84 | 1.73 | 0.052 | 3.02 | 0.108 | 6.21 |
| Positive 3 | 84 | 7.70 | 0.291 | 3.77 | 0.323 | 4.19 |
| Allergen = rMal d 4, Lot 111, I3325 | ||||||
| Positive 1 | 84 | 0.63 | 0.027 | 4.31 | 0.037 | 5.84 |
| Positive 2 | 84 | 1.66 | 0.055 | 3.29 | 0.103 | 6.23 |
| Positive 3 | 84 | 7.40 | 0.255 | 3.44 | 0.500 | 6.75 |
| Allergen = rMal d 4, Lot 111, I3474 | ||||||
| Positive 1 | 84 | 0.67 | 0.025 | 3.73 | 0.036 | 5.35 |
| Positive 2 | 84 | 1.74 | 0.049 | 2.84 | 0.102 | 5.90 |
| Positive 3 | 84 | 7.71 | 0.217 | 2.82 | 0.350 | 4.54 |
| Allergen = rMal d 4, Lot 112, l3325 | ||||||
| Positive 1 | 84 | 0.65 | 0.028 | 4.25 | 0.038 | 5.76 |
| Positive 2 | 84 | 1.66 | 0.060 | 3.58 | 0.105 | 6.29 |
| Positive 3 | 84 | 7.56 | 0.265 | 3.51 | 0.533 | 7.06 |
| Allergen = rMal d 4, Lot 112, l3474 | ||||||
| Positive 1 | 84 | 0.69 | 0.022 | 3.13 | 0.041 | 5.88 |
| Positive 2 | 84 | 1.75 | 0.056 | 3.23 | 0.090 | 5.16 |
| Positive 3 | 84 | 7.90 | 0.264 | 3.35 | 0.377 | 4.78 |
| Allergen = rMal d 4, Lot 201, l3325 | ||||||
| Positive 1 | 80 | 0.59 | 0.022 | 3.74 | 0.028 | 4.70 |
| Positive 2 | 80 | 1.43 | 0.053 | 3.73 | 0.060 | 4.24 |
| Positive 3 | 80 | 6.61 | 0.218 | 3.30 | 0.268 | 4.06 |
| Allergen = rMal d 4, Lot 201, l3476 | ||||||
| Positive 1 | 80 | 0.64 | 0.021 | 3.24 | 0.036 | 5.56 |
| Positive 2 | 80 | 1.52 | 0.045 | 2.93 | 0.077 | 5.08 |
| Positive 3 | 80 | 7.21 | 0.119 | 1.65 | 0.330 | 4.58 |
| Allergen = rPru av 1, Lot 110, l3325 | ||||||
| Positive 1 | 84 | 0.58 | 0.024 | 4.13 | 0.037 | 6.48 |
| Positive 2* | 84 | 2.34 | 0.083 | 3.53 | 0.337 | 14.30 |
| Positive 2** | 80 | 2.41 | 0.084 | 3.49 | 0.165 | 6.84 |
| Positive 3 | 84 | 6.22 | 0.267 | 4.29 | 0.432 | 6.94 |
| Allergen = rPru av 1, Lot 110, l3474 | ||||||
| Positive 1 | 84 | 0.60 | 0.024 | 4.01 | 0.044 | 7.22 |
| Positive 2 | 84 | 2.50 | 0.088 | 3.50 | 0.142 | 5.67 |
| Positive 3 | 84 | 6.39 | 0.232 | 3.63 | 0.428 | 6.70 |
| Allergen = rPru av 1, Lot 111, l3325 | ||||||
| Positive 1 | 84 | 0.58 | 0.022 | 3.76 | 0.042 | 7.21 |
| Positive 2* | 84 | 2.35 | 0.058 | 2.46 | 0.338 | 14.31 |
| Positive 2** | 80 | 2.41 | 0.059 | 2.43 | 0.179 | 7.41 |
| Positive 3 | 84 | 6.29 | 0.197 | 3.14 | 0.454 | 7.22 |
| Allergen = rPru av 1, Lot 111, l3474 | ||||||
| Positive 1 | 84 | 0.60 | 0.022 | 3.70 | 0.041 | 6.74 |
| Positive 2 | 84 | 2.49 | 0.103 | 4.16 | 0.156 | 6.28 |
| Positive 3 | 84 | 6.50 | 0.275 | 4.23 | 0.394 | 6.06 |
| Positive 1 | 84 | 0.65 | 0.024 | 3.70 | 0.047 | 7.26 |
| Positive 2* | 84 | 2.57 | 0.096 | 3.74 | 0.359 | 13.96 |
| Positive 2** | 80 | 2.64 | 0.098 | 3.73 | 0.186 | 7.06 |
| Positive 3 | 84 | 7.91 | 0.257 | 3.24 | 0.552 | 6.98 |
| Allergen = rPru av 1, Lot 112, I3474 | ||||||
| Positive 1 | 84 | 0.69 | 0.025 | 3.66 | 0.044 | 6.42 |
| Positive 2 | 84 | 2.78 | 0.095 | 3.43 | 0.179 | 6.45 |
| Positive 3 | 84 | 8.29 | 0.365 | 4.40 | 0.535 | 6.45 |
| Allergen = rPru av 1, Lot 201, I3325 | ||||||
| Positive 1 | 80 | 0.56 | 0.020 | 3.62 | 0.039 | 6.94 |
| Positive 2 | 80 | 2.29 | 0.076 | 3.34 | 0.130 | 5.66 |
| Positive 3 | 80 | 6.83 | 0.207 | 3.03 | 0.307 | 4.49 |
| Allergen = rPru av 1, Lot 201, I3476 | ||||||
| Positive 1* | 80 | 0.60 | 0.066 | 11.16 | 0.074 | 12.41 |
| Positive 1** | 79 | 0.60 | 0.017 | 2.86 | 0.044 | 7.33 |
| Positive 2 | 80 | 2.48 | 0.128 | 5.17 | 0.211 | 8.51 |
| Positive 3 | 80 | 7.37 | 0.375 | 5.09 | 0.662 | 8.98 |
| *Outliers detected on Day 6, Runs 1 and 2, Replicates 1 and 2*Outliers detected on Day 20, Run 1, Replicate 2 | **No outliers used in calculation | |||||
| Allergen = rPru av 3, Lot 110, I3325 | ||||||
| Positive 1 | 84 | 0.56 | 0.020 | 3.51 | 0.032 | 5.81 |
| Positive 2 | 84 | 1.48 | 0.044 | 2.97 | 0.090 | 6.04 |
| Positive 3 | 84 | 9.30 | 0.398 | 4.28 | 0.697 | 7.49 |
| Allergen = rPru av 3, Lot 110, I3474 | ||||||
| Positive 1 | 84 | 0.59 | 0.022 | 3.63 | 0.034 | 5.76 |
| Positive 2 | 84 | 1.55 | 0.050 | 3.22 | 0.079 | 5.08 |
| Allergen = rPru av 3, Lot 111, 13325 | ||||||
| Positive 1 | 84 | 0.56 | 0.021 | 3.74 | 0.036 | 6.42 |
| Positive 2 | 84 | 1.49 | 0.055 | 3.68 | 0.092 | 6.19 |
| Positive 3 | 84 | 9.28 | 0.366 | 3.94 | 0.598 | 6.45 |
| Allergen = rPru av 3, Lot 111, 13474 | ||||||
| Positive 1 | 84 | 0.59 | 0.020 | 3.34 | 0.034 | 5.74 |
| Positive 2 | 84 | 1.56 | 0.050 | 3.21 | 0.079 | 5.03 |
| Positive 3 | 84 | 9.66 | 0.331 | 3.43 | 0.509 | 5.27 |
{3}------------------------------------------------
Positive 1
Positive 2
Positive 3
0.027
0.114
0.226
4.68
4.08
4.01
0.044
0.204
0.391
7.60
7.32
6.95
0:58
2.79
5.63
84
84
84
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{7}------------------------------------------------
| Allergen = rPru av 3, Lot 112, I3325 | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Positive 1 | 84 | 0.56 | 0.024 | 4.25 | 0.032 | 5.60 | ||||||
| Positive 2 | 84 | 1.47 | 0.041 | 2.82 | 0.086 | 5.85 | ||||||
| Positive 3 | 84 | 9.49 | 0.290 | 3.05 | 0.645 | 6.80 | ||||||
| Allergen = rPru av 3, Lot 112, I3474 | ||||||||||||
| Positive 1 | 84 | 0.59 | 0.021 | 3.62 | 0.034 | 5.66 | ||||||
| Positive 2 | 84 | 1.55 | 0.058 | 3.74 | 0.075 | 4.84 | ||||||
| Positive 3 | 84 | 9.89 | 0.300 | 3.03 | 0.485 | 4.90 | ||||||
| Allergen = rPru av 3, Lot 201, I3325 | ||||||||||||
| Positive 1* | 80 | 0.48 | 0.058 | 12.20 | 0.061 | 12.8 | ||||||
| Positive 1** | 79 | 0.48 | 0.025 | 5.17 | 0.035 | 7.23 | ||||||
| Positive 2 | 80 | 1.20 | 0.53 | 4.40 | 0.96 | 8.01 | ||||||
| Positive 3 | 80 | 7.52 | 0.236 | 3.14 | 0.468 | 6.23 | ||||||
| Allergen = rPru av 3, Lot 201, I3476 | ||||||||||||
| Positive 1 | 80 | 0.51 | 0.015 | 2.88 | 0.035 | 6.73 | ||||||
| Positive 2 | 80 | 1.30 | 0.047 | 3.60 | 0.097 | 7.51 | ||||||
| Positive 3 | 80 | 8.25 | 0.213 | 2.58 | 0.484 | 5.86 | ||||||
| Allergen = rPru av 4, Lot 110, I3325 | ||||||||||||
| Positive 1 | 84 | 0.62 | 0.026 | 4.13 | 0.035 | 5.68 | ||||||
| Positive 2* | 84 | 1.27 | 0.048 | 3.78 | 0.223 | 17.5 | ||||||
| Positive 2** | 82 | 1.30 | 0.049 | 3.73 | 0.098 | 7.56 | ||||||
| Positive 3 | 84 | 8.75 | 0.297 | 3.40 | 0.644 | 7.36 | ||||||
| Allergen = rPru av 4, Lot 110, I3474 | ||||||||||||
| Positive 1 | 84 | 0.66 | 0.028 | 4.23 | 0.043 | 6.47 | ||||||
| Positive 2 | 84 | 1.36 | 0.043 | 3.14 | 0.080 | 5.89 | ||||||
| Positive 3 | 84 | 9.09 | 0.309 | 3.40 | 0.409 | 4.50 | ||||||
| Allergen = rPru av 4, Lot 111, I3325 | ||||||||||||
| Positive 1 | 84 | 0.62 | 0.022 | 3.61 | 0.035 | 5.56 | ||||||
| Positive 2* | 84 | 1.27 | 0.042 | 3.33 | 0.221 | 17.3 | ||||||
| Positive 2** | 82 | 1.30 | 0.043 | 3.29 | 0.092 | 7.08 | ||||||
| Positive 3 | 84 | 8.63 | 0.349 | 4.04 | 0.692 | 8.02 | ||||||
| Allergen = rPru av 4, Lot 111, I3474 | ||||||||||||
| Positive 1 | 84 | 0.66 | 0.028 | 4.20 | 0.044 | 6.57 | ||||||
| Positive 2 | 84 | 1.37 | 0.041 | 2.96 | 0.070 | 5.07 | ||||||
| Positive 3 | 84 | 9.06 | 0.408 | 4.50 | 0.505 | 5.57 |
{8}------------------------------------------------
.
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| Allergen = rPru av 4, Lot 112, I3325 | |||||||
|---|---|---|---|---|---|---|---|
| Positive 1 | 84 | 0.62 | 0.022 | 3.59 | 0.040 | 6.51 | |
| Positive 2* | 84 | 1.29 | 0.042 | 3.29 | 0.222 | 17.21 | |
| Positive 2** | 82 | 1.30 | 0.043 | 3.29 | 0.092 | 7.08 | |
| Positive 3 | 84 | 8.63 | 0.410 | 4.73 | 0.647 | 7.45 | |
| Allergen = rPru av 4, Lot 112, I3474 | |||||||
| Positive 1 | 84 | 0.67 | 0.021 | 3.16 | 0.033 | 4.95 | |
| Positive 2 | 84 | 1.39 | 0.048 | 3.46 | 0.087 | 6.21 | |
| Positive 3 | 84 | 6.17 | 0.388 | 4.23 | 0.601 | 6.55 | |
| Allergen = rPru av 4, Lot 201, I3325 | |||||||
| Positive 1 | 80 | 0.63 | 0.018 | 2.94 | 0.035 | 5.54 | |
| Positive 2 | 82 | 1.19 | 0.029 | 2.45 | 0.056 | 4.72 | |
| Positive 3 | 80 | 7.18 | 0.258 | 3.58 | 0.554 | 7.71 | |
| Allergen = rPru av 4, Lot 201, I3476 | |||||||
| Positive 1 | 80 | 0.68 | 0.019 | 2.81 | 0.040 | 5.92 | |
| Positive 2 | 80 | 1.25 | 0.038 | 3.06 | 0.080 | 6.38 | |
| Positive 3 | 80 | 7.71 | 0.275 | 3.56 | 0.680 | 8.82 | |
| *Outliers detected on Day 12, Run 1, Replicates 1 and 2 | |||||||
| **No outliers used in calculation | |||||||
| Allergen = nPru p 3, Lot 110, I3325 | |||||||
| Positive 1 | 84 | 0.58 | 0.024 | 4.22 | 0.039 | 6.82 | |
| Positive 2* | 84 | 1.97 | 0.063 | 3.22 | 1.484 | 75.41 | |
| Positive 2** | 80 | 1.65 | 0.060 | 3.63 | 0.111 | 6.75 | |
| Positive 3 | 84 | 9.19 | 0.342 | 3.73 | 0.644 | 7.01 | |
| Allergen = nPru p 3, Lot 110, I3474 | |||||||
| Positive 1 | 84 | 0.61 | 0.023 | 3.69 | 0.032 | 5.28 | |
| Positive 2* | 84 | 2.08 | 0.104 | 4.98 | 1.634 | 78.56 | |
| Positive 2** | 80 | 1.72 | 0.068 | 3.91 | 0.097 | 5.62 | |
| Positive 3 | 84 | 9.45 | 0.291 | 3.07 | 0.457 | 4.83 | |
| Allergen = nPru p 3, Lot 111, I3325 | |||||||
| Positive 1 | 84 | 0.58 | 0.022 | 3.70 | 0.037 | 6.26 | |
| Positive 2* | 84 | 1.99 | 0.061 | 3.06 | 1.524 | 76.70 | |
| Positive 2** | 80 | 1.66 | 0.048 | 2.87 | 0.100 | 6.01 | |
| Positive 3 | 84 | 9.19 | 0.241 | 2.62 | 0.643 | 7.00 | |
| Allergen = nPru p 3, Lot 111, I3474 | |||||||
| Positive 1 | 84 | 0.62 | 0.018 | 2.92 | 0.031 | 4.95 | |
| Positive 2* | 84 | 2.08 | 0.130 | 6.24 | 1.613 | 77.39 | |
| Positive 2** | 80 | 1.73 | 0.055 | 3.18 | 0.095 | 5.51 | |
| Positive 3 | 84 | 9.53 | 0.269 | 2.82 | 0.434 | 4.55 | |
| Allergen = nPru p 3, Lot 112, I3325 | |||||||
| Positive 1 | 84 | 0.56 | 0.024 | 4.32 | 0.038 | 6.79 | |
| Positive 2* | 84 | 1.95 | 0.064 | 3.28 | 1.531 | 78.70 | |
| Positive 2** | 80 | 1.61 | 0.57 | 3.50 | 0.109 | 6.74 | |
| Positive 3 | 84 | 9.25 | 0.282 | 3.05 | 0.626 | 6.77 | |
| Allergen = nPru p 3, Lot 112, I3474 | |||||||
| Positive 1 | 84 | 0.60 | 0.022 | 3.69 | 0.034 | 5.71 | |
| Positive 2* | 84 | 2.05 | 0.152 | 7.43 | 1.654 | 80.67 | |
| Positive 2** | 80 | 1.69 | 0.041 | 2.44 | 0.094 | 5.55 | |
| Positive 3 | 84 | 9.68 | 2.98 | 3.08 | 0.461 | 4.76 | |
| Allergen = nPru p 3, Lot 201, I3325 | |||||||
| Positive 1 | 80 | 0.52 | 0.022 | 4.16 | 0.037 | 7.17 | |
| Positive 2 | 80 | 1.49 | 0.053 | 3.56 | 0.085 | 5.70 | |
| Positive 3 | 80 | 9.05 | 0.272 | 3.00 | 0.356 | 3.93 | |
| Allergen = nPru p 3, Lot 201, I3476 | |||||||
| Positive 1 | 80 | 0.56 | 0.021 | 3.73 | 0.036 | 6.49 | |
| Positive 2 | 80 | 1.57 | 0.045 | 2.90 | 0.104 | 6.64 | |
| Positive 3 | 80 | 9.58 | 0.289 | 3.02 | 0.486 | 5.07 | |
| *Outliers detected on Day 10, Runs 1 and 2, Replicates 1 and 2**No outliers used in calculation |
:
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{9}------------------------------------------------
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Lot-to-Lot variability between four lots on instrument 13325 is presented in the Table 4.
:
:
{10}------------------------------------------------
| Sample | N | Mean(kU/L) | SD(kU/L) | CV% | SD(kU/L) | CV% |
|---|---|---|---|---|---|---|
| Positive 1 | 332 | 0.57 | 0.066 | 11.57 | 0.071 | 12.5 |
| Allergen = rBet v 2, Lots 110, 111, 112, 201, 13325 | ||||||
| Positive 2 | 332 | 1.55 | 0.140 | 9.06 | 0.157 | 10.1 |
| Positive 3 | 332 | 7.85 | 0.773 | 9.86 | 0.880 | 11.2 |
| Allergen = rMal d 1, Lots 110, 111, 112, 201, 13325 | ||||||
| Positive 1 | 332 | 0.56 | 0.067 | 12.01 | 0.073 | 13.0 |
| Positive 2 | 332 | 2.51 | 0.370 | 14.76 | 0.395 | 15.7 |
| Positive 3 | 332 | 5.45 | 0.657 | 12.06 | 0.713 | 13.0 |
| Allergen = rMal d 4, Lots 110, 111, 112, 201, 13325 | ||||||
| Positive 1 | 332 | 0.63 | 0.036 | 5.69 | 0.041 | 6.49 |
| Positive 2 | 332 | 1.60 | 0.123 | 7.66 | 0.143 | 8.94 |
| Positive 3 | 332 | 7.24 | 0.472 | 6.52 | 0.596 | 8.23 |
| Allergen = rPru av 1, Lots 110, 111, 112, 201, 13325 | ||||||
| Positive 1 | 332 | 0.59 | 0.049 | 8.32 | 0.055 | 9.29 |
| Positive 2 | 332 | 2.39 | 0.191 | 7.99 | 0.327 | 13.7 |
| Positive 3 | 332 | 6.81 | 0.791 | 11.62 | 0.853 | 12.5 |
| Allergen = rPru av 3, Lots 110, 111, 112, 201, 13325 | ||||||
| Positive 1 | 332 | 0.54 | 0.053 | 9.75 | 0.056 | 10.3 |
| Positive 2 | 332 | 1.41 | 0.145 | 10.25 | 0.158 | 11.1 |
| Positive 3 | 332 | 8.91 | 0.947 | 10.63 | 1.035 | 11.6 |
| Allergen = rPru av 4, Lots 110, 111, 112, 201, 13325 | ||||||
| Positive 1 | 332 | 0.62 | 0.027 | 4.33 | 0.036 | 5.83 |
| Positive 2 | 334 | 1.26 | 0.109 | 8.67 | 0.198 | 15.7 |
| Positive 3 | 332 | 8.32 | 0.829 | 9.95 | 0.928 | 11.1 |
Table 4 – Lot-to-Lot Precision Results
and the comments of the
1
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{11}------------------------------------------------
| Positive 1 | 332 | 0.56 | 0.038 | 6.70 | 0.045 | 7.93 |
|---|---|---|---|---|---|---|
| Positive 2* | 332 | 1.85 | 0.728 | 39.33 | 1.351 | 72.99 |
| Positive 2** | 320 | 1.60 | 0.091 | 5.67 | 0.123 | 7.71 |
| Positive 3 | 332 | 9.07 | 0.469 | 5.17 | 0.864 | 9.52 |
No outliers used in calculation
Precision of rBet v 2, rMal d 1, rMal d 4, rPru av 3, rPru av 4, and nPru p 3 meet the criteria for acceptable repeatability, within-lab, and lot-to-lot precision. Repeatability is less than 15% for all allergen lots, within-lab precision is less than 15% for all allergen lots, and lot-to-lot precision is less than 20% for all seven allergens. The negative control remained negative (<0.10 kU/L) throughout precision testing on all allergens.
8.2 Detection Limits
The working range for the The IMMULITE 2000 3gAllergy Specific IgE Universal Kit is 0.10 - 100 kU/L standardized to the 2nd WHO IRP (75/502) for human serum IgE. The Limit of Blank (LoB):
Four blank samples were tested in replicates of two, with one run per day, over five days, using two instruments and three lots of allergen. A total of 80 data points were collected for each allergen lot. The LoB was calculated for each sample using the nonparametric method in accordance with CLSI EP17-A. The Limit of Blank was determined separately for each allergen lot and was established as the highest of the three. The LoB results are presented in Table 5.
| Allergen | Lot | Limit ofBlank(kU/L) |
|---|---|---|
| rBet v 2(A127) | 111 | 0.03 |
| rBet v 2(A127) | 112 | 0.02 |
| rBet v 2(A127) | 201 | 0.03 |
| rMal d 1(A464) | 110 | 0.02 |
| rMal d 1(A464) | 111 | 0.02 |
| rMal d 1(A464) | 201 | 0.02 |
| rMal d 4(A796) | 111 | 0.02 |
| rMal d 4(A796) | 112 | 0.02 |
| rMal d 4(A796) | 201 | 0.00 |
| rPru av 1(A597) | 111 | 0.02 |
| rPru av 1(A597) | 112 | 0.02 |
| rPru av 1(A597) | 201 | 0.00 |
Table 5 - Limit of Blank Results Summary
{12}------------------------------------------------
| Allergen | Lot | Limit ofBlank(kU/L) |
|---|---|---|
| rPru av 3(A599) | 111 | 0.06 |
| rPru av 3(A599) | 112 | 0.05 |
| 201 | 0.01 | |
| rPru av 4(A600) | 111 | |
| rPru av 4(A600) | 112 | 0.02 |
| 201 | 0.01 | |
| nPru p 3(A603) | 111 | |
| nPru p 3(A603) | 112 | 0.02 |
| 201 | 0.01 |
The Limit of Blank (highest value expected for a sample with no analyte) was ≤0.03 kU/L for rBet v 2, rMal d 1, rMal d 4, rPru av 1, rPru av 3, and 0.06 kU/L for rPru av 4.
The Limit of Detection (LoD):
Four low positive samples were tested in replicates of two, with one run per day, over five days, using two instruments and three lots of allergen A total of at least 60 data points were collected for each allergen lot. The LoD was calculated using the formula: LoD = LoBMax + cpSDcop. The Limit of Detection was determined separately for each allergen lot and was established as the highest of the three. The LoB results are presented in Table 6.
| Allergen | Lot | Limit ofDetection(kU/L) |
|---|---|---|
| rBet v 2(A127) | 111 | 0.05 |
| rBet v 2(A127) | 112 | 0.05 |
| rBet v 2(A127) | 201 | 0.06 |
| rMal d 1(A464) | 110 | 0.04 |
| rMal d 1(A464) | 111 | 0.04 |
| rMal d 1(A464) | 201 | 0.04 |
| rMal d 4(A796) | 111 | 0.06 |
| rMal d 4(A796) | 112 | 0.04 |
| rMal d 4(A796) | 201 | 0.04 |
| rPru av 1(A597) | 111 | 0.06 |
| rPru av 1(A597) | 112 | 0.06 |
| rPru av 1(A597) | 201 | 0.05 |
| rPru av 3(A599) | 111 | 0.09 |
| rPru av 3(A599) | 112 | 0.08 |
| rPru av 3(A599) | 201 | 0.09 |
Table 6 - Limit of Detection Results Summary
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| Allergen | Lot | Limit ofDetection(kU/L) |
|---|---|---|
| rPru av 4(A600) | 111 | 0.04 |
| rPru av 4(A600) | 112 | 0.03 |
| rPru av 4(A600) | 201 | 0.05 |
| nPru p 3(A603) | 111 | 0.04 |
| nPru p 3(A603) | 112 | 0.05 |
| nPru p 3(A603) | 201 | 0.04 |
The Limit of Detection (lowest detectable concentration) was ≤0.10 kU/L for rBet v 2, rMal d 1, rMal d 4, rPru av 1, rPru av 3, rPru av 4, and nPru p 3.
8.3 Specificity (Inhibition) Studies:
Specificity of each allergen was verified through competitive inhibition testing using a single serum sample or pool of sera. A negative sample was used to measure the background response.
To initiate the inhibition experiment, minimally 5 levels of 5-fold diluted inhibitor extract were mixed with sample or pool at a ratio of 1:1 to achieve final inhibitor concentrations of 50 µg/mL and lower. The inhibitor/sample mixtures were incubated at room temperature (15-28°C) for 1 hour allowing the immunological reaction to occur. Each sample mixture containing the inhibitor extract and appropriate controls were assayed with one lot of each allergen. The percent (%) inhibition was calculated according to the following formula:
[(C - A)/C] x 100
C = mean response of the positive control (positive sample - negative sample)
A = mean response of sample with inhibitor extract
The inhibition demonstrates that the allergens tested are inhibited by the relevant inhibitor extract in a concentration dependent fashion. Also, the target % inhibition of 50% for the highest inhibitor concentration tested was met. These results indicate specificity of the rBet v 2, rMal d 1, rMal d 4, rPru av 1, rPru av 3, rPru av 4, and nPru p 3 allergens.
{14}------------------------------------------------
8.4 Inhibition Using Negative Controls:
Additional inhibition studies were conducted to show that the specific allergens are not crossreacting to unrelated allergens. Three irrelevant allergens as well as any related components were included as additional controls. The related components were other components of the parent allergen or another component from the same group. The final inhibitor concentrations of the additional inhibitors ranged from 500 µg/mL to 1250 µg/mL, determined as 10x the concentration needed to achieve ~100% inhibition on its own allergen device. Each allergen with the irrelevant and related extracts did not generate inhibition greater than 15%. These results indicate specificity of the rBet v 2, rMal d 1, rMal d 4, rPru av 3, rPru av 4, and nPru p 3 allergens.
8.5 Linearity:
The assay is calibrated to the WHO 2nd IRP 75/502 reference standard for total IgE. The working range is supported in the following manner: Each allergen was scaled to confirm linearity. The calibration curve for the assay is utilized for reporting IgE dose values for all allergens assayed. To confirm the working range of 0.10 to 100 kU/L, a linearity study was performed with the calibrator antibody using a minimum of 3 samples scaled throughout the reportable range of the assay.
Two positive samples were diluted with a negative sample at levels ranging from 20% to 100% per CLSI EP06-A. The negative sample was run neat as a control. Each sample was run in replicates of three with two allergen lots. The expected dose (kU/L) was extrapolated from the neat positive value and the linearity dilutions. A linear regression was performed by plotting the observed dose (y-axis) versus the expected dose (x-axis) as shown in Table 7.
| Allergen | Lot | RegressionEquation | ﺎ | N | Slope 95% Cl | Intercept 95% Cl | Range Tested (kU/L) |
|---|---|---|---|---|---|---|---|
| rBet v 2 | 111 | y = 1,003x + 0.006 | 0.998 | 12 | 0.953 to 1.053 | -0.050 to 0.061 | 0.46 to 13.08 |
| 112 | y = 1.035x + 0.006 | 0.998 | 12 | 0.987 to 1.083 | -0.043 to 0.056 | 0.43 to 12.81 | |
| rMal d 1 | 110 | y = 1.012x + 0.091 | 1.000 | 12 | 0.986 to 1.039 | 0.002 to 0.180 | 1.48 to 24.74 |
| 111 | y = 1.036 - 0.075 | 0. 899 | 12 | 1.001 to 1.070 | -0.199 to 0.049 | 1.42 to 26.33 | |
| 111 | y = 0.958 + 0.042 | 0. 999 | 12 | 0.921 to 0.995 | 0.011 to 0.074 | 0.35 to 11.55 | |
| rMal d 4 | 112 | y = 0.984x + 0.018 | 0,998 | 12 | 0.936 to 1.032 | -0.022 to 0.058 | 0.32 to 11.58 |
| rPru av 1 | 111 | y = 1,047x - 0.030 | 0.999 | 12 | 1.013 to 1.081 | -0.053 to -0.007 | 0.24 to 14.08 |
| 112 | y = 1.054x + 0.020 | 0.998 | 12 | 0.999 to 1.110 | -0.014 to 0.055 | 0.25 to 18.52 | |
| 111 | y = 1,004x + 0,048 | 0.999 | 12 | 0.978 to 1,031 | 0.023 to 0.074 | 0.43 to 13.55 | |
| rPru av 3 | 112 | y = 0,992x + 0.058 | 0.999 | 12 | 0.961 to 1.023 | 0.028 to 0.088 | 0.44 to 13.36 |
| rPru av 4 | 111 | y = 0.967 + 0.018 | 1.000 | 12 | 0.945 to 0.989 | -0.003 to 0.040 | 0.38 to 19.95 |
| 112 | y = 0.984x + 0.034 | 1,000 | 12 | 0.960 to 1.009 | 0.010 to 0.058 | 0.41 to 19.35 | |
| nPru p 3 | 111 | y = 0.989x + 0.049 | 0.999 | 12 | 0.960 to 1.019 | 0.018 to 0.081 | 0.47 to 15.62 |
| 112 | y = 1.000x + 0.022 | 0.999 | 12 | 0.966 to 1.034 | -0.014 to 0.057 | 0.43 to 15.29 |
Table 7: Linearity Table
{15}------------------------------------------------
9. Clinical Performance Testing:
Clinical performance was demonstrated by testing serum samples against specific allergens from clinically diagnosed atopic and non-atopic individuals. Allergen-specific testing was obtained using the IMMULITE® 2000 3gAllergy™ Specific IgE Universal Kit.
Data summary agreement of the IMMULITE® 2000 3gAllergy™ Specific IgE Universal Kit test results to clinical data is shown in Table 8.
| Clinical Diagnosis Data | |||
|---|---|---|---|
| IMMULITE® 2000 Analyzer | Clinical | Normal | Total |
| Positive | 153 | 9 | 162 |
| Negative | 174 | 810 | 984 |
| Total | 327 | 819 | 1,146 |
| 46.8% | 98.9% | 84.0% | |
| Sensitivity | Specificity | Agreement | |
| Lower Confidence Interval | 42.1% | 98.1% | 82% |
| Upper Confidence Interval | 51.5% | 99.4% | 86% |
| Allergens included: rBet v 2, rMal d 1, rPru av 1, rPru av 3, rPru av 4, nPru p 3 and rMal d 4 |
Table 8: Clinical Data Summary
IMMULITE® 2000 3gAllergy™ Specific IgE Universal Kit test results for all allergens compare well with clinical documentation of presence of signs, symptoms and other diagnostic evidence of allergen sensitivity
10. Conclusion:
The IMMULITE® 2000 3gAllergy™ Specific IgE Universal Kit is substantially equivalent to other products in commercial distribution intended for similar use. Most notably, it is substantially equivalent to the currently marketed device. The substantial equivalence of the device is supported by clinical and non-clinical testing and was found to be comparable and supports the claims of substantial equivalence, product safety and effectiveness. Based on the testing completed and the comparisons with predicate device, the IMMULITE® 2000 3gAllergy™ Specific IgE Universal Kit does not raise any new questions on safety and effectiveness and the results support a determination of substantial equivalence.
{16}------------------------------------------------
Image /page/16/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles a stylized caduceus or a person with flowing robes.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
SIEMENS HEALTHCARE DIAGNOSTICS, INC. May 28, 2014 C/O MR. ERNEST JOSEPH SENIOR MANAGER REGULATORY AFFAIRS IMMULITE AND RIA PRODUCT LINES 511 BENEDICT AVENUE TARRYTOWN, NY, 10591
Re: K132801
Trade/Device Name: IMMULITE 2000 3gAllery™ Specific IgE Universal Kit Regulation Number: 21 CFR § 866.5750 Regulation Name: Radioallergosorbent (RAST) immunological test system Regulatory Class: Class II Product Code: DHB Dated: May 2, 2014 Received: May 5. 2014
Dear Mr. Joseph:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical
{17}------------------------------------------------
Page 2 - Mr. Ernest Joseph
device-related adverse cvents) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/McdicalDevices/ResourcesforYou/Industry/default.htm Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safetv/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours.
Maria M. Chan -S
Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health (OIR) Center for Devices and Radiological Health
Enclosure
{18}------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.
510(k) Number (if known) K132801
Device Name
IMMULITE® 2000 3gAllergy™ Specific IgE Universal Kit
Indications for Use (Describe)
The 3gAllergy™ Specific IgE Universal Kit is for in vitro diagnostic use with the IMMULITE® 2000 Analyzer -- for the quantitative measurement of allergen-specific IgE in human serum, as an aid in the clinical diagnosis of IgE-mediated allergic disorders. The test results are to be used in conjunction with clinical findings and other laboratory tests.
Type of Use (Select one or both, as applicable)
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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FOR FDA USE ONLY
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Elizabeth A. Stafford -S
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§ 866.5750 Radioallergosorbent (RAST) immunological test system.
(a)
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.(b)
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](https://510k.innolitics.com/device/[K923044](https://510k.innolitics.com/device/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.