← Product Code [DGC](/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DGC) · K193493 # ADVIA Centaur Total IgE (tIgE) (K193493) _Siemens Healthcare Diagnostics, Inc. · DGC · Jan 15, 2020 · Immunology · SESE_ **Canonical URL:** https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DGC/K193493 ## Device Facts - **Applicant:** Siemens Healthcare Diagnostics, Inc. - **Product Code:** [DGC](/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DGC.md) - **Decision Date:** Jan 15, 2020 - **Decision:** SESE - **Submission Type:** Traditional - **Regulation:** 21 CFR 866.5510 - **Device Class:** Class 2 - **Review Panel:** Immunology ## Indications for Use For in vitro diagnostic use in the quantitative determination of total IgE in serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur®, ADVIA Centaur XP, and ADVIA Centaur XPT systems. ## Device Story ADVIA Centaur Total IgE (tIgE) is a two-site sandwich immunoassay using direct chemiluminometric technology. It measures total IgE in serum and plasma (EDTA and lithium heparin) samples. The assay utilizes a goat anti-human IgE antibody labeled with acridinium ester (Lite Reagent) and a mouse anti-human IgE antibody coupled to paramagnetic particles (Solid Phase Reagent). The device is used in clinical laboratory settings on the ADVIA Centaur family of analyzers. Results are determined via a 2-point calibration curve and a master curve. Healthcare providers use the quantitative IgE results to assist in clinical decision-making related to immunological conditions. The device benefits patients by providing standardized IgE measurements for diagnostic assessment. ## Clinical Evidence No clinical data. Evidence consists of analytical performance testing, including interference studies (spiking K2-EDTA and lithium heparin at 3x and 5x concentrations) and matrix comparison studies. Matrix comparison used 73 paired serum/K2-EDTA samples and 73 paired serum/Li-heparin samples, demonstrating equivalence with slopes of 0.99 and 1.00 respectively and correlation coefficients of 1.00. ## Technological Characteristics Two-site sandwich immunoassay; direct chemiluminometric technology. Capture antibody: mouse anti-human IgE on paramagnetic particles. Detection antibody: goat anti-human IgE labeled with acridinium ester. Sample volume: 30 µL. Calibration: 2-point. Traceability: WHO 75/502. Analyzers: ADVIA Centaur, XP, XPT. Standards: CLSI EP07-ed3, CLSI EP17-A2, CLSI EP09-A3. ## Regulatory Identification An immunoglobulins A, G, M, D, and E immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the immunoglobulins A, G, M, D, an E (serum antibodies) in serum. Measurement of these immunoglobulins aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents. ## Predicate Devices - Acs Total Ige Immunoassay ([K920372](/device/K920372.md)) ## Submission Summary (Full Text) > This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com. > > Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/). {0} FDA U.S. FOOD & DRUG ADMINISTRATION # 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ## I Background Information: A 510(k) Number K193493 B Applicant Siemens Healthcare Diagnostics Inc. C Proprietary and Established Names ADVIA Centaur Total IgE (tIgE) D Regulatory Information | Product Code(s) | Classification | Regulation Section | Panel | | --- | --- | --- | --- | | DGC | Class II | 866.5510 | IM | ## II Submission/Device Overview: A Purpose for Submission: Modification of a previously cleared device: addition of Li-Heparin and K2-EDTA plasma matrices. B Measurand: Total IgE C Type of Test: Quantitative, Chemiluminescent ## III Intended Use/Indications for Use: Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993-0002 www.fda.gov {1} K193493 - Page 2 of 7 A Intended Use(s): See Indications for Use below. B Indication(s) for Use: For in vitro diagnostic use in the quantitative determination of total IgE in serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur, ADVIA Centaur XP, and ADVIA Centaur XPT systems. C Special Conditions for Use Statement(s): Rx - For Prescription Use Only D Special Instrument Requirements: ADVIA Centaur, ADVIA Centaur XP, and ADVIA Centaur XPT IV Device/System Characteristics: A Device Description: The ADVIA Centaur Total IgE (tIgE) reagent kit contains the following: ADVIA Centaur Total IgE Ready Pack primary reagent pack consist of the ADVIA Centaur tIgE Lite Reagent and Solid Phase Reagents: - Lite Reagent: 5.0 mL/pack of goat anti-human IgE antibody (~2.4 µg/mL) labeled with acridinium ester in buffer with sodium azide (0.12%), protein stabilizers, and preservatives. - Solid Phase Reagent: 22.5 mL/pack of mouse anti-human IgE antibody (~0.02 mg/mL) covalently coupled to paramagnetic particles in buffer with protein stabilizers, sodium azide (0.11%), and preservatives. Materials Required but not provided - ADVIA Centaur Calibrator 80 consists of low and high levels of human IgE in equine serum and preservatives. Optional Reagents - ADVIA Centaur IgE Master Curve Material (MCM) consists of MCM 1 that is lyophilized human plasma with sodium azide (0.1% after reconstitution) and preservatives, and MCM 2-7 that are various levels of IgE in lyophilized human plasma with sodium azide (0.1% after reconstitution) and preservatives. - ADVIA Centaur IgE Diluent consist of IgE-free human plasma with sodium azide (0.1%). B Principle of Operation: {2} The ADVIA Centaur Total IgE (tIgE) assay is a fully automated, two-site sandwich immunoassay using direct chemiluminescent technology. The sample is incubated with both the Lite and Solid Phase Reagents simultaneously for 7.5 minutes at 37°C. After incubation, the immuno-complex is washed, and the Acid Reagent and Base Reagent are added to initiate the chemiluminescent reaction. A direct relationship exists between the amount of total IgE present in the patient sample and the amount of relative light units (RLUs) detected by the system. V Substantial Equivalence Information: A Predicate Device Name(s): Acs Total Ige Immunoassay B Predicate 510(k) Number(s): K920372 C Comparison with Predicate(s): | Device & Predicate Device(s): | K193493 | K920372 | | --- | --- | --- | | Device Trade Name | ADVIA Centaur Total IgE (tIgE) | Acs Total Ige Immunoassay | | General Device Characteristic Similarities | | | | Intended Use/Indications for Use | For in vitro diagnostic use in the quantitative determination of total IgE in serum and plasma (EDTA and lithium heparin) using the ADVIA Centaur, ADVIA Centaur XP, and ADVIA Centaur XPT systems. | For in vitro diagnostic use in the quantitative determination of total IgE in serum using the ADVIA Centaur, ADVIA Centaur XP, and ADVIA Centaur XPT systems. | | Operating Principle | Two-site sandwich immunoassay | Same | | Assay Technology | Direct chemiluminescent | Same | | Measurement | Quantitative | Same | | Sample Volume | 30 μL | Same | | Detection Antibody | Goat anti-human IgE antibody labeled with acridinium ester | Same | | Capture Antibody | Mouse anti-human IgE antibody covalently coupled to paramagnetic particles | Same | | Traceability/Standardization | World Health Organization (WHO) 75/502 | Same | | Calibration | Two-point | Same | | Calibrator/Levels | ADVIA Centaur Calibrator 80/two levels | Same | K193493 - Page 3 of 7 {3} | Controls/Levels | Commercial Controls/ two levels | Same | | --- | --- | --- | | Master Curve Materials (MCM) | Seven levels (MCM1–7) | Same | | **General Device Characteristic Differences** | | | | Sample Type | Serum, plasma (EDTA and lithium heparin) | Serum | | Detection Capability | LoB: 1.5 IU/mL LoD: 2.0 IU/mL LoQ: 2.5 IU/mL | Analytical Sensitivity: 1.5 IU/mL | | Assay Range | 2.5–3000 IU/mL | 1.5–3000 IU/mL | VI Standards/Guidance Documents Referenced: CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline—Third Edition CLSI EP06-A, Evaluation of Linearity of Quantitative Measurement Procedures: A Statistical Approach; Approved Guideline CLSI EP07, 3rd Edition, Interference Testing in Clinical Chemistry CLSI EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline—Second Edition VII Performance Characteristics (if/when applicable): A Analytical Performance: 1. Precision/Reproducibility: The precision and reproducibility of the assay were demonstrated in K920372. 2. Linearity: The linearity of the assay was demonstrated in K920372. 3. Analytical Specificity/Interference: The analytical specificity was demonstrated in K920372. Interference was evaluated with hemoglobin, triglycerides and bilirubin in K920372. To evaluate the performance of the ADVIA Centaur Total IgE (tIgE) assay in the presence of K2-EDTA and lithium heparin, one sample at low and one at high level of tIgE for each matrix were used to titrate the EDTA and heparin anticoagulants in order to simulate the effect of partially filled blood collection plasma tube. The nominal K2-EDTA and lithium K193493 - Page 4 of 7 {4} heparin concentrations are 1.8 mg/mL and 15.0 U/mL in blood collection tubes, respectively. Both K2-EDTA and lithium heparin were spiked at three times and five times the additive concentration for testing. Testing was performed in six replicates per sample on one ADVIA Centaur XP instrument using one lot of reagent. The recovery was calculated as the difference between the means of the test samples spiked with the interferent and control samples spiked with the same volume of the interferent vehicle. Results summarized in the table below show no significant assay interference was demonstrated with K2-EDTA and lithium heparin at the indicated test concentrations. | Interferent | Test concentration | Low level sample | | High level sample | | | --- | --- | --- | --- | --- | --- | | | | Mean (IU/mL) | Recovery (%) | Mean (IU/mL) | Recovery (%) | | K2-EDTA | 1.8 mg/mL | 121.5 | 100 | 1624.1 | 100 | | | 5.4 mg/mL | 122.8 | 101.1 | 1555.7 | 95.8 | | | 9.0 mg/mL | 119.4 | 98.3 | 1646.1 | 101.4 | | Lithium heparin | 15 U/mL | 167.5 | 100 | 1450.1 | 100 | | | 45 U/mL | 167.6 | 100 | 1542.6 | 106.4 | | | 75 U/mL | 164.7 | 98.3 | 1433.7 | 98.9 | 4. Assay Reportable Range: The claimed measuring range is from 2.5 IU/mL to 3000 IU/mL. 5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods): The traceability and reagent stability were established in K920372. 6. Detection Limit: The Limit of Blank (LoB), Limit of Detection (LoD) and Limit of Quantitation for the ADVIA Centaur Total IgE (tIgE) assay were determined in accordance with the CLSI guideline EP17-A2. The LoB was determined using two lots of reagents and one ADVIA Centaur XP instrument. For lot 1, four analyte-free serum samples were tested in five replicates per sample, two runs per day for five days to obtain a total of 240 replicates. For lot 2, five analyte-free serum samples were tested in five replicates per sample, two runs per day for five days, to obtain a total of 300 replicates. The LoB was estimated as the 95th percentile of the measurements for each of the lots tested and determined to be 0.69 IU/mL and 0.28 IU/mL for the two lots of reagents. The claimed LoB is 1.5 IU/mL. The LoD was determined using 10 patient serum pools with low analyte levels. Each sample was tested in five replicates per run, two runs per day, for six days on one ADVIA Centaur XP instrument using two lots of reagents. A total of 605 replicates was obtained for reagent lot 1 and 557 replicates for reagent lot 2. The LoD was calculated as the $\mathrm{LoB} + 1.645 \times \mathrm{SD}$ of the replicates for the low-level samples and determined as $1.20 \mathrm{IU} / \mathrm{mL}$ and $1.21 \mathrm{IU} / \mathrm{mL}$ for the two lots of reagents. The claimed LoD is $2.0 \mathrm{IU} / \mathrm{mL}$. K193493 - Page 5 of 7 {5} The LoQ was determined using 10 serum samples comprised of patient pools with low analyte levels. Each sample was tested in six replicates per run, two runs per day, for five days on one ADVIA Centaur XP instrument using two lots of reagents. A total of 600 replicates was obtained for reagent lot 1 and 420 replicates for reagent lot 2. The LoQ, defined as the mean value of the sample which fulfills the specification for the total within-laboratory imprecision ≤ 20% CV is 1.64 IU/mL and 1.75 IU/mL for the two lots of reagents. The claimed LoQ is 2.5 IU/mL which is the lower limit of the measuring range claimed for the assay. 7. Assay Cut-Off: Not applicable B Comparison Studies: 1. Method Comparison with Predicate Device: The method comparison with predicate device was presented in K920372. 2. Matrix Comparison: To demonstrate that Li-Heparin plasma and K2-EDTA plasma samples yield results comparable with serum samples by the ADVIA Centaur Total IgE (tIgE) assay, a study was performed by using 73 serum/K2-EDTA plasma paired samples and 73 serum/Li-heparin plasma paired samples. Paired samples were each tested in singleton with one reagent lot on one ADVIA Centaur XP system. The Deming regression analysis was performed, and the results are summarized in the following table: | Comparison | Sample Range (IU/mL) | N | Slope (95% CI) | Intercept (95% CI) | Correlation Coefficient (r) | | --- | --- | --- | --- | --- | --- | | K2-EDTA plasma vs. serum | 2.80 – 2748.84 | 73 | 0.99 (0.98 – 1.01) | 0.28 (0.09 – 0.48) | 1.00 | | Lithium Heparin plasma vs. serum | | | 1.00 (0.99 – 1.02) | 0.18 (-0.10 – 0.46) | 1.00 | | N = Number of samples tested | | | | | | The data support the addition of K2-EDTA plasma and Li-heparin plasma sample types to the ADVIA Centaur Total IgE (tIgE) assay. C Clinical Studies: 1. Clinical Sensitivity: Not applicable 2. Clinical Specificity: K193493 - Page 6 of 7 {6} Not applicable 3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable): Not applicable D. Clinical Cut-Off: Not applicable E. Expected Values/Reference Range: The expected values were established in K920372. 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. K193493 - Page 7 of 7 --- **Source:** [https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DGC/K193493](https://fda.innolitics.com/submissions/IM/subpart-f%E2%80%94immunological-test-systems/DGC/K193493) **Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact). **Cite:** Innolitics at https://innolitics.com