(421 days)
Automated latex enhanced immunoassay for the quantitative in vitro determination of total immunoglobulin E (1gE) in human serum or plasma (EDTA, heparin, citrate) using the ARCHITECT c Systems. The measurement of total IgE is useful in the clinical diagnosis of IgE-mediated allergies, if used in conjunction with other clinical studies.
The Quantia IgE reagent is a suspension of polystyrene latex particles of uniform size coated with mouse anti-human IgE. When a sample containing IgE is mixed with the latex reagent and the reaction buffer included in the kit, agglutination occurs. The degree of agglutination is directly proportional to the concentration of IgE in the sample and is determined by measuring the decrease of transmitted light caused by the aggregates. Methodology: Turbidimetric/Immunoturbidimetric.
The provided document outlines the acceptance criteria and study results for the Quantia IgE assay, a device for quantitatively determining total IgE in human serum or plasma. It's important to note that this document is a 510(k) summary, focusing on demonstrating substantial equivalence to a predicate device after a modification, rather than a comprehensive de novo approval study. Therefore, some information typically found in a de novo clinical trial report (e.g., specific details on training set size, number of experts for training ground truth) might not be explicitly detailed.
Here's an analysis of the provided information:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are generally implied by the performance characteristics presented and their comparison to the predicate device or established clinical standards (e.g., CLSI guidelines). The document focuses on demonstrating that the modified device performs as well as the predicate and meets relevant analytical performance metrics.
| Performance Metric | Predicate Device (K050493) Acceptance Criteria/Performance | Subject Device (Modified Quantia IgE) Reported Performance |
|---|---|---|
| Linearity (Reportable Range) | 25.0 - 1000.0 IU/mL | 20.0 - 1000.0 IU/mL (Acceptable linearity demonstrated across this range) |
| Limit of Blank (LoB) | Not defined | 6.2 IU/mL |
| Limit of Detection (LoD) | 12.9 IU/mL | 11.6 IU/mL |
| Limit of Quantitation (LoQ) | 25.0 IU/mL | 20.0 IU/mL |
| Precision (Total %CV) | < 6% for Level II and mixture of Levels I & II Control; ≤ 15% for Level I Control | Controls:Control I: 2.8%1:1 Mix: 1.0%Control II: 0.9%Serum Panels:Panel A (26.9 IU/mL): 4.9%Panel B (139.1 IU/mL): 1.3%Panel C (461.6 IU/mL): 1.2% |
| Prozone Interference | < 10% up to 138 IU/mL (Rheumatoid factor) for general interference. No prozone for undiluted samples up to 26,000.0 IU/mL | No significant interference (within ± 5%) for common interferents (Bilirubin, Hemoglobin, Lipemia) at specified levels. No significant interference (within ± 10%) for HAMA, RF (up to 138 IU/mL) and various drugs. No prozone interference for undiluted samples containing up to 25,470.7 IU/mL of IgE. |
| Sample Matrix Comparison (Slope vs. Serum) | Na-EDTA: 0.968 (95% CI: 0.963 to 0.973)K-EDTA: 0.982 (95% CI: 0.976 to 0.989)Na-Heparin: 0.978 (95% CI: 0.973 to 0.983)Li-Heparin: 0.978 (95% CI: 0.973 to 0.983)Citrate: 0.963 (95% CI: 0.955 to 0.972) | Na-EDTA: 0.98 (95% CI*: 0.97 to 1.00)K-EDTA: 1.01 (95% CI: 0.99 to 1.03)Na-Heparin: 1.00 (95% CI: 0.98 to 1.01)Li-Heparin: 0.98 (95% CI: 0.98 to 1.00)Na-Citrate: 0.97 (95% CI: 0.96 to 0.99) |
| Sample Stability | Max Storage:20-25°C: 1 day2-8°C: 2 days-20°C: 12 days | Max Storage:20-25°C: 7 days2-8°C: 7 days-20°C: 6 months |
The table clearly shows that the modified device's performance metrics are either improved (e.g., lower LoD, LoQ, extended stability) or remain comparable to the predicate device, demonstrating that the device meets or exceeds the previous performance. The linearity range was expanded downwards from 25.0 to 20.0 IU/mL. The precision values reported for the subject device are well within the specified acceptance criteria for the predicate.
2. Sample Size Used for the Test Set and Data Provenance
The document provides sample sizes for various analytical validation studies:
- Sample Matrix Comparison:
- Predicate device: Five sets of 52 paired samples were run (total 260 samples).
- Subject device: Forty paired samples were run (serum vs. various plasma types).
- Limit of Blank (LoB), Limit of Detection (LoD), Limit of Quantitation (LoQ):
- LoB: n ≥ 60 replicates of zero-analyte samples.
- LoD: n ≥ 60 replicates of low-analyte level samples.
- LoQ: n ≥ 60 replicates of low-analyte level samples.
- Precision:
- Control (Level I, Mixture I&II, Level II): 50 replicates each (for predicate data summary).
- Subject device: 80 replicates for "Panel 50 IU/mL", "Control I", "1:1 Mix Control I and II", "Control II", "Panel 800 IU/mL" (tested in a minimum of 2 replicates, twice per day on 20 days).
- Additionally, 3 native serum pools (Panel A, B, C) were tested with 48 replicates each (in a minimum of 2 replicates, twice per day on 12 days).
Data Provenance: The document does not explicitly state the country of origin for the data or whether the studies were retrospective or prospective. However, based on the nature of analytical validation studies for an in-vitro diagnostic device, these are typically prospective laboratory studies conducted at the manufacturer's R&D facilities or contracted labs.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
For an in-vitro diagnostic (IVD) device like Quantia IgE, the ground truth for performance evaluation (e.g., linearity, LoD, LoQ, precision, matrix effects) is established through analytical reference methods and calibrated standards, not human expert review. These studies rely on precise laboratory measurements and established protocols (e.g., CLSI guidelines). Therefore, there are no "experts" in the sense of radiologists reviewing images to establish ground truth.
4. Adjudication Method for the Test Set
Not applicable for analytical performance studies of an IVD. Adjudication methods (e.g., 2+1, 3+1) are typically used in clinical studies, particularly for diagnostic imaging or subjective assessments, where human agreement on a diagnosis or finding is crucial. Here, the values are quantitative measurements compared to reference values or statistical criteria.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. This device is an in-vitro diagnostic assay for measuring total IgE levels, not an imaging device or AI-assisted diagnostic tool that would involve human readers interpreting results. Therefore, an MRMC study is irrelevant to its validation.
6. Standalone (Algorithm Only) Performance
This entire submission describes the standalone performance of the Quantia IgE assay, a laboratory test. It is not an "algorithm" in the typical sense of AI, but rather a biochemical assay system. All performance metrics described (linearity, LoD, LoQ, precision, etc.) are characteristics of the assay system itself, without human interpretation beyond standard laboratory procedures and result reporting.
7. Type of Ground Truth Used
The ground truth used for these analytical performance studies is based on:
- Reference Standards/Calibrators: For linearity, LoD, LoQ, and IgE International Standard Recovery, the ground truth is established by using highly characterized, traceable calibrators and reference materials with known concentrations.
- Statistical Definitions/Methodologies: The definitions for LoB, LoD, and LoQ explicitly state how they are determined using a certain number of replicates of zero-analyte or low-analyte samples, and statistical calculations (e.g., 95th percentile, mean + 2 SD).
- Established CLSI Protocols: The studies explicitly state that they were performed based on guidance from CLSI (Clinical and Laboratory Standards Institute) protocols, such as NCCLS EP6-A (now EP06), EP17-A2, EP07-A2, EP37, and EP05-A3. These protocols outline the scientifically accepted methods for establishing analytical performance characteristics.
8. Sample Size for the Training Set
This document describes a "Special 510(k)" for a modification to an existing device (Quantia IgE) to demonstrate substantial equivalence. For IVD analytical performance studies, there isn't a "training set" in the machine learning sense alongside a "test set." The studies performed are the analytical validation studies on actual samples or controls covering the relevant range. The sample sizes for these studies are provided above (e.g., 40 paired samples for matrix comparison, ≥60 replicates for LoD/LoQ, 80 replicates for precision controls, 48 for native serum panels).
9. How the Ground Truth for the Training Set Was Established
As explained under points 3 and 7, the concept of a "training set" and "ground truth established by experts" for this type of device and study is not directly applicable. The "training" for such an IVD device happens during its development and optimization phases, where various reagent formulations and assay parameters are tested against known concentration panels to achieve optimal performance. The "ground truth" during this development is based on the known concentrations of calibrators and reference materials, and the adherence to established analytical performance standards. The studies detailed in this 510(k) summary are the formal validation (test set) of the modified device's performance.
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February 21, 2023
Biokit, S.A. Angels Roma Regulatory Affairs & Design Quality Director Av. Can Montcau. 7 Llica d'Amunt, Barcelona 08186 Spain
Re: K214068
Trade/Device Name: Quantia IgE Regulation Number: 21 CFR 866.5510 Regulation Name: Immunoglobulins A, G, M, D, And E Immunological Test System Regulatory Class: Class II Product Code: DGC Dated: October 28, 2022 Received: October 31, 2022
Dear Angels Roma:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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
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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Ying Mao -S
Ying Mao, Ph.D. Branch Chief Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K214068
Device Name Quantia IgE
Indications for Use (Describe)
Automated latex enhanced immunoassay for the quantitative in vitro determination of total immunoglobulin E (1gE) in human serum or plasma (EDTA, heparin, citrate) using the ARCHITECT c Systems. The measurement of total IgE is useful in the clinical diagnosis of IgE-mediated allergies, if used in conjunction with other clinical studies.
| 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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510(k) Summary
This 510(k) Summary is being submitted in accordance with the requirements of 21 CER 807.92 and the Safe Medical Device Act of 1990.
| Submission Type | K214068 - Special 510(k) |
|---|---|
| Submitter's Information | Biokit, S.A.Av. Can Montcau, 7Lliçà d'Amunt, Barcelona 08186Spain |
| Contact Person | Àngels RomaQuality & Regulatory Affairs VPPhone: +34 (938) 609-000Email: aroma@werfen.com |
| Preparation Date | February 11th, 2023 |
| Device Trade Name | Quantia IgE (IgE, Antigen, Antiserum, Control) |
| Regulatory Information | Regulation Number21 CFR 866.5510Regulation DescriptionImmunoglobulins A, G, M, D and E immunological test systemClassificationClass IIProduct CodeDGCClassification PanelImmunology |
| Predicate Device | K050493Quantia IgE |
| Device Description | The Quantia IgE reagent is a suspension of polystyrene latex particles of uniform size coated with mouse anti-human IgE. When a sample containing IgE is mixed with the latex reagent and the reaction buffer included in the kit, agglutination occurs. The degree of agglutination is directly proportional to the concentration of IgE in the sample and is determined by measuring the decrease of transmitted light caused by the aggregates. Methodology: Turbidimetric/Immunoturbidimetric. |
| Indications for Use /Intended Use | Automated latex enhanced immunoassay for thequantitative in vitro determination of totalimmunoglobulin E (IgE) in human serum or plasma(EDTA, heparin, citrate) using the ARCHITECT cSystems. The measurement of total IgE is useful in the |
| clinical diagnosis of IgE-mediated allergies, if used inconjunction with other clinical studies. |
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Description of the Modification: The sample volume that is used by the assay is changed from 3.5 µL to 10.5 µL. Due to this modification, additional changes have been implemented in the assay parameters: Read times are changed from 26-27 to 24-25, the Sample Probe water SmartWash is added and the lowlinearity is changed from 25.0 to 20.0 IU/mL. The correlation factor in the assay file is changed from 1.0000 to 1.0500. The changes to the Instruction for Use are detailed below.
| Current Insert Summary and Principle(Excerpt) | Updated Insert Summary and Principle(Excerpt)Revisions in italic and highlights |
|---|---|
| PRINCIPLES OF THE PROCEDURE | PRINCIPLES OF THE PROCEDURE |
| ---- (additional information is added) | For additional information on system and assaytechnology, refer to the ARCHITECT SystemOperations Manual, Section 3. |
| REAGENTS | REAGENTS |
| Reagent Kit | Kit Contents |
| ---- (additional information is added) | Volumes (mL) listed in the following tableindicate the volume per vial. |
| ---- (additional information is added) | Test per vial set 69 |
| Indications of Reagent DeteriorationDeterioration of the reagents may be indicatedwhen a calibration error occurs or a controlvalue is out of the specified range.Associated test results are invalid, and samplesmust be retested.Assay recalibration may be necessary.For troubleshooting information, refer to theARCHITECT System Operations Manual, Section10. |
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| ---- (additional information is added) | INSTRUMENT PROCEDURE | ||
|---|---|---|---|
| The Quantia IgE assay file must be installed onthe ARCHITECT c System prior to performingthe assay.For detailed information on assay file installationand viewing and editing assay parameters, referto the ARCHITECT System Operations Manual,Section 2.For information on printing assay parameters,refer to the ARCHITECT System OperationsManual, Section 5.For a detailed description of system procedures,refer to the ARCHITECT System OperationsManual. | |||
| SPECIMEN COLLECTION AND HANDLING | SPECIMEN COLLECTION ANDPREPARATION FOR ANALYSIS | ||
| Suitable Specimens | Specimen Types | ||
| Serum: Use fresh serum collected by standardvenipucture techniques. Ensure complete clotformation has taken place prior tocentrifugation. Centrifuge according to tube | Specimen Types | ||
| manufacturer's instructions to ensure properseparation of serum blood cells. Gel separatortubes were not tested. | *Serum Serum tubes | ||
| Some specimens, especially those from patientsreceiving anticoagulant or thrombolytic | *Plasma Acceptable anticoagulants are: | ||
| therapy, may take longer to complete their | Sodium EDTA | ||
| clotting processes. Fibrin clots may | Potassium EDTA | ||
| subsequently form in these sera and the clotscould cause erroneous test results. | Sodium heparin | ||
| Plasma: Use plasma collected by standardvenipuncture techniques. The acceptableanticoagulanants are sodium EDTA, potassiumEDTA, sodium heparin, lithium heparin, andcitrate. Ensure centrifugation is adequate toremove platelets. Centrifuge according to tube | Lithium heparin | ||
| manufacturer's instructions to ensure properseparation of plasma from bloods cells. Gel | Sodium citrate | ||
| separator tubes were not tested. | * Gel separator tubes were not tested. | ||
| For total sample volume requirements, refer to theASSAY PARAMETERS sections of this packageinsert and Section 5 of the ARCHITECT SystemOperations Manual. | Other specimen types, collection tube types, andanticoagulants have not been verified with thisassay.The instrument does not provide the capability toverify specimen types. It is the responsibility ofthe operator to verify that the correctspecimen types are used in the assay. | ||
| Sample Matrix (Serum vs. Plasma)Five sets of 52 paired samples were run. SodiumEDTA plasma, potassium EDTA plasma, sodium | Sample Matrix (Serum vs. Plasma)Forty paired samples were run. Sodium EDTAplasma, potassium EDTA plasma, sodium |
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| Slope | Y - Intercept | |
|---|---|---|
| Na-EDTA | 0.968(95% CI: 0.963 to 0.973) | -1.553(95% CI: -3.068 to -0.007) |
| K-EDTA | 0.982(95% CI: 0.976 to 0.989) | -1.878(95% CI: -3.873 to 0.117) |
| Na-Heparin | 0.978(95% CI: 0.973 to 0.983) | -0.461(95% CI: -1.983 to 1.060) |
| Li-Heparin | 0.978(95% CI: 0.973 to 0.983) | -1.272(95% CI: -2.761 to 0.218) |
| Citrate | 0.963(95% CI: 0.955 to 0.972) | -2.226(95% CI: -4.702 to 0.250) |
sodium citrate plasma paired to serum samples were used. The linear regression statistics are shown below.
| Slope | Y-Intercept | |
|---|---|---|
| Na-EDTA | 0.98(95% CI*: 0.97 to 1.00) | -1.08(95% CI: -3.83 to 1.47) |
| K-EDTA | 1.01(95% CI: 0.99 to 1.03) | 0.80(95% CI: -0.77 to 2.19) |
| Na-Heparin | 1.00(95% CI: 0.98 to 1.01) | -1.22(95% CI: -3.19 to 0.69) |
| Li-Heparin | 0.98(95% CI: 0.98 to 1.00) | 1.23(95% CI: -0.47 to 2.19) |
| Na-Citrate | 0.97(95% CI: 0.96 to 0.99) | -0.74(95% CI: -2.39 to 0.91) |
Specimen Storage
| Specimen Type | Temperature | Maximum StorageTime | Special Instructions |
|---|---|---|---|
| Serum/Plasma | 20 to 25°C | 1 day | Specimens may be storedon the clot. |
| Serum/Plasma | 2 to 8 °C | 2 days | |
| Serum/Plasma | -20°C | 12 days | Remove serum or plasmafrom the clot. |
If testing will be delaved longer than the maximum 20 to 25°C or 2 to 8°C storage time, remove serum or plasma from the clot and store frozen (-20°C).
Each laboratory may establish a range around -20°C from either the freezer manufacturer's specifications or your laboratory standard operating procedure(s) for specimen storage.
NOTE: Stored specimens must be inspected for particulates. If present, mix and centrifuge the specimen to remove particulates prior to testing.
Specimen Shipping
Package and label specimens in compliance with applicable state, federal, and international regulations covering the transport of clinical specimens and infectious substances. Do not exceed the storage limitations listed above.
Specimen Storage
| Temperature | Maximum Storage | BibliographicReference |
|---|---|---|
| 20 to 25°C | 7 days | 8 |
| 2 to 8°C | 7 days | 8, 9 |
| -20°C | 6 months | 8 |
Guder et al.8 suggest storage of frozen specimens at -20°C for no longer than the time interval cited above. However, limitations of laboratory equipment make it necessary in practice for clinical laboratories to establish a range around -20°C for specimen storage. This temperature range may be established from either the freezer manufacturer's specifications or your laboratory standard operating procedure(s) for specimen storage.
NOTE: Stored specimens must be inspected for particulates. If present, mix and centrifuge the specimen to remove particulates prior to testing.
---- (additional information is added)
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| PROCEDURE | PROCEDURE | ||||||
|---|---|---|---|---|---|---|---|
| Materials Required but not Provided | Materials Required but not Provided | ||||||
| ---- (additional information is added) | For information on materials required foroperation of the instrument, refer to theARCHITECT System Operations Manual, Section1.For information on materials required formaintenance procedures, refer to theARCHITECT System Operations Manual, Section9. | ||||||
| ---- (additional information is added) | Quality Control Guidance | ||||||
| Refer to "Basic QC Practices" by James OWestgard, Ph.D. for guidance on laboratoryquality control practices. | |||||||
| RESULTS | RESULTS | ||||||
| Refer to Appendix C of the ARCHITECT SystemOperations Manual for information on resultscalculations. | CalculationFor additional information on resultscalculations, refer to the ARCHITECT SystemOperations Manual, Appendix C. | ||||||
| ---- (additional information is added) | Interpretation of ResultsAs with all analyte determinations, the IgE valueshould be used in conjunction with informationavailable from clinical evaluation and otherdiagnostic procedures. | ||||||
| ---- (additional information is added) | FlagsSome results may contain information in theFlags field. For a description of the flags thatmay appear in this field, refer to the ARCHITECTSystem Operations Manual, Section 5. | ||||||
| ---- (additional information is added) | Reportable IntervalBased on representative data for the limit ofquantitation (LoQ) and the limit of detection(LoD), the ranges over which results can bereported are provided below according to thedefinitions from CLSI EP34, 1st ed. | ||||||
| Analytical Measuring Interval (AMI)a Units (IU/mL) 20.0 - 1000.0 Extended Measuring Interval (EMI)b 1000.0 - 10 000.0 a AMI: The AMI is determined by the range ofvalues in IU/mL that demonstrated acceptableperformance for linearity, imprecision, and |
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werfer
LIMITATIONS OF THE PROCEDURE
Refer to the SPECIMEN COLLECTION AND HANDLING and SPECIFIC PERFORMANCE CHARACTERISTICS
sections of this package insert.
No cross-reactivity studies have been conducted with heterophile antibodies.
There is no prozone interference for undiluted samples containing up to 26,000.0 IU/mL of IgE. Sample concentrations higher than 26,000.0 IU/mL have not been tested.
As the limit of quantification of Quantia IgE is 25.0 IU/mL, it is not recommended to use this test for children less than 12 months of age.
SPECIFIC PERFORMANCE CHARACTERISTICS
---- (additional information is added)
Linearity
Linearity was assessed according to Clinical and Laboratory Standards Institute (CLSI) protocol NCCLS EP6-A.12 The reportable range of the Quantia IgE assay is 25.0 to 1000.0 IU/mL.
b EMI: The EMI extends from the upper limit of quantitation (ULoQ) to the ULoQ x dilution factor. The value reflects a 1:10 dilution factor. NOTE: The default Low Linearity value of the assay file corresponds to the lower limit of the analytical measuring interval. Samples with an IgE value below the lower limit of the AMI are reported as < 20.0 IU/mL.
LIMITATIONS OF THE PROCEDURE
Refer to the SPECIMEN COLLECTION AND PREPARATION FOR ANALYSIS and SPECIFIC PERFORMANCE CHARACTERISTICS sections of this package insert. No cross-reactivity studies have been conducted with heterophile antibodies. There is no prozone interference for undiluted samples containing up to 25 470.7 IU/mL of IgE. Sample concentrations higher than 25 470.7 IU/mL have not been tested. As the limit of quantification of Quantia IgE is
20.0 IU/mL, it is not recommended to use this test for children less than 12 months of age.
SPECIFIC PERFORMANCE CHARACTERISTICS
Representative performance data are provided in this section. Results obtained in individual laboratories mav varv.
Linearity
A study was performed based on guidance from CLSI EP06 2nd ed. Two high-analyte samples (human serum IgE at approximately 1040.1 and 1018.1 IU/mL) and 2 zero-analyte samples (IgEdepleted serum) were combined at different proportions to make 2 linearity panels that each consisted of samples with concentrations evenly distributed across the intended analytical measuring interval.
The assay demonstrated acceptable linearity across the analytical measuring interval of 20.0 to 1000.0 IU/mL.
Limit of Quantification (LOQ)
The LOQ of the Quantia IgE assay is 25.0 IU/mL. The LOQ was determined using dilutions of the 100 IU/mL level of the Quantia IgE Calibrator prepared in physiologic saline. The LOQ is defined as the
Lower Limits of Measurement
A study was performed based on guidance from CLSI EP17-A2. The limit of blank (LoB), limit of detection (LoD), and limit of quantitation (LoQ) values are summarized below. These
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| lowest analyte concentration that can be measuredwith a within-run CV below 20% and the recovery iswithin ± 20% of expected value. | representative data support the lower limit of theanalytical measuring interval. | |||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Limit of Detection (LOD)The LOD of the Quantia IgE assay is 12.9 IU/mL,calculated by running 30 replicates of saline. LOD isdefined as the mean concentration of an analyte-freesample + 2 SD, where SD is the within-run standarddeviation. | ||||||||||||||||
| IU/mL LoBa 6.2 LoDb 11.6 LoQc 20.0 a The LoB represents the 95th percentile from n ≥ 60 replicates of zero-analyte samples.b The LoD represents the lowest concentration at which the analyte can be detected with 95% probability based on n ≥ 60 replicates of low-analyte level samples.c The LoQ is defined as the lowest concentration at which a maximum allowable precision of 20 %CV and a maximum allowable bias of 20% were met and was determined from n ≥ 60 replicates of low-analyte level samples and where the assay is linear. | ||||||||||||||||
| Interfering Substances...Rheumatoid factor interference is less than 10% up to 138 IU/mL.For a comprehensive review of interfering substances, refer to the publication by Young et al.13 | Interfering Substances...Potentially Interfering Endogenous SubstancesA study was performed based on guidance from CLSI EP07-A2. and CLSI EP37, 1st ed. Each substance was tested at 1 analyte level (approximately 90.0 IU/mL). | |||||||||||||||
| No Significant Interference (Interference within ± 5%) Potentially Interfering Substance Interferent Level(mg/dL) Bilirubin (conjugated) 40 Bilirubin (unconjugated) 40 Hemoglobin 1000 Lipemia (chyle) 2.4 AU/cm at 660 nm Lipemia (triglyceride) 1500 | ||||||||||||||||
| Potentially Interfering Other SubstancesA study was performed based on guidance from CLSI EP07-A2, CLSI EP07, 3rd ed. and CLSI EP37, 1st ed. | ||||||||||||||||
| No Significant Interference (Interference within ± 10%) Potentially InterferingSubstance InterferentConcentration IgE Target(IU/mL) % Difference HAMA 0.100 mg/dL 99.0 0.4 RF 138 IU/mL 90.0 1.3 | ||||||||||||||||
| Potentially Interfering DrugsA study was performed based on guidance from CLSI EP07-A2 and CLSI EP37, 1st ed. Each |
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Precision
The precision of the Quantia IgE assay is < 6% Total CV for Level II and a mixture of Levels I and II Control, and ≤ 15% for Level I Control (Quantia Ferritin/Myoglobin/IgE Control). Studies were performed using CLSI protocol NCCLS EP15-A.14 Representative data are summarized below.
| Control | Level I | Mixture ofI and II | Level II |
|---|---|---|---|
| N | 50 | 50 | 50 |
| Mean (IU/mL) | 46.3* | 228.3 | 414.6 |
| Within Run %CV | 13.8 | 2.9 | 2.1 |
| Total %CV | 14.5 | 3.4 | 2.4 |
*Concentrations near the LOQ value produce slightly higher CVs.
substance was tested at 1 analyte level (approximately 99.0 IU/mL).
| No Significant Interference (Interference within ± 10%) | |
|---|---|
| Potentially Interfering Drug | Interferent Level(mg/dL) |
| Acetaminophen | 15.6 |
| Acetylcysteine | 15.0 |
| Acetylsalicylic acid | 3.00 |
| Ampicillin | 7.50 |
| Cefoxitin | 660 |
| Cetirizine | 0.435 |
| Cyclosporine | 0.180 |
| Diphenhydramine | 0.0774 |
| Doxycycline | 1.80 |
| Fexofenadine | 0.116 |
| Heparin | 330 units/dL |
| Ibuprofen | 21.9 |
| Levodopa | 0.750 |
| Methyldopa | 2.25 |
| Metronidazole | 12.3 |
| Mometasone | 0.000045 |
| Phenylbutazone | 32.1 |
| Prednisolone | 0.120 |
| Rifampicin | 4.80 |
| Salicylic Acid | 2.86 |
| Theophylline | 6.00 |
Interferences from medication or endogenous substances may affect results.
Precision
Within-Laboratory Precision
A study was performed based on guidance from CLSI EP05-A3. Testing was conducted using 3 lots of the Quantia IgE reagent, 1 lot of the Quantia IgE Calibrator, 1 lot of the Quantia Ferritin/Myoglobin/IgE Control, and 1 instrument. Two controls, 1:1 mixture of control I and II, and 2 serum panels were tested in a minimum of 2 replicates, twice per day on 20 days.
Additional testing was conducted with 3 native serum pools using the same number of reagent, calibrator, and control lots and instruments utilized in the 20-day study. The 3 serum panels (Panel A, B, and C) were tested in a minimum of 2 replicates, twice per day on 12 days.
The performance from a representative combination is shown in the following table.
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| Key to Symbols | |
|---|---|
- • ---- New symbol is added.
| Mean | Within-Run(Repeatability) | Within-Laborator(Total)a | ||||
|---|---|---|---|---|---|---|
| Sample | n | (IU/mL) | SD | %CV | SD | %CV |
| Panel 50 IU/mL | 80 | 53.4 | 2.1 | 3.9 | 2.1 | 3.9 |
| Control I | 80 | 69.6 | 1.9 | 2.7 | 2.0 | 2.8 |
| 1:1 Mix Control I and II | 80 | 242.7 | 1.7 | 0.7 | 2.3 | 1.0 |
| Control II | 80 | 418.0 | 2.5 | 0.6 | 3.7 | 0.9 |
| Panel 800 IU/mL | 80 | 881.2 | 8.6 | 1.0 | 11.5 | 1.3 |
| Panel A | 48 | 26.9 | 0.9 | 3.3 | 1.3 | 4.9 |
| Panel B | 48 | 139.1 | 0.7 | 0.5 | 1.9 | 1.3 |
| Panel C | 48 | 461.6 | 1.7 | 0.4 | 5.4 | 1.2 |
^a Includes within-run, between-run, and between-day variability.
Key to Symbols
. • • Rx ONLY
use by or on the order of a
hysician only (applicable to USA
Massification only).
ARCHITECT cSystems Assays Parameters
| Configure assay parameters - General | ||||
|---|---|---|---|---|
| ● General | O Calibration | O SmartWash | O Results | O Interpretation |
| Assay: IgENumber: 2908 | Type: Photometric | Version: + | ||
| Run controls for onboard reagents by: Lot | ||||
| ● Reaction definition | O Reagent / Sample | O Validity checks | ||
| Reaction mode: End up | ||||
| Primary / Secondary | Read times | |||
| Wavelength: 572 / None | Main: 26 - 27 | |||
| Last required read: 27 | ||||
| Absorbance range: | Color correction: | |||
| Sample blank type: Self | Blank: 19 - 20 | |||
| O Reaction definition | ● Reagent / Sample | O Validity checks | ||
| Reagent: IGEOBDiluent: Saline | Reagent volume: 140 | R170R2 | ||
| Diluent dispense mode: Type 0 | Water volume: | |||
| Dispense mode: Type 0 | Type 2 | |||
| Diluted sample | Diluent | Water | Default dilution | |
| Dilution name Sample | Dilution factor | |||
| STANDARD: 3.5 | 1:1 | |||
| Dil 1 : 15.0 | 3.5 | 135 | 1:10.00 O | |
| O Reaction definition | O Reagent / Sample | ● Validity checks | ||
| Reaction check: | Rate Ratio | |||
| Read time: | A 26-27B 18-19 | |||
| Calculation limits:Minimum: | 0.5000 - 9.00000.0500 | |||
| Maximum absorbance variation: | ||||
| O Calibrators | ● Volumes | O Intervals | O Validity checks | |
| Calibrator: IgE | Diluted sample | |||
| Calibrator level | Sample | Diluent Water | ||
| Blank: Water | 3.5 | |||
| Cal 1: IgE1 | 3.5 | |||
| Cal 2: IgE2 | 3.5 | |||
| Cal 3: IgE3 | 3.5 | |||
| Cal 4: IgE4 | 3.5 | |||
| Cal 5: IgE5 | 3.5 |
---- (section deleted)
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| Quantia IgE Serum/Plasma-Conventional and SI Units | ||
|---|---|---|
| Configure assay parameters - Results | ||
| O General | O SmartWash● Results | O Interpretation |
| Assay: IgEDilution default range: | Assay number: 2908Result units: IU/mL | |
| Low-Linearity: 25.0High-Linearity: 1000.0 | ||
| Gender and age specific ranges:** | ||
| GENDERAGE (UNITS) | NORMAL | EXTREME |
| Configure result units | ||
| Assay: IgEVersion: †Result units: IU/mLDecimal places: | 1 [Range 0 - 4] | |
| Correlation factor: 1.0000 | ||
| Intercept: 0.0000 |
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| Reason SubmissionQualifies as Special 510(k) | This submission for the Quantia IgE assay meets the criteria for aSpecial 510(k) outlined in the FDA guidance “The Special 510(k)Program: Guidance for Industry and Food and DrugAdministration Staff” (September 13, 2019) based on the following: |
|---|---|
| The proposed change is submitted by the manufacturer legally authorized to market the existing device. Performance data is needed to evaluate the change. There is a well-established method to evaluate the change. The data can be reviewed in a summary or risk analysis format. | |
| In addition, the changes in this submission do not introduce: Changes to indications for use or intended use Changes to operating principle |
| Design Control Activities | The following studies were performed to verify performance of themodified device on ARCHITECT c8000 instrument: | |
|---|---|---|
| • Precision | ||
| • | Limit of blank (LoB) | |
| • | Limit of detection (LoD) | |
| • | Limit of quantitation (LoQ) | |
| • | Linearity | |
| • | Extended Measuring Interval/Autodilution | |
| • | Prozone | |
| • | Interferences | |
| • | Tube type/Matrix comparison | |
| • | Method Comparison | |
| • | IgE International Standard recovery |
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Comparison to Predicate Device (K050493)
The following is a description of the similarities and differences between the predicate device; Quantia IgE (K050493), and the subject device, modified Quantia IgE, to demonstrate substantial equivalence.
| Similarities | ||
|---|---|---|
| Item | Predicate Device (K050493) | Subject Device |
| Indications for Use /Intended Use | Quantia IgE is an automated latex enhanced immunoassay for the quantitative in vitro determination of immunoglobulin E (IgE) in human serum or plasma (EDTA, heparin, citrate) using the ARCHITECT c Systems. The measurement of IgE is useful in the clinical diagnosis of IgE-mediated allergies, if used in conjunction with other clinical studies. | Quantia IgE is an automated latex enhanced immunoassay for the quantitative in vitro determination of total immunoglobulin E (IgE) in human serum or plasma (EDTA, heparin, citrate) using the ARCHITECT c Systems. The measurement of total IgE is useful in the clinical diagnosis of IgE-mediated allergies, if used in conjunction with other clinical studies. |
| Measurand | IgE | Same |
| Type of Test | Quantitative | Same |
| Methodology | Latex-enhanced immuoturbidimetric assay | Same |
| Sample Type | Human serum or plasma (EDTA, heparin, citrate) | Same |
| Cut-off | N/A | Same |
| Kit Composition | The Quantia IgE kit consists of:Latex Reagent: Suspension of polystyrene latex particles coated with anti-human IgE monoclonal antibody containing bovine serum albumin, glycine buffer, stabilizers and preservative. Reaction Buffer: Glycine buffer containing bovine serum albumin, stabilizers and preservative. | Same |
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| Differences | ||
|---|---|---|
| Item | Predicate Device (K050493) | Subject Device |
| Linearity | 25.0 - 1000.0 IU/mL | 20.0 - 1000.0 IU/mL |
| Limit of Blank (LoB) | Not defined. | 6.2 IU/mL |
| Limit of Detection (LoD) | 12.9 IU/mL | 11.6 IU/mL |
| Limit of Quantitation (LoQ) | 25.0 IU/mL | 20.0 IU/mL |
The conclusions drawn from the nonclinical and clinical tests demonstrate that the device is as safe, as effective, and performs as well as the legally marketed device (K050493 Quantia IgE) identified at the beginning of this section.
§ 866.5510 Immunoglobulins A, G, M, D, and E immunological test system.
(a)
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.(b)
Classification. Class II (performance standards).