(50 days)
Immunoassay for the in vitro quantitative determination of immunoglobulin E in human serum and plasma. Determination of total IgE is useful as an aid in the diagnosis of allergic diseases. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the Roche Elecsys 2010 and MODULAR ANALYTICS E170 (Elecsys module) immunoassay analyzers.
The Elecsys IgE II immunoassay is a two step sandwich immunoassay with streptavidin microparticles and electrochemiluminescence detection. Results are determined using a calibration curve that is generated specifically on each instrument by a 2 point calibration and a master curve provided with the reagent bar code.
The given document is a 510(k) summary for the Elecsys IgE II Immunoassay. It describes the device, its intended use, and compares it to a predicate device. However, it does not contain specific acceptance criteria or a dedicated study section detailing how the device met those criteria in the format typically used for AI/ML device evaluations.
The document focuses on demonstrating substantial equivalence to a previously approved device (Elecsys IgE Immunoassay, K984326, K961481/A003) for the purpose of 510(k) clearance. This means the assessment is primarily a device comparison rather than a standalone performance study against pre-defined acceptance criteria for a novel device.
Therefore, many of the requested details about acceptance criteria, study design, sample sizes, ground truth establishment, expert involvement, and MRMC studies are not present in this type of submission.
Here's a breakdown based on the information available:
1. Table of Acceptance Criteria and Reported Device Performance
As this is a substantial equivalence submission for an in vitro diagnostic (IVD) immunoassay, the "acceptance criteria" are implicitly met by demonstrating comparable performance to the predicate device across various analytical characteristics. There isn't a single table of "acceptance criteria" with pass/fail thresholds in the typical sense for AI/ML performance. Instead, the document presents comparative performance data to show the new device is "substantially equivalent" to the predicate.
The table below summarizes the key analytical performance characteristics presented in the document, comparing the Elecsys IgE II (Modified Device) to the predicate Elecsys IgE. The "acceptance criteria" here are effectively that the new device's performance should be comparable enough to the predicate to be considered substantially equivalent.
| Performance Characteristic | Predicate Device (Elecsys IgE) | Elecsys IgE II (Modified Device) | "Acceptance Criteria" (Implicit for Substantial Equivalence) | Outcome |
|---|---|---|---|---|
| Intended Use | Immunoassay for IgE quantification in human serum and plasma; aid in diagnosis of allergic diseases. | Same | Functionally equivalent to predicate. | Met |
| Analyzers | Roche Elecsys 1010/2010 and MODULAR ANALYTICS E170 | Roche Elecsys 2010 and MODULAR ANALYTICS E170 | Compatible with similar clinical analyzer platforms. | Met |
| Traceability | Standardized against 2nd IRP WHO Reference Standard 75/502 | Same | Same standardization as predicate. | Met |
| Assay Protocol | Sandwich | Same | Same assay principle. | Met |
| Sample Type | Serum and plasma | Same | Same clinical utility. | Met |
| Calibrator, Calibration Verification & Controls | IgE CalSet, IgE CalCheck, PreciControl Universal | Same | Uses same calibration materials and controls. | Met |
| Measuring Range | 0.10 - 2500 IU/mL | Same | Same analytical range. | Met |
| Analytical Sensitivity | 0.10 IU/mL | Same | Same lower limit of detection. | Met |
| Functional Sensitivity | 0.50 IU/ml | Same | Same functional lower limit. | Met |
| Composition | R1: 2.4 mg/L AB-Bi, buffer, preservative; R2: 4.8 mg/L AB-Ru, buffer, preservative; M: 0.72 mg/ml streptavidin-coated microparticles, preservative | R1: 2.5 mg/L (mono-Bi)AB-Bi, buffer, preservative; R2: 5.5 mg/L AB-Ru, buffer, preservative; M: 0.72 mg/ml streptavidin-coated microparticles, preservative | Minor compositional changes that do not alter fundamental performance. | Met |
| Dilution Recommendation | > 60 IU/mL | > 125 IU/mL | Acceptable adjustment based on method validation. | Met |
| Interferences (Bilirubin) | No affect up to 37 mg/dl | Same | Comparable resistance to common interferents. | Met |
| Interferences (Hemoglobin) | No affect up to 1.1 g/dl | No affect up to 0.1 g/dl | While the value is different, the FDA found it acceptable for substantial equivalence. | Met |
| Interferences (Triglycerides) | No affect up to 2200 mg/dl | Same | Comparable resistance to common interferents. | Met |
| Interferences (Biotin) | No affect up to 100 ng/ml | Same | Comparable resistance to common interferents. | Met |
| Precision (Elecsys 2010 Intra-assay CV) | HS1 3.6% @ 5.18 IU/mL; HS2 3.2% @ 398 IU/mL; HS3 2.4% @ 1010 IU/mL | HS1 4.1% @ 32.7 IU/mL; HS2 2.4% @ 265 IU/mL; HS3 2.6% @ 1295 IU/mL | Comparable precision performance. | Met |
| Precision (Elecsys 2010 Total CV) | HS1 4.2% @ 5.18 IU/mL; HS2 3.9% @ 398 IU/mL; HS3 3.1% @ 1010 IU/mL | HS1 5.1% @ 32.7 IU/mL; HS2 3.8% @ 265 IU/mL; HS3 3.9% @ 1295 IU/mL | Comparable precision performance. | Met |
| Precision (E170 Intra-assay CV) | HS1 2.3% @ 3.36 IU/mL; HS2 2.2% @ 457 IU/mL; HS3 2.6% @ 1128 IU/mL | HS1 1.4% @ 4.4 IU/mL; HS2 0.7% @ 261 IU/mL; HS3 1.0% @ 1018 IU/mL | Comparable precision performance. | Met |
| Precision (E170 Total CV) | HS1 4.3% @ 3.31 IU/mL; HS2 3.8% @ 443 IU/mL; HS3 6.5% @ 1215 IU/mL | HS1 2.7% @ 30.2 IU/mL; HS2 2.8% @ 245 IU/mL; HS3 3.4% @ 1207 IU/mL | Comparable precision performance. | Met |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set (Clinical Performance): The document does not explicitly present a "test set" in the context of clinical performance data in the way an AI/ML device would. Instead, it compares analytical performance characteristics (sensitivity, measuring range, precision, interference) of the new device against the predicate.
- For precision studies, the data points represent multiple measurements ("HS1", "HS2", "HS3" at different IgE concentrations) for intra-assay and total variation. The exact number of individual patient samples or replicates used to derive these CVs is not specified in the summary, but typical precision studies involve multiple runs over several days.
- For interference studies, it indicates "No affect up to," implying specific concentrations of potential interferents were tested. The number of samples or replicates used for these tests is not specified.
- Data Provenance: Not explicitly stated, but for IVD assays, analytical performance studies are typically conducted by the manufacturer in a controlled laboratory setting. It's likely a mix of internal validation studies, and possibly some external site testing, but specific countries or retrospective/prospective nature is not detailed.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
Not applicable for this type of IVD immunoassay submission. The "ground truth" for analytical performance studies is based on established laboratory measurement techniques, reference standards (like WHO Reference Standard 75/502 for IgE), and accepted statistical methods for evaluating precision, sensitivity, etc. There are no "experts" establishing a subjective ground truth for image interpretation or diagnosis in this context.
4. Adjudication Method for the Test Set
Not applicable. As described above, this is an analytical performance assessment, not a clinical adjudication of diagnostic outcomes by human readers.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
Not applicable. This device is an in vitro diagnostic immunoassay, not an AI/ML diagnostic aid intended to assist human readers (e.g., radiologists interpreting images). Therefore, an MRMC study is not relevant.
6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done
Not applicable. The device is a laboratory instrument and reagent system that quantitatively measures IgE. Its performance is inherent to the assay and instrument, and it operates without human intervention in the result generation itself, but a lab technician operates the instrument. It is not an "algorithm" in the AI/ML sense.
7. The Type of Ground Truth Used
The ground truth for the performance characteristics presented (e.g., measuring range, analytical sensitivity, functional sensitivity, precision) is based on:
- Reference Standards: Specifically, the 2nd IRP WHO Reference Standard 75/502 for IgE.
- Defined Analytical Methods: The quantitative measurement of IgE following standardized laboratory procedures.
- Statistical Analysis: Metrics like Coefficient of Variation (CV) for precision are derived from repeated measurements using established statistical methods.
8. The Sample Size for the Training Set
Not applicable. This device is an immunoassay, not a machine learning algorithm that requires a "training set."
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" for this type of immunoassay.
§ 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).