(157 days)
System reagent for the quantitative determination of IgG immunoglobulins in human serum, plasma and cerebrospinal fluid on Beckman Coulter AU analyzers. The measurement of IgG aids in the diagnosis of abnormal protein metabolism and the body's lack of ability to resist infectious agents.
The device consists of two reagents: R1 buffer (Tris buffer pH 7.2, polyethylene glycol 6000) and R2 (goat anti-IgG antiserum). The reagents contain sodium azide as preservative.
When a sample is mixed with R1 buffer and R2 antiserum solution, human IgG reacts specifically with anti-human IgG antibodies to yield insoluble aggregates. Immune complexes formed in solution scatter light in proportion to their size, shape and concentration. Turbidimeters then measure the reduction of incidence light due to reflection, absorption or scatter. In the AU procedure, the decrease in intensity of light transmitted (increase in absorbance) through particles suspended in solution is as a result of complexes formed during the antigen-antibody reaction.
The provided text describes a 510(k) premarket notification for a medical device called "IgG Regulation Number: 21 CFR 866.5510" (Trade/Device Name: IgG). This device is a system reagent for the quantitative determination of IgG immunoglobulins in human serum, plasma, and cerebrospinal fluid on Beckman Coulter AU analyzers. The document details the comparison testing performed to demonstrate substantial equivalence to a predicate device.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
1. A table of acceptance criteria and the reported device performance
The document doesn't explicitly present a "table of acceptance criteria" in the format of pass/fail thresholds. Instead, it compares the performance of the candidate device (IgG Reagent on DxC 700 AU Beckman Coulter Analyzers) to the predicate device (Olympus IgG Reagent (K073490) on AU400/400ᵉ/480, AU600/640/640ᵉ/680, and AU2700/5400/AU5800 Beckman Coulter Analyzers). The acceptance criterion is essentially that the candidate device's performance is "substantially equivalent" to the predicate, meaning it should perform at least as well as the predicate for key metrics.
Here's a table summarizing the comparison, with the predicate's performance serving as the de-facto acceptance criteria for equivalence:
| Feature | Predicate Device Performance (Acceptance Criteria for Equivalence) | Candidate Device Performance (Reported Performance) | Met? |
|---|---|---|---|
| Precision | |||
| Serum & Plasma | With-run: $\le$ ±3.5% mg/dL | ||
| Total: $\le$ ±6.0% mg/dL | Same | Yes (stated "Same") | |
| CSF | With-run: $\le$ ±6.0% or ±0.4 mg/dL | ||
| Total: $\le$ ±7.5% or ±0.5mg/dL | Same | Yes (stated "Same") | |
| Sensitivity (LoQ) | |||
| Serum & Plasma | 75 mg/dL | Same | Yes (stated "Same") |
| CSF | 2 mg/dL | Same | Yes (stated "Same") |
| Interference | |||
| Serum & Plasma | Bilirubin: Interference less than 3% up to 40 mg/dL | ||
| Hemolysis: Interference less than 3% up to 500 mg/dL | |||
| Lipemia: Interference less than 5% up to 1000 mg/dL Intralipid | |||
| RF: Interference less than 7% up to 1200 IU/mL Rheumatoid Factor | Similar | ||
| The criteria for No Significant Interference (NSI) is recovery within 10% of the initial value. | |||
| Bilirubin: NSI up to 40 mg/dL Bilirubin | |||
| Hemolysis: NSI up to 500 mg/dL Hemolysate | |||
| Lipemia: NSI up to 1000 mg/dL Intralipid | |||
| RF: NSI up to 1200 IU/mL Rheumatoid Factor | Yes (stated "Similar" and provided comparable NSI criteria) | ||
| CSF | Bilirubin: Interference less than 3% up to 40 mg/dL | ||
| Hemolysis: Interference less than 3% up to 500 mg/dL | |||
| Lipemia: Interference less than 5% up to 1000 mg/dL Intralipid | |||
| RF: Interference less than 7% up to 1200 IU/mL Rheumatoid Factor | Similar | ||
| The criteria for No Significant Interference (NSI) is recovery within 10% of the initial value. | |||
| Bilirubin: NSI up to 40 mg/dL Bilirubin | |||
| Hemolysis: NSI up to 500 mg/dL Hemolysate | |||
| Lipemia: NSI up to 1000 mg/dL Intralipid | |||
| RF: NSI up to 1200 IU/mL Rheumatoid Factor | Yes (stated "Similar" and provided comparable NSI criteria) | ||
| Analytic Range | Serum & Plasma: 75 – 3000 mg/dL | ||
| CSF: 2 - 50 mg/dL | Same | Yes (stated "Same") | |
| Onboard Stability | 90 Days | Same | Yes (stated "Same") |
| Calibration Stability | Serum & Plasma: 90 Days | ||
| CSF: 2 Days | Same | Yes (stated "Same") |
The study proving the device meets the acceptance criteria:
The study conducted is a comparative performance study between the candidate device and its predicate.
2. Sample size used for the test set and the data provenance
The document mentions "Comparison testing" was conducted, including "Method Comparison, Linearity, Sensitivity, Reference Interval, Interference, In use (On board) & Calibrator Stability, Precision, Prozone, Auto-dilution." However, it does not specify the sample sizes used for each of these tests.
Regarding data provenance: The document does not specify the country of origin of the data. It does not explicitly state whether the data was retrospective or prospective. Given the context of a 510(k) submission for an in vitro diagnostic device, the data would typically be generated in a controlled manner, likely through prospective experimental studies, to demonstrate performance characteristics.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This information is not applicable and not provided in the document. This device is an in-vitro diagnostic (IVD) for quantitative measurement of immunoglobulins. The "ground truth" for such devices is established through reference methods, calibrated materials, or highly accurate laboratory techniques, rather than expert consensus (e.g., radiological reads). The device measures a biomarker quantitatively, so the "truth" is the actual concentration of IgG, determined by a highly accurate measurement system.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
This information is not applicable and not provided. Adjudication methods like "2+1" or "3+1" are relevant for subjective interpretations (e.g., image reading) where multiple human readers might disagree, requiring a third or fourth reader to resolve discrepancies. For a quantitative IVD, the measurement itself is the "output," and its accuracy is assessed against a reference method or known concentration standards, not by human adjudication of its output.
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
This information is not applicable and not provided. An MRMC study is typically performed for AI or computer-aided detection/diagnosis (CAD) systems that assist human readers (e.g., radiologists interpreting images). This device is a lab assay system, not an AI system assisting human interpretation.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the performance data presented (Precision, Sensitivity, Interference, Analytical Range, Stability) for the "Candidate Device: IgG Reagent" are inherent performance characteristics of the assay system itself, irrespective of human intervention in the interpretation of the result. The device quantitatively determines IgG levels. The study assesses the accuracy, precision, and other analytical performance parameters of the device's measurement capability in a standalone fashion.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The "ground truth" for this type of quantitative in-vitro diagnostic device would be established by:
- Reference materials/standards with known concentrations: Calibrators and controls with certified IgG concentrations are used to verify the accuracy and linearity of the measurement.
- Reference methods: Highly accurate and precise laboratory methods (e.g., isotope dilution mass spectrometry for some analytes, or established validated methods) that serve as the gold standard for measuring the analyte.
- Sample spiking: Adding known quantities of the analyte to samples to assess recovery.
While the document doesn't explicitly state the specific ground truth methods for each test, the standard practice for IVDs involves these types of analytical validation studies.
8. The sample size for the training set
This information is not applicable and not provided. This device is a chemical reagent and an assay system, not a machine learning or AI model that requires a "training set" in the computational sense. The device's performance is based on chemical reactions and optical detection, not learned patterns from data.
9. How the ground truth for the training set was established
This information is not applicable for the same reasons as #8. No "training set" in the AI/ML context exists for this type of device.
§ 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).