(105 days)
The ADVIA Centaur Active-B12 (Holotranscobalamin)(AB12) assay is for in vitro diagnostic use in the quantitative measurement of holotranscobalamin (holoTC) in human serum using the ADVIA Centaur XP system. Active-B12 (holotranscobalamin) is used as an aid in the diagnosis and treatment of vitamin B12 deficiency.
The ADVIA Centaur AB12 assay is a fully automated, two-step direct immunoassay using chemiluminescent technology. The assay utilizes an acridinium ester-labeled anti-transcobalamin antibody as the Lite Reagent. The Solid Phase consists of biotinylated anti-holotranscobalamin antibody coupled to streptavidin-coated magnetic latex microparticles.
Here's an analysis of the provided text regarding the ADVIA Centaur Active-B12 (Holotranscobalamin) (AB12) assay, structured to address your specific questions about acceptance criteria and the supporting study:
It's important to note that this document is a 510(k) summary, which is a high-level overview. It describes a modification to an already cleared device (K160757), primarily focusing on a change in calibration traceability. Therefore, detailed study protocols and raw data are not typically included in this summary. The summary focuses on demonstrating that the modified device is substantially equivalent to the predicate device and that the modification did not negatively impact its performance.
Since this is a summary of a modification intended to show substantial equivalence, the "acceptance criteria" discussed are largely in the context of ensuring the modification did not degrade performance.
1. Table of Acceptance Criteria and Reported Device Performance
The document states that "The device passed all of the tests based on pre-determined Pass/Fail criteria." However, the specific numerical acceptance criteria for each test are not explicitly provided in this 510(k) summary. It lists the types of tests performed and implies that the results were satisfactory.
| Test Type | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| Accuracy by correlation | Performance comparable to predicate / within acceptable limits | Passed |
| Dilution Linearity | Performance comparable to predicate / within acceptable limits | Passed |
| 20-day precision (repeatability and within-run) | Performance comparable to predicate / within acceptable limits | Passed |
| Detection capability (Limit of blank / detection / quantification) | Performance comparable to predicate / within acceptable limits | Passed (Limit of Quantitation: 5.0 pmol/L) |
| Dilution recovery of WHO IRP (NIBSC 03/178) | Accurate recovery of the WHO Standard | Passed |
| Proficiency sample testing | Performance comparable to predicate / within acceptable limits | Passed |
| Reference range / expected value for asymptomatic population | Comparable to predicate / clinically acceptable reference interval | Mean: 90.24 pmol/L (95% CI: 27.24 to 169.62 pmol/L) - Comparable to predicate (81.91 pmol/L, 95% CI: 28.96 to 168.90 pmol/L) |
2. Sample Size Used for the Test Set and Data Provenance
The summary does not explicitly state the sample sizes used for the various validation tests (Accuracy, Linearity, Precision, Detection Limits, Recovery, Proficiency, or Reference Range).
- Data Provenance: Not explicitly stated, but the reference range study provides a mean and 95% central reference interval for an "asymptomatic population," implying human serum samples. The device itself is for in vitro diagnostic use in human serum. The data would have been collected in the course of validating the device. The manufacturer is Axis-Shield Diagnostics Ltd. in Scotland, UK, so it's plausible the data collection occurred there or in other regions where they conducted studies. The study is retrospective in the sense that these tests are performed after the device (or its modification) has been developed, but the sample collection itself for the reference range could be prospective.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts
This type of information is not applicable and not provided in the context of this device. This is an in vitro diagnostic (IVD) assay that measures a biomarker (holotranscobalamin) directly. The "ground truth" for the test set is established by the analytical reference methods or reference materials (like the WHO International Standard), not by human experts interpreting images or complex clinical scenarios.
4. Adjudication Method for the Test Set
This is not applicable for this type of IVD device. Adjudication methods (like 2+1, 3+1) are typically used in studies involving human interpretation of medical images or clinical data where there might be inter-reader variability. For an IVD assay, the result is a quantitative measurement, and the "ground truth" is based on the accuracy and precision of the analytical measurement itself, often against a validated reference method or material.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This type of study is for evaluating human performance, often with and without AI assistance, especially in radiology or pathology. This device is an automated IVD assay, not an AI-assisted human interpretation tool.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
This device is a standalone algorithm/assay in the sense that it performs the measurement automatically without human intervention during the measurement process. The "performance" mentioned (accuracy, linearity, precision, etc.) are all standalone performance metrics of the assay itself. There is no "human-in-the-loop" once the sample is loaded onto the ADVIA Centaur XP system for this specific measurement.
7. The Type of Ground Truth Used
The ground truth for evaluating the performance of this IVD assay is primarily based on:
- Reference Materials: Specifically, the WHO International Standard for Holotranscobalamin (NIBSC Code 03/178) is highlighted as the new traceability standard for calibration. This serves as a primary ground truth for accurate measurement.
- Comparative Methods: The "Accuracy by correlation" likely involved comparing results from the modified device with those obtained using a reference method or the predicate device.
- Defined Concentrations: For tests like dilution linearity, precision, and detection capability, samples with precisely known or established concentrations of holotranscobalamin are used.
8. The Sample Size for the Training Set
The document does not explicitly mention a "training set" sample size as this is not a machine learning or AI algorithm in the contemporary sense that would require a separate training phase with a distinct dataset for model building. The calibration process implicitly "trains" the device to measure correctly against known standards. The calibration itself uses "2-point Calibration using 2 level calibrators" (Low – 19 pmol/L, High - 121 pmol/L). However, this is not a "training set" in the context of complex ML models.
9. How the Ground Truth for the Training Set Was Established
Given that there isn't a traditional "training set" for a machine learning model, the "ground truth" for the calibration materials (which serve a similar function of establishing correct performance parameters) is established through:
- Reference to the WHO International Standard (NIBSC Code 03/178): The primary modification in this 510(k) is to make the calibration traceable to this international standard. This standard itself would have been value-assigned through a rigorous international collaborative study.
- Internal Reference Material: The predicate device used an "Internal reference material; recombinant holotranscobalamin and phosphate buffer with protein (bovine) stabilizers." This internal standard would have been characterized and assigned values through the manufacturer's own internal assay development and validation processes, likely against an existing recognized reference method or material.
In summary, this 510(k) pertains to a minor modification (calibration traceability) of an existing in vitro diagnostic test. The evaluation focuses on ensuring the modification did not alter the fundamental performance characteristics, and the "acceptance criteria" are implied to be that the modified device performs comparably to the predicate and meets standard analytical performance requirements for IVDs. The "study" refers to a series of analytical verification and validation tests rather than clinical trials with human readers or AI algorithms.
§ 862.1810 Vitamin B
12 test system.(a)
Identification. A vitamin B12 test system is a device intended to measure vitamin B12 in serum, plasma, and urine. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.(b)
Classification. Class II.