(59 days)
The Access Vitamin B12 assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of vitamin B12 levels in human serum and plasma (heparin) using the Access Immunoassay Systems. Measurements obtained by this device are used in the diagnosis and treatment of anemias of gastrointestinal malabsorption.
The Access Vitamin B12 assay is a competitive binding immunoenzymatic assay. The Access Vitamin B12 reagent kit is in a liquid ready-to-use format designed for optimal performance on Beckman Coulter's immunoassay analyzers. Each reagent kit contains two reagent packs. Other items needed to run the assay include substrate, calibrators, and wash buffer.
The provided document is a 510(k) Premarket Notification from the FDA for a diagnostic device, the "Access Vitamin B12" assay, manufactured by Beckman Coulter, Inc. It details the device's technical characteristics, its intended use, a comparison to a predicate device, and summaries of performance studies.
Here's the breakdown of the acceptance criteria and study proving the device meets them, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document describes the acceptance criteria and observed performance for several analytical studies conducted to demonstrate substantial equivalence of the new Access Vitamin B12 assay on the Dxl 9000 Access Immunoassay Analyzer to the predicate device.
| Performance Characteristic | Acceptance Criteria | Reported Device Performance | Met Criteria? |
|---|---|---|---|
| Method Comparison | R$^2 \ge 0.90$ | R$^2 = 0.97$ | Yes |
| Slope of 1.00 ± 0.14 | Slope = 1.00 (95% CI: 0.96 - 1.02) | Yes | |
| Intercept (No explicit criterion, but 0 is ideal) | Intercept = 6.1 (95% CI: -0.16 - 15) | Yes (Implied) | |
| Imprecision | SD $\le 12$ pg/mL for values $\le 100$ pg/mL | Observed total SD between 6 – 9 for samples $\le 100$ pg/mL | Yes |
| CV $\le 12.0$ % for values $> 100$ pg/mL | Observed total %CV between 2.7% and 7.7% for samples $> 100$ pg/mL | Yes | |
| Linearity | (Implicitly: demonstrate linearity throughout AMR) | Met the acceptance criterion; linear throughout 68 - 1,500 pg/mL | Yes |
| Limit of Detection (LoD) | LoD $\le 68$ pg/mL (50 pmol/L) | Observed LoD = 49 pg/mL (36 pmol/L) | Yes |
| Limit of Blank (LoB) | (Implicitly: demonstrate LoB value) | Claimed LoB = 50 pg/mL (37 pmol/L); Estimated LoB = 35 pg/mL (26 pmol/L) | Yes (Estimated LoB is lower than claimed) |
| Limit of Quantitation (LoQ) | LoQ $\le 68$ pg/mL (50 pmol/L) | Estimated LoQ (20% CV) = 42 pg/mL; Maximum observed LoQ = 68 pg/mL; Reported LoQ as 49 pg/mL (following CLSI EP17-A2 recommendation that LoQ $\ge$ LoD) | Yes |
2. Sample Size Used for the Test Set and Data Provenance
- Method Comparison: N = 122 samples.
- Imprecision: 6 serum samples with varying Vitamin B12 concentrations were assayed. Each sample was assayed in duplicate, twice per day, over 21 days (resulting in 84 replicates per sample, 6 samples x 84 replicates = 504 total assays for imprecision).
- Linearity, LoB, LoD, LoQ: Specific sample sizes for these studies are not explicitly stated as 'N' values in the text, but the studies were performed (e.g., "verification studies") following CLSI protocols.
- Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. Given it's a clinical laboratory device study for regulatory submission, they are typically prospective analytical validation studies conducted in a controlled lab environment.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
N/A. This device is a quantitative diagnostic assay (Vitamin B12 levels) rather than an AI/ML-based image analysis or pattern recognition device that would typically rely on expert human consensus for ground truth. The "ground truth" for these analytical performance studies is established by the reference methods (predicate device measurements, defined concentrations for linearity/imprecision, and analytical standards for LoB/LoD/LoQ).
4. Adjudication Method (e.g., 2+1, 3+1, none) for the Test Set
N/A. Adjudication methods are not applicable here since the "ground truth" is determined by established analytical measurements and reference values, not by human interpretation requiring consensus.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
N/A. MRMC studies are typically performed for imaging devices or AI-assisted diagnostic tools where human readers interpret cases, and the AI's impact on reader performance is assessed. This is a standalone in-vitro diagnostic (IVD) assay designed to provide quantitative results, not assist human readers in interpreting complex cases. The study effectively compares the new instrument (Dxl 9000) to the predicate instrument (Access Immunoassay System), not human readers.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
While the term "standalone" is often used in the context of AI algorithms, this device functions as a standalone quantitative diagnostic assay. The performance studies (Method Comparison, Imprecision, Linearity, LoB/LoD/LoQ) demonstrate the analytical performance of the device itself (the "algorithm" being the assay chemistry and instrument processing) without human intervention in the result determination. The results are quantitative outputs (pg/mL or pmol/L of Vitamin B12).
7. The Type of Ground Truth Used
The ground truth for the analytical performance studies was established through:
- Method Comparison: Comparison against the predicate Access Vitamin B12 assay run on the Access Immunoassay System.
- Imprecision: Known or consistent concentrations of Vitamin B12 samples measured repeatedly.
- Linearity: Serially diluted samples or samples prepared with known, varied concentrations.
- LoB/LoD/LoQ: Use of blank samples, low-concentration samples, and statistical methods (CLSI EP17-A2 protocol) to determine limits.
Overall, the ground truth relies on analytical reference methods, known sample concentrations, and statistical methods as per industry best practices (CLSI guidelines) for IVD devices.
8. The Sample Size for the Training Set
N/A. This is a specific analytical test kit (immunoassay) that functions based on established biochemical principles, not a machine learning algorithm that requires a "training set" in the conventional sense of AI. Its performance is inherent to its design and chemical reagents, validated through the analytical performance studies described.
9. How the Ground Truth for the Training Set Was Established
N/A. As stated above, this device does not utilize a training set in the AI sense. Its "ground truth" for development and validation are based on chemical and analytical principles and reference standards.
§ 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.