(130 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® Active-B12 (AB12) quality control is for in vitro diagnostic use to monitor the precision and accuracy of the ADVIA Centaur AB12 (Holotranscobalamin) assay using the ADVIA Centaur systems.
The ADVIA Centaur® Active-B12 (AB12) Master Curve Material (MCM) is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur AB12 (Holotranscobalamin) assay using the ADVIA Centaur systems.
The ADVIA Centaur AB12 assay is a fully automated, two-step direct immunoassay using chemiluminescent technology. The assay utilizes an acridinium ester-labeled antitranscobalamin antibody as the Lite Reagent. The Solid Phase consists of biotinylated antiholotranscobalamin antibody coupled to streptavidin-coated magnetic latex microparticles.
This document describes the ADVIA Centaur Active-B12 (Holotranscobalamin) (AB12) assay, a device for in vitro diagnostic use in the quantitative measurement of holotranscobalamin (holoTC) in human serum to aid in the diagnosis and treatment of vitamin B12 deficiency.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. A table of acceptance criteria and the reported device performance:
| Performance Characteristic | Acceptance Criteria (from predicate or general principles) | Reported Device Performance (ADVIA Centaur AB12) |
|---|---|---|
| Linearity | Not explicitly stated (evaluated according to CLSI protocol EP6-A) | 5.00 - 146.00 pmol/L |
| Dilution Linearity | Not explicitly stated (recovery and parallelism assessed) | Average recovery: 93.77% (Range: 90.86% - 98.61%) |
| Measuring Interval | Not explicitly stated (range of measurable concentrations) | 5.00 - 146.00 pmol/L |
| Limit of Blank (LoB) | Not explicitly stated (determined as per CLSI Document EP17-A2) | 0.74 pmol/L |
| Limit of Detection (LoD) | Not explicitly stated (determined as per CLSI Document EP17-A2, 95% probability) | 1.08 pmol/L |
| Limit of Quantitation (LoQ) | Not explicitly stated (determined as per CLSI Document EP17-A2, total CV of 8%) | 5.00 pmol/L |
| High Dose Hook Effect | No significant hook effect (specifically, assaying greater than 146.00 pmol/L) | No hook effect observed up to 1867.80 pmol/L |
| Cross-reactivity | ≤ 10% cross-reactivity with specified substances | Apotranscobalamin: 0.2% / -0.1% |
| Haptocorrin: -0.4% / -0.4% | ||
| Interference | ≤ 10% interference with specified substances at indicated concentrations | All tested substances (Biotin, Cholesterol, Conjugated Bilirubin, Hemoglobin, Human IgG, Methotrexate, Perimethamine, Rheumatoid Factor, Silwet L720, Total Protein, Unconjugated Bilirubin, Triglyceride) demonstrated ≤ 10% interference at the specified highest concentrations. |
| Precision (Within-Lab %CV) | Not explicitly stated (compared to predicate, which has Total %CV ≤ 5.8%) | Within-Lab (Total) %CV ≤ 4.7% (Range: 4.0% - 4.7%) |
| Precision (Repeatability %CV) | Not explicitly stated (compared to predicate, which has Within-run %CV ≤ 4.4%) | Repeatability (Within-run) %CV ≤ 3.2% (Range: 1.8% - 3.2%) |
| Method Comparison (Correlation with Predicate) | Not explicitly stated (substantially equivalent performance expected) | r = 0.95 (Passing-Bablok regression: ADVIA Centaur AB12 = 0.97 (CMIA) - 0.99 pmol/L) |
| Expected Values (Reference Interval) | Not explicitly stated (established for the assay) | 95% central reference interval from 28.96 – 168.90 pmol/L |
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):
- Linearity: The number of samples used is not explicitly stated, but it involved "Two samples containing high levels of active-B12" mixed with "a pool of artificial serum matrix."
- Dilution Linearity: Five samples were used.
- Detection Capability (LoB, LoD, LoQ): The raw sample sizes for these determinations are not specified but are described as being determined according to CLSI Document EP17-A2, which typically involves multiple replicates and measurements.
- High Dose Hook: Patient samples with "active-B12 levels as high as 1867.80 pmol/L" were tested. The exact number of samples is not stated.
- Cross-reactivity: Populations evaluated included "other B12 proteins apotranscobalamin and haptocorrin" at two different concentrations each. The number of samples per concentration is not stated.
- Interference: The number of unique samples or runs for each interfering substance is not explicitly stated.
- Precision: Five serum precision panel members were used. Each sample was tested in replicates of 2 in two runs per day over 20 days, resulting in 80 observations per sample for each reagent lot.
- Method Comparison: 104 serum samples were used.
- Expected Values (Reference Range): 241 apparently healthy males (n = 103) and females (n = 138) were used. The age range was 21 - 67 years.
The document does not explicitly state the country of origin of the data or whether the studies were retrospective or prospective, beyond stating that the device is manufactured by Axis-Shield Diagnostics Ltd. in Scotland, UK. The reference range study involved "apparently healthy males and females," suggesting prospective collection for that specific study.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience):
This device is an in-vitro diagnostic assay for quantitative measurement of holotranscobalamin. The "ground truth" for such assays is typically established by established reference methods, calibrated standards, or the concentration values determined by a legally marketed predicate device. Experts are not directly involved in establishing "ground truth" for individual test results in the same way they would be for image interpretation.
- For method comparison, the "ground truth" reference values were obtained from the ARCHITECT Active-B12 (Holotranscobalamin) assay (K112443), which is the legally marketed predicate device.
- For reference range establishment, the "ground truth" is derived from the statistical analysis of results from a healthy population, following established protocols (EP28-A3c).
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:
Not applicable. This is not a study involving human interpretation or subjective assessment that would require adjudication. The performance is based on quantitative measurements.
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 is an in-vitro diagnostic device, not an AI-assisted diagnostic tool that involves human readers interpreting cases.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
Yes, the studies presented are standalone performance evaluations of the ADVIA Centaur Active-B12 assay. The performance characteristics (linearity, precision, detection capability, interference, cross-reactivity, method comparison) are intrinsic to the device and do not involve human intervention in the interpretive output generation. The assay quantitatively measures holotranscobalamin levels.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):
The ground truth used depends on the specific performance characteristic:
- Assay values for clinical samples: The ARCHITECT Active-B12 (Holotranscobalamin) assay (CMIA) was used as the comparator or "reference" for method comparison studies.
- Known concentrations: For studies like linearity, dilution linearity, detection capability, high dose hook, cross-reactivity, and interference, the "ground truth" is based on known spiked concentrations of substances or defined samples with expected values (e.g., precision panel members with established active-B12 concentrations).
- Population statistics: For expected values (reference range), the "ground truth" is derived from statistical analysis of a healthy reference population, following CLSI guidelines.
8. The sample size for the training set:
Not applicable. This device is an in-vitro diagnostic assay, not a machine learning or AI model that requires a distinct training set in the conventional sense. The "training" or development of such assays involves reagent formulation, optimization, and calibration based on known standards and samples, but not a "training set" like that used for algorithms.
9. How the ground truth for the training set was established:
Not applicable. As explained in point 8, there isn't a "training set" for an in-vitro diagnostic assay in the same way there is for an AI algorithm. The assay is developed and optimized using known standards and calibrated samples, where the "ground truth" for these is established through highly accurate reference methods or certified reference materials. The calibration of the device itself relies on "Master Curve Material" (MCM) with established values.
§ 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.