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The Axis-Shield Active-B12 (Holotranscobalamin) assay is an enzyme-immunoassay (EIA) for the quantitative determination of holotranscobalamin (HoloTC) in human serum. HoloTC (vitamin B12 bound to transcobalamin) is used as an aid in the diagnosis and treatment of vitamin B12 deficiency.

Device Description

The Axis-Shield Active-B12 (Holotranscobalamin) device contains the following components: a microtitre plate with 8 x 12-well breakapart strips coated with a anti-holotranscobalamin murine monoclonal antibody, in a resealable foil pack with desiccant; ready-to-use calibrators, low and high controls (phosphate buffer containing protein (bovine) stabiliser and sodium azide preservative with or without recombinant HoloTC); ready-to-use pre-treatment solution; murine anti-human transcobalamin alkaline phosphatase conjugate; para-NitroPhenyl Phosphate (pNPP) substrate; wash buffer (8x); ready-to-use stop solution.

AI/ML Overview

Here is a breakdown of the acceptance criteria and study information for the Axis-Shield Active-B12 (Holotranscobalamin) device, based on the provided 510(k) summary:

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Predicate)	Reported Device Performance (Axis-Shield Active-B12)
Intended Use	Quantitative determination of Holotranscobalamin in human serum, aid in diagnosis and treatment of vitamin B12 deficiency.	Quantitative determination of holotranscobalamin (HoloTC) in human serum, aid in diagnosis and treatment of vitamin B12 deficiency.
Antibodies Employed	Murine monoclonal antibody 3C4, Murine monoclonal antibody 3-11	Murine monoclonal antibody 3C4, Murine monoclonal antibody 3-11
Specimen Type	Serum and Serum Separator	Serum and Serum Separator
Measuring Interval	5.0 to 128.0 pmol/L	10 to 128 pmol/L
Detection Limits	Limit of Quantitation of ≤ 5.0 pmol/L	Limit of Quantitation of 8.3 pmol/L (Limit of Blank: 4.9 pmol/L, Limit of Detection: 8.1 pmol/L)
Linearity on Dilution	LOQ to Calibrator F	LOQ to Calibrator F (demonstrated linearity from 5.3 to 156.0 pmol/L)
Expected Values (95% range) in Asymptomatic Population	25.1 to 165.0 pmol/L (n=181)	21 to 123 pmol/L (n=135)
Cross-reactivity (Apotranscobalamin)	No detectable carryover with Apotranscobalamin at 500 pmol/L	Maximum deviation in holotranscobalamin concentration of ≤10% in the presence of 500 pmol/L apotranscobalamin (ranged from -5% to 1%).
Cross-reactivity (Haptocorrin)	No detectable carryover with Haptocorrin at 5000 pmol/L	Maximum deviation in holotranscobalamin concentration of ≤10% in the presence of 5000 pmol/L haptocorrin (ranged from -5% to 1%).
Interference (Bilirubin)	≤ 10% with Bilirubin at 20 mg/dL	Maximum deviation in holotranscobalamin concentration of ≤10% with Bilirubin at 30 mg/dL (reported no interference found up to 300 mg/dL in separate table for device performance).
Interference (Haemoglobin)	≤ 10% with Haemoglobin at 200 mg/dL	Maximum deviation in holotranscobalamin concentration of ≤10% with Haemoglobin at 5 mg/mL (reported no interference found up to 500 mg/dL in separate table for device performance).
Interference (Triglycerides)	≤ 10% with Triglycerides at 850 mg/dL	Maximum deviation in holotranscobalamin concentration of ≤10% with Triglycerides at 30 mg/mL (reported no interference found up to 3000 mg/dL in separate table for device performance).
Interference (Rheumatoid Factor)	≤ 10% with Rheumatoid Factor at 70 IU/mL	Maximum deviation in holotranscobalamin concentration of ≤10% with Rheumatoid Factor at 75 IU/mL (reported no interference found up to 7500 IU/dL in separate table for device performance).
Interference (Total Protein)	≤ 10% with Total protein at 10 g/dL	Maximum deviation in holotranscobalamin concentration of ≤10% with Total protein at 90 mg/mL (reported no interference found up to 9000 mg/dL in separate table for device performance).
Imprecision (Total %CV)	≤ 5.8%	≤ 11.5% (observed range from 4.8% to 11.5% across various samples and conditions)
Imprecision (Within-run %CV)	0.97	> 0.97
Matrix Comparison (Serum clot vs SST) - Correlation (r)	0.98	0.98
Matrix Comparison (Serum clot vs SST) - Overall % bias	36 specimens** were used for the correlation study comparing serum (clot) and serum separator (SST) tubes. Data provenance not specified, likely retrospective from a clinical setting.

Method Comparison: 111 specimens from apparently healthy adults were used. Data provenance not specified, but the description "apparently healthy adults" suggests prospective collection or selection from a healthy cohort.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This device is an in-vitro diagnostic assay for quantitative determination of a biomarker (Holotranscobalamin). The ground truth for such assays is typically established through:

Reference Methods: Comparison to established, clinically validated methods (like the predicate device) or gold standard analytical techniques.
Known Concentrations: Use of samples with known, spiked concentrations for analytical performance validation (e.g., linearity, detection limits).
Clinical Diagnosis: Correlating assay results with clinical diagnosis of B12 deficiency (though a direct study for this is not detailed for the subject device beyond the general "aid in diagnosis").

Thus, the ground truth is established through laboratory measurements and comparison to a legally marketed predicate device, rather than through expert consensus on diagnostic images or interpretations. Therefore, there were no human experts establishing the ground truth in the way described (e.g., radiologists interpreting images).

4. Adjudication method for the test set

Not applicable, as this is a quantitative diagnostic assay. Adjudication methods like 2+1 or 3+1 are typically used for qualitative or interpretive tasks, often in imaging, where human experts might disagree.

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 immunoassay device, not an AI-assisted diagnostic tool that aids human readers.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

Yes, this device is a standalone (algorithm only) device if you consider the "algorithm" to be the immunoassay protocol and the detector quantifying the colored end-product. There is no human-in-the-loop for the final quantitative result generation from the assay. The intent is for the device to provide a direct quantitative holotranscobalamin level.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth used for demonstrating substantial equivalence and performance was primarily based on:

Comparison to the predicate device: The ARCHITECT Active-B12 (Holotranscobalamin) assay served as the reference standard for the method comparison study. This implies the predicate's results were considered the "ground truth" for comparative purposes.
Analytical validation standards: For metrics like linearity, detection limits, cross-reactivity, and interference, the ground truth is established by carefully prepared samples with known concentrations or compositions, following established analytical chemistry principles.
Internal reference materials/controls: For precision studies, characterized control samples with established mean values are used.

8. The sample size for the training set

This device is a traditional immunoassay, not a machine learning or AI algorithm in the modern sense that requires a "training set" for model development. Therefore, there is no explicit training set as would be understood in AI/ML validation. The development and optimization of the assay would have involved various experimental batches and iterative improvements, but these do not constitute a formal "training set" in the context of AI regulatory submissions.

9. How the ground truth for the training set was established

Not applicable, as there is no formal "training set" in the AI/ML sense. The development of the assay involved standard biochemical and immunological research and development processes.

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