ARCHITECT 25-OH Vitamin D 5P02, ARCHITECT 25-OH Vitamin D 5P02 Calibrators, ARCHITECT 25-OH Vitamin D 5P02 Controls by ABBOTT LABORATORIES

The ARCHITECT 25-OH Vitamin D assay is a chemiluminescent microparticle immunoassay (CMIA) for the quantitative determination of 25-hydroxyvitamin D (25 OH vitamin D) in human serum and plasma. The ARCHITECT 25-OH Vitamin D assay is to be used as an aid in the assessment of vitamin D sufficiency.

The ARCHITECT 25-OH Vitamin D Calibrators are for the ARCHITECT iSystem when used for the quantitative determination of 25 hydroxyvitamin D (25-OH vitamin D) in human serum and plasma.

The ARCHITECT 25-OH Vitamin D Controls are for the estimation of test precision and the detection of systematic analytical deviations of the ARCHITECT iSystem when used for the quantitative determination of 25-hydroxyvitamin D (25-OH vitamin D) in human serum and plasma.

Device Description

The ARCHITECT 25-OH Vitamin D assay is a quantitative delayed one-step competitive immunoassay to determine the presence of vitamin D in human serum and plasma using CMIA technology with flexible assay protocols, referred to as Chemiflex. The reagent kit contains Microparticles, Conjugate, and Assay Diluent. The calibrators contain PBS buffer and human serum, with different concentrations of 25-OH vitamin D. The controls contain 25-OH vitamin D prepared in PBS buffer with human serum.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the ARCHITECT 25-OH Vitamin D assay, based on the provided document:

Acceptance Criteria and Reported Device Performance

Note: The document does not explicitly state "acceptance criteria" but rather presents successful study results that demonstrate the device's performance meets regulatory expectations. Where a specific criterion is not explicitly stated, I've inferred it from the presented study objective or common clinical laboratory standards (e.g., "acceptable precision").

Category	Acceptance Criteria (Inferred/Stated)	Reported Device Performance
Precision (Within-Laboratory)	Samples 8.0 ng/mL: CV% 500 mg/dL showed significant negative bias (up to -17.5% at 800 mg/dL).
Biotin (up to 30 ng/mL): Acceptable (e.g., -2.8% to 0.8%). Higher levels targeted (35 ng/mL) still acceptable (-2.8% to 0.8%).
Cholesterol (up to 500 mg/dL): Acceptable (e.g., -3.7% to 1.4%). Higher levels targeted (550 mg/dL) still acceptable (-3.7% to 1.4%).
Interference (Rheumatoid Factor & Heterophilic Antibody)	RF at ≤ 800 IU/mL and GARA at ≤ 1 ug/mL within acceptable limits of interference.	RF (≤ 800 IU/mL): -2.3% to 1.6% (Not susceptible to interference).
GARA (≤ 1 ug/mL): -2.7% to 3.9% (Not susceptible to interference).
Interference (Other Medical Conditions)	Minimal bias compared to LC-MS/MS for specified conditions.	Pregnant Females (1st Trimester, n=40): Mean % Bias 4.5%
Pregnant Females (2nd Trimester, n=40): Mean % Bias -2.2%
Pregnant Females (3rd Trimester, n=40): Mean % Bias 0.1% (Not susceptible to interference).
Hemodialysis Patients (n=44): Mean % Bias -15.3% (Susceptible to interference, as observed in published data).
Method Comparison (vs. ID-LC-MS/MS)	Satisfactory agreement with reference method (Passing-Bablok slope ~1, intercept ~0, high r-value).	Passing-Bablok regression: slope = 1.02, intercept = -0.99, r = 0.99 (Acceptable).
Tube Type Equivalency	Lower and upper one-sided 95% CL around the % difference within ± 10% across the measuring interval.	All evaluated tube types (serum separator tubes (SST), dipotassium EDTA, tripotassium EDTA, sodium heparin, lithium heparin powder, PST lithium heparin gel) met the criteria, with Passing-Bablok slopes close to 1 and r-values of 1.00.
Specimen Stability	% difference of ± 10% compared to baseline for specified storage conditions.	2 to 8°C for > 12 days: Acceptable.
Approximately 22°C or 30°C for ≥ 72 hours: Acceptable.
≥ 4 freeze/thaw cycles after 2 to 8°C for ≥ 12 days: Acceptable.
Manual Dilution	Acceptable % recovery for diluted samples.	1:2 dilution factor: 96.8% mean recovery.
1:3 dilution factor: 97.1% mean recovery.
1:4 dilution factor: 103.7% mean recovery (Demonstrated ability to recover manually-diluted samples).
Measuring Interval	Supported by precision, linearity, LoQ, and bias data.	3.4 to 155.9 ng/mL (8.5 to 389.8 nmol/L).

Study Details for ARCHITECT 25-OH Vitamin D assay

Sample sizes used for the test set and the data provenance:
- Reference Range/Expected Values Study:
  - Sample Size: A minimum of 120 specimens for each season (Summer and Winter), total combining 283 samples (142 male, 141 female).
  - Data Provenance: Prospective collection from apparently healthy individuals (21+ years old) from 3 different geographical locations in the 48 contiguous United States (north, south, and central).
- 20-Day Precision (Within-Laboratory):
  - Sample Size: 3 controls and 7 human serum panels (each tested over a total of 358-360 replicates).
  - Data Provenance: Not specified, but generally internally prepared controls and human serum panels.
- Linearity:
  - Sample Size: 12 sample pools (spanning the measuring interval).
  - Data Provenance: Prepared low-level 25-OH vitamin D sample (diluting human serum with Calibrator A) and high-level 25-OH vitamin D sample (spiking normal human serum with 25-OH vitamin D3 stock solution).
- Limits of Blank (LoB), Detection (LoD), and Quantitation (LoQ):
  - Sample Size: 4 zero-analyte samples (Calibrator A) tested in ≥ 5 replicates; 14 low-level samples (7 unique target concentrations) tested in ≥ 10 replicates.
  - Data Provenance: Zero-analyte samples (Calibrator A) and low-level samples prepared gravimetrically by diluting normal human serum with Calibrator A.
- Specificity - Cross-Reactivity (Non-Vitamin D Analogs):
  - Sample Size: Not explicitly stated, but each potential cross-reactant evaluated at three analyte levels (20, 30, 40 ng/mL), with each sample tested in a minimum of 12 replicates.
  - Data Provenance: Serum samples obtained and divided into test and reference aliquots.
- Specificity - 25-OH Vitamin D3 Cross-Reactivity:
  - Sample Size: Three analyte levels (20, 30, 40 ng/mL), each tested in a minimum of 12 replicates.
  - Data Provenance: 25-OH vitamin D3 stock solution (NIST SRM 2972) added to Calibrator A or calibrator/control diluent.
- Specificity - 25-OH Vitamin D2 Cross-Reactivity:
  - Sample Size: Not explicitly stated, but using endogenous serum specimens at 25-OH vitamin D2 concentrations near 26 ng/mL and 68 ng/mL, each tested in a minimum of 2 replicates.
  - Data Provenance: Endogenous (non-spiked) serum specimens obtained from approved vendors.
- Interference (Endogenous Substance):
  - Sample Size: Not explicitly stated, but each sample was tested in a minimum of 12 replicates for various interfering substances at different analyte levels.
  - Data Provenance: Test samples containing potentially-interfering endogenous substances compared to reference samples.
- Interference (Rheumatoid Factor and Heterophilic Antibody):
  - Sample Size: Samples prepared at three analyte levels (20, 30, 40 ng/mL), each tested in a minimum of 12 replicates.
  - Data Provenance: Human serum samples supplemented with RF stock solution or GARA stock solution.
- Interference (Other Medical Conditions):
  - Sample Size: 40 pregnant females (1st Trimester), 40 pregnant females (2nd Trimester), 40 pregnant females (3rd Trimester), 44 hemodialysis patients.
  - Data Provenance: Specimens sourced from individuals with these medical conditions.
- Method Comparison:
  - Sample Size: A minimum of 100 human serum specimens.
  - Data Provenance: Normal human serum specimens, no more than 10% spiked with 25-OH vitamin D stock solution.
- Tube Type Equivalency:
  - Sample Size: Samples from a minimum of 40 donors (each donor contributing samples to control and evaluation tube types).
  - Data Provenance: Specimens obtained from a specimen vendor.
- Specimen Stability:
  - Sample Size: 14 serum specimens and 14 plasma specimens.
  - Data Provenance: Specimens obtained from a specimen vendor.
- Manual Dilution:
  - Sample Size: A minimum of 13 unique donor specimens.
  - Data Provenance: Specimens spiked with 25-OH vitamin D stock solution and diluted with Calibrator A.
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 (IVD) assay for quantitative measurement. The "ground truth" for these types of assays is typically established using highly accurate, well-characterized reference methods or reference materials.
- For the method comparison study, the comparator method was Isotope Dilution - Liquid Chromatography - Tandem Mass Spectrometry (ID-LC-MS/MS), which is a gold standard reference method for vitamin D measurement. This method does not involve human expert consensus in the same way an imaging study might. The "expertise" lies in the robust analytical method itself and the operators who run it in a reference laboratory setting.
- For standardization, the ARCHITECT 25-OH Vitamin D assay is standardized against NIST SRM 2972 (National Institute of Standards & Technology Standard Reference Material 2972). NIST SRMs are highly certified reference materials, established through rigorous analytical processes, not human expert consensus.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable. This is a quantitative IVD assay, not a diagnostic imaging or classification device where human adjudication of results is typical for establishing ground truth. The performance is assessed against analytical standards and reference methods (like ID-LC-MS/MS).
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:
- No. This is an automated in vitro diagnostic assay. It measures a biomarker concentration directly and does not involve human "readers" or "AI assistance" in the interpretation of complex images or signals in the context of an MRMC study.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance studies presented (precision, linearity, LoB/LoD/LoQ, specificity, interference, tube type equivalency, specimen stability, manual dilution) are all standalone performance evaluations of the ARCHITECT 25-OH Vitamin D assay system (reagents, calibrators, controls, and ARCHITECT i2000SR instrument). The results are generated directly by the automated system without human-in-the-loop interpretative performance.
- The Method Comparison study directly compares the device's quantitative output to an ID-LC-MS/MS reference method, effectively demonstrating its standalone analytical performance against a gold standard.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The primary ground truth for the quantitative measurement of 25-OH Vitamin D is the Isotope Dilution - Liquid Chromatography - Tandem Mass Spectrometry (ID-LC-MS/MS) method, which serves as the reference method in the method comparison study.
- Additionally, NIST SRM 2972 is used for standardization, representing a highly characterized and certified reference material.
- For certain aspects like reference ranges, the "ground truth" is derived from statistical analysis of a healthy population.
The sample size for the training set:
- This document describes performance validation studies for an IVD assay, not an AI/ML model. Therefore, there is no "training set" in the context of machine learning. The assay's "training" or calibration involves using dedicated calibrators provided with the kit, such as the ARCHITECT 25-OH Vitamin D 5P02 Calibrators, which cover a range of known 25-OH vitamin D concentrations (0.0-160.0 ng/mL). The specific number of calibration runs performed to establish the curve for a general assay is not considered a "training set" in the AI/ML sense.
How the ground truth for the training set was established:
- As noted above, there is no "training set" in the AI/ML sense. For the calibrators (which serve a similar function to training data in informing the assay's output), the document states:
  - "Calibrators A-F contain PBS buffer and human serum. Calibrators B-F also contain different concentrations of 25-OH vitamin D."
  - "The ARCHITECT 25-OH Vitamin D assay is standardized against NIST SRM 2972 (National Institute of Standards & Technology Standard Reference Material 2972)."
- This indicates that the "ground truth" for the calibrators is established by preparing them with known, precisely measured concentrations of 25-OH vitamin D, traceable to a recognized international standard (NIST SRM 2972).

Summary

Regulation Number and Section

§ 862.1825 Vitamin D test system.

(a)
Identification. A vitamin D test system is a device intended for use in clinical laboratories for the quantitative determination of 25-hydroxyvitamin D (25-OH-D) and other hydroxylated metabolites of vitamin D in serum or plasma to be used in the assessment of vitamin D sufficiency.(b)
Classification. Class II (special controls). Vitamin D test systems must comply with the following special controls:(1) Labeling in conformance with 21 CFR 809.10 and
(2) Compliance with existing standards of the National Committee on Clinical Laboratory Standards.