FDA 510(k) Search - By Innolitics (SaMD and AI Experts)

The Diazyme 25-OH Vitamin D EIA Kit is designed for the quantification of total 25-OH Vitamin D in human serum and plasma. The assay results are to be used in parallel with other clinical data to assess the Vitamin D status of a patient. For in vitro diagnostic use only.

The 25-OH Vitamin D EIA Control Kit is intended for use as quality controls for the Diazyme 25-OH Vitamin D EIA Kit only. For in vitro diagnostic use only.

Device Description

The Diazyme 25-hydroxy (25-OH) Vitamin D EIA uses the enzyme immuno-assay technology (EIA). It is based on the competition (for a 25-OH Vitamin D antibody) between a 25-OH Vitamin D conjugate coated on a microplate and the 25-OH Vitamin D content of a serum sample. Vitamin D samples are first extracted for 15 min at room temperature using reagent EX and deep-well pre-dilution strips. The extracted Vitamin D samples are then transferred to the coated microplate wells and the addition of reagent R1 (containing an antibody for 25-OH Vitamin D) allows for the competition to proceed. After a first incubation, the microplate is washed and reagent R2 (HRP-labeled secondary antibody) is added. Following a second incubation and a washing step, reagent R3 (TMB substrate) is added. After a final incubation step, the reaction is stopped by adding the STOP solution and the colorimetric signal of the microplate is measured at 450 nm (primary wavelength) to which the background signal can be subtracted by using a secondary wavelengths (620 to 650 nm). The 25-OH Vitamin D concentration of a patient sample is inversely proportional to the measured absorbance at 450 nm. The whole assay procedure takes about two hours. 25-OH Vitamin D EIA calibrator set is intended for use as a calibration for the Diazyme 25-OH Vitamin D EIA kit only. Six calibration levels are needed for each run. Calibrators are treated exactly the same as patient samples.

25-OH Vitamin D EIA 2-point control kit is intended for use with the Diazyme 25-OH Vitamin D EIA kit only. Controls are treated exactly the same as patient samples. The quality controls assist laboratory users in verification steps ensuring that the assay reagents are functioning correctly. Users are instructed to verify the calibration curve with the controls.

AI/ML Overview

Here's an analysis of the provided 510(k) summary, specifically focusing on the acceptance criteria and study details for the Diazyme 25-OH Vitamin D EIA Kit:

Introduction
The Diazyme 25-OH Vitamin D EIA Kit is designed for the quantification of total 25-OH Vitamin D in human serum and plasma, with results used alongside other clinical data to assess Vitamin D status. The following sections detail the performance criteria and the studies conducted to demonstrate its effectiveness.

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implied/Standard)	Reported Device Performance (Diazyme 25-OH Vitamin D EIA Kit)
Precision	CV% typically 0.9).	n: 58
		Slope: 0.941
		Intercept: +1.448
		Correlation coefficient: 0.930
		Range of values: 11.9 ng/mL - 131.5 ng/mL
Matrix Comparison (Serum vs. Plasma)	Good agreement (e.g., R^2 > 0.95, slope near 1, intercept near 0).	Li-Heparin plasma vs. Serum: y = 0.993x + 1.855, R^2 = 0.961
		K3-EDTA plasma vs. Serum: y = 1.006x + 2.901, R^2 = 0.967
Reference Range Study	Establish a representative reference range for a healthy population.	n: 157
		Lowest Conc: 8.4 ng/mL
		Highest Conc: 61.3 ng/mL
		Median Conc: 29.1 ng/mL
		Observed Range (2.5th-97.5th percentile): 12.0 to 55.0 ng/mL

2. Sample Sizes Used for the Test Set and Data Provenance

Precision Study:
- Sample Size: 10 precision levels (2 serum controls, 8 serum samples). Each specimen had 80 measurements in total (20 days * 4 measurements/day). So, 10 samples * 80 measurements each = 800 individual data points.
- Data Provenance: Not explicitly stated, but derived from internal laboratory testing using serum controls and serum samples. Likely prospective internal testing.
Linearity/Reportable Range:
- Sample Size: 11 levels of linearity prepared from a high and low serum sample. Each level was tested in triplicates.
- Data Provenance: Not explicitly stated, but derived from internal laboratory testing using spiked serum samples. Likely prospective internal testing.
LoB/LoD/LoQ:
- Sample Size: Not explicitly detailed beyond stating the methodology. This typically involves multiple replicates of blank, low-concentration, and representative samples over several runs.
- Data Provenance: Not explicitly stated, but derived from internal laboratory testing. Likely prospective internal testing.
Interference Study:
- Sample Size: Not explicitly stated for the number of tested samples, but experiments focused on a set of common interfering substances.
- Data Provenance: Not explicitly stated, but derived from internal laboratory testing. Likely prospective internal testing using spiked samples.
Cross-Reactivity Study:
- Sample Size: Not explicitly detailed for the number of replicates or unique samples, but involved testing specific Vitamin D metabolites.
- Data Provenance: Not explicitly stated, but derived from internal laboratory testing using serum pool samples spiked with various cross-reactants. Likely prospective internal testing.
Method Comparison:
- Sample Size: 58 human serum samples (7 of which were spiked).
- Data Provenance: Human serum samples. The origin (country) is not specified, but the testing was internal. The nature suggests these were likely prospective or retrospectively collected clinical samples used in a prospective comparison study.
Matrix Comparison:
- Sample Size: 66 matched sets of serum, K3-EDTA plasma, and Li-Heparin plasma. Includes seven spiked patient samples.
- Data Provenance: Matched human samples in different matrices. The origin (country) is not specified. Likely prospective or retrospectively collected clinical samples used in a prospective comparison study.
Reference Range Study:
- Sample Size: 157 apparently healthy individuals.
- Data Provenance: Samples from three different US geographical locations: 47 from Pennsylvania (Northern U.S.), 56 from Tennessee (Central U.S.), and 54 from Texas (Southern U.S.). These were obtained from certified commercial sources (ProMedDx, LLC and Dx Biosamples) or collected under an IRB approved protocol. This indicates retrospective collection of samples from defined populations.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

This type of in-vitro diagnostic device (EIA kit) does not typically involve human experts for establishing ground truth in the way AI/imaging devices do (e.g., radiologists reviewing images). Instead, the "ground truth" or reference values are established by:

Reference Methods: For method comparison, the predicate device (IDS 25-OH Vitamin D EIA, K021163) serves as the reference against which the new device is compared. This predicate device itself would have undergone its own rigorous validation.
Known Concentrations: For studies like linearity, LoB/LoD/LoQ, interference, and cross-reactivity, ground truth is established by preparing samples with known, precisely measured concentrations of the analyte or interfering/cross-reacting substances. This is done in a laboratory setting using calibrated equipment and certified reference materials.
Clinical Standards: For the reference range study, the ground truth is the measured 25-OH Vitamin D concentration in a statistically representative healthy population, measured by the Diazyme device itself.

Therefore, the concept of "number of experts" adjudicating ground truth in the context of clinical pathology or imaging is not applicable here. The expertise lies in the rigorous adherence to established laboratory guidelines (CLSI protocols) and the use of reference methods/materials.

4. Adjudication Method for the Test Set

Again, for an in-vitro diagnostic assay measuring an analyte, adjudication methods like N+1 or 2+1 (common in AI imaging) are not applicable. The "adjudication" is inherent in the analytical process:

Predicate Device: For method comparison, the predicate device's measurement serves as the standard.
Statistical Analysis: Results are compared using statistical methods (e.g., linear regression, correlation coefficient) to determine agreement and equivalence, based on predefined statistical acceptance criteria.
CLSI Guidelines: Adherence to CLSI (Clinical and Laboratory Standards Institute) protocols ensures standardized and robust evaluation.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, an MRMC comparative effectiveness study was not done.
This type of study is primarily relevant for diagnostic imaging or interpretation tasks where multiple human readers interpret cases, and AI assistance might influence their performance.
The Diazyme 25-OH Vitamin D EIA Kit is an automated laboratory test for quantitative measurement of an analyte, not an interpretation task performed by human readers.

6. Standalone Performance (Algorithm Only Without Human-in-the-Loop Performance)

Yes, standalone performance was done.
The performance metrics reported (precision, linearity, LoB/LoD/LoQ, interference, cross-reactivity, and method/matrix comparison) all represent the performance of the Diazyme 25-OH Vitamin D EIA Kit itself, as an "algorithm only" in the sense of an automated test.
There is no "human-in-the-loop" interaction for interpreting or modifying the test results generated by the EIA kit; the results are directly quantitative measurements.

7. Type of Ground Truth Used

The ground truth used depends on the specific study:

Known concentrations/Reference materials: For precision, linearity, LoB/LoD/LoQ, interference, and cross-reactivity studies. These are precisely prepared samples with a known amount of the analyte or interfering substance.
Comparison to a Legally Marketed Predicate Device: For the method comparison study, the measurements obtained by the predicate device (IDS 25-OH Vitamin D EIA, K021163) served as the comparative ground truth.
Patient Outcome Data: Not directly used as ground truth for performance validation, although the assay results are intended to be used in parallel with other clinical data to assess Vitamin D status, which could indirectly relate to patient outcomes. However, the regulatory submission focuses on analytical performance rather than direct impact on patient outcomes.

8. Sample Size for the Training Set

This device is an EIA kit, which is a chemical assay, not an AI/machine learning algorithm that requires a "training set" in the conventional computational sense.
Therefore, the concept of a "training set" is not applicable here. The development of the assay's reagents and protocols would involve optimization and piloting, but not an ML-style training dataset.

9. How the Ground Truth for the Training Set Was Established

As the concept of a training set is not applicable, the method of establishing its ground truth is also not applicable.
The "ground truth" during the development and optimization of such an assay would be based on established biochemical principles, spiked samples with known concentrations, and comparisons to established gold-standard methods or reference laboratories during the R&D phase.

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.