(264 days)
ST AIA-PACK 25-OH Vitamin D is designed for in vitro diagnostic use only for the quantitative measurement of total 25-hydroxyvitamin D (25-OH vitamin D) in human serum, Na-heparinized plasma or EDTA plasma on TOSOH AIA System Analyzers. The Tosoh ST AIA-PACK 25-OH Vitamin D is intended as an aid in the determination of Vitamin D sufficiency.
The ST AIA-PACK 25-OH Vitamin D Calibrator Set is intended for in vitro diagnostic use only for the calibration of the ST AIA-PACK 25-OH Vitamin D assay.
The ST AIA-PACK 25-OH Vitamin D is a one-step delayed competitive enzyme immunoassay which, after sample pretreatment, is performed entirely in the ST AIA-PACK 25-OH Vitamin D test cup. Sample pretreatment reagents (containing sodium hydroxide) disassociate 25-OH vitamin D from its binding proteins in the test sample. 25-OH vitamin D present in the pretreated sample is bound to 25-OH vitamin D-specific monoclonal antibody immobilized on magnetic beads. After that, the enzymelabeled 25-OH vitamin D is added to the reaction mixture. The enzyme-labeled 25-OH vitamin D competes with 25-OH vitamin D for binding to the antibody on magnetic beads in the reaction mixture.
After the second incubation, the magnetic beads are washed to remove the unbound enzymelabeled 25-OH vitamin D and are then incubated with a fluorogenic substrate, 4- methylumbellifery phosphate (4MUP). The amount of enzyme-labeled 25-OH vitamin D that binds to the beads is inversely proportional to the 25-0H vitamin D concentration in the test sample. A standard curve is constructed, and unknown 25-OH vitamin D concentrations are calculated using this curve.
The ST AIA-PACK 25-OH Vitamin D Calibrator Set contains human sera with assigned levels of 25-OH Vitamin D. The calibrator set consists of six calibrators with assigned concentrations of approximately 0, 8, 17, 33, 66 and 135 ng/mL. Each level contains the assigned concentration of the 25-OH vitamin D (described on each vial) with sodium azide as a preservative.
This looks like a 510(k) Summary for a medical device called "ST AIA-PACK 25-OH Vitamin D" and its associated calibrator set. The document describes the device, its intended use, and provides evidence of its performance and substantial equivalence to a predicate device.
Let's break down the requested information based on the provided text.
1. A table of acceptance criteria and the reported device performance
The document doesn't explicitly state "acceptance criteria" in a separate section with pass/fail thresholds against which the performance is measured. Instead, it presents performance characteristics and largely uses the performance of the predicate device or established clinical standards (like CLSI guidelines) as a benchmark for comparison or to demonstrate expected performance.
However, we can infer some criteria from the presented performance characteristics.
| Performance Characteristic | Acceptance Criteria (inferred/implied) | Reported Device Performance |
|---|---|---|
| Precision | Equal to or exceed predicate calibrator traceability (K123131). | Within-run precision: 1.3 - 3.9% |
| Between run precision: 1.5 - 3.1% | ||
| Between day precision: 2.2 - 4.1% | ||
| Total precision: 2.6 - 4.9% | ||
| Between lot precision: 1.1 - 3.1% | ||
| Statement: "The precision equals or exceeds the precision obtained with the predicate calibrator traceability for (k)123131." | ||
| Linearity | Demonstrated to be linear within the assay range. | Linear from 4.0 ng/mL to 120 ng/mL. |
| Statement: "There is no change in linearity from K123131." | ||
| Standardization & Traceability | Traceable to ID-LC/MS/MS 25-OH Vitamin D RMP (University of Ghent). Bias should be acceptable. | Weighted Deming regression analysis (vs. RMP): |
| Slope: 0.98 (0.92 - 1.05) | ||
| Intercept: -0.48 (-1.89 - 0.92) | ||
| Corr Coef (R): 0.965 | ||
| Bias: -0.23 (-0.71%) | ||
| The study concludes that the assay is traceable to the RMP. | ||
| Method Comparison (vs. Predicate) | Demonstrate acceptable correlation and bias against predicate. | Deming regression analysis (vs. Predicate): |
| Slope: 0.808 (0.801 to 0.816) | ||
| Intercept: 0.26 (-0.15 to 0.67) | ||
| Corr Coef (R): 0.9979 | ||
| Bias: -8.90 (-20.25%) | ||
| This comparison demonstrates the change in bias introduced by the standardization process. | ||
| Reference Ranges | Establish a representative reference interval. | Reference Interval: 12.3 – 60.0 ng/mL (based on 252 healthy individuals). |
| Limit of Detection (LoD) | Determined according to CLSI guideline EP17-A. | LoD: 3.2 ng/mL (determined by 12 measurements of 5 low-level samples across 3 lots) |
| Limit of Quantitation (LoQ) | Determined according to CLSI guideline EP17-A. | Functional sensitivity (LoQ): 3.3 ng/mL at 20% CV. |
| Limit of Blank (LoB) | Determined according to CLSI guideline EP17-A. | LoB: 1.6 ng/mL (determined by 60 measurements of 3 different blank specimens) |
2. Sample sizes used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
- Precision:
- Sample Size: Three levels of unaltered serum specimens (Serum-B and Serum-C) and three spiked serum specimens (Serum-E and Serum-F) were assayed. Each level involved 2 replicates in a single run, 2 times a day for 20 non-consecutive days, across 2 analyzers and 2 lots of reagents. This totaled 40 runs and 80 determinants per lot.
- Data Provenance: Not explicitly stated, but typically clinical laboratory studies are prospective and involve samples collected for internal validation or purchased from biorepositories. No country of origin is mentioned.
- Linearity:
- Sample Size: Not explicitly stated, but typically involves a series of diluted samples to cover the assay range.
- Data Provenance: Not explicitly stated.
- Standardization and Traceability (Method Comparison vs. RMP):
- Sample Size: 111 serum specimens.
- Data Provenance: The RMP (Reference Measurement Procedure) was performed at the University of Ghent, in Ghent, Belgium. The samples were value-assigned by the Ghent University ID-LC-MS/MS RMP. This suggests these were likely retrospective samples used for standardization purposes in a prospective study design to validate the device's traceability.
- Method Comparison (vs. Predicate):
- Sample Size: 181 unaltered serum specimens.
- Data Provenance: Not explicitly stated, but likely from various sources for routine clinical testing. Implied to be a prospective comparison study.
- Reference Ranges:
- Sample Size: 252 serum samples (111 females, 141 males).
- Data Provenance: Specimens were obtained from "apparently healthy individuals" in Maryland, Pennsylvania, Wisconsin, and Southern California (USA). Samples were collected in March, May, June, and July, indicating a prospective collection over several months.
- Limit of Detection and Limit of Quantitation:
- LoB: 60 measurements of 3 different blank specimens.
- LoD: 12 measurements of 5 low-level sample ranges, using 3 lots of reagents.
- LoQ: Series of low Vitamin D samples assayed in replicates of 8 for 5 days (total 40 replicates per sample).
- Data Provenance: Not explicitly stated.
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)
- For this in vitro diagnostic device, "ground truth" is primarily established by highly accurate reference methods or clinical standards, rather than expert consensus on interpretation.
- Standardization and Traceability: The ground truth for this segment was the ID-LC/MS/MS 25-OH Vitamin D Reference Measurement Procedure (RMP) at the University of Ghent. This is a highly specialized analytical chemistry method considered the "gold standard" for measuring 25-OH Vitamin D, not typically performed by individual "experts" in the clinical sense, but rather by trained laboratory personnel following precise protocols. The qualifications of the individuals performing the RMP are implied to be high-level analytical chemists/technicians experienced in ID-LC/MS/MS.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
- Adjudication methods like 2+1 or 3+1 are typically used in clinical imaging studies where subjective interpretation is involved.
- For an in vitro diagnostic device measuring a quantitative analyte like 25-OH Vitamin D, the "adjudication" is inherent in the analytical method's precision, accuracy, and traceability to a recognized reference method (like the ID-LC/MS/MS RMP). Discordant results would be investigated through re-testing or troubleshooting, not through a consensus of human reviewers. Therefore, the concept of a multi-observer adjudication method is not applicable here.
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
- This is an in vitro diagnostic device for measuring a biochemical marker (Vitamin D). The concept of "multi-reader multi-case (MRMC) comparative effectiveness study" for human readers improving with or without AI assistance is not applicable to this type of device. There is no "reading" of images or complex data by human experts being assisted by AI in the context of this submission. The device performs an automated quantitative measurement.
6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done
- This device is an automated, standalone assay system. Its performance characteristics (precision, linearity, LoD, LoQ, method comparison) are its standalone performance without continuous human intervention in the interpretive phase. While humans operate the instrument and perform quality control, the measurement itself is algorithmic. Therefore, the presented studies (precision, linearity, method comparison, etc.) represent the standalone performance of the device algorithm.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- The primary ground truth used for validating the accuracy and standardization of the device is the Isotope Dilution-Liquid Chromatography/Tandem Mass Spectrometry (ID-LC/MS/MS) 25-OH Vitamin D Reference Measurement Procedure (RMP). This is a highly accurate and precise analytical method recognized as the gold standard for 25-OH Vitamin D measurement, traceable to NIST Standard Reference Material (SRM) 2972.
8. The sample size for the training set
- This document describes a 510(k) submission for a diagnostic assay, not a machine learning or AI algorithm in the context of typical training/test sets. The "training" for such an assay involves the development and optimization of the reagents, assay protocol, and calibration procedures using various samples. There isn't a single, defined "training set" sample size in the sense of AI model development.
- The "training" data, in an analogous sense, would be all the samples and experiments conducted during the development phase to establish the assay's performance characteristics, optimize reagent concentrations, and set initial calibrator values. This information is typically not detailed in a 510(k) summary as a single "training set."
9. How the ground truth for the training set was established
- As mentioned above, the concept of a distinct "training set" with ground truth in the AI sense is not directly applicable here. However, the development and initial calibration of the assay would have relied on highly characterized samples, likely correlated with established reference methods or primary standards (such as those traceable to NIST SRMs) to ensure accuracy and consistency from the earliest stages of development. The subsequent "standardization" step (as described in the document, traceable to the University of Ghent's ID-LC/MS/MS RMP) represents a formal validation and adjustment process to ensure consistency with recognized reference methods.
§ 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.