VITROS IMMUNODIAGNOSTIC PRODUCTS FOLATE REAGENT PACK 1/2, VITROS IMMUNODIAGNOSTIC PRODUCTS VITAMIN B12/FOLATE REAGENT P3 by Ortho-Clinical Diagnostics, Inc.

& 2. The VITROS Immunodiagnostic Products Folate Reagent Pack 1/2 and the VITROS Immunodiagnostic Products Vitamin B12/Folate Reagent Pack 3 - for the in vitro quantitative measurement of folate in human serum and plasma (heparin) and whole blood (red cell folate), to aid in the differential diagnosis of anemia.
The VITROS Immunodiagnostic Products Folate Calibrators - for in vitro use in the calibration of the VITROS Immunodiagnostic System for the quantitative measurement of folate in human serum and plasma (heparin).
The VITROS Immunodiagnostic Products Red Cell Folate Pack - for whole blood sample preparation, to allow the in vitro quantitative measurement of red cell folate using the VITROS Immunodiagnostic System.

Device Description

The VITROS Immunodiagnostic System uses luminescence as the signal in the quantitative and semi-quantitative determination of selected analytes in human body fluids, commonly serum, plasma and urine. Coated microwells are used as the solid phase separation system.

The system is comprised of three main elements:

The VITROS Immunodiagnostic Products range of products, in this case VITROS Immunodiagnostic Products Folate Reagent Pack, VITROS Immunodiagnostic Products Folate Calibrators and the VITROS Immunodiagnostic System. The VITROS Folate Reagent Pack consists of: The VITROS Immunodiagnostic Products Folate Reagent Pack 1/2 and the VITROS Immunodiagnostic Products Vitamin B12/Folate Reagent Pack 3
The VITROS Immunodiagnostic System instrumentation, which provides automated use of the immunoassay kits.
Common reagents used by the VITROS System in each assay. The VITROS Immunodiagnostic Products Signal Reagent and VITROS Immunodiagnostic Products Universal Wash Reagent were cleared as part of the VITROS Immunodiagnostic Products Total T3 510(k) pre-market notification (K984310).

The VITROS System and common reagents are dedicated specifically only for use with the VITROS Immunodiagnostic Products range of immunoassay products.

AI/ML Overview

Here's an analysis of the provided text, focusing on acceptance criteria and the study proving the device meets them. It's important to note that the document is a 510(k) summary, which often
focuses on substantial equivalence to a predicate device rather than exhaustive performance studies with strict "acceptance criteria" as might be defined for a novel device. The "acceptance
criteria" here are primarily implied by the demonstration of substantial equivalence and correlation to the predicate.

Acceptance Criteria and Performance Comparison

The document describes two devices:

(a) VITROS Folate assay (for serum and plasma folate)
(b) VITROS Red Cell Folate Pack (for red cell folate)

Both are compared to the Bio-Rad Quantaphase II Folate Radioassay (K935286) as the predicate device. The primary "acceptance criterion" appears to be demonstrating substantial equivalence
to this predicate device by showing a good correlation and acceptable bias in measurements.

Table of Acceptance Criteria (Implied) and Reported Device Performance

Criterion Type	Specific Criterion (Implied/Predicate Performance)	VITROS Folate Assay (Serum/Plasma) Performance	VITROS Red Cell Folate Pack Performance
Substantial Equivalence	Demonstrated by strong correlation and acceptable bias to predicate.	Relationship: VITROS = 0.999 x Bio-Rad + 0.676 ng/mL	Relationship: VITROS = 1.17 x Bio-Rad + 4.0 ng/mL
Correlation (r): 0.979
Bias: 17% overall positive bias. (Acknowledged as "true numerical differences")
Calibration Range	0 – 20 ng/mL (matches predicate)	0 – 20 ng/mL	0 – 20 ng/mL
Basic Principle	To be consistent with predicate method or clinically acceptable alternative.	Solid phase assay (different from predicate's radioassay, but deemed acceptable)	Solid phase assay (different from predicate's radioassay, but deemed acceptable)
Tracer	To be consistent with predicate method or clinically acceptable alternative.	Enzyme labeled (different from predicate's 125Iodine, but deemed acceptable)	Enzyme labeled (different from predicate's 125I, but deemed acceptable)
Instrumentation	To be consistent with predicate method or clinically acceptable alternative.	VITROS Immunodiagnostic System (different from predicate's Gamma Counter, but deemed acceptable)	VITROS Immunodiagnostic System (different from predicate's Gamma Counter, but deemed acceptable)
Sample Type	Serum or plasma (EDTA)	Serum, plasma (heparin) (Broader than predicate, includes heparin plasma)	Whole blood (EDTA or heparin) (Broader than predicate, includes heparin)
Binding protein	Folate binding protein	Folate binding protein, purified from bovine milk (More specific description, but functionally equivalent)	Folate binding protein
Sample volume	200 µL	53 µL (Significantly lower than predicate)	53 µL (Significantly lower than predicate)
Incubation time/temp	1 hour at room temperature.	73 mins at 37 °C (Different from predicate, but within acceptable limits for a new method)	Whole blood prep: 90 mins room temp; Folate assay: 73 mins at 37°C (Different from predicate, but deemed acceptable)
Analytical Sensitivity	Implied to be adequate for intended use (not explicitly stated).	Tested, results referred to package insert.	Not explicitly mentioned for Red Cell Folate.
Specificity	Implied to be adequate for intended use (not explicitly stated).	Tested, results referred to package insert.	Not explicitly mentioned for Red Cell Folate.
Precision	Implied to be adequate for intended use (not explicitly stated).	Tested, results referred to package insert.	Tested, results referred to package insert.
Dilution (Linearity)	Implied to be adequate for intended use (not explicitly stated).	Tested, results referred to package insert.	Tested, results referred to package insert.
Expected Values	Implied to be established.	Tested, results referred to package insert.	Tested, results referred to package insert.

Study Details

The studies performed for both the VITROS Folate assay and the VITROS Red Cell Folate Pack
are primarily comparative effectiveness studies against the predicate device.

Sample size for the test set and data provenance:
- Test Set Sample Size: Not explicitly stated as a number of samples. The document mentions "samples from a variety of clinical categories" and "patient specimens covering a variety
  of clinical categories." This suggests a diverse patient population was used, but the exact count is not provided.
- Data Provenance: Not explicitly stated (e.g., country of origin, retrospective/prospective). However, the use of "patient specimens" and "currently commercially available reagents"
  implies real-world samples from a clinical setting. It's likely a retrospective collection as is common for these types of studies comparing new assays to established ones.
Number of experts used to establish the ground truth for the test set and their qualifications:
- Not Applicable. For an in vitro diagnostic (IVD) quantitative assay, the "ground truth" is typically defined by the measurement results from a recognized reference method or a
  well-established predicate device, not by expert interpretation. In this case, the predicate device (Bio-Rad Quantaphase II Folate Radioassay) serves as the de facto "ground truth"
  for comparison purposes.
Adjudication method for the test set:
- Not Applicable. As per the point above, adjudication by multiple experts is not relevant for establishing ground truth for a quantitative chemical assay. The comparison is made
  between the new device's readings and the predicate device's readings.
If a multi reader multi case (MRMC) comparative effectiveness study was done, and the effect size of how much human readers improve with AI vs without AI assistance:
- Not Applicable. This is an in vitro diagnostic device (quantitative assay), not an AI-assisted diagnostic imaging or interpretation system. Therefore, MRMC studies and human reader
  improvement with AI assistance are not relevant.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, implicitly. The VITROS Folate assay and Red Cell Folate Pack are standalone automated IVD systems. Their performance metrics (correlation, bias, analytical characteristics)
  are measured inherently without human interpretation of the result itself. Human involvement is in sample preparation, loading, and reviewing the reported numerical values, but the
  measurement process is automated.
The type of ground truth used:
- Predicate Device Measurements: The ground truth for this substantial equivalence argument is the measurement results obtained from the Bio-Rad Quantaphase II Folate Radioassay
  (K935286).
- Analytical Performance: Additional "ground truths" are established internally for analytical performance characteristics (precision, linearity, expected values) using laboratory
  standards and methods, but the primary comparison is to the predicate.
The sample size for the training set:
- Not Applicable/Not Provided. For an IVD assay, there isn't typically a "training set" in the machine learning sense. The assay is developed using analytical chemistry principles,
  reagent formulation, and instrument calibration. The studies described are performance verification or validation tests rather than model training.
How the ground truth for the training set was established:
- Not Applicable. As there's no "training set" in the machine learning context, this question is not relevant. The development of the assay relies on established scientific principles
  and internal validation of reagents and methods.

Summary

Regulation Number and Section

§ 862.1295 Folic acid test system.

(a)
Identification. A folic acid test system is a device intended to measure the vitamin folic acid in plasma and serum. Folic acid measurements are used in the diagnosis and treatment of megaloblastic anemia, which is characterized by the presence of megaloblasts (an abnormal red blood cell series) in the bone marrow.(b)
Classification. Class II.