VIDAS PROESTERONE (PRG) (30 409) by BIOMERIEUX, INC.

The VIDAS Progesterone (PRG) assay is intended for use with a Vitek ImmunoDiagnostic Assay Systems (VIDAS) as an automated enzyme-linked fluorescent immunoassay (ELFA) for the quantit determination of progesterone in serum or plasma. The VIDAS Progesterone assay is intended for us an aid in the diagnosis and treatment of disorders of the overies and placenta.

Device Description

The VIDAS Progesterone (PRG) assay is an enzyme-linked fluorescent immunoassay (ELFA) that is performed in an automated VIDAS instrument. All assay temperature are controlled by the instrument. A pipette tip-like disposable device, the Solid Phase Receptacle (SPR), serves as a solid phase for the assay as well as a pipetting device. At the time of manufacture, the SPR is coated with mouse anti-progesterone antibodies. Reagents for the assay are located in the sealed Reagent Strips. The sample is transferred into the well containing a progesterone derivative conjugated with alkaline phosphatase. Wash steps remove unbound conjugate. A fluorescent substrate, 4-methylumbellifory! phosphate, is cycled through the SPR and flouresences. The intensity of fluorescence is measured by the optical scanner in the instrument; it is inversely proportional to the progesterone concentration present in the sample.

AI/ML Overview

Here's an analysis of the provided text regarding the acceptance criteria and study for the VIDAS Progesterone (PRG) Assay:

Acceptance Criteria and Device Performance for VIDAS Progesterone (PRG) Assay

Based on the provided 510(k) summary, the acceptance criteria are implicitly derived from the non-clinical and clinical study summaries. The device's reported performance is directly stated.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Acceptance Criteria (Implicit)	Reported Device Performance
Specificity/Cross-Reactivity	Minimal to no cross-reactivity with other hormones except specified progesterone metabolites.	No cross-reactivity with testosterone, corticosterone, 20a hydroxy-progesterone, 60 hydroxyprogesterone, 16a hydroxyprogesterone, Estrone, Estriol, Estradiol. Cross-reactivity exists with 5a and 5B dilhydroxyprogesterone. Minimal cross-reactivity with 17a hydroxyprogesterone and deoxycorticosterone, but deemed unlikely to cause false elevation due to low normal concentrations.
Interfering Substances	No significant interference from common sample collection components or endogenous substances.	No interference with dry glass tubes with separating gel, lithium heparin, EDTA. No interference with hemoglobin, lipids, or bilirubin at tested concentrations.
Precision/Reproducibility	Acceptable levels of intra-assay precision and inter-assay/inter-instrument reproducibility.	Intra-assay precision: CV ranging from 14.3% (0.46 ng/ml) to 3.8% (45.1 ng/ml).Inter-assay reproducibility (8 weeks): CV ranging from 24.3% (0.4 ng/ml) to 3.1% (45 ng/ml).Inter-assay, inter-instrument reproducibility: CV not exceeding 5.4% for five different serum samples across eight assays on different instruments.
Correlation with Predicate Device	Strong positive correlation with the predicate device (DPC Coat-A-Count Progesterone assay).	Correlation coefficient of 0.985 with the DPC Coat-A-Count Progesterone assay. Line equation: y = 1.0193x + -0.453.
Sensitivity (Limit of Detection)	A defined and acceptable limit of detection for progesterone.	Limit of detection determined to be 0.1 ng/ml of progesterone with a 95% confidence interval.
Calibration Stability	Master curve validity ensured by the calibrator over the kit's shelf life.	Body of data supports the use of a single calibrator for this purpose, ensuring master curve validity.

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

The document does not explicitly state the sample size for the clinical test set used for correlation, sensitivity, or calibration studies.

The provenance of the data (e.g., country of origin, retrospective or prospective) is not mentioned in the provided summary.

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

This information is not applicable in the context of this diagnostic assay. For assays like the VIDAS Progesterone test, the "ground truth" for the test set is typically established by comparative analysis with a well-established predicate device or reference method, not by expert interpretation of images or clinical data. The DPC Coat-A-Count Progesterone assay served as the predicate device against which the VIDAS assay was compared.

4. Adjudication Method for the Test Set

The concept of an "adjudication method" (like 2+1, 3+1) is not applicable here. Adjudication methods are typically used in clinical trials or studies involving human readers and subjective interpretations (e.g., radiology studies) to resolve discrepancies among experts. For quantitative assays like this, the comparison is directly between the result of the new device and the result of the predicate/reference method.

5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done. MRMC studies are used to evaluate the performance of human readers, sometimes with and without AI assistance, typically in medical imaging. This document describes a diagnostic assay, not an imaging device that would involve human readers interpreting AI outputs.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done

The performance detailed in this summary is effectively standalone performance. The VIDAS Progesterone assay is an automated Enzyme-Linked Fluorescent Immunoassay (ELFA) performed entirely by the VIDAS instrument. While a human initiates the test and interprets the numerical result, the "performance" of the device itself (accuracy, precision, sensitivity, etc.) is measured based on the automated output. There isn't a "human-in-the-loop" component that actively modifies the assay's output during the measurement process.

7. The Type of Ground Truth Used

The primary ground truth used for the clinical validation was comparison with a legally marketed predicate device, specifically the DPC Coat-A-Count Progesterone assay. This serves as the reference standard against which the new device's performance (correlation) is measured. The limit of detection and precision studies also use controlled samples with known progesterone concentrations.

8. The Sample Size for the Training Set

The document does not provide information on a "training set" in the context of machine learning or AI models. This device is a biochemical assay, not a software algorithm that undergoes a training phase with a distinct dataset. The development and optimization of such assays involve method development and validation, but not typically a "training set" as defined in AI/ML contexts.

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

As discussed in point 8, there is no explicit "training set" mentioned or implied for this biochemical assay in the context of AI/ML. The "ground truth" for the development and optimization of the assay's reagents and methodology would have been established through standard chemical and biological assay development practices, using reference materials and established analytical techniques.

Summary

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510 (k) Summary Safety and Effectiveness Information for VIDAS Progesterone (PRG) Assay

K 965084

Submitter Terry McGovern Quality Assurance and Regulatory Affairs Manager bioMerieux Vitek, Inc. 1022 Hingham Street Rockland, MA 02370 tel. (617) 871-4442, extension 116 fax (617) 871-3470

JAN - 9 1997

Summary preparation date - 1/6/97

The Product Classification for the VIDAS Progesterone (PRG) assay is under 21CFR 862.1620 Progesterone test system and is a Class I, Triage Tier II test system. The product classification numb for the VIDAS Progesterone (PRG) is 75 JLS. The common or usual name is Enzyme-linked Fluorescent Immunoassay (ELFA) for the quantitative detection of progesterone.

The DPC Coat-A-Count Progesterone assay was used as the predicate device for the determination of substantial equivalence.

The technological characteristics of the bioMerieux Progesterone enzyme-linked | fluorescent immunoassay (ELFA) are different from the radiological method (RIA) of DPC Progesterone Coat-A-Count in that ELFA uses enzymes as labels instead of redioisotopes. Therefore enzyme activity not radioactivity is measured. Enzyme-linked fluorescent immunoassay is a well established method for assaying analytes present in human serum or plasma.

Non-clinical (analytical) study summary

Crossreactivity Specificity studies demonstrate that the monoclonal antibody used in the VIDA 1. PRG assay is specific for progesterone. No cross-reactivity is seen with testosterone, corticosterone, 20a hydroxy-progesterone, 60 hydroxyprogesterone, 16a hydroxyprogesterone, Corticosterone, Estrone, Estriol and Estradiol. Cross-reactivity does exist with two metabolites of progesterone, specifically 5a and SB dilhydroxyprogesterone. The package insert cautions customers that individuals undergoing micronized progesterone therapy may exhibit elevated results when using the VIDAS PRG assay. 17a hydroxyprogesterone and decrycorticosterone demonstrated minimal crossreactivity. However, the normal concentrations found in a patient sera is far below that of
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progesterone. For example, in women, 17 a hydroxyprogesterone is 0.4ng/ml during the follicular phase and 1.8ng/ml in the luteal phase. In men the normal concentration is Ing/ml. For deoxycorticosterone the normal range is 40 - 160pg/ml. It is not likely that the VIDAS PRG assay will cause a falsely elevated progesterone result, due to the relative weak sera concentrations of 170 hydroxyprogesterone and deoxycorticosterone.

1. Interfering Substances No interference in VIDAS PRG assay performance was seen with servan collected in dry glass tubes containing a separating gel, and tubes containing lithium heparin and EDTA. No interference in the VIDAS PRG assay performance was seen with a range of concentrations of hemoglobin, lipids, or bilirubin.
1. Precision/Reproducibility Intra-assay precision stodies showed coefficients of variation ranging from 14.3% for 0.46 ng/ml to 3.8% for 45.1 ng/ml. Inter-assay reproducibility over a eight-week time period showed coefficients of variation ranging from 24.3% for 0.4 ng/ml to 3.1% for 45 norml. Inter-assay, inter-instrument reproducibility for five different serum samples in eight assays on different instruments vields coefficients of variation that do not exceed 5.4%.

Clinical study summary

1. Correlation

Comparison of the VIDAS PRG assay with the DPC Coat-A-Count Progesterone assay yie 8. line with the equation y = 1.0193x + -0.453 and a correlation coefficient of 0.985.
The calibrator in the kit ensures that the master curve stored by the VIDAS instrument is valid ﺷ for the shelf life of that kit. The body of data supports the use of a single calibrator for this purpose.
1. Sensitivity The limit of detection is determined to be 0.1 ng/ml of progesterone with: a 95 % confidence interval.

The conclusions drawn from the non-clinical and clinical tests demonstrate that the VIDAS PRG assey. if used as instructed in the package insert, is safe, effective and performs as well as or better than the legally marketed device identified in this submittal. The package insert should always be consulted along with the Operator's Manual to ensure that the assay is being performed properly. For additional information, references are listed in the package insert.

21.9

Regulation Number and Section

§ 862.1620 Progesterone test system.

(a)
Identification. A progesterone test system is a device intended to measure progesterone (a female hormone) in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of disorders of the ovaries or placenta.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 862.9.