(233 days)
The MeMed BV test is an automated semi-quantitative immunoassay that measures three non-microbial (host) proteins (TRAIL, IP-10, and CRP) in adult and pediatric serum samples and is intended for use in conjunction with clinical assessments and other laboratory findings as an aid to differentiate bacterial from viral infection. The MeMed BV is indicated for use in patients presenting to the emergency department or urgent care center and with samples collected at hospital admission from patients with suspected acute bacterial or viral infection, who have had symptoms for less than seven days. The MeMed BV test generates a numeric score that falls within discrete interpretation bins based on the increasing likelihood of bacterial infection.
The Med BV® ("BV Test" or the "Test") is an In-Vitro-Diagnostic device that measures in parallel the blood concentrations of TRAIL, IP-10 and CRP. The Test consists of an automated analyzer with built-in hardware and software that conduct chemiluminescencebased analyte measurements of patient serum samples and their computational integration (MeMed Key®), and a disposable cartridge that contains the reagents and controls needed to detect the analytes of interest (MeMed BV® cartridge). The Test generates an answer to each sample, with a test run time of approximately 15 minutes.
The provided text is a 510(k) Summary for a modified medical device, the MeMed BV. It describes the device, its intended use, technological characteristics, and a comparison to a previously cleared predicate device. However, it explicitly states that the purpose of this specific 510(k) notice is for a modification to the already cleared device, primarily concerning an alternative manufacturing process for a component (Antibody-Alkaline Phosphatase conjugation chemistry) and a new buffer formulation.
The document does not provide detailed acceptance criteria or the full study findings that would typically be presented for a de novo clearance or a 510(k) for a novel device. Instead, it refers to prior studies for the original cleared device and asserts that the modified device's performance is equivalent.
Therefore, many of the requested details about acceptance criteria, detailed study results, sample sizes, ground truth establishment, and expert involvement are not present in the provided document for this specific submission (K222332). The document focuses on demonstrating that the modification does not negatively impact the performance, based on studies referencing the original device's validation.
Here's a breakdown of what can be extracted and what is missing:
1. Acceptance Criteria and Reported Device Performance
The document states: "The modified version of the MeMed BV has been tested according to the methods, protocols, and acceptance criteria used to support the previously 510(k)-cleared device. These methods apply to the device that is the subject of this Special 510(k) and were used in verification and validation ("V&V") of the modifications. The studies tested the performance of the measurement procedure for each individual measurand - CRP, IP-10, and TRAIL, as well as the performance of the measurement procedure for the MeMed BV® test score that is based on the computational integration of the three measurands. Testing included precision/reproducibility, LoQ, linearity, hook effect, interference/cross-reactivity, and method comparison testing. All testing indicated equivalent performance to the 510(k)-cleared MeMed BV."
This document does not list the specific numerical acceptance criteria or detailed results for performance metrics like sensitivity, specificity, or AUC as it is a Special 510(k) for a modification, not an initial clearance. It merely states that the modified device's performance was equivalent to the previously cleared predicate device, and the types of tests conducted for V&V.
| Performance Metric (Types of Studies Conducted) | Acceptance Criteria (Not Explicitly Stated in Document) | Reported Device Performance (as stated in document) |
|---|---|---|
| Precision/Reproducibility | (Presumed to be within pre-defined limits for predicate) | Indicated equivalent performance to 510(k)-cleared MeMed BV |
| Limit of Quantitation (LoQ) | (Presumed to be within pre-defined limits for predicate) | Indicated equivalent performance to 510(k)-cleared MeMed BV |
| Linearity | (Presumed to be within pre-defined limits for predicate) | Indicated equivalent performance to 510(k)-cleared MeMed BV |
| Hook Effect | (Presumed to be within pre-defined limits for predicate) | Indicated equivalent performance to 510(k)-cleared MeMed BV |
| Interference/Cross-Reactivity | (Presumed to be within pre-defined limits for predicate) | Indicated equivalent performance to 510(k)-cleared MeMed BV |
| Method Comparison | (Presumed to demonstrate agreement with predicate) | Indicated equivalent performance to 510(k)-cleared MeMed BV |
| Measurement of TRAIL, IP-10, CRP | (Quantitative limits for immunoassays, not specified) | Indicated equivalent performance to 510(k)-cleared MeMed BV |
| MeMed BV® test score | (Algorithm output performance, not specified) | Indicated equivalent performance to 510(k)-cleared MeMed BV |
2. Sample Size Used for the Test Set and Data Provenance
The document does not provide details on the specific sample sizes used for the test set or the data provenance (country of origin, retrospective/prospective). It refers to the validation done for the previously cleared device.
3. Number of Experts Used to Establish Ground Truth and Qualifications
The document does not provide details on the number or qualifications of experts used to establish ground truth because it's a submission for a modification, not a de novo clearance. Ground truth would have been established during the original device's clearance.
4. Adjudication Method for the Test Set
The document does not provide details on any adjudication method.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
The document does not mention or describe an MRMC comparative effectiveness study or any effect size related to human readers improving with AI vs. without AI assistance. The MeMed BV is an in-vitro diagnostic (IVD) device measuring biomarkers, not an AI imaging or diagnostic algorithm designed to assist human readers in image interpretation.
6. Standalone (Algorithm Only) Performance Study
The document describes the device as an "automated semi-quantitative immunoassay that measures three non-microbial (host) proteins (TRAIL, IP-10, and CRP)... The MeMed BV test generates a numeric score that falls within discrete interpretation bins." This indicates it is a standalone algorithm in the sense that it processes the biomarker measurements and outputs a score. However, it's not a standalone AI performance study in the context of, for example, a diagnostic imaging algorithm being compared to expert interpretation. It's a measurement technology combined with a computational integration.
The performance studies mentioned ("precision/reproducibility, LoQ, linearity, hook effect, interference/cross-reactivity, and method comparison testing") are typical for standalone IVD device performance.
7. Type of Ground Truth Used
The document indicates the device "is intended for use in conjunction with clinical assessments and other laboratory findings as an aid to differentiate bacterial from viral infection." This strongly implies that the ground truth for the original validation studies would have been established based on clinical diagnoses, confirmed microbiological cultures/PCR, and a thorough review of patient outcomes and medical records by expert clinicians. However, the exact methodology for ground truth establishment for the original device is not detailed in this document.
8. Sample Size for the Training Set
The document does not provide any information regarding the sample size for a training set. As this is an IVD device and not explicitly an AI/machine learning model where "training sets" are typically discussed, this information might not be presented in this format, or it would have been part of the original device's clearance. The "computational integration" aspect implies an algorithm, but training details are not given.
9. How the Ground Truth for the Training Set Was Established
Similarly, the document does not provide any information on how the ground truth for any training set was established.
§ 866.3215 Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis.
(a)
Identification. A device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis is identified as an in vitro device intended for the detection and qualitative and/or quantitative measurement of one or more non-microbial analytes in human clinical specimens to aid in the assessment of patients with suspected sepsis when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include the device's detailed Indications for Use statement describing what the device detects and measures, the results provided to the user, whether the measure is qualitative and/or quantitative, the clinical indications for which the test is to be used, and the specific population(s) for which the device use is intended.
(2) Premarket notification submissions must include detailed documentation of the device description, including (as applicable), all device components, software, ancillary reagents required but not provided, explanation of the device principle and methodology, and for molecular devices include detailed documentation of the primer/probe sequence, design, and rationale for sequence selection.
(3) Premarket notification submissions must include detailed documentation of applicable analytical studies, such as, analytical sensitivity (Limit of Detection, Limit of Blank, and Limit of Quantitation), precision, reproducibility, analytical measuring range, interference, cross-reactivity, and specimen stability.
(4) Premarket notification submissions must include detailed documentation of a prospective clinical study or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information:
(i) Results must demonstrate adequate device performance relative to a well-accepted comparator.
(ii) Clinical sample results must demonstrate consistency of device output throughout the device measuring range likely to be encountered in the Intended Use population.
(iii) Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the Indications for Use(s), and results of all statistical analyses.
(5) Premarket notification submissions must include evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics (
e.g., age, racial, ethnic, and gender distribution) similar to the Intended Use population.(6) As part of the risk management activities performed under 21 CFR 820.30 design controls, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument.
(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling, and a detailed explanation of the interpretation of the limitations of the samples (
e.g., collected on day of diagnosis) must be included in the device's 21 CFR 809.10(b)(10) compliant labeling.