(90 days)
MDx-Chex™ for BC-GP is intended for use as an external positive assayed control to monitor the performance of the qualitative detection of Gram-positive bacteria and associated antimicrobial resistance genes, by the Luminex VERIGENE® Gram-Positive Blood Culture Nucleic Acid Test (BC-GP) on Luminex VERIGENE® systems. The MDx-Chex™ for BC-GP Positive and Negative Controls are composed of a buffered solution with stabilized erythrocytes and leukocytes in a matrix of blood culture media components. Positive bacteria: Staphylococcus aureus, Staphylococus epidermidis, Staphylococcus lugdunensis, Streptococcus agalactiae, Streptococcus pneumoniae, Streptococus pyogenes, Enterococcus faecium, Streptococus faecium, Streptococus anginosus group; Species: Staphylococcus spp., Streptococcus spp.; antimicrobial resistance genes: mecA, vanA and vanB. Negative Control: buffered solution only. This product is not intended to replace manufacturer controls provided with the device.
MDx-Chex™ for BC-GP is a quality control kit consisting of positive and negative controls for the Luminex VERIGENE® Gram-Positive Blood Culture Test (BC-GP). The MDx-Chex™ for BC-GP Positive Control is positive for pathogens and resistance mechanisms in the VERIGENE BC-GP test (See Table 1). The MDx-Chex™ for BC-GP Negative Control is negative for pathogens and resistance mechanisms in the VERIGENE BC-GP test. Each control mix also controls for blood and blood culture media components that have been identified is inhibitors to DNA hybridization assays, namely hemoglobin, leukocyte DNA, and anticoagulants.
The MDx-Chex™ for BC-GP quality control kit contains stabilized blood components, blood culture media components, and inactivated, intact microorganisms resulting in a full-process, cellular-based control for the Luminex VERIGENE BC-GP panel.
Here's a breakdown of the acceptance criteria and the study used to prove the device meets these criteria, based on the provided text:
Device: MDx-Chex™ for BC-GP (Assayed Quality Control Material For Clinical Microbiology Assays)
Intended Use: To monitor the performance of qualitative detection of Gram-positive bacteria and associated antimicrobial resistance genes by the Luminex VERIGENE® Gram-Positive Blood Culture Nucleic Acid Test (BC-GP) on Luminex VERIGENE® systems.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criterion for all performance studies is ≥ 90% agreement with expected results.
| Study Type | Acceptance Criteria (PPA/NPA) | Reported Device Performance (PPA/NPA) |
|---|---|---|
| Multi-Site Precision (Reproducibility) | ||
| Positive Control | ≥ 90% | 100% (90/90) |
| Negative Control | ≥ 90% | 100% (90/90) |
| Single-Site Precision (Repeatability) | ||
| Positive Control | ≥ 90% | 100% (60/60) |
| Negative Control | ≥ 90% | 100% (60/60) |
| Lot-to-Lot Reproducibility | ||
| Positive Control Lot 22343 | ≥ 90% | 90% (9/10) |
| Positive Control Lot 22353 | ≥ 90% | 100% (10/10) |
| Positive Control Lot 22355 | ≥ 90% | 90% (9/10) |
| Negative Control Lot 22343 | ≥ 90% | 100% (10/10) |
| Negative Control Lot 22353 | ≥ 90% | 100% (10/10) |
| Negative Control Lot 22355 | ≥ 90% | 100% (10/10) |
| Within-Run Precision | ||
| Positive Control | ≥ 90% | 100% (10/10) |
| Negative Control | ≥ 90% | 100% (10/10) |
| Closed-Vial Stability (All Data Combined @ Day 0) | ||
| Positive Control | ≥ 90% | 100% (60/60) |
| Negative Control | ≥ 90% | 100% (60/60) |
| Closed-Vial Stability (All Data Combined @ Day 61+) | ||
| Positive Control (2-8°C) | ≥ 90% | 100% (60/60) |
| Positive Control (20-25°C) | ≥ 90% | 100% (60/60) |
| Negative Control (2-8°C) | ≥ 90% | 100% (60/60) |
| Negative Control (20-25°C) | ≥ 90% | 100% (60/60) |
| Closed-Vial Stability (Per Lot @ Day 0) | ||
| Positive Control (all lots) | ≥ 90% | 100% (20/20) for each lot |
| Negative Control (all lots) | ≥ 90% | 100% (20/20) for each lot |
| Closed-Vial Stability (Per Lot @ Day 61+) | ||
| Positive Control (all lots, both temps) | ≥ 90% | 100% (20/20) for each lot/temp |
| Negative Control (all lots, both temps) | ≥ 90% | 100% (20/20) for each lot/temp |
| Shipping Stability (Summer) | ||
| Positive Control (2-8°C) | ≥ 90% | 100% (20/20) |
| Positive Control (20-25°C) | ≥ 90% | 100% (20/20) |
| Negative Control (2-8°C) | ≥ 90% | 100% (20/20) |
| Negative Control (20-25°C) | ≥ 90% | 100% (20/20) |
| Shipping Stability (Winter) | ||
| Positive Control (2-8°C) | ≥ 90% | 100% (20/20) |
| Positive Control (20-25°C) | ≥ 90% | 100% (20/20) |
| Negative Control (2-8°C) | ≥ 90% | 100% (20/20) |
| Negative Control (20-25°C) | ≥ 90% | 100% (20/20) |
| Matrix Effect | ||
| Positive Control Matrix | ≥ 90% | 100% (3/3) |
| Clinical Matrix (Positive) | ≥ 90% | 100% (3/3) |
| Negative Control Matrix | ≥ 90% | 100% (3/3) |
| Clinical Matrix (Negative) | ≥ 90% | 100% (3/3) |
2. Sample Size Used for the Test Set and Data Provenance
- Multi-Site Precision (Reproducibility):
- Sample Size: 30 positive control samples and 30 negative control samples per lot (for each site, making a total of 90 positive and 90 negative samples across 3 sites for 1 lot, and 180 total runs per control type for all lots). The study used 3 lots, so effectively 30 positive and 30 negative tests per lot across 3 sites.
- Provenanc: Not explicitly stated, but implies a prospective study conducted at 3 different sites as part of device validation.
- Single-Site Precision (Repeatability):
- Sample Size: 20 samples per control type (positive and negative control tubes), 40 samples per MDx-Chex™ for BC-GP lot. Across 3 lots, this accumulated to 120 runs (20 runs per control type per lot across 3 lots).
- Provenance: Not explicitly stated, but implies a prospective study conducted at a single site as part of device validation.
- Lot-to-Lot Reproducibility:
- Sample Size: For the Lot-to-lot study, data from 10 positive and 10 negative control tubes per lot (30 data points per control type across 3 lots, totaling 60 data points). For the within-run precision, 10 tests for each positive and negative control tube from one lot (total of 20 tests).
- Provenance: Not explicitly stated, but implies a prospective study.
- Closed-Vial Stability and Shipping Stability:
- Sample Size: 20 positive and 20 negative control samples per MDx-Chex lot, collected at different data collection timepoints and stored at room (25°C) and refrigerated (2°C) temperatures. With 3 lots, this amounts to 60 positive and 60 negative total samples tested for each storage condition and time point. For shipping stability, one lot with 20 samples per control type for each simulated shipping profile.
- Provenance: Not explicitly stated, but implies a prospective study.
- Matrix Effect:
- Sample Size: Simulated positive MDx-Chex™ for BC-GP matrix and simulated positive clinical sample were tested in triplicate (3 samples each). Similarly, non-spiked simulated samples (negative controls) were tested in triplicate.
- Provenance: Not explicitly stated, but implies a prospective study.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
This device is an assayed quality control material for in vitro diagnostic tests. The ground truth (i.e., whether a control is 'positive' or 'negative' for specific pathogens/resistance genes) is inherent to the control material's design and formulation, not established by human experts interpreting results. The controls contain "inactivated, intact microorganisms" and specific resistance genes, and are designed to elicit a known positive or negative result on the target diagnostic system.
4. Adjudication Method for the Test Set
Adjudication methods like "2+1" or "3+1" are typically used for studies where human interpretation or consensus is required to establish ground truth (e.g., image interpretation). For an in vitro diagnostic quality control material like MDx-Chex™ for BC-GP, the "ground truth" of what the control should detect is pre-defined by its composition. There is no human adjudication process described or expected. The results from the Luminex VERIGENE® system are compared directly to the expected outcome of the quality control material.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic devices that involve human interpretation (e.g., radiologists reading images) and assessing how AI assistance might improve human performance. MDx-Chex™ for BC-GP is a quality control material for an automated molecular diagnostic test (Luminex VERIGENE® BC-GP) and does not involve human interpretation in the same way. The studies focus on the performance and stability of the control material itself.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, implicitly, the studies evaluate the "standalone" performance of the MDx-Chex™ controls when processed by the Luminex VERIGENE® System. Since the device is a quality control material, its "performance" is its ability to consistently produce the expected positive or negative results on the target instrument. The data presented demonstrates the consistency of these expected results. There's no "human-in-the-loop" component for the performance of the control material, other than operators performing the assay.
7. The Type of Ground Truth Used
The ground truth is pre-defined by the engineered composition of the quality control material.
- For the Positive Control, the ground truth is "Detected" for specific Gram-positive bacteria (e.g., Staphylococcus aureus, Enterococcus faecalis, Streptococcus pneumoniae) and antimicrobial resistance genes (mecA, vanA, vanB) that are intentionally included in the control.
- For the Negative Control, the ground truth is "Not Detected" because it is a buffered solution only, without the target microorganisms or resistance genes.
8. The Sample Size for the Training Set
Not applicable. This device is a quality control material, not an AI/machine learning algorithm that requires a training set. Its purpose is to monitor the performance of another diagnostic assay (Luminex VERIGENE® BC-GP), not to make diagnostic predictions itself.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no training set for this device.
§ 866.3920 Assayed quality control material for clinical microbiology assays.
(a)
Identification. An assayed quality control material for clinical microbiology assays is a device indicated for use in a test system to estimate test precision or to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. This type of device consists of single or multiple microbiological analytes intended for use with either qualitative or quantitative assays.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed device description documentation and information concerning the composition of the quality control material, including, as appropriate:
(i) Analyte concentration;
(ii) Expected values;
(iii) Analyte source;
(iv) Base matrix;
(v) Added components;
(vi) Safety and handling information; and
(vii) Detailed instructions for use.
(2) Premarket notification submissions must include detailed documentation, including line data as well as detailed study protocols and a statistical analysis plan used to establish performance, including:
(i) Description of the process for value assignment and validation.
(ii) Description of the protocol(s) used to establish stability.
(iii) Line data establishing precision/reproducibility.
(iv) Where applicable, assessment of matrix effects and any significant differences between the quality control material and typical patient samples in terms of conditions known to cause analytical error or affect assay performance.
(v) Where applicable, identify or define traceability or relationship to a domestic or international standard reference material and/or method.
(vi) Where applicable, detailed documentation related to studies for surrogate controls.
(3) Premarket notification submissions must include an adequate mitigation (e.g., real-time stability program) to the risk of false results due to potential modifications to the assays specified in the device's 21 CFR 809.10 compliant labeling.
(4) Your 21 CFR 809.10 compliant labeling must include the following:
(i) The intended use of your 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include the following:
(A) Assayed control material analyte(s);
(B) Whether the material is intended for quantitative or qualitative assays;
(C) Stating if the material is a surrogate control; and
(D) The system(s), instrument(s), or test(s) for which the quality control material is intended.
(ii) The intended use in your 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include the following statement: “This product is not intended to replace manufacturer controls provided with the device.”
(iii) A limiting statement that reads “Quality control materials should be used in accordance with local, state, federal regulations, and accreditation requirements.”