(56 days)
FilmArray RP2/RP2plus Control Panel is intended for use as an external positive and negative assayed quality control to monitor performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Adenovirus, Coronavirus, Human Metapneumovirus, Human Rhinovirus/ Enterovirus, Influenza A subtype H1, Influenza A subtype H1-2009, Influenza A subtype H3, Influenza B, Middle East Respiratory Syndrome Coronavirus, Parainfluenza Virus, Respiratory Syncytial Virus, Bordetella parapertussis, Chlamydia pneumonia, and Mycoplasma pneumoniae by BioFire's FilmArray® RP2 and RP2plus assays on the FilmArray® Torch Systems. FilmArray RP2/RP2plus Control Panel is composed of synthetic RNA designed for and intended to be used solely with the FilmArray® RP2 and RP2plus assays. This product is not intended to replace manufacturer controls provided with the test system.
FilmArray RP2/RP2plus Control Panel, P/N M315, is a quality control panel consisting of controls, FilmArray RP2/RP2plus Positive (Positive Control), P/N M31721, and FilmArray RP2/RP2plus Negative, (Negative Control), P/N M31621. The Positive Control contains noninfectious surrogate control material; a solution of synthetic RNA transcripts in buffers, stabilizers and preservatives. The RNA carries segments of all respiratory pathogens detected by the FilmArray® RP2 and RP2plus assays (Table 1. below) on the FilmArray® 2.0 or FilmArray® Torch systems. The RNA in the Negative Control is non-specific RNA in buffers, stabilizers and preservatives. Each liquid control of FilmArray RP2/RP2plus Control Panel M265 is processed separately according to FilmArray® RP2 and RP2plus assays manufacturer's Instructions for Use for patient samples (nasopharyngeal swabs) obtained from individuals suspected of respiratory tract infection and placed in Viral Transport Media (VTM)).
The document describes the FilmArray RP2/RP2plus Control Panel, an assayed quality control material for clinical microbiology assays. The acceptance criteria and the study proving the device meets these criteria are detailed, focusing on its performance in monitoring BioFire's FilmArray® RP2 and RP2plus assays.
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for the FilmArray RP2/RP2plus Control Panel are implied by the performance metrics reported in the summary tables. The primary acceptance criteria appear to be:
- Correct Positive Control Result: All respiratory pathogen analytes in the Positive Control should be correctly detected.
- Correct Negative Control Result: No respiratory pathogens should be detected.
- Low Invalid Rate: A low or zero percentage of invalid results.
| Acceptance Criteria | Reported Device Performance (Internal & External Studies Combined) |
|---|---|
| Percent Correct Positive Control Results | 100% (150/150) |
| Percent Correct Negative Control Results | 99.4% (150/151) |
| Percent Invalid Results | 0% (0/301) |
2. Sample Size and Data Provenance
The study involved both an internal and an external study.
- Internal Study (MMQCI):
- Sample Size: 121 tests (60 Positive Controls, 61 Negative Controls)
- Provenance: Retrospective data from MMQCI (Saco, Maine, USA) over 20 days, involving 4 pouch lots and 4 operators.
- External Study (Clinical Sites):
- Sample Size: 180 tests (90 Positive Controls, 90 Negative Controls)
- Provenance: Retrospective data from 3 CLIA-certified clinical sites (country not specified, but likely USA given FDA submission) between July and August 2017, over a period of 10 days, using 3 FilmArray RP2 pouch lots and multiple operators.
Combined Test Set Sample Size: 301 total tests (150 Positive Control, 151 Negative Control)
3. Number of Experts and Qualifications for Ground Truth
This device is an assayed quality control material for an in vitro diagnostic (IVD) test, not an AI or imaging device requiring expert interpretation of medical images. Therefore, the concept of "experts used to establish the ground truth" in the traditional sense of medical image interpretation (e.g., radiologists) does not apply here.
The "ground truth" for this device is the known composition of the control panel:
- Positive Control: Contains synthetic RNA transcripts for specific respiratory pathogens. The ground truth is that these pathogens should be detected.
- Negative Control: Contains non-specific RNA. The ground truth is that no specific respiratory pathogens should be detected.
The performance of the device is evaluated against this pre-defined, engineered ground truth. There are no "experts" establishing clinical diagnoses for the test set.
4. Adjudication Method for the Test Set
Not applicable. As described above, the ground truth is pre-defined by the engineered composition of the control material, not through human interpretation or adjudication processes like 2+1 or 3+1 that are common in AI or diagnostic studies where human agreement is required to establish a consensus diagnosis for real patient data.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
Not applicable. The device is a quality control material, not a diagnostic device that assists human readers. Therefore, an MRMC study comparing human readers with and without AI assistance is not relevant to its evaluation.
6. Standalone Performance
Yes, the performance data presented is for the standalone performance of the FilmArray RP2/RP2plus Control Panel when run on the BioFire FilmArray® RP2 and RP2plus assays. The results indicate how well the control panel itself triggers the expected (positive or negative) outcome on the assay. The study assesses the characteristics of the control material, not how the control material assists humans in interpreting an assay result. The control material validates the assay's performance, ensuring its reliability.
7. Type of Ground Truth Used
The ground truth used is the engineered composition or known content of the control materials.
- For the Positive Control, the ground truth is the presence of specific synthetic RNA sequences designed to be detected by the FilmArray® RP2/RP2plus assays.
- For the Negative Control, the ground truth is the absence of these specific RNA sequences.
This is a form of analytical gold standard based on the intentional design and manufacturing of the control reagents.
8. Sample Size for the Training Set
Not applicable. The FilmArray RP2/RP2plus Control Panel is a manufactured reagent product, not an AI algorithm that requires a training set. The performance studies described are for validation and verification of the manufactured product's consistency and effectiveness as a quality control.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as there is no training set for this type of device. The "ground truth" for the control materials is inherent in their design and manufacturing specifications.
§ 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.”