(277 days)
SPOTFIRE® RSP Positive Control is intended for use as an external positive assayed quality control to monitor performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Bordetella parapertussis, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae, Adenovirus, seasonal Coronavirus, Coronavirus SARS-CoV-2, Human Metapneumovirus, Human Rhinovirus, Influenza A Subtype H1-2009, Influenza A Subtype H3, Influenza B, Parainfluenza Virus and Respiratory Syncytial Virus using the BIOFIRE® SPOTFIRE® Respiratory (R) Panel performed on the BIOFIRE® SPOTFIRE® System. SPOTFIRE RSP Positive Control is comprised of in vitro RNA transcripts and stabilizing solution and is designed for and intended to be used solely with the BIOFIRE SPOTFIRE R Panel. This product is not intended to replace manufacturer internal controls provided with the device.
SPOTFIRE® RSP Negative Control is intended for use as an external negative assayed quality control to monitor performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Bordetella parapertussis, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae, Adenovirus, seasonal Coronavirus, Coronavirus SARS-CoV-2, Human Metapneumovirus, Human Rhinovirus, Influenza A Subtype H1-2009, Influenza A Subtype H3, Influenza B, Parainfluenza Virus and Respiratory Syncytial Virus using the BIOFIRE® SPOTFIRE® Respiratory (R) Panel performed on the BIOFIRE® SPOTFIRE® System. SPOTFIRE RSP Negative Control is comprised of a solution that does not contain target analytes and is designed for and intended to be used solely with the BIOFIRE SPOTFIRE R Panel. This product is not intended to replace manufacturer internal controls provided with the device.
SPOTFIRE® RSP Pos & Neg Controls, P/N M425, is a quality control panel consisting of 2 separate kits of ready-to-use, liquid controls, SPOTFIRE® RSP Positive Control (Positive Control), P/N M42638 and SPOTFIRE® RSP Negative Control (Negative Control), P/N M42738. The Positive Control contains non-infectious surrogate control material; a solution of synthetic RNA transcripts in buffer, stabilizers and preservatives. The RNA in the Positive Control carries RNA segments of all the respiratory pathogens detected by the BIOFIRE® SPOTFIRE® Respiratory (R) Panel on the BIOFIRE® SPOTFIRE® System (see Table 1 below) and is specifically designed for and intended to be used solely with the SPOTFIRE R Panel assay on the SPOTFIRE System. The Negative Control contains buffer and preservatives with no RNA. Each liquid control of SPOTFIRE® RSP Pos & Neg Controls, P/N M425, is processed separately according to the SPOTFIRE R Panel assay manufacturer's Instructions for Use for Quality Control testing.
The provided text describes the acceptance criteria and the study that proves the device (SPOTFIRE® RSP Pos & Neg Controls) meets those criteria. The device being reviewed is a quality control material for clinical microbiology assays, not an AI/ML-enabled diagnostic device. Therefore, many of the requested categories pertaining to AI/ML device studies (e.g., number of experts for ground truth, adjudication methods, MRMC studies, effect size of human reader improvement with AI, standalone performance, training set details) are not applicable to this submission.
However, I can extract the relevant information regarding the acceptance criteria and the performance study for this quality control material.
Here's the information based on the provided text, focusing on what is applicable to the described device and study:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated as numerical thresholds (e.g., "sensitivity must be > 90%"). Instead, the document refers to "predetermined criteria" for reproducibility that were met. The reported performance is an "overall correct result rate."
| Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|
| Reproducibility of SPOTFIRE RSP Positive and RSP Negative Control is acceptable. | Overall correct result rate of 99.7%. |
| (External Sites) Predetermined acceptance criteria for reproducibility met. | Overall success rate of 99.6%. |
| (Internal Sites) Predetermined acceptance criteria for reproducibility met. | Overall correct result rate of 100%. |
2. Sample Size Used for the Test Set and Data Provenance
- Total Test Results: 361 initially, leading to 351 valid test results after repeating invalid ones.
- External Performance Study (Test Set): 232 initially, leading to 225 valid controls after repeating invalid ones.
- Data Provenance: Prospective, collected from 5 near-patient clinical sites across the US (presumably, given the context of FDA submission, though not explicitly stated but implied by "near-patient clinical sites" in the context of an FDA filing for a US company).
- Internal Study (Test Set): 129 initially, leading to 126 valid results after repeating invalid ones.
- Data Provenance: Prospective, conducted at MMQCI facility in Saco, Maine, USA.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
- Not Applicable. This is a quality control material where the "ground truth" is inherent to the control material itself (i.e., whether it should be positive for specific analytes or negative for all analytes). The "correctness" of the result is determined by its agreement with the expected outcome for that control. The study evaluates the reproducibility and performance of the control and the assay system, not a diagnostic decision requiring expert consensus.
4. Adjudication Method for the Test Set
- Not Applicable. As this is a quality control material, the "ground truth" for each control (whether it should yield a positive or negative result) is predefined by its composition. There is no human adjudication process for categorizing results as "correct" or "incorrect" beyond comparing them to the expected outcome based on the control's design. Invalid results were repeated as per BioFire instructions.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- Not Applicable. This is not an AI/ML-enabled diagnostic device. No human readers, AI assistance, or comparative effectiveness studies of this nature were performed.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
- Not Applicable. This is a physical quality control material used with an in-vitro diagnostic system (BIOFIRE® SPOTFIRE® System). Its performance is evaluated within that system, not as a standalone algorithm.
7. The Type of Ground Truth Used
- Defined Composition: The ground truth for the SPOTFIRE® RSP Positive Control is the presence of synthetic RNA transcripts corresponding to specific respiratory pathogens, manufactured to be detected by the BIOFIRE® SPOTFIRE® Respiratory (R) Panel.
- Defined Absence: The ground truth for the SPOTFIRE® RSP Negative Control is the absence of target analytes, designed to yield a negative result.
- The "correct" result for each control is based on its predetermined design and expected performance with the intended assay.
8. The Sample Size for the Training Set
- Not Applicable. As this is a quality control material and not an AI/ML model, there is no "training set." The study described evaluates the performance and reproducibility of the manufactured control materials within their intended use.
9. How the Ground Truth for the Training Set Was Established
- Not Applicable. See point 8.
§ 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.”