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The Xpert Xpress CoV-2/Flu/RSV plus test, performed on the GeneXpert Xpress System, is an automated multiplexed real-time reverse transcriptase polymerase chain reaction (RT-PCR) test intended for use in the simultaneous in vitro qualitative detection and differentiation of severe acute respiratory syndrome coronavirus (SARS-CoV-2), influenza A, influenza B, and/or respiratory syncytial virus (RSV) viral RNA in nasopharyngeal swab and anterior nasal swab specimens collected from individuals with signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory tract infection due to SARS-CoV-2, influenza A, influenza B, and RSV can be similar.

The Xpert Xpress CoV-2/Flu/RSV plus test is intended for use in the differential detection of SARS-CoV-2, influenza A, influenza B and/or RSV RNA and aids in the diagnosis of COVID-19, influenza and/or RSV infections if used in conjunction with other clinical and epidemiological information, and laboratory findings. SARS-CoV-2, influenza A, influenza B, and RSV viral RNA are generally detectable in nasopharyngeal swab and anterior nasal swab specimens during the acute phase of infection.

Positive results are indicative of the presence of the identified virus, but do not rule out bacterial infection or co-infection with other pathogens not detected by the test. The agent (s) detected by the Xpert Xpress CoV-2/Flu/RSV plus test may not be the definite cause of the disease.

Negative results do not preclude SARS-CoV-2, influenza A, influenza B and/or RSV infection. The results of this test should not be used as the sole basis for diagnosis, treatment or other patient management decisions.

The Xpert Xpress CoV-2/Flu/RSV plus test is an automated in vitro diagnostic test for the simultaneous qualitative detection and differentiation of SARS-CoV-2, Flu A, Flu B, and RSV viral RNA in nasopharyngeal swab (NPS) and anterior nasal swab (NS) specimens collected from individuals showing signs and symptoms of respiratory viral infection.

The Xpert Xpress CoV-2/Flu/RSV plus test is performed on GeneXpert Xpress System, which consist of a GeneXpert IV instrument that executes sample preparation, nucleic acid amplification and real-time fluorescent signal detection for the tests, and a GeneXpert Hub with preloaded GeneXpert Xpress software for running the tests and viewing the test results. The GeneXpert Hub accessory integrates the computer, touchscreen monitor and barcode scanner. Each of the GeneXpert modules in the GeneXpert IV instrument can perform independent sample preparation and testing. The GeneXpert Xpress System requires the use of single-use disposable cartridges that hold the RT-PCR reagents and host sample purification, nucleic acid amplification, and detection of the target sequences. Because the cartridges are self-contained, cross-contamination between samples is minimized.

The Xpert Xpress CoV-2/Flu/RSV plus test includes reagents for the detection of SARS-CoV-2, Flu A, Flu B and RSV viral RNA from NPS and NS specimens. The primers and probes in the Xpert Xpress CoV-2/Flu/RSV plus test are designed to amplify and detect unique sequences in the genes that encode the following proteins: SARS-CoV-2 nucleocapsid (N), SARS-CoV-2 envelope (E), SARS-CoV-2 RNA-dependent RNA polymerase (RdRP), influenza A matrix (M), influenza A basic polymerase (PB2), influenza A acidic protein (PA), influenza B matrix (M), influenza B non-structural protein (NS), and the RSV A and RSV B nucleocapsid.

A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge utilized by the GeneXpert instrument. The SPC is present to control for adequate processing of the sample and to monitor for the presence of potential inhibitor(s) in the RT-PCR reaction. The SPC also ensures that the RT-PCR reaction conditions (temperature and time) are appropriate for the amplification reaction and that the RT-PCR reagents are functional. The PCC verifies reagent rehydration, PCR tube filling, and confirms that all reaction components are present in the cartridge including monitoring for probe integrity and dye stability.

The Xpert Xpress CoV-2/Flu/RSV plus test is designed for use with NPS or NS specimens collected with nylon flocked swabs and placed into viral transport medium (VTM), Universal Transport Medium (UTM), or eNAT®. The ancillary specimen collection kits, swabs and transport media validated for use with the Xpert Xpress CoV-2/Flu/RSV plus test included:

• Nasopharyngeal Sample Collection Kit for Viruses

• Copan UTM® 3C057N (Flexible Minitip Flocked Swab with UTM® Medium without Beads)
• Copan eNAT® Molecular Collection and Preservation Medium P/N 6U074S01 (Flexible Minitap Flocked Swab with eNAT® Medium)

• Nasal Sample Collection Kit for Viruses

• Copan UTM® 3C064N (Regular Flocked Swab with UTM® Medium without Beads)
• Copan eNAT® Molecular Collection and Preservation Medium P/N 6U073S01 (Regular Flocked Swab with eNAT® Medium)

• Alternatively, swabs and transport media can be obtained separately:

• Nylon flocked swab (Copan P/N 502CS01, 503CS01)
• Viral Transport Medium, 3 mL (Copan P/N 330C, 3C047N, BD Universal Transport Medium, Remel M4RT, or Remel M5)

The ancillary reagents allow NPS and NS specimens from patients to be collected, preserved and transported to laboratory prior to analysis with the Xpert Xpress CoV 2/Flu/RSV plus test.

Based on the provided FDA 510(k) clearance letter and summary, here's an analysis of the acceptance criteria and study that proves the device meets them:

Important Note: This document describes a "Special 510(k) submission." This type of submission is used when changes are made to a previously cleared device that do not affect its fundamental technology, intended use, or safety/effectiveness. In this specific case, the changes were to the Assay Definition File (ADF) – essentially software parameter settings. Therefore, the "study that proves the device meets the acceptance criteria" largely relies on re-analysis of existing studies from the original device clearance (K242071) rather than entirely new, large-scale clinical trials.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document doesn't explicitly state quantitative acceptance criteria in a dedicated table. However, since this is a Special 510(k) for software parameter changes, the primary "acceptance criteria" appear to be demonstrating non-inferiority or equivalency to the previously cleared predicate device in terms of:

• Valid Test Runs: The number of tests that yield a valid result.
• Non-Determinate (ND) Test Results: The number of tests that do not yield a definitive positive or negative result (e.g., "NO RESULT").
• Performance Claims: That the modifications did not negatively impact the overall analytical and clinical performance claims established for the predicate device (sensitivity, specificity for detecting SARS-CoV-2, Flu A, Flu B, and RSV).

Inferred Acceptance Criteria and Reported Performance:

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

• Sample Size:
  • Main analysis: 16,264 test results. This number represents the re-analysis of "verification, validation and flex studies data from the original studies."
  • SARS-CoV-2 only test mode analysis: 25 test results.
  • Simulated conditions for revised algorithm: The document mentions "Test cartridges were simulated to generate SARS-CoV-2 INVALID and SPC FAIL conditions," but does not explicitly state the number of simulated tests.
• Data Provenance: The data used for re-analysis originated from the "original studies" (K242071 submission). The document does not specify the country of origin or whether these original studies were retrospective or prospective, though typical clinical validation studies for IVDs are often prospective. Given it references "flex study," those can sometimes include both retrospective and prospective elements.

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

The document does not provide information on the number or qualifications of experts used to establish the ground truth. This is likely because the ground truth was established during the original predicate device clearance (K242071) and this Special 510(k) focused on demonstrating equivalence in specific software-related metrics through re-analysis. For IVD devices like this, ground truth is typically established by comparing against a highly sensitive and specific reference method (e.g., an FDA-cleared laboratory developed test or a combination of clinical diagnosis and other accepted testing methods).

4. Adjudication Method for the Test Set

The document does not specify any adjudication method (e.g., 2+1, 3+1, none) for the test set. Again, this specific submission involved re-analysis of existing data rather than new clinical trials where such adjudication might be more explicitly detailed if human reads were involved. For an automated RT-PCR test, adjudication as typically understood for image-based AI would not be directly applicable.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted or is not mentioned in this document. This is an in vitro diagnostic device (RT-PCR test), not an AI-assisted diagnostic imaging system that would typically involve human readers interpreting images with or without AI assistance. The device is fully automated.

6. Standalone Performance (Algorithm Only)

Yes, the performance evaluated here is inherently standalone (algorithm only). The Xpert Xpress CoV-2/Flu/RSV plus is an automated RT-PCR test system. Its output is directly generated by the instrument and its embedded software (ADF). The "performance data" detailed in section 18.5 describes how the device's algorithmic and software changes affected its ability to produce valid results and interpret them correctly, without human intervention in the result generation.

7. Type of Ground Truth Used

The document does not explicitly state the type of ground truth used for the original studies, beyond stating "analytical, clinical and flex studies data." For RT-PCR assays, the ground truth for clinical performance is typically established by:

• Clinical Reference Method: Comparison against a highly sensitive and specific laboratory reference method (e.g., another FDA-cleared or EUA-authorized RT-PCR test, or a composite reference standard using multiple methods).
• Clinical Diagnosis/Outcomes Data (less common for purely diagnostic tests): While the device aids in diagnosis ("aids in the diagnosis of COVID-19, influenza and/or RSV infections if used in conjunction with other clinical and epidemiological information, and laboratory findings"), the performance claims themselves are based on detection of viral RNA, rather than patient outcomes as primary ground truth.

Given the nature of a molecular diagnostic test for viral RNA, the ground truth for the performance claims (sensitivity, specificity) of the original device would have been established by comparing the device's results against a highly reliable reference molecular test, often considered the "gold standard" for pathogen detection.

8. Sample Size for the Training Set

The document does not provide information on the sample size for the training set. This is because:

• This is an RT-PCR test, not a deep learning AI model that undergoes "training" in the typical machine learning sense. The "algorithm" here refers to the pre-defined logical rules and parameters within the Assay Definition File (ADF) for interpreting RT-PCR signals.
• The re-analysis was performed on verification, validation, and flex studies data, which are typically considered test or validation sets in the context of device development, not training sets.

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

As noted above, a "training set" and associated ground truth establishment in the context of deep learning AI are not applicable to this RT-PCR device. The "ground truth" for the device's performance relies on the known characteristics of the viral targets and the performance of the RT-PCR chemistry against reference methods.

Ask a specific question about this device

The Xpert Xpress CoV-2/Flu/RSV plus test, performed on the GeneXpert Dx and GeneXpert Infinity Systems, is an automated multiplexed real-time reverse transcriptase polymerase chain reaction (RT-PCR) test intended for use in the simultaneous in vitro qualitative detection and differentiation of severe acute respiratory syndrome coronavirus (SARS-CoV-2), influenza A, influenza B, and/or respiratory syncytial virus (RSV) viral RNA in nasopharyngeal swab and anterior nasal swab specimens collected from individuals with signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory tract infection due to SARS-CoV-2, influenza A, influenza B, and RSV can be similar.

The Xpert Xpress CoV-2/Flu/RSV plus test is intended for use in the differential detection of SARS-CoV-2, influenza A, influenza B and/or RSV RNA and aids in the diagnosis of COVID-19, influenza and/or RSV infections if used in conjunction with other clinical and epidemiological information, and laboratory findings. SARS-CoV-2, influenza A, influenza B, and RSV viral RNA are generally detectable in nasopharyngeal swab and anterior nasal swab specimens during the acute phase of infection.

Positive results are indicative of the presence of the identified virus, but do not rule out bacterial infection or co-infection with other pathogens not detected by the test. The agent (s) detected by the Xpert Xpress CoV-2/Flu/RSV plus test may not be the definite cause of the disease.

Negative results do not preclude SARS-CoV-2, influenza A, influenza B and/or RSV infection. The results of this test should not be used as the sole basis for diagnosis, treatment or other patient management decisions.

The Xpert Xpress CoV-2/Flu/RSV plus test is an automated in vitro diagnostic test for the simultaneous qualitative detection and differentiation of SARS-CoV-2, Flu A, Flu B, and RSV viral RNA in nasopharyngeal swab (NPS) and anterior nasal swab (NS) specimens collected from individuals showing signs and symptoms of respiratory viral infection.

The Xpert Xpress CoV-2/Flu/RSV plus test is performed on GeneXpert Instrument Systems (GeneXpert Dx, GeneXpert Infinity-48s and GeneXpert Infinity-80 systems, GeneXpert System with Touchscreen), which consist of an instrument, computer or touchscreen, and preloaded software for running tests and viewing the results. The GeneXpert Instrument Systems automate and integrate sample preparation, nucleic acid extraction and amplification, and detection of the target sequences in simple or complex samples using real-time reverse transcription (RT)-polymerase chain reaction (PCR) and PCR technology. Depending on the instrument, the GeneXpert Instrument Systems can have from 1 and up to 80 randomly accessible modules, each capable of performing separate sample preparation and real-time RT-PCR and PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time RT-PCR and PCR as well as detection. The systems require the use of single-use disposable cartridges that hold the RT-PCR reagents and host sample purification, nucleic acid amplification, and detection of the target sequences. Because the cartridges are self-contained, cross-contamination between samples is minimized.

The Xpert Xpress CoV-2/Flu/RSV plus test includes reagents for the detection of SARS-CoV-2, Flu A, Flu B and RSV viral RNA from NPS and NS specimens. The primers and probes in the Xpert Xpress CoV-2/Flu/RSV plus test are designed to amplify and detect unique sequences in the genes that encode the following proteins: SARS-CoV-2 nucleocapsid (N), SARS-CoV-2 envelope (E), SARS-CoV-2 RNA-dependent RNA polymerase (RdRP), influenza A matrix (M), influenza A basic polymerase (PB2), influenza A acidic protein (PA), influenza B matrix (M), influenza B non-structural protein (NS), and the RSV A and RSV B nucleocapsid.

A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge utilized by the GeneXpert instrument. The SPC is present to control for adequate processing of the sample and to monitor for the presence of potential inhibitor(s) in the RT-PCR reaction. The SPC also ensures that the RT-PCR reaction conditions (temperature and time) are appropriate for the amplification reaction and that the RT-PCR reagents are functional. The PCC verifies reagent rehydration, PCR tube filling, and confirms that all reaction components are present in the cartridge including monitoring for probe integrity and dye stability.

The Xpert Xpress CoV-2/Flu/RSV plus test is designed for use with NPS or NS specimens collected with nylon flocked swabs and placed into viral transport medium (VTM), Universal Transport Medium (UTM), or eNAT®.

The FDA 510(k) Clearance Letter for the Xpert Xpress CoV-2/Flu/RSV plus device describes modifications to an existing PCR test. The information provided outlines the acceptance criteria implicitly through the modifications and performance data presented. However, it's important to note that this document is a 510(k) summary, which provides a high-level overview of the submission and does not contain the full details of all studies conducted. Therefore, some requested information may not be explicitly present in the provided text.

Based on the provided text, here's an analysis:

Summary of Acceptance Criteria and Device Performance

The core of this 510(k) submission is a "Special 510(k)" which means the device (Xpert Xpress CoV-2/Flu/RSV plus) is largely the same as a previously cleared predicate device (K231481), but with minor design changes. Therefore, the acceptance criteria are implicitly tied to demonstrating that these changes do not negatively impact the previously established performance claims of the predicate device.

Specifically, the modifications include:

1. Turning off Signal Loss Detection (SLD) for the Flu B channel.
2. Revising the result reporting algorithm for the SARS-CoV-2 only test mode.
   • Previously: SARS-CoV-2 NEGATIVE if SARS-CoV-2 analyte result is INVALID and SPC is FAIL.
   • Revised: INVALID GeneXpert test result if SARS-CoV-2 analyte result is INVALID and SPC is FAIL.

Table of Acceptance Criteria (Implicit) and Reported Device Performance:

Study Details Proving Acceptance:

1. Sample sizes used for the test set and the data provenance:

   • Test Set (Re-analysis Data):
     • Analytical Test Results: 15,645
     • Clinical, Reproducibility-Precision, and Single-Site Precision Test Results: 9,525 (comprising 8,535 specimens and 990 controls).
   • Data Provenance: The document does not explicitly state the country of origin or whether the data was retrospective or prospective for the re-analyzed verification and validation studies. However, since it refers to "original studies" (K231481), it implies data previously collected and used for the predicate device's clearance.

2. Number of experts used to establish the ground truth for the test set and their qualifications:

   • This information is not provided in the given text. For an in vitro diagnostic (IVD) device like this, ground truth is typically established by comparative methods (e.g., another FDA-cleared PCR test, or a consensus of multiple clinical/laboratory results), not by human expert readers in the way an imaging AI device might use radiologists. The "ground truth" for this device's performance would be the presence or absence of viral RNA, determined by well-established laboratory methods.

3. Adjudication method for the test set:

   • This information is not provided and is generally not applicable to the type of re-analysis done for an IVD device where ground truth is established by laboratory methods rather than human interpretation requiring adjudication.

4. If a multi-reader multi-case (MRMC) comparative effectiveness study was done:

   • No, an MRMC study was not done. This type of study is primarily relevant for imaging AI devices that assist human readers in interpretation. This device is an automated, standalone diagnostic test.

5. If a standalone (i.e. algorithm only without human-in-the loop performance) was done:

   • Yes, implicitly. The re-analysis of performance data, particularly the comparison between the original and updated Assay Definition Files (ADF) and the verification of the revised algorithm, represents the standalone performance of the device's software (algorithm) logic. The device itself is an automated system.

6. The type of ground truth used:

   • Implicitly, the ground truth was established by laboratory reference methods (e.g., RT-PCR) for the original clinical specimens. For the re-analysis, the "ground truth" for evaluating the impact of the changes was the consistency of results and proper operation of the updated algorithm against the expected behavior, confirmed by the original analytical and clinical study data. For the SARS-CoV-2 algorithm change, "test cartridges were simulated to generate SARS-CoV-2 INVALID and SPC FAIL conditions," meaning the ground truth for this specific verification was a controlled simulation designed to trigger the specific algorithm conditions.

7. The sample size for the training set:

   • Not explicitly stated in relation to this Special 510(k) submission. As this is a modification to an existing device, it's likely that the original training/development data for the predicate device were used, but the size of that dataset is not provided here. The 15,645 analytical test results and 9,525 clinical/precision test results mentioned are re-analyzed verification and validation data, not training data.

8. How the ground truth for the training set was established:

   • Not explicitly stated in the provided text. For an RT-PCR diagnostic, the ground truth for training/development would typically involve characterized clinical samples or contrived samples with known viral concentrations and presence/absence of targets, verified by highly sensitive and specific reference methods (e.g., sequencing, confirmatory PCRs, or sometimes clinical outcomes correlated with virology).

Ask a specific question about this device

The Xpert Xpress CoV-2/Flu/RSV plus test, performed on the GeneXpert Xpress System, is an automated multiplexed real-time reverse transcriptase polymerase chain reaction (RT-PCR) test intended for use in the simultaneous in vitro qualitative detection and differentiation of severe acute respiratory syndrome coronavirus (SARS-CoV-2), influenza A, influenza B, and/or respiratory syncytial virus (RSV) viral RNA in nasopharyngeal swab anterior nasal swab specimens collected from individuals with signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory tract infection due to SARS-CoV-2, influenza B, and RSV can be similar.

The Xpert Xpress CoV-2/Flu/RSV plus is intended for use in the differential detection of SARS-CoV-2, influera A, influenza B, and/or RSV RNA and aids in the diagnosis of COVID-19, influenza, and/or RSV infections if used in conjunction with other clinical and epidemiological information, and laboratory findings. SARS-CoV-2, influenza A. influenza B, and RSV viral RNA are generally detectable in nasopharyngeal swab and anterior nasal swab specimens during the acute phase of infection.

Positive results are indicative of the identified virus, but do not rule out bacterial infection or co-infection with other pathogens not detected by the test. The agent (s) detected by the Xpert Xpress CoV-2/Flu/RSV plus test may not be the definite cause of the disease.

Negative results do not preclude SARS-CoV-2, influenza A virus, and/or RSV infection. The results of this test should not be used as the sole basis for treatment or other patient management decisions.

The Xpert Xpress CoV-2/Flu/RSV plus test is an automated in vitro diagnostic test for the simultaneous qualitative detection and differentiation of SARS-CoV-2. Flu A. Flu B. and RSV viral RNA in nasopharyngeal swab (NPS) and anterior nasal swab (NS) specimens collected from individuals showing signs and symptoms of respiratory viral infection.

The Xpert Xpress CoV-2/Flu/RSV plus test is performed on GeneXpert Xpress System, which consist of a GeneXpert IV instrument that executes sample preparation, nucleic acid amplification and real-time fluorescent signal detection for the tests, and a GeneXpert Hub with preloaded GeneXpert Xpress software for running the tests and viewing the test results. The GeneXpert Hub accessory integrates the computer, touchscreen monitor and barcode scanner. Each of the GeneXpert modules in the GeneXpert IV instrument can perform independent sample preparation and testing. The GeneXpert Xpress System requires the use of single-use disposable cartridges that hold the RT-PCR reagents and host sample purification, nucleic acid amplification, and detection of the target sequences. Because the cartridges are self-contained, cross-contamination between samples is minimized.

The Xpert Xpress CoV-2/Flu/RSV plus test cartridge includes reagents for the detection of SARS-CoV-2, Flu A, Flu B and RSV viral RNA from NPS and NS specimens. The primers and probes in the Xpert Xpress CoV-2/Flu/RSV plus test are designed to amplify and detect unique sequences in the genes that encode the following proteins: SARS-CoV-2 nucleocapsid (N), SARS-CoV-2 envelope (E), SARS-CoV-2 RNA-dependent RNA polymerase (RdRP), influenza A matrix (M), influenza A basic polymerase (PB2), influenza A acidic protein (PA), influenza B matrix (M), influenza B non-structural protein (NS), and the RSV A and RSV B nucleocapsid. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge utilized by the GeneXpert Xpress System. The SPC is present to control for adequate processing of the sample and to monitor for the presence of potential inhibitor(s) in the RT-PCR reaction. The SPC also ensures that the RT-PCR reaction conditions (temperature and time) are appropriate for the amplification reaction and that the RT-PCR reagents are functional. The PCC verifies reagent rehydration, PCR tube filling, and confirms that all reaction components are present in the cartridge including monitoring for probe integrity and dye stability.

The Xpert Xpress CoV-2/Flu/RSV plus test is designed for use with NPS or NS specimens collected with nylon flocked swabs and placed into viral transport medium (VTM), Universal Transport Medium (UTM), or eNAT®. The ancillary specimen collection kits, swabs and transport media validated for use with the Xpert Xpress CoV-2/Flu/RSV plus test include:

• Nasopharyngeal Sample Collection Kit for Viruses
  • Copan UTM® 3C057N (Flexible Minitip Flocked Swab with UTM® Medium O without Beads)
  • Copan eNAT® Molecular Collection and Preservation Medium P/N 6U074S01 о (Flexible Minitip Flocked Swab with eNAT® Medium)
• Becton Dickinson Universal Viral Transport Kit P/N 220531 (Flexible Minitip o Flocked Swab with UVT Medium)
• Nasal Sample Collection Kit for Viruses
  • Copan UTM® 3C064N (Regular Flocked Swab with UTM® Medium without O Beads)
  • Copan eNAT® Molecular Collection and Preservation Medium P/N 6U073S01 O (Regular Flocked Swab with eNAT® Medium)
• Alternatively, swabs and transport media can be obtained separately: ●
  • Nylon flocked swab (Copan P/N 502CS01, 503CS01) o
  • Viral transport medium, 3 mL (Copan P/N 330C, 3C047N, BD Universal O Transport Medium, Remel M4RT or Remel M5)

These ancillary reagents allow NPS and NS specimens from patients to be collected, preserved and transported to laboratory prior to analysis with the Xpert Xpress CoV-2/Flu/RSV plus test.

The provided document is a 510(k) Summary for the Cepheid Xpert Xpress CoV-2/Flu/RSV plus test. It details the performance studies conducted to demonstrate substantial equivalence to a predicate device. Here's a breakdown of the acceptance criteria and study proving the device meets them, based on the provided text:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly demonstrated through the reported performance in both analytical and clinical studies, aiming for high levels of agreement with established methods. The summarized performance data serves as the proof that the device meets these (implied) acceptance criteria.

Table of Acceptance Criteria and Reported Device Performance:

Since explicit acceptance criteria values (e.g., "PPA must be >= 95%") are not explicitly stated in the provided text as separate criteria, I will infer them from the reported strong performance and the nature of a 510(k) submission, where substantial equivalence to a predicate device is the goal. The reported performance is the validation that it meets the expected performance for such a device.

Ask a specific question about this device

The Xpert Xpress CoV-2/Flu/RSV plus test, performed on the GeneXpert Infinity Systems, is an automated multiplexed real-time reverse transcriptase chain reaction (RT-PCR) test intended for use in viro qualitative detection and differentiation of severe acute respiratory syndrome coronavirus (SARS-CoV-2), influenza B, and/or respiratory syncytial virus (RSV) viral RNA in nasopharyngeal swab specimens collected from individuals with signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory tract infection due to SARS-CoV-2, influenza A, influenza B, and RSV can be similar.

The Xpert Xpress CoV-2/Flu/RSV plus is intended for use in the differential detection of SARS-CoV-2, influenza B and or RSV RNA and aids in the diagnosis of COVID-19, influenza and/or RSV infections if used in conjunction with other clinical and epidemiological information, and laboratory findings. SARS-CoV-2, influenza B, and RSV viral RNA are generally detectable in nasopharyngeal swab anterior nasal swab specimens during the acute phase of infection.

Positive results are indicative of the identified virus, but do not rule out bacterial infection or co-infection with other pathogens not detected by the test. The agent(s) detected by the Xpert Xpress COV-2/Flu/RSV plus test may not be the definite cause of disease.

Negative results do not preclude SARS-CoV-2, influenza B, and/or RSV infection. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

The Xpert Xpress CoV-2/Flw/RSV plus test is an automated in vitro diagnostic test for the simultaneous qualitative detection and differentiation of SARS-CoV-2, Flu A, Flu B, and RSV viral RNA in nasopharyngeal swab (NPS) and anterior nasal swab (NS) specimens collected from individuals showing signs and symptoms of respiratory viral infection.

The Xpert Xpress CoV-2/Flu/RSV plus test is performed on GeneXpert Instrument Systems (GeneXpert Dx, GeneXpert Infinity-48s and GeneXpert Infinity-80 systems), which consist of an instrument, computer, and preloaded software for running tests and viewing the results. The GeneXpert Instrument Systems automate and integrate sample preparation, nucleic acid extraction and amplification, and detection of the target sequences in simple or complex samples using real-time reverse transcription (RT)-polymerase chain reaction (PCR) and PCR assays. Depending on the instrument, the GeneXpert Instrument Systems can have from 1 and up to 80 randomly accessible modules, each capable of performing separate sample preparation and real-time RT-PCR and PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time RT-PCR and PCR as well as detection. The systems require the use of single-use disposable cartridges that hold the RT-PCR reagents and host sample purification, nucleic acid amplification, and detection of the target sequences. Because the cartridges are selfcontained, cross-contamination between samples is minimized.

The Xpert Xpress CoV-2/Flu/RSV plus test includes reagents for the detection of SARS-CoV-2, Flu A. Flu B and RSV viral RNA from NPS and NS specimens. The primers and probes in the Xpert Xpress CoV-2/Flu/RSV plus test are designed to amplify and detect unique sequences in the genes that encode the following proteins: SARS-CoV-2 nucleocapsid (N), SARS-CoV-2 envelope (E), SARS-CoV-2 RNA-dependent RNA polymerase (RdRP), influenza A matrix (M), influenza A basic polymerase (PB2), influenza A acidic protein (PA), influenza B matrix (M), influenza B non-structural protein (NS), and the RSV A and RSV B nucleocapsid. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge utilized by the GeneXpert instrument. The SPC is present to control for adequate processing of the sample and to monitor for the presence of potential inhibitor(s) in the RT-PCR reaction. The SPC also ensures that the RT-PCR reaction conditions (temperature and time) are appropriate for the amplification reaction and that the RT-PCR reagents are functional. The PCC verifies reagent rehydration, PCR tube filling, and confirms that all reaction components are present in the cartridge including monitoring for probe integrity and dye stability.

The Xpert Xpress CoV-2/Flu/RSV plus test is designed for use with NPS or NS specimens collected with nylon flocked swabs and placed into viral transport medium (VTM), Universal Transport Medium (UTM), or eNAT®.

Acceptance Criteria and Study Details for Xpert Xpress CoV-2/Flu/RSV plus

The Xpert Xpress CoV-2/Flu/RSV plus test is an automated multiplexed real-time reverse transcriptase polymerase chain reaction (RT-PCR) test intended for the qualitative detection and differentiation of SARS-CoV-2, Influenza A, Influenza B, and/or Respiratory Syncytial Virus (RSV) viral RNA in nasopharyngeal swab (NPS) and anterior nasal swab (NS) specimens.

The performance of the device was evaluated through analytical and clinical studies.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for this device are implicitly derived from the observed clinical performance, demonstrating acceptable Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to a U.S. FDA-cleared molecular reference method.

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

• Clinical Performance Study:
  • SARS-CoV-2: A total of 5051 specimens (2536 NPS and 2515 NS) yielded valid results and were included in the performance evaluation.
    • NPS: 462 True Positives, 37 False Positives, 2023 True Negatives, 14 False Negatives.
    • NS: 448 True Positives, 24 False Positives, 2035 True Negatives, 8 False Negatives.
  • Flu A/B/RSV: A total of 5954 specimens (3011 NPS and 2943 NS) yielded valid results and were included in the performance evaluation.
    • NPS:
      • Flu A: 191 True Positives, 24 False Positives, 2794 True Negatives, 2 False Negatives.
      • Flu B: 57 True Positives, 0 False Positives, 2952 True Negatives, 2 False Negatives.
      • RSV: 71 True Positives, 0 False Positives, 2939 True Negatives, 1 False Negative.
    • NS:
      • Flu A: 196 True Positives, 18 False Positives, 2725 True Negatives, 4 False Negatives.
      • Flu B: 34 True Positives, 3 False Positives, 2906 True Negatives, 0 False Negatives.
      • RSV: 69 True Positives, 0 False Positives, 2871 True Negatives, 3 False Negatives.
• Data Provenance:
  • Prospective Data: Fresh (98.9%) and frozen (1.1%) specimens (Category I) were prospectively collected and tested in 2022 from 33 geographically diverse sites in the United States.
  • Retrospective Data: Archived prospectively collected frozen clinical specimens (Category II) from the 2016-2017 influenza season were used to supplement the sample size for Flu/RSV. These were primarily collected from the US.

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

The document does not explicitly state the number or qualifications of experts used to establish the ground truth. Instead, the ground truth was established by comparing the Xpert Xpress CoV-2/Flu/RSV plus test results to results from a U.S. FDA-cleared molecular respiratory panel for SARS-CoV-2 and a U.S. FDA-cleared molecular Flu A/B/RSV assay for their respective targets.

4. Adjudication Method for the Test Set

Discrepant results between the Xpert Xpress CoV-2/Flu/RSV plus test and the comparator method were investigated as follows:

• SARS-CoV-2 target: Discrepant results were investigated using a U.S. FDA EUA SARS-CoV-2 molecular test.
• Flu A/B/RSV targets: Discrepant results were investigated using a U.S. FDA-cleared molecular respiratory panel.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly conducted as the device is an in-vitro diagnostic (IVD) test, not an AI-powered diagnostic imaging device involving human readers.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done

Yes, the studies presented are generally standalone performance evaluations of the device (an automated test) without human-in-the-loop adjustment of the result. The device automates sample preparation, nucleic acid extraction, amplification, and detection, and provides results automatically ("algorithm only"). The clinical performance compares the device's output directly to accepted reference methods.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The ground truth for the clinical performance study was established using U.S. FDA-cleared molecular reference methods for viral detection:

• A U.S. FDA-cleared molecular respiratory panel for SARS-CoV-2.
• A U.S. FDA-cleared molecular Flu A/B/RSV assay for Flu A, Flu B, and RSV.
• For discrepant results, additional U.S. FDA EUA SARS-CoV-2 molecular test or U.S. FDA-cleared molecular respiratory panel was used for adjudication.

8. The Sample Size for the Training Set

The document does not specify a distinct "training set" for the clinical performance study as is typical for AI/ML models. For IVD devices like this, the development process (which would involve internal analytical studies and optimization) constitutes the "training" equivalent. The analytical studies describe the evaluation of analytical sensitivity, inclusivity (wet-testing of multiple strains), and exclusivity, which would directly inform the device's design and parameters. For example:

• Analytical sensitivity (LoD) testing involved 2 reagent lots and 20 replicates per virus/lot combination.
• Analytical reactivity (inclusivity wet-testing) involved testing 102 respiratory viral strains (18 SARS-CoV-2, 69 influenza, 15 RSV) at ~3x LoD, with 3 replicates per strain.

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

For the analytical "training" phase:

• Analytical Sensitivity (LoD): Ground truth was established by using known concentrations of inactivated viruses and international standards (e.g., NATtrol SARS-CoV-2, 1st WHO International Standard, cultured Flu A, Flu B, and RSV strains) spiked into negative clinical matrices. The LoD was determined by Probit regression analysis and verified as the lowest concentration yielding 95% positive results.
• Analytical Reactivity (Inclusivity): Ground truth was established by testing known viral strains at specified concentrations (~3x LoD) and expecting a positive detection for the corresponding target.
• Analytical Specificity (Exclusivity): Ground truth was established by testing a panel of known microorganisms and expecting negative results for all targets, thus confirming no cross-reactivity. These were either cultured microorganisms or synthetic RNA/genomic DNA at known concentrations.

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