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The cobas® Influenza A/B & RSV Nucleic acid test for use on the cobas® Liat® System (cobas® Influenza A/B & RSV) is an automated multiplex real-time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of Influenza A virus, Influenza B virus and respiratory syncytial virus (RSV) RNA in nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. The test is intended for use as an aid in the differential diagnosis of Influenza A, Influenza B, and RSV in humans and is not intended to detect Influenza C.

Negative results do not preclude Influenza virus or RSV infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.

Performance characteristics for Influenza A were established during the 2013-2014 and the 2014-2015 influenza seasons when Influenza A/H3 and A/H1N1 pandemic were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary.

If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL3+ facility is available to receive and culture specimens.

The cobas® Liat® Influenza A/B & RSV Nucleic Acid Test for use on the cobas® Liat® System (cobas® Influenza A/B & RSV) is an automated in vitro diagnostic test for the qualitative detection of Influenza A, Influenza B, and RSV RNA in nasopharyngeal swab (NPS) specimens. The sample-to-result time is ~20 minutes.

The assay is performed on the Analyzer which automates and integrates sample purification, nucleic acid amplification, and detection of the target sequence in biological samples using realtime RT-PCR assays. The assay targets a well-conserved region of the matrix gene of Influenza A (Inf A target), the non-structure protein gene of Influenza B (Inf B target), and the matrix gene of RSV (RSV target). An Internal Process Control (IPC) is also included. The IPC is present to control for adequate processing of the target virus through all steps of the assay process and to monitor the presence of inhibitors in the RT-PCR reactions.

The System consists of an instrument and preloaded software for running tests and viewing the results. The system requires the use of a single-use disposable cobas® Influenza A/B & RSV assay tube that holds the nucleic acid purification and RT-PCR reagents, and hosts the sample preparation and RT-PCR processes.

The detection module monitors the reaction in real-time, while an on-board computer analyzes the collected data and outputs an interpreted result. The latter is displayed in the assay report on the integrated LCD touch screen of the cobas® Liat® Analyzer and in an electronic file. The report can be printed directly through a USB or network-connected printer. The results can also be exported to an external server, middleware or data management system, or to a Laboratory Information System (LIS).

The provided text describes a 510(k) premarket notification for a medical device: "cobas Influenza A/B & RSV nucleic acid test for use on the cobas Liat System." This document is focused on demonstrating the substantial equivalence of a modified device to a previously cleared predicate device, specifically regarding a change in the negative control buffer and positive control diluent. It does not contain detailed information about initial acceptance criteria, a comprehensive study proving the device met those criteria, sample sizes for test sets, data provenance, expert adjudication, MRMC studies, standalone performance, or training set details that would be typical for a de novo device clearance or a more extensive clinical validation study.

Therefore, many of the requested details cannot be extracted from this document. The document primarily states that the performance claims were not impacted by the change, implying that the performance previously demonstrated for the predicate device still holds true.

Here's what can be extracted and what cannot:

1. Table of acceptance criteria and reported device performance:

The document doesn't explicitly lay out "acceptance criteria" for a new device but rather compares the performance aspects of the submitted device (with the changed control materials) to the predicate device. It asserts that performance claims were not impacted. The relevant performance aspects of the predicate device (which the current device is deemed equivalent to) are listed, essentially serving as the implied performance to be met.

2. Sample sized used for the test set and the data provenance:

• The document states: "Performance of the cobas® Influenza A/B & RSV assay when used with NEG BUF as a negative control and positive control diluent was assessed."
• Sample size and data provenance are NOT explicitly stated. This document focuses on demonstrating that a change to control materials did not impact performance, rather than providing the full details of a new clinical study. The original predicate device's performance characteristics for Influenza A were established during the 2013-2014 and 2014-2015 influenza seasons, implying retrospective data from those periods for the predicate. However, details of the assessment of the impact of the control material change (which is the focus of this 510(k)) are not provided.

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

• NOT explicitly stated. This type of detail is typically found in clinical study reports for initial device approvals, not usually in a 510(k) for a minor modification like a control reagent change. The ground truth for real-time PCR assays like this is usually established by highly sensitive and specific laboratory methods (e.g., cell culture, sequencing, or a gold-standard PCR).

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set:

• NOT applicable/explicitly stated. This refers to human reader adjudication for image-based AI devices. This document describes an in vitro diagnostic (IVD) PCR assay, which ideally has a definitive laboratory-based ground truth rather than subjective human interpretation needing adjudication.

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 a PCR assay, not an AI-assisted diagnostic imaging device that involves human readers.

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

• Partially Applicable. The cobas Liat System is an automated assay that processes samples and outputs results. The "performance" described (Limit of Detection, Reactivity, etc.) inherently represents its standalone (algorithm/instrument only) performance. There is no human interpretation component that would require a human-in-the-loop study.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc):

• For molecular diagnostic tests like this, the ground truth is typically established by:
  • Clinically confirmed cases: Samples from patients with confirmed infections by other validated methods (e.g., viral culture, sequencing, or a highly sensitive and specific reference PCR method).
  • Characterized challenge panels: Samples with known concentrations of the target analytes and related organisms.
• The document implies that the ground truth for the predicate's performance was based on the presence/absence of viral RNA and likely confirmed by other laboratory methods. It references "established during the 2013-2014 and the 2014-2015 Influenza seasons," which suggests clinical samples with confirmed infection statuses.

8. The sample size for the training set:

• NOT applicable/explicitly stated. This is not an AI/machine learning device that typically has a "training set" in the common sense. It's a PCR assay with defined reagents and a fixed algorithm. The development would involve analytical verification and validation, but not machine learning "training."

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

• NOT applicable. See point 8.

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The cobas® Influenza A/B & RSV Nucleic acid test for use on the cobas® Liat® System (cobas® Influenza A/B & RSV) is an automated multiplex real-time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of Influenza A virus, Influenza B virus and respiratory syncytial virus (RSV) RNA in nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection with clinical and epidemiological risk factors. The test is intended for use as an aid in the differential diagnosis of Influenza B, and RSV in humans and is not intended to detect Influenza C.

Negative results do not preclude Influenza virus or RSV infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule-out bacterial infection with other viruses. The agent detected may not be the definite cause of disease.

Performance characteristics for Influenza A were established during the 2013-2014 and the 2014-2015 Influenza seasons when Influenza A/H3 and A/H/N1 pandemic were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary.

If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.

The cobas® Influenza A/B & RSV Nucleic Acid Test for use on the cobas® Liat® System (cobas® Influenza A/B & RSV) is an automated in vitro diagnostic test for the qualitative detection of Influenza A, Influenza B, and RSV RNA in nasopharyngeal swab (NPS) specimens. The sample-to-result time is ~20 minutes.

The assay is performed on the cobas® Liat® Analyzer which automates and integrates sample purification, nucleic acid amplification, and detection of the target sequence in biological samples using real-time RT-PCR assays. The assay targets a well-conserved region of the matrix gene of Influenza A (Inf A target), the non-structure protein gene of Influenza B (Inf B target), and the matrix gene of RSV (RSV target). An Internal Process Control (IPC) is also included. The IPC is present to control for adequate processing of the target virus through all steps of the assay process and to monitor the presence of inhibitors in the RT-PCR reactions.

The cobas® Liat® System consists of an instrument and preloaded software for running tests and viewing the results. The system requires the use of a single-use disposable cobas® Influenza A/B & RSV assay tube that holds the nucleic acid purification and RT-PCR reagents, and hosts the sample preparation and RT-PCR processes.

The detection module monitors the reaction in real-time, while an on-board computer analyzes the collected data and outputs an interpreted result. The latter is displayed in the assay report on the integrated LCD touch screen of the cobas® Liat® Analyzer and in an electronic file. The report can be printed directly through a USB or network-connected printer. The results can also be exported to an external server, middleware or data management system, or to a Laboratory Information System (LIS).

Here's a breakdown of the acceptance criteria and study information for the cobas® Influenza A/B & RSV Nucleic acid test, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The document primarily focuses on demonstrating that the modified device (cobas® Influenza A/B & RSV Assay Script v1.16) has equivalent performance to the predicate device (cobas® Influenza A/B & RSV Assay Script v1.15). Therefore, the acceptance criteria are largely implicitly tied to matching or maintaining the performance characteristics of the predicate device.

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

• Sample Size: The test set included "multiple sample types" for each configuration of the assay script (v1.15 and v1.16). Specifically, these included negative controls, positive controls, negative specimens, and positive specimens containing co-formulated Influenza A, Influenza B, and RSV target material at a concentration of 3X the Limit of Detection (LoD). For the 3X LoD samples, mean Ct values were assessed.
• Data Provenance: The document does not explicitly state the country of origin. It indicates the study was conducted internally by Roche Molecular Diagnostics (RMD), Pleasanton, CA. It is a retrospective study in the sense that it compares a modified version of the software (v1.16) against a previously cleared version (v1.15) using defined sample types, rather than collecting new clinical samples from patients.

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

Not applicable. This study is an analytical performance assessment comparing a software version against a previous version, not a clinical study involving diagnosis by experts. The "ground truth" for the test set specimens (e.g., negative controls, positive controls, 3X LoD samples) would have been established by the manufacturer's internal quality control and characterization processes.

4. Adjudication Method for the Test Set

Not applicable, as this was an analytical comparison study of software versions, not a clinical trial requiring adjudication of diagnostic outcomes.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No. This was not a multi-reader, multi-case comparative effectiveness study. It was a technical comparison of an updated software algorithm (Assay Script v1.16) against a previous version (v1.15) for an existing in vitro diagnostic device. Therefore, there's no mention of human readers or improved performance with AI assistance.

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

Yes, this study is inherently a standalone performance assessment of the updated algorithm. The cobas® Liat® System is an automated system that outputs an interpreted result directly (qualitative detection of viral RNA). The study assessed the impact of the algorithm change on these automated results.

7. The Type of Ground Truth Used

The ground truth for the test set samples used in this study was based on:

• Defined characteristics of controls: Negative controls and positive controls have known compositions.
• Spiked samples: Positive specimens containing co-formulated target material at a known concentration (3X LoD) were used, allowing for a quantitative ground truth for viral load.

8. The Sample Size for the Training Set

The document does not provide information about a training set. The changes implemented were to an "Algorithm parameter" and "Correction of defects (bug fixes)" in the assay script. This suggests the changes were based on identifying and addressing specific performance characteristics or issues with the original algorithm, rather than a re-training of a machine learning model.

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

Not applicable, as a discrete "training set" in the context of machine learning model development is not mentioned or implied by the description of the software changes. The algorithm modifications were likely based on internal engineering analysis and optimization to address specific performance aspects (like tolerating early Cts) or bug fixes within the existing RT-PCR assay interpretation.

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The cobas® Influenza A/B Nucleic acid test for use on the cobas® Liat® System (cobas® Influenza A/B) is an automated multiplex real-time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of Influenza A virus and Influenza B virus RNA in nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. The test is intended for use as an aid in the differential diagnosis of Influenza A and Influenza B in humans and is not intended to detect Influenza C.

Negative results do not preclude Influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.

Performance characteristics for Influenza A were established when Influenza A/H1 and A/H3 were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary.

If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL3+ facility is available to receive and culture specimens.

The cobas® Influenza A/B & RSV Nucleic acid test for use on the cobas® Liat® System (cobas® Influenza A/B & RSV) is an automated multiplex real-time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of Influenza A virus. Influenza B virus and respiratory syncytial virus (RSV) RNA in nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. The test is intended for use as an aid in the differential diagnosis of Influenza A. Influenza B. and RSV in humans and is not intended to detect Influenza C. Negative results do not preclude Influenza virus or RSV infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule-out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. Performance characteristics for Influenza A were established during the 2013-2014 and the 2014-2015 Influenza seasons when Influenza A/H3 and A/H1N1 pandemic were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary. If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL3+ facility is available to receive and culture specimens.

The cobas® Strep A nucleic acid test for use on the cobas® Liat® System (cobas® Strep A) is a qualitative in vitro diagnostic test for the detection of Streptococcus pyogenes (Group A ß-hemolytic Streptococcus, Strep A) in throat swab specimens from patients with signs and symptoms of pharyngitis.

The cobas® Strep A assay utilizes nucleic acid purification and polymerase chain reaction (PCR) technology to detect Streptococcus pyogenes by targeting a segment of the Streptococcus pyogenes genome.

The cobas® Strep A Nucleic acid test for use on the cobas® Liat® System is intended for professional use in a clinical laboratory setting or point-of care (POC) location.

The cobas® Influenza A/B Nucleic Acid Test for use on the cobas® Liat® System is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of Influenza type A and type B viral RNA. The assay is performed on the cobas® Liat® System. The system automates and integrates sample purification, nucleic acid amplification, and detection of the target sequence in biological samples using real-time RT-PCR assays. The cobas® Liat® Analyzer consists of an instrument and preloaded software for running tests and viewing the results. The cobas® Liat® System consists of the analyzer and a single-use disposable cobas® Influenza A/B assay tube that holds the sample purification and RT-PCR reagents and hosts the sample preparation and RT-PCR processes. Other than adding the sample to the cobas® Influenza A/B assay tube, no reagent preparation or additional steps are required. Because each cobas® Influenza A/B assay tube is self-contained, cross-contamination between samples is minimized. Turnaround time for a test is 20 minutes.

The cobas® Liat® Influenza A/B & RSV Nucleic Acid Test for use on the cobas® Liat® System is an automated in vitro diagnostic test for the qualitative detection of Influenza B, and RSV RNA in nasopharyngeal swab (NPS) specimens. The sample-to-result time is ~20 minutes.

The assay is performed on the Analyzer which automates and integrates sample purification, nucleic acid amplification, and detection of the target sequence in biological samples using realtime PCR assays. The assay targets a well-conserved region of the matrix gene of Influenza A (Inf A target), the non-structure protein gene of Influenza B (Inf B target), and the matrix gene of RSV (RSV target). An Internal Process Control (IPC) is also included. The IPC is present to control for adequate processing of the target virus through all steps of the assay process and to monitor the presence of inhibitors in the RT-PCR reactions.

The System consists of an instrument and preloaded software for running tests and viewing the results. The system requires the use of a single-use disposable cobas® Influenza A/B & RSV assay tube that holds the nucleic acid purification and RT-PCR reagents, and hosts the sample preparation and RT-PCR processes.

The cobas® Strep Nucleic Acid Test for use on the cobas® Liat® System is a rapid, automated in vitro diagnostic test for the qualitative detection of Streptococcus pyogenes (Group A B -hemolytic Streptococcus, Strep A) DNA in throat swab specimens in Amies media.

The assay utilizes silica magnetic bead-based nucleic acid extraction, and TagMan probe-based real-time PCR amplification and detection. The assay targets a well-conserved region of the spy1258 gene of Strep A. An Internal Process Control (IPC) is also included. The IC is present to control for adequate processing of the target bacteria and to monitor the presence of inhibitors in the sample preparation and PCR.

The cobas® Liat® System automates and integrates sample purification, nucleic acid amplification, and detection of the target sequence in biological samples. Other than adding the sample to the cobas® Strep A assay tube, no reagent preparation or additional steps are required.

The system consists of an instrument with integrated software for running tests and analyzing the results. The system requires the use of a single-use disposable cobas® Strep A assay tube that holds all the sample purification and PCR reagents and hosts the sample preparation and PCR processes.

The provided text describes three distinct devices:

1. cobas® Influenza A/B Nucleic acid test for use on the cobas® Liat® System
2. cobas® Influenza A/B & RSV Nucleic acid test for use on the cobas® Liat® System
3. cobas® Strep A Nucleic acid test for use on the cobas® Liat® System

The submission K200065 is a 510(k) premarket notification for an update to the core software (Software 3.3) for these existing devices, rather than a new device or a new clinical study to establish primary performance. The key point is that the assay performance of each device was evaluated to ensure that the software changes did not impact the overall assay performance or claims when compared to the previously cleared software versions. Therefore, the provided document explicitly states that "analytical or clinical performance has not changed."

This means that the acceptance criteria and performance data for these devices were established in their original 510(k) submissions (K191729 for cobas Influenza A/B, K153544 for cobas Influenza A/B & RSV, and K141338 for cobas Strep A). The current submission (K200065) refers to these predicate devices for their performance characteristics.

Given this, I will extract the relevant performance data from the descriptions of the predicate devices as provided in the "Comparison of the... Assay with cobas® Liat® Analyzer Software 3.3 to the Predicate Device" tables for each assay.

1. cobas® Influenza A/B Nucleic acid test for use on the cobas® Liat® System

1. Table of Acceptance Criteria and Reported Device Performance

None of the provided sections for the cobas® Influenza A/B test (pages 5-13) specify explicit acceptance criteria or numerical performance metrics for Influenza A/B, beyond stating its intended use for qualitative detection and discrimination. The comparison table (pages 9-10) focuses on technological characteristics and states "Same" for most items, including a clinical laboratory improvement amendments (CLIA) waiver (CW150003). The conclusion explicitly states that "Performance of the cobas® Influenza A/B assay with cobas® Liat® Analyzer Software 3.3 was evaluated. The result of this evaluation determined that the overall cobas® Influenza A/B assay performance and claims were not impacted by changes implemented in cobas® Liat® Analyzer Software 3.3, when compared to the current commercially available core software version." This implies that the performance as established in K191729 is maintained. However, the specific metrics from K191729 are not detailed in this document.

2. Sample size used for the test set and the data provenance

Not provided in this document as it refers to prior clearance (K191729). The current submission is for a software update, and performance was "evaluated" to ensure no impact.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Not applicable/provided for this software update.

4. Adjudication method for the test set

Not applicable/provided for this software update.

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 a nucleic acid test, not an imaging AI diagnostic.

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

This is an automated in vitro diagnostic test, which inherently operates in a standalone manner. The results are output on a screen.

7. The type of ground truth used

Not detailed as this submission is for a software update. The original K191729 likely used a reference method (e.g., culture or another FDA-cleared molecular assay) as the ground truth.

8. The sample size for the training set

Not applicable/provided as this is a software update for an existing assay.

9. How the ground truth for the training set was established

Not applicable/provided.

2. cobas® Influenza A/B & RSV Nucleic acid test for use on the cobas® Liat® System

1. Table of Acceptance Criteria and Reported Device Performance

The provided text (pages 14-22) does not specify explicit numerical acceptance criteria for sensitivity or specificity for Flu A, Flu B, or RSV. However, it lists several performance characteristics from the predicate device (K153544) that were confirmed to be unchanged by the software update.

Study Proving Device Meets Acceptance Criteria:
The document states: "Performance of the cobas® Influenza A/B & RSV assay with cobas® Liat® Analyzer Software 3.3 was evaluated. The result of this evaluation determined that the overall cobas® Influenza A/B & RSV assay performance and claims were not impacted by changes implemented in cobas® Liat® Analyzer Software 3.3, when compared to the current commercially available core software version." (page 21). This evaluation confirms that the modified device (with Software 3.3) maintains the performance characteristics established by the predicate device (K153544). Specific details of this evaluation (e.g., sample size, specific tests) are not provided in this summary.

2. Sample size used for the test set and the data provenance

The document does not detail the sample size or provenance for the evaluation performed for this software update (K200065). These details would have been part of the original K153544 submission. For the current submission, a "performance evaluation" was conducted to ensure no impact from the software changes.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Not applicable/provided for this software update.

4. Adjudication method for the test set

Not applicable/provided for this software update.

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 a nucleic acid test.

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

Yes, this is an automated in vitro diagnostic test, operating in a standalone manner with results displayed directly to the user.

7. The type of ground truth used

Not detailed in this document. For the original K153544, it would have been a reference method such as viral culture or another FDA-cleared molecular assay.

8. The sample size for the training set

Not applicable/provided.

9. How the ground truth for the training set was established

Not applicable/provided.

3. cobas® Strep A Nucleic acid test for use on the cobas® Liat® System

1. Table of Acceptance Criteria and Reported Device Performance

The provided text (pages 23-30) does not specify explicit numerical acceptance criteria for sensitivity or specificity for Strep A. However, it lists several performance characteristics from the predicate device (K141338) that were confirmed to be unchanged by the software update.

Study Proving Device Meets Acceptance Criteria:
The document states: "Performance of the cobas® Strep A assay with cobas® Liat® Analyzer Software 3.3 was evaluated. The result of this evaluation determined that the overall cobas® Strep A assay performance and claims were not impacted by changes implemented in cobas® Liat® Analyzer Software 3.3, when compared to the current commercially available core software version." (page 29). This evaluation confirms that the modified device (with Software 3.3) maintains the performance characteristics established by the predicate device (K141338). Specific details of this evaluation (e.g., sample size, specific tests) are not provided in this summary.

2. Sample size used for the test set and the data provenance

The document does not detail the sample size or provenance for the evaluation performed for this software update (K200065). These details would have been part of the original K141338 submission. For the current submission, a "performance evaluation" was conducted to ensure no impact from the software changes.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

Not applicable/provided for this software update.

4. Adjudication method for the test set

Not applicable/provided for this software update.

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 a nucleic acid test.

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

Yes, this is an automated in vitro diagnostic test, operating in a standalone manner with results displayed directly to the user.

7. The type of ground truth used

Not detailed in this document. For the original K141338, it would have been a reference method such as bacterial culture or another FDA-cleared molecular assay.

8. The sample size for the training set

Not applicable/provided.

9. How the ground truth for the training set was established

Not applicable/provided.

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The cobas® Influenza A/B Nucleic acid test for use on the cobas® Liat® System (cobas® Influenza A/B) is an automated multiplex real-time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of Influenza A virus and Influenza B virus RNA in nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection in conjunction with clinical and evidemiological risk factors. The test is intended for use as an aid in the differential diagnosis of Influenza A and Influenza B in humans and is not intended to detect Influenza C.

Negative results do not preclude Influenza virus infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.

Performance characteristics for Influenza A were established when Influenza A/H1 and A/H3 were the predominant Influenza A viruses in circulation. When other Influenza A viruses are emerging, performance characteristics may vary.

If infection with a novel Influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL3+ facility is available to receive and culture specimens.

The cobas® Influenza A/B assay is a rapid, automated in vitro diagnostic test for qualitative detection and differentiation of Influenza type A and type B viral RNA. The assay is performed on the cobas® Liat® System. The system automates and integrates sample purification, nucleic acid amplification, and detection of the target sequence in biological samples using real-time RT-PCR assays. The cobas® Liat® Analyzer consists of an instrument and preloaded software for running tests and viewing the results. The cobas® Liat® System consists of the analyzer and a single-use disposable cobas® Influenza A/B assay tube that holds the sample purification and RT-PCR reagents and hosts the sample preparation and RT-PCR processes. Other than adding the sample to the cobas® Influenza A/B assay tube, no reagent preparation or additional steps are required. Because each cobas® Influenza A/B assay tube is self-contained, cross-contamination between samples is minimized. Turnaround time for a test is 20 minutes.

The cobas® Influenza A/B assay includes reagents for the detection and differentiation of Influenza A and B viral RNA in nasopharyngeal swab (NPS) specimens in universal transport media (UTM) from patients suspected of having Influenza. The assay targets a well-conserved region of the matrix gene of Influenza A viral RNA (Inf A target) and non-structural protein (NS) gene of Influenza B (Inf B target). An Internal Process Control (IPC) is also included. The IPC is present to control for adequate processing of the target viruses through all steps of the assay process and to monitor the presence of inhibitors in the RT-PCR reactions.

The cobas® Influenza A/B assay tube uses a flexible tube as a sample processing vessel. It contains all requisite PCR reagents pre-packed in assay tube segments separated by breakable seals. When a cobas® Influenza A/B assay tube containing a raw biological sample is inserted into the cobas Liat® Analyzer. multiple sample processing actuators in the cobas® Liat Analyzer compress the cobas® Influenza A/B assay tube to selectively release the reagents, moving the sample from one segment to the next, and controlling reaction conditions. An embedded microprocessor controls and coordinates these actions to perform all required assay processes, including sample preparation, nucleic acid extraction, target concentration enrichment, inhibitor removal, nucleic acid elution, and real-time PCR. All assay steps are performed within the closed and self-contained cobas® Influenza A/B assay tube, minimizing cross-contamination between samples.

The detection module monitors the reaction in real-time, while an on-board computer analyzes the collected data and outputs an interpreted result. The latter is displayed in the assay report on the integrated LCD touch screen of the cobas® Liat® Analyzer and in an electronic file. The report can be printed directly through a USB or network-connected printer. The results can also be exported to an external server, middleware or data management system, or to a Laboratory Information System (LIS).

The provided document does not contain information related to an AI/ML-based device; instead, it describes a nucleic acid amplification test (NAT) for the detection of Influenza A/B. Therefore, many of the requested details, such as MRMC studies, training set specifics, and expert adjudication, which are pertinent to AI/ML device evaluations, are not applicable to this submission.

However, I can extract the relevant information regarding the device's performance evaluation and acceptance criteria for this specific type of diagnostic test.

Acceptance Criteria and Reported Device Performance

The document describes the cobas® Influenza A/B Nucleic acid test for use on the cobas® Liat® System. This is a real-time RT-PCR assay for the qualitative detection and differentiation of Influenza A and B viral RNA. The evaluation focuses on demonstrating that the performance of the updated software version (FABA v1.35) is equivalent to the previously cleared version (FABA v1.31) and does not negatively impact the assay's existing performance claims.

Since this is a diagnostic test and not an AI/ML device, the performance is primarily evaluated in terms of its analytical and clinical performance as a diagnostic test, rather than typical AI metrics like AUC, sensitivity, or specificity for an AI model. The document states that the overall cobas® Influenza A/B assay performance and claims were not impacted by changes implemented in FABA v1.35.

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

"Equivalent performance of the modified device and the current commercial device has been demonstrated, and analytical or clinical performance has not changed." |
| Regulatory Equivalence | Substantial equivalence to the predicate device (K111387 and CW150003). | The modified device is substantially equivalent to the predicate device, as originally cleared through K111386 and CLIA waived through CW150003. |

Important Note: The document focuses on demonstrating that the software update (FABA v1.35) does not degrade the already established performance of the cobas® Influenza A/B assay. It does not re-establish the primary performance characteristics (e.g., clinical sensitivity, specificity) from scratch, but rather ensures the new software maintains the established performance. Therefore, detailed performance metrics (like percentages for sensitivity/specificity) for the entire assay are not reiterated in this summary specifically for the software update, as they were presumably part of the original clearance.

Study Details for the Software Update (FABA v1.35)

1. Sample Size Used for the Test Set and Data Provenance:

   • The document states that the performance was evaluated using "data from submissions (K111386, CW150003), internal studies, release testing, and the field."
   • Specific sample sizes for these evaluations are not provided in this summary.
   • Data provenance (e.g., country of origin, retrospective/prospective) is not specified for these combined data sources, beyond "internal studies, release testing, and the field." The reference to previous FDA clearances (K111386, CW150003) implies that some data would have been derived from clinical samples used in those original studies, which are typically prospective for diagnostic assay clearances.

2. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications:

   • This is a diagnostic assay, and ground truth for such tests is typically established through a combination of reference methods (e.g., viral culture, another cleared PCR assay, or a composite reference standard) rather than human expert consensus on images.
   • Therefore, the concept of "experts" in the context of radiologists or similar interpreters for AI/ML models is not applicable here. The ground truth for influenza detection would be based on the established gold standard for virological diagnosis.

3. Adjudication Method for the Test Set:

   • Not applicable in the context of an AI/ML model's output being adjudicated by human experts. For a diagnostic assay, discrepant results between the investigational device and the reference method would typically undergo further investigation (e.g., retesting, re-extraction), but not "adjudication" by multiple human readers of an output.

4. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:

   • No. This is a diagnostic RT-PCR assay, not an AI/ML system that assists human readers in interpreting medical images or data. Therefore, an MRMC study comparing human readers with and without AI assistance is not relevant or performed for this type of device.

5. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:

   • In a sense, yes, the "algorithm" (the RT-PCR chemistry and instrument's software interpretation) is standalone in that it provides a direct qualitative result (Influenza A detected, Influenza B detected, Negative, Invalid) without requiring human interpretation of raw signals beyond basic quality control. The human "in the loop" is the laboratory technologist performing the test and reviewing the automated result, but not interpreting nuanced images or complex data as in AI applications. The performance evaluation therefore focuses on the accuracy and reliability of these automated results.

6. The Type of Ground Truth Used:

   • The document does not explicitly state the ground truth methodology for the software update evaluation, but for the initial assay clearances (K111386, CW150003) mentioned, the ground truth for an influenza diagnostic test would typically be established by:
     • Composite Reference Standard (CRS): Often involves multiple methods, such as viral culture, another FDA-cleared molecular assay, and/or clinical presentation.
     • Clinical Diagnosis: Corroborated by symptoms and potentially other lab findings.
     • Reference Laboratory PCR: Testing using highly sensitive and specific laboratory-developed or research-use only PCR tests considered to be expert-level.
   • The critical aspect of this submission is demonstrating that the changes in the software (FABA v1.35) do not alter the established performance characteristics, meaning the ground truth from prior studies remained valid against the updated software's performance.

7. The Sample Size for the Training Set:

   • Not applicable in the context of an AI/ML training set. This is a rule-based diagnostic algorithm for PCR analysis, not a machine learning model that requires explicit training data in the same way. The software changes refer to updates in logic and bug fixes, developed based on internal R&D processes and prior performance data, not a "training set" for model parameters.

8. How the Ground Truth for the Training Set Was Established:

   • Not applicable as there is no "training set" in the AI/ML sense for this type of device. The logic and cut-offs for the RT-PCR assay are based on established molecular biology principles and analytical validation, refined and verified through various studies to define detection thresholds and interpretation rules.

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1. The cobas® Influenza A/B & RSV Nucleic Acid Test for Use on the cobas® Liat System (cobas® Liat Influenza A/B & RSV) is an automated multiplex real-time RT-PCR assay for the rapid in vitro qualitative detection and discrimination of influenza A virus, influenza B virus and respiratory syncytial virus (RSV) RNA in nasopharyngeal swab specimens from patients with signs and symptoms of respiratory infection in conjunction with clinical and epidemiological risk factors. The test is intended for use as an aid in the diagnosis and differentiation of influenza B, and RSV in humans and is not intended to detect influenza C.
   Negative results do not preclude influenza virus or RSV infection and should not be used as the sole basis for treatment or other patient management decisions. Conversely, positive results do not ruleout bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.

Performance characteristics for influenza A were established during the 2013-2014 and the 2014-2015 influenza seasons when influenza A/H3 and A/H1N1 pandemic were the predominant influenza A viruses in circulation. When other influenza A viruses are emerging, performance characteristics may vary.

If infection with a novel influenza A virus is suspected based on current clinical and epidemiological screening criteria recommended by public health authorities, specimens should be collected with appropriate infection control precautions for novel virulent Influenza viruses and sent to state or local health department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.

2. The cobas® Influenza A/B & RSV Quality Control Kit contains External Controls for use with the cobas® Liat Influenza A/B & RSV assay. External Controls are run during the Add cobas® Liat Influenza A/B & RSV Tube Lot procedure. Additional External Controls should be tested in accordance with local, state, federal and/or accrediting organization requirements as applicable.

The cobas Liat Influenza A/B & RSV Nucleic Acid Test for Use on the cobas Liat System ("cobas" Liat Influenza A/B & RSV assay") is a rapid, automated in vitro diagnostic test for the qualitative detection of influenza A, influenza B, and RSV RNA in nasopharyngeal swab (NPS) specimens eluted in viral transport media.

The assay targets a well-conserved region of the matrix gene of influenza A (Inf A target), the non-structural protein gene of influenza B (Inf B target), and the matrix gene of RSV (RSV target). An Internal Process Control (IPC) is also included. The IPC is present to control for adequate processing of the target viruses and to monitor the presence of inhibitors in the sample preparation and RT-PCR.

The assay utilizes a single-use disposable cobas® Liat Tube that holds the sample purification and PCR reagents, and hosts the sample preparation and PCR processes. The cobas Liat Tube uses a flexible tube as a sample vessel. It contains all required unit dose reagents pre-packed in tube segments, separated by peelable seals, in the order of reagent use.

The cobas "Liat System automates and integrates sample purification, nucleic acid amplification, and detection of the target sequence in biological samples. The cobas Liat System performs all assay steps from clinical sample and reports assay result automatically. During the testing process. multiple sample processing actuators of the cobas " Liat System compress the cobas" Liat Tube to selectively release reagents from tube segments, move the sample from one segment to another, and control reaction volume, temperature, and time to conduct sample preparation, nucleic acid extraction, target enrichment, inhibitor removal, nucleic acid elution and real-time PCR. An embedded microprocessor controls and coordinates the actions of these sample processors to perform all required assay processes within the closed cobas Liat Tube.

Positive and negative controls are provided in the cobas® Influenza A/B & RSV Quality Control Kit. The positive control comprises inactivated Influenza B and RSV virus in a dried format. The negative control comprises Universal Transport Media (UTM).

To perform the cobas Liat Influenza A/B & RSV assay, an operator first collects a nasopharyngeal swab and places the swab into UTM. The operator transfers the sample into cobas " Liat Influenza A/B & RSV assay tube using a transfer pipette, and scans the tube barcode to identify the test and the sample barcode to code the sample ID with the assay run on the cobas® Liat System. The cobas® Liat Tube is then inserted into the cobas® Liat System. The system performs all the test steps and outputs interpreted results (e.g. Influenza A Detected, Influenza B Not Detected, RSV Not Detected) in ~20 minutes. A report of the interpreted results can be viewed on the cobas " Liat System's LCD screen, and printed directly through a USB or network connected printer. No reagent preparation or additional steps are required other than adding the sample to the cobas Liat Tube. Because all the reagents are contained within the cobas Liat Tube and no sample or reagent needs to be removed from the tube, crosscontamination between samples is minimized.

The results are interpreted by the cobas Liat System software from measured fluorescent signals and real time curve recognition algorithm. All possible final test results are described below.

Here's a breakdown of the acceptance criteria and study details for the cobas® Liat Influenza A/B & RSV Nucleic Acid Test, based on the provided document:

1. Table of Acceptance Criteria & Reported Device Performance

The document doesn't explicitly lay out "acceptance criteria" in a single, aggregated table with pass/fail marks. Instead, it presents performance data for various analytical and clinical studies. For the clinical studies, it provides percentage agreements and confidence intervals. The "acceptance criteria" can be inferred from the reported performance, implying that these values were considered acceptable by the FDA for substantial equivalence.

Here's a table summarizing the key performance metrics from the study. For acceptance criteria, we'll assume that the reported performance figures met the internal thresholds set by the manufacturer and deemed sufficient by the FDA for 510(k) clearance.

Inferred Acceptance Criteria / Reported Performance for cobas® Liat Influenza A/B & RSV Assay

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

• Clinical Test Set Sample Size:

  • Prospective Specimens: 1,350 nasopharyngeal swab (NPS) specimens.
  • Retrospective Specimens: 292 nasopharyngeal swab (NPS) specimens.
  • Total Clinical Samples: 1,642 specimens.

• Analytical Test Set Sample Size (Reproducibility): Approximately 900 runs (10 panel members × 3 replicates × 2 operators × 5 days × 3 sites).

• Data Provenance:

  • Country of Origin: United States (US). Prospective specimens were collected during the 2013-2014 and 2014-2015 flu seasons.
  • Retrospective/Prospective: The study included both prospective and retrospective clinical specimens. Prospective specimens were collected from patients with signs and symptoms of respiratory infection and tested at 12 CLIA waived healthcare facilities. Retrospective specimens were obtained from two reference laboratories and distributed to 3 of the 12 CLIA waived sites for testing.

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

The document states that the cobas Liat Influenza A/B & RSV assay results were compared against an "FDA-cleared laboratory-based multiplexed real-time reverse transcriptase PCR (RT-PCR) test (comparator test)."

• Number of Experts: Not explicitly stated as "experts" for ground truth adjudication in the traditional sense, as it relies on a comparator laboratory test. However, the interpretation of the comparator PCR results would implicitly rely on qualified laboratory personnel.
• Qualifications of Experts: Not detailed. It's inferred that the personnel performing and interpreting the comparator FDA-cleared RT-PCR tests were qualified laboratory technologists/scientists. For discordant results in prospective samples, PCR/sequencing was used as a tie-breaker. This would also imply qualified laboratory personnel.

4. Adjudication Method for the Test Set

• For the primary comparison, the cobas Liat assay results were compared directly against the FDA-cleared laboratory-based multiplexed real-time RT-PCR test (comparator test).
• For discordant results between the cobas Liat and the comparator test in the prospective specimens (specifically, when Liat was positive and comparator negative), PCR/sequencing was used as a "tie-breaker" or confirmatory method. For Influenza A, 41 such specimens were tested, with 18 confirmed positive and 23 negative by PCR/sequencing. For Inf B, 6 such specimens were tested, with 5 confirmed positive and 1 negative. For RSV, 15 such specimens were tested, with 3 confirmed positive and 12 negative.
• For retrospective specimens with discordant results (Liat positive, comparator negative), a similar PCR/sequencing method was used, though with fewer details on the number of confirmed cases (e.g., 1 Inf A sample was negative by PCR/sequencing, all 6 RSV samples were positive).

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

This document describes the performance of an in vitro diagnostic (IVD) nucleic acid amplification test (NAAT), not an AI-assisted imaging device or a decision support system with human readers. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable to this device.

6. If a Standalone (i.e., Algorithm Only Without Human-in-the-Loop Performance) Was Done

The cobas® Liat system is an automated diagnostic system (sample-to-answer) that performs nucleic acid purification, amplification, and detection, and provides an automated interpretation of the results. The results are reported as "Detected" or "Not Detected" for each virus by the instrument's software. As such, the performance data presented (e.g., clinical sensitivity and specificity) intrinsically represent the "standalone" performance of the algorithm/system, as human interpretation of complex signals (like in radiology) is minimized or absent in the final result determination. The operators (nurses and technologists) are responsible for sample collection, loading, and initiating the test, but the interpretation is automated.

7. The Type of Ground Truth Used

The primary ground truth for the clinical validation was an FDA-cleared laboratory-based multiplexed real-time RT-PCR test (comparator test). For discordant results, PCR/sequencing was used as a confirmatory method to establish a more definitive ground truth.

8. The Sample Size for the Training Set

The document does not specify a separate "training set" in the context of machine learning or AI models. This device is a molecular diagnostic assay (RT-PCR) with predefined chemical reactions and detection logic. Its "development" would involve optimizing reagents, primer/probe design, and reaction conditions, rather than training an algorithm on a distinct dataset. The performance characteristics described are from validation studies, not from a "training" phase.

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

Given that this is an RT-PCR assay and not an AI/ML device that requires a "training set" with ground truth in the AI context, this question is not applicable. The "ground truth" for developing such an assay would come from extensive analytical characterization against known viral positive and negative samples, including quantified viral loads, verified by traditional virological methods (e.g., cell culture infectivity assays, reference PCR methods).

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