Search Results

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.

Ask a specific question about this device

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.

Ask a specific question about this device