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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.

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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).

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The Xpert® C. difficile/Epi test is a qualitative in vitro diagnostic test for detection of toxin B gene sequences and for presumptive identification of 027/NAP1/BI strains of toxigenic Clostridioides difficile from unformed (liquid or soft) stool specimens collected from patients suspected of having C. difficile infection (CDI). Presumptive identification of 027/NAP1/BI strains of C. difficile is by detection of binary toxin (CDT) gene sequences and the single base pair deletion at nucleotide 117 in the tcdC gene. The tcdC gene encodes for a negative regulator in C. difficile toxin production. The test is performed on the GeneXpert® Instrument Systems and utilizes automated real-time polymerase chain reaction (PCR) to detect toxin gene sequences associated with toxin producing C. difficile. The Xpert® C. difficile/Epi test is intended as an aid in the diagnosis of CDI. Detection of 027/NAP/Bl strains of C. difficile by the Xpert® C. difficile/Evi test is presumptive and is solely for enidemiological purposes and is not intended to guide or monitor treatment for C. difficile infections. Concomitant culture is necessary only if further typing or organism recovery is required.

The Xpert C. difficile/Epi test is an automated in vitro diagnostic test for qualitative detection of toxin producing Clostridioides difficile (formerly known as Clostridium difficile) directly from unformed (liquid or soft) stool specimens of patients suspected of having Clostridioides difficile infection (CDI). The test detects the toxin B gene (tcdB), the binary toxin (CDT) gene, and the single base pair deletion at nucleotide 117 (tcdCΔ117) within the gene encoding TcdC, a negative regulator of toxin production. The combined presence of the genes encoding toxin B and binary toxin and the tcdCA117 deletion has been associated with a hypervirulent C. difficile strain known as 027/NAP1/BI, which has been associated with severe disease outbreaks in healthcare facilities worldwide.

The test is performed on the GeneXpert® Instrument Systems (comprised of the GeneXpert® Dx System. GeneXpert® System with Touchscreen, and GeneXpert® Infinity System). In the GeneXpert® Instrument Systems, sample preparation, amplification, and real-time detection are all fully automated and completely integrated. The single-use disposable Xpert C. difficile/Evi cartridge, required by the platform for use, holds the PCR reagents and hosts the PCR process. Because the cartridge is self-contained, cross-contamination between samples is minimized.

The Xpert C. difficile/Epi test includes reagents for the detection of toxigenic C. difficile and the detection of sequences for presumptive identification of 027/NAP 1/BI strains. In addition, the test reagents include an internal sample processing control (SPC) to ensure adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR Assay. The SPC also ensures that the PCR conditions (temperature and time) are appropriate for the amplification reaction and that the PCR reagents are functional. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

The Xpert C. difficile/Evi test system performs sample preparation and real-time, multiplex polymerase chain reaction (PCR) for detection of target-specific DNA. A swab is inserted into the stool specimen and then placed in a tube containing Sample Reagent. Following brief vortexing, the content of the Sample Reagent is transferred to the Sample Chamber of the disposable fluidic cartridge (the Xpert C. difficile/Epi cartridge). The user initiates a test from the system user interface of the GeneXpert® Instrument Systems and places the cartridge with sample into a GeneXpert® instrument system which performs hands-off real-time PCR for detection of C. difficile DNA.

Depending on the specific instrument, a GeneXpert® instrument system may contain 1-80 modules, each of which are randomly accessible and capable of performing separate sample preparation and real-time PCR tests for the detection of gene sequences for C. difficile toxin B and binary toxin and the tcdCA117 deletion in less than 45 minutes. 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 PCR and detection.

Each instrument in the GeneXpert® instrument family is equipped with a Windows OS-based personal computer that is preloaded with software applications for running the tests and viewing the results, as described in Table 1.

The provided document is a 510(k) summary for the Cepheid Xpert C. difficile/Epi test. It details the device's characteristics, intended use, and performance studies conducted to demonstrate substantial equivalence to a predicate device and compliance with special controls.

Here's a breakdown of the requested information based on the provided text:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly state formal acceptance criteria with numerical targets (e.g., minimum sensitivity/specificity percentages). Instead, it summarizes "verification studies" to demonstrate performance and compliance. The key performance indicators mentioned relate to agreement with expected results and accurate identification of strains.

2. Sample sized used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Sample Size for Test Set:
  • Prepared Cartridge Hold Time Study: Not explicitly stated how many "contrived positive" and "negative" samples were used, only that they were held for "various times under three (3) hold environments."
  • Functional Testing: Not explicitly stated how many "contrived positive" and "negative" samples were used.
  • Inclusivity Study: 26 C. difficile strains were tested (18 from previous study K110203 and 8 additional strains for K243730).
• Data Provenance: The document does not specify the country of origin of the data or whether the studies were retrospective or prospective. The studies mentioned (Hold Time, Functional Testing, Inclusivity) appear to be laboratory-based verification studies, rather than clinical trials with patient samples.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

The document does not mention the use of experts to establish ground truth for the test set. The performance studies appear to be analytical verification studies using contrived samples and known bacterial strains, implying that the ground truth for these studies was established by laboratory methods rather than expert consensus on clinical samples.

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

The document does not describe any adjudication method for establishing ground truth, as the studies are analytical verification studies using controlled samples with known statuses (contrived positive/negative, specific C. difficile strains).

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

A multi-reader multi-case (MRMC) comparative effectiveness study was not done. The device is a diagnostic assay (Nucleic Acid Amplification Test) for infectious disease, not an AI-powered image analysis tool requiring human reader interpretation. No mention of AI assistance or human readers is present.

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

Yes, the studies described (Prepared Cartridge Hold Time, Functional Testing, Inclusivity) assess the performance of the Xpert C. difficile/Epi test in a standalone manner. The device is an automated in vitro diagnostic test that performs sample preparation, amplification, and real-time detection without human intervention in the result determination process. It's an "algorithm-only" performance in the sense that the instrument provides a final result based on its internal processes.

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

The ground truth for the verification studies was based on:

• Known status of contrived samples: "contrived positive (C. difficile cells added to negative matrix) and negative (negative matrix only) samples" for hold time and functional testing.
• Known bacterial strains: "C. difficile strains selected to broadly represent the majority of C. difficile toxinotypes encountered in practice" for the inclusivity study, where accurate identification of these known strains served as the ground truth.

8. The sample size for the training set

The document does not mention a "training set" in the context of machine learning or AI. This is a diagnostic assay, and its development likely involved traditional analytical validation and verification rather than an AI model requiring a training set.

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

Not applicable, as no training set (in the AI/ML sense) is mentioned or implied for this device.

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The Xpert Xpress CoV-2 plus test, performed on the GeneXpert Xpress System, is a rapid real-time RT-PCR test intended for the qualitative detection of SARS-CoV-2 RNA in nasopharyngeal and anterior nasal swab specimens collected from individuals with signs and symptoms of respiratory tract infection.

The Xpert Xpress CoV-2 plus test is intended for use as an aid in the diagnosis of COVID-19 if used in conjunction with other clinical, epidemiologic, and laboratory findings. Positive results are indicative of the presence of SARS-CoV-2 RNA. Positive results do not rule out bacterial infection or co-infection with other pathogens.

Negative results do not preclude SARS-CoV-2 infection. The results of this test should not be used as for diagnosis and patient management decisions.

The Xpert Xpress CoV-2 plus test is a rapid, automated in vitro diagnostic test for the qualitative detection of viral RNA from SARS-CoV-2 in nasopharyngeal swab (NPS) and anterior nasal swab (NS) specimens collected from individuals with signs and symptoms of respiratory tract infection.

The Xpert Xpress CoV-2 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 selfcontained, cross-contamination between samples is minimized.

The Xpert Xpress CoV-2 plus test includes reagents for the detection of viral RNA from SARS-CoV-2 in NPS and NS specimens. The primers and probes in the Xpert Xpress CoV-2 plus test are designed to amplify and detect unique sequences in the genes that encode the following SARS-CoV-2 proteins: nucleocapsid (N2), envelope (E), and RNA-dependent RNA polymerase (RdRP). A Sample Processing Control (SPC) and a Probe Check Control (PCC) are also included in the cartridge serving as internal controls. 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 plus test is designed for use with NPS or NS specimen collected with nylon flocked swabs and placed into viral transport medium (VTM), Universal Transport Medium (UTM) or eNAT®.

Acceptance Criteria and Study for Xpert Xpress CoV-2 plus

The Xpert Xpress CoV-2 plus test is a rapid real-time RT-PCR test for the qualitative detection of SARS-CoV-2 RNA in nasopharyngeal and anterior nasal swab specimens. The study aims to demonstrate substantial equivalence to a predicate device (K230440) by evaluating its analytical and clinical performance.

1. Table of Acceptance Criteria and Reported Device Performance

2. Sample Sizes and Data Provenance

• Test Set (Clinical Performance):

  • Total specimens: 1783
    • NPS (Nasopharyngeal Swab): 883
    • NS (Anterior Nasal Swab): 900
  • Data Provenance: Prospective clinical specimens collected from individuals showing signs and symptoms of respiratory infection in the United States (22 geographically diverse CLIA-waived sites). Data was collected in 2022.

• Analytical Performance Test Sets:

  • Limit of Detection (LoD):
    • NPS-UTM/VTM: At least 40 replicates (2 reagent lots x 20 replicates)
    • NPS-eNAT: At least 40 replicates (2 reagent lots x 20 replicates)
    • NS-UTM/VTM: At least 40 replicates (2 reagent lots x 20 replicates)
    • WHO First International Standard (NS-UTM/VTM): 20 replicates
  • Analytical Reactivity (Wet-testing): 61 SARS-CoV-2 strains, 3 replicates per strain (total 183 tests).
  • Analytical Specificity (Wet-testing): 62 microorganisms, 3 replicates per organism (total 186 tests).
  • Microbial Interference: 18 commensal microorganisms, 8 replicates per strain (total 144 tests) with SARS-CoV-2.
  • Potentially Interfering Substances: 23 substances, 8 replicates for negative samples and 8 replicates for positive samples (total up to 368 tests, plus re-tests).
  • Carryover Contamination: 40 positive samples, 42 negative samples.
  • Reproducibility: 3 panel members (Negative, Low Pos, Mod Pos), 90 observations per panel member (3 Sites x 3 Operators x 1 Lot x 5 Days x 1 Run x 2 Replicates = 90). Total 270 observations.

3. Number of Experts and Qualifications for Ground Truth (Test Set)

The document does not explicitly state the number of experts used to establish the ground truth for the clinical test set or their specific qualifications (e.g., radiologist with 10 years of experience). However, the ground truth was established by a "U.S. FDA-cleared molecular respiratory panel that included SARS-CoV-2," indicating an established and validated laboratory method. Discrepant results were investigated using a "U.S FDA EUA SARS-CoV-2 molecular test," further relying on FDA-authorized assays as the reference standard.

4. Adjudication Method (Test Set)

The adjudication method used for the clinical test set was a discrepant analysis. "Discrepant results between Xpert Xpress CoV-2 plus and the comparator were investigated using a U.S FDA EUA SARS-CoV-2 molecular test." This implies that for any cases where the Xpert Xpress CoV-2 plus result differed from the initial FDA-cleared comparator panel, a third, independent FDA EUA molecular test was used to determine the true positive or negative status.

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

There is no MRMC comparative effectiveness study mentioned in the provided text. The study focuses on the standalone performance of the device against a comparator device, not on human reader performance with or without AI assistance.

6. Standalone Performance Study

Yes, a standalone performance study was done. The entire "Performance Studies" section (1.4) details the analytical and clinical performance of the device itself (algorithm only, without human-in-the-loop performance). The clinical performance evaluation directly compares the Xpert Xpress CoV-2 plus test results to those of an FDA-cleared molecular respiratory panel.

7. Type of Ground Truth Used

For the clinical performance study, the ground truth was established by an FDA-cleared molecular respiratory panel and, in cases of discrepancy, by a U.S. FDA EUA SARS-CoV-2 molecular test. This falls under the category of reference standard laboratory testing rather than expert consensus, pathology, or outcomes data.

For analytical performance studies, the ground truth was established by spiking known concentrations/quantities of inactivated SARS-CoV-2 virus, genomic RNA, or other microorganisms into negative matrices, or by using established international standards (e.g., WHO First International Standard).

8. Sample Size for the Training Set

The document does not mention the sample size for the training set. This is a premarket notification (510(k)) and focuses on the performance testing of the final device, not on the developmental or training phases of its underlying algorithm. As a PCR-based diagnostic, it's unlikely to have a "training set" in the same sense as an AI/ML-based device; its analytical performance is determined by the specific primers and probes and their chemical/biological interactions.

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

Since no "training set" is explicit for this PCR diagnostic, there is no information provided on how its ground truth might have been established. The development of PCR assays typically involves careful design and validation of primers and probes against known genomic sequences and wet-lab testing with characterized samples, rather than machine learning training on a dedicated dataset.

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The Xpert® MRSA/SA Skin and Soft Tissue Infection test (Xpert MRSA/SA SSTI test) performed on the GeneXpert® Instrument Systems is a qualitative in vitro diagnostic test intended for the detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) from skin and soft tissue infection swabs. The test utilizes automated real-time polymerase chain reaction (PCR) to detect MRSA/SA DNA. The Xpert MRSA/SA SSTI test is indicated for use in conjunction with other laboratory tests, such as microbiology culture, and clinical data available to the clinician as an aid in the detection of MRSA/SA from skin and soft tissue infections. The Xpert MRSA/SA SSTI test is not intended to monitor treatment for MRSA/SA infections. Concomitant cultures for SA and MRSA are necessary to recover organisms for susceptibility testing or epidemiological typing. In a mixed culture containing MRSA/SA and other organisms (e.g., Gram-negative bacilli, yeast), results can be false negative or variable depending on the concentration of MRSA/SA present, particularly if the concentration of MRSA/SA is close to the limit of detection (LoD) of the test.

The Xpert MRSA/SA SSTI (Xpert MRSA/SA Skin and Soft Tissue Infection) test is an automated in vitro diagnostic DNA test for the qualitative, simultaneous detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) directly from skin and soft tissue specimen swabs. The specimen is collected on a double swab, one of which is placed in a tube containing elution reagent. Following brief vortexing, the eluted material is transferred to a different, uniquely labeled sample chamber of a disposable fluidic cartridge (the Xpert MRSA/SA SSTI cartridge).

The test is performed on the GeneXpert® Instrument Systems (comprised of the GeneXpert® Dx System, GeneXpert® System with Touchscreen, and GeneXpert® Infinity System). In the GeneXpert® Instrument Systems, sample preparation, amplification, and real-time detection are all fully automated and completely integrated. The platform requires the use of singleuse disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized.

The user initiates a test from the system user interface of the GeneXpert® Instrument Systems platform and places the cartridge with sample into a GeneXpert® instrument system which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of SA and MRSA DNA.

Depending upon the specific instrument, a GeneXpert® instrument system may contain 1–80 modules, each which are randomly accessible and capable of performing separate sample preparation and real-time 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 ICORE® thermocycler for performing real-time PCR and detection.

The Xpert MRSA/SA SSTI test kit includes reagents for the simultaneous detection of the target organisms, SA and MRSA. The primers and probes in the Xpert MRSA/SA SSTI test detect nucleic acid sequences of the staphylococcal protein A (spa), the gene for methicillin/oxacillin resistance (mecA), and staphylococcal cassette chromosome (SCCmec) inserted in the SA chromosomal attB site.

The test includes a sample processing control (SPC) to control for adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. The SPC also ensures that the PCR conditions (temperature and time) are appropriate for the amplification reaction and that the PCR reagents are functional. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

The Xpert MRSA/SA SSTI test performed on the GeneXpert® Instrument Systems provides results in approximately 62 minutes.

The provided text is a 510(k) summary for a medical device called Xpert MRSA/SA SSTI. It describes a diagnostic test for Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) from skin and soft tissue infection swabs, performed on the GeneXpert Instrument Systems.

The document does not contain information about the design of a study to prove acceptance criteria using a test set of data with expert ground truth, human reader performance, or multi-reader multi-case studies.

Instead, it details a Special 510(k) submission to modify an already cleared and legally marketed device (Xpert MRSA/SA SSTI, K080837). The specific modification is to include the GeneXpert® Infinity System instruments as a compatible platform for the test.

Therefore, the performance data presented is focused on demonstrating that the performance of the test on the new instrument platform (GeneXpert Infinity) is equivalent to its performance on previously cleared platforms (GeneXpert Dx System, GeneXpert System with Touchscreen). This is a bridging study rather than a primary clinical validation or an AI performance study as implied by many of the questions.

Given this, I cannot answer all your questions as the relevant information is not in the provided text. However, I will answer what is available and clarify what is missing.

Acceptance Criteria and Reported Device Performance

The acceptance criteria here refer to demonstrating equivalent performance of the Xpert MRSA/SA SSTI test when run on the new GeneXpert Infinity System compared to the previously cleared GeneXpert Dx System.

Study Details (Based on available information)

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

   • The document mentions "contrived positive (MRSA cells added to negative matrix) and negative (negative matrix only) samples" for functional testing. It does not provide the specific number of samples (sample size) used in these studies.
   • Data Provenance: The data appears to be prospective as it's generated from specific verification studies ("prepared cartridge hold time study and functional testing") conducted for this 510(k) submission. The country of origin is not specified but implicitly North American given the FDA submission.

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

   • This is a molecular diagnostic test, not an AI image analysis device. The "ground truth" for the functional testing would be the known concentration/presence of MRSA/SA cells in the contrived samples. This is established by the assay design and sample preparation, not by expert interpretation.
   • Therefore, this question does not apply to the type of study described.

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

   • Not applicable. This relates to expert consensus in interpreting complex data, which is not the ground truth methodology for this type of molecular test. The measurements (Ct values, presence/absence of signal) are quantitative and objective.

4. 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:

   • No, an MRMC study was not done. This is a diagnostic device for detecting specific DNA sequences, not an AI-powered device assisting human readers.

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

   • The device itself (Xpert MRSA/SA SSTI test on the GeneXpert Instrument Systems) is a standalone automated diagnostic test. Its "performance" is the detection of specific DNA sequences. The studies assess the instrument's ability to run the test and yield equivalent results. The "functional testing" mentioned is effectively the standalone performance of the assay on the new instrument.

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

   • The ground truth for the functional testing was contrived samples with known positive and negative status (e.g., negative matrix, or MRSA cells added to negative matrix where the concentration of MRSA/SA is known). This allows for direct assessment of sensitivity and specificity against a known standard.

7. The sample size for the training set:

   • This device is based on real-time PCR technology, not machine learning that requires a "training set" in the conventional sense. The test's probes and primers are designed based on biological knowledge of the target sequences.
   • Therefore, this question does not apply.

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

   • Not applicable, as there is no traditional "training set" for this type of diagnostic device.

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The Xpert® vanA test performed on the GeneXpert® Instrument Systems is a qualitative in vitro diagnostic test designed for detection of the vanA gene sequence associated with vancomycin resistance in bacteria obtained from rectal swab specimens from patients at risk for intestinal colonization with vancomycin-resistant bacteria. The test utilizes automated real-time polymerase chain reaction (PCR) to detect the vanA gene that is frequently associated with vancomycin-resistant enterococci (VRE). The Xpert vanA test is intended to aid in the recognition, prevention, and control of vancomycin-resistant organisms that colonize patients in healthcare settings. The Xpert vanA test is not intended to diagnose infections caused by vancomycin-resistant bacteria nor to guide or monitor treatment for vancomycin-resistant bacterial infections. Concomitant cultures are necessary to recover organisms for identification of vancomycin-resistant bacteria, antimicrobial susceptibility testing, and for epidemiological typing.

The Xpert van4 test is an automated in vitro diagnostic test for the qualitative detection of the vanA gene sequence associated with vancomycin resistance in bacteria obtained directly from rectal swab specimens. The specimen is collected on a double swab, one of which is placed in a tube containing sample reagent. Following brief vortexing, the content of the sample reagent is transferred to the uniquely labeled Sample Chamber of a disposable fluidic cartridge (the Xpert vanA cartridge). The user initiates a test from the user interface of the GeneXpert® instrument system platform and places the cartridge with sample into the GeneXpert® instrument system which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for the detection of vanA DNA.

In the GeneXpert® Instrument Systems (comprised of the GeneXpert® Dx System, GeneXpert® System with Touchscreen, and GeneXpert® Infinity System), sample preparation, amplification, and real-time detection are all fully automated and completely integrated. The platform requires the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized.

Depending on the specific instrument, a GeneXpert® instrument system may contain 1-80 modules, each of which are randomly accessible and capable of performing separate sample preparation and real-time 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 PCR and detection.

The Xpert van4 test includes reagents for the detection of the gene for vancomycin resistance (van4) as well as an internal sample processing control (SPC) to control for adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. The SPC also ensures that the PCR conditions (temperature and time) are appropriate for the amplification reaction and that the PCR reagents are functional. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

The Xpert van 4 test performed on the GeneXpert® Instrument Systems provides results in less than 45 minutes.

Each instrument in the GeneXpert® instrument family is equipped with a Windows OS-based personal computer that is preloaded with software applications for running the tests and viewing the results, as described in Table 1.

The provided text describes a 510(k) premarket notification for the Cepheid Xpert vanA test. This submission is for a modification to an already cleared device (Xpert vanA, K092953) to include the GeneXpert Infinity System instruments. As such, the document primarily focuses on demonstrating that the performance of the modified device is equivalent to the predicate device and does not present a full de novo study with a comprehensive set of acceptance criteria and performance statistics like sensitivity and specificity against a clinical ground truth.

Here's an analysis of the available information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal acceptance criteria with numerical targets for the verification studies. Instead, it describes "verification studies" aiming to show equivalence to the predicate device. The performance is reported qualitatively as "100% agreement of reportable results" and "no statistically significant differences in Ct values."

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

The document mentions "both contrived positive (vancomycin-resistant (vanA) Enterococcus faecalis cells added to negative matrix) and negative matrix only) samples" for functional testing. However, it does not specify the sample size for these contrived samples.

The data provenance is from verification studies conducted by the manufacturer (Cepheid) to demonstrate the performance of the Xpert vanA test on the GeneXpert Infinity System instruments. The samples are contrived, meaning they were prepared in a laboratory setting, rather than derived from a patient population (i.e., not prospective or retrospective clinical data in the traditional sense).

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

Given that the test set consisted of "contrived positive" and "negative matrix only" samples, the ground truth was established by the known composition of these laboratory-prepared samples. There is no mention of external experts or clinical adjudication for these ground truths, as the samples were artificially created with a defined vanA status.

4. Adjudication Method for the Test Set

No explicit adjudication method is mentioned. For contrived samples with a known composition, formal adjudication by a panel of experts is typically not performed or necessary. The "ground truth" is inherent in the preparation of the samples.

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 question is not applicable to this submission. The Xpert vanA test is a qualitative in vitro diagnostic test that uses automated real-time PCR to detect the vanA gene sequence. It is a fully automated system, and human interpretation of results is minimal (typically reading a "detected" or "not detected" output). There is no "AI" or "human reader" component in the diagnostic process that would warrant an MRMC study or an assessment of human reader improvement with AI assistance.

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

Yes, the performance evaluated here is essentially standalone (algorithm only). The Xpert vanA test is an automated system where sample preparation, amplification, and real-time detection are fully integrated. The "device performance" refers to the automated output of the system.

7. The Type of Ground Truth Used

The ground truth for the verification studies was based on known, contrived samples. For the "contrived positive" samples, the ground truth was the presence of vanA positive Enterococcus faecalis cells. For "negative matrix only" samples, the ground truth was the absence of vanA.

8. The Sample Size for the Training Set

This document does not provide information about a "training set." This submission focuses on verification studies for a modification to a previously cleared device. Diagnostic devices like this typically undergo extensive development and validation, but the details of the initial development (including training sets for algorithms, if any) are not part of this specific 510(k) summary for a modification. The test is based on PCR, not machine learning that would require a distinct "training set."

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

Since no training set is mentioned or applicable in the context of this PCR-based diagnostic device and modification, how its ground truth was established is not provided in the document.

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The Xpert® SA Nasal Complete test performed on the GeneXpert® Instrument Systems is a qualitative in vitro diagnostic test designed for detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) from nasal swabs in patients at risk for nasal colonization. The test utilizes automated real-time polymerase chain reaction (PCR) to detect MRSA/SA DNA. The Xpert SA Nasal Complete test is intended to aid in the prevention and control of MRSA/SA infections in healthcare settings. The Xpert SA Nasal Complete test is not intended to diagnose, guide or monitor treatment for MRSA/SA infections, or provide results of susceptibility to methicillin. A negative result does not preclude MRSA/SA nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.

The Xpert SA Nasal Complete test is an automated in vitro diagnostic DNA test for the qualitative, simultaneous detection of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) directly from nasal swabs. The specimen is collected on a double swab, one of which is placed in a tube containing elution reagent. Following brief vortexing, the eluted material is transferred to different, uniquely-labeled chamber of the disposable fluidic cartridge (the Xpert SA Nasal Complete cartridge). The user initiates a test from the user interface of the GeneXpert® Instrument Systems and places the cartridge with sample into the GeneXpert® Instrument System platform, which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of S. aureus (including MRSA) DNA.

In the GeneXpert® Instrument Systems (comprised of the GeneXpert® Dx Systems, GeneXpert® System with Touchscreen, and GeneXpert® Infinity Systems), sample preparation, amplification, and real-time detection are all fully-automated and completely integrated. The platform requires the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, cross-contamination between samples is minimized.

Depending on the specific instrument, the GeneXpert® Instrument Systems may contain 1–80 modules, each of which are randomly accessible and capable of performing separate sample preparation and real-time 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 PCR and detection.

The Xpert SA Nasal Complete test kit includes reagents for the simultaneous detection of SA and MRSA targets. The primers and probes provided in the Xpert SA Nasal Complete test kit detects nucleic acid sequences of the staphylococcal protein A (spa), the gene for methicillin/oxacillin resistance (mecA), and staphylococcal cassette chromosome (SCCmec) inserted in the SA chromosomal attB site.

The Xpert SA Nasal Complete cartridge includes a sample processing control (SPC) to control for adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dve stability.

The Xpert SA Nasal Complete test performed on the GeneXpert® Instrument Systems provides results in approximately 65 minutes.

Each instrument in the GeneXpert® Instrument family is equipped with a Windows OS-based personal computer that is preloaded with software applications for running the tests and viewing the results, as described in Table 1.

Acceptance Criteria and Study Details for Xpert SA Nasal Complete (K243070)

This submission (K243070) seeks to modify the existing Xpert SA Nasal Complete device (K100822) to include the GeneXpert® Infinity Systems instruments in its compatible instrument family. The study described focuses on demonstrating equivalent performance on the new instrument systems.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document doesn't explicitly state quantitative acceptance criteria for clinical performance (e.g., sensitivity, specificity) for this specific 510(k) submission (K243070). This is likely because the core assay and its clinical performance were extensively validated and accepted during the original clearance of K100822, and this submission focuses on adding new compatible instruments while demonstrating equivalent performance.

However, based on the studies conducted, the implicit acceptance criteria relate to demonstrating equivalent performance on the new GeneXpert Infinity Systems compared to the predicate device run on previously cleared GeneXpert systems.

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

The document describes two types of studies impacting the acceptance criteria:

• Prepared Cartridge Hold Time Study:

  • Sample Size: Not explicitly stated. The study involved verifying a maximum acceptable hold time. This would typically involve testing multiple samples at various time points within and beyond the proposed hold time.
  • Data Provenance: Not specified, but likely laboratory-based controlled studies.

• Functional Testing:

  • Sample Size: Not explicitly stated. The study used "both contrived positive (MRSA added to negative matrix) and negative (negative matrix only) samples." It also notes "Each target of the Xpert SA Nasal Complete test was analyzed." This implies a sufficient number of samples to represent positive and negative outcomes for both SA and MRSA targets.
  • Data Provenance: Not specified, but based on the description of "contrived positive" and "negative matrix," it is a retrospective laboratory-based study using controlled samples. The materials used (e.g., negative matrix) would be laboratory-sourced.

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

Not Applicable for this particular submission. The ground truth for the functional testing was established by the nature of the contrived samples:

• Contrived positive samples: MRSA added to negative matrix, meaning the positive status was known and intentionally created.
• Negative samples: Negative matrix only, meaning the negative status was known and intentionally created.

This type of study does not require human expert interpretation to establish the ground truth of the samples.

4. Adjudication Method for the Test Set

Not Applicable. As the ground truth was established by the deliberate creation of contrived positive and negative samples, no adjudication by human experts was required to determine the true status of the samples.

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

No, a MRMC comparative effectiveness study was not done. This submission (K243070) is for a device modification to expand compatible instruments rather than to assess human reader improvement with AI assistance. The device in question is an automated in vitro diagnostic test that provides a qualitative result (positive/negative) directly, without requiring human interpretation for its primary output.

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

Yes, a standalone performance study was effectively done. The Xpert SA Nasal Complete test is an automated nucleic acid amplification test (NAAT). The "functional testing" described assesses the device's ability to correctly identify contrived positive and negative samples when run on the new GeneXpert Infinity Systems instruments, independently determining the presence or absence of the target DNA. This is a standalone performance evaluation of the device itself.

7. The Type of Ground Truth Used

The ground truth used for the functional testing was established by the deliberate creation of contrived samples. This includes:

• Contrived positive samples: MRSA added to a negative matrix, where the presence of the pathogen (MRSA) is known and controlled.
• Negative samples: Negative matrix only, where the absence of the pathogen is known and controlled.

This methods ensures a definitive and known ground truth.

8. The Sample Size for the Training Set

Not applicable/Not explicitly stated. The Xpert SA Nasal Complete test is a PCR-based diagnostic with specific primers and probes for target DNA. It is not typically a machine learning/AI model that undergoes "training" in the traditional sense with a distinct training set. The assay's design (primers, probes, thermocycling protocols) would have been developed and optimized during its initial development, but this isn't referred to as a "training set" in the context of this type of device. The current submission is a modification focusing on instrument compatibility.

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

Not applicable. As noted above, the concept of a "training set" and its associated ground truth establishment is not directly relevant to this PCR-based diagnostic device in the context of this submission. The assay's analytical performance and target specificity are inherent to its biochemical design.

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The Xpert Xpress CoV-2 plus test, performed on the GeneXpert Infinity Systems, is a rapid real-time RT-PCR test intended for the qualitative detection of SARS-CoV-2 RNA in nasopharyngeal and anterior nasal swab specimens collected from individuals with signs and symptoms of respiratory tract infection.

The Xpert Xpress CoV-2 plus test is intended for use as an aid in the diagnosis of COVID-19 if used in conjunction with other clinical, epidemiologic, and laboratory findings. Positive results are indicative of the presence of SARS-CoV-2 RNA. Positive results do not rule out bacterial infection or co-infection with other pathogens.

Negative results do not preclude SARS-CoV-2 infection. The results of this test should not be used as for diagnosis and patient management decisions.

The Xpert Xpress CoV-2 plus test is a rapid, automated in vitro diagnostic test for the qualitative detection of viral RNA from SARS-CoV-2 in nasopharyngeal swab (NPS) and anterior nasal swab (NS) specimens obtained from individuals with signs and symptoms of respiratory tract infection.

The Xpert Xpress CoV-2 plus test is performed on the Cepheid 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 cartridges during the testing process is minimized.

The Xpert Xpress CoV-2 plus test includes reagents for the detection of viral RNA from SARS-CoV-2 in NPS and NS specimens. The primers and probes in the Xpert Xpress CoV-2 plus test are designed to amplify and detect sequences in the genes that encode the following SARS-CoV-2 proteins: nucleocapsid (N2), envelope (E), and RNA-dependent RNA polymerase (RdRP). 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 dve stability.

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

Here's a breakdown of the acceptance criteria and the study details for the Cepheid Xpert Xpress CoV-2 plus, based on the provided document:

Acceptance Criteria and Device Performance

Note: The document explicitly states the "claimed LoD" which can be interpreted as an acceptance criterion for analytical sensitivity. For clinical performance, the reported PPA and NPA values serve as the acceptance criteria.

Study Details

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

• Clinical Performance Test Set:

  • Initial Specimens: 4047 specimens (2029 Nasopharyngeal Swab (NPS) and 2018 Anterior Nasal Swab (NS)).
  • Valid Specimens (after exclusions): 3750 specimens (1879 NPS and 1871 NS).
  • Data Provenance: United States (32 geographically diverse sites), prospectively collected, fresh (98.6%) and frozen (1.4%) clinical specimens collected in 2022.

• Analytical Performance Test Sets:

  • LoD (NPS & NS): Replicates of 20 per reagent lot (2 lots).
  • LoD (WHO Standard): 20 replicates.
  • Analytical Inclusivity (Wet Testing): 61 SARS-CoV-2 strains, 3 replicates each.
  • Analytical Exclusivity (Wet Testing): 62 microorganisms, 3 replicates each.
  • Microbial Interference: 18 commensal microorganisms, 8 replicates each with SARS-CoV-2.
  • Potentially Interfering Substances: 23 substances, 8 replicates each for negative and positive samples.
  • Carryover Contamination: 40 positive samples and 42 negative samples.
  • Reproducibility: 144 observations per panel member (3 sites x 2 operators x 3 lots x 2 days/lot x 2 runs x 2 replicates).
  • Single-Site Precision: 80 observations per panel member (1 site x 1 operator x 1 lot x 20 days x 2 runs x 2 replicates).
  • Data Provenance: Not explicitly stated for analytical studies, but typically performed in-house or by contracted labs. The substances and strains used are clearly defined.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

• The clinical performance study used a U.S. FDA-cleared molecular respiratory panel that includes SARS-CoV-2 as the comparator (reference method). This type of comparator assay is itself considered a "ground truth" established by its own regulatory clearance process, relying on its validated accuracy rather than individual expert adjudication for each case in this study.
• Qualifications of experts: Not applicable as ground truth was established by a cleared molecular diagnostic test.

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

• Clinical Performance: The comparator was a U.S. FDA-cleared molecular respiratory panel. For discrepant results with this comparator, additional testing was performed using a U.S. FDA EUA SARS-CoV-2 molecular test. The text indicates that these discrepant test results were used to resolve the discrepancies (e.g., 7/9 SARS-CoV-2 negative; 8/28 SARS-CoV-2 positive from the specific footnotes), implying a third party or a consensus reference method was used for discordant samples. This suggests a form of discrepant analysis, where a third, highly accurate method or a re-test with a known method, is used to resolve differences between the investigational device and the primary comparator.

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 submission describes a molecular diagnostic test (in vitro diagnostic device), not an imaging-based AI diagnostic device requiring human reader interpretation in an MRMC study. The device provides a direct qualitative result (POSITIVE/NEGATIVE).

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

• Yes, this is a standalone device. The Xpert Xpress CoV-2 plus test is an automated, real-time RT-PCR test performed on GeneXpert Instrument Systems. Its output is a qualitative result (SARS-CoV-2 POSITIVE or NEGATIVE) based on the algorithm within the instrument, without human interpretation of raw data for diagnosis. Although human operators load samples and review results, the diagnostic determination itself is made by the system.

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

• Clinical Performance: The ground truth for clinical performance was established by concordance with a U.S. FDA-cleared molecular respiratory panel and, for discrepant cases, a U.S. FDA EUA SARS-CoV-2 molecular test. This represents a highly accurate molecular diagnostic reference method.
• Analytical Performance: Ground truth for analytical studies was established using known concentrations of inactivated SARS-CoV-2 virus, WHO International Standard for SARS-CoV-2 RNA, genomic RNA/DNA of various microorganisms, and in silico analyses against sequence databases.

8. The sample size for the training set

• Not explicitly stated in terms of a "training set". For molecular diagnostic tests, "training" typically refers to the development and optimization of the primer and probe design, and algorithmic thresholds. This development process often involves internal studies and iterations rather than a distinct "training set" in the machine learning sense. The extensive analytical performance studies (LoD, inclusivity, exclusivity) serve to validate the developed algorithm's performance against diverse known samples. In silico analyses involved millions of SARS-CoV-2 sequences.

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

• As noted above, a distinct "training set" in the machine learning context is not explicitly described. However, the ground truth for optimizing the assay's primers, probes, and detection thresholds would have been established through:
  • Known concentrations of synthetic SARS-CoV-2 genetic material or inactivated virus.
  • In silico analysis against extensive public sequence databases (e.g., GISAID, NCBI) to identify target regions and ensure inclusivity of variants while maintaining exclusivity against other pathogens.
  • Laboratory-prepared samples with known microbial content and concentrations used to optimize and validate analytical performance characteristics like sensitivity and specificity.

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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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The Xpert® FII & FV test is a qualitative in vitro diagnostic genotyping test for the detection of Factor II and Factor V alleles from sodium citrate or EDTA anticoagulated whole blood. The test is performed on the Cepheid GeneXpert® Instrument Systems. This test is intended to provide results for Factor II (G20210A) and Factor V Leiden (G1691A) mutations as an aid in the diagnosis in individuals with suspected thrombophilia.

The Cepheid Xpert® FII & FV is a rapid, automated DNA test for detecting FII and FV normal and mutant alleles directly from sodium citrate or EDTA anticoagulated whole blood specimens. Blood specimens are drawn into either sodium citrate or EDTA anticoagulant tubes. Following brief mixing of the sample, 50 uL of the blood sample is transferred to the bottom wall of the Sample opening of the Xpert FII & FV test cartridge. The user initiates a test from the system user interface and places the cartridge into the GeneXpert® Instrument system instrument platform (comprised of the GeneXpert Dx Systems and GeneXpert Infinity Systems), which performs hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of DNA. In the GeneXpert Instrument Systems platform, sample preparation, amplification, and real-time detection are all fully-automated and completely integrated.

The GeneXpert Instrument Systems have 1 to 80 randomly accessible modules, depending upon the instrument, that are each capable of performing separate sample preparation and real- time 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 PCR and detection.

The Xpert FII & FV test includes reagents for the detection of Factor II and Factor V normal and mutant alleles. The primers and probes in the Xpert FII & FV test determine the genotype of the Factor II gene (at position 20210) and the Factor V gene (at position 1691). The test includes a Sample Processing Control to confirm adequate processing of the target bacteria and to monitor the presence of inhibitor(s) in the PCR assay. The Probe Check Control (PCC) verifies reagent rehydration, PCR tube filling in the cartridge, probe integrity, and dye stability.

The test is performed on the Cepheid GeneXpert Instrument Systems, which automate and integrate sample purification, nucleic acid amplification of the target sequences in simple or complex samples using real-time PCR. The systems consist of an instrument, personal computer, and preloaded software for running the tests and viewing the results. The GeneXpert Instrument Systems require the use of single-use disposable cartridges that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained, crosscontamination between samples is minimized. In this platform, additional sample preparation, amplification, and real-time detection are all fully- automated and completely integrated. The Xpert FII & FV test performed on the GeneXpert Instrument Systems provides results in approximately 30 minutes.

The FDA 510(k) summary for the Cepheid Xpert® FII & FV device outlines its performance and validation, primarily focusing on demonstrating substantial equivalence to a predicate device when used with new instrument systems (GeneXpert Infinity Systems).

Here's an analysis of the provided information against your requested criteria:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not provide a formal table of quantitative acceptance criteria with corresponding performance metrics like sensitivity, specificity, accuracy, etc. This is typical for a Special 510(k) submission where the primary objective is to demonstrate that a change (new instrument compatibility) does not negatively impact the existing, previously cleared performance.

Instead, the "Performance Data" section states:

• Acceptance Criteria (Implicit): That the performance claims of the Xpert FII & FV test were not impacted by the use of the GeneXpert Infinity Systems.
• Reported Device Performance: This was assessed through verification studies, including a "Cartridge Hold Time study" and a "Functional Testing study." The document explicitly states that the results "determined that the performance claims of the Xpert FII & FV test were not impacted."

Therefore, the performance is essentially stated as "comparable to the predicate device and original claims," rather than providing new specific rates (e.g., "99% sensitivity," "98% specificity").

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

The document does not explicitly state the sample sizes for the "Cartridge Hold Time study" and "Functional Testing study." It only mentions that these were "verification studies."

• Data Provenance: Not specified in terms of country of origin.
• Retrospective or Prospective: Not explicitly stated, but typically, verification studies like these for in vitro diagnostic devices would involve prospective testing of samples under controlled conditions to assess functionality and stability on the new instrument.

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

This type of information is not applicable to this device and study. The Xpert® FII & FV test is a qualitative in vitro diagnostic genotyping test for detecting specific DNA mutations (Factor II and Factor V alleles). The "ground truth" for such a device is established by the known genetic status of the samples used in the studies (e.g., confirmed Factor II or Factor V mutation presence/absence via reference methods or defined synthetic constructs), not by expert human interpretation of images or other subjective data. No human experts are used to establish ground truth for this kind of molecular diagnostic test performance.

4. Adjudication Method for the Test Set

Not applicable. As explained above, the "ground truth" for a genotyping test is based on direct molecular confirmation, not on subjective interpretations requiring adjudication.

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

Not applicable. The Xpert® FII & FV is an automated diagnostic test that provides a definitive genetic result. It does not involve human readers interpreting output that would be improved with AI assistance, nor is it a diagnostic imaging device where MRMC studies are common.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

This is the primary mode of operation for this device. The Xpert® FII & FV test is an automated system as described: "perform[s] hands-off real-time, multiplex polymerase chain reaction (PCR) for detection of DNA." The results ("Result," "Not Detected," or "Invalid") are generated by the instrument's internal algorithms based on PCR amplification signals. The human interaction is limited to sample loading and initiating the test. Therefore, the "Functional Testing study" and "Cartridge Hold Time study" effectively assess the standalone performance of the algorithm and instrument system.

7. The Type of Ground Truth Used

The ground truth for a genotyping test is based on the presence or absence of specific DNA sequences/mutations. While not explicitly stated how this truth was established for the specific "verification studies," for molecular diagnostic tests, ground truth is typically confirmed using:

• Reference molecular methods: Such as Sanger sequencing or highly validated in-house PCR assays.
• Characterized samples: Samples with known genetic status (e.g., from biobanks, synthetic constructs, or previously validated patient samples).
• Clinical diagnosis/outcomes data: In some cases, to correlate the genetic findings with the clinical presentation, although for genotyping tests, the primary ground truth is molecular.

Given the nature of this device, it would be based on the confirmed genetic status of the samples.

8. The Sample Size for the Training Set

This information is not provided. As this is a Special 510(k) for an instrument change, the focus is on verification rather than a full re-validation involving new training sets. The underlying algorithms and core test technology (primers, probes, PCR) remain the same as the predicate device. Training sets would have been used in the original development and validation of the Xpert® FII & FV test (K082118).

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

Not provided in this document as it pertains to the original development of the predicate device (K082118), not this Special 510(k). For the original development, ground truth would have been established as described in point 7 (reference molecular methods, characterized samples).

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