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The Revogene® instrument is intended for in vitro diagnostic (IVD) use in performing nucleic acid testing of specific IVD assays in clinical laboratories. Revogene is capable of automated lysis and dilution of samples originating from various clinical specimen types. Revogene performs automated amplification and detection of target nucleic acid sequences by fluorescence-based real-time PCR.

The Revogene is a PCR instrument that automates lysis and dilution of samples, followed by nucleic acid amplification, and detection of target sequences by fluorescence-based real-time PCR. Revogene runs are orchestrated by a combination of software, firmware and instrument control protocol that ensures the adequate combination times and temperatures for sample homogenization and PCR analysis. The Revogene instrument acquires fluorescence signals generated during amplification. The signals are then interpreted by the system using embedded calculation algorithms.

The Revogene requires the use of a 'PIE', i.e., an assay-specific cartridge to which a patient sample is added. The PIE contains the reagents needed to process a sample and to perform a PCR amplification. When the number of assay PIEs to be run is lower than eight, the user fills empty spaces with "MOCK PIE", which are cartridges that simulate the presence of an assay PIE to confer thermal and rotational balance.

The Revogene instrument subject of this Premarket Notification is substantially equivalent to the Revogene instrument cleared under K222779. Meridian is submitting this 510(k) Premarket Notification to implement a photomultiplier tube (PMT) cooling system. This cooling system keeps the PMT environment at a temperature that prevents the appearance of fluorescence glitches, which may stop the Revogene instrument

The provided document is a 510(k) Premarket Notification for a modified medical device, the Revogene instrument. It focuses on the changes made to an existing device (K222779) and its substantial equivalence to the predicate device.

The document does not contain information about acceptance criteria or a detailed study proving the device meets specific acceptance criteria, as one might find in a clinical trial report for an initial device clearance.

Instead, it describes the performance characteristics of functional testing conducted to demonstrate that the modifications (PMT cooling system and Windows 10 upgrade) do not adversely affect the device's performance compared to the predicate. The goal of this submission is to show substantial equivalence, not to establish new performance acceptance criteria.

Therefore, I cannot provide a table of acceptance criteria and reported device performance in the traditional sense, nor can I answer many of your specific questions about study design, sample sizes, ground truth establishment, or expert adjudication, as this information is not present in the provided text.

However, I can extract the available information regarding the functional testing that was performed to support the substantial equivalence claim.

Summary of Available Information on Device Performance and Testing:

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

The document does not explicitly state quantitative acceptance criteria. Instead, it describes general observations and conclusions from functional testing. The implicit acceptance criterion is "no statistically significant differences" and "operates as expected and yields expected assay results."

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

• Sample Size for Test Set: The document states "contrived and negative samples in relevant clinical matrix using the following assays...". However, it does not specify the number of samples or runs used for this functional testing.
• Data Provenance: Not explicitly stated, but given it's a regulatory submission by a US company, the testing would typically be conducted according to established protocols within their R&D or QA departments. It is retrospective relative to the design changes, but the testing itself is performed to support the new device version. No information on country of origin of data beyond the manufacturer's location.

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

• This information is not provided as the testing described is functional performance testing of the instrument, not typically involving expert interpretation of patient samples for ground truth establishment. The "ground truth" here is the expected performance of control samples within the assays.

4. Adjudication method for the test set

• This is not applicable/provided. The testing focuses on the instrument's functional output (e.g., Ct values, glitch occurrence) rather than interpretation of results that would require adjudication.

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

• No, this was not done. The device is an instrumentation for clinical multiplex test systems, meaning it processes samples and detects nucleic acids. It does not output images or data that require human readers for interpretation in the way an AI diagnostic imaging device would. Therefore, an MRMC study is not relevant to this type of device or its modifications.

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

• The device itself is a standalone instrument that performs automated lysis, dilution, amplification, and detection. The "algorithm" here refers to the embedded calculation algorithms within the system that interpret fluorescence signals to determine results. The functional testing described is a form of standalone performance evaluation for the modified instrument. There is no human-in-the-loop component mentioned for the actual nucleic acid detection and interpretation process of the instrument.

7. The type of ground truth used

• The ground truth for the functional testing appears to be based on the expected outcomes from known contrived and negative samples when run with specific IVD assays (Revogene® Strep A, Revogene® Carba C and Revogene® SARS-CoV-2). Essentially, the "ground truth" is the established performance of the assays themselves on control materials, and the instrument must correctly process these, showing no statistical degradation from the predicate.

8. The sample size for the training set

• This information is not provided and is generally not applicable in the context of hardware modifications to an existing IVD instrument as described. The "training set" concept is typically relevant for machine learning algorithms, which are not detailed here beyond "embedded calculation algorithms" that likely leverage established PCR physics and signal processing rather than iterative machine learning training.

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

• This information is not provided as there is no mention of a traditional "training set" in the machine learning sense. The established performance of the assays with known control materials serves as the reference for evaluating the modified instrument.

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The Revogene® instrument is intended for in vitro diagnostic (IVD) use in performing nucleic acid testing of specific IVD assays in clinical laboratories. Revogene is capable of automated lysis and dilution of samples originating from various clinical specimen types. Revogene performs automated amplification and detection of target nucleic acid sequences by fluorescence-based real-time PCR.

The Revogene® instrument is intended for in vitro diagnostic (IVD) use in performing nucleic acid testing of specific IVD assays in clinical laboratories. Revogene is capable of automated lysis and dilution of samples originating from various clinical specimen types. Revogene performs automated amplification and detection of target nucleic acid sequences by fluorescence-based real-time PCR.

The provided document is an FDA 510(k) Substantial Equivalence Determination Decision Summary for the Revogene instrument.
Crucially, this submission (K222779) is a "Special 510(k)" for a firmware modification only, specifically to add a cooling sequence before lid opening in the event of a run interruption.

Therefore, the document does not contain information about a study to prove the device's diagnostic performance against acceptance criteria in the typical sense of analytical or clinical performance (e.g., sensitivity, specificity for detecting a disease). Instead, the performance demonstrated here relates to the safety feature implemented by the firmware update.

Based on the provided text, here's an analysis of the acceptance criteria and study that address the firmware modification:

1. Table of Acceptance Criteria and Reported Device Performance:

The document implicitly defines the acceptance criteria for this specific modification: the firmware update must successfully implement a cooling sequence before lid opening when a run is interrupted, to prevent access to hot parts.

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

The document does not detail specific sample sizes or data provenance (e.g., country of origin, retrospective/prospective) for testing this firmware modification. This is expected given the nature of a Special 510(k) for a safety-related firmware update. The FDA's decision to clear the device implies they were satisfied with the internal validation conducted by the manufacturer to demonstrate the successful implementation of this safety feature. No clinical data or large-scale analytical testing is typically required for such minor safety updates.

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

Not applicable for this type of firmware modification. The ground truth here is a functional safety requirement (i.e., "are hot parts accessible when a run is aborted after the update?"). This would be verified through engineering testing and safety assessments, not typically by expert consensus of clinical or radiological images.

4. Adjudication method for the test set:

Not applicable. This is not a study assessing diagnostic performance where adjudication of ambiguous results would be necessary.

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 device is an instrument for molecular diagnostics (nucleic acid testing), not an AI-assisted diagnostic imaging device.

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

Not directly applicable in the typical sense (e.g., for an AI algorithm). The device itself operates "standalone" in its function of automated lysis, amplification, and detection, but the "performance" discussed here is a safety feature of its firmware, not its diagnostic accuracy.

7. The type of ground truth used:

The ground truth for this specific firmware modification is a functional safety performance objective. The "truth" is whether the cooling sequence activates as intended upon run interruption and whether it effectively prevents access to hot parts, thereby improving user safety. This would be established through engineering functional testing and safety verification protocols.

8. The sample size for the training set:

Not applicable. This is a firmware modification for a safety feature, not a machine learning algorithm that requires a "training set."

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

Not applicable. As above, no training set for a machine learning model is involved.

Summary of the document's relevance to your request:

The provided document is an FDA clearance letter for a firmware upgrade to an existing medical device, the Revogene instrument. This is a very specific type of submission (Special 510(k)) that focuses on demonstrating that a minor change does not adversely affect the device's safety or effectiveness, or alter its fundamental scientific technology.

Therefore, the typical metrics and study designs used for evaluating the diagnostic performance of new AI/ML-based devices (e.g., sensitivity, specificity, MRMC studies, ground truth established by expert consensus or pathology) are not present or applicable here. The "acceptance criteria" and "study" are focused solely on verifying the successful and safe implementation of the firmware's added cooling sequence upon run interruption.

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The Revogene® instrument is intended for in vitro diagnostic (IVD) use in performing nucleic acid testing of specific IVD assays in clinical laboratories. Revogene is capable of automated lysis and dilution of samples originating from various clinical specimen types. Revogene performs automated amplification and detection of target nucleic acid sequences by fluorescence-based real-time PCR.

The Revogene was previously cleared under K170558. Meridian Biosciences, Inc. is submitting this 510(k) to implement a software modification to the Revogene that updates the current software with a PMT surveillance algorithm. The software monitors raw data fluorescence signal during assay testing and identifies issues due to a malfunction of the photomultiplier tube (the "PMT"), a key component in the Revogene instrument's optics system used in the management of fluorescence signals. Upon detection of a PMT malfunction, the PMT surveillance algorithm software produces a specific error code to the user labeled "Detection Error" and will lock the instrument thereby preventing further use.

The provided text describes a 510(k) submission for a software modification to the Revogene instrument, specifically the addition of a PMT (photomultiplier tube) surveillance algorithm. This modification is intended to monitor raw data fluorescence signals and identify issues due to a malfunction of the PMT, a key component in the instrument's optics system. Upon detection of a PMT malfunction, the algorithm produces an error code and locks the instrument, preventing further use.

The document states that this change does not affect the device's intended use nor alter the device's fundamental scientific technology. Therefore, the acceptance criteria and performance study details are focused on validating the new PMT surveillance algorithm's functionality and ensuring it does not negatively impact the previously cleared performance of the Revogene instrument.

Based on the provided text, a formal table of acceptance criteria and reported device performance, akin to what would be provided for a diagnostic or AI algorithm's clinical performance, is not explicitly present for the PMT surveillance algorithm itself. The document emphasizes that the modification is minor and focuses on the software's ability to detect and report PMT malfunctions.

However, we can infer the acceptance criteria and study proving the device meets them from the description of the software modification and the context of a 510(k) submission for a software update.

Here's a breakdown based on the provided information, addressing each point as much as possible:

Acceptance Criteria and Reported Device Performance

The core acceptance criterion for this software modification is that the PMT surveillance algorithm successfully detects and reports PMT malfunctions. The reported performance would be the successful implementation of this functionality.

Inferred Acceptance Criteria Table:

Study Proving Acceptance Criteria:

The document implicitly indicates that a validation study was performed to demonstrate the functionality of the PMT surveillance algorithm. While details are scarce, the submission implies that the testing confirmed the algorithm's ability to detect PMT issues and trigger the appropriate error and lock-out mechanisms.

Detailed Study Information (Based on Inferences and General 510(k) Practices for Software Updates)

1. A table of acceptance criteria and the reported device performance:
   (See above table for inferred criteria and performance, as direct explicit table is not provided in the document for the new software feature). The document stresses that the overall performance characteristics of the Revogene instrument remain as previously cleared (K170558, K170557, etc.), and this software update doesn't change those.

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

   • Test Set Sample Size: Not explicitly stated for the PMT surveillance algorithm. For a software update of this nature (detecting a hardware malfunction), the "test set" would likely involve inducing PMT malfunctions (or simulating conditions that would lead to them) on multiple instruments to verify the algorithm's response. The general statement "The submitted information demonstrates that the modified Revogene instrument is safe, effective" implies a sufficient level of testing.
   • Data Provenance: Not specified. Given it's a software update for a commercialized instrument, the testing would typically be performed internally by the manufacturer (Meridian Bioscience, Inc.). It's likely retrospective in that it's testing a new feature on existing hardware, but the testing itself would be prospective for evaluating the new software. Country of origin not specified, but the manufacturer is based in Ohio, USA.

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

   • This is unlikely to involve a panel of "experts" in the same way an AI diagnostic algorithm's ground truth is established. The ground truth for a PMT malfunction would be a measurable hardware degradation or induced failure that clearly indicates the PMT is not functioning correctly. This would be established by engineers or instrument specialists, not clinical experts like radiologists.

4. Adjudication method for the test set:

   • Not applicable in the context of this software update. Adjudication methods like 2+1 or 3+1 are typically for establishing ground truth for subjective human interpretations (e.g., medical image reads). Here, the judgment is objective: either the PMT is malfunctioning or it's not, and the software either detects it or it doesn't.

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

   • No. An MRMC study is not relevant for this type of software modification. MRMC studies are used to evaluate the impact of an AI algorithm on human reader performance for tasks involving perception and interpretation (e.g., diagnosing disease from medical images). This software is performing an automated internal diagnostic check on the instrument itself, not assisting human clinical interpretation.

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

   • Yes, implicitly. The PMT surveillance algorithm operates automatically as an internal check. Its performance is evaluated purely on its ability to detect PMT malfunctions and trigger the pre-defined error and lock-out, without human intervention in its real-time operation.

7. The type of ground truth used:

   • Instrumental/Hardware Ground Truth: The ground truth would be based on objective measurements and engineered conditions that reliably indicate a PMT malfunction within the Revogene instrument's optics system. This could involve simulating PMT degradation, intentionally causing component failures, or verifying against known hardware states.

8. The sample size for the training set:

   • Not specified. For a diagnostic algorithm like this, the "training set" would involve data collected from instrument operations, potentially including data from instruments with known good or failing PMT conditions, to develop and refine the detection algorithms. The complexity of the algorithm (e.g., rule-based vs. machine learning) would influence the need for and size of a specific "training set." Given the description, it sounds more like a rule-based or threshold-based detection system rather than a complex machine learning model that requires a large, annotated training set in the typical sense.

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

   • If a "training set" was used (e.g., for setting detection thresholds or developing rules), the ground truth would have been established by engineering teams through controlled experiments, measurements of PMT performance over time, and potentially by inducing known PMT issues on instruments. This would involve characterization of the instrument's optical signals under various conditions, including states indicative of PMT malfunction.

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The revogene™ instrument is intended for in vitro diagnostic (IVD) use in performing nucleic acid testing of specific IVD assays in clinical laboratories. The revogene™ is capable of automated lysis and dilution of samples originating from various clinical specimen types. revogene™ performs automated amplification and detection of target nucleic acid sequences by fluorescence-based real-time PCR.

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The provided text is a 510(k) premarket notification letter from the FDA to GENEPOC INC. regarding their Revogene device. It details the regulatory classification, general controls, and indications for use of the device.

However, the document does not contain the specific information required to answer your request about acceptance criteria and the study proving the device meets those criteria. Specifically, the document does not provide:

• A table of acceptance criteria and reported device performance.
• Details on the sample size used for the test set or its data provenance.
• The number or qualifications of experts used for ground truth establishment.
• Information on adjudication methods.
• Details on multi-reader multi-case (MRMC) comparative effectiveness studies.
• Standalone algorithm performance.
• The type of ground truth used.
• Sample size for the training set or how its ground truth was established.

The document is purely administrative, confirming the FDA's substantial equivalence determination and outlining regulatory obligations. It does not delve into the technical performance studies or the clinical trials typically associated with proving a device meets acceptance criteria.

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The Luminex® ARIES® M1 System is an in vitro diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® M1 System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification of target nucleic acid sequences by fluorescence-based PCR.

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This document is a FDA clearance letter for the Luminex ARIES® M1 System, an in vitro diagnostic (IVD) platform. It primarily describes the regulatory approval rather than a detailed study proving the device meets specific acceptance criteria with performance metrics.

Therefore, the requested information about acceptance criteria, device performance, sample sizes, ground truth establishment, expert qualifications, and specific study designs (like MRMC or standalone performance) is not available within the provided text.

The document states the "ARIES® M1 System is an in vitro diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories" and that it "is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification of target nucleic acid sequences by fluorescence-based PCR." This is a description of its capabilities rather than performance statistics.

To answer your request, a detailed performance study report from Luminex Corporation would be required, which is typically a separate document submitted to the FDA as part of the 510(k) application, but not included in this clearance letter.

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The Luminex ARIES® System is an in vitro diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence-based PCR.

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I am sorry, but the provided text does not contain information about acceptance criteria, device performance tables, sample sizes for test sets, data provenance, number or qualifications of experts, adjudication methods, MRMC study results, standalone performance, type of ground truth used, or details about the training set for the ARIES® System. The document is an FDA 510(k) clearance letter and an Indications for Use statement, which primarily confirm regulatory approval and describe the system's intended function.

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The Luminex ARIES® System is an in vitro diagnostic (IVD) platform that performs nucleic acid based tests in clinical laboratories. The Luminex ARIES® System is capable of automated extraction and purification of nucleic acids from multiple sample types as well as the automated amplification and detection of target nucleic acid sequences by fluorescence-based PCR.

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This document, K151917, is a 510(k) premarket notification for the Luminex ARIES® System, an in vitro diagnostic (IVD) platform. However, the provided text does not contain any information regarding acceptance criteria, study details, performance data, sample sizes, ground truth establishment, or expert qualifications.

The document primarily focuses on:

• The FDA's determination of substantial equivalence for the device.
• Regulatory information and responsibilities for the manufacturer.
• The Indications for Use statement for the ARIES® System.

Therefore, I cannot fulfill your request for the specific details about acceptance criteria and the study that proves the device meets them, as that information is not present in the provided text.

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Alere™ i Influenza A & B:

The Alere™ i Influenza A & B assay performed on the Alere™ i Instrument is a rapid molecular in vitro diagnostic test utilizing an isothermal nucleic acid amplification technology for the qualitative detection and discrimination of influenza A and B viral RNA in nasal swabs from patients with signs and symptoms of respiratory infection. It is intended for use as an aid in the differential diagnosis of influenza A and B viral infections in humans in conjunction with clinical and epidemiological risk factors. The assay is not intended to detect the presence of influenza C virus.

Negative results do not preclude influenza virus infection and should not be used as the sole basis for diagnosis, treatment or other patient management decisions.

Performance characteristics for influenza A were established during the 2012-2013 influenza A/H3 and A/H1N1 pandemic were the predominant influenza A viruses in circulation. When other influenza A viruses are emerging, performance characteristics may vary.

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

Alere™ i Strep A:

Alere™ i Strep A is a rapid, instrument-based, molecular in vitro diagnostic test utilizing isothermal nucleic acid amplification technology for the qualitative detection of Streptococcus pyogenes, Group A Streptococcus bacterial nucleic acid in throat swab specimens obtained from patients with signs and symptoms of pharyngitis. It is intended to aid in the rapid diagnosis of Group A Streptococcus bacterial infections.

All negative test results should be confirmed by bacterial culture because negative results do not prection with Group A Streptococcus and should not be used as the sole basis for treatment.

Alere™ i Influenza A & B is a rapid, instrument-based isothermal tests for the qualitative detection and differentiation of influenza A and influenza B from nasal swabs collected from patients presenting with signs and symptoms of respiratory infection. Alere™ i Strep A is a rapid, instrument-based isothermal test for the qualitative detection of Group A Strep from throat swab specimens. Both Alere™ i Influenza A & B and Alere™ i Strep A Systems utilize isothermal nucleic acid amplification technology and are comprised of:

• . Sample Receiver – single use, disposable containing the elution buffer
• . Test Base – single use, disposable comprising two sealed reaction tubes, each containing a lyophilized pellet
• Transfer Cartridge single use, disposable for transfer of the eluted sample to the Test Base, and ●
• Alere™ i Instrument – repeat use reader

The reaction tubes in the Alere™ i Influenza A & B Test Base contain the reagents required for amplification of the target nucleic acid and an internal control. Alere™ i Influenza A & B utilizes a pair of templates (similar to primers) for the specific amplification of RNA from influenza A and B and a fluorescently labeled molecular beacon designed to specifically identify the amplified RNA targets.

The reaction tubes in the Alere™ i Strep A Test Base contain the reagents required for Group A Strep bacterial lysis and the subsequent amplification of the target nucleic acid and an internal control. Alere™ i Strep A utilizes a pair of templates (similar to primers) for the specific amplification of DNA from Group A Strep and a fluorescently labeled molecular beacon designed to specifically identify the amplified nucleic acid target.

Both assays are performed within the confinement of the Test Base, and no other part of the Alere™ i Instrument has contact with the sample during the amplification process. This reduces the risk of instrument contamination and sample carry-over between measurements.

To perform the assay, the Sample Receiver and Test Base are inserted into the Alere™ i Instrument and the elution buffer is automatically heated by the instrument. The sample is added to the Sample Receiver and transferred via the Transfer Cartridge to the Test Base, resuspending the lyophilized pellets contained within the Test Base and initiating bacterial lysis (for Alere™ i Strep A) and target amplification. Heating, mixing and detection by fluorescence is provided by the instrument, with results automatically reported.

Results are displayed by the Alere™ i Instrument and are also stored in an on-board archive and are assigned to a sample ID that has been entered into the Alere™ i Instrument by the operator, and the date/time the test was performed. Data can be retrieved and downloaded by the operator at any time after testing. An external Alere™ Universal Printer can be attached via USB to the Alere™ i Instrument to print test results.

The provided document describes the Alere™ i Instrument, Alere™ i Influenza A & B, and Alere™ i Strep A devices. This submission focuses on a software modification to the Alere™ i Instrument to allow it to run both the Influenza A & B and Strep A assays, rather than changes to the assays themselves. Therefore, the "acceptance criteria" and "device performance" in this context refer to demonstrating that the software modification does not negatively impact the performance of the previously cleared assays.

Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Rationale for the Study: The primary goal of this 510(k) submission (K151690) is to demonstrate that a software modification to the Alere™ i Instrument, which enables it to run both the Alere™ i Influenza A & B and Alere™ i Strep A assays, does not alter the established safety and effectiveness of these assays. The previous versions of these tests (Alere™ i Influenza A & B, K141520 and Alere™ i Strep A, K141757) were already cleared. Therefore, the study focuses on validating the software modification.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of numerical "acceptance criteria" for clinical performance that needed to be met by a de novo study of the device. Instead, the acceptance criterion for this submission is implicitly that the software modification does not change the performance of the previously cleared assays. The reported "performance" for the modified device is that its functionality remains unchanged compared to the predicate devices.

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

The document explicitly states: "Software verification and validation studies performed demonstrated that Alere™ i Influenza A & B and Alere™ i Strep A assay functionality remains unchanged due to this change."

However, no specific sample sizes for a "test set" (e.g., number of patient samples, artificial samples) used in these software validation studies are provided in the excerpt. The data provenance (country of origin, retrospective/prospective) is also not detailed for these specific software validation studies. Given that the submission asserts "no changes to the Alere™ i Influenza A & B or Alere™ i Strep A tests," it's highly probable that the software validation primarily involved testing with internal samples or simulated data to ensure proper functionality and integration, rather than a new full-scale clinical study with patient samples. The information indicates the tests themselves had established performance characteristics from previous submissions.

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

Since the study described here is focused on software validation and demonstrating unchanged functionality of existing assays, rather than determining the initial clinical accuracy of the assays against a clinical ground truth, there is no mention of experts establishing a ground truth for a test set in this context.

4. Adjudication Method for the Test Set

As there is no mention of a clinical test set requiring expert ground truth, no adjudication method is described.

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

No MRMC comparative effectiveness study was mentioned. The device is an in vitro diagnostic test, not an AI software intended to assist human readers in image interpretation or a similar task. It is a standalone instrument that provides qualitative diagnostic results.

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

Yes, the performance of the Alere™ i Instrument is inherently standalone. The device processes the sample and provides an automated qualitative result ("Influenza A Detect", "Influenza B Detect", "Strep A Detect", or "Not Detected"). The "Software verification and validation studies" described would have assessed this standalone performance with the modified software.

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

For the original clinical performance studies of the Alere™ i Influenza A & B (K141520) and Alere™ i Strep A (K141757) assays, the ground truth would typically involve:

• For Influenza A & B: Viral culture as the gold standard, or potentially a highly multiplexed PCR reference method, on patient nasal swab samples.
• For Strep A: Bacterial culture as the gold standard on patient throat swab samples.

However, for this specific submission (K151690), the "software validation" would likely use pre-characterized samples (e.g., positive and negative control samples, spiked samples with known concentrations of nucleic acid targets) or previously run clinical samples with known results from predicate studies, to verify that the software processes them identically and yields the same results. The document does not specify the ground truth for these software validation studies, but it would not be a new clinical ground truth establishment.

8. The Sample Size for the Training Set

No training set is mentioned in the context of this software modification. The assays themselves are isothermal nucleic acid amplification tests, not machine learning algorithms that require a training set in the typical sense. Any "training" would have been part of the initial development and optimization of the assays prior to the K141520 and K141757 submissions.

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

Not applicable, as no training set for a machine learning model is described.

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The BD Viper LT System is intended for in vitro diagnostic (IVD) use in clinical laboratories to perform automated extraction of nucleic acids from multiple specimen types, amplification of target nucleic acid sequences by Strand Displacement Amplification (SDA) and detection of amplified nucleic acid using a two color fluorescence detection system. The BD Viper LT is for use only with in vitro diagnostic tests labeled for use on the system.

The BD Viper LT System is a table-top instrument that is designed to be fully contained on a standard laboratory bench-top. The system performs automated extraction of nucleic acids from multiple specimen types in addition to amplification and detection of target nucleic acid sequences when utilized with legally marketed in vitro diagnostic assays.

Here's an analysis of the acceptance criteria and study data for the BD Viper™ LT System, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

The document primarily focuses on the technical specifications of the BD Viper LT System and states that its clinical utility was assessed in a separate submission. Therefore, the "acceptance criteria" presented here are the technical specifications of the instrument, and the "reported device performance" implies that internal studies validated these specifications. No specific pass/fail metrics or clinical performance numbers are provided within this document for the BD Viper LT System itself, beyond the statement that studies were conducted to validate the specifications.

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

The document states: "Internal studies were conducted to validate the instrument specifications presented in Tables 2-3." However, it does not provide any details regarding the sample size used for these internal studies, nor does it specify the data provenance (e.g., country of origin, retrospective or prospective nature).

It does mention that the "Clinical utility of the BD Viper LT System was assessed during clearance of the BD ProbeTec GCQ Amplified DNA Assay as presented in a separate premarket submission (K140448)." This suggests that any clinical data pertaining to its actual performance with patient samples would be found in that separate submission, not in this one focused on the instrument itself.

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

Not applicable for the data presented in this document. The listed acceptance criteria relate to instrument specifications (temperature, optics), which would typically be validated through engineering and laboratory measurements, not through expert review for ground truth in a diagnostic sense.

4. Adjudication Method for the Test Set:

Not applicable. Given that the validation studies were for instrument specifications, there would not be an adjudication method in the way one would for diagnostic imaging or clinical interpretation.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size:

Not applicable. This document describes an automated laboratory instrument (BD Viper LT System). MRMC studies are typically performed for technologies that involve human interpretation, such as medical imaging AI, to assess how AI assistance impacts human reader performance.

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

The entire "device" described here, the BD Viper LT System, is an automated standalone instrument designed for nucleic acid extraction, amplification, and detection. Its performance as an automated system is its standalone performance. The document explicitly states its function as performing "automated extraction of nucleic acids," "amplification," and "detection."

7. The Type of Ground Truth Used:

For the instrument specifications (thermal and optical), the "ground truth" would be established by precision laboratory instruments and calibration standards. These are objective physical measurements rather than expert consensus, pathology, or outcomes data, which are typically associated with diagnostic performance.

8. The Sample Size for the Training Set:

Not applicable. Automated laboratory instruments like the BD Viper LT System are typically designed and engineered based on physical principles, chemical reactions, and optical mechanics. They do not undergo "training" in the same way machine learning algorithms do, which require large training sets.

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

Not applicable for the same reasons as point 8. The "ground truth" for the development of such an instrument would be the accurate and precise operation of its various components as designed, validated through engineering tests and calibrations.

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The QuantStudio™ Dx Real-Time PCR Instrument with QuantStudio™ Dx Software is intended to perform fluorescence-based PCR to provide detection of FDA cleared and approved nucleic acid sequences in human-derived specimens. The QuantStudio™ Dx Real-Time PCR Instrument with QuantStudio™ Dx Software is intended for in vitro diagnostic use by trained laboratory technologists in combination with nucleic acid reagent kits/tests manufactured and labeled for diagnostic purposes on this instrument.

The QuantStudio™ Dx Real-Time PCR Instrument is a bench top Real-Time PCR instrument that uses fluorescent-based polymerase chain reaction (PCR) reagents to provide qualitative or quantitative detection of target nucleic acid sequences (targets) using real-time analysis.
The QuantStudio™ Dx Real-Time PCR Instrument system includes the following components:

• QuantStudio™ Dx Real-Time PCR instrument with embedded graphical user . interface (eGUI) Touchscreen
• Thermal Block, also referred to as the sample block, with associated Heated Cover . and Plate Adaptor
• Calibration and verification materials for instrument qualification .
• . Computer workstation with a monitor, keyboard and mouse
• QuantStudio™ Dx instrument software .

Here's an analysis of the provided text to extract information about the acceptance criteria and the study demonstrating the device meets them:

K123955: QuantStudio™ Dx Real-Time PCR Instrument

This submission concerns the QuantStudio™ Dx Real-Time PCR Instrument, which is a benchtop real-time PCR instrument intended for in vitro diagnostic use to detect FDA-cleared and approved nucleic acid sequences in human-derived specimens. The performance data presented focuses on its use with the Quidel® Molecular Real-Time PCR Direct C. difficile Tox A/B Assay.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly derived from the "Precision/Reproducibility" and "Detection Limit" sections, and then more explicitly in the "Comparison Studies" section through performance metrics like sensitivity and specificity against a reference method (Tissue Culture Cytotoxicity Assay and Enhanced Toxigenic Culture).

Implicit Acceptance Criteria (Analytical Performance):

Explicit Acceptance Criteria (Clinical Performance against Reference Method):

2. Sample Size and Data Provenance for the Test Set

• Analytical Test Set (Precision/Reproducibility):

  • Precision: A "blinded four-member panel consisting of C. difficile positive and negative sample" tested over 12 days by 2 operators, twice a day, using a single assay lot. The total number of tests for each panel member would be 48 (2 operators * 2 times/day * 12 days). For example, 0.3x LoD shows 88% detection, implying 42 positive results out of 48 total tests.
  • Reproducibility: A "blinded and randomized study panel" tested at three (3) test sites. Each site tested the panel for five (5) days in triplicate on each instrument, by two operators. Each operator ran the panel once a day. This means for each panel member, at each site, there were 30 tests (2 operators * 5 days * 3 replicates). Total tests for each panel member across all three sites would be 90 (30 tests/site * 3 sites).
  • Data Provenance: Not explicitly stated for analytical studies, but given the manufacturer's location and the mention of Quidel, it's likely primarily US-based or an international corporate R&D setting. The study is prospective in nature, designed specifically for this validation.

• Clinical Test Set (Comparison Studies):

  • Sample Size: 792 samples initially collected. 788 specimens were used for the Tissue Culture Cytotoxicity Assay comparison, and 791 specimens were used for the Enhanced Toxigenic Culture comparison (due to removed invalid/indeterminate results).
  • Data Provenance: Prospective study conducted from August to November 2012. Samples were "collected from patients suspected of having Clostridium difficile-associated disease (CDAD) at four (4) distinct geographical sites across the United States."

3. Number of Experts and Qualifications for Ground Truth

• Analytical Studies: Ground truth for analytical studies (precision, reproducibility, LoD) is typically based on known concentrations of the target analyte (like C. difficile strains in CFU/mL) prepared in a laboratory setting. No external "experts" are typically involved in establishing this ground truth beyond the scientific personnel designing and executing the standard preparations and dilutions.

• Clinical Studies:

  • Tissue Culture Cytotoxicity Assay: This is a laboratory-based reference method for detecting C. difficile toxin. The "experts" involved would be the laboratory personnel performing and interpreting this gold standard assay. Their qualifications are not specified but would typically involve trained medical technologists or microbiologists.
  • Enhanced Toxigenic Culture: This is another laboratory-based reference method. Similar to the cytotoxicity assay, the "experts" would be trained laboratory personnel. Their qualifications are not specified.
  • The document does not mention a panel of experts for consensus reading of raw data or images. The ground truth relies on established laboratory methodologies.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method involving multiple human readers for the test set.

• For the analytical studies, results are based on direct output from the instrument (detection yes/no, Ct values) against predetermined concentrations, so no adjudication is required.
• For the clinical comparison studies, the "ground truth" (reference standard) is provided by the Tissue Culture Cytotoxicity Assay and Enhanced Toxigenic Culture. Discordant results between the Quidel Molecular Direct C. difficile Assay on the QuantStudio™ Dx and these reference methods were further investigated by testing with an "FDA-cleared molecular device." This serves as a form of secondary adjudication or reconciliation for discordant results but does not involve human readers adjudicating an algorithm's output. For example:
  • For the Cytotoxicity comparison, 45 Quidel Positive/Tissue Culture Negative were re-tested with an FDA-cleared molecular device: 35 positive, 9 negative.
  • 7 Quidel Negative/Tissue Culture Positive were re-tested with an FDA-cleared molecular device: 2 positive, 5 negative.
  • Similar reconciliation was done for the Enhanced Toxigenic Culture comparison.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study focuses on the standalone performance of the instrument with a specific diagnostic assay, and its concordance with established reference laboratory methods. There is no mention of human readers evaluating cases with and without AI assistance.

6. Standalone (Algorithm Only) Performance

Yes, the studies presented demonstrate standalone performance of the QuantStudio™ Dx Real-Time PCR Instrument (in conjunction with the Quidel Molecular Direct C. difficile Assay). The data provided (detection rates, Ct values, sensitivity, specificity) represent the performance of the instrument/assay system without direct human-in-the-loop intervention for result interpretation beyond running the assay and reviewing its output.

7. Type of Ground Truth Used

• Analytical Studies (Precision, Reproducibility, LoD): Known concentrations of specific C. difficile strains (e.g., ATCC BAA-1870 and ATCC BAA-1872) diluted in a negative fecal matrix. This is a form of analytical (spiked) ground truth.
• Clinical Studies (Comparison Studies):
  • Tissue Culture Cytotoxicity Assay: An established laboratory method for detecting C. difficile toxin.
  • Enhanced Toxigenic Culture: An established laboratory method for detecting toxigenic C. difficile.
  • For discordant results, an "FDA-cleared molecular device" was used for reconciliation.
    These are all forms of reference standard (laboratory-based) ground truth.

8. Sample Size for the Training Set

The document does not provide information on a training set sample size. The submission describes the performance validation of the instrument when used with a specific diagnostic assay, rather than the development and training of a machine learning algorithm. PCR instruments perform predefined biochemical reactions and detect fluorescence signals based on set parameters, they do not typically undergo "training" in the machine learning sense.

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

Since there is no mention of a training set for a machine learning algorithm, there is no information provided on how ground truth was established for a training set. The instrument's operation is based on established PCR principles and specified assay parameters.

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