Search Results

The Influenza A/B Typing Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

• For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture.

• To provide epidemiological information for surveillance of circulating influenza viruses.

Performance characteristics for influenza were established during a season when seasonal influenza viruses A(H1N1) and A(H3N2) were the predominant influenza A viruses in circulation and during a season when the A(H1N1)pdm09 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses.

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

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 unless a BSL 3E facility is available to receive and culture specimens.

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A Subtyping Kit (VER 4)

The Influenza A Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

• For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3) and/or A(H1)pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;

• To provide epidemiological information for surveillance of circulating influenza viruses.

Performance characteristics for influenza were established during a season when seasonal influenza viruses A(H1N1) and A(H3N2) were the predominant influenza A viruses in circulation and during a season when the A(H1N1)pdm09 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses.

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

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 unless a BSL 3E facility is available to receive and culture specimens.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza B Lineage Genotyping Kit (VER 1.1 and 2)

The Influenza B Lineage Genotyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

• For the determination of the genetic lineage of human influenza B viruses as B/Victoria or B/Yamagata lineage from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) from human patients with signs and symptoms of respiratory infection and/or from viral culture;

• To provide epidemiologic information for surveillance of circulating influenza viruses.

Performance characteristics for influenza B lineage genotyping were established during a season when influenza B/Victoria and B/Yamagata lineages were in circulation.

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

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza A/H5 Subtyping Kit (VER 4)

The Influenza A/H5 Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

• For the presumptive identification of virus in patients who may be infected with influenza A subtype A(H5) (Asian lineage) from viral RNA in human respiratory specimens, conjunctival swabs, and viral culture in conjunction with clinical and epidemiological risk factors;

• To provide epidemiologic information for surveillance of circulating influenza viruses.

Performance characteristics for influenza were established during a season when seasonal influenza viruses A(H1N1) and A(H3N2) were the predominant influenza A viruses in circulation and during a season when the A(H1N1)pdm09 influenza virus was the predominant influenza A virus in circulation. Performance characteristics may vary with other emerging influenza A viruses.

Testing with the influenza H5a and H5b primer and probe sets should not be performed unless the patient meets the most current U.S.Department of Health and Human Services (DHHS) clinical and epidemiologic criteria for testing suspect A(H5) specimens. The definitive identification of influenza A(H5) (Asian lineage) either directly from patient specimens or from virus cultures requires additional laboratory testing, along with clinical and epidemiological assessment in consultation with national influenza surveillance experts.

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

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 unless a BSL 3E facility is available to receive and culture specimens.

The CDC Human Influenza Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with the CDC device. The panel is configured in four separate kits. Each kit consists of oligonucleotide primers, fluorescently labeled hydrolysis probes, and controls which are used in rRT-PCR assays for the in vitro qualitative detection and characterization of influenza virus RNA in respiratory specimens from patients presenting with influenza-like illness (ILI) or from viral culture.

Oligonucleotide primers and probes for detection of influenza A, influenza B, and influenza A of swine origin were selected from highly conserved regions of the matrix (M), non-structural (NS), and nucleoprotein (NP) genes, respectively. Oligonucleotide primers and probes for characterization and differentiation of influenza A(H3) and A(H1)pdm09 viruses, avian influenza A(H5) viruses, and genetic lineages of influenza B were selected from highly conserved regions of their hemagglutinin (HA) genes. Oligonucleotide primers and probes to detect the human RNase P gene (RP) in control samples and clinical specimens is also included in the panel.

The provided document, K243274: CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel, is an FDA 510(k) clearance letter. This document primarily describes the device, its intended use, and confirms its substantial equivalence to a previously cleared predicate device (K243931). Critically, it states that no analytical or clinical testing was performed for this specific modification, as the submission was to add a Predetermined Change Control Plan (PCCP).

Therefore, the document does not contain the detailed study results, acceptance criteria, sample sizes, ground truth establishment, or expert involvement for the original validation of the device's performance. It explicitly states that "The performance characteristics of the CDC Flu rRT-PCR Dx Panel... were previously established and remain the same as the predicate device (K243931)."

As such, I cannot provide the specific information requested in the prompt based on the provided text alone. The prompt asks for details of "the device" meeting acceptance criteria, and this document pertains to a modification that did not involve re-evaluating performance.

However, I can interpret what would typically be sought for such an analysis in the context of an in vitro diagnostic (IVD) PCR panel like the one described. I will outline what the acceptance criteria and the study that proves the device meets them would likely entail for an IVD, but with the explicit understanding that the provided document does not contain these details.

Based on the provided document, the device's performance characteristics were "previously established" for the predicate device (K243931) and are simply carried over here as "remaining the same." The current submission (K243274) is for adding a Predetermined Change Control Plan (PCCP) and states that "No analytical testing was performed for this modification" and "No clinical testing was performed for this modification."

Therefore, the detailed information regarding acceptance criteria, reported performance, sample sizes, expert involvement, and ground truth establishment for the original validation of this device is NOT present in the provided text. The tables and descriptions below represent what would typically be expected for an FDA cleared RT-PCR diagnostic panel, assuming the original studies were conducted to industry standards, but are not extracted directly from the given document.

Acceptance Criteria and Device Performance (Hypothetical for an RT-PCR IVD)

For a real-time RT-PCR diagnostic panel like the CDC Human Influenza Virus Panel, acceptance criteria and performance would typically focus on analytical sensitivity (Limit of Detection - LoD), analytical specificity (cross-reactivity, inclusivity), and clinical performance (sensitivity, specificity).

1. Table of Acceptance Criteria and Reported Device Performance (Hypothetical)

Ask a specific question about this device

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit (VER 2)

The Influenza A/B Typing Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and evidemiological information:

· For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture.

· To provide epidemiological information for surveillance of circulating influenza viruses.

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A Subtyping Kit (VER 4)

The Influenza A Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

· For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3) and/or A(H1)pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture:

· To provide epidemiological information for surveillance of circulating influenza viruses.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza B Lineage Genotyping Kit (VER 1.1 and 2)

The Influenza B Lineage Genotyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic realtime PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

• For the determination of the genetic lineage of human influenza B viruses as B/Victoria or B/Yamagata lineage from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) from human patients with signs and symptoms of respiratory infection and/or from viral culture;

· To provide epidemiologic information for surveillance of circulating influenza viruses.

CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza A/H5 Subtyping Kit (VER 4)

The Influenza A/H5 Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

· For the presumptive identification of virus in patients who may be infected with influenza A subtype A(H5) (Asian lineage) from viral RNA in human respiratory specimens, conjunctival swabs, and viral culture in conjunction with clinical and epidemiological risk factors;

· To provide epidemiologic information for surveillance of circulating influenza viruses.

The CDC Human Influenza Real-Time RT-PCR Diagnostic Panel consists of four real-time RT-PCR (rRT-PCR) assays used on IVD-labeled real-time PCR instruments that has been FDA-cleared for use with this device. The panel is configured in four separate kits: Influenza A/B Typing kit, Influenza A/H5 Subtyping kit, and Influenza B Genotyping kit. Each kit consists of oligonucleotide primers, fluorescently labeled hydrolysis probes, and controls which are used in rRT-PCR assays for the in vitro qualitative detection of influenza virus RNA in respiratory and conjunctival specimens from patients presenting with influenza-like illness (IL). Oligonucleotide primers and probes for detection of influenza A, influenza B, and 2009 influenza A (swine origin) were selected from highly conserved regions of the matrix (M), non-structural (NS), and nucleoprotein (NP) genes, respectively. Oligonucleotide primers and probes for characterization and differentiation of influenza A(H3) and A(H1)pdm09 viruses, genetic lineages of influenza A(H5) viruses were selected from highly conserved regions of their HA genes. Oligonucleotide primers and probes to detect the human RNase P gene (RP) in control samples and clinical specimens are also included in the panel.

The provided text describes the acceptance criteria and study proving the device meets those criteria for the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel: Influenza A/H5 Subtyping Kit (VER 4), specifically concerning the addition of conjunctival swabs as a specimen type.

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

1. Table of acceptance criteria and the reported device performance:

The document does not explicitly present a table of acceptance criteria in terms of specific quantitative thresholds (e.g., minimum sensitivity/specificity percentages) for clinical performance. Instead, it describes an evaluation based on demonstrating successful detection capabilities and similarity to a predicate device. The performance is reported descriptively based on the clinical study results.

Reported Device Performance (for Influenza A/H5 Subtyping Kit (VER 4) on conjunctival swabs):

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

• Clinical Test Set Sample Size:
  • 46 total cases (44 confirmed, 2 probable) initially considered.
  • 35 confirmed cases were assessed for performance due to exclusion of 9 cases where not all necessary assay reagents were used.
  • 2 probable cases were assessed.
  • The document also specifies the number of clinical specimens available for testing: e.g., 32 confirmed cases had subject-matched paired URT and CS specimens, 3 confirmed cases had only CS specimens, 1 probable case had subject-matched paired URT and CS specimens, and 1 probable case had only a CS specimen.
• Data Provenance:
  • Country of Origin: US (from public health investigations in the US).
  • Retrospective or Prospective: The data was collected from specimens from March to November 2024 as part of public health investigations into outbreaks. This indicates a retrospective collection of existing specimens from human cases.

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

• The ground truth for confirmed/probable cases of A/H5N1 was established based on "the criteria described in the current Council of State and Territory Epidemiologists (CSTE) document 24-ID-09." The document does not specify the number of individual experts or their qualifications directly. This refers to established public health guidelines rather than individual expert consensus.

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

• The ground truth was established by adherence to existing CSTE criteria, not through a human reader adjudication process of the device's output. The device results were compared against these established "confirmed or probable case status."

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, an MRMC comparative effectiveness study was not done. This document describes the validation of a laboratory diagnostic kit (RT-PCR) with specific specimen types and does not involve human readers interpreting images or AI assistance.

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

• Yes, this is effectively a standalone performance study. The device itself is an RT-PCR diagnostic panel. The "performance" described is that of the kit (reagents and controls run on a PCR instrument) in detecting viral RNA, without human interpretation of raw data beyond reading the instrument's output based on established cut-offs (e.g., Ct values). It's an "algorithm only" in the sense that the test results in a definitive positive, negative, or inconclusive outcome based on chemical reactions and signal detection.

7. The type of ground truth used:

• The ground truth for the clinical performance evaluation was based on "confirmed or probable case status for each case on the criteria described in the current Council of State and Territory Epidemiologists (CSTE) document 24-ID-09." This can be categorized as outcomes data/epidemiological criteria as determined by public health authorities.

8. The sample size for the training set:

• The document describes the validation of a diagnostic panel (PCR-based), not an AI algorithm. Therefore, there is no specific "training set" in the machine learning sense. The device's components (primers, probes) and their performance characteristics are established through analytical studies (e.g., LoD, interfering substances) and clinical validation with patient samples. The development of such a kit is based on extensive prior knowledge of influenza virus genetics and PCR technology, but not a "training set" in the context of supervised learning for AI.

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

• As there is no "training set" in the AI sense, this question is not applicable to the device described. The "ground truth" for the analytical development of the RT-PCR panel would be based on well-characterized viral samples (e.g., BPL inactivated virus with known concentrations) and established laboratory techniques for nucleic acid detection.

Ask a specific question about this device

The Influenza A Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

· For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3) and/or A(H1)pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;

· To provide epidemiologic information for surveillance of circulating influenza viruses.

The Influenza A Subtyping Kit contains components of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel that is used in rRT-PCR assays on an FDA-cleared in vitro diagnostic real-time PCR instrument. The primer and probe sets contained in the Influenza A Subtyping Kit are designed for the detection and characterization of influenza type A viruses that infect humans.

The Influenza A Subtyping Kit consists of oligonucleotide primers and dual-labeled hydrolysis (TagMan®) probes and controls. which may be used in rRT-PCR assays for the in vitro qualitative detection and characterization of the human influenza virus RNA in respiratory specimens from patients presenting with influenza-like illness (IL). The oligonucleotide primers and probes for detection of Influenza A and 2009 Influenza A (swine origin) were selected from highly conserved regions of the matrix (M), and the nucleoprotein (NP), respectively. Oligonucleotide primers and probes for characterization and differentiation of seasonal influenza A(H3) and A(H1)pdm09 viruses were selected from highly conserved regions of their respective HA genes. Detection of viral RNA not only aids in the diagnosis of illness caused by seasonal. newly emerging, and novel influenza viruses in patients with ILI, but also provides epidemiological and surveillance information on influenza and aids in the presumptive laboratory identification of specific novel influenza A viruses.

Here's a breakdown of the acceptance criteria and the study proving the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are implied through the performance metrics evaluated and compared to the predicate device and NGS as a gold standard. The core idea is that the modified assay should perform equivalently or better than the previous version, especially for strains with the 3' mutation.

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

• Sample Size (Clinical Evaluation):
  • Positive Specimen Panel: 60 influenza A(H3) specimens (30 with 3' mutation, 30 without 3' mutation).
  • Negative Specimen Panel: 60 negative specimens (from symptomatic patients known to be positive for influenza H1N1).
  • Total Clinical Test Set: 120 specimens (60 positive, 60 negative).
• Data Provenance: Retrospective study. Clinical specimens were collected from patients during previous influenza seasons in the United States.

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

Not applicable. The ground truth for the clinical test set was established using Next Generation Sequencing (NGS) and direct clinical specimen classification, not through expert consensus of visual or diagnostic interpretation.

4. Adjudication Method for the Test Set

Not applicable. The ground truth for the clinical test set was established via Next Generation Sequencing (NGS), which directly determines the genetic identity of the virus, rather than a consensus among human reviewers.

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 in vitro diagnostic real-time RT-PCR diagnostic panel, not an AI-assisted diagnostic tool that would involve human readers interpreting AI output.

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

Yes, the performance evaluation in this submission is of the standalone device (algorithm only). The RT-PCR assay itself provides the result, without human interpretation of the assay's primary output (e.g., a visual scan of a reaction). The results are considered definitive from the machine output.

7. The Type of Ground Truth Used

• Analytical Performance: The ground truth for analytical sensitivity (LoD) and inclusivity studies was based on known, quantified viral stocks (EID50/mL or ID50/mL) of specific influenza strains.
• Clinical Performance: The ground truth for positive and negative clinical specimens was established using Next Generation Sequencing (NGS) as the comparator assay. This method directly confirms the identity and specific genetic characteristics (e.g., presence of 3' mutation) of the influenza virus in the samples.

8. The Sample Size for the Training Set

The document does not explicitly state a "training set" in the context of device development. This is a modification to an existing RT-PCR assay, and the "development" or "training" of such a device primarily involves bioinformatic analysis, primer/probe design adjustments, and analytical testing with known isolates. The "in-silico analysis" described (Process 1: assessment of primers against global H3N2 sequence information from GISAID EpiFlu database; Process 2: BLAST against NCBI nr/nt database) serves a similar function to a training set for algorithm-based devices by informing the optimal primer and probe sequences. No numerical sample size is provided for these bioinformatic databases.

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

As noted above, for an RT-PCR assay, the "training set" concept is different from an AI/ML context. The ground truth for informing the primer/probe design (which is effectively the "training" data for the assay's specificity and sensitivity for detecting target sequences) was established through:

• GISAID EpiFlu database: This database contains comprehensive, publicly shared influenza sequence information, used to assess potential primer and probe sets against known H3N2 sequences and calculate nucleotide mismatches. The sequences in this database are derived from laboratories globally undergoing influenza surveillance.
• NCBI BLAST+ against the nr/nt database: This is a vast database of non-redundant nucleotide sequences, against which primer sequences were compared to confirm inclusivity for H3 Influenza virus HA segments and exclusivity against non-target sequences.

This information is based on established genetic sequences, which serve as the fundamental "ground truth" for designing molecular diagnostic assays.

Ask a specific question about this device

The Non-variola Orthopoxvirus Real-ime PCR Primer and Probe Set is intended for the in vitro qualitative presumptive detection of non-variola Orthopoxvirus DNA extracted from human pustular rash specimens and viral cell culture lysates submitted to a Centers for Disease Control and Prevention designated laboratory. The assay detects nonvariola Orthopoxvirus DNA, including vaccinia, cowpox, monkeypox and ectromelia viruses at varying concentrations. This assay does not differentiate vaccinia virus or monkeypox virus from other orthopoxviruses detected by this assay and does not detect variola virus. Refer to the CDC algorithm, Acute, Generalized Vesicular or Pustular Rash Illness Testing Protocol in the United States for recommended testing and evaluation algorithms for patients presenting with acute, generalized pustular or vesicular rash illness.

Results of this assay are for the identification of non-variola Orthopoxvirus DNA. These results must be used in conjunction with other diagnostic assays and clinical observations to diagnose Orthopoxvirus infection. The assay should only be used to test specimens with low/moderate risk of smallpox exists, viral culture should not be attempted. Negative results obtained with this device do not prection virus infection and should not be used as the sole basis for treatment or other patient management decisions.

Use is limited to Centers for Disease Control and Prevention designated laboratories.

Unchanged from original submission (K221834).

The provided text is a 510(k) Summary for the "Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set". This document primarily focuses on demonstrating substantial equivalence to a predicate device and outlines the intended use and some general performance characteristic categories.

However, the document does not include detailed information regarding:

• A table of acceptance criteria and reported device performance.
• Sample sizes used for test sets or their data provenance.
• Number of experts used to establish ground truth or their qualifications.
• Adjudication methods.
• Multi-reader multi-case (MRMC) comparative effectiveness study results.
• Standalone (algorithm only) performance.
• Specific types of ground truth used (beyond implying laboratory testing).
• Sample size for training sets.
• How ground truth for training sets was established.

Instead, for performance characteristics, the document states: "Inquiries regarding performance characteristics for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set should be directed to the Centers for Disease Control and Prevention." It mentions that the Limit of Detection (LOD) was determined through an analytical sensitivity study and broadly references analytical sensitivity and specificity, as well as clinical performance, but without providing the detailed results or methodologies for these studies within this summary.

The document highlights the device's intended use for in vitro qualitative presumptive detection of non-variola Orthopoxvirus DNA and the need to use results in conjunction with other diagnostic assays and clinical observations. It also specifies use limitations to "Centers for Disease Control and Prevention designated laboratories."

Therefore, based solely on the provided text, I cannot provide the requested detailed information regarding acceptance criteria and study particulars. The document explicitly directs inquiries about these performance characteristics to the CDC.

Ask a specific question about this device

The Non-variola Orthopoxvirus Real-ime PCR Primer and Probe Set is intended for the in vitro qualitative presumptive detection of non-variola Orthopoxvirus DNA extracted from human pustular rash specimens and viral cell culture lysates submitted to a Laboratory Response Network (LRN) reference laboratory. The assay detects non-variola Orthopoxvirus DNA, including vaccinia, cowpox, monkeypox and ectromelia viruses at varying concentrations. This assay does not differentiate vaccinia virus or monkeypox virus from other orthopoxviruses detected by this assay and does not detect variola virus. Refer to the CDC algorithm, Acute, Generalized Vesicular or Pustular Rash IIIness Testing Protocol in the United States for recommended testing and evaluation algorithms for patients presenting with acute, generalized pustular or vesicular rash illness.

Results of this assay are for the identification of non-variola Orthopoxvirus DNA. These results must be used in conjunction with other diagnostic assays and clinical observations to diagnose Orthopoxvirus infection. The assay should only be used to test specimens with low/moderate risk of smallpox exists, viral culture should not be attempted. Negative results obtained with this device do not prection virus infection and should not be used as the sole basis for treatment or other patient management decisions.

Use is limited to Centers for Disease Control and Prevention designated laboratories.

Unchanged from original submission (K221658).

This document, a 510(k) summary for the "Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set" (K221834) from the Centers for Disease Control and Prevention (CDC), does not provide details on acceptance criteria or the specific study proving the device meets those criteria directly within the provided text.

Instead, it refers to a predicate device (K221658) and indicates that the current submission (K221834) is similar, with the main change being labeling. It explicitly states:

• "Unchanged from original submission (K221658)" for Device Description, Principle of Operation, Sample Types, and Instrumentation/Software.
• For "Analytical Limit of Detection (LoD)", "Analytical Sensitivity and Specificity", and "Clinical Performance," it repeatedly states: "Inquiries regarding performance characteristics for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set should be directed to the Centers for Disease Control and Prevention."

Therefore, based solely on the provided text, the specific information requested cannot be fully extracted. However, I can provide a template of what such an answer would look like if the information were available, and address what can be inferred or is explicitly absent.

Unable to fully answer based on provided text. The document refers to a predicate device and directs inquiries for performance characteristics to the CDC, rather than detailing them.

Here's an overview of the requested information based on what is and isn't present in the document:

1. Table of Acceptance Criteria and Reported Device Performance
This information is not provided in the document.

2. Sample Size Used for the Test Set and Data Provenance
This information is not provided in the document. The document refers to performance characteristics from a previous submission (K221658) and states inquiries should be directed to the CDC.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
This information is not provided in the document. As this is an in vitro diagnostic (PCR test), ground truth would likely be established through a combination of culture, sequencing, or other highly sensitive and specific reference methods, rather than expert interpretation of images/clinical findings.

4. Adjudication Method
This information is not applicable/provided in the context of a PCR assay. Adjudication methods like 2+1 or 3+1 are typically used for subjective evaluations (e.g., image interpretation by radiologists or pathologists).

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
This information is not applicable/provided in the context of this device. An MRMC study is relevant for devices involving human interpretation (e.g., AI for radiology). This device is a molecular diagnostic assay.

6. Standalone Performance Study
Yes, this device is inherently a standalone algorithm/assay without human-in-the-loop performance measurement beyond the technician performing the PCR and interpreting the quantitative PCR cycles. The document implies such a performance study must have been conducted for the predicate device (K221658) when it mentions "Analytical Limit of Detection (LoD)," "Analytical Sensitivity and Specificity," and "Clinical Performance" studies, even though the results are not detailed here.

7. Type of Ground Truth Used
For a PCR assay, the ground truth for performance studies (LoD, analytical sensitivity, clinical performance) would typically be established by:

• Reference Methods: Culture, sequencing, or a validated gold-standard molecular test for the detection of non-variola Orthopoxviruses.
• Well-characterized samples: Use of known positive and negative controls, spiked samples, and clinical samples with confirmed infection status.
  This specific detail is not provided in the document, but these are the standard ground truth types for such a device.

8. Sample Size for the Training Set
This information is not provided in the document. For PCR primer and probe design, a "training set" might refer to the genomic sequences used to design the primers and probes. For assay validation, there isn't a "training set" in the machine learning sense; rather, there are analytical and clinical validation samples.

9. How the Ground Truth for the Training Set was Established
This information is not provided in the document, and the concept of "ground truth for a training set" is less directly applicable in the same way as it is for machine learning models. For a PCR assay, primer and probe sequences are designed based on conserved regions of target genomes. Validation samples would then have their true status established by highly reliable reference methods.

Ask a specific question about this device

The Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set is intended for the in vitro qualitative presumptive detection of non-variola Orthopoxvirus DNA extracted from human pustular rash specimens and viral cell culture lysates submitted to a Laboratory Response Network (LRN) reference laboratory. The assay detects non-variola Orthopoxvirus DNA, including Vaccinia, Cowpox, Monkeypox and Ectromelia viruses at varying concentrations. This assay does not differentiate Vaccinia virus or Monkeypox virus from other Orthopoxviruses detected by this assay and does not detect Variola virus. Refer to the CDC algorithm, Acute, Generalized Vesicular or Pustular Rash Illness Testing Protocol in the United States for recommended testing and evaluation algorithms for patients presenting with acute, generalized pustular or vesicular rash illness.

Results of this assay are for the identification of non-variola Orthopoxvirus DNA. These results must be used in conjunction with other diagnostic assays and clinical observations to diagnose Orthopoxvirus infection. The assay should only be used to test specimens with low/moderate risk of smallpox exists, viral culture should not be attempted. Negative results obtained with this device do not prection and should not be used as the sole basis for treatment or other patient management decisions.

Use is limited to Laboratory Response Network (LRN) designated laboratories.

The Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set uses a fluorogenic probe, consisting of an oliqonucleotide with a reporter dye (FAM) attached to the 5′ end and a quencher dye (BHQ1) attached at or near the 3′ end. The probe anneals to a specific target sequence located between the forward and reverse primers. During the extension phase of the PCR cycle, the 5' nuclease activity of the Taq polymerase degrades the probe causing the reporter dye to separate from the quencher dye, thereby generating a fluorescent signal. With each cycle, additional reporter dye molecules are cleaved from their respective probes and the fluorescence intensity is monitored during the PCR in real-time. The Taq polymerase used in this assay is inactive at room temperature and is activated by incubation at 95°C, thus minimizing the production of nonspecific amplification products.

Each extracted DNA sample is tested using the Non-variola Orthopoxvirus Real-time PCR Primer and Probe set alonq with an internal control primer and probe set(s) to demonstrate adequate DNA extraction, proper function of common reagents and equipment, and the absence of inhibitory substances.

This document is a 510(k) summary for the Non-variola Orthopoxvirus Real-time PCR Primer and Probe Set, submitted by the Centers for Disease Control and Prevention (CDC). It is a re-submission (K221658) of a previously cleared device (K181205). The document largely states that many aspects of the device are unchanged from the previous submission and directs further inquiries about performance characteristics to the CDC.

Based on the provided text, many of the requested details are not explicitly stated in this FDA summary document. The document refers to an "Original Submission (K181205)" for comparison and states that for most performance characteristics, inquiries should be directed to the CDC. However, based on the information available:

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

The document does not explicitly state "acceptance criteria" in a tabulated format or provide detailed "reported device performance" in this summary. It mentions an "Analytical Limit of Detection (LoD)" and "Analytical Sensitivity and Specificity" studies were performed. It also indicates "Clinical Performance" studies were conducted, but the results for these are not presented here. Given that this is a re-submission with an "Unchanged" intended use and principle of operation, the acceptance criteria and performance would likely be similar to or supported by the original submission (K181205).

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

This information is not explicitly provided in the text. It states that inquiries regarding performance characteristics should be directed to the CDC.

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)

This information is not explicitly provided in the text.

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

This information is not explicitly provided in the text.

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 device is a PCR primer and probe set for detecting viral DNA, not an AI-assisted diagnostic device. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed.

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

This device is a molecular diagnostic assay. Its performance is inherent to the chemical reactions and detection system, and it operates "stand-alone" in the sense that the test result is directly outputted by the instrumentation without human real-time modification of the analytical process. However, human interpretation of the results and clinical context is required as stated in the Indications for Use: "Results of this assay are for the identification of non-variola Orthopoxvirus DNA. These results must be used in conjunction with other diagnostic assays and clinical observations to diagnose Orthopoxvirus infection."

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

The document refers to "identification of non-variola Orthopoxvirus DNA" as the output. The ground truth for such molecular tests typically involves:

• Validated reference strains/samples: For analytical sensitivity and specificity, the ground truth would be precisely known viral DNA concentrations or the known presence/absence of target and non-target organisms.
• Clinical diagnosis/outcome: For clinical performance, the ground truth would be established through a combination of other diagnostic assays, clinical observations, and potentially follow-up outcomes, as implied by the statement "These results must be used in conjunction with other diagnostic assays and clinical observations to diagnose Orthopoxvirus infection."

Specific details are not provided in this summary.

8. The sample size for the training set

This information is not provided in the text. As a PCR diagnostic kit, there isn't typically a "training set" in the machine learning sense. Instead, development involves assay design, optimization, and then validation studies.

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

Not applicable as there is no "training set" in the machine learning context for this type of device. Assay optimization and validation (which could be considered analogous to "training" and "testing" in a broad sense for a traditional diagnostic) would rely on well-characterized samples with established viral content.

Ask a specific question about this device

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A/B Typing Kit (VER 2)
The Influenza A/B Typing Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

• · For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture.
• · To provide epidemiological information for surveillance of circulating influenza viruses.

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A Subtyping Kit (VER 3)
The Influenza A Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

• · For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3) and/or A(H1)pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], nasal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
• · To provide epidemiological information for surveillance of circulating influenza viruses.

CDC Human Influenza Real-Time RT-PCR Diagnostic Panel: Influenza A/H5 Subtyping Kit (VER 4)
The Influenza A/H5 Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:

• · For the presumptive identification of virus in patients who may be infected with influenza A subtype A(H5) (Asian lineage) from viral RNA in human respiratory specimens and viral culture in conjunction with clinical and epidemiological risk factors;
• · To provide epidemiological information for surveillance of circulating influenza viruses.

The CDC Human Influenza Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR system. The panel is configured in four separate kits. Each kit consists of oligonucleotide primers, fluorescently labeled hydrolysis probes, and controls which are used in rRT-PCR assays for the in vitro qualitative detection and characterization of influenza virus RNA in respiratory specimens from patients presenting with influenza-like illness (ILI). Oligonucleotide primers and probes for detection of influenza A, influenza B, and 2009 influenza A (swine origin) were selected from highly conserved regions of the matrix (M), non-structural (NS), and nucleoprotein (NP) genes, respectively. Oligonucleotide primers and probes for characterization and differentiation of influenza A(H3) and A(H1)pdm(9 viruses and genetic lineages of influenza B were selected from highly conserved regions of their HA genes. Oligonucleotide primers and probes to detect the human RNase P gene (RP) in control samples and clinical specimens is also included in the panel.

Here's a breakdown of the acceptance criteria and study information for the CDC Human Influenza Virus Real-time RT-PCR Diagnostic Panel, based on the provided text:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are primarily related to analytical sensitivity (Limit of Detection - LOD) and inclusivity for various influenza A strains, and analytical specificity (cross-reactivity and exclusivity). The clinical performance evaluation also serves as a form of acceptance criteria for positive and negative agreement with previously characterized samples.

Study Details:

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

• LOD Equivalency & Confirmation:

  • Sample Size: Varies by virus strain and specific assay. For LOD equivalency, triplicate samples of serial dilutions were tested. For LOD confirmation, 20 individually extracted samples were tested for each target.
  • Data Provenance: Virus strains are identified by name and origin (e.g., A/Michigan/45/2015, A/Illinois/20/2018, A/Hong Kong/4801/2014, A/Abu Dhabi/240/2018, A/duck/Vietnam/NCVD-1544/2012, A/duck/Vietnam/NCVD-17A231/2016). Specific country of origin for all strains is not explicitly stated but implied from nomenclature.
  • Retrospective/Prospective: Experimental, controlled laboratory studies using characterized virus stocks.

• Inclusivity:

  • Sample Size: 10 influenza A(H1N1)pdm09 viruses and 24 influenza A viruses of various types/subtypes. Each virus sample was tested in triplicate.
  • Data Provenance: Virus strains represented temporal, geographic, and genetic diversity (e.g., A/Florida/81/2018, A/Alaska/35/2018, A/Switzerland/8060/2017).
  • Retrospective/Prospective: Experimental, controlled laboratory studies using characterized virus stocks.

• Analytical Specificity (Cross-Reactivity & Exclusivity):

  • Sample Size: Cross-reactivity: Various influenza viruses (e.g., A/Perth/16/2009, B/Maryland/15/2016) tested in triplicate. Exclusivity: 35 organisms (16 viruses, 18 bacteria, 1 yeast) tested.
  • Data Provenance: Organisms are identified by strain name.
  • Retrospective/Prospective: Experimental, controlled laboratory studies using characterized stocks of various organisms.

• Clinical Performance Evaluation:

  • Sample Size:
    • Modified InfA Assay: 62 positive (35 A(H1N1)pdm09, 27 A(H3N2)) and 50 negative residual human respiratory clinical specimens.
    • Modified pdmInfA and pdmH1 Assays: 35 positive (for A(H1N1)pdm09) and 50 negative residual human respiratory clinical specimens.
  • Data Provenance: Residual human respiratory clinical specimens collected from patients during previous influenza seasons in the United States (2011-12 and 2013-14).
  • Retrospective/Prospective: Retrospective.

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

The document does not specify the number or qualifications of experts used to establish ground truth. For the analytical studies (LOD, inclusivity, specificity), the ground truth is based on the known identity and titer of the cultured virus or bacterial/yeast strains. For the clinical performance evaluation, the ground truth for "positive" or "negative" status was established by prior testing (comparator) with the FDA-cleared CDC Human Influenza Real-Time RT-PCR Diagnostic Panel (K190302), which implicitly would have been validated using established laboratory methods or expert consensus in its own clearance process.

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

No explicit adjudication method (like 2+1 or 3+1 consensus) is described. The analytical studies often cite "number of positive replicates out of three total replicates tested," implying a direct comparison to the expected outcome from the known sample. For clinical studies, the comparator is the already FDA-cleared predicate device.

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 is not applicable. The device is an in vitro diagnostic real-time RT-PCR diagnostic panel, not an AI-assisted diagnostic tool that humans interpret. There are no "human readers" in the context of interpreting the device's output, nor is there a multi-reader multi-case study described.

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

Yes, the studies described are standalone because the device itself is a diagnostic assay (a collection of reagents and controls) that produces a result (detection/characterization of viral RNA) through a real-time RT-PCR instrument. While laboratory personnel operate the instrument and interpret the output, the core performance studies evaluate the assay's ability to detect the target without human intervention influencing the assay's chemical and enzymatic reactions. The term "algorithm" is not directly applicable in the same way as with AI software, but the assay's 'logic' for detection is intrinsic to its design.

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

• For Analytical Studies (LOD, Inclusivity, Specificity): The ground truth is based on known, characterized viral and microbial strains with established titers (e.g., TCID50/mL or EID50/mL) or concentrations (CFU/mL, ng/µL). This is a highly controlled laboratory ground truth.
• For Clinical Performance Evaluation: The ground truth was established by prior testing with the FDA-cleared CDC Human Influenza Real-Time RT-PCR Diagnostic Panel (K190302), acting as the comparator or reference method for the collected residual human respiratory clinical specimens.

8. The sample size for the training set

The document does not explicitly describe a separate "training set" in the context of machine learning or AI. This device is a RT-PCR based assay, and its development would typically involve empirical optimization and validation against a variety of known strains and clinical samples rather than a formal training set for an AI model.

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

As there is no explicit "training set" described for an AI model, this question is not directly applicable. For the development and optimization of the RT-PCR assays, ground truth for evaluating probe and primer design would have been established through a combination of sequencing data to identify conserved regions and target specificity, and testing against known, characterized viral isolates/strains to ensure desired reactivity.

Ask a specific question about this device

The B. anthracis Real-Time PCR Assay is an in vitro diagnostic test for the qualitative detection of plasmid and chromosomal DNA sequences from B. anthracis. The assay can be used to test human respiratory samples, whole blood, serum, plasma, swabs from lesions, cerebrospinal fluid, and bacterial culture isolates from individuals suspected of having anthrax.

Results generated from direct specimentesting are presumptive for the identification of B. anthracis. Results generated from culture isolate testing should be used in conventional methods for identification of Bacillus anthracis isolates as part of the LRN Bacillus anthracis Testing Algorithm. The diagnosis of anthrax infection must be made based on history, signs, symptoms, exposure likelihood, and other laboratory evidences, in addition to the identification of B. anthracis from cultures or detection directly in clinical specimens.

Use is limited to Laboratory Response Network (LRN) designated laboratories.

The B. anthracis Real-time PCR Assay is also intended for environmental specimen testing for biothreat detection and response. FDA has not evaluated claims related to the use of this assay on environmental specimens.

The B. anthracis Real-time PCR Assay uses a fluorogenic probe, consisting of an oligonucleotide with a reporter dve (FAM) attached to the 5' end and a quencher dye (BHQ1) attached at or near the 3′ end. The probe anneals to a specific target sequence located between the forward and reverse primers. During the extension phase of the PCR cycle, the 5′ nuclease activity of Taq polymerase degrades the probe causing the reporter dye to separate from the quencher dye and a fluorescent signal is generated. With each cycle, additional reporter dye molecules are cleaved from their respective probes and the fluorescence intensity is monitored during the PCR. The Tag polymerase used in this assay is inactive at room temperature. It must be activated by incubation at 95°C, which also minimizes the production of nonspecific amplification products.

Each extracted DNA sample is tested with three B. anthracis primer and probe sets run as individual reactions. The primer and probe sets target genes encoding virulence factors as well as conserved regions of DNA from the B. anthracis chromosome. All primer and probe sets must be positive for the overall result of the B. anthracis Real-time PCR Assay to be interpreted as positive. Any result that is positive for some, but not all target regions, is still considered equivocal and follow-up laboratory investigation should be performed per the LRN Bacillus anthracis testing algorithm.

The provided document is a 510(k) premarket notification for the B. anthracis Real-time PCR Assay. It indicates substantial equivalence to a predicate device and provides information on its intended use, device description, and a comparison with the predicate. However, it explicitly directs inquiries regarding performance characteristics (including analytical limit of detection, analytical sensitivity and specificity, and clinical performance) to the Centers for Disease Control and Prevention. Therefore, the acceptance criteria and the study that proves the device meets those criteria are not detailed within this document.

Here is a summary of the information that is available in the document, and what is explicitly stated as not available:

1. Table of Acceptance Criteria and Reported Device Performance

• Not available in the provided document. The document directs inquiries regarding performance characteristics to the Centers for Disease Control and Prevention.

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

• Not available in the provided document. The document states that inquiries regarding analytical LoD, analytical sensitivity and specificity, and clinical performance should be directed to the Centers for Disease Control and Prevention. This would include information about sample sizes and data provenance for validation studies.

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

• Not applicable / Not available in the provided document. For a PCR assay, the "ground truth" is typically established by definitive laboratory methods (e.g., bacterial culture, sequencing, or a reference method) rather than expert opinion on images or clinical assessments. The details of how ground truth was established for the analytical and clinical performance studies are not present.

4. Adjudication method for the test set

• Not applicable / Not available in the provided document. See point 3.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, and the effect size of how much human readers improve with AI vs without AI assistance

• Not applicable. This device is a diagnostic PCR assay, not an AI-assisted imaging or diagnostic tool that involves human readers in the traditional sense of an MRMC study.

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

• Yes, implicitly. The device is a Real-time PCR Assay, which is an in vitro diagnostic test. Its performance inherently refers to its standalone analytical and clinical performance in detecting target DNA sequences. While human operators are involved in running the assay and interpreting results, the "algorithm" (the PCR chemistry and detection) itself functions stand-alone. However, specific details of "standalone performance" metrics (like sensitivity, specificity, accuracy against a reference standard) are not provided and are referred to the CDC.

7. The type of ground truth used

• For a PCR assay detecting DNA sequences from B. anthracis, the ground truth for performance studies would typically be established by a "gold standard" laboratory method, such as:
  • Bacterial culture and identification: Confirmation of B. anthracis growth and subsequent identification using conventional microbiological methods (e.g., phenotypic differences, susceptibility testing).
  • Reference molecular methods: Other validated PCR assays or DNA sequencing for definitive identification.
• Specific details of how ground truth was established for the validation studies are not available in the provided document.

8. The sample size for the training set

• Not applicable. For a PCR assay, there isn't a "training set" in the machine learning sense. The assay is developed based on known genetic targets of B. anthracis. Development involves optimizing primer/probe design and assay conditions, but not "training" an algorithm on a dataset.

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

• Not applicable. See point 8.

Ask a specific question about this device

The Influenza A/B Typing Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:
· For qualitative detection of influenza virus type A or B viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NPS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
· To provide epidemiologic information for surveillance of circulating influenza viruses.

The Influenza A Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:
· For determination of the subtype of seasonal human influenza A viruses as seasonal A(H3), and/or A(H1)pdm09 from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) and lower respiratory tract specimens (including bronchoalveolar lavage [BAL], bronchial wash [BW], tracheal aspirate [TA], sputum, and lung tissue) from human patients with signs and symptoms of respiratory infection and or from viral culture;
· To provide epidemiologic information for surveillance of circulating influenza viruses.

The Influenza B Lineage Genotyping Kit contains reagents and controls of the CDC Human Influenza Virus Real-Time RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR ) assays on an in vitro diagnostic realtime PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:
· For the determination of the genetic lineage of human influenza B viruses as B/Victoria or B/Yamagata lineage from viral RNA in upper respiratory tract clinical specimens (including nasopharyngeal swabs [NS], throat swabs [TS], nasal aspirates [NA], nasal washes [NW] and dual nasopharyngeal/throat swabs [NPS/TS]) from human patients with signs and symptoms of respiratory infection and/or from viral culture;
· To provide epidemiologic information for surveillance of circulating influenza viruses.

The Influenza A/H5 Subtyping Kit contains reagents and controls of the CDC Human Influenza Virus RT-PCR Diagnostic Panel and is intended for use in real-time RT-PCR ) assays on an in vitro diagnostic real-time PCR instrument that has been FDA-cleared for use with this kit in conjunction with clinical and epidemiological information:
· For the presumptive identification of virus in patients who may be infected with influenza A subtype A(H5) (Asian lineage) from viral RNA in human respiratory specimens and viral culture in conjunction with clinical and epidemiological risk factors;
· To provide epidemiologic information for surveillance of circulating influenza viruses.

The CDC Human Influenza Real-Time RT-PCR Diagnostic Panel is used in real-time RT-PCR (rRT-PCR) assays on an in vitro diagnostic real-time PCR system. The panel is configured in four separate kits. Each kit consists of oligonucleotide primers, fluorescently labeled hydrolysis probes, and controls which are used in rRT-PCR assays for the in vitro qualitative detection and characterization of influenza virus RNA in respiratory specimens from patients presenting with influenza-like illness (ILI). Oligonucleotide primers and probes for detection of influenza A, influenza B, and 2009 influenza A (swine origin) were selected from highly conserved regions of the matrix (M), non-structural (NS), and nucleoprotein (NP) genes, respectively. Oligonucleotide primers and probes for characterization and differentiation of influenza A(H3) and A(H1)pdm(9 viruses and genetic lineages of influenza B were selected from highly conserved regions of their HA genes. Oligonucleotide primers and probes to detect the human RNase P gene (RP) in control samples and clinical specimens is also included in the panel.

Here's a breakdown of the acceptance criteria and study details based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

The document focuses on demonstrating substantial equivalence of the modified device (with new PCR instruments) to a predicate device. The key acceptance criteria are related to analytical sensitivity (Limit of Detection or LOD) and reproducibility, and clinical agreement.

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

• Analytical Sensitivity (LOD):

  • For each virus type and dilution: Triplicate samples were tested. The testing involved multiple influenza viruses (e.g., A/H3N2, A/H1N1pdm09, B/Victoria, B/Yamagata, A/H5N8) and two enzyme systems (SuperScript and qScript) across the original instrument and the two new instruments. It's difficult to give a single "sample size" number but it involved a substantial number of replicates across various conditions to establish LOD.
  • Data Provenance: The samples were "characterized influenza viruses of known egg infectious dose 50% titer," diluted in BPL-treated A549 cells in viral transport medium (VTM). This indicates laboratory-prepared, controlled samples.

• Analytical Precision (Reproducibility):

  • Sample Size: A blinded panel of 5 contrived samples (moderate positive A/H3N2, moderate positive B/Victoria, negative, low positive A/H3N2, low positive B/Victoria). Each sample was tested by two analysts at each of three sites, over five different days. This means for each contrived sample, there were $3 \text{ sites} \times 2 \text{ analysts} \times 5 \text{ days} = 30$ results. Across the 5 samples this totals $5 \text{ samples} \times 30 \text{ tests/sample} = 150$ tests for the QSDx and 150 for the QMDx.
  • Data Provenance: Contrived samples (BPL-treated A549 cells in VTM, spiked with BPL-treated influenza A(H3N2) or B/Victoria virus).

• Carryover and Cross-contamination:

  • Sample Size: An alternating pattern of high positive (HP) and negative (N) contrived samples. There were 5 high positive samples and 5 negative samples tested across 5 runs. The tables show 5 sets of HP samples and 5 sets of N samples for each assay (InfA, H5a, H5b, RP). For each assay, this means $5 \text{ HP samples} \times 5 \text{ runs} = 25$ tests and $5 \text{ N samples} \times 5 \text{ runs} = 25$ tests.
  • Data Provenance: Contrived samples (BPL-inactivated influenza A/gyrfalcon/41088-6/2014 (H5N8) in A549 cells).

• Clinical Performance Evaluation:

  • Sample Size: A total of 50 clinical specimens and 10 contrived samples with influenza A(H5) were used as positive samples (totaling 60 positive samples if the contrived A(H5) are counted separate from the 50 general clinical positives). And 50 negative specimens. So, a total of 100 retrospective samples (50 positive, 50 negative) were evaluated against the QSDx and QMDx independently.
  • Data Provenance:
    • Retrospective clinical specimens: Collected during the 2013-2014 influenza seasons. (Country of origin not specified, but given the CDC involvement, likely U.S.)
    • Contrived samples: The 10 A(H5) samples were "prepared with BPL-inactivated influenza A(H5) virus in a suspension of human A549 cells and virus transport medium."

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

The document does not explicitly mention the number of experts or their specific qualifications for establishing ground truth for the test set (clinical performance evaluation).

• For the analytical studies (LOD, reproducibility, carryover), the ground truth was established by the known characteristics of the prepared viral stocks and dilutions.
• For the clinical performance, the ground truth was established by the "previously determined" results using the FDA-cleared Applied Biosystems™ 7500 Fast Dx. This implies that the predicate device serves as the ground truth. It does not state that independent experts re-adjudicated these samples, but rather that the previously established results from a gold-standard method were used.

4. Adjudication Method for the Test Set:

No explicit adjudication method (e.g., 2+1, 3+1) is described for the clinical test set. The clinical samples were "previously determined to be positive using the Applied Biosystems™ 7500 Fast Dx." This implies the predicate device's results were considered the reference standard for comparison.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance:

This device is an in-vitro diagnostic (IVD) RT-PCR kit, not an AI-assisted diagnostic imaging device that involves human "readers" or AI assistance to humans. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed.

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

The entire study focuses on the standalone performance of the device (RT-PCR kit with its associated instruments). The device is an automated molecular diagnostic assay, not an AI algorithm. Its performance is evaluated objectively based on its ability to detect and characterize viral RNA. While human analysts perform the procedure and interpret the output, the core 'performance' refers to the analytical and clinical accuracy of the molecular reactions and instrument readings.

7. The Type of Ground Truth Used:

• Analytical Studies (LOD, Reproducibility, Carryover): The ground truth was based on known concentrations of characterized viral stocks (EID50/mL titer) and the specific composition of contrived samples (known to be positive or negative for certain influenza strains). This is a form of laboratory-established ground truth.
• Clinical Performance Evaluation: The ground truth for the clinical specimens was derived from results previously obtained using the FDA-cleared Applied Biosystems™ 7500 Fast Dx. This acts as a reference standard from a legally marketed and established device. For the A(H5) samples, it was based on the known composition of the contrived samples.

8. The Sample Size for the Training Set:

The document describes an evaluation study for substantial equivalence of a molecular diagnostic kit with new instrument platforms. It does not mention a "training set" in the context of machine learning. The "training" for such a molecular kit would involve the extensive R&D and optimization of the primer/probe sets and PCR conditions during the device's development, not a data-based training set for an AI algorithm.

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

As mentioned above, there is no explicit "training set" in the machine learning sense described in this document. The ground truth for the development and optimization of such a diagnostic panel typically involves:

• Known viral isolates/strains: Using cultured viruses with confirmed identity and titer.
• Sequencing data: To design highly specific and sensitive primers/probes targeting conserved regions of the viral genome.
• Clinical validation: Testing against a large panel of clinical samples, where the true infection status (ground truth) is established through gold-standard methods (e.g., viral culture, sequencing, or other highly sensitive and specific molecular tests) performed by expert laboratories.

The document briefly states: "Oligonucleotide primers and probes for detection of influenza A, influenza B, and 2009 influenza A (swine origin) were selected from highly conserved regions of the matrix (M), non-structural (NS), and nucleoprotein (NP) genes, respectively. Oligonucleotide primers and probes for characterization and differentiation of influenza A(H3) and A(H1)pdm(9 viruses and genetic lineages of influenza B were selected from highly conserved regions of their HA genes." This suggests an established ground truth based on genomic sequencing and bioinformatic analysis to design the assay.

Ask a specific question about this device

Ask a specific question about this device