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The Applied Biosystems TaqPath COVID-19, Flu A, Flu B, RSV Select Panel is a multiplex, real-time reverse transcription polymerase chain reaction (RT-PCR) in vitro diagnostic test for the qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza B virus, and respiratory syncytial virus (RSV). Nucleic acids are isolated and purified from nasopharyngeal (NP) swab and anterior nasal (AN) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection. Clinical signs and symptoms of respiratory viral infection due to SARS-CoV-2, influenza, and RSV can be similar. This test is intended to aid in the differential diagnosis of SARS-CoV-2, influenza B, and RSV A/B (undifferentiated) infections in humans and is not intended to detect influenza C virus infections.

Nucleic acids from the viral organisms identified by this test are generally detectable in NP and AN swab specimens during the acute phase of infection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of respiratory tract infective of the presence of the identified virus and aids in diagnosis if used in conjunction with other clinical and epidemiological information, and laboratory findings.

The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results do not rule out coinfection with other organism(s) detected by the Applied Biosystems TaqPath COVID-19, Flu A, Flu B, RSV Select Panel may not be the definite cause of disease. Negative results do not preclude SARS-CoV-2, influenza A virus, influenza B virus, or RSV infections.

The Applied Biosystems TaqPath COVID-19, Flu A, Flu B, RSV Select Panel is intended for use by qualified and trained clinical laboratory personnel specifically instructed and trained in the techniques of real-time PCR and in vitro diagnostic procedures.

The Applied Biosystems™ TaqPath™ COVID-19, Flu A, Flu B, RSV Select Panel is a multiplex, real-time reverse transcription polymerase chain reaction (RT-PCR) test. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A, influenza B, respiratory syncytial virus (RSV) A/B and RNase P primer and probe sets are designed to detect viral RNA in nasopharyngeal (NP) and anterior nasal (AN) swab specimens from individuals exhibiting signs and symptoms of a respiratory tract infection.

Each TaqPath™ COVID-19, Flu A, Flu B, RSV Select Panel includes the following components:

• TaqPath™ COVID-19, Flu A, Flu B, RSV Select Assay-Multiplex assays that contain . primer and probe sets specific to the following targets:
  • Three SARS-CoV-2 targets (Orfla, Orf1b, and N genes) .
  • . Two influenza A virus targets (PB1 & M genes)
    • I Two influenza B virus targets (M & NS genes)
    • . Three RSV targets (NP, M, and L protein genes)
    • l RNase P (internal human sample collection control)
• TaqPath™ COVID-19, Flu A, Flu B, RSV Select Positive Control—Inactivated viral . control that contains SARS-CoV-2, influenza A, influenza B, and RSV.
• TaqPath™ COVID-19, Flu A, Flu B, RSV Select Negative Control—MS2 packaged RNA . control that contains targets specific to RNase P genomic regions targeted by the assay.
• TaqPath™ 1-Step Select Master Mix (No ROX)—Ready-to-use PCR mix, including . reverse transcriptase, polymerase, dNTPs, salts, and buffer.
• . Package Insert -- Provides the instructions and the link to download the instructions for use and other assets (including the ADF)
• An Assay Definition File (ADF) applicable to the instrument used in the workflow . (available via download).

In addition to the SARS-CoV-2, influenza A, influenza B and RSV viral assay targets, the assay portion of the panel includes RNase P, which serves as an endogenous internal process control to monitor extraction and amplification of each clinical sample. The TaqPath™ COVID-19, Flu A, Flu B, RSV Select Panel also contains external process positive and negative controls. The positive control (PC) component included is an inactivated viral control that contains SARS-CoV-2, influenza A, influenza B, and RSV viruses. The PC monitors extraction and real-time RT-PCR by demonstrating that each of the four viruses can be detected when present and that RNase P is not detected when absent. The negative control (NC) component included is an MS2 packaged RNA control that contains targets specific to RNase P genomic regions targeted by the assay. The NC also monitors extraction and real-time RT-PCR by demonstrating RNase P can be detected when present and that the four viruses are not detected when absent. The TaqPath™ 1-Step Select Master Mix (No ROX) included as a component of the kit is a ready-to-use PCR mix which contains a deoxyribonucleotide triphosphate mix (dNTPs), enzymes, and other components to permit reverse transcription and amplification of the assay targets. The TagPath™ 1-Step Select Master Mix (No ROX) also contains ribonuclease (RNase) inhibitors as well as deoxyuridine triphosphate (dUTP) and uracil N-glycosylase (known as UNG or UDG).

The TaqPath™ COVID-19, Flu A, Flu B, RSV Select Panel is provided in two overall kit configurations: either 200 reactions or 1.000 reactions.

The provided text describes the analytical and clinical performance studies of the "Applied Biosystems TaqPath COVID-19, Flu A, Flu B, RSV Select Panel" (hereafter referred to as "the Device"). This device is an in vitro diagnostic test for the qualitative detection and differentiation of SARS-CoV-2, influenza A, influenza B, and respiratory syncytial virus (RSV).

Below is a breakdown of the acceptance criteria and study details based on the provided information, presented in the requested format.

Acceptance Criteria and Device Performance

The acceptance criteria for this diagnostic device are primarily demonstrated through various analytical performance evaluations (Limit of Detection, Inclusivity/Reactivity, Precision, Interfering Substances, Cross-Reactivity, Stability, Carryover) and clinical performance studies (PPA and NPA against a comparator device). The studies aim to show that the device performs as expected and is "substantially equivalent" to a legally marketed predicate device.

1. Table of Acceptance Criteria and Reported Device Performance

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

• Clinical Performance Study (Prospective Cohort):

  • Subjects: 1,909 subjects enrolled (1,840 prospectively, 69 enrichment).
  • Test Set (Evaluable Specimens): 1,620 Nasopharyngeal (NP) swabs and 1,541 Anterior Nasal (AN) swabs were included in the final data analysis for the prospective cohort. (Minor adjustments for inconclusive comparator results in Flu A, specifically 1,539 AN and 1,616 NP for Flu A analysis).
  • Enrichment Study: 69 subjects, yielding 69 NP swabs and 68 AN swabs for analysis.
  • Data Provenance:
    • Country of Origin: Not explicitly stated as a single country, but "14 different collection sites across the U.S." indicate United States data.
    • Retrospective or Prospective: Primarily prospective data, with an "enrichment phase" also involving prospective collection from subjects with confirmed positive PCR results for Flu A, Flu B, and/or RSV.
    • Specimen Handling: Specimens were tested either fresh (Category I) or frozen (Category II).

• Analytical Studies (Test Sets):

  • LoD Confirmation: At least 24 replicates per virus strain/specimen type.
  • Precision (within-lab): 96 replicates for each panel member.
  • Reproducibility (site-to-site): 9 replicates per panel member (3 sites x 3 reagent lots x 1 replicate/lot). Total ~270 replicates per analyte level across 3 sites.
  • Interfering Substances: 3 replicates per substance/condition.
  • Competitive Interference: 3 replicates per condition.
  • Cross-Reactivity & Microbial Interference: 3 replicates per organism/condition.
  • Specimen Stability: Multiple replicates per time point/storage condition.
  • Eluate Stability: Multiple replicates per time point/storage condition.
  • Fresh vs Frozen Equivalency: Multiple replicates per F/T cycle and concentration.
  • In-Use and Hold Time Stability: Multiple replicates per time point/F/T cycle.
  • Carryover Cross-Contamination: 492 replicates (negative wells).
  • RNase P Internal Control Cutoff Confirmation: Individually collected NP and AN swabs (specific number not given for the initial confirmation, but the follow-up AN study used 138 AN samples).
  • Matrix Equivalency: Multiple replicates per matrix and concentration.

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

• For the clinical performance study, the ground truth appears to be established by a comparator FDA-cleared molecular test.
• The document does not specify the number or qualifications of human experts (e.g., radiologists, pathologists) involved in establishing the ground truth for any of the studies. This is typical for molecular diagnostic assays where the "ground truth" is often defined by the results of a highly sensitive and specific reference method (e.g., another molecular test or a composite reference method incorporating multiple tests or clinical findings).

4. Adjudication Method for the Test Set

• For the clinical performance study, samples that produced a discordant call between the Device and the comparator test were further tested with "another FDA cleared molecular assay" (a resolver assay). This implies a reconciliation method where a third test acts as an adjudicator for discordant results between the device under evaluation and the primary comparator.
• The specific rules for how the resolver assay's result determined the final ground truth (e.g., 2+1 majority rule, or if the resolver result was the final truth) are not explicitly detailed but are common in diagnostic test evaluation.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done

• No, an MRMC comparative effectiveness study was not done. The evaluated device is a molecular diagnostic test (RT-PCR kit), not an imaging AI algorithm that typically involves human readers. The performance is assessed based on the device's ability to detect viral nucleic acids against a comparator molecular test, not on improvements in human reader performance.

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

• Yes, the primary evaluation of this device is a standalone performance study. The "TaqPath™ COVID-19, Flu A, Flu B, RSV Select Panel" is a laboratory-based RT-PCR diagnostic kit. Its performance, as detailed in the analytical and clinical studies, is measured by its output (detection/differentiation of viral targets) directly from patient samples, independent of human interpretation or "human-in-the-loop" assistance for the test result itself. The Diomni™ Software provides automated interpretation, making it an algorithm-only result at the interpretation stage.

7. The Type of Ground Truth Used

• For analytical studies (e.g., LoD, Inclusivity, Precision, Interference, Cross-Reactivity, Stability), the ground truth was established by contrived samples with known concentrations of viral material or known presence/absence of interfering/cross-reactive substances. This is a common and appropriate method for analytical validation.
• For the clinical performance study, the ground truth was established by an FDA-cleared molecular test (comparator device), supplemented by a resolver FDA-cleared molecular assay for discordant results. This constitutes a form of "composite reference standard" where the truth is determined by a highly reliable, already approved diagnostic method.

8. The Sample Size for the Training Set

• The document describes the validation of a diagnostic kit, not an AI model requiring a separate "training set" in the machine learning sense. The information provided heavily details the test set performance (analytical and clinical validation).
• While the "Diomni™ Software" performs data analysis and interpretation based on "assay-specific parameters from the Assay Definition File (ADF)," the document does not specify a distinct training set size typically associated with machine learning model development. The "training" of such a system would typically involve internal development data used to establish parameters like Cq cutoffs, but this is not detailed as a separate "training set" with specific sample numbers. The development study that determined the RNase P IC cutoff of Cq = 33.0 could be considered part of the "training" or parameter establishment phase, but no sample size is given for it.

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

• As noted above, a distinct "training set" for an AI/algorithm is not explicitly described in the context of this diagnostic kit's submission. The "ground truth" for establishing device parameters (like Cq cutoffs) would generally come from extensive analytical experiments and internal validation studies using characterized samples (e.g., known concentrations of viruses, negative controls).
• For example, the preliminary LoD determined by probit analysis and the RNase P IC cutoff determined in a development study are examples of how internal parameters were established. These processes rely on highly controlled experiments with well-defined inputs (the "ground truth" being the known composition of the contrived samples).

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