Predicate Devices

Reference Devices

AI/ML (Artificial Intelligence / Machine Learning)

No
The description focuses on RT-PCR technology and automated interpretation based on predefined thresholds (amplification status of targets and controls). While there is mention of "training" the algorithm, this appears to refer to calibrating the assay cutoff using spiked samples, not training a complex AI/ML model. There is no mention of AI, ML, or related terms in the document.

Therapeutic

No.
The device is a diagnostic test intended for the qualitative detection and differentiation of viral nucleic acids to aid in differential diagnosis, not to provide therapy.

Diagnostic

Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "intended for use as an aid in the differential diagnosis" of various viral infections.

SaMD (Software as a Medical Device)

No

The device description explicitly states that the system is comprised of an instrument with associated hardware and accessories, disposable microfluidic cartridges, master mixes, unitized reagent strips, and extraction reagents, in addition to the software. This indicates it is a hardware and software system, not software-only.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use explicitly states that the device is a test intended for the "simultaneous, qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A, influenza B, and/or respiratory syncytial virus (RSV) nucleic acid in nasopharyngeal swab (NPS) and anterior nasal swab (ANS) specimens from individuals with signs and symptoms of respiratory tract infection." This describes a test performed in vitro (outside the body) on biological specimens to provide information for diagnosis.
Aid in Diagnosis: The intended use also states that the test is intended for use "as an aid in the differential diagnosis of SARS-CoV-2, influenza A, influenza B, and/or RSV infection" and "as an aid in the diagnosis of SARS-CoV-2 infection." This directly aligns with the purpose of IVDs, which are used to assist in the diagnosis of diseases or other conditions.
Specimen Type: The test is performed on "nasopharyngeal swab (NPS) and anterior nasal swab (ANS) specimens," which are biological samples collected from the patient.
Device Description: The description details a system that performs "sample preparation including target lysis, Total Nucleic Acid (TNA) extraction and concentration, reagent rehydration, target nucleic acid amplification and detection using real-time PCR." These are all processes performed in vitro on the collected specimens.

Based on the definition of an In Vitro Diagnostic device, which is a medical device intended for use in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological or pathological state, or concerning a congenital abnormality, or to monitor therapeutic measures, this device clearly fits that description.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

BD Respiratory Viral Panel for BD MAXTM System:
BD Respiratory Viral Panel for BD MAX™ System is an automated multiplexed real-time reverse transcriptase polymerase chain reaction (RT- PCR) test intended for the simultaneous, qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza B, and/or respiratory syncytial virus (RSV) nucleic acid in nasopharyngeal swab (NPS) and anterior nasal swab (ANS) specimens from individuals with signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory tract infection due to SARS-COV-2, influenza, and RSV can be similar.
BD Respiratory Viral Panel for BD MAX™ System is intended for use as an aid in the differential diagnosis of SARS-CoV-2, influenza A, influenza B, and/or RSV infection if used in conjunction with other clinical and epidemiological information, and laboratory findings. SARS-CoV- 2, influenza B, and RSV viral nucleic acid are generally detectable in NPS and ANS specimens during the acute phase of infection.
Positive results do not rule out co-infection with other organisms. The agent(s) detected by the BD Respiratory Viral Panel for BD MAX™ System may not be the definitive cause of disease.
Negative results do not preclude SARS-CoV-2, influenza B, and/or RSV infection.
The results of this test should not be used as the sole basis for other patient management decisions.

BD Respiratory Viral Panel-SCV2 for BD MAX™ System:
BD Respiratory Viral Panel-SCV2 for BD MAX™ System is an automated multiplexed real-time reverse transcriptase polymerase chain reaction (RT-PCR) test intended for the simultaneous, qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral nucleic acid in nasopharyngeal swab (NPS) and anterior nasal swab (ANS) specimens from individuals with signs and symptoms of respiratory tract infection. SARS-CoV-2 viral RNA is generally detectable in NPS and ANS specimens during the acute phase of infection.
The BD Respiratory Viral Panel-SCV2 for BD MAX™ System is intended for use as an aid in the diagnosis of SARS-CoV-2 infection if used in conjunction with other clinical and epidemiological information, and laboratory findings.
Positive results do not rule out co-infection with other organisms. The agent detected by the BD Respiratory Viral Panel-SCV2 for BD MAX™ System may not be the definitive cause of disease.
Negative results do not preclude SARS-CoV-2 infection.
The results of this test should not be used as the sole basis for diagnosis, treatment management decisions.

Product codes (comma separated list FDA assigned to the subject device)

QOF, QQX

Device Description

The BD Respiratory Viral Panel (BD RVP) and BD Respiratory Viral Panel-SCV2 (BD RVP-SCV2) along with the BD MAXTM System are comprised of an instrument with associated hardware and accessories, disposable microfluidic cartridges, master mixes, unitized reagent strips, and extraction reagents. The instrument automates sample preparation including target lysis, Total Nucleic Acid (TNA) extraction and concentration, reagent rehydration, target nucleic acid amplification and detection using real-time PCR. The assay includes a Sample Processing Control (SPC) that is present in the Extraction Tube. The SPC monitors RNA extraction steps, thermal cycling steps, reagent integrity and the presence of inhibitory substances. The BD MAX™ System software automatically interprets test results. For the BD Respiratory Viral Panel for BD MAX™ System and BD Respiratory Viral Panel-SCV2 for BD MAX™ System, a test result may be called as POS, NEG or UNR (Unresolved) based on the amplification status of the targets and of the Sample Processing Control. IND (Indeterminate) or INC (Incomplete) results are due to BD MAX™ System failure.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

nasopharyngeal swab (NPS) and anterior nasal swab (ANS) specimens

Indicated Patient Age Range

Not Found

Intended User / Care Setting

For Prescription Use Only, For in vitro diagnostic use only

Description of the training set, sample size, data source, and annotation protocol

The assay cut-off for the BD Respiratory Viral Panel for BD MAX™ was established based on PCR based metrics taken together by the BD MAX software algorithm to make the qualitative decision whether a curve is to be considered positive or negative. These metrics (e.g., Ct, RFU endpoints, signal-to-noise ratios) are initially set by default parameters defined by the instrument. As the product undergoes product development, the data is supplemented, and the algorithm is adjusted ("trained") using viral cultures spiked into clinical background matrices at levels surrounding the limit of detection and expected clinical range.

The assay cut-off for the BD Respiratory Viral Panel-SCV2 for BD MAX™ was established based on PCR based metrics taken together by the BD MAX software algorithm to make the qualitative decision whether a curve is to be considered positive or negative. These metrics (e.g., Ct. RFU endpoints, signal-to-noise ratios) are initially set by default parameters defined by the instrument. As the product undergoes product development, the data is supplemented, and the algorithm is adjusted ("trained") using viral cultures spiked into clinical background matrices at levels surrounding the limit of detection and expected clinical range.

Description of the test set, sample size, data source, and annotation protocol

For BD Respiratory Viral Panel for BD MAX™ System:

Prospective Clinical Evaluation:
Sample Size: 1562 nasopharyngeal swabs and 1566 nasal swabs from 2,005 enrolled subjects.
Data Source: Subjects enrolled at six geographically distinct U.S. study sites and two geographically distinct sites in Europe from January to August 2022. Specimens were collected as either prospective archived/frozen (Category II) or prospective fresh (Category I).
Annotation Protocol: The performance was evaluated in comparison to a composite method of two out of three highly sensitive molecular assays (NAATS) that are FDA authorized under EUA for SARS-CoV-2. For influenza B, and RSV, the performance was evaluated in comparison to an FDA-cleared high sensitivity RT-PCR assay.

Retrospective Clinical Evaluation:
Nasopharyngeal Swabs:
Sample Size: 240 frozen retrospective nasopharyngeal swabs.
Data Source: Specimens obtained from two (2) external sources with historical positive or negative results for either influenza B or RSV, collected as part of routine patient care between December 2019 and January 2022.
Annotation Protocol: Specimens were tested in a blinded and randomized fashion with the BD Respiratory Viral Panel for BD MAX™ System at three different testing sites and a reference method (RM) at one testing site. The RM for influenza B, and RSV was an FDA-cleared high sensitivity RT-PCR assay.

Nasal Swabs:
Sample Size: 187 frozen retrospective nasal swabs.
Data Source: Specimens obtained from six (6) external sources with historical positive or negative results for either influenza B or RSV, collected between February 2021 and February 2023.
Annotation Protocol: Specimens were tested in a blinded and randomized fashion with the BD Respiratory Viral Panel for BD MAX™ System at four different testing sites and a reference method (RM) at one testing site. The RM for influenza B, and RSV was an FDA-cleared high sensitivity RT-PCR assay.

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

BD Respiratory Viral Panel for BD MAX™ System:

Precision:
Study Type: Within-laboratory precision.
Sample Size: 144 replicates for each of Moderate Positive (3x LoD) and Low Positive (2x LoD) for SARS-CoV-2, Flu A, Flu B, and RSV. 288 replicates for True Negative.
Key Results:

Moderate Positive (3x LoD): 100% agreement for all targets (SARS-CoV-2, Flu A, Flu B, RSV).
Low Positive (2x LoD): 100% for SARS-CoV-2, 97.2% for Flu A, 99.3% for Flu B, 99.3% for RSV.
True Negative: 100% negative agreement for all targets.

Reproducibility (Site-to-Site):
Study Type: Site-to-site reproducibility.
Sample Size: 90 replicates for Moderate Positive (3x LoD) and Low Positive (2x LoD) for each target. 180 replicates for True Negative.
Key Results:

Moderate Positive (3x LoD): 100% for SARS-CoV-2, 97.8% for Flu A, 100% for Flu B, 100% for RSV.
Low Positive (2x LoD): 100% for SARS-CoV-2, 96.7% for Flu A, 100% for Flu B, 100% for RSV.
True Negative: 100% negative agreement for all targets.

Reproducibility (Lot-to-Lot):
Study Type: Lot-to-lot reproducibility.
Sample Size: 179/180 replicates for Moderate Positive (3x LoD) and 180 replicates for Low Positive (2x LoD) for each target. 360 replicates for True Negative.
Key Results:

Moderate Positive (3x LoD): 99.4% for SARS-CoV-2, 100% for Flu A, 98.9% for Flu B, 100% for RSV.
Low Positive (2x LoD): 100% for SARS-CoV-2, 97.8% for Flu A, 100% for Flu B, 100% for RSV.
True Negative: 100% negative agreement for all targets.

Limit of Detection (LoD):
Study Type: Analytical sensitivity.
Key Results: Demonstrated lowest detectable concentrations:

SARS-CoV-2: 700 copies/mL (Nasopharyngeal & Nasal)
Influenza A/H1N1/Brisbane: 5.6E-03 TCID50/mL
Influenza A/H1N1/Guangdong-Maonan: 2.49E-01 TCID50/mL
Influenza A/H3N2/Kansas: 2.8E-01 TCID50/mL
Influenza B/Colorado: 6.8E-03 TCID50/mL
Influenza B/Phuket: 2.9E-02 TCID50/mL (NP), 9.6E-03 TCID50/mL (Nasal)
RSV A: 3.1E-02 TCID50/mL
RSV B: 1.7E-02 TCID50/mL (NP), 5.6E-03 TCID50/mL (Nasal)

Interfering Substances:
Study Type: Interference evaluation.
Key Results: Whole blood (human) found to interfere above 0.2% v/v for SARS-CoV-2. FluMist Quadrivalent Vaccine also showed interference. No other substances caused reportable interference.

Mixed Infection/Competitive Interference:
Study Type: Interference testing.
Sample Size: 20 replicates per condition.
Key Results: No interference observed between high concentrations of one analyte and low concentrations of others.

Cross-Reactivity:
Study Type: In silico analysis and wet lab testing.
Sample Size: 52 organisms and 1 nasopharyngeal pool.
Key Results: No relevant cross-reactivity discovered for SARS-CoV-2, Influenza A, Influenza B, and RSV. All organisms tested produced negative results.

Sample Stability:
Study Type: Stability testing in UVT/UTM and BD Molecular RVP Sample Buffer Tube.
Key Results: Stable for various temperatures and durations (e.g., 25±2 °C for 12 hours in UVT/UTM, 2-8 °C for 72 hours in UVT/UTM, etc.).

Carryover / Cross-Contamination:
Study Type: Carryover study.
Sample Size: 108 positive and 108 negative samples.
Key Results: One false positive result (0.93%) was obtained from 108 negative samples tested.

Clinical Performance Evaluation (Prospective - Nasopharyngeal Swab):
Study Type: Multi-center study.
Sample Size: 1545 compliant specimens for SARS-CoV-2, 1562 for Flu A, Flu B, RSV.
Key Results:

SARS-CoV-2: Overall PPA 98.9% (517/523), NPA 97.7% (999/1022).
Flu A: Overall PPA 96.7% (59/61), NPA 99.5% (1494/1501).
Flu B: Overall PPA No data, NPA 99.9% (1561/1562).
RSV: Overall PPA 100.0% (12/12), NPA 100.0% (1550/1550).

Clinical Performance Evaluation (Prospective - Anterior Nasal Swab):
Study Type: Multi-center study.
Sample Size: 1561 compliant specimens for SARS-CoV-2, 1564 for Flu A, Flu B, RSV.
Key Results:

SARS-CoV-2: Overall PPA 98.4% (478/486), NPA 97.7% (1050/1075).
Flu A: Overall PPA 96.9% (62/64), NPA 99.7% (1496/1500).
Flu B: Overall PPA No data, NPA 100.0% (1564/1564).
RSV: Overall PPA 91.7% (11/12), NPA 99.9% (1551/1552).

Clinical Performance Evaluation (Retrospective - Nasopharyngeal Swab):
Study Type: Retrospective study.
Sample Size: 240 specimens.
Key Results:

Flu B: PPA 100.0% (58/58), NPA 98.9% (180/182).
RSV: PPA 98.4% (62/63), NPA 100.0% (177/177).

Clinical Performance Evaluation (Retrospective - Nasal Swab):
Study Type: Retrospective study.
Sample Size: 187 specimens.
Key Results:

Flu B: PPA 100.0% (12/12), NPA 98.9% (172/174).
RSV: PPA 100.0% (15/15), NPA 99.4% (170/171).

Non-Reportable Rate:
Study Type: Non-reportable rate analysis.
Key Results: Initial non-reportable rates were 0.9% for nasopharyngeal and 1.1% for nasal specimens. Following valid repeat, 0.1% remained non-reportable for both types.

BD Respiratory Viral Panel-SCV2 for BD MAX™ System:

Precision:
Study Type: Within-laboratory precision.
Sample Size: 144 replicates for Moderate Positive (3x LoD) and Low Positive (2x LoD) for SARS-CoV-2. 288 replicates for True Negative.
Key Results:

Moderate Positive (3x LoD): 100% agreement.
Low Positive (2x LoD): 100% agreement.
True Negative: 100% negative agreement.

Reproducibility (Site-to-Site):
Study Type: Site-to-site reproducibility.
Sample Size: 90 replicates for Moderate Positive (3x LoD) and Low Positive (2x LoD) for SARS-CoV-2. 180 replicates for True Negative.
Key Results:

Moderate Positive (3x LoD): 100% agreement.
Low Positive (2x LoD): 100% agreement.
True Negative: 100% negative agreement.

Reproducibility (Lot-to-Lot):
Study Type: Lot-to-lot reproducibility.
Sample Size: 179/180 replicates for Moderate Positive (3x LoD) and 180 replicates for Low Positive (2x LoD) for SARS-CoV-2. 360 replicates for True Negative.
Key Results:

Moderate Positive (3x LoD): 99.4% agreement.
Low Positive (2x LoD): 100% agreement.
True Negative: 100% negative agreement.

Limit of Detection (LoD):
Study Type: Analytical sensitivity.
Key Results: Demonstrated LoD for SARS-CoV-2: 700 copies/mL (Nasopharyngeal & Nasal).

Interfering Substances:
Study Type: Interference evaluation.
Key Results: Whole blood (human) found to interfere above 0.2% v/v. No other substances caused reportable interference.

Cross-Reactivity:
Study Type: In silico analysis and wet lab testing.
Sample Size: 52 organisms and 1 nasopharyngeal pool (for BD Respiratory Viral Panel-SCV2 for BD MAX™ System).
Key Results: No relevant cross-reactivity discovered for SARS-CoV-2. All organisms tested produced negative results.

Sample Stability:
Study Type: Stability testing in UVT/UTM and BD Molecular RVP Sample Buffer Tube.
Key Results: Stable for various temperatures and durations (e.g., 25±2 °C for 48 hours in UVT/UTM, 2-8 °C for 72 hours in UVT/UTM, etc.).

Carryover / Cross-Contamination:
Study Type: Carryover study.
Sample Size: 108 positive and 108 negative samples.
Key Results: One false positive result (0.93%) was obtained from 108 negative samples tested.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

BD Respiratory Viral Panel for BD MAX™ System (Prospective Clinical Evaluation):

Nasopharyngeal Swab Specimens:
SARS-CoV-2:
Positive Percent Agreement (PPA): 98.9% (517/523) with a 95% CI of (97.5%, 99.5%)
Negative Percent Agreement (NPA): 97.7% (999/1022) with a 95% CI of (96.6%, 98.5%)
Flu A:
Positive Percent Agreement (PPA): 96.7% (59/61) with a 95% CI of (88.8%, 99.1%)
Negative Percent Agreement (NPA): 99.5% (1494/1501) with a 95% CI of (99.0%, 99.8%)
Flu B:
Positive Percent Agreement (PPA): No data for PPA rate calculation
Negative Percent Agreement (NPA): 99.9% (1561/1562) with a 95% CI of (99.6%, 100.0%)
RSV:
Positive Percent Agreement (PPA): 100.0% (12/12) with a 95% CI of (75.8%, 100.0%)
Negative Percent Agreement (NPA): 100.0% (1550/1550) with a 95% CI of (99.8%, 100.0%)

Anterior Nasal Swab Specimens:
SARS-CoV-2:
Positive Percent Agreement (PPA): 98.4% (478/486) with a 95% CI of (96.8%, 99.2%)
Negative Percent Agreement (NPA): 97.7% (1050/1075) with a 95% CI of (96.6%, 98.4%)
Flu A:
Positive Percent Agreement (PPA): 96.9% (62/64) with a 95% CI of (89.3%, 99.1%)
Negative Percent Agreement (NPA): 99.7% (1496/1500) with a 95% CI of (99.3%, 99.9%)
Flu B:
Positive Percent Agreement (PPA): No data for PPA rate calculation
Negative Percent Agreement (NPA): 100.0% (1564/1564) with a 95% CI of (99.8%, 100.0%)
RSV:
Positive Percent Agreement (PPA): 91.7% (11/12) with a 95% CI of (64.6%, 98.5%)
Negative Percent Agreement (NPA): 99.9% (1551/1552) with a 95% CI of (99.6%, 100.0%)

BD Respiratory Viral Panel for BD MAX™ System (Retrospective Clinical Evaluation):

Retrospective Nasopharyngeal Swab Specimens:
Flu B:
Positive Percent Agreement (PPA): 100.0% (58/58) with a 95% CI of (93.8%, 100.0%)
Negative Percent Agreement (NPA): 98.9% (180/182) with a 95% CI of (96.1%, 99.7%)
RSV:
Positive Percent Agreement (PPA): 98.4% (62/63) with a 95% CI of (91.5%, 99.7%)
Negative Percent Agreement (NPA): 100.0% (177/177) with a 95% CI of (97.9%, 100.0%)

Retrospective Nasal Swab Specimens:
Flu B:
Positive Percent Agreement (PPA): 100.0% (12/12) with a 95% CI of (75.8%, 100.0%)
Negative Percent Agreement (NPA): 98.9% (172/174) with a 95% CI of (95.9%, 99.7%)
RSV:
Positive Percent Agreement (PPA): 100.0% (15/15) with a 95% CI of (79.6%, 100.0%)
Negative Percent Agreement (NPA): 99.4% (170/171) with a 95% CI of (96.8%, 99.9%)

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

BioFire Respiratory Panel 2.1 (RP2.1) (DEN200031)

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

BioFire COVID-19 Test 2, K211079/K221460

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 866.3981 Device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test.

(a)
Identification. A device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test is an in vitro diagnostic device intended for the detection and identification of SARS-CoV-2 and other microbial agents when in a multi-target test in human clinical respiratory specimens from patients suspected of respiratory infection who are at risk for exposure or who may have been exposed to these agents. The device is intended to aid in the diagnosis of respiratory infection in conjunction with other clinical, epidemiologic, and laboratory data or other risk factors.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The intended use in the labeling required under § 809.10 of this chapter must include a description of the following: Analytes and targets the device detects and identifies, the specimen types tested, the results provided to the user, the clinical indications for which the test is to be used, the specific intended population(s), the intended use locations including testing location(s) where the device is to be used (if applicable), and other conditions of use as appropriate.
(2) Any sample collection device used must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of specimen types claimed by this device; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.
(3) The labeling required under § 809.10(b) of this chapter must include:
(i) A detailed device description, including reagents, instruments, ancillary materials, all control elements, and a detailed explanation of the methodology, including all pre-analytical methods for processing of specimens;
(ii) Detailed descriptions of the performance characteristics of the device for each specimen type claimed in the intended use based on analytical studies including the following, as applicable: Limit of Detection, inclusivity, cross-reactivity, interfering substances, competitive inhibition, carryover/cross contamination, specimen stability, precision, reproducibility, and clinical studies;
(iii) Detailed descriptions of the test procedure(s), the interpretation of test results for clinical specimens, and acceptance criteria for any quality control testing;
(iv) A warning statement that viral culture should not be attempted in cases of positive results for SARS-CoV-2 and/or any similar microbial agents unless a facility with an appropriate level of laboratory biosafety (
e.g., BSL 3 and BSL 3+, etc.) is available to receive and culture specimens; and(v) A prominent statement that device performance has not been established for specimens collected from individuals not identified in the intended use population (
e.g., when applicable, that device performance has not been established in individuals without signs or symptoms of respiratory infection).(vi) Limiting statements that indicate that:
(A) A negative test result does not preclude the possibility of infection;
(B) The test results should be interpreted in conjunction with other clinical and laboratory data available to the clinician;
(C) There is a risk of incorrect results due to the presence of nucleic acid sequence variants in the targeted pathogens;
(D) That positive and negative predictive values are highly dependent on prevalence;
(E) Accurate results are dependent on adequate specimen collection, transport, storage, and processing. Failure to observe proper procedures in any one of these steps can lead to incorrect results; and
(F) When applicable (
e.g., recommended by the Centers for Disease Control and Prevention, by current well-accepted clinical guidelines, or by published peer-reviewed literature), that the clinical performance may be affected by testing a specific clinical subpopulation or for a specific claimed specimen type.(4) Design verification and validation must include:
(i) Detailed documentation, including performance results, from a clinical study that includes prospective (sequential) samples for each claimed specimen type and, as appropriate, additional characterized clinical samples. The clinical study must be performed on a study population consistent with the intended use population and compare the device performance to results obtained using a comparator that FDA has determined is appropriate. Detailed documentation must include the clinical study protocol (including a predefined statistical analysis plan), study report, testing results, and results of all statistical analyses.
(ii) Risk analysis and documentation demonstrating how risk control measures are implemented to address device system hazards, such as Failure Modes Effects Analysis and/or Hazard Analysis. This documentation must include a detailed description of a protocol (including all procedures and methods) for the continuous monitoring, identification, and handling of genetic mutations and/or novel respiratory pathogen isolates or strains (
e.g., regular review of published literature and periodic in silico analysis of target sequences to detect possible mismatches). All results of this protocol, including any findings, must be documented and must include any additional data analysis that is requested by FDA in response to any performance concerns identified under this section or identified by FDA during routine evaluation. Additionally, if requested by FDA, these evaluations must be submitted to FDA for FDA review within 48 hours of the request. Results that are reasonably interpreted to support the conclusion that novel respiratory pathogen strains or isolates impact the stated expected performance of the device must be sent to FDA immediately.(iii) A detailed description of the identity, phylogenetic relationship, and other recognized characterization of the respiratory pathogen(s) that the device is designed to detect. In addition, detailed documentation describing how to interpret the device results and other measures that might be needed for a laboratory diagnosis of respiratory infection.
(iv) A detailed device description, including device components, ancillary reagents required but not provided, and a detailed explanation of the methodology, including molecular target(s) for each analyte, design of target detection reagents, rationale for target selection, limiting factors of the device (
e.g., saturation level of hybridization and maximum amplification and detection cycle number, etc.), internal and external controls, and computational path from collected raw data to reported result (e.g., how collected raw signals are converted into a reported signal and result), as applicable.(v) A detailed description of device software, including software applications and hardware-based devices that incorporate software. The detailed description must include documentation of verification, validation, and hazard analysis and risk assessment activities, including an assessment of the impact of threats and vulnerabilities on device functionality and end users/patients as part of cybersecurity review.
(vi) For devices intended for the detection and identification of microbial agents for which an FDA recommended reference panel is available, design verification and validation must include the performance results of an analytical study testing the FDA recommended reference panel of characterized samples. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses.
(vii) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens, the design verification and validation must include a detailed description of the identity, phylogenetic relationship, or other recognized characterization of the Influenza A and B viruses that the device is designed to detect, a description of how the device results might be used in a diagnostic algorithm and other measures that might be needed for a laboratory identification of Influenza A or B virus and of specific Influenza A virus subtypes, and a description of the clinical and epidemiological parameters that are relevant to a patient case diagnosis of Influenza A or B and of specific Influenza A virus subtypes. An evaluation of the device compared to a currently appropriate and FDA accepted comparator method. Detailed documentation must be kept of that study and its results, including the study protocol, study report for the proposed intended use, testing results, and results of all statistical analyses.
(5) When applicable, performance results of the analytical study testing the FDA recommended reference panel described in paragraph (b)(4)(vi) of this section must be included in the device's labeling under § 809.10(b) of this chapter.
(6) For devices with an intended use that includes detection of Influenza A and Influenza B viruses and/or detection and differentiation between the Influenza A virus subtypes in human clinical specimens in addition to detection of SARS-CoV-2 and similar microbial agents, the required labeling under § 809.10(b) of this chapter must include the following:
(i) Where applicable, a limiting statement that performance characteristics for Influenza A were established when Influenza A/H3 and A/H1-2009 (or other pertinent Influenza A subtypes) were the predominant Influenza A viruses in circulation.
(ii) Where applicable, a warning statement that reads 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 departments for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.
(iii) Where the device results interpretation involves combining the outputs of several targets to get the final results, such as a device that both detects Influenza A and differentiates all known Influenza A subtypes that are currently circulating, the device's labeling must include a clear interpretation instruction for all valid and invalid output combinations, and recommendations for any required followup actions or retesting in the case of an unusual or unexpected device result.
(iv) A limiting statement that if a specimen yields a positive result for Influenza A, but produces negative test results for all specific influenza A subtypes intended to be differentiated (
i.e., H1-2009 and H3), this result requires notification of appropriate local, State, or Federal public health authorities to determine necessary measures for verification and to further determine whether the specimen represents a novel strain of Influenza A.(7) If one of the actions listed at section 564(b)(1)(A) through (D) of the Federal Food, Drug, and Cosmetic Act occurs with respect to an influenza viral strain, or if the Secretary of Health and Human Services determines, under section 319(a) of the Public Health Service Act, that a disease or disorder presents a public health emergency, or that a public health emergency otherwise exists, with respect to an influenza viral strain:
(i) Within 30 days from the date that FDA notifies manufacturers that characterized viral samples are available for test evaluation, the manufacturer must have testing performed on the device with those influenza viral samples in accordance with a standardized protocol considered and determined by FDA to be acceptable and appropriate.
(ii) Within 60 days from the date that FDA notifies manufacturers that characterized influenza viral samples are available for test evaluation and continuing until 3 years from that date, the results of the influenza emergency analytical reactivity testing, including the detailed information for the virus tested as described in the certificate of authentication, must be included as part of the device's labeling in a tabular format, either by:
(A) Placing the results directly in the device's labeling required under § 809.10(b) of this chapter that accompanies the device in a separate section of the labeling where analytical reactivity testing data can be found, but separate from the annual analytical reactivity testing results; or
(B) In a section of the device's label or in other labeling that accompanies the device, prominently providing a hyperlink to the manufacturer's public website where the analytical reactivity testing data can be found. The manufacturer's website, as well as the primary part of the manufacturer's website that discusses the device, must provide a prominently placed hyperlink to the website containing this information and must allow unrestricted viewing access.

Summary

0

Date: July 31, 2023

Image /page/0/Picture/1 description: The image contains the logos of the Department of Health and Human Services (HHS) and the Food and Drug Administration (FDA). The HHS logo is on the left and features a stylized human figure. The FDA logo is on the right and includes the FDA acronym in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

BD Integrated Diagnostic Solutions/ Kathy Barnecut Staff Regulatory Affairs Specialist Becton, Dickinson & Company 7 Loveton Circle Sparks, Maryland 21152

Re: K230956

Trade/Device Name: BD Respiratory Viral Panel (BD RVP) for BD MAX System; BD Respiratory Viral Panel-SCV2 (BD RVP-SCV2) for BD MAX System Regulation Number: 21 CFR 866.3981 Regulation Name: Device To Detect And Identify Nucleic Acid Targets In Respiratory Specimens From Microbial Agents That Cause The SARS-Cov-2 Respiratory Infection And Other Microbial Agents When In A Multi-Target Test Regulatory Class: Class II Product Code: QOF, QQX Dated: April 4, 2023 Received: April 4, 2023

Dear Kathy Barnecut:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

1

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Joseph Briggs -S

Joseph Briggs, Ph.D. Deputy Branch Chief Viral Respiratory and HPV Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K230956

Device Name

BD Respiratory Viral Panel for BD MAXTM System; BD Respiratory Viral Panel-SCV2 for BD MAX™ System

Indications for Use (Describe)

BD Respiratory Viral Panel for BD MAXTM System:

BD Respiratory Viral Panel for BD MAX™ System is an automated multiplexed real-time reverse transcriptase polymerase chain reaction (RT- PCR) test intended for the simultaneous, qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza B, and/or respiratory syncytial virus (RSV) nucleic acid in nasopharyngeal swab (NPS) and anterior nasal swab (ANS) specimens from individuals with signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory tract infection due to SARS-COV-2, influenza, and RSV can be similar.

BD Respiratory Viral Panel for BD MAX™ System is intended for use as an aid in the differential diagnosis of SARS-CoV-2, influenza A, influenza B, and/or RSV infection if used in conjunction with other clinical and epidemiological information, and laboratory findings. SARS-CoV- 2, influenza B, and RSV viral nucleic acid are generally detectable in NPS and ANS specimens during the acute phase of infection.

Positive results do not rule out co-infection with other organisms. The agent(s) detected by the BD Respiratory Viral Panel for BD MAX™ System may not be the definitive cause of disease.

Negative results do not preclude SARS-CoV-2, influenza B, and/or RSV infection.

The results of this test should not be used as the sole basis for other patient management decisions.

BD Respiratory Viral Panel-SCV2 for BD MAX™ System:

BD Respiratory Viral Panel-SCV2 for BD MAX™ System is an automated multiplexed real-time reverse transcriptase polymerase chain reaction (RT-PCR) test intended for the simultaneous, qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral nucleic acid in nasopharyngeal swab (NPS) and anterior nasal swab (ANS) specimens from individuals with signs and symptoms of respiratory tract infection. SARS-CoV-2 viral RNA is generally detectable in NPS and ANS specimens during the acute phase of infection.

The BD Respiratory Viral Panel-SCV2 for BD MAX™ System is intended for use as an aid in the diagnosis of SARS-CoV-2 infection if used in conjunction with other clinical and epidemiological information, and laboratory findings.

Positive results do not rule out co-infection with other organisms. The agent detected by the BD Respiratory Viral Panel-SCV2 for BD MAX™ System may not be the definitive cause of disease.

Negative results do not preclude SARS-CoV-2 infection.

The results of this test should not be used as the sole basis for diagnosis, treatment management decisions.

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X Prescription Use (Part 21 CFR 801 Subpart D)

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4

510(k) Summary

BD Respiratory Viral Panel for BD MAX™ System & BD Respiratory Viral Panel-SCV2 for BD MAX™ System

Summary Preparation Date:

06/30/2022

Submitted by:

Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152

Contact:

Kathy Barnecut, RAC Staff Regulatory Affairs Specialist Tel: 858-210-2284 Email: kathy.barnecut(@bd.com

Device Trade Names:

BD Respiratory Viral Panel for BD MAX™ System (445373) BD Respiratory Viral Panel-SCV2 for BD MAX™ System (445361)

Common Names:

Device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test.

Regulatory Information

Regulation section:

866.3981 - Device to detect and identify nucleic acid targets in respiratory specimens from microbial agents that cause the SARS-CoV-2 respiratory infection and other microbial agents when in a multi-target test

Classification:

Class II

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Panel:

Microbiology

Product Code(s):

QOF - Multi-Target Respiratory Specimen Nucleic Acid Test Including SARS-CoV-2 And Other Microbial Agents

QQX - Respiratory Specimen Nucleic Acid SARS-CoV-2 Test

Predicate Device

BioFire Respiratory Panel 2.1 (RP2.1) (DEN200031)

Device Establishment

Becton, Dickinson and Company 7 Loveton Circle Sparks, MD 21152 Registration Number: 1119779

Performance Standards

Class II Special Controls as per 21 CFR 866.3981

Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays, October 9, 2009.

Intended Use

BD Respiratory Viral Panel for BD MAX™ System:

BD Respiratory Viral Panel for BD MAX™ System is an automated multiplexed real-time reverse transcriptase polymerase chain reaction (RT- PCR) test intended for the simultaneous, qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A, influenza B, and/or respiratory syncytial virus (RSV) nucleic acid in nasopharyngeal swab (NPS) and anterior nasal swab (ANS) specimens from individuals with signs and symptoms of respiratory tract infection. Clinical signs and symptoms of respiratory tract infection due to SARS-CoV-2, influenza, and RSV can be similar.

BD Respiratory Viral Panel for BD MAXTM System is intended for use as an aid in the differential diagnosis of SARS-CoV-2, influenza A, influenza B, and/or RSV infection if used in conjunction with other clinical and epidemiological information, and laboratory findings. SARS-CoV- 2, influenza A, influenza B, and RSV viral nucleic acid are generally detectable in NPS and ANS specimens during the acute phase of infection.

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Positive results do not rule out co-infection with other organisms. The agent(s) detected by the BD Respiratory Viral Panel for BD MAX™ System may not be the definitive cause of disease.

Negative results do not preclude SARS-CoV-2, influenza B, and/or RSV infection.

The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

BD Respiratory Viral Panel-SCV2 for BD MAX™ System:

BD Respiratory Viral Panel-SCV2 for BD MAX™ System is an automated multiplexed real-time reverse transcriptase polymerase chain reaction (RT-PCR) test intended for the simultaneous, qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral nucleic acid in nasopharyngeal swab (NPS) and anterior nasal swab (ANS) specimens from individuals with signs and symptoms of respiratory tract infection. SARS-CoV-2 viral RNA is generally detectable in NPS and ANS specimens during the acute phase of infection.

The BD Respiratory Viral Panel-SCV2 for BD MAX™ System is intended for use as an aid in the diagnosis of SARS-CoV-2 infection if used in conjunction with other clinical and epidemiological information, and laboratory findings.

Positive results do not rule out co-infection with other organisms. The agent detected by the BD Respiratory Viral Panel-SCV2 for BD MAX™ System may not be the definitive cause of disease.

Negative results do not preclude SARS-CoV-2 infection.

The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.

Special Conditions for Use Statement:

For Prescription Use Only For in vitro diagnostic use only

Special Instrument Requirements:

BD Respiratory Viral Panel for BD MAX™ System and BD Respiratory Viral Panel-SCV2 for BD MAXTM System are performed on the BD MAXTM System.

Device Description

The BD Respiratory Viral Panel (BD RVP) and BD Respiratory Viral Panel-SCV2 (BD RVP-SCV2) along with the BD MAXTM System are comprised of an instrument with associated hardware and accessories, disposable microfluidic cartridges, master mixes, unitized reagent strips, and extraction reagents. The instrument automates sample preparation including target lysis, Total Nucleic Acid (TNA) extraction and concentration, reagent rehydration, target nucleic acid

7

amplification and detection using real-time PCR. The assay includes a Sample Processing Control (SPC) that is present in the Extraction Tube. The SPC monitors RNA extraction steps, thermal cycling steps, reagent integrity and the presence of inhibitory substances. The BD MAX™ System software automatically interprets test results. For the BD Respiratory Viral Panel for BD MAX™ System and BD Respiratory Viral Panel-SCV2 for BD MAX™ System, a test result may be called as POS, NEG or UNR (Unresolved) based on the amplification status of the targets and of the Sample Processing Control. IND (Indeterminate) or INC (Incomplete) results are due to BD MAX™ System failure.

Test Principle

The BD Respiratory Viral Panel for BD MAX™ System and BD Respiratory Viral Panel-SCV2 for BD MAX™ System assays are designed for use with a nasopharyngeal or anterior nasal swabs collected in BD Universal Viral Transport System (UVT) or Copan Universal Transport Media System (UTM). Once collected, the UVT/UTM patient sample is vortexed and 750ul is transferred to the BD Molecular RVP Sample Buffer Tube (SBT) provided with the BD Respiratory Viral Panel for BD MAX™ System. placed in the BD MAX™ System. For all sample types the SBTs are vortexed and then loaded into the BD MAX system along with the Unitized Reagent Strips, Master Mix, Extraction Tubes, and PCR Cartridges. No further operator intervention is necessary.

The BD RVP Unitized Reagent Strip contains a combination of lytic and extraction reagents designed to perform cell lysis and TNA extraction. Nucleic acids released from the target organisms are captured on magnetic affinity beads. The beads, together with the bound nucleic acids, are washed and the nucleic acids are eluted by a combination of heat and pH variation. Eluted TNA is added to neutralization buffer, mixed, and transferred to BD Respiratory Viral Panel master mix for rehydration. After reconstitution, the BD MAX™ System dispenses a fixed volume of RT-PCR-ready solution containing extracted nucleic acids into the PCR Cartridge. Microvalves on the cartridge are sealed by the system prior to initiating PCR in order to contain the amplification mixture and thus prevent evaporation and contamination.

The amplified cDNA targets are detected using hydrolysis (TaqMan®) probes, labeled at one end with a fluorescent reporter dye (fluorophore), and at the other end, with a quencher moiety. Probes labeled with different fluorophores are used to detect the target analytes in different optical channels of the BD MAX™ System. When the probes are in their native state, the fluorescence of the fluorophore is quenched due to its proximity to the quencher. However, in the presence of target cDNA, the probes hybridize to their complementary sequences and are hydrolyzed by the 5'-3' exonuclease activity of the DNA polymerase as it synthesizes the nascent strand along the cDNA template. As a result, the fluorophores are separated from the quencher molecules and fluorescence is emitted. The amount of fluorescence detected in the optical channels is directly proportional to the quantity of the corresponding probe that is hydrolyzed. The BD MAX™ System monitors these signals at each cycle of the PCR and interprets the data at the end of the reaction to provide qualitative test results for each analyte.

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Substantial Equivalence1

Indication for Use Comparison:

The BD Respiratory Viral Panel for BD MAX™ System and BD Respiratory Viral Panel-SCV2 for BD MAX™ System have a similar intended use as their predicate device, except for fewer targeted analytes in the BD Respiratory Viral Panel for BD MAX™ System as opposed to the BioFire Respiratory Panel 2.1 (RP2.1), DEN200031. All BD Respiratory Viral Panel for BD MAX™ System analytes are included in the BioFire Respiratory Panel 2.1 (RP2.1). The BD Respiratory Viral Panel-SCV2 for BD MAX™ System has the same analyte target as the BioFire COVID-19 Test 2, K211079/K221460.

Technological Comparison:

The BD MAX™ Assays have similar principle of operation as their predicate, the BioFire Respiratory Panel 2.1 (RP2.1), DEN200031, and BioFire COVID-19 Test 2, K211079/K221460. All assay reagent kits contain the materials required to complete tests and includes the hydration solution, sample buffer, and sample handling components such as transfer pipettes. All assays, subject devices and predicates, are used to test patient samples in a closed system that stores all the necessary reagents for sample preparation reverse transcription, polymerase chain reaction (PCR), and detection in order to isolate, amplify, and detect nucleic acid from multiple pathogens. Minor differences can be observed in the detection chemistry where the BD Respiratory Viral Panel for BD MAX™ System and the BD Respiratory Viral Panel-SCV2 for BD MAX™ System utilize paired reporter and quencher fluorescence labeled probes (TaqMan Technology) as opposed to the BioFire Respiratory Panel 2.1 (RP2.1) and BioFire COVID-19 Test 2 which utilize a two Step Nested multiplex PCR where sequences from the first RT-PCR/PCR are amplified using fluorescence double stranded binding dye. The minor differences between the subject and predicate devices do not raise any new questions of safety or effectiveness.

Table 1 provides the similarities and differences between the BD Respiratory Viral Panel for BD MAX™ System and BD Respiratory Viral Panel-SCV2 for BD MAX™ System, respectively, in comparison to their predicate devices.

The term "substantial equivalence" as used in this 510(1) notification is limited to the definition of substantial equivalence as found in the Federal Food, Drug and Cosmetic Act, as amended ander 21 CFR 807, Subpatt E under which a device can be marketed without pre-market approval or reclassification of substantial equivalency under this notification is not intended to have any bearing whatsoever on the resolution of patent infringement suits or any other patent matters. No statements related to, or in support of substantial equivalence herein shall be construed as an admission against interest under the US Patent Laws on the courts.

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Device and Predicate Device	Subject Device (K230956)	DEN200031 (Predicate Device)
Device Trade Name	BD Respiratory Viral Panel for BD MAX TM System	BD Respiratory Viral Panel-SCV2 for BD MAX TM System	BioFire Respiratory Panel 2.1 (RP2.1)
Regulation Number	21 CFR 866.3981	21 CFR 866.3981	Same
Regulation Name	Multi-Target Respiratory Specimen Nucleic Acid Test Including Sars-Cov-2 And Other Microbial Agents	Multi-Target Respiratory Specimen Nucleic Acid Test Including Sars-Cov-2 And Other Microbial Agents	Same
Product Code	QOF	QQX	QOF
Device and
Device	Predicate	Subject Device (K230956)	DEN200031 (Predicate Device)
Intended Use		BD Respiratory Viral Panel for BD MAX™ BD Respiratory Viral Panel-SCV2 for BD System is an automated multiplexed real-MAX™ System is an automated multiplexed real-time reverse transcriptase polymerase chain reaction (RT-PCR) test intended for the polymerase chain reaction (RT-PCR) test intended for the simultaneous, qualitative detection and intended for the simultaneous, qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A, influenza B, and/or respiratory syncytial virus (RSV) nucleic acid in nasopharyngeal swab (NPS) and anterior nasal swab (ANS) nasopharyngeal swab (NPS) and anterior specimens from individuals with signs and nasal swab (ANS) specimens from symptoms of respiratory tract infection. individuals with signs and symptoms of SARS-CoV-2 viral RNA is generally respiratory tract infection. Clinical signs and detectable in NPS and ANS specimens symptoms of respiratory tract infection due during the acute phase of infection. to SARS-CoV-2, influenza, and RSV can be similar.
The BD Respiratory Viral Panel-SCV2 for BD MAX™ System is intended for use as an aid in the diagnosis of SARS-CoV-2
BD Respiratory Viral Panel for BD MAX™ System is intended for use as an aid in the infection if used in conjunction with other differential diagnosis of SARS-CoV-2, clinical and epidemiological information, influenza A, influenza B, and/or RSV and laboratory findings. infection if used in conjunction with other clinical and epidemiological information, Positive results do not rule out co-infection with other organisms. The agent detected by and laboratory findings. SARS-CoV-2, with other organisms. The agent(s) detected by influenza A, influenza B, and RSV viral the BD Respiratory Viral Panel-SCV2 for nucleic acid are generally detectable in NPS BD MAX™ System may not be the and ANS specimens during the acute phase definitive cause of disease. of infection.
Negative results do not preclude SARS-CoV-2 infection.
Positive results do not rule out co-infection with other organisms. The agent(s) detected	The BIOFIRE Respiratory Panel 2.1 (RP2.1) is a PCR based multiplexed nucleic acid test intended for use with the BIOFIRE FilmArray 2.0 or BIOFIRE FilmArray Torch systems for the simultaneous qualitative detection and identification of multiple respiratory viral and bacterial nucleic acids in nasopharyngeal swabs (NPS) obtained from individuals suspected of respiratory tract infections, including COVID-19.
The following organism types and subtypes are identified using the BIOFIRE RP2.1:
• Adenovirus
• Coronavirus 229E
• Coronavirus HKU1
• Coronavirus NL63
• Coronavirus OC43
• Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2)
• Human Metapneumovirus
• Human Rhinovirus/Enterovirus
• Influenza A, including subtypes H1, H1-2009, and H3
• Influenza B
• Parainfluenza Virus 1
• Parainfluenza Virus 2
• Parainfluenza Virus 3
• Parainfluenza Virus 4
• Respiratory Syncytial Virus
• Bordetella parapertussis (IS1001)
Device and
Device	Predicate	Subject Device (K230956)	DEN200031 (Predicate Device)
		by the BD Respiratory Viral Panel for BD
MAX™ System may not be the definitive
cause of disease.	Bordetella pertussis (ptxP) Chlamydia pneumoniae, and Mycoplasma pneumoniae
		Negative results do not preclude SARS-
CoV-2, influenza A, influenza B, and/or
RSV infection.	Nucleic acids from the respiratory viral
and bacterial organisms identified by this
test are generally detectable in NPS
specimens during the acute phase of
infection. The detection and identification
		The results of this test should not be used as
the sole basis for diagnosis, treatment, or
other patient management decisions.	of specific viral and bacterial nucleic acids
from individuals exhibiting signs and/or
symptoms of respiratory infection is
indicative of the presence of the identified
microorganism and aids in the diagnosis
of respiratory infection if used in
conjunction with other clinical and
epidemiological information. The results
of this test should not be used as the sole
basis for diagnosis, treatment, or other
patient management decisions.
		The results of this test should not be used as
the sole basis for diagnosis, treatment, or
other patient management decisions.	Negative results in the setting of a
respiratory illness may be due to infection
with pathogens that are not detected by
this test, or lower respiratory tract
infection that may not be detected by an
NPS specimen. Positive results do not rule
out coinfection with other organisms. The
agent(s) detected by the BIOFIRE RP2
may not be the definite cause of disease.
Additional laboratory testing (e.g.,
bacterial and viral culture,
immunofluorescence, and radiography)
may be necessary when evaluating a
Device and
Predicate	Subject Device (K230956)	DEN200031 (Predicate Device)
Device		patient with possible respiratory tract
infection.

Condition for use	For prescription use
For in vitro diagnostic use only.	Same
Sample Types	Nasopharyngeal swab specimen Nasal swab specimen	Nasopharyngeal swab specimen
Patient Population	Individuals suspected of COVID-19 by their healthcare provider	Individuals suspected of respiratory tract
infections, including COVID-19
Device and Predicate
Device	Subject Device (K230956)	DEN200031 (Predicate Device)
Analyte Targets	The following organism types are
identified using the BD Respiratory Viral
Panel for BD MAXTM System:
Severe Acute Respiratory Syndrome
Coronavirus (SARS-CoV-2), Influenza A, Influenza B, and Respiratory Syncytial Virus	SARS-CoV-2	The following organism types and
subtypes are identified using the BioFire
RP2.1:
Adenovirus, Coronavirus 229E, Coronavirus HKU1, Coronavirus NL63, Coronavirus OC43, Severe Acute Respiratory Syndrome
Coronavirus (SARS-CoV-2), Human Metapneumovirus, Human Rhinovirus/Enterovirus, Influenza A, including subtypes H1,
H1-2009, and H3, Influenza B, Parainfluenza Virus 1, Parainfluenza Virus 2, Parainfluenza Virus 3, Parainfluenza Virus 4, Respiratory Syncytial Virus, Bordetella parapertussis (IS1001), Bordetella pertussis (ptxP), Chlamydia pneumoniae, and Mycoplasma pneumoniae
Sample
Preparation
Procedure	Automated by BD MAXTM System		Automated by BioFire FilmArray 2.0 or
BioFire FilmArray Torch systems
Amplification
Technology	Real-Time PCR		Nested multiplex RT-PCR
Analyte	RNA		RNA/DNA
Device and Predicate Device	Subject Device (K230956)	DEN200031 (Predicate Device)
Detection Chemistry	Paired reporter and quencher fluorescence labeled probes (TaqMan Technology) using fluorescence resonance energy transfer	Two Step Nested multiplex PCR:
Reverse transcription, followed by multiplexed first stage PCR reaction (PCR1).

Multiple simultaneous second stage PCR reactions (PCR2) to amplify sequence within the PCR1 products using fluorescence double stranded binding dye Endpoint melting curve data to detect target specific amplicons | |
| Control used | 1. The RNA Internal Control (RNase P)
2. External Positive and negative controls | Two process controls:

RNA Process Control (IC)
PCR2 Control (A positive result indicates that PCR2 was successful) | |
| Result Analysis | Based on PCR cycle threshold analysis | Endpoint melting curve data to detect target-specific amplicons | |
| Test Interpretation | Automated test interpretation and report generation. User cannot access raw data. | Same | |
| Time to Result | About 2 hours | About 45 min | |

Table 1. BD Respiratory Viral Panel for BD MAX™ System Substantial Equivalence Comparison

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11

12

13

14

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Analytical Performance Evaluation

BD Respiratory Viral Panel for BD MAX™ System and BD Respiratory Viral Panel-SCV2 for BD MAX™ System performance testing provided as part of this submission was conducted in accordance with the Respiratory Viral Panel Multiplex Nucleic Acid Assay - Class II Special Control Guidance for Industry and FDA Staff [October 9, 2009] and Class II Special Controls as per 21 CFR 866.3981. Additional consideration was also taken in regarding of COVID-19 and the Policy for Evaluating Impact of Viral Mutations on COVID-19 Tests (Revised) [January 12, 2023] in terms of evaluating the impact of identified variants on the BD MAX-SARS-CoV-2 primers and probes.

BD Respiratory Viral Panel for BD MAXTM System:

Precision

Within-laboratory precision was evaluated for the BD Respiratory Viral Panel at one site with one (1) reagent lot. Testing was performed over twelve (12) days, with two (2) operators performing two (2) runs per day for a total of forty-eight (48) runs. Test samples were contrived in simulated nasopharyngeal matrix and included SARS-CoV-2, Influenza B. and RSV panel members. Each panel member was tested in three (3) replicates. The following target concentrations were used for each target organism contained in each panel member:

· Moderate positive (MP): 3x LoD
· Low Positive (LP): 2x LoD
· True Negative (TN): No target

Precision study results are described in Table 2.

| Sample Concentration | SARS-CoV-2
(N), 95% CI | Flu A
(N), 95% CI | Flu B
(N), 95% CI | RSV
(N), 95% CI |
|----------------------------|-------------------------------|---------------------------------|---------------------------------|---------------------------------|
| Moderate Positive (3x LoD) | 100%
(144/144)
97.4-100 | 100%
(144/144)
97.4-100 | 100%
(144/144)
97.4-100 | 100%
(144/144)
97.4-100 |
| Low Positive (2x LoD) | 100%
(144/144)
97.4-100 | 97.2%
(140/144)
93.1-98.9 | 99.3%
(143/144)
96.2-99.9 | 99.3%
(143/144)
96.2-99.9 |
| True Negativea | 100%
(288/288)
98.7-100 | 100%
(288/288)
98.7-100 | 100%
(288/288)
98.7-100 | 100%
(288/288)
98.7-100 |

Table 2. Overall Precision Study Results Using One Lot of the BD Respiratory Viral
Panel (Percent Agreement with Expected Results)

ª For the True Negative category, the reported agreement indicates percent of negative results.

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Reproducibility

For the Site-to-Site reproducibility study, three (3) sites (two external and one internal) were provided the same panels as described for the Precision study above. Each site performed testing on five (5) distinct days (consecutive or not), wherein each day, one (1) panel was tested by two (2) technologists. Each panel member was tested in three (3) replicates.

The site-to-site reproducibility is presented below in Table 3 by target analyte. Ct, internal criterion used to determine a final assay result, was selected as an additional means of assessing assay reproducibility. Overall mean Ct values with variance components (SD and %CV) are shown in Table 4.

| Sample Concentration | SARS-CoV-2
(N), 95% CI | Flu A
(N), 95% CI | Flu B
(N), 95% CI | RSV
(N), 95% CI |
|----------------------------|-------------------------------|-------------------------------|-------------------------------|-------------------------------|
| Moderate Positive (3x LoD) | 100%
(90/90)
95.9-100 | 97.8%
(88/90)
92.3-99.4 | 100%
(90/90)
95.9-100 | 100%
(90/90)
95.9-100 |
| Low Positive (2x LoD) | 100%
(90/90)
95.9-100 | 96.7%
(87/90)
90.7-98.9 | 100%
(90/90)
95.9-100 | 100%
(90/90)
95.9-100 |
| True Negativea | 100%
(180/180)
97.9-100 | 100%
(180/180)
97.9-100 | 100%
(180/180)
97.9-100 | 100%
(180/180)
97.9-100 |

Table 3. Site-to-Site Reproducibility Study Results using One (1) Lot of the BD Respiratory Viral Panel (Percent Agreement with Expected Results)

a For the True Negative category, the reported agreement indicates percent of negative results.

		Table 4. Site-to-Site Reproducibility Across Sites, Days, Runs, and Replicates (Ct Values)

| Target | Level | N | Mean
Ct | Within Run | | Between Run | | Between Day | | Between Site | | Total | |
|--------|-------|----|------------|------------|--------|-------------|--------|-------------|--------|--------------|--------|-------|--------|
| | | | | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) |
| CoV-2 | LP | 90 | 33.3 | 0.74 | 2.2 | 0.00 | 0.0 | 0.00 | 0.0 | 0.54 | 1.6 | 0.92 | 2.8 |
| CoV-2 | MP | 90 | 33.0 | 0.45 | 1.4 | 0.08 | 0.2 | 0.00 | 0.0 | 0.74 | 2.2 | 0.87 | 2.6 |
| Flu A | LP | 87 | 34.9 | 1.31 | 3.8 | 0.36 | 1.0 | 0.00 | 0.0 | 0.51 | 1.5 | 1.45 | 4.2 |
| Flu A | MP | 88 | 33.5 | 1.03 | 3.1 | 0.37 | 1.1 | 0.00 | 0.0 | 0.20 | 0.6 | 1.11 | 3.3 |
| Flu B | LP | 90 | 33.6 | 1.25 | 3.7 | 0.00 | 0.0 | 0.29 | 0.9 | 0.20 | 0.6 | 1.29 | 3.9 |
| Flu B | MP | 90 | 33.0 | 0.67 | 2.0 | 0.00 | 0.0 | 0.20 | 0.6 | 0.15 | 0.5 | 0.72 | 2.2 |
| RSV | LP | 90 | 32.4 | 1.32 | 4.1 | 0.00 | 0.0 | 0.00 | 0.0 | 0.00 | 0.0 | 1.32 | 4.1 |
| RSV | MP | 90 | 31.9 | 0.92 | 2.9 | 0.00 | 0.0 | 0.00 | 0.0 | 0.13 | 0.4 | 0.92 | 2.9 |

For the Lot-to-Lot reproducibility study, one (1) internal site was provided the same panels as described for the Precision study above. Three (3) reagent lots were tested across five (5) distinct days (consecutive or not) using one (1) BD MAX™, wherein each day, two (2) panels were tested by two (2) technologists. Each panel member was tested in three (3) replicates.

17

The lot-to-lot reproducibility is presented below in Table 5 by target analyte. Ct, internal criterion used to determine a final assay result, was selected as an additional means of assessing assay reproducibility. Overall mean Ct values with variance components (SD and %CV) are shown in Table 6.

Table 5. Lot-to-Lot Reproducibility Study Results using Three (3) Lots of the BD
Respiratory Viral Panel (Percent Agreement with Expected Results)

| Sample Concentration | SARS-CoV-2
(N), 95% CI | Flu A
(N), 95%
CI | Flu B
(N), 95%
CI | RSV
(N), 95%
CI |
|----------------------------|---------------------------------|---------------------------------|---------------------------------|-------------------------------|
| Moderate Positive (3x LoD) | 99.4%
(179/180)
96.9-99.9 | 100%
(180/180)
97.9-100 | 98.9%
(178/180)
96.0-99.7 | 100%
(180/180)
97.9-100 |
| Low Positive (2x LoD) | 100%
(180/180)
97.9-100 | 97.8%
(176/180)
94.4-99.1 | 100%
(180/180)
97.9-100 | 100%
(180/180)
97.9-100 |
| True Negativea | 100%
(360/360)
98.9-100 | 100%
(360/360)
98.9-100 | 100%
(360/360)
98.9-100 | 100%
(360/360)
98.9-100 |

a For the True Negative category, the reported agreement indicates percent of negative results.

Table 6. Lot-to-Lot Reproducibility across Operators, Days, Runs, and Replicates (Ct Values)

| Target | Level | N | Mean Ct | Lot | | Day | | Operator | | Run | | Within Run
(Repeatability) | | Total | |
|--------|-------|-----|---------|------|-------|------|-------|----------|-------|------|-------|-------------------------------|-------|-------|-------|
| | | | | SD | CV(%) | SD | CV(%) | SD | CV(%) | SD | CV(%) | SD | CV(%) | SD | CV(%) |
| CoV-2 | MP | 179 | 33.7 | 0.26 | 0.8 | 0.06 | 0.2 | 0.10 | 0.3 | 0.00 | 0.0 | 0.61 | 1.8 | 0.67 | 2.0 |
| CoV-2 | LP | 180 | 33.9 | 0.24 | 0.7 | 0.18 | 0.5 | 0.12 | 0.3 | 0.00 | 0.0 | 0.64 | 1.9 | 0.72 | 2.1 |
| Flu A | MP | 180 | 33.2 | 0.26 | 0.8 | 0.00 | 0.0 | 0.00 | 0.0 | 0.00 | 0.0 | 1.05 | 3.2 | 1.08 | 3.3 |
| Flu A | LP | 176 | 34.3 | 0.44 | 1.3 | 0.44 | 1.3 | 0.00 | 0.0 | 0.23 | 0.7 | 1.40 | 4.1 | 1.55 | 4.5 |
| Flu B | MP | 178 | 33.3 | 0.30 | 0.9 | 0.36 | 1.1 | 0.00 | 0.0 | 0.16 | 0.5 | 1.30 | 3.9 | 1.39 | 4.2 |
| Flu B | LP | 180 | 34.1 | 0.00 | 0.0 | 0.17 | 0.5 | 0.00 | 0.0 | 0.22 | 0.6 | 1.20 | 3.5 | 1.23 | 3.6 |
| RSV | MP | 180 | 31.9 | 0.58 | 1.8 | 0.00 | 0.0 | 0.00 | 0.0 | 0.00 | 0.0 | 1.12 | 3.5 | 1.26 | 4.0 |
| RSV | LP | 180 | 32.7 | 0.60 | 1.8 | 0.00 | 0.0 | 0.00 | 0.0 | 0.05 | 0.1 | 0.87 | 2.7 | 1.06 | 3.2 |

Linearity

Not applicable. This is a qualitative assay.

Limit of Detection (LoD)

The analytical sensitivity of the BD Respiratory Viral Panel for BD MAX™ System was assessed in both nasopharyngeal and nasal clinical matrix across seven respiratory viruses. LoD studies determine the lowest detectable concentration of virus at which approximately 95% of all (true positive) replicates test positive. Analysis of SARS-CoV-2 was completed with a Probit statistical methodology. Analysis of of three strains of of influenza (H1N1/Brisbane, A

18

H1N1(pdm09)/Guangdong-Maonan, and H3N2/Kansas), influenza B (Colorado and Phuket/3073/13), RSV A and RSV B was completed with a limiting dilution with 3-fold serial dilutions between each level. A minimum of five determination levels and one negative level across three (3) reagent lots were tested. Confirmation of the estimated LoD was performed with one reagent lot in replicates of 20 prepared in nasopharyngeal and nasal matrix and are reported in Table 7. To confirm that the co-spiking of analytes does not impact analytical sensitivity, the LoD was also confirmed with one strain per analyte.

Strain	LoD Concentration (in UVT)
	Nasopharyngeal	Nasal
SARS-CoV-2 (USA-WA1/2020)	700 copies/mL	700 copies/mL
Influenza A/H1N1/Brisbane/59/07	5.6E-03 TCID50/mL	5.6E-03 TCID50/mL
Influenza A/H1N1/Guangdong-
Maonan/ SWL 1536/19	2.49E-01 TCID50/mL	2.49E-01 TCID50/mL
Influenza A/H3N2/Kansas/14/17	2.8E-01 TCID50/mL	2.8E-01 TCID50/mL
Influenza B/Colorado/6/17	6.8E-03 TCID50/mL	6.8E-03 TCID50/mL
Influenza B/Phuket/3073/13	2.9E-02 TCID50/mL	9.6E-03 TCID50/mL
RSV A 2006 Isolate	3.1E-02 TCID50/mL	3.1E-02 TCID50/mL
RSV B CH93(18)-18	1.7E-02 TCID50/mL	5.6E-03 TCID50/mL

				Table 7. BD Respiratory Viral Panel for BD MAX™ System Limit of Detection
--	--	--	--	---------------------------------------------------------------------------	--

Inclusivity

An in silico alignment of the BD Respiratory Viral Panel primers and probes demonstrated that the performance of the BD Respiratory Viral Panel reagents for the BD MAX™ system is not directly impacted by the presence of mutations in known SARS-CoV-2 viral variants. As of June 10, 2022, BD continues to monitor all lineages for the following WHO labeled Variants of Concern, Alpha, Beta, Gamma, Delta, and Mu. In all cases greater than 99% of the sequenced isolates are a perfect match to all primers and probes in either the N1 or N2 set. Given similar performance from both the N1 and N2 channel, either will back up the other in the event of performance degradation through genetic drift. Additionally, BD continues to monitor all lineages of the WHO Omicron label, including sublineages within BA.1, BA.2, BA.2.12.1, BA.3, BA.4, and BA.5. All Omicron genomes contain a mutation that affects the N1 probe 3 bases from the 5' end. (Mutation C28311T). Each Omicron sub-lineage has a percentage of sequences that are a perfect match to either the N1 or N2 primer-set as follows: BA.1 at 99.47%, BA.2 at 98.95%, BA.2.12.1 at 99.63%, BA.3 at 100%, BA.4 at 96.87% and BA.5 at 99.55%.

An in-silico comparison of the influenza A primer set was performed using all available high quality Influenza A M1 (matrix protein) gene sequences submitted to the NCBI GenBank database as of January 02, 2022 (n=44,468). Multiple alignment of the matrix gene showed that 90.3% of sequences are a perfect match to the primer/probe set while an additional 9.5% of sequences have a single base mismatch in the 5' end of a single primer. Multiple mismatches to the primers and probe occurred in only 0.2% of sequences.

An in-silico comparison of the influenza B primer sets was performed using all available high quality Influenza B M1 gene and HA gene sequences submitted to the NCBI GenBank database

19

as of January 02, 2022. A total of 11,683 matrix and 18,559 HA sequences were used in this analysis. Multiple alignment of the M1 gene showed that 97.1% of sequences are a perfect match to the primer/probe set and 76.7% of HA sequences are a perfect match.

An in-silico comparison of the RSV primer sets was performed using all available high quality RSV M gene and N gene sequences submitted to the NCBI GenBank database as of January 02, 2022 (N=3,443). Alignments against the M and N gene showed that the primer/probe sets are a perfect match to 83.0% of sequences in the database, 92.3% of the sequences were a perfect match to the M primer/probe set, and 90.1% were a perfect match to the N primer/probe set region. In total, 99.4% are a perfect match to either the M gene or the N gene primer sets.

BD Respiratory Viral Panel for BD MAX™ System was evaluated against multiple strains of SARS-CoV-2, influenza A HINI and H3N2, influenza B including both the Yamagata and Victoria lineages, and RSV including both A and B. A total of 11 SARS-CoV-2, 30 influenza A. 10 influenza B, and 5 RSV strains were evaluated at levels near the analytical LoD. Three replicates were tested for each strain. Refer to Table 8 for the BD Respiratory Viral Panel for BD MAX™ System analytical reactivity/inclusivity.

| Virus | Strain | Source | Concentration
Detected | Relative
LoD | Positive
Results/
Total |
|------------|--------------------------------------------------------|-----------------------------|---------------------------|-----------------|-------------------------------|
| SARS-CoV-2 | Hong Kong/VM200001061/2020 | ZeptoMetrix®
0810590CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Italy-INMI1 | ZeptoMetrix®
0810589CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Alpha, (B.1.1.7) USA/
CA_CDC_5574/2020 | ZeptoMetrix®
0810612CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Alpha, (B.1.1.7)
England/204820464/2020 | ZeptoMetrix®
0810614CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | eta, (B.1.351) South Africa/
KRISP-K005325/2020 | ZeptoMetrix®
0810613CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Kappa, (B.1.617.1) USA/
CA-Stanford-15_S02/2021 | ZeptoMetrix®
0810623CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | amma, (P1) Japan/ TY7-503/2021 | ZeptoMetrix®
0810616CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Ita, (B.1.617.2) USA/
PHC658/2021 | ZeptoMetrix®
0810624CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Iota, (B.1.526_2021) NY-
Wadsworth-21025952-01/2021 | ZeptoMetrix®
0810619CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Zeta, (P2_2021) NY-
Wadsworth-21006055-01/2021 | ZeptoMetrix®
0810618CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Omicron (BA.1) USA/ GA-EHC-
2811C/2021 | ATCC®
VR-3347HK | 2100 copies/mL | 3x LoD | 3/3 |

Table 8. Analytical Reactivity/Inclusivity for the BD Respiratory Viral Panel for the BD
MAXTM System

20

Assay Measuring Range

Not applicable. This is a qualitative assay.

Interfering Substances

Twenty-three (23) biological and chemical substances that may be present in nasopharyngeal or anterior nasal swab specimens were evaluated for potential interference with the BD Respiratory Viral Panel for BD MAX™ System in the absence and presence of assay analytes (SARS-CoV-2, influenza A, influenza B, and RSV). Whole blood (human) was found to interfere at levels above 0.2% volume/volume for SARS-CoV-2. Results demonstrated no reportable interference from any other substance at the concentrations tested (refer to Table 9).

21

Endogenous and Commercial Exogenous Substances Tested with BD Respiratory Viral Panel for the BD MAX™ Table 9. System

| Substance | Active Ingredient Tested | Positive Testing (Positive/Total) | (Negative/ Total) | Result |
|------------------------------------|---------- | | | Oral anesthetic
and analgesic | Benzocaine | | Menthol | Biologicals | Purified Mucin | | (human) | 2% v/v | | Leukocytes | FluMist
Quadrivalent
Vaccine | Live, attenuated
Flu A and Flu B
strains | 6.67% v/v | 3/3 | | | | | | | Nasal Sprays/
Drops | Zinc | | Phenylephrine | | Oxymetazoline | | with preservatives | 5% v/v | Corticosteroids | Beclomethasone | | Dexamethasone | | Flunisolide | | Triamcinolone | | Budesonide | | Mometasone | | Fluticasone | | | Nasal Gel | Luffa opperculata | | Sulfur | Homeopathic
Allergy Relief | Galphimia glauca | | Histaminum | | hydrocloricum | Antiviral Drug | Zanamivir | Antibiotic | Mupirocin | Antibacterial | Tobramycin | Concentration
| | | Negative Testing
--------------------------------------|-------------------------|-----------------------------------|-------------|-------------|-----|---------------------------------------|--------|
| | SARS-CoV-2 | Influenza A | Influenza B | RSV | | |
| 0.8 mg/mL | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| | | | | | | |
| 60 µg/mL | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
Whole Blood
| 1/3 | 3/3 | 3/3 | 3/3 | 3/3 | I |
| 2% v/v | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| 3/3 | 3/3 | 3/3 | 0/3 | I |
| 6.67E-04% v/v | 3/3 | 3/3 | 3/3 | 3/3 | 0/3 | I |
| 6.67E-08% v/v | 3/3 | 3/3 | 3/3 | 3/3 | 2/3 | I |
| 6.67E-12% v/v | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| 1 mg/mL | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| 5% v/v | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| 5% v/v | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
Sodium Chloride
| 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| 17% v/v | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| 17% v/v | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| 17% v/v | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| 17% v/v | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| 17% v/v | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| 17% v/v | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| 17% v/v | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| | | | | | | |
| | | | | | | |
| | | | | | | |
| 5% v/v | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| | | | | | | |
| | | | | | | |
| 3.3 mg/mL | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| 10 mg/mL | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |
| 4 µg/mL | 3/3 | 3/3 | 3/3 | 3/3 | 3/3 | NI |

22

Mixed Infection/Competitive Interference

To assess potential competitive interference between SARS-CoV-2, influenza A, influenza B, and RSV samples were tested in replicates of twenty (20) where low (approximately 2x their respective LoD) concentration of three analytes were mixed with high (approximately 1.00E+06 genome copies/mL in UVT) concentration of the other analyte. None of the analytes present at a very high concentration interfered with the detection of low levels of the other three analytes, refer to Table 10.

| Condition | High Virus (1.00E+06
copies/mL) | Low Virus (~2x
LoD) | Positive / Total | | | |
|-----------|------------------------------------|-------------------------------|------------------|-------|-------|-------|
| | | | SARS-CoV-2 | Flu A | Flu B | RSV |
| 1 | SARS-CoV-2 | Flu A / Flu B / RSV | 20/20 | 20/20 | 20/20 | 20/20 |
| 2 | Flu A | SARS-CoV-2 / Flu
B / RSV | 20/20 | 20/20 | 20/20 | 20/20 |
| 3 | Flu B | SARS-CoV-2 / Flu
A / RSV | 20/20 | 19/20 | 20/20 | 20/20 |
| 4 | RSV | SARS-CoV-2 / Flu
A / Flu B | 19/20 | 19/20 | 19/20 | 20/20 |

Table 10. Mixed Infection Results for the BD Respiratory Viral Panel for the BD MAX™
System

Cross-Reactivity

An in silico analysis was performed to evaluate the potential for all primers and probes contained within the BD Respiratory Viral Panel for BD MAX™ System master mix to amplify and detect unintended organisms. Each primer was 'BLAST' against the full nt database and alignments were kept if there were no more than three (3) base pair mismatches across the length of the primer, the 3' end of the primer matched the subject sequence, and no gaps were introduced to "force" an alignment. The plus/minus orientation between the primer (query) and the subject (database sequence) was determined, and all two-primer combinations (including each primer with itself) were identified where one primer matched the plus strand and the other matched the minus, representing potential amplicons were kept if the minus strand primer was downstream of the plus strand primer and the resulting amplicons were less than or equal to 3,000 base pairs long.

SARS-CoV-2: All identified hits are either SARS-CoV-2 or a closely related coronavirus from non-human species. No relevant cross-reactivity was discovered.

Influenza A: No relevant cross-reactivity was discovered.

Influenza B: No relevant cross-reactivity was discovered.

Respiratory syncytial virus: No relevant cross-reactivity was discovered.

Additionally, fifty-two (52) organisms and one (1) nasopharyngeal pool were evaluated for cross-reactivity with the BD Respiratory Viral Panel for BD MAX™ System. The bacterial

23

cells, yeasts, and viruses were tested in the BD Molecular RVP Sample Buffer Tube. All organisms tested produced negative results when tested at the concentration listed in Table 11.

BD Respiratory Viral Panel for the BD MAX™ System Cross-Reactivity Table 11. Results

24

| Organism | Source | Concentration Tested | Negative Results
Obtained (Negative
Result/Total) |
|-------------------------------------------------------------|-----------------------------|----------------------|---------------------------------------------------------|
| Adenovirus - Type 1 | ZeptoMetrix® 0810050CF | 1.00E+05 TCID50/mL | 3/3 |
| Adenovirus - Type 4 | ZeptoMetrix® 0810070CF | 1.00E+05 TCID50/mL | 3/3 |
| Adenovirus - Type 7 | ZeptoMetrix® 0810021CF | 1.00E+05 TCID50/mL | 3/3 |
| Aspergillus flavus | ZeptoMetrix® 0801598 | 1.00E+06 CFU/mL | 3/3 |
| Aspergillus fumigatus | ZeptoMetrix® 0801716 | 1.00E+06 CFU/mL | 3/3 |
| Aspergillus terreus | ZeptoMetrix® 0801827 | 1.00E+06 CFU/mL | 3/3 |
| Aspergillus niger | ZeptoMetrix® 0801601 | 1.00E+06 CFU/mL | 3/3 |
| Bordetella pertussis | ZeptoMetrix® 0801459 | 1.00E+06 CFU/mL | 3/3 |
| Bordetella parapertussis | ZeptoMetrix® 08001461 | 1.00E+06 CFU/mL | 3/3 |
| Candida albicans | ATCC® 18804 | 1.00E+06 CFU/mL | 3/3 |
| Chlamydophila
pneumoniae | ATCC® 53592 | 1.00E+06 IFU/mL | 3/3 |
| Corynebacterium
diphtheriae | ZeptoMetrix® 0801882 | 1.00E+06 CFU/mL | 3/3 |
| Cytomegalovirus | ZeptoMetrix® 0810003CF | 1.00E+05 copies/mL | 3/3 |
| Enterovirus B (Echovirus
6) | ZeptoMetrix® 0810076CF | 1.00E+05 units/mL | 3/3 |
| Enterovirus C
(Coxsackievirus A16) | ZeptoMetrix® 0810107CF | 1.00E+05 TCID50/mL | 3/3 |
| Enterovirus D68 | ZeptoMetrix® 0810237CF | 1.00E+05 TCID50/mL | 3/3 |
| Epstein Barr virus | ZeptoMetrix® 0810008CF | 1.00E+05 copies/mL | 3/3 |
| Escherichia coli | ATCC® 35401 | 1.00E+06 CFU/mL | 3/3 |
| Fusobacterium
necrophorum | ATCC® 25286 | 1.00E+06 CFU/mL | 3/3 |
| Haemophilus influenzae | ZeptoMetrix® 0801679 | 1.00E+06 CFU/mL | 3/3 |
| Herpes simplex virus
Type 1 | ZeptoMetrix® 0810005CF | 1.00E+05 TCID50/mL | 3/3 |
| Herpes simplex virus
Type 2 | ZeptoMetrix® 0810006CF | 1.00E+05 TCID50/mL | 3/3 |
| Human coronavirus 229E | ATCC® VR-740 | 1.00E+05 TCID50/mL | 3/3 |
| Human coronavirus
HKU1a | ATCC® VR-3262SD | 1.00E+05 GC/mL | 3/3 |
| Human coronavirus
NL63 | ZeptoMetrix® 0810228CF | 1.00E+07 copies/mL | 3/3 |
| Human coronavirus
OC43 | ZeptoMetrix® 0810024CF | 1.00E+05 TCID50/mL | 3/3 |
| Human
Metapneumovirus | ZeptoMetrix® 0810161CF | 1.00E+05 TCID50/mL | 3/3 |
| Lactobacillus acidophilus | ATCC® 4356 | 1.00E+06 CFU/mL | 3/3 |
| Legionella pneumophila | ATCC® 33152 | 1.00E+06 CFU/mL | 3/3 |
| Measles | ZeptoMetrix® 0810025CF | 1.00E+05 TCID50/mL | 3/3 |
| MERS-coronavirus | ZeptoMetrix®
0810228CFHI | 1.00E+07 copies/mL | 3/3 |
| Moraxella catarrhalis | ZeptoMetrix® 0801509 | 1.00E+06 CFU/mL | 3/3 |
| Mumps | ZeptoMetrix® 0810079CF | 1.00E+05 TCID50/mL | 3/3 |
| Mycobacterium | ATCC® 25177DQ | 1.00E+06 copies/mL | 3/3 |
| tuberculosisª | | | |
| Mycoplasma genitalium | ATCC® 33530 | 1.00E+06 cells/mL | 3/3 |
| Mycoplasma pneumoniae | ATCC® 15531-TTR | 1.00E+06 CFU/mL | 3/3 |
| Neisseria meningitidis | ATCC® 13077 | 1.00E+06 CFU/mL | 3/3 |
| Neisseria gonorrhoeae | ATCC® 19424 | 1.00E+06 CFU/mL | 3/3 |
| Parainfluenza virus 1 | ZeptoMetrix® 0810014CF | 1.00E+05 TCID50/mL | 3/3 |
| Parainfluenza virus 2 | ZeptoMetrix® 0810504CF | 2.12E+05 TCID50/mL | 3/3 |
| Parainfluenza virus 3 | ZeptoMetrix® 0810016CF | 1.00E+05 TCID50/mL | 3/3 |
| Parainfluenza virus 4 | ZeptoMetrix®
0810060BCF | 1.00E+05 TCID50/mL | 3/3 |
| Pneumocystis jirovecii | ATCC® PRA-159 | 1.00E+06 cells/mL | 3/3 |
| Expressed and pooled
human nasopharyngeal
swab matrix | Internal | N/A | 3/3 |
| Pseudomonas aeruginosa | ATCC® 10145 | 1.00E+06 CFU/mL | 3/3 |
| Rhinovirus | ZeptoMetrix® 0810284CF | 1.00E+05 TCID50/mL | 3/3 |
| SARS-Coronavirusª | ATCC® VR-3280SD | 1.00E+05 GE/mL | 3/3 |
| Staphylococcus aureus | ATCC® 43300 | 1.00E+06 CFU/mL | 3/3 |
| Staphylococcus
epidermidis | ATCC® 12228 | 1.00E+06 CFU/mL | 3/3 |
| Streptococcus
pneumoniae | ZeptoMetrix® 0804222 | 1.00E+06 CFU/mL | 3/3 |
| Streptococcus pyogenes | ATCC® 49399 | 1.00E+06 CFU/mL | 3/3 |
| Streptococcus salivarius | ZeptoMetrix® 0801896 | 1.00E+06 CFU/mL | 3/3 |
| Varicella-zoster virus | ZeptoMetrix® 0810167CF | 1.00E+07 copies/mL | 3/3 |

25

a Genomic DNA or RNA tested

Microbial Interference

Fifty-two (52) organisms and one (1) nasopharyngeal pool were evaluated for potential interference with the BD Respiratory Viral Panel for BD MAX™ System. Organisms were tested at high concentration (≥106 CFU/mL, cells/mL, genome equivalents/mL, ≥106 IFU/mL or TCIDso/mL, or highest concentration available) in the presence of assay analytes (SARS-CoV-2, influenza A, influenza B, and RSV) co-spiked at 3x LoD. Refer to Table 12.

Table 12. Microbial Interference Testing Results for the BD Respiratory Viral Panel for the BD MAX™ System

| Organism | Source | Concentration
Tested | Positive Results Obtained
(Positive Results / Total) | | | |
|----------------------------------------------------------------|-----------------------------|-------------------------|---------------------------------------------------------|-------|-------|-----|
| | | | SARS-
CoV-2 | Flu A | Flu B | RSV |
| Adenovirus -
Type 1 | ZeptoMetrix®
0810050CF | 1.00E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Adenovirus -
Type 4 | ZeptoMetrix®
0810070CF | 1.00E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Adenovirus - | ZeptoMetrix® | 1.00E+05 | 3/3 | 3/3 | 3/3 | 3/3 |
| Organism | Source | Concentration
Tested | Positive Results Obtained
(Positive Results / Total) | | | |
| | | | SARS-
CoV-2 | Flu A | Flu B | RSV |
| Type 7 | 0810021CF | TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Aspergillus flavus | ZeptoMetrix®
0801598 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Aspergillus
fumigatus | ZeptoMetrix®
0801716 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Aspergillus
terreus | ZeptoMetrix®
0801827 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Aspergillus niger | ZeptoMetrix®
0801601 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Bordetella
pertussis | ZeptoMetrix®
0801459 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Bordetella
parapertussis | ZeptoMetrix®
08001461 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Candida albicans | ATCC® 18804 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Chlamydophila
pneumoniae | ATCC® 53592 | 1.00E+06
IFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Corynebacterium
diphtheriae | ZeptoMetrix®
0801882 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Cytomegalovirus | ZeptoMetrix®
0810003CF | 1.00E+05
copies/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Enterovirus B
(Echovirus 6) | ZeptoMetrix®
0810076CF | 1.00E+05
units/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Enterovirus C
(Coxsackievirus
A16) | ZeptoMetrix®
0810107CF | 1.00E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Enterovirus D68 | ZeptoMetrix®
0810237CF | 1.00E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Epstein Barr virus | ZeptoMetrix®
0810008CF | 1.00E+05
copies/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Escherichia coli | ATCC® 35401 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Fusobacterium
necrophorum | ATCC® 25286 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Haemophilus
influenzae | ZeptoMetrix®
0801679 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Herpes simplex
virus Type 1 | ZeptoMetrix®
0810005CF | 1.00E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Herpes simplex
virus Type 2 | ZeptoMetrix®
0810006CF | 1.00E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Human
coronavirus 229E | ATCC® VR-740 | 1.00E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Human
coronavirus
HKU1a | ATCC® VR-
3262SD | 1.00E+05
GC/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| | | Concentration | Positive Results Obtained
(Positive Results / Total) | | | |
| Organism
Source | | Tested | SARS-
CoV-2 | Flu A | Flu B | RSV |
| Human
coronavirus NL63 | ZeptoMetrix®
0810228CF | 1.00E+07
copies/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Human
coronavirus OC43 | ZeptoMetrix®
0810024CF | 1.00E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Human
Metapneumovirus | ZeptoMetrix®
0810161CF | 1.00E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Lactobacillus
acidophilus | ATCC® 4356 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Legionella
pneumophila | ATCC® 33152 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Measles | ZeptoMetrix®
0810025CF | 1.00E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| MERS-
coronavirus | ZeptoMetrix®
0810575CFHI | 1.00E+07
copies/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Moraxella
catarrhalis | ZeptoMetrix®
0801509 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Mumps | ZeptoMetrix®
0810079CF | 1.00E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Mycobacterium
tuberculosisa | ATCC®
25177DQ | 1.00E+06
copies/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Mycoplasma
genitalium | ATCC® 33530 | 1.00E+06
cells/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Mycoplasma
pneumoniae | ATCC® 15531-
TTR | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Neisseria
meningitidis | ATCC® 13077 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Neisseria
gonorrhoeae | ATCC® 19424 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Parainfluenza
virus 1 | ZeptoMetrix®
0810014CF | 1.00E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Parainfluenza
virus 2 | ZeptoMetrix®
0810504CF | 2.12E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Parainfluenza
virus 3 | ZeptoMetrix®
0810016CF | 1.00E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Parainfluenza
virus 4 | ZeptoMetrix®
0810060BCF | 1.00E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Pneumocystis
jirovecii | ATCC® PRA-
159 | 1.00E+06
cells/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Expressed and
pooled human
nasopharyngeal
swab matrix | Internal | N/A | 3/3 | 3/3 | 3/3 | 3/3 |
| Pseudomonas
aeruginosa | ATCC® 10145 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Organism | Source | Concentration
Tested | Positive Results Obtained
(Positive Results / Total) | | | |
| | | | SARS-
CoV-2 | Flu A | Flu B | RSV |
| Rhinovirus | ZeptoMetrix®
0810284CF | 1.00E+05
TCID50/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| SARS-
Coronavirusª | ATCC® VR-
3280SD | 1.00E+05
GE/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Staphylococcus
aureus | ATCC® 43300 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Staphylococcus
epidermidis | ATCC® 12228 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Streptococcus
pneumoniae | ZeptoMetrix®
0804222 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Streptococcus
pyogenes | ATCC® 49399 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Streptococcus
salivarius | ZeptoMetrix®
0801896 | 1.00E+06
CFU/mL | 3/3 | 3/3 | 3/3 | 3/3 |
| Varicella-zoster
virus | ZeptoMetrix®
0810167CF | 1.00E+07
copies/mL | 3/3 | 3/3 | 3/3 | 3/3 |

26

27

28

a Genomic DNA or RNA tested

Sample Stability

BD Respiratory Viral Panel for BD MAX™ System stability for SARS-CoV-2, influenza A, influenza B and RSV in nasopharyngeal matrix and in anterior nasal swab matrix expressed in UVT/UTM (neat) as well both post transfer of UVT/UTM matrix into sample buffer tubes (nested) was evaluated. Specimens were constructed using clinical nasopharyngeal or anterior nasal matrix spiked at 3X LoD. Refer to Table 13 for the BD Respiratory Viral Panel Assay for BD MAX™ System Specimen Stability.

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Specimen Stability	Temperature	Duration
In UVT/UTM	25 ± 2 °C	12 hours
In UVT/UTM	2-8 °C	72 hours
In BD Molecular RVP Sample Buffer Tube	25 ± 2 °C	24 hours
In BD Molecular RVP Sample Buffer Tube	2-8 °C	120 hours

Table 13. BD Respiratory Viral Panel Assay for BD MAX™ System Specimen Stability

Assay Cut-off

The assay cut-off for the BD Respiratory Viral Panel for BD MAX™ was established based on PCR based metrics taken together by the BD MAX software algorithm to make the qualitative decision whether a curve is to be considered positive or negative. These metrics (e.g., Ct, RFU endpoints, signal-to-noise ratios) are initially set by default parameters defined by the instrument. As the product undergoes product development, the data is supplemented, and the algorithm is adjusted ("trained") using viral cultures spiked into clinical background matrices at levels surrounding the limit of detection and expected clinical range. In conclusion, testing of clinical specimens were used to confirm adequate separation between the value observed in positive specimens in each target detection channel and the assay cutoff.

Matrix Equivalency

Matrix Equivalency between nasopharyngeal swab, and simulated nasopharyngeal matrix was evaluated using heat inactivated SARS-CoV-2 (USA-WA/2020 strain), influenza A (H1N1/Brisbane), influenza B (Phuket/3073/13) and RSV A culture fluids spiked into negative nasopharyngeal, nasal and simulated matrix to prepare contrived low positive (approximately 2x LoD) and moderate positive (approximately 5x LoD) samples for each sample type. A total of thirty (30) low positive, fifteen (15) moderate positive, and fifteen (15) negative samples were tested.

Simulated nasopharyngeal matrix was demonstrated to be equivalent to nasopharyngeal and nasal in UVT matrix

Fresh vs Frozen

A study was performed with the BD Respiratory Viral Panel for BD MAX™ System using fresh and frozen nasopharyngeal swabs in UVT which showed that there were no adverse effects from freezing and thawing of specimens. The data generated are considered acceptable to support testing of archived, frozen specimens in the Clinical Study to evaluate the performance of the BD Respiratory Viral Panel for BD MAX™ System.

Carryover / Cross-Contamination

A study was conducted to investigate within-run carryover and between-run carryover while processing samples with high viral load of SARS-CoV-2 in the BD Respiratory Viral Panel for BD MAX™ System. High positive samples contained heat inactivated SARS-CoV-2 spiked into pooled nasal swab matrix at a concentration of ≥1.94E+07 copies/mL. The negative samples

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consisted of simulated nasopharyngeal matrix without any target analyte. Twelve (12) replicates of the high positive panel member and 12 replicates of the negative panel member were tested in nine (9) runs by alternating negative and positive samples, using three BD MAX™ Systems. A total of 108 positive and 108 negative samples were tested. Of the 108 negative samples tested, one (1) false positive result was obtained (0.93%, 95% CI: 0.16-5.06%).

Expected Values

In the BD Respiratory Viral Panel for BD MAX™ System clinical study, reportable results from specimens compliant at the specimen and PCR levels were obtained from 8 geographically diverse sites. Nasopharyngeal specimens totaled 1,562 for all assay targets. Nasal specimens totaled 1,566 for all assay targets. The number and percentage of positive cases per target, as determined by BD Respiratory Viral Panel for BD MAX™ System, are presented in Table 14.

Table 14. BD Respiratory Viral Panel for BD MAX™ System Positivity Rate Per Target and Specimen Type

Analyte	Nasopharyngeal	Nasal
SARS-CoV-2	34.6% (541/1562)	32.2% (504/1566)
Flu A	4.2% (66/1562)	4.2% (66/1566)
Flu B	0.1% (1/1562)	0.0% (0/1566)
RSV	0.8% (12/1562)	0.8% (12/1566)

External Control Validation

Assay run controls are not provided as part of the BD Respiratory Viral Panel for BD MAX™ System. BD recommends the use of Microbiologics controls. Studies have been performed to verify the use of Microbiologics Helix Elite™ Molecular Standards with the BD Respiratory Viral Panel for BD MAX™ System. The combination of Microbiologics SARS-CoV-2 Positive Control, Influenza A/B and Respiratory Syncytial Virus (RSV) Positive Control will be used as the external positive control. Microbiologics Negative Cellularity Control (NCC) will be used as the external negative control.

Usabilitv Study

A usability study has been performed to determine whether a representative sample of untrained professionals could correctly prepare samples for the BD MAX Respiratory Viral Panel for BD MAX™ System. The participants were presentative mock sample, and all other materials required to process the mock sample. They were asked to go through simulating the assay preparation and perform every step as realistically as possible. The use scenario being studied in this evaluation was the expected use scenario that an intended user would go through when preparing samples for molecular assays in a clinical environment. The study demonstrated usability with the target user population for safe and effective use of the product.

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BD Respiratory Viral Panel-SCV2 for BD MAX™ System:

Precision

Within-laboratory precision was evaluated for the BD Respiratory Viral Panel-SCV2 at one (1) site with one (1) reagent lot. Testing was performed over 12 days, with two operators performing 2 runs per day for a total of 48 runs. Test samples were contrived in simulated nasopharyngeal matrix and included SARS-CoV-2 panel members. Each panel member was tested in three replicates. The following target concentrations were used for each target organism contained in each panel member:

· Moderate positive (MP): 3x LoD
· Low Positive (LP): 2x LoD
· True Negative (TN): No target

Precision study results are described in Table 15.

Table 15. Overall Precision Study Results Using One Lot of the BD Respiratory Viral Panel (Percent Agreement with Expected Results)

| Sample Concentration | SARS-CoV-2
(N), 95% CI |
|----------------------------|-----------------------------|
| Moderate Positive (3x LoD) | 100%
(144/144), 97.4-100 |
| Low Positive (2x LoD) | 100%
(144/144), 97.4-100 |
| True Negativea | 100%
(288/288), 98.7-100 |

a For the True Negative category, the reported agreement indicates percent of negative results.

Reproducibility

For the Site-to-Site reproducibility study, three (3) sites (two external and one internal) were provided the same panels as described for the Precision study above. Each site performed testing on five (5) distinct days (consecutive or not), wherein each day, one (1) panel was tested by two (2) technologists. Each panel member was tested in three (3) replicates.

The qualitative and quantitative reproducibility is presented below in Table 16 by target analyte. Ct, internal criterion used to determine a final assay result, was selected as an additional means of assessing assay reproducibility. Overall mean Ct values with variance components (SD and %CV) are shown in Table 17.

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Table 16. Site-to-Site Reproducibility Study Results using One (1) Lot of the BD Respiratory Viral Panel (Percent Agreement with Expected Results)

| Sample Concentration | SARS-CoV-2
(N), 95% CI |
|----------------------------|-----------------------------|
| Moderate Positive (3x LoD) | 100%
(90/90), 95.9-100 |
| Low Positive (2x LoD) | 100%
(90/90), 95.9-100 |
| True Negativea | 100%
(180/180), 97.9-100 |

a For the True Negative category, the reported agreement indicates percent of negative results.

Table 17. Site-to-Site Quantitative Reproducibility Across Sites, Days, Runs, and Replicates

Target	Level	N	Mean Ct	Within Run		Between Run		Between Day		Between Site		Total
				SD	CV (%)	SD	CV (%)	SD	CV (%)	SD	CV (%)	SD	CV (%)
CoV-2	LP	90	33.3	0.74	2.2	0.00	0.0	0.00	0.0	0.54	1.6	0.92	2.8
CoV-2	MP	90	33.0	0.45	1.4	0.08	0.2	0.00	0.0	0.74	2.2	0.87	2.6

For the Lot-to-Lot reproducibility study, one (1) internal site was provided the same panels as described for the Precision study above. Three (3) reagent lots were tested across five (5) distinct days (consecutive or not) on one (1) BD MAX™, wherein each day, two (2) panels were tested by two (2) technologists. Each panel member was tested in three replicates.

The qualitative and quantitative reproducibility is presented below in Table 18 by target analyte. Ct, internal criterion used to determine a final assay result, was selected as an additional means of assessing assay reproducibility. Overall mean Ct values with variance components (SD and %CV) are shown in Table 19.

Table 18. Lot-to-Lot Reproducibility Study Results using Three (3) Lots of the BD Respiratory Viral Panel (Percent Agreement with Expected Results)

Sample Concentration	SARS-CoV-2 (N), 95% CI
Moderate Positive (3x LoD)	99.4%
(179/180), 96.9-99.9
Low Positive (2x LoD)	100%
(180/180), 97.9-100
True Negativea	100%
(360/360), 98.9-100

a For the True Negative category, the reported agreement indicates percent of negative results.

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Table 19. Lot-to-Lot Quantitative Reproducibility Across Operators, Days, Runs, and
Replicates

Target	Level	N	Mean Ct	Lot		Day		Operator		Run		Within Run (Repeatability)		Total
				SD	CV(%)	SD	CV(%)	SD	CV(%)	SD	CV(%)	SD	CV(%)	SD	CV(%)
CoV-2	MP	179	33.7	0.26	0.8	0.06	0.2	0.10	0.3	0.00	0.0	0.61	1.8	0.67	2.0
CoV-2	LP	180	33.9	0.24	0.7	0.18	0.5	0.12	0.3	0.00	0.0	0.64	1.9	0.72	2.1

Linearity

Not applicable. This is a qualitative assay.

Limit of Detection (LoD)

The analytical sensitivity of the BD Respiratory Panel-SCV2 for BD MAX™ System was assessed in both nasopharyngeal and nasal clinical matrices. LoD studies determine the lowest detectable concentration of virus at which approximately 95% of all (true positive) replicates test positive. Analysis of SARS-CoV-2 was completed with a Probit statistical methodology across three (3) reagent lots. Confirmation of the estimated LoD was performed with one reagent lot in replicates of 20 prepared in nasopharyngeal and nasal matrix are reported in Table 20.

					Table 20. BD Respiratory Viral Panel-SCV2 for BD MAX™ System Limit of Detection
--	--	--	--	--	---------------------------------------------------------------------------------

Strain	LoD Concentration (in UVT)
	Nasopharyngeal	Nasal
SARS-CoV-2 (USA-WA1/2020)	700 copies/mL	700 copies/mL

Inclusivity

An in silico alignment of the BD Respiratory Viral Panel - SCV2 primers and probes demonstrated that the performance of the BD Respiratory Viral Panel - SCV2 reagents for the BD MAX™ system is not directly impacted by the presence of mutations in known SARS-CoV-2 viral variants. As of June 10, 2022, BD continues to monitor all lineages and sublineages for the following WHO labeled Variants of Concern, Alpha, Beta, Gamma, Delta, and Mu. In all cases greater than 99% of the sequenced isolates are a perfect match to all primers and probes in either the N1 or N2 set. Given similar performance from both the N1 and N2 channel, either will back up the other in the event of performance degradation through genetic drift. Additionally, BD continues to monitor all lineages of the WHO Omicron label, including sublineages within BA.1, BA.2, BA.2.12.1, BA.3, BA.4, and BA.5. All Omicron genomes contain a mutation that affects the N1 probe 3 bases from the 5' end. (Mutation C28311T). Each Omicron sublineage has a percentage of sequences that are a perfect match to either the N1 or N2 primer-set as follows: BA.1 at 99.47%, BA.2 at 98.95%, BA.2.12.1 at 99.63%, BA.3 at 100%, BA.4 at 96.87% and BA.5 at 99.55%.

BD Respiratory Viral Panel-SCV2 for BD MAX™ System was evaluated against multiple strains of SARS-CoV-2. A total of 11 SARS-CoV-2 strains were evaluated at levels near the analytical LoD. Three replicates were tested for each strain, refer to Table 21.

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| Virus | Strain | Source | Concentration
Detected | Relative
LoD | Positive
Results/Total |
|----------------|------------------------------------------------------------|-------------------------|---------------------------|-----------------|---------------------------|
| SARS-
CoV-2 | Hong Kong /
VM200001061/2020 | ZeptoMetrix 0810590CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Italy-INMI1 | ZeptoMetrix 0810589CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Alpha, (B.1.1.7) USA /
CA CDC 5574/2020 | ZeptoMetrix 0810612CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Alpha, (B.1.1.7)
England/204820464/2020 | ZeptoMetrix 0810614CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Beta, (B.1.351) South Africa
/ KRISP-K005325/2020 | ZeptoMetrix 0810613CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Kappa, (B.1.617.1) USA /
CA-Stanford-15 S02/2021 | ZeptoMetrix 0810623CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Gamma, (P1) Japan / TY7-
503/2021 | ZeptoMetrix 0810616CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Delta, (B.1.617.2) USA /
PHC658/2021 | ZeptoMetrix 0810624CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Iota, (B.1.526_2021) NY-
Wadsworth-21025952-
01/2021 | ZeptoMetrix 0810619CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Zeta, (P2_2021) NY-
Wadsworth-21006055-
01/2021 | ZeptoMetrix 0810618CFHI | 2100 copies/mL | 3x LoD | 3/3 |
| | Omicron (BA.1) USA/GA-
EHC- 2811C/2021 | ATCC VR-3347HK | 2100 copies/mL | 3x LoD | 3/3 |

Table 21. Analytical Reactivity/Inclusivity for the BD Respiratory Viral Panel-SCV2 for the BD MAX™ System

Assay Measuring Range

Not applicable. This is a qualitative assay.

Interfering Substances

Twenty-four (24) biological and chemical substances that may be present in nasopharyngeal or anterior nasal swab specimens were evaluated for potential interference with the BD Respiratory Viral Panel-SCV2 for BD MAX™ System using simulated nasopharyngeal matrix. Whole blood (human) was found to interfere at levels above 0.2% volume/volume. Results demonstrated no reportable interference from any other substance tested at the reported clinically relevant concentrations (refer to Table 22).

35

| Substance | Active Ingredient | Concentration
Tested | SARS-CoV-2
Positive Testing
(Positive/Total) | Negative
Testing
(Negative/Total) | Result |
|------------------------------------|-------------------------------------------------|-------------------------|----------------------------------------------------|-----------------------------------------|--------|
| Oral anesthetic
and analgesic | Benzocaine
Menthol | 0.8 mg/mL | 3/3 | 3/3 | NI |
| Biologicals | Purified Mucin | 60 µg/mL | 3/3 | 3/3 | NI |
| | Whole Blood
(human) | 2% v/v | 1/3 | 3/3 | I |
| | Leukocytes | 0.2% v/v | 3/3 | 3/3 | NI |
| | Leukocytes | 2% v/v | 3/3 | 3/3 | NI |
| FluMist
Quadrivalent
Vaccine | Live, attenuated Flu
A and Flu B strains | 6.67% v/v | 3/3 | 3/3 | NI |
| Nasal
Sprays/Drops | Zinc | 1 mg/mL | 3/3 | 3/3 | NI |
| | Phenylephrine | 5% v/v | 3/3 | 3/3 | NI |
| | Oxymetazoline | 5% v/v | 3/3 | 3/3 | NI |
| | Sodium Chloride
with preservatives | 5% v/v | 3/3 | 3/3 | NI |
| Corticosteroids | Beclomethasone | 17% v/v | 3/3 | 3/3 | NI |
| | Dexamethasone | 17% v/v | 3/3 | 3/3 | NI |
| | Flunisolide | 17% v/v | 3/3 | 3/3 | NI |
| | Triamcinolone | 17% v/v | 3/3 | 3/3 | NI |
| | Budesonide | 17% v/v | 3/3 | 3/3 | NI |
| | Mometasone | 17% v/v | 3/3 | 3/3 | NI |
| | Fluticasone | 17% v/v | 3/3 | 3/3 | NI |
| Nasal Gel | Luffa operculata
Sulfur | | | | |
| Homeopathic
Allergy Relief | Galphimia glauca
Histaminum
hydrocloricum | 5% v/v | 3/3 | 3/3 | NI |
| Antiviral Drug | Zanamivir | 3.3 mg/mL | 3/3 | 3/3 | NI |
| Antibiotic | Mupirocin | 10 mg/mL | 3/3 | 3/3 | NI |
| Antibacterial | Tobramycin | 4 µg/mL | 3/3 | 3/3 | NI |

Table 22. Endogenous and Commercial Exogenous Substances Tested with BD Respiratory Viral Panel-SCV2 for the BD MAX™ System

Cross-Reactivity

An in silico analysis was performed to evaluate the potential for all primers and probes contained within the BD Respiratory Viral Panel-SCV2 for BD MAX™ System master mix to amplify and detect unintended organisms. Each primer was 'BLAST' against the full nt database and alignments were kept if there were no more than three (3) base pair mismatches across the length of the primer, the 3' end of the primer matched the subject sequence, and no gaps were introduced to "force" an alignment. The plus/minus orientation between the primer (query) and the subject (database sequence) was determined, and all two-primer combinations (including each primer with itself) were identified where one primer matched the plus strand and the other matched the minus, representing potential amplicons. Amplicons were kept if

36

the minus strand primer was downstream of the plus strand primer and the resulting amplicons were less than or equal to 3,000 base pairs long.

SARS-CoV-2: All identified hits are either SARS-CoV-2 or a closely related coronavirus from non-human species. No relevant cross-reactivity was discovered.

Additionally, fifty-two (52) organisms and one (1) nasopharyngeal pool were evaluated for cross-reactivity with the BD Respiratory Viral Panel-SCV2 for BD MAX™ System. The bacterial cells, yeasts, and viruses were tested in the BD Molecular RVP Sample Buffer Tube. All organisms tested produced negative results when tested at the concentration listed in Table 23.

| Organism | Source | Concentration Tested | Negative Results
Obtained (Negative
Result/Total) |
|------------------------------------|------------------------|----------------------|---------------------------------------------------------|
| Adenovirus - Type 1 | ZeptoMetrix® 0810050CF | 1.00E+05 TCID50/mL | 3/3 |
| Adenovirus - Type 4 | ZeptoMetrix® 0810070CF | 1.00E+05 TCID50/mL | 3/3 |
| Adenovirus - Type 7 | ZeptoMetrix® 0810021CF | 1.00E+05 TCID50/mL | 3/3 |
| Aspergillus flavus | ZeptoMetrix® 0801598 | 1.00E+06 CFU/mL | 3/3 |
| Aspergillus fumigatus | ZeptoMetrix® 0801716 | 1.00E+06 CFU/mL | 3/3 |
| Aspergillus terreus | ZeptoMetrix® 0801827 | 1.00E+06 CFU/mL | 3/3 |
| Aspergillus niger | ZeptoMetrix® 0801601 | 1.00E+06 CFU/mL | 3/3 |
| Bordetella pertussis | ZeptoMetrix® 0801459 | 1.00E+06 CFU/mL | 3/3 |
| Bordetella parapertussis | ZeptoMetrix® 0801461 | 1.00E+06 CFU/mL | 3/3 |
| Candida albicans | ATCC® 18804 | 1.00E+06 CFU/mL | 3/3 |
| Chlamydophila pneumoniae | ATCC® 53592 | 1.00E+06 IFU/mL | 3/3 |
| Corynebacterium diphtheriae | ZeptoMetrix® 0801882 | 1.00E+06 CFU/mL | 3/3 |
| Cytomegalovirus | ZeptoMetrix® 0810003CF | 1.00E+05 copies/mL | 3/3 |
| Enterovirus B (Echovirus 6) | ZeptoMetrix® 0810076CF | 1.00E+05 units/mL | 3/3 |
| Enterovirus C (Coxsackievirus A16) | ZeptoMetrix® 0810107CF | 1.00E+05 TCID50/mL | 3/3 |
| Enterovirus D68 | ZeptoMetrix® 0810237CF | 1.00E+05 TCID50/mL | 3/3 |
| Epstein Barr virus | ZeptoMetrix® 0810008CF | 1.00E+05 copies/mL | 3/3 |
| Escherichia coli | ATCC® 35401 | 1.00E+06 CFU/mL | 3/3 |
| Fusobacterium necrophorum | ATCC® 25286 | 1.00E+06 CFU/mL | 3/3 |
| Haemophilus influenzae | ZeptoMetrix® 0801679 | 1.00E+06 CFU/mL | 3/3 |
| Herpes simplex virus Type 1 | ZeptoMetrix® 0810005CF | 1.00E+05 TCID50/mL | 3/3 |
| Herpes simplex virus Type 2 | ZeptoMetrix® 0810006CF | 1.00E+05 TCID50/mL | 3/3 |
| Human coronavirus 229E | ATCC® VR-740 | 1.00E+05 TCID50/mL | 3/3 |
| Human coronavirus HKU1a | ATCC® VR-3262SD | 1.00E+05 GC/mL | 3/3 |
| Human coronavirus NL63 | ZeptoMetrix® 0810228CF | 1.00E+07 copies/mL | 3/3 |
| Human coronavirus OC43 | ZeptoMetrix® 0810024CF | 1.00E+05 TCID50/mL | 3/3 |
| Human Metapneumovirus | ZeptoMetrix® 0810161CF | 1.00E+05 TCID50/mL | 3/3 |
| Influenza A | ZeptoMetrix® 0810244CF | 1.00E+06 copies/mL | 3/3 |
| Influenza B | ZeptoMetrix® 0810515CF | 1.00E+06 copies/mL | 3/3 |

Table 23. BD Respiratory Viral Panel-SCV2 for the BD MAX™ System Cross-Reactivity Results

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| Organism | Source | Concentration Tested | Negative Results
Obtained (Negative
Result/Total) |
|----------------------------------------------------------|-----------------------------|----------------------|---------------------------------------------------------|
| Lactobacillus acidophilus | ATCC® 4356 | 1.00E+06 CFU/mL | 3/3 |
| Legionella pneumophila | ATCC® 33152 | 1.00E+06 CFU/mL | 3/3 |
| Measles | ZeptoMetrix® 0810025CF | 1.00E+05 TCID50/mL | 3/3 |
| MERS-coronavirus | ZeptoMetrix®
0810228CFHI | 1.00E+07 copies/mL | 3/3 |
| Moraxella catarrhalis | ZeptoMetrix® 0801509 | 1.00E+06 CFU/mL | 3/3 |
| Mumps | ZeptoMetrix® 0810079CF | 1.00E+05 TCID50/mL | 3/3 |
| Mycobacterium tuberculosisa | ATCC® 25177DQ | 1.00E+06 copies/mL | 3/3 |
| Mycoplasma genitalium | ATCC® 33530 | 1.00E+06 cells/mL | 3/3 |
| Mycoplasma pneumoniae | ATCC® 15531-TTR | 1.00E+06 CFU/mL | 3/3 |
| Neisseria meningitidis | ATCC® 13077 | 1.00E+06 CFU/mL | 3/3 |
| Neisseria gonorrhoeae | ATCC® 19424 | 1.00E+06 CFU/mL | 3/3 |
| Parainfluenza virus 1 | ZeptoMetrix® 0810014CF | 1.00E+05 TCID50/mL | 3/3 |
| Parainfluenza virus 2 | ZeptoMetrix® 0810504CF | 2.12E+05 TCID50/mL | 3/3 |
| Parainfluenza virus 3 | ZeptoMetrix® 0810016CF | 1.00E+05 TCID50/mL | 3/3 |
| Parainfluenza virus 4 | ZeptoMetrix®
0810060BCF | 1.00E+05 TCID50/mL | 3/3 |
| Pneumocystis jirovecii | ATCC® PRA-159 | 1.00E+06 cells/mL | 3/3 |
| Expressed and pooled human
nasopharyngeal swab matrix | Internal | n/a | 3/3 |
| Pseudomonas aeruginosa | ATCC® 10145 | 1.00E+06 CFU/mL | 3/3 |
| Respiratory syncytial virus | ZeptoMetrix®
0810040CFA | 1.00E+06 copies/mL | 3/3 |
| Rhinovirus | ZeptoMetrix® 0810284CF | 1.00E+05 TCID50/mL | 3/3 |
| SARS-Coronavirusa | ATCC® VR-3280SD | 1.00E+05 GE/mL | 3/3 |
| Staphylococcus aureus | ATCC® 43300 | 1.00E+06 CFU/mL | 3/3 |
| Staphylococcus epidermis | ATCC® 12228 | 1.00E+06 CFU/mL | 3/3 |
| Streptococcus pneumoniae | ZeptoMetrix® 0804222 | 1.00E+06 CFU/mL | 3/3 |
| Streptococcus pyogenes | ATCC® 49399 | 1.00E+06 CFU/mL | 3/3 |
| Streptococcus salivarius | ZeptoMetrix® 0801896 | 1.00E+06 CFU/mL | 3/3 |
| Varicella-zoster virus | ZeptoMetrix® 0810167CF | 1.00E+07 copies/mL | 3/3 |
| Organism | Source | Concentration Tested | Positive / Total
SARS-CoV-2 |
| Adenovirus - Type 1 | ZeptoMetrix® 0810050CF | 1.00E+05 TCID50/mL | 3/3 |
| Adenovirus - Type 4 | ZeptoMetrix® 0810070CF | 1.00E+05 TCID50/mL | 3/3 |
| Adenovirus - Type 7 | ZeptoMetrix® 0810021CF | 1.00E+05 TCID50/mL | 3/3 |
| Aspergillus flavus | ZeptoMetrix® 0801598 | 1.00E+06 CFU/mL | 3/3 |
| Aspergillus fumigatus | ZeptoMetrix® 0801716 | 1.00E+06 CFU/mL | 3/3 |
| Aspergillus terreus | ZeptoMetrix® 0801827 | 1.00E+06 CFU/mL | 3/3 |
| Aspergillus niger | ZeptoMetrix® 0801601 | 1.00E+06 CFU/mL | 3/3 |
| Bordetella pertussis | ZeptoMetrix® 0801459 | 1.00E+06 CFU/mL | 3/3 |
| Bordetella parapertussis | ZeptoMetrix® 0801461 | 1.00E+06 CFU/mL | 3/3 |
| Candida albicans | ATCC® 18804 | 1.00E+06 CFU/mL | 3/3 |
| Chlamydophila pneumoniae | ATCC® 53592 | 1.00E+06 IFU/mL | 3/3 |
| Corynebacterium diphtheriae | ZeptoMetrix® 0801882 | 1.00E+06 CFU/mL | 3/3 |
| Cytomegalovirus | ZeptoMetrix® 0810003CF | 1.00E+05 copies/mL | 3/3 |
| Enterovirus B (Echovirus 6) | ZeptoMetrix® 0810076CF | 1.00E+05 units/mL | 3/3 |
| Enterovirus C
(Coxsackievirus A16) | ZeptoMetrix® 0810107CF | 1.00E+05 TCID50/mL | 3/3 |
| Enterovirus D68 | ZeptoMetrix® 0810237CF | 1.00E+05 TCID50/mL | 3/3 |
| Epstein Barr virus | ZeptoMetrix® 0810008CF | 1.00E+05 copies/mL | 3/3 |
| Escherichia coli | ATCC® 35401 | 1.00E+06 CFU/mL | 3/3 |
| Fusobacterium necrophorum | ATCC® 25286 | 1.00E+06 CFU/mL | 3/3 |
| Haemophilus influenzae | ZeptoMetrix® 0801679 | 1.00E+06 CFU/mL | 3/3 |
| Herpes simplex virus Type 1 | ZeptoMetrix® 0810005CF | 1.00E+05 TCID50/mL | 3/3 |
| Herpes simplex virus Type 2 | ZeptoMetrix® 0810006CF | 1.00E+05 TCID50/mL | 3/3 |
| Human coronavirus 229E | ATCC® VR-740 | 1.00E+05 TCID50/mL | 3/3 |
| Human coronavirus HKU1a | ATCC® VR-3262SD | 1.00E+05 GC/mL | 3/3 |
| Human coronavirus NL63 | ZeptoMetrix® 0810228CF | 1.00E+07 copies/mL | 3/3 |
| Human coronavirus OC43 | ZeptoMetrix® 0810024CF | 1.00E+05 TCID50/mL | 3/3 |
| Human Metapneumovirus | ZeptoMetrix® 0810161CF | 1.00E+05 TCID50/mL | 3/3 |
| Influenza A | ZeptoMetrix® 0810244CF | 1.00E+06 copies/mL | 20/20 |
| Influenza B | ZeptoMetrix® 0810515CF | 1.00E+06 copies/mL | 20/20 |
| Lactobacillus acidophilus | ATCC® 4356 | 1.00E+06 CFU/mL | 3/3 |
| Legionella pneumophila | ATCC® 33152 | 1.00E+06 CFU/mL | 3/3 |
| Measles | ZeptoMetrix® 0810025CF | 1.00E+05 TCID50/mL | 3/3 |
| MERS-coronavirus | ZeptoMetrix®
0810228CFHI | 1.00E+07 copies/mL | 3/3 |
| Moraxella catarrhalis | ZeptoMetrix® 0801509 | 1.00E+06 CFU/mL | 3/3 |
| Mumps | ZeptoMetrix® 0810079CF | 1.00E+05 TCID50/mL | 3/3 |
| Mycobacterium
tuberculosisa | ATCC® 25177DQ | 1.00E+06 copies/mL | 3/3 |
| Mycoplasma genitalium | ATCC® 33530 | 1.00E+06 cells/mL | 3/3 |
| Mycoplasma pneumoniae | ATCC® 15531-TTR | 1.00E+06 CFU/mL | 3/3 |
| Neisseria meningitidis | ATCC® 13077 | 1.00E+06 CFU/mL | 3/3 |
| Organism | Source | Concentration Tested | Positive / Total
SARS-CoV-2 |
| Parainfluenza virus 1 | ZeptoMetrix® 0810014CF | 1.00E+05 TCID50/mL | 3/3 |
| Parainfluenza virus 2 | ZeptoMetrix® 0810504CF | 2.12E+05 TCID50/mL | 3/3 |
| Parainfluenza virus 3 | ZeptoMetrix® 0810016CF | 1.00E+05 TCID50/mL | 3/3 |
| Parainfluenza virus 4 | ZeptoMetrix® 0810060BCF | 1.00E+05 TCID50/mL | 3/3 |
| Pneumocystis jirovecii | ATCC® PRA-159 | 1.00E+06 cells/mL | 3/3 |
| Pooled human expressed
nasopharyngeal swab matrix | Internal | n/a | 3/3 |
| Pseudomonas aeruginosa | ATCC® 10145 | 1.00E+06 CFU/mL | 3/3 |
| Respiratory syncytial virus | ZeptoMetrix® 0810040CFA | 1.00E+06 copies/mL | 20/20 |
| Rhinovirus | ZeptoMetrix® 0810284CF | 1.00E+05 TCID50/mL | 3/3 |
| SARS-Coronavirusa | ATCC® VR-3280SD | 1.00E+05 GE /mL | 3/3 |
| Staphylococcus aureus | ATCC® 43300 | 1.00E+06 CFU/mL | 3/3 |
| Staphylococcus epidermis | ATCC® 12228 | 1.00E+06 CFU/mL | 3/3 |
| Streptococcus pneumoniae | ZeptoMetrix® 0804222 | 1.00E+06 CFU/mL | 3/3 |
| Streptococcus pyogenes | ATCC® 49399 | 1.00E+06 CFU/mL | 3/3 |
| Streptococcus salivarius | ZeptoMetrix® 0801896 | 1.00E+06 CFU/mL | 3/3 |
| Varicella-zoster virus | ZeptoMetrix® 0810167CF | 1.00E+07 copies/mL | 3/3 |

a Genomic DNA or RNA tested.

Microbial Interference

Fifty-two (52) organisms and one (1) nasopharyngeal pool were evaluated for potential interference with the BD Respiratory Viral Panel-SCV2 for BD MAX™ System. Organisms were tested at high concentration (≥106 CFU/mL, cells/mL, genome equivalents/mL, ≥105 IFU/mL or TCIDso/mL, or highest concentration available) in the presence of SARS-CoV-2 spiked at 3x LoD, refer to Table 24.

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Table 24. Microbial Interference Testing Results for the BD Respiratory Viral Panel-SCV2 for the BD MAX™ System

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a Genomic DNA or RNA tested

Sample Stability

BD Respiratory Viral Panel-SCV2 for BD MAX™ System stability for SARS-CoV-2 in nasopharyngeal matrix and in anterior nasal swab matrix expressed in UVT/UTM (neat) as well both post transfer of UVT/UTM matrix into sample buffer tubes (nested) was evaluated. Specimens were constructed using clinical nasopharyngeal or anterior nasal matrix spiked at 3X LoD. Refer to Table 25 for the BD Respiratory Viral Panel-SCV2 Assay for BD MAX™ System Specimen Stability.

Table 25. BD Respiratory Viral Panel-SCV2 Assay for BD MAX™ System Specimen Stability

Specimen Stability	Temperature	Duration
In UVT/UTM	25 ± 2 °C	48 hours
	2–8 °C	72 hours
In BD Molecular RVP Sample Buffer Tube	25 ± 2 °C	48 hours
	2–8 °C	120 hours

Assay Cut-Off

The assay cut-off for the BD Respiratory Viral Panel-SCV2 for BD MAX™ was established based on PCR based metrics taken together by the BD MAX software algorithm to make the qualitative decision whether a curve is to be considered positive or negative. These metrics (e.g., Ct. RFU endpoints, signal-to-noise ratios) are initially set by default parameters defined by the instrument. As the product undergoes product development, the data is supplemented, and the algorithm is adjusted ("trained") using viral cultures spiked into clinical background matrices at levels

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surrounding the limit of detection and expected clinical range. In conclusion, testing of clinical specimens were used to confirm adequate separation between the value observed in positive specimens in each target detection channel and the assay cutoff.

Matrix Equivalency

Equivalence between nasopharyngeal swab, nasal swab, and simulated nasopharyngeal matrix was evaluated using heat inactivated SARS-CoV-2 (USA-WA/2020 strain) spiked into negative nasopharyngeal, nasal and simulated matrix to prepare contrived low positive (approximately 2x LoD) and moderate positive (approximately 5x LoD) samples for each sample type. A total of thirty (30) low positive, fifteen (15) moderate positive, and fifteen (15) negative samples were tested.

Fresh vs Frozen

A study was performed with the BD Respiratory Viral Panel-SCV2 for BD MAX™ System using fresh and frozen nasopharyngeal swabs which showed that there were no adverse effects from freezing and thawing of specimens. The data generated are considered acceptable to support testing of archived, frozen specimens in the Clinical Study to evaluate the performance of the BD Respiratory Viral Panel-SCV2 for BD MAX™ System.

Carryover / Cross-Contamination

A study was conducted to investigate within-run carryover and between-run carryover while processing samples with high viral load of SARS-CoV-2 in the BD Respiratory Viral Panel -SCV2. High positive samples contained heat inactivated SARS-CoV-2 spiked into pooled nasal swab matrix at a concentration of ≥1.94E+07 copies/mL. The negative samples consisted of simulated nasopharyngeal matrix without any target analyte. Twelve (12) replicates of the high positive panel member and 12 replicates of the negative panel member were tested in nine (9) runs by alternating negative and positive samples, using three BD MAX™ Systems or a total of 108 positive and 108 negative samples tested. Of the 108 negative samples tested, one (1) false positive result was obtained (0.93%, 95% CI: 0.16-5.06%).

Expected Values

In the BD Respiratory Viral Panel-SCV2 for BD MAX™ System clinical study, reportable results from specimens compliant at the specimen and PCR levels were obtained from 8 geographically diverse sites. Nasopharyngeal and nasal specimens totaled 1.566 respectively. The number and percentage of positive cases per target, as determined by BD Respiratory Viral Panel-SCV2 for BD MAXTM System, are presented in Table 26.

Table 26. BD Respiratory Viral Panel-SCV2 for BD MAX™ System Positivity Rate per Specimen Type

Analyte	Nasopharyngeal	Nasal
SARS-CoV-2	34.6% (541/1562)	32.2% (504/1566)

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External Control Validation

Assay run controls are not provided as part of the BD Respiratory Viral Panel-SCV2 for BD MAX™ System. BD recommends the use of Microbiologics controls. Studies have been performed to verify the use of Microbiologics Helix Elite™ Molecular Standards with the BD Respiratory Viral Panel-SCV2 for BD MAX™ System. The combination of Microbiologics SARS-CoV-2 Positive Control as positive external control. Microbiologics Negative Cellularity Control (NCC) will be used as the external negative control.

Usability Study

A usability study has been performed to determine whether a representative sample of untrained professionals could correctly prepare samples for the BD MAX Respiratory Viral Panel for BD MAX™ System. The participants were presentative mock sample, and all other materials required to process the mock sample. They were asked to go through simulating the assay preparation and perform every step as realistically as possible. The use scenario being studied in this evaluation was the expected use scenario that an intended user would go through when preparing samples for molecular assays in a clinical environment. The study demonstrated usability with the target user population for safe and effective use of the product.

Clinical Performance Evaluation

BD Respiratory Viral Panel for BD MAX™ System Clinical Summary:

The performance of the BD Respiratory Viral Panel for BD MAX™ System was evaluated in comparison to a composite method of two out of three highly sensitive molecular assays (NAATS) that are FDA authorized under EUA for SARS-CoV-2. Any specimen that tested positive by two EUA assays was considered positive for SARS-CoV-2, whereas any specimen that tested negative by two EUA assays was considered negative. For influenza B, and RSV, the performance of the BD Respiratory Viral Panel for BD MAX™ System was evaluated in comparison to an FDA-cleared high sensitivity RT-PCR assay.

Prospective Clinical Evaluation

Clinical performance characteristics of the BD Respiratory Viral Panel for BD MAX™ System were established during a multi-center study where subjects were prospectively enrolled at six geographically distinct U.S. study sites and two geographically distinct sites in Europe from January up to August 2022. Four sites performed BD Respiratory Viral Panel for BD MAX™ System testing and/or reference method testing. For consented adult or pediatric subjects presenting with symptoms of respiratory viral infection, one nasopharyngeal swab and/or one nasal swab were collected and placed in validated transport medium. From a total of 2,005 subjects enrolled, 1562 nasopharyngeal swabs and 1566 nasal swabs were included in the performance calculations. Between January and beginning of April 2022, specimens were prospectively collected from all comers meeting the study eligibility criteria and immediately frozen for later testing as prospective archived/frozen (Category II) specimens. Between mid-April up to August 2022, specimens were prospectively collected from all comers meeting the eligibility criteria and

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tested fresh as prospective fresh (Category I). For nasopharyngeal specimens, the numbers of compliant specimens with reportable comparator and BD Respiratory Viral Panel for BD MAX™ System were 1,545 for SARS-CoV-2 and 1,562 for Flu A, Flu B, and RSV. For nasal specimens, the numbers of compliant specimens with reportable comparator and BD Respiratory Viral Panel for BD MAX™ System were 1,561 for SARS-CoV-2 and 1,564 for Flu A, Flu B, and RSV. Table 27 provides a summary of demographic and vaccination information for the 1562 nasopharyngeal swabs and 1566 nasal swabs included in the performance calculations.

| Demographics and

Vaccination	Characteristics	NP (N=1562)	NS (N=1566)
Gender	Female	61.7% (963/1562)	61.6% (964/1566)
	Male	38.3% (599/1562)	38.4% (602/1566)
Age Group	0 - 5 years	1.3% (20/1562)	1.3% (20/1566)
	6 - 21 years	10.2% (159/1562)	10.2% (160/1566)
	22 - 59 years	57.5% (898/1562)	57.4% (899/1566)
	> 59 years	31.0% (485/1562)	31.1% (487/1566)
Patient Population	Outpatient	95.9%
(1498/1562)	95.8%
(1500/1566)
	Hospitalized	3.1% (48/1562)	3.1% (49/1566)
	Emergency	1.0% (15/1562)	1.0% (16/1566)
	Unknown	0.1% (1/1562)	0.1% (1/1566)
Immuno-compromised	Yes	3.3% (51/1562)	3.3% (51/1566)
	No	95.0%
(1484/1562)	95.0%
(1488/1566)
	Unknown	1.7% (27/1562)	1.7% (27/1566)
Received Flu Vaccine	No	72.5%
(1132/1562)	72.6%
(1137/1566)
	Yes	27.5% (430/1562)	27.4% (429/1566)
Received COVID-19
Vaccine	No	25.3% (395/1562)	25.5% (399/1566)
	Yes	74.7%
(1167/1562)	74.5%
(1167/1566)
Number of COVID-19
Vaccine Doses	1	4.9% (77/1562)	5.0% (78/1566)
	2	35.3% (552/1562)	35.2% (551/1566)
	3	31.6% (494/1562)	31.5% (494/1566)
	4	2.8% (44/1562)	2.8% (44/1566)

Demographic and Vaccination Summary for Prospective BD Respiratory Table 2. Viral Panel for BD MAX™ System Clinical Evaluation

The BD Respiratory Viral Panel for BD MAX™ System prospective nasopharyngeal swab specimens testing performance data against comparator methods are provided in Table 28 by analyte.

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| Analyte | Sample
Type | Positive Percent Agreement | | Negative Percent Agreement | |
|-------------|----------------|----------------------------------|-----------------|----------------------------|-----------------|
| | | % (TP/(TP+FN)) | 95% CI | % (TN/(TN + FP)) | 95% CI |
| SARS-CoV-2a | Fresh | 99.5% (370/372) | (98.1%, 99.9%) | 98.8% (641/649) | (97.6%, 99.4%) |
| | Frozen | 97.4% (147/151) | (93.4%, 99.0%) | 96.0% (358/373) | (93.5%, 97.5%) |
| | Overall | 98.9% (517/523) | (97.5%, 99.5%) | 97.7% (999/1022) | (96.6%, 98.5%) |
| Flu Ab | Fresh | 96.7% (58/60) | (88.6%, 99.1%) | 99.3% (955/962) | (98.5%, 99.6%) |
| | Frozen | 100.0% (1/1) | (20.7%, 100.0%) | 100.0% (539/539) | (99.3%, 100.0%) |
| | Overall | 96.7% (59/61) | (88.8%, 99.1%) | 99.5% (1494/1501) | (99.0%, 99.8%) |
| Flu Bc | Fresh | No data for PPA rate calculation | | 99.9% (1021/1022) | (99.4%, 100.0%) |
| | Frozen | No data for PPA rate calculation | | 100.0% (540/540) | (99.3%, 100.0%) |
| | Overall | No data for PPA rate calculation | | 99.9% (1561/1562) | (99.6%, 100.0%) |
| RSV | Fresh | 100.0% (11/11) | (74.1%, 100.0%) | 100.0% (1011/1011) | (99.6%, 100.0%) |
| | Frozen | 100.0% (1/1) | (20.7%, 100.0%) | 100.0% (539/539) | (99.3%, 100.0%) |
| | Overall | 100.0% (12/12) | (75.8%, 100.0%) | 100.0% (1550/1550) | (99.8%, 100.0%) |

Table 28. BD Respiratory Viral Panel for BD MAX™ System Clinical Performance Summary in Prospectively Collected Nasopharyngeal Swab Specimens

a SARS-CoV-2 was detected in 3/6 FN specimens with all three composite comparator methods. SARS-CoV-2 was detected in 15/23 FP specimens with one of the three composite comparator methods.

b Tu A was detected in both FN specimens when tested with an independent mothod. Flu A was detected in 3/7 FP specimens when tested with an independent molecular method. Flu A was Equivocal in 1/7 FP specimens when tested with an independent method.

·Flu B was not detected in the single FP specimen when tested with an independent molecular method.

The BD Respiratory Viral Panel for BD MAX™ System prospective anterior nasal swab specimens testing performance data against comparator methods are provided in Table 29 by analyte.

		Positive Percent Agreement		Negative Percent Agreement
Analyte	Sample Type	% (TP/(TP+FN))	95% CI	% (TN/(TN + FP))	95% CI
SARS-CoV-2a	Fresh	98.8% (340/344)	(97.0%, 99.5%)	98.2% (665/677)	(96.9%, 99.0%)
	Frozen	97.2% (138/142)	(93.0%, 98.9%)	96.7% (385/398)	(94.5%, 98.1%)
	Overall	98.4% (478/486)	(96.8%, 99.2%)	97.7% (1050/1075)	(96.6%, 98.4%)
Flu Ab	Fresh	96.8% (61/63)	(89.1%, 99.1%)	99.6% (958/962)	(98.9%, 99.8%)
	Frozen	100.0% (1/1)	(20.7%, 100.0%)	100.0% (538/538)	(99.3%, 100.0%)
	Overall	96.9% (62/64)	(89.3%, 99.1%)	99.7% (1496/1500)	(99.3%, 99.9%)
Flu B	Fresh	No data for PPA rate calculation		100.0% (1025/1025)	(99.6%, 100.0%)
	Frozen	No data for PPA rate calculation		100.0% (539/539)	(99.3%, 100.0%)
	Overall	No data for PPA rate calculation		100.0% (1564/1564)	(99.8%, 100.0%)
RSVc	Fresh	100.0% (11/11)	(74.1%, 100.0%)	99.9% (1013/1014)	(99.4%, 100.0%)
	Frozen	0.0% (0/1)	(0.0%, 79.3%)	100.0% (538/538)	(99.3%, 100.0%)
	Overall	91.7% (11/12)	(64.6%, 98.5%)	99.9% (1551/1552)	(99.6%, 100.0%)

Table 29. BD Respiratory Viral Panel for BD MAX™ System Clinical Performance
Summary in Prospectively Collected Anterior Nasal Swab Specimens

a SARS-CoV-2 was detected in 2/8 FN specimens with all three composite comparator methods. SARS-CoV-2 was detected in 17/25 FP specimens with one of the three composite comparator methods.

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bFlu A was not detected in both FN specimens when tested with an independent mothod. Flu A was detected in 1/4 FP specimens when tested with an independent molecular method.

'RSV was detected in the single FN specimen when tested with an independent molecular method. RSV was detected in the single FP specimen when tested with an independent molecular method.

Retrospective Clinical Evaluation

Clinical performance characteristics of the BD Respiratory Viral Panel for BD MAX™ System were determined from a total of 240 frozen retrospective nasopharyngeal swabs in UVT/UTM obtained from two (2) external sources with historical positive or negative results for either influenza B or RSV. The specimens were collected as part of routine patient care between December 2019 and January 2022. All the specimens were tested in a blinded and randomized fashion with the BD Respiratory Viral Panel for BD MAX™ System at three different testing sites and reference method (RM) at one testing site. The RM for influenza B, and RSV was an FDAcleared high sensitivity RT-PCR assay. Table 30 provides a summary of demographic information for the 240 retrospective nasopharyngeal samples.

Demographics	Characteristics	Total (N=240)
Gender	Female	37.5% (90/240)
	Male	37.5% (90/240)
	Unknown	25.0% (60/240)
Age Group	0 - 5 years	26.7% (64/240)
	6 - 21 years	20.8% (50/240)
	22 - 59 years	32.5% (78/240)
	> 59 years	20.0% (48/240)

Table 30. Demographic Summary for Retrospective BD Respiratory Viral Panel for BD MAXTM System Clinical Evaluation: Nasopharyngeal Swab Samples

Table 31 describes the performance characteristics of the BD Respiratory Viral Panel for BD MAXTM System that were observed during the clinical evaluation.

Table 31. BD Respiratory Viral Panel for BD MAX™ System Clinical Performance Summary in Retrospective Nasopharyngeal Swab Specimens

	Positive Percent Agreement		Negative Percent Agreement
Analyte	% (TP/(TP+FN))	95% CI	% (TN/(TN + FP))	95% CI
Flu Ba	100.0% (58/58)	(93.8%, 100.0%)	98.9% (180/182)	(96.1%, 99.7%)
RSVb	98.4% (62/63)	(91.5%, 99.7%)	100.0% (177/177)	(97.9%, 100.0%)

a Influenza B was detected in 1/2 FP when tested with an independent molecular method.

bRSV was detected in the single FN when tested with an independent molecular method.

Clinical performance characteristics of the BD Respiratory Viral Panel for BD MAX™ System were determined from a total of 187 frozen retrospective nasal swabs in UVT/UTM obtained from six (6) external sources with historical positive or negative results for either influenza B or RSV. Specimens were collected between February 2021 and February 2023. All the specimens were tested in a blinded and randomized fashion with the BD Respiratory Viral Panel for BD MAX™ System at four different testing sites and reference method (RM) at one testing site. The RM for

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influenza B, and RSV was an FDA-cleared high sensitivity RT-PCR assay. Table 32 provides a summary of demographic information for the 187 retrospective nasal samples.

Table 32: Demographic Summary for Retrospective BD Respiratory Viral Panel for BD
MAXTM System Clinical Evaluation: Nasal Swab Samples

Demographics	Characteristics	Total (N=187)
Gender	Female	50.8% (95/187)
	Male	49.2% (92/187)
Age Group	0 - 5 years	8.6% (16/187)
	6 - 21 years	16.0% (30/187)
	22 - 59 years	62.0% (116/187)
	> 59 years	13.4% (25/187)

One (1) specimen generated an Unresolved (UNR) assay result for both Flu B and RSV and was excluded from the performance analysis. Table 33 describes the performance characteristics of the BD Respiratory Viral Panel for BD MAXTM System that were observed during the clinical evaluation.

Table 33: BD Respiratory Viral Panel for BD MAX™ System Clinical Performance Summary in Retrospective Nasal Swab Specimens

Analyte	Positive Percent Agreement		Negative Percent Agreement
	% (TP/(TP+FN))	95% CI	% (TN/(TN + FP))	95% CI
Flu Ba	100.0% (12/12)	(75.8%, 100.0%)	98.9% (172/174)	(95.9%, 99.7%)
RSVb	100.0% (15/15)	(79.6%, 100.0%)	99.4% (170/171)	(96.8%, 99.9%)

4 Influenza B was detected in 2/2 FP when tested with an independent molecular method.

*Five of 20 RSV positive archived samples by the source laboratory were not confirmed by the comparator method. RSV was not detected in the single FN when tested with an independent molecular method.

Non-Reportable Rate

Of all the specimens initially evaluated with the BD Respiratory Viral Panel for BD MAX™ System Clinical, the initial total rates of non-reportable results were 0.9% and 1.1% for

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nasopharyngeal and nasal specimens, respectively. Following a valid repeat, 0.1% remained nonreportable for both specimen types. Results are shown in Table 34.

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Table 34. Non-Reportable Rates

| Sample Type | Unresolved (UNR) Rate | | Indeterminate (IND) Rate | | Incomplete (INC) Rate | | Total Non-Reportable Rate
(UNR+IND+INC) | |
|----------------|-----------------------|--------------|--------------------------|--------------|-----------------------|--------------|--------------------------------------------|--------------|
| | Initial | Valid Repeat | Initial | Valid Repeat | Initial | Valid Repeat | Initial | Valid Repeat |
| | (95% CI) | (95% CI) | (95% CI) | (95% CI) | (95% CI) | (95% CI) | (95% CI) | (95% CI) |
| Nasopharyngeal | 0.1% | 0.1% | 0.0% | 0.0% | 0.8% | 0.0% | 0.9% | 0.1% |
| | (1/1563) | (1/1563) | (0/1563) | (0/1563) | (13/1563) | (0/1563) | (14/1563) | (1/1563) |
| | (0.0%, 0.4%) | (0.0%, 0.4%) | (0.0%, 0.2%) | (0.0%, 0.2%) | (0.5%, 1.4%) | (0.0%, 0.2%) | (0.5%, 1.5%) | (0.0%, 0.4%) |
| Nasal | 0.1% | 0.1% | 0.1% | 0.0% | 0.8% | 0.0% | 1.1% | 0.1% |
| | (2/1568) | (2/1568) | (2/1568) | (0/1568) | (13/1568) | (0/1568) | (17/1568) | (2/1568) |
| | (0.0%, 0.5%) | (0.0%, 0.5%) | (0.0%, 0.5%) | (0.0%, 0.2%) | (0.5%, 1.4%) | (0.0%, 0.2%) | (0.7%, 1.7%) | (0.0%, 0.5%) |

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Conclusion

The analytical and clinical information in this premarket notification is complete and supports a substantial equivalence decision for the BD Respiratory Viral Panel or BD MAX™ System and the BD Respiratory Viral Panel-SVC2 for BD MAX™ System.