(87 days)
Not Found
No
The description details a standard RT-PCR assay and automated system for detecting viral nucleic acids. There is no mention of AI or ML being used for analysis, interpretation, or any other function. The results are determined by comparing fluorescence signals to a predetermined cut-off.
No
Explanation: This device is an in vitro diagnostic test designed to detect and differentiate specific viruses. It is intended to aid in diagnosis, not to treat or cure a disease.
Yes
The "Intended Use / Indications for Use" section explicitly states that the assay is an "in vitro diagnostic test" and is "intended to aid in the differential diagnosis" of specific viral infections. Additionally, the "Device Description" classifies it as a "Class II in vitro diagnostic device."
No
The device is an in vitro diagnostic test that involves physical steps like sample lysis, nucleic acid capture, and RT-PCR, performed on a hardware system (Panther Fusion system). While software is undoubtedly involved in controlling the system and analyzing results, the device itself is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Explicit Statement: The "Intended Use / Indications for Use" section clearly states that the Panther Fusion® SARS-CoV-2/Flu A/B/RSV assay is an "in vitro diagnostic test".
- Device Description: The "Device Description" section also explicitly classifies the assay as a "Class II in vitro diagnostic device" and provides its product code (QOF).
- Purpose: The intended use describes the device's purpose as detecting and differentiating specific viruses from patient specimens (nasopharyngeal and anterior nasal swabs) to aid in diagnosis. This is a core function of an in vitro diagnostic device.
- Methodology: The description of the assay's methodology (nucleic acid isolation, purification, and real-time PCR) is consistent with in vitro diagnostic procedures.
- Regulatory Classification: The mention of the device's classification under 21 CFR 866.3981 further confirms its status as an IVD.
N/A
Intended Use / Indications for Use
The Panther Fusion® SARS-CoV-2/Flu A/B/RSV assay is a fully automated multiplexed real-time polymerase chain reaction (RT-PCR) in vitro diagnostic test intended for the qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (Flu A), influenza B virus (Flu B), and respiratory syncytial virus (RSV). Nucleic acids are isolated and purified from nasopharyngeal (NP) swab specimens and anterior nasal (AN) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection. Clinical signs and symptoms of respiratory viral infection due to SARS-CoV-2, influenza, and RSV can be similar. This assay is intended to aid in the differential diagnosis of SARS-CoV-2, Flu A, Flu B, and RSV infections in humans and is not intended to detect influenza C virus infections.
Nucleic acids from the viral organisms identified by this test are generally detectable in NP and AN swab specimens during the acute phase of infection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of respiratory tract infective of the presence of the identified virus and aids in diagnosis if used in conjunction with other clinical and epidemiological information, and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.
Positive results do not rule out coinfection with other organism(s) detected by the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay may not be the definite cause of disease. Negative results do not preclude SARS-CoV-2, influenza A virus, influenza B virus, or RSV infections. This assay is designed for use on the Panther Fusion system.
Product codes
QOF, OOI
Device Description
The Panther Fusion SARS-CoV-2/Flu A/B/RSV assay is classified as a Class II in vitro diagnostic device per 21 CFR 866.3981 and has product code QOF. The Panther Fusion SARS-CoV-2/Flu A/B/RSV assay is designed for use on the fully automated Panther Fusion System.
The Panther Fusion system is a class II exempt device under 21CFR 862.2570 that has product code OOI.
The Panther Fusion SARS-CoV-2/Flu A/B/RSV assay is a multiplex real-time reverse transcriptase PCR (RT-PCR) in vitro diagnostic test developed for use on the fully automated Panther Fusion system to detect and differentiate SARS-CoV-2, influenza A, influenza B, and respiratory syncytial virus (RSV) directly from nasopharyngeal and anterior nasal swab specimens, from individuals exhibiting signs and symptoms of a respiratory tract infection.
The Panther Fusion SARS-CoV-2/Flu A/B/RSV assay involves the following steps: sample lysis, nucleic acid capture and elution transfer, and multiplex RT-PCR where analytes (when present) are simultaneously amplified, detected and differentiated. Nucleic acid capture and elution takes place in a single tube on the Panther Fusion system. The eluate is transferred to the Panther Fusion system reaction tube containing the assay reagents. Multiplex RT-PCR is then performed for the eluted nucleic acid on the Panther Fusion system.
Sample lysis, nucleic acid capture, and elution: Prior to processing and testing on the Panther Fusion system, specimens are transferred to a Specimen Lysis Tube containing specimen transport media (STM). Alternatively, samples can be collected with the RespDirect Collection kit which contains enhanced specimen transport media (eSTM). STM and eSTM lyse the cells, release target nucleic acid and protect them from degradation during storage. The Internal Control-S (IC-S) is added to each test specimen and controls via the working Panther Fusion Capture Reagent-S (wFCR-S). The IC-S is the reagent used to monitor specimen processing, amplification and detection. Magnetic particles with covalently bound oligonucleotides mediate the nucleic acid capture. Capture oligonucleotides hybridize to nucleic acid in the test specimen. Hybridized nucleic acid is then separated from the lysed specimen in a magnetic field. Wash steps remove extraneous components from the reaction tube. The elution step elutes purified nucleic acid. During the nucleic acid capture and elution step, total nucleic acid is isolated from specimens.
Elution transfer and RT-PCR: During the elution transfer step, eluted nucleic acid is transferred to a Panther Fusion tube already containing oil and reconstituted mastermix. Target amplification occurs via RT-PCR. A reverse transcriptase generates a DNA copy of the target sequence. Target specific forward and reverse primers and probes then amplify targets while simultaneously detecting and discriminating multiple target types via multiplex RT-PCR. The Panther Fusion system compares the fluorescence signal to a predetermined cut-off to produce a qualitative result for the presence or absence of the analyte. The positive result for each analyte will be accompanied by the cycle threshold (Ct value). The analytes and the channel used for their detection on the Panther Fusion system are summarized in the table below.
| Analyte | Gene Targeted | Instrument Channel | Dye |
|---|---|---|---|
| SARS-CoV-2 | ORF1ab | ROX | Cal Red 610 |
| Influenza A Virus | Matrix | FAM | Fluorescein (FAM) |
| Respiratory Syncytial Virus A/B | Matrix | HEX | Cal Orange 560 |
| Influenza B Virus | Matrix | RED647 | Quasar 670 (Q670) |
| Internal Control | Not applicable | RED677 | Quasar 705 (Q705) |
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
nasopharyngeal (NP) swab specimens, anterior nasal (AN) swab specimens
Indicated Patient Age Range
all ages
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Clinical Performance with Prospectively Collected Anterior Nasal Swab Specimens collected in eSTM (RespDirect)
A non-interventional, prospective, multicenter study was conducted. One thousand thirty three (1033) male and female individuals of all ages attending one of nine participating medical facilities (collection sites) in the US and who were exhibiting signs and/or symptoms of respiratory infection consistent with COVID-19, influenza, or RSV were enrolled in the prospective study between January 2023 and May 2023. Two (2) anterior nasal (AN) swab specimens were collected from each individual: one specimen for comparator testing was always collected by a healthcare professional (HCP) using a synthetic flocked swab and placed into UTM/VTM, and one specimen for Panther Fusion SARS-CoV-2/Flu A/B/RSV assay testing alternated between collection by the HCP or by the individual (under HCP supervision) using the RespDirect flocked swab in eSTM. Patient-collected specimens from minors were collected either by the minor or a guardian. AN swab specimens were tested either fresh (Category I specimens) or frozen (Category II specimens) with the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay at three U.S. testing sites.
The Panther Fusion SARS-CoV-2/Flu A/B/RSV assay was evaluated for SARS-CoV-2 performance by comparing the candidate device testing results to a composite comparator algorithm (CCA) consisting of up to three highly sensitive US FDA EUA SARS-CoV-2 molecular tests. A final CCA result was assigned when two of the three composite comparator assays were in concordance. The comparator method utilized to establish performance for the Flu A, Flu B, and RSV targets was a US FDA-cleared molecular Flu A/B/RSV assay.
Supplemental Clinical Data for Low Prevalence Analytes (Category III Specimens) - Anterior Nasal Swab Specimens in RespDirect eSTM
Two hundred and ten (210) male and female individuals of all ages attending one of six participating medical facilities (collection sites) in the US and who were exhibiting signs and/or symptoms of respiratory infection consistent with COVID-19, influenza, or RSV and had a positive standard of care (SOC) test result for Flu A, Flu B, and/or RSV were enrolled in the enrichment study between October 2023 and February 2024. Two (2) nasal swab specimens were collected from each individual: one specimen for comparator testing was always collected by a healthcare professional (HCP) using a synthetic flocked swab and placed into UTM/VTM, and one specimen for Panther Fusion SARS-CoV-2/Flu A/B/RSV assay testing alternated between collection by the HCP or by the individual (under HCP supervision) using the RespDirect flocked swab in eSTM. Patient-collected specimens from minors were collected either by the minor or a guardian. All enrichment study specimens were frozen prior to testing with the Panther Fusion SARS-CoV-2/ Flu A/B/RSV assay at one U.S. site.
Testing results from a U.S. FDA-cleared molecular Flu A/B/RSV assay were used to establish performance for Flu A, Flu B, and RSV targets for the enrichment study. Enrichment study specimens were collected to supplement the data for Flu A/B/RSV only because of the low prevalence of these viruses in prospective specimens, and therefore underwent comparator testing only for Flu A/B/RSV.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Summary of Performance Testing - Bench (Analytical Studies)
- Limit of Detection (LOD)
- Analytical Reactivity (Inclusivity)
- Analytical Exclusivity
- Cross Reactivity of Microorganisms
- Interfering Substances
- Competitive Interference/Co-Infection
- Within Laboratory Precision-Repeatability
- Matrix Equivalency
- Specimen Stability (VTM/UTM)
- Shipping Stability
- On-Board Stability
- Shelf-Life Stability
Summary of Performance Testing – Clinical
Clinical Performance with Prospectively Collected Anterior Nasal Swab Specimens collected in eSTM (RespDirect)
- Study type: Non-interventional, prospective, multicenter study
- Sample size: 1033 individuals enrolled, 1021 evaluable AN swab specimens (1011 tested fresh, 10 tested after freezing).
- Key results:
- SARS-CoV-2: PPA = 99.1% (95.0, 99.8), NPA = 99.0% (98.1, 99.5)
- Flu A: PPA = 100% (74.1-100), NPA = 99.9% (99.4, 100)
- Flu B: PPA = 83.3% (43.6, 97.0), NPA = 99.8% (99.3, 99.9)
- RSV: PPA = 100% (20.7, 100), NPA = 99.9% (99.4, 100)
Supplemental Clinical Data for Low Prevalence Analytes (Category III Specimens) - Anterior Nasal Swab Specimens in RespDirect eSTM
- Study type: Enrichment phase of the clinical study
- Sample size: 210 individuals enrolled, 205 nasal swab specimens tested.
- Key results:
- Flu A: PPA = 97.2% (90.3-99.2), NPA = 93.2% (87.6-96.4)
- Flu B: PPA = 97.8% (88.4-99.6), NPA = 99.4% (96.5-99.9)
- RSV: PPA = 98.4% (91.3-99.7), NPA = 95.8% (91.2-98.1)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Positive Percent Agreement (PPA), Negative Percent Agreement (NPA)
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 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.
0
November 15, 2024
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.
Hologic, Inc. Vlada Rudenko Regulatory Affairs Specialist 10210 Genetic Center Dr. San Diego, California 92121
Re: K242465
Trade/Device Name: Panther Fusion SARS-CoV-2/Flu A/B/RSV assay 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, OOI Dated: August 19, 2024 Received: August 20, 2024
Dear Vlada Rudenko:
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 (the 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 available 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
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safetyreporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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-regulatory
2
assistance/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,
Image /page/2/Picture/3 description: The image shows the name "Anna M. Mielech" in a large, bold font. Below the name, there is a "-S". The background of the image has a light blue watermark of the letters "FDA".
Anna Mielech, Ph.D. Deputy Branch Chief (Acting) Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
3
Indications for Use
510(k) Number (if known) K242465
Device Name Panther Fusion SARS-CoV-2/Flu A/B/RSV assay
Indications for Use (Describe)
The Panther Fusion® SARS-CoV-2/Flu A/B/RSV assay is a fully automated multiplexed real-time polymerase chain reaction (RT-PCR) in vitro diagnostic test intended for the qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (Flu A), influenza B virus (Flu B), and respiratory syncytial virus (RSV). Nucleic acids are isolated and purified from nasopharyngeal (NP) swab specimens and anterior nasal (AN) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection. Clinical signs and symptoms of respiratory viral infection due to SARS-CoV-2, influenza, and RSV can be similar. This assay is intended to aid in the differential diagnosis of SARS-CoV-2, Flu A, Flu B, and RSV infections in humans and is not intended to detect influenza C virus infections.
Nucleic acids from the viral organisms identified by this test are generally detectable in NP and AN swab specimens during the acute phase of infection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of respiratory tract infective of the presence of the identified virus and aids in diagnosis if used in conjunction with other clinical and epidemiological information, and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.
Positive results do not rule out coinfection with other organism(s) detected by the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay may not be the definite cause of disease. Negative results do not preclude SARS-CoV-2, influenza A virus, influenza B virus, or RSV infections. This assay is designed for use on the Panther Fusion system.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
| X Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) | |
|---|---|---|
| -- | --------------------------------------------------------------------------------------------------------------------------- | ---------------------------------------------------------- |
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510(k) SUMMARY
Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay
I. SUBMITTER
| Hologic, Inc. |
|---|
| 10210 Genetic Center Dr. |
| San Diego, CA 92121 |
- Contact Person: Vlada Rudenko, MA Regulatory Affairs Specialist vlada.rudenko@hologic.com Phone: 858-410-7967
Date Prepared: October 15, 2024
II. DEVICE
| Proprietary/Trade Name: | Panther Fusion SARS-CoV-2/Flu A/B/RSV assay |
|---|---|
| Classification Name: | Multi-Target Respiratory Specimen Nucleic Acid Test Including |
| SARS-CoV-2 And Other Microbial Agents | |
| Regulation Number: | 21 CFR 866.3981 |
| Regulatory Class: | Class II |
| Product Code: | QOF |
| Secondary Product Code: | OOI |
III. PREDICATE DEVICE
The predicate device is the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay for testing with nasopharyngeal swab and anterior nasal swab specimens collected in UTM/VTM. The purpose of this pre-market submission is to add an anterior nasal swab collected in Enhanced Transport Medium (eSTM), collected from patients with signs and/or symptoms of respiratory infection, as a validated specimen type to the currently marketed Panther Fusion SARS-CoV- 2/Flu A/B/RSV assay (K241240; cleared July 18, 2024).
IV. DEVICE DESCRIPTION
Proprietary/Trade Name: Panther Fusion SARS-CoV-2/Flu A/B/RSV assay
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The Panther Fusion SARS-CoV-2/Flu A/B/RSV assay is classified as a Class II in vitro diagnostic device per 21 CFR 866.3981 and has product code QOF. The Panther Fusion SARS-CoV-2/Flu A/B/RSV assay is designed for use on the fully automated Panther Fusion System.
The Panther Fusion system is a class II exempt device under 21CFR 862.2570 that has product code OOI.
Brief Description of Assay Principles
The assay principles are as follows and remain unchanged from the previous submission. The Panther Fusion SARS-CoV-2/Flu A/B/RSV assay is a multiplex real-time reverse transcriptase PCR (RT-PCR) in vitro diagnostic test developed for use on the fully automated Panther Fusion system to detect and differentiate SARS-CoV-2, influenza A, influenza B, and respiratory syncytial virus (RSV) directly from nasopharyngeal and anterior nasal swab specimens, from individuals exhibiting signs and symptoms of a respiratory tract infection.
The Panther Fusion SARS-CoV-2/Flu A/B/RSV assay involves the following steps: sample lysis, nucleic acid capture and elution transfer, and multiplex RT-PCR where analytes (when present) are simultaneously amplified, detected and differentiated. Nucleic acid capture and elution takes place in a single tube on the Panther Fusion system. The eluate is transferred to the Panther Fusion system reaction tube containing the assay reagents. Multiplex RT-PCR is then performed for the eluted nucleic acid on the Panther Fusion system.
Sample lysis, nucleic acid capture, and elution: Prior to processing and testing on the Panther Fusion system, specimens are transferred to a Specimen Lysis Tube containing specimen transport media (STM). Alternatively, samples can be collected with the RespDirect Collection kit which contains enhanced specimen transport media (eSTM). STM and eSTM lyse the cells, release target nucleic acid and protect them from degradation during storage. The Internal Control-S (IC-S) is added to each test specimen and controls via the working Panther Fusion Capture Reagent-S (wFCR-S). The IC-S is the reagent used to monitor specimen processing, amplification and detection. Magnetic particles with covalently bound oligonucleotides mediate the nucleic acid capture. Capture oligonucleotides hybridize to nucleic
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acid in the test specimen. Hybridized nucleic acid is then separated from the lysed specimen in a magnetic field. Wash steps remove extraneous components from the reaction tube. The elution step elutes purified nucleic acid. During the nucleic acid capture and elution step, total nucleic acid is isolated from specimens.
Elution transfer and RT-PCR: During the elution transfer step, eluted nucleic acid is transferred to a Panther Fusion tube already containing oil and reconstituted mastermix. Target amplification occurs via RT-PCR. A reverse transcriptase generates a DNA copy of the target sequence. Target specific forward and reverse primers and probes then amplify targets while simultaneously detecting and discriminating multiple target types via multiplex RT-PCR. The Panther Fusion system compares the fluorescence signal to a predetermined cut-off to produce a qualitative result for the presence or absence of the analyte. The positive result for each analyte will be accompanied by the cycle threshold (Ct value). The analytes and the channel used for their detection on the Panther Fusion system are summarized in the table below.
| Analyte | Gene Targeted | Instrument Channel | Dye |
|---|---|---|---|
| SARS-CoV-2 | ORF1ab | ROX | Cal Red 610 |
| Influenza A Virus | Matrix | FAM | Fluorescein (FAM) |
| Respiratory Syncytial Virus A/B | Matrix | HEX | Cal Orange 560 |
| Influenza B Virus | Matrix | RED647 | Quasar 670 (Q670) |
| Internal Control | Not applicable | RED677 | Quasar 705 (Q705) |
V. INDICATIONS FOR USE
The Panther Fusion SARS-CoV-2/Flu A/B/RSV assay is a fully automated multiplexed real-time polymerase chain reaction (RT-PCR) in vitro diagnostic test intended for the qualitative detection and differentiation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (Flu A), influenza B virus (Flu B), and respiratory syncytial virus (RSV).
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Nucleic acids are isolated and purified from nasopharyngeal (NP) swab specimens and anterior nasal (AN) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection. Clinical signs and symptoms of respiratory viral infection due to SARS-CoV-2, influenza, and RSV can be similar. This assay is intended to aid in the differential diagnosis of SARS-CoV-2, Flu A, Flu B, and RSV infections in humans and is not intended to detect influenza C virus infections.
Nucleic acids from the viral organisms identified by this test are generally detectable in NP and AN swab specimen during the acute phase of infection and identification of specific viral nucleic acids from individuals exhibiting signs and symptoms of respiratory tract infection are indicative of the presence of the identified virus and aids in diagnosis if used in conjunction with other clinical and epidemiological information, and laboratory findings. The results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions.
Positive results do not rule out coinfection with other organisms. The organism(s) detected by the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay may not be the definite cause of disease. Negative results do not preclude SARS-CoV-2, influenza A virus, influenza B virus, or RSV infections. This assay is designed for use on the Panther Fusion system.
VI. COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE
The predicate device is the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay for use with nasopharyngeal (NP) swab specimens collected in Viral/Universal Transport Medium (VTM/UTM) or Enhanced Specimen Transport Medium (eSTM) (RespDirect Collection Kit) and anterior nasal (AN) swab specimen collected in VTM/UTM (K241240, cleared July 18, 2024, Hologic, San Diego, CA)).
Both the predicate and subject devices utilize the same technology, run on the automated Panther Fusion system, and have similar intended uses. The only difference is that this premarket submission adds an anterior nasal swab specimen collected in eSTM to the intended use.
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A comparison of the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay for use with NP and AN swab specimens to the predicate device is summarized in Table 1 (similarities) and Table 2 (differences).
| Item | Predicate Device
Panther Fusion SARS-CoV-2/Flu
A/B/RSV Assay (NP Swab in
VTM/UTM or eSTM
(RespDirect) and AN Swab in
VTM/UTM, K241240)) | Subject Device
Panther Fusion SARS-CoV-
2/Flu A/B/RSV Assay (NP and
AN Swab in VTM/UTM or
eSTM) |
|------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------|
| Technology/
Principle of
Operation | Reverse transcriptase multiplexed
polymerase chain reaction test | Same |
| Platform | Automated Panther Fusion System | Same |
| Assay Targets | 4 targets:
SARS-CoV-2,
Flu A,
Flu B,
RSV (RSV A/RSV B) | Same |
| Assay Results | Qualitative | Same |
| Function | Detection of RNA from SARS-CoV-2,
Flu A, Flu B, and RSV | Same |
Table 1: Similarities Between Predicate Device and Subject Device
| Predicate Device | Subject Device | |
|---|---|---|
| Item | Panther Fusion SARS-CoV-2/Flu | |
| A/B/RSV Assay (NP Swab in | ||
| VTM/UTM or eSTM | ||
| (RespDirect) and AN Swab in | ||
| VTM/UTM, K241240)) | Panther Fusion SARS-CoV-2/Flu | |
| A/B/RSV Assay (NP and AN | ||
| Swab in VTM/UTM or eSTM | ||
| Intended Use | The Panther Fusion SARS-CoV- | |
| 2/Flu A/B/RSV assay is a fully | ||
| automated multiplexed real-time | ||
| polymerase chain reaction (RT- | ||
| PCR) in vitro diagnostic test | ||
| intended for the qualitative | ||
| detection and differentiation of | ||
| severe acute respiratory syndrome | The Panther Fusion SARS-CoV- | |
| 2/Flu A/B/RSV assay is a fully | ||
| automated multiplexed real-time | ||
| polymerase chain reaction (RT- | ||
| PCR) in vitro diagnostic test | ||
| intended for the qualitative | ||
| detection and differentiation of | ||
| severe acute respiratory syndrome | ||
| Item | Predicate Device | Subject Device |
| Panther Fusion SARS-CoV-2/Flu | ||
| A/B/RSV Assay (NP Swab in | ||
| VTM/UTM or eSTM | ||
| (RespDirect) and AN Swab in | ||
| VTM/UTM, K241240)) | Panther Fusion SARS-CoV-2/Flu | |
| A/B/RSV Assay (NP and AN | ||
| Swab in VTM/UTM or eSTM | ||
| coronavirus 2 (SARS-CoV-2), | ||
| influenza A virus (Flu A), influenza | ||
| B virus (Flu B), and respiratory | ||
| syncytial virus (RSV). | ||
| Nucleic acids are isolated and | ||
| purified from nasopharyngeal (NP) | ||
| swab specimens and anterior nasal | ||
| (AN) swab specimens obtained | ||
| from individuals exhibiting signs | ||
| and symptoms of a respiratory tract | ||
| infection. Clinical signs and | ||
| symptoms of respiratory viral | ||
| infection due to SARS-CoV-2, | ||
| influenza, and RSV can be similar. | ||
| This assay is intended to aid in the | ||
| differential diagnosis of SARS- | ||
| CoV-2, Flu A, Flu B, and RSV | ||
| infections in humans and is not | ||
| intended to detect influenza C virus | ||
| infections. | coronavirus 2 (SARS-CoV-2), | |
| influenza A virus (Flu A), influenza | ||
| B virus (Flu B), and respiratory | ||
| syncytial virus (RSV). | ||
| Nucleic acids are isolated and | ||
| purified from nasopharyngeal (NP) | ||
| swab specimens and anterior nasal | ||
| (AN) swab specimens obtained | ||
| from individuals exhibiting signs | ||
| and symptoms of a respiratory tract | ||
| infection. Clinical signs and | ||
| symptoms of respiratory viral | ||
| infection due to SARS-CoV-2, | ||
| influenza, and RSV can be similar. | ||
| This assay is intended to aid in the | ||
| differential diagnosis of SARS- | ||
| CoV-2, Flu A, Flu B, and RSV | ||
| infections in humans and is not | ||
| intended to detect influenza C virus | ||
| infections. | ||
| Nucleic acids from the viral | ||
| organisms identified by this test are | ||
| generally detectable in NP and AN | ||
| swab specimens during the acute | ||
| phase of infection. The detection | ||
| and identification of specific | ||
| viral nucleic acids from individuals | ||
| exhibiting signs and symptoms of | ||
| respiratory tract infection | ||
| are indicative of the presence of the | ||
| identified virus and aids in | ||
| diagnosis if used in conjunction | ||
| with other clinical and | ||
| epidemiological information, and | ||
| laboratory findings. The results of | ||
| this test should not be used as the | ||
| sole basis for diagnosis, treatment, | ||
| or other patient management | ||
| decisions. | Nucleic acids from the viral | |
| organisms identified by this test are | ||
| generally detectable in NP and | ||
| AN swab specimens during the | ||
| acute phase of infection. The | ||
| detection and identification of | ||
| specific viral nucleic acids from | ||
| individuals exhibiting signs and | ||
| symptoms of respiratory tract | ||
| infection are indicative of the | ||
| presence of the identified virus and | ||
| aids in diagnosis if used in | ||
| conjunction with other clinical and | ||
| epidemiological information, and | ||
| laboratory findings. The results of | ||
| this test should not be used as the | ||
| sole basis for diagnosis, treatment, | ||
| or other patient management | ||
| Predicate Device | Subject Device | |
| Item | Panther Fusion SARS-CoV-2/Flu | |
| A/B/RSV Assay (NP Swab in | ||
| VTM/UTM or eSTM | ||
| (RespDirect) and AN Swab in | ||
| VTM/UTM, K241240)) | Panther Fusion SARS-CoV-2/Flu | |
| A/B/RSV Assay (NP and AN | ||
| Swab in VTM/UTM or eSTM | ||
| Positive results do not rule out | ||
| coinfection with other organisms. | ||
| The organism(s) detected by | ||
| the Panther Fusion SARS-CoV- | ||
| 2/Flu A/B/RSV assay may not be | ||
| the definite cause of disease. | ||
| Negative results do not preclude | ||
| SARS-CoV-2, influenza A virus, | ||
| influenza B virus, or RSV | ||
| infections. This assay is designed | ||
| for use on the Panther Fusion | ||
| system. | ||
| The Hologic RespDirect Collection | ||
| Kit is cleared for NP swab | ||
| specimens only for testing with the | ||
| Panther Fusion SARS-CoV-2/Flu | ||
| A/B/RSV Assay. | Positive results do not rule out | |
| coinfection with other organisms. | ||
| The organism(s) detected by | ||
| the Panther Fusion SARS-CoV- | ||
| 2/Flu A/B/RSV assay may not be | ||
| the definite cause of disease. | ||
| Negative results do not preclude | ||
| SARS-CoV-2, influenza A virus, | ||
| influenza B virus, or RSV | ||
| infections. This assay is designed | ||
| for use on the Panther Fusion | ||
| system. | ||
| Specimen Types | • Nasopharyngeal (NP) swab | |
| specimens collected in | ||
| VTM/UTM or eSTM | ||
| (RespDirect) and anterior nasal | ||
| (AN) specimens collected in | ||
| VTM/UTM | • Nasopharyngeal and anterior | |
| nasal swab specimens collected | ||
| in VTM/UTM or eSTM | ||
| (RespDirect) |
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VII. GUIDANCE DOCUMENTS REFERENCED
- The 510(k) Program: Evaluating Substantial Equivalence in Premarket Notifications . [510(k)], issued July 28, 2014
- . Guidance for Industry and FDA Staff: Content of Premarket Submissions for Device Software Functions, issued June 14, 2023
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- . Electronic Submission Template for Medical Device 510(k) Submissions, issued October 2, 2023
- Cybersecurity in Medical Devices: Quality System Considerations and Content . of Premarket Submissions, September 27, 2023
- Respiratory Viral Panel Multiplex Nucleic Acid Assay Class II Special . Controls Guidance for Industry and FDA Staff, October 9, 2009
VIII. PERFORMANCE DATA
Summary of Performance Testing - Bench (Analytical Studies)
The following analytical studies previously submitted in K22276 and K241240 were performed to demonstrate the performance of the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay with nasopharyngeal swab specimens and anterior nasal swabs in UTM/VTM collected from individuals exhibiting signs and symptoms of a respiratory tract infection.
- . Limit of Detection (LOD)
- Analytical Reactivity (Inclusivity)
- Analytical Exclusivity ●
- Cross Reactivity of Microorganisms ●
- Interfering Substances ●
- Competitive Interference/Co-Infection ●
- Within Laboratory Precision-Repeatability ●
- Matrix Equivalency ●
- Specimen Stability (VTM/UTM) ●
- Shipping Stability ●
- On-Board Stability ●
- Shelf-Life Stability ●
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Summary of Performance Testing – Clinical
Clinical Performance with Prospectively Collected Anterior Nasal Swab Specimens collected in eSTM (RespDirect)
A non-interventional, prospective, multicenter study was conducted. One thousand thirty three (1033) male and female individuals of all ages attending one of nine participating medical facilities (collection sites) in the US and who were exhibiting signs and/or symptoms of respiratory infection consistent with COVID-19, influenza, or RSV were enrolled in the prospective study between January 2023 and May 2023. Two (2) anterior nasal (AN) swab specimens were collected from each individual: one specimen for comparator testing was always collected by a healthcare professional (HCP) using a synthetic flocked swab and placed into UTM/VTM, and one specimen for Panther Fusion SARS-CoV-2/Flu A/B/RSV assay testing alternated between collection by the HCP or by the individual (under HCP supervision) using the RespDirect flocked swab in eSTM. Patient-collected specimens from minors were collected either by the minor or a guardian. AN swab specimens were tested either fresh (Category I specimens) or frozen (Category II specimens) with the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay at three U.S. testing sites.
The Panther Fusion SARS-CoV-2/Flu A/B/RSV assay was evaluated for SARS-CoV-2 performance by comparing the candidate device testing results to a composite comparator algorithm (CCA) consisting of up to three highly sensitive US FDA EUA SARS-CoV-2 molecular tests. A final CCA result was assigned when two of the three composite comparator assays were in concordance. The comparator method utilized to establish performance for the Flu A, Flu B, and RSV targets was a US FDA-cleared molecular Flu A/B/RSV assay.
There were 1033 individuals enrolled in the prospective study. Four individuals were withdrawn, and 10 individuals were not evaluable for at least one target: one individual had their Panther Fusion SARS-CoV-2/Flu A/B/RSV specimen withdrawn, seven did not have a valid final Panther Fusion SARS-CoV-2/Flu A/B/RSV assay result, and two had unknown CCA results.
A total of 1032 nasal swab specimens from the prospective study were tested in valid Panther Fusion SARS-CoV-2/Flu A/B/RSV assay runs, including 11 (1.1%) with initial invalid results.
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Upon retest, four specimens yielded valid results and seven yielded invalid results, for a total of 1025 (99.3%) specimens with final valid results.
The final data set consisted of 1021 evaluable AN swab specimens in the prospective study, of which 1011 were tested fresh (Category I specimens) with the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay and 10 were tested after freezing (Category II specimens); not all were evaluable for all analytes.
The performance of the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay for the detection of SARS-CoV-2, Flu A, Flu B, and RSV for prospective AN swab specimens in RespDirect eSTM is described in Table 3.
Table 3. Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay Performance in Prospectively Collected Anterior Nasal Swab Specimens in RespDirect eSTM
| Target
Virus | Prevalence1
(%) | PPA | | NPA | |
|-----------------|--------------------|------------|----------------------|------------|----------------------|
| | | TP/(TP+FN) | % (95% CI)2 | TN/(TN+FP) | % (95% CI)2 |
| SARS-CoV-2 | 10.8 | 109/110 | 99.1
(95.0, 99.8) | 900/909 | 99.0
(98.1, 99.5) |
| Flu A | 1.1 | 11/11 | 100
(74.1-100) | 1009/1010 | 99.9
(99.4, 100) |
| Flu B | 0.6 | 5/6 | 83.3
(43.6, 97.0) | 1013/1015 | 99.8
(99.3, 99.9) |
| RSV | 0.1 | 1/1 | 100
(20.7, 100) | 1019/1020 | 99.9
(99.4, 100) |
CI = confidence interval, FN = false negative, NPA = negative percent agreement, PPA = positive percent agreement, TP = true positive, TN = true negative. 1 Study prevalence reported.
2Score CI.
Supplemental Clinical Data for Low Prevalence Analytes (Category III Specimens) - Anterior Nasal Swab Specimens in RespDirect eSTM
Flu A, Flu B and RSV were of lower prevalence and were not encountered in sufficiently large numbers during the prospective clinical study to adequately demonstrate assay performance with AN swab specimens collected with the RespDirect Collection Kit in eSTM media.
To supplement the results of the prospective clinical study, an enrichment phase of the study
14
Hologic, Inc.
was initiated. Two hundred and ten (210) male and female individuals of all ages attending one of six participating medical facilities (collection sites) in the US and who were exhibiting signs and/or symptoms of respiratory infection consistent with COVID-19, influenza, or RSV and had a positive standard of care (SOC) test result for Flu A, Flu B, and/or RSV were enrolled in the enrichment study between October 2023 and February 2024. Two (2) nasal swab specimens were collected from each individual: one specimen for comparator testing was always collected by a healthcare professional (HCP) using a synthetic flocked swab and placed into UTM/VTM, and one specimen for Panther Fusion SARS-CoV-2/Flu A/B/RSV assay testing alternated between collection by the HCP or by the individual (under HCP supervision) using the RespDirect flocked swab in eSTM. Patient-collected specimens from minors were collected either by the minor or a guardian. All enrichment study specimens were frozen prior to testing with the Panther Fusion SARS-CoV-2/ Flu A/B/RSV assay at one U.S. site.
Testing results from a U.S. FDA-cleared molecular Flu A/B/RSV assay were used to establish performance for Flu A, Flu B, and RSV targets for the enrichment study. Enrichment study specimens were collected to supplement the data for Flu A/B/RSV only because of the low prevalence of these viruses in prospective specimens, and therefore underwent comparator testing only for Flu A/B/RSV.
There were 210 individuals enrolled in the enrichment study. Six individuals were withdrawn.
A total of 205 nasal swab specimens from the enrichment study were tested in valid Panther Fusion SARS-CoV-2/Flu A/B/ RSV assay runs. Two (2) of these specimens were invalid by the candidate device during testing, for an initial invalid rate of 1.0% (2/205). Upon retesting, both specimens obtained valid results for a total of 205/205 (100%) specimens with final valid results.
The performance of the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay for the detection of Flu A, Flu B, and RSV for AN swab specimens in RespDirect eSTM for the enrichment study is described in Table 4. PPA was calculated for enrichment study specimens that were confirmed positive for at least one target analyte. NPA was calculated for specimens that had a 510(k) Summary 11
15
negative result on the comparator assay although they were confirmed positive for one of the other targets.
| PPA | NPA1 | |||||
|---|---|---|---|---|---|---|
| Target Virus | TP/ | |||||
| (TP+FN) | % | 95% CI | TN/ | |||
| (TN+FP) | % | 95% CI | ||||
| Flu A | 69/71 | 97.2 | 90.3-99.2 | 124/133 | 93.2 | 87.6-96.4 |
| Flu B | 44/45 | 97.8 | 88.4-99.6 | 158/159 | 99.4 | 96.5-99.9 |
| RSV | 60/61 | 98.4 | 91.3-99.7 | 137/143 | 95.8 | 91.2-98.1 |
Table 4. Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay Performance for the Enrichment Study with AN Swab Specimens in RespDirect eSTM
CI = confidence interval; FN = false positive; NPA = negative percent agreement; PPA = positive percent agreement, TN = true negative; TP = true positive;
1 All samples enrolled in the enrichment study were SOC positive for Flu A, Flu B, and/or RSV. The NPA for the enrichment study was calculated using results from all evaluable samples with a negative comparator result for the analyte of interest.
Conclusion Drawn from the Clinical Performance Studies
The data from the prospective and the enrichment studies demonstrate that the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay performs as expected for detecting SARS-CoV-2, Flu A, Flu B, and RSV nucleic acids in AN swab sample collected with the RespDirect Collection Kit in eSTM.
IX. CONCLUSIONS
The prospective study and enrichment study were conducted to establish the performance characteristics of the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay on the Panther Fusion System using AN swab specimens in eSTM from individuals exhibiting signs and/or symptoms of respiratory infection.
The results from the clinical study demonstrate that the Panther Fusion SARS-CoV- 2/Flu A/B/RSV assay performs comparably to the predicate device currently marketed for the intended use with nasopharyngeal swab specimens collected in VTM/UTM or eSTM (RespDirect) and anterior nasal (AN) swab specimens collected in VTM/UTM.