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.

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.

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.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

Target Virus	Acceptance Criteria (Implicit for New Specimen Type)	Reported Performance (Prospective AN Swab) PPA % (95% CI) [n/N]	Reported Performance (Prospective AN Swab) NPA % (95% CI) [n/N]	Reported Performance (Retrospective AN Swab) PPA % (95% CI) [n/N]	Reported Performance (Retrospective AN Swab) NPA % (95% CI) [n/N]
SARS-CoV-2	Comparable to predicate device; high PPA/NPA expected for molecular tests.	94.8 (90.1, 97.3) [146/154]	98.8 (98.0, 99.3) [1023/1035]	N/A (Not reported separately)	N/A (Not reported separately)
Flu A	Comparable to predicate device; high PPA/NPA expected for molecular tests.	91.8 (80.8, 96.8) [45/49]	99.6 (99.0, 99.8) [1135/1140]	97.9 (89.1, 99.6) [47/48]	98.4 (94.4, 99.6) [123/125]
Flu B	Comparable to predicate device; high PPA/NPA expected for molecular tests.	66.7 (20.8, 93.9) [2/3]	99.7 (99.3, 99.9) [1183/1186]	97.2 (90.3, 99.2) [69/71]	100 (96.4, 100) [102/102]
RSV	Comparable to predicate device; high PPA/NPA expected for molecular tests.	94.4 (74.2, 99.0) [17/18]	99.8 (99.4, 100) [1169/1171]	98.0 (89.5, 99.6) [49/50]	99.2 (95.5, 99.9) [122/123]

Note on Acceptance Criteria: The document explicitly states the goal is to demonstrate "comparable" performance to the predicate device (which uses an NP swab) for the new anterior nasal (AN) swab specimen type. While specific numerical acceptance criteria (e.g., "PPA must be >X%") are not provided in this summary, the reported performance metrics (PPA, NPA, and their confidence intervals) are presented to demonstrate this comparability and overall effectiveness for diagnostic use, as typical for molecular assays expanding their indications. The high NPA values for all targets indicate good specificity, and generally high PPA values indicate good sensitivity, especially when considering the confidence intervals. The lower PPA for Flu B in the prospective study was addressed and supported by the retrospective study, which showed strong performance.

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

Prospective Clinical Study (Anterior Nasal Swab):
- Sample Size: 1,268 individuals were enrolled. 1,230 AN swab specimens were tested, resulting in 1,189 evaluable specimens for analysis (not all evaluable for all analytes).
- Data Provenance: Prospective, multicenter study conducted in the US. Specimens were collected from individuals attending nine participating medical facilities in the US during the 2022-2023 respiratory infection season.
Retrospective Clinical Study (Anterior Nasal Swab - Supplement for Flu B and RSV):
- Sample Size: 175 preselected retrospective specimens.
- Data Provenance: Retrospective. The origin country is not explicitly stated but is implied to be related to the US context from the prospective study.
Analytical Studies (Reprocessing from K222736):
- Sample Size: Not explicitly stated as "sample size" for each analytical study detail, but refers to the number of replicates/conditions tested for LOD, inclusivity, exclusivity, etc. For example, Flu B LoD confirmation involved 28 replicates per panel.
- Data Provenance: Already existing data from the previous 510(k) submission (K222736) using Nasopharyngeal (NP) swabs, reprocessed with the updated software.

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

The document does not mention the use of experts to establish ground truth for the clinical test sets. Instead, the ground truth was established by comparing the candidate device's results to reference molecular assays:

SARS-CoV-2: 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 comparator assays were in concordance.
Flu A, Flu B, and RSV: A US FDA-cleared molecular Flu A/B/RSV assay.

4. Adjudication Method for the Test Set

SARS-CoV-2 Ground Truth: For SARS-CoV-2, a composite comparator algorithm (CCA) was used. A final CCA result was assigned when "two of the three composite comparator assays were in concordance." This effectively acts as an adjudication method where agreement among a majority of reference tests determines the ground truth.
Flu A, Flu B, RSV Ground Truth: For Flu A, Flu B, and RSV, a single "US FDA-cleared molecular Flu A/B/RSV assay" was used as the comparator method. There's no mention of an adjudication process among multiple comparators for these targets.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not explicitly mentioned or conducted. This type of study is more common for imaging devices or diagnostics that involve subjective interpretation by human readers. This device is an automated molecular diagnostic assay, where the output is objective (positive/negative, Ct value).

6. Standalone (Algorithm Only) Performance Study

Yes, the performance data presented (PPA, NPA) directly reflects the standalone performance of the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay. It is compared to a ground truth established by other molecular tests, without human interpretation of the assay's output influencing the performance metrics. The assay itself is automated, so its performance is inherently "algorithm only" in the context of generating results.

7. Type of Ground Truth Used

Molecular Comparator Assays: The ground truth for the clinical test sets (both prospective and retrospective) was established using other legally marketed and highly sensitive molecular diagnostic tests.
- For SARS-CoV-2: A composite of up to three US FDA EUA SARS-CoV-2 molecular tests.
- For Flu A, Flu B, RSV: A US FDA-cleared molecular Flu A/B/RSV assay.

8. Sample Size for the Training Set

The document does not explicitly state the sample size used for the training set. This submission focuses on the validation of an existing assay with a new specimen type (anterior nasal swab) and a software update (Adaptive Crosstalk Correction). The original development and training data for the core assay (K222736) would have been described in that prior submission, but are not detailed here for this specific submission's scope. The mention of "reprocessed with validated Results Processor Tool" for previously submitted analytical studies also suggests reuse of data rather than new training.

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

Since the document doesn't explicitly detail a new "training set" for this specific submission, it also doesn't describe how ground truth for such a set was established. It's likely that the original assay development followed similar methods of using well-characterized samples or comparator assays for internal development and optimization.
Regarding the Adaptive Crosstalk Correction (ACC) factor, the validation involved "testing of SARS-CoV-2 positive clinical specimens that are representative of those that yielded false positive Flu B results in the field." This indicates that the problem the ACC addresses arose from real-world performance, and the resolution was validated against specific clinical scenarios rather than a formal "training set" in the machine learning sense.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there is a symbol representing the Department of Health & Human Services-USA. To the right, there is a blue square with the letters 'FDA' inside. Next to the square, the words 'U.S. FOOD & DRUG' are written in blue, with the word 'ADMINISTRATION' written in a smaller font size below.

Hologic, Inc. Vlada Rudenko Regulatory Affair Specialist 10210 Genetic Center Dr. San Diego, California 92121

Re: K241240

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 Dated: April 29, 2024 Received: May 3, 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.

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"

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(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 OS 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.

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 mediation-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 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) K241240

Device Name Panther Fusion SARS-CoV-2/Flu A/B/RSV assay

Indications for Use (Describe)

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.

Type of Use (Select one or both, as applicable)
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☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)
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510(k) SUMMARY

K241240

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: July 3, 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 IncludingSARS-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 specimens. The purpose of this pre-market submission is to (1) add an anterior nasal swab collected in viral/universal transport medium (VTM/UTM), collected from symptomatic patients, as a validated specimen type to the currently marketed Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay (K222736; cleared May 16, 2023) and (2) to implement an Adaptive Crosstalk Correction (ACC) factor in the Assay Definition Module (ADM) software to eliminate potential under correction of crosstalk between the SARS-CoV-2 (ROX) channel and the Flu B channel (RED647).

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IV. DEVICE DESCRIPTION

Proprietary/Trade Name: Panther Fusion SARS-CoV-2/Flu A/B/RSV assay

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.

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.

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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)

The Panther Fusion system software has been updated from version 7.2.5 in the initial Panther Fusion SARS-CoV-2/Flu A/B/RSV assay with nasopharyngeal swab specimens collected in VTM/UTM or the RespDirect Collection Kit under 510(k) clearance K222736 (cleared May 16, 2023) to version 7.2.7 used in this submission, and the current on-market system software version 7.2.9. The Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay Definition Module (ADM) software has been updated from version 1.1.5.9 in the initial 510(k) clearance K222736 to ADM

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software version 1.2.5.6 in the current submission supporting the addition of an anterior nasal swab specimen collected in VTM/UTM for processing on the Panther Fusion system and the introduction of the Adaptive Crosstalk Correction (ACC) factor explained below.

The ACC algorithm evaluates the correlation between the SARS-CoV-2 and Flu B fluorescence signals and applies crosstalk compensation when correlation of the fluorescence signals between the two analytes exceeds a pre-set threshold indicating the presence of measurable crosstalk signal. Implementation of the ACC software update reduces the potential for occasional Flu B false positives in presence of SARS-CoV-2 positives without adversely affecting safety and effectiveness of the device. Validation of the ACC ADM software update demonstrated through assay and software verification and analytical/clinical wet-testing demonstrates that the assay and system performance is equivalent to the released on-market assay performance.

V. INDICATIONS FOR USE

The intended use has been updated to include the anterior nasal swab specimen type claim. The updated intended use is as follows:

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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.

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.

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) (K222736, cleared May 16, 2023, 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 (1) an anterior nasal swab specimen collected in VTM/UTM to the intended use and (2) implements an Adaptive Crosstalk Correction (ACC) factor in the Assay Definition Module (ADM) software to eliminate potential under correction of crosstalk between the SARS-CoV-2 (ROX) channel and the Flu B channel (RED647).

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 (cleared for NP swab specimens only) is summarized in Table 1 (similarities) and Table 2 (differences).

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Item	Predicate Device	Subject Device
	Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay (NP Swab in VTM/UTM or eSTM (RespDirect), K222736))	Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay (NP Swab in VTM/UTM or eSTM and anterior nasal swab in VTM/UTM)
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

		Table 2: Differences Between Predicate Device and Subject Device

Item	Predicate Device	Subject Device
	Panther Fusion SARS-CoV-2/FluA/B/RSV Assay (NP Swab inVTM/UTM or eSTM(RespDirect), K222736))	Panther Fusion SARS-CoV-2/FluA/B/RSV Assay (NP Swab inVTM/UTM or eSTM andanterior nasal swab inVTM/UTM)
Intended Use	The Panther Fusion SARS-CoV-2/Flu A/B/RSV assay is a fullyautomated multiplexed real-timepolymerase chain reaction (RT-PCR) in vitro diagnostic testintended for the qualitativedetection and differentiation ofsevere acute respiratory syndromecoronavirus 2 (SARS-CoV-2),influenza A virus (Flu A), influenzaB virus (Flu B), and respiratorysyncytial virus (RSV).Nucleic acids are isolated and	The Panther Fusion SARS-CoV-2/Flu A/B/RSV assay is a fullyautomated multiplexed real-timepolymerase chain reaction (RT-PCR) in vitro diagnostic testintended for the qualitativedetection and differentiation ofsevere acute respiratory syndromecoronavirus 2 (SARS-CoV-2),influenza A virus (Flu A), influenzaB virus (Flu B), and respiratorysyncytial virus (RSV).Nucleic acids are isolated and
	Predicate Device	Subject Device
Item	Panther Fusion SARS-CoV-2/FluA/B/RSV Assay (NP Swab inVTM/UTM or eSTM(RespDirect), K222736))	Panther Fusion SARS-CoV-2/FluA/B/RSV Assay (NP Swab inVTM/UTM or eSTM andanterior nasal swab inVTM/UTM)
	purified from nasopharyngeal (NP)specimens obtained fromindividuals exhibiting signs andsymptoms of a respiratory tractinfection. Clinical signs andsymptoms of respiratory viralinfection due to SARS-CoV-2,influenza, and RSV can be similar.This assay is intended to aid in thedifferential diagnosis of SARS-CoV-2, Flu A, Flu B, and RSVinfections in humans and is notintended to detect influenza C virusinfections.Nucleic acids from the viral	purified from nasopharyngeal (NP)swab specimens and anterior nasal(AN) swab specimens obtainedfrom individuals exhibiting signsand symptoms of a respiratory tractinfection. Clinical signs andsymptoms of respiratory viralinfection due to SARS-CoV-2,influenza, and RSV can be similar.This assay is intended to aid in thedifferential diagnosis of SARS-CoV-2, Flu A, Flu B, and RSVinfections in humans and is notintended to detect influenza C virusinfections.Nucleic acids from the viral
	organisms identified by this test aregenerally detectable in NPspecimens during the acute phase ofinfection. The detection andidentification of specificviral nucleic acids from individualsexhibiting signs and symptoms ofrespiratory tract infectionare indicative of the presence of theidentified virus and aids indiagnosis if used in conjunctionwith other clinical andepidemiological information, andlaboratory findings. The results ofthis test should not be used as thesole basis for diagnosis, treatment,or other patient managementdecisions.Positive results do not rule out	organisms identified by this test aregenerally detectable in NP andAN swab specimens during theacute phase of infection. Thedetection and identification ofspecific viral nucleic acids fromindividuals exhibiting signs andsymptoms of respiratory tractinfection are indicative of thepresence of the identified virus andaids in diagnosis if used inconjunction with other clinical andepidemiological information, andlaboratory findings. The results ofthis test should not be used as thesole basis for diagnosis, treatment,or other patient managementdecisions.
	coinfection with other organisms.The organism(s) detected bythe Panther Fusion SARS-CoV-	Positive results do not rule outcoinfection with other organisms.The organism(s) detected by
	Predicate Device	Subject Device
Item	Panther Fusion SARS-CoV-2/FluA/B/RSV Assay (NP Swab inVTM/UTM or eSTM(RespDirect), K222736))	Panther Fusion SARS-CoV-2/FluA/B/RSV Assay (NP Swab inVTM/UTM or eSTM andanterior nasal swab inVTM/UTM)
	2/Flu A/B/RSV assay may not bethe definite cause of disease.Negative results do not precludeSARS-CoV-2, influenza A virus,influenza B virus, or RSVinfections. This assay is designedfor use on the Panther Fusionsystem.The Hologic RespDirect CollectionKit can be used to collect NPspecimens for testing with thePanther Fusion SARS-CoV-2/FluA/B/RSV Assay. Additionally,other NP swabs (not providedwith the Hologic RespDirectCollection Kit) may be used tocollect NP specimens in 3mL ofVTM or UTM.Ancillary Collection Kit:Hologic RespDirect Collection KitThe Hologic RespDirect CollectionKit is intended to be used for thecollection of nasopharyngeal (NP)swab specimens (collected by ahealthcare provider) for testing withthe Panther Fusion SARS-CoV-2/Flu A/B/RSV assay.	the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay may not bethe definite cause of disease.Negative results do not precludeSARS-CoV-2, influenza A virus,influenza B virus, or RSVinfections. This assay is designedfor use on the Panther Fusionsystem.The Hologic RespDirect CollectionKit is cleared for NP swabspecimens only for testing with thePanther Fusion SARS-CoV-2/FluA/B/RSV assay.
Specimen Types	Nasopharyngeal swabspecimen collected inVTM/UTM or eSTM(RespDirect)	Nasopharyngeal swabspecimen collected inVTM/UTM or eSTM(RespDirect) Anterior nasal swabspecimen collected inVTM/UTM
	Predicate Device	Subject Device
Item	Panther Fusion SARS-CoV-2/FluA/B/RSV Assay (NP Swab inVTM/UTM or eSTM(RespDirect), K222736))	Panther Fusion SARS-CoV-2/FluA/B/RSV Assay (NP Swab inVTM/UTM or eSTM andanterior nasal swab inVTM/UTM)
Adaptive CrosstalkCorrectionImplemented	• No	• Yes

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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
. 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 were performed to demonstrate the performance of the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay with nasopharyngeal swab specimens collected from individuals exhibiting signs and symptoms of a respiratory tract infection. Analytical results for NP swabs represent results from the most challenging claimed clinical matrix type. With the exception of one study (i.e., Cutoff Study), all data from the analytical studies performed in NP swab matrix that were previously submitted with initial 510(k) submission K222736 (cleared

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May 16, 2023) were reprocessed with validated Results Processor Tool version 3.1.1.0 (RP tool) and Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay Sequence File version 1.2.4.6 with the Adaptive Crosstalk Compensation factor. Data produced in the Cutoff study were generated with single target panels/samples which are not affected by Adaptive Crosstalk Correction since cross talk only impacts results where SARS-CoV-2 and Flu B are present. Since the Cutoff study data did not contain that condition, re-analysis was not required.

The same testing and acceptance criteria were utilized in the reanalysis of NP swab matrix studies previously submitted in K222736. The implementation of the ACC software update affectively resolves the potential for unexpected Flu B positive results in the presence of SARS-CoV-2. The validation of the ACC ADM software change demonstrated through assay and software verification and analytical/clinical wet-testing demonstrates that the assay and system performance is equivalent to the released on-market assay performance.

The following studies previously submitted in K222736 were reprocessed with validated Results Processor Tool version 3.1.1.0 (RP tool) and Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay Sequence File version 1.2.4.6 with the Adaptive Crosstalk Compensation factor. No changes to the previously performed study conclusions occurred after the reanalysis with ACC.

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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Additional supplemental analytical testing was performed to ensure that the Adaptive Crosstalk Correction factor added to the ADM software is effective in eliminating occasional occurrence of false Flu B positive results in the presence of SARS-CoV-2 positives and to verify that the software update does not impact the performance of the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay when processed with the Assay Sequence File version 1.2.4.6. Studies included confirmation of the Limit of Detection (LoD) for Flu B, confirmation of no Competitive Interference between high SARS-CoV-2 concentration and low Flu B concentration coinfections and testing of SARS-CoV-2 positive clinical specimens that are representative of those that yielded false positive Flu B results in the field. A representative thermocycler that previously demonstrated unexpected Flu B positive results in the presence of SARS-CoV-2 using assay sequence file version 1.2.5.3 due to under correction of crosstalk between SARS-CoV-2 and Flu B channels (Red647/Q670) was used in these studies.

Title	Description of Testing
Confirmation of the Limit ofDetection (LoD) for Flu B	Flu B LoD was confirmed with single target spiked and co-spikedpanels. Panels consisted of cultured virus for one Victoria and oneYamagata strain for Flu B that is identical to that used to originallyestablish the LoD. Testing was performed at 1xLoD as well as half alog above and below the LoD. Testing also consisted of a co-spikedpanel that is positive for one strain of SARS-CoV-2, Flu A, Flu B,and RSV at 3xLoD each. Pooled negative clinical nasopharyngeal(NP) swab in VTM/UTM matrix was used. 28 replicates were testedper panel.
	All panels were made in pooled negative clinical NP swabVTM/UTM processed into STM matrix at a 1:1.56 ratio. NegativeNP samples were screened for negativity using the Panther FusionSARS-CoV-2/Flu A/B/RSV assay and pooled.
	Flu B Yamagata was detected at 96% (27/28) and Flu B Victoria wasdetected at 100% (28/28) at 1xLoD; both strains had <95% detectionat half log below their respective LoDs. At 3x LoD, all analytes weredetected at 100% (28/28). The LoD's for both strains of Flu B wereconfirmed to be the same as previously established. All analytes inthe co-spiked samples were confirmed at 3x LoD.
	Competitive interference withhigh SARS-CoV-2 and low Flu B
	Testing consisted of one SARS-CoV-2 strain and one Flu B strain.Flu B was tested at 3x LoD and SARS-CoV-2 at 1e4 TCID50/mL.Pooled negative clinical nasopharyngeal (NP) swab in VTM/UTMmatrix was used. The panel was tested at three replicates. Flu B was100% positive at 3x LoD in the presence of high titer SARS-CoV-2at 1e4 TCID50/mL. demonstrating no competitive interference. These

Table 4 Supplemental Analytical and Clinical Testing with Adaptive Crosstalk Correction

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Title	Description of Testing
results align with data originally produced without the ACC.
Resolution of unexpected Flu Bpositives in the presence ofSARS-CoV-2	Resolution of unexpected Flu B positives in the presence of SARS-CoV-2 with Adaptive Crosstalk Correction in assay version 1.2.4.6was demonstrated with individual NP swab in VTM/UTM clinicalspecimens naturally positive for SARS-CoV-2. Ten individualclinical specimens were tested at one replicate each to produce tenunexpected Flu B positive results using assay sequence file version1.2.5.3. All specimens that produced unexpected Flu B positiveresults were retested at one replicate each using assay sequence fileversion 1.2.4.6 which has Adaptive Crosstalk Correctionimplemented. One replicate per specimen was tested in each assaysequence file version for a total of two replicates per specimen orpanel. Resolution of unexpected Flu B positives in the presence ofSARS-CoV-2 with ACC in assay version 1.2.4.6 was demonstratedfor all ten clinical specimens.

Title

Description of Testing

results align with data originally produced without the ACC.

Resolution of unexpected Flu Bpositives in the presence ofSARS-CoV-2

Resolution of unexpected Flu B positives in the presence of SARS-CoV-2 with Adaptive Crosstalk Correction in assay version 1.2.4.6was demonstrated with individual NP swab in VTM/UTM clinicalspecimens naturally positive for SARS-CoV-2. Ten individualclinical specimens were tested at one replicate each to produce tenunexpected Flu B positive results using assay sequence file version1.2.5.3. All specimens that produced unexpected Flu B positiveresults were retested at one replicate each using assay sequence fileversion 1.2.4.6 which has Adaptive Crosstalk Correctionimplemented. One replicate per specimen was tested in each assaysequence file version for a total of two replicates per specimen orpanel. Resolution of unexpected Flu B positives in the presence ofSARS-CoV-2 with ACC in assay version 1.2.4.6 was demonstratedfor all ten clinical specimens.

Summary of Performance Testing - Clinical

Clinical Performance with Prospectively Collected Anterior Nasal Swab Specimens

A non-interventional, prospective, multicenter study was conducted. One thousand two hundred and sixty-eight (1,268) 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 symptoms of respiratory viral infection consistent with COVID-19, influenza, or RSV were enrolled during the 2022-2023 respiratory infection season. Two (2) anterior nasal swab (AN) swab specimens were collected from each consented individual using synthetic flocked swabs and stored in tubes containing universal/viral transport medium (UTM/VTM). All specimens for candidate testing were tested fresh (i.e., never frozen before testing).

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.

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Of the 1,268 subjects, (2) subjects were withdrawn. A total of 1230 nasal swab specimens in VTM/UTM were tested in valid Panther Fusion SARS-CoV-2/Flu A/B/RSV assay runs, including 10 (0.8%) with initial invalid results. Upon retest, 6 of the 10 specimens yielded valid results and 4 yielded invalid results, for a total of 1226 (99.7%) specimens with final valid results.

The final data set consisted of 1189 evaluable nasal swab specimens in VTM/UTM; not all were evaluable for all analytes. Non-evaluable specimens were excluded from the performance analyses for the following reasons: withdrawn Panther Fusion SARS-CoV-2/Flu A/B/RSV assay specimen (40 VTM/UTM), invalid or missing Panther Fusion SARS-CoV-2/Flu A/B/RSV assay result (4 VTM/UTM), unknown comparator method result (33 VTM/UTM each for SARS-CoV-2, Flu A, Flu B, and RSV).

The performance of the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay for the detection of all target viruses in prospective AN swab specimen is summarized in Table 5.

Prospectively Collected AN Swab Specimens in UTM/VTM
Target Virus	PPA% (95% CI) [n/N]	NPA% (95% CI) [n/N]
SARS-CoV-2	94.8 (90.1, 97.3)[146/154]	98.8 (98.0, 99.3)[1023/1035]
Flu A	91.8 (80.8, 96.8)[45/49]	99.6 (99.0, 99.8)[1135/1140]
Flu B	66.7 (20.8, 93.9)[2/3]	99.7 (99.3, 99.9)[1183/1186]
RSV	94.4 (74.2, 99.0)	99.8 (99.4, 100)

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Table 5: Clinical Performance of the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay in

[1169/1171]

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Clinical Performance with Retrospective Anterior Nasal Swab Specimens

Flu B and RSV were of lower prevalence during the prospective clinical study and were therefore not encountered in large enough numbers to adequately demonstrate assay performance in AN swab specimens in VTM/UTM. Testing of 175 preselected retrospective specimens was performed to supplement the results of the prospective specimen population. In addition to evaluating Flu B and RSV positive specimens. Flu A positive specimens were included in the study. All known positive specimens underwent confirmatory testing using a US FDA-cleared molecular Flu A/B/RSV assay. Two (2) specimens were not included in the performance analyses because of a missing comparator result.

The performance of the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay for the detection of influenza A, influenza B, and RSV viruses in retrospective AN swab specimen is summarized in Table 6.

	PPA	NPA
Target Virus	% (95% CI) [n/N]	% (95% CI) [n/N]
Flu A	97.9 (89.1, 99.6)[47/48]	98.4 (94.4, 99.6)[123/125]
Flu B	97.2 (90.3, 99.2)[69/71]	100 (96.4, 100)[102/102]
RSV	98.0 (89.5, 99.6)[49/50]	99.2 (95.5, 99.9)[122/123]

Table 6: Clinical Performance of the Panther Fusion SARS-CoV-2/Flu A/B/RSV Assay in Retrospective AN Swab Specimens in UTM/VTM

Conclusion Drawn from Clinical Results

This study was conducted to establish the performance characteristics of the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay on the Panther/Panther Fusion system using anterior nasal swab specimens in UTM/VTM from symptomatic male and female subjects.

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The conclusion drawn from the clinical study demonstrates that the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay is as safe and effective for the evaluation of the additional anterior nasal swab specimen type and performs comparably to the predicate device currently marketed for the intended use with nasopharyngeal swab specimens.

IX. CONCLUSIONS

The analytical and clinical study results demonstrate that the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay for testing anterior nasal swab specimens on the Panther Fusion system performs comparably to the currently marketed predicate device with a nasopharyngeal swab claim. Hardware and software verification and validation demonstrate that the Panther Fusion SARS-CoV-2/Flu A/B/RSV assay on the Panther Fusion system will perform as intended.

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.