The Panther Fusion® AdV/hMPV/RV assay is a multiplex real-time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and differentiation of Adenovirus (AdV), human Metapneumovirus (hMPV), and Rhinovirus (RV). Nucleic acids are isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection.

This assay is intended to aid in the differential diagnosis of Adenovirus, human Metapneumovirus, and Rhinovirus infections in humans. Negative results do not preclude Adenovirus, human Metapneumovirus, and Rhinovirus infections and should not be used as the sole basis for treatment or other management decisions. This assay is designed for use on the Panther Fusion system.

Device Description

The Panther Fusion AdV/hMPV/RV assay is a multiplex real-time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and differentiation of Adenovirus (AdV) human Metapneumovirus (RV). Nucleic acids are isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection.

Prior to processing and testing on the Panther Fusion system, specimen Lysis Tube containing specimen transport media (STM) that lyses the cells, releases target nucleic acid and protects 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 lC-S in the reagent monitors specimen processing, and detection. Capture oligonucleotides hybridize to nucleic acid in the test specimen. Hybridized nucleic acid is then specimen in a magnetic field. Wash steps remove extraneous components from the reaction tube. The elution step elutes acid. During the nucleic acid capture and elution step, total nucleic acid is isolated from specimens.

During the elution transfer step, eluted nucleic acid is transferred to a Panther Fusion tube already containing oil and reconstituted masternix. For RV, hMPV, and internal control targets, amplification occurs via RT-PCR. A reverse transcriptase step qenerates DNA copies of the target sequence. For AdV, target amplification occurs via PCR. For all targets, specific forward and reverse primers and probes amplify targets while simultaneously detecting and discriminating multiplex PCR. The Panther Fusion system compares the fluorescence signal to a predece a qualitative result for the presence or absence of the analyte. The assay analytes (Adenovirus, human Metapheumovirus, and Internal Control) through specific gene targets (Hexon, Nucleocapsid, 5' UTR, and n/a, respectively) are detected in different channels of the Panther Fusion system (HEX, ROX, FAM, and RED677, respectively).

AI/ML Overview

The provided text describes a 510(k) premarket notification for the "Panther Fusion AdV/hMPV/RV Assay," an in vitro diagnostic test. The notification details the device, its intended use, and a comparison to a predicate device. Crucially, it highlights that the subject device incorporates "software algorithm changes" to improve hMPV specificity, specifically to decrease false positives, without significantly altering clinical results or assay claims.

However, the document states: "All analytical and clinical data used to support the predicate device intended use and performance was re-analyzed with the updated software. All pre-determined acceptance criteria from the original protocols were met." It does not provide the specific acceptance criteria or the detailed results of this re-analysis, nor does it describe a new study conducted to prove the device meets acceptance criteria. It only affirms that the previous data, when re-analyzed with the new software, continued to meet the original acceptance criteria.

Because the document only states that original acceptance criteria were met by re-analysis of existing data, and does not outline specific acceptance criteria or an independently designed study for the new software, I can only infer information from what is provided.

Here's an attempt to answer your questions based on the limited information that can be extracted or reasonably inferred from the provided text:

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

The document does not provide a specific table of acceptance criteria or reported device performance for the new software. It only states: "All pre-determined acceptance criteria from the original protocols were met." Without the original protocols, the exact acceptance criteria and the specific performance metrics (e.g., sensitivity, specificity, accuracy) are not available in this document. The focus of the changes is on improving hMPV specificity, implying that this was a key performance area.

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

The document states: "All analytical and clinical data used to support the predicate device intended use and performance was re-analyzed with the updated software." This indicates that the same test set (both analytical and clinical data) used for the predicate device was re-used for the updated software. The sample size and data provenance are therefore not detailed in this document, as it refers to pre-existing data. It doesn't specify if the original data was retrospective or prospective, nor its country of origin.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This information is not provided in the document. The study described is a re-analysis of previously established analytical and clinical data for an in-vitro diagnostic test. Establishing "ground truth" for clinical samples in an IVD context typically involves clinical diagnosis or other validated laboratory methods, rather than expert radiology reads as might be the case for imaging AI.

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

This information is not provided in the document. As an IVD device, the "adjudication method" in the context of clinical studies for diagnostic accuracy would typically refer to how the true status of a specimen (positive/negative for a pathogen) was determined.

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

No, an MRMC comparative effectiveness study was not done or described. This device is an in-vitro diagnostic test (a laboratory assay), not an AI imaging analysis tool that assists human readers. Therefore, the concept of "human readers improve with AI vs without AI assistance" does not apply here.

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

The device is an in-vitro diagnostic test that operates on a "Panther Fusion system." The "software algorithm changes" affect how the assay results are processed and interpreted by the system itself. This is essentially a "standalone" or "algorithm only" performance, as the algorithm's output directly determines the qualitative detection and differentiation of the viruses. Human intervention likely involves sample preparation and loading, and subsequent interpretation of the system's output. The re-analysis was of the system's performance with the new software.

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

The document relates to an In Vitro Diagnostic (IVD) test for nucleic acid detection. For such assays, "ground truth" for the test set would typically be established by:

Reference laboratory methods: Such as highly sensitive and specific PCR methods, sequencing, or culture that are considered gold standard.
Clinical diagnosis: Based on a physician's assessment, symptoms, and other diagnostic tests.
Composite reference standard: A combination of clinical and laboratory findings.

The exact type of ground truth used for the original predicate device data (which was re-analyzed) is not specified in this document.

8. The sample size for the training set

The document states that "All analytical and clinical data used to support the predicate device intended use and performance was re-analyzed with the updated software." This implies that the software updates likely occurred after the initial assay development. It's not explicitly stated that a new training set was used for the "software algorithm changes." The changes are presumably based on internal development and validation, potentially informed by performance issues (like the hMPV false positives). Details about any specific training set for the software algorithm are not provided.

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

As there is no specific mention of a separate training set for the new algorithm within this document, the method for establishing its ground truth is also not provided. If the algorithm was developed iteratively based on observed performance issues (e.g., false positives), the "ground truth" for its development would be based on the established true status of the samples that generated those observed issues, similar to how the ground truth is established for the test set (reference methods or clinical diagnosis).

Summary

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food & Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Hologic, Inc. Jon Kukowski Regulatory Affairs Specialist 10210 Genetic Center Dr San Diego, California 92121

Re: K231017

Trade/Device Name: Panther Fusion AdV/hMPV/RV Assay Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Viral Panel Multiplex Nucleic Acid Assay Regulatory Class: Class II Product Code: OCC, OEM, OOI Dated: April 7, 2023 Received: April 10, 2023

Dear Jon Kukowski:

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

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

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

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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

For comprehensive regulatory information about 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

Submission Number (if known)

K231017 Device Name

Panther Fusion AdV/hMPV/RV Assay

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

Over-The-Counter Use (21 CFR 801 Subpart C)

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510(k) Summary

Prepared on: 2023-05-02

Contact Details

Applicant Name	Hologic, Inc.
Applicant Address	10210 Genetic Center Dr San Diego CA 92121 United States
Applicant Contact Telephone	218-791-1313
Applicant Contact	Mr. Jon Kukowski
Applicant Contact Email	jonathan.kukowski@hologic.com
Device Name		21 CFR 807.92(a)(2)
Device Trade Name	Panther Fusion AdV/hMPV/RV Assay
Common Name	Respiratory viral panel multiplex nucleic acid assay
Classification Name	Respiratory Virus Panel Nucleic Acid Assay System
Regulation Number	866.3980
Product Code	OCC
Legally Marketed Predicate Devices		21 CFR 807.92(a)(3)
Predicate #	Predicate Trade Name (Primary Predicate is listed first)		Product Code
K172629	Panther Fusion AdV/hMPV/RV Assay		OCC
Device Description Summary		21 CFR 807.92(a)(4)

Nucleic acid capture and elution

Elution transfer and RT-PCR

Panther Fusion AdV/hMPV/RV Assay

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Assay Components

The reagents required to perform the Panther Fusion AdV/hMPV/RV assay are packaged and sold separately. There are 7 boxes containing 9 reagents which are required for sample processing. IA description of the components that are required to perform the Panther Fusion AdV/hMPV/RV assay are detailed below.

Box 1 - Panther Fusion AdV/hMPV/RV Assay Cartridges

Box 2 - Panther Fusion Extraction Reagent-S (contains Panther Fusion Capture Reagent-S and Panther Fusion Enhancer Reagent-S)

Box 3 Panther Fusion Internal Control-S
Box 4 - Panther Fusion Reconstitution Buffer I

Box 5 - Panther Fusion Elution Buffer

Box 6 - Panther Fusion Oil

Box 7 - Panther Fusion AdV/hMPV/RV Assay Controls (Panther Fusion AdV/hMPV/RV Positive Control

and Panther Fusion Negative Control)

In addition, select components can also be ordered in the following bundles:

· Panther Fusion Universal Fluids Kit: (contains Panther Fusion Oil and Panther Fusion Elution Buffer),

• Panther Fusion Assay Fluids I-S: (contains Parther Fusion Reagents-S, Panther Fusion Internal Control-S, and Panther Fusion Reconstitution Buffer I).

Intended Use/Indications for Use

The Panther Fusion® AdV/hMPV/RV assay is a multiplex real-time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and differentiation of Adenovirus (AdV), human Metapneumovirus (RV). Nucleic acids are isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of a respiratory tract infection.

This assay is intended to aid in the differential diagnois of Adenovirus, and Rhinovirus, and Rhinovirus infections in humans. Negative results do not preclude Adenovirus, human Metapneumovirus, and Rhinovirus infections and should not be used as the sole basis for treatment or other management decisions. This assay is designed for use on the Panther Fusion system.

Indications for Use Comparison

The subject device includes software algorithm changes in the predicate device. Implementation of these changes will improve hMPV specificity (decrease the number of false positives) without significantly changing the clinical results or assay claims. The indications for use of the subject device are the same as those of the predicate device.

Technological Comparison

The subject device and predicate device share technological characteristics, including the method of detection, intended use, specimen type, components, ancillaries, reagent formulation, packaging, principles of operation, and instrument platform.

The difference between the two devices is the software utilized to run the assay. The subject device with system software version 7.2.7 and assay software version 2.3.5.4, including algorithm changes to address false positive hMPV results of high RV true positive results.

Non-Clinical and/or Clinical Tests Summary & Conclusions 21 CFR 807.92(b)

All analytical and clinical data used to support the predicate device intended use and performance was re-analyzed with the updated software. All pre-determined acceptance criteria from the original protocols were met. The conclusions drawn from the nonclinical and clinical studies demonstrate that the Panther Fusion AdV/hMPV/RV assay on the Panther Fusion system is as safe and effective, and performs comparably to the predicate device currently marketed for the same intended use.

21 CFR 807.92(a)(5)

21 CFR 807.92(a)(6)

Regulation Number and Section

§ 866.3980 Respiratory viral panel multiplex nucleic acid assay.

(a)
Identification. A respiratory viral panel multiplex nucleic acid assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify multiple viral nucleic acids extracted from human respiratory specimens or viral culture. The detection and identification of a specific viral nucleic acid from individuals exhibiting signs and symptoms of respiratory infection aids in the diagnosis of respiratory viral infection when used in conjunction with other clinical and laboratory findings. The device is intended for detection and identification of a combination of the following viruses:(1) Influenza A and Influenza B;
(2) Influenza A subtype H1 and Influenza A subtype H3;
(3) Respiratory Syncytial Virus subtype A and Respiratory Syncytial Virus subtype B;
(4) Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3 virus;
(5) Human Metapneumovirus;
(6) Rhinovirus; and
(7) Adenovirus.
(b)
Classification. Class II (special controls). The special controls are:(1) FDA's guidance document entitled “Class II Special Controls Guidance Document: Respiratory Viral Panel Multiplex Nucleic Acid Assay;”
(2) For a device that detects and identifies Human Metapneumovirus, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Human Metapneumovirus (hMPV) Using Nucleic Acid Assays;” and
(3) For a device that detects and differentiates Influenza A subtype H1 and subtype H3, FDA's guidance document entitled “Class II Special Controls Guidance Document: Testing for Detection and Differentiation of Influenza A Virus Subtypes Using Multiplex Nucleic Acid Assays.” See § 866.1(e) for the availability of these guidance documents.