The Prodesse® Pro hMPV®+ Assay is a Real-Time PCR (RT-PCR) in vitro diagnostic test for the qualitative detection of human Metapneumovirus (hMPV) nucleic acid isolated and purified from nasopharyngeal swab (NP) specimens obtained from individuals exhibiting signs and symptoms of acute respiratory infection. This Assay targets a highly conserved region of the Nucleocapsid gene of hMPV. The detection of hMPV nucleic acid from symptomatic patients aids in the diagnosis of human respiratory hMPV infection if used in conjunction with other clinical and laboratory findings. This test is not intended to differentiate the four genetic sub-lineages of hMPV.

Negative results do not preclude hMPV infection and should not be used as the sole basis for diagnosis, treatment or other management decisions.

Device Description

The Pro hMPV+ Assay enables detection of human Metapneumovirus and internal control nucleic acid. Nasopharyngeal swab specimens are collected from patients with signs and symptoms of a respiratory infection using a polyester, rayon or nylon tipped swab and placed into viral transport medium.

A Universal Internal Control (UIC) is added to each sample prior to nucleic acid isolation to monitor for inhibitors present in the specimens. The isolation and purification of the nucleic acids is performed using either a MagNA Pure LC Instrument (Roche) and the MagNA Pure Total Nucleic Acid Isolation Kit (Roche) or a NucliSENS® easyMAG™ System (bioMérieux) and the Automated Magnetic Extraction Reagents (bioMérieux).

The purified nucleic acids are added to Pro hMPV+ Supermix along with enzymes included in the Pro hMPV+ Assay Kit. The Pro hMPV+ Supermix contains oligonucleotide primers complementary to a highly conserved region of the Nucleocapsid gene of hMPV and a targetspecific oligonucleotide probe dual-labeled with a reporter dye attached to the 5'-end and a quencher dve attached to nucleotide #7 from the 5 end.

Reverse transcription of the RNA in the sample into complementary DNA (cDNA) and subsequent amplification of DNA is performed in a Cepheid SmartCycler® II instrument. In this process, the probe anneals specifically to the template followed by primer extension and amplification. The Pro hMPV+ Assay is based on Taqman chemistry, which utilizes the 5' - 3' exonuclease activity of the Taq polymerase to cleave the probe thus separating the reporter dye from the quencher. This generates an increase in fluorescent signal upon excitation from a light source. With each cycle, additional reporter dye molecules are cleaved from their respective probes, further increasing fluorescent signal. The amount of fluorescence at any given cycle is dependent on the amount of amplification products present at that time. Fluorescent intensity is monitored during each PCR cycle by the SmartCyclerII instrument.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Prodesse® Pro hMPV®+ Assay, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state numerical acceptance criteria in terms of sensitivity, specificity, or predictive values. Instead, the "Verification/Validation Result" column of the "SUBSTANTIAL EQUIVALENCE" table functions as the reported performance, indicating that the modified device continues to meet the performance claims of the predicate device.

Acceptance Criteria (Implied)	Reported (Modified) Device Performance
Ability to detect target organisms at the limit of detection (LOD)	The UIC (Universal Internal Control) did not affect the ability of the Pro hMPV+ Assay to detect target organisms at the limit of detection, as evinced by the results of Analytical Sensitivity, IC Interference, Extractor Equivalency, and Sample Stability studies.
Clinical performance of the Pro hMPV+ Assay	A retrospective clinical comparison study demonstrated the modified Pro hMPV+ Assay with UIC continues to meet the performance claims for the current Pro hMPV+ Assay.
All clinical and analytical performance/functionality remains unchanged from the previous device	Verification and validation studies performed demonstrated that all clinical and analytical performance/functionality remains unchanged from the previous device.

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

The document mentions a "retrospective clinical comparison study" (page 2), but does not specify the sample size used for this study. It also does not explicitly state the country of origin. The term "retrospective" indicates that the data was collected prior to the study being designed.

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

The document does not provide information on the number of experts used or their qualifications for establishing ground truth in the clinical comparison study.

4. Adjudication Method for the Test Set

The document does not specify any adjudication method for the test set used in the clinical comparison study.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and the Effect Size of Human Readers Improve with AI vs. Without AI Assistance

This question is not applicable to this device. The Prodesse® Pro hMPV®+ Assay is an in vitro diagnostic test (Real-Time PCR) for qualitative detection of nucleic acid, not an AI-powered diagnostic imaging or interpretation device that would involve human readers or MRMC studies.

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

Yes, the studies described (analytical sensitivity, IC interference, extractor equivalency, and sample stability) and the clinical comparison study effectively demonstrate the standalone performance of the assay as an in vitro diagnostic test. The "algorithm" here is the assay's chemical and enzymatic process, and its performance is evaluated in isolation.

7. The Type of Ground Truth Used

Based on the nature of the device (a diagnostic test for a pathogen), the ground truth for human Metapneumovirus (hMPV) infection would likely be based on clinical diagnosis in conjunction with other laboratory findings, as suggested by the intended use statement: "The detection of hMPV nucleic acid from symptomatic patients aids in the diagnosis of human respiratory hMPV infection if used in conjunction with other clinical and laboratory findings."
For the analytical studies (LOD, interference, etc.), the ground truth would be established by controlled experiments with known concentrations of the target analyte (hMPV nucleic acid) and known interfering substances.

8. The Sample Size for the Training Set

The document does not mention a training set sample size. This is common for predicate-based 510(k) submissions where the device "continues to meet the performance claims" of an already approved device, rather than being a de novo artificial intelligence or machine learning device that requires explicit training data. The development of the original predicate device would have involved internal optimization and validation, but these details are not provided for this submission.

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

As no explicit "training set" is mentioned in the context of this 510(k) submission (due to it being a modification of an existing device), the method for establishing ground truth for a training set (if one were used in the original development) is not described. For the development and optimization of the original assay, ground truth would have been established through methods similar to those described in point 7, involving known positive and negative controls, spiked samples, and potentially clinical samples with confirmed hMPV status.

Summary

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K132200

Page 1 of 3 8/13/2013

510(k) SUMMARY

CONTACT

Emily Ziegler Scientist I Gen-Probe Prodesse, Inc. 20925 Crossroads Circle Waukesha, W153186

AUG 1 4 2013

NAME OF DEVICE

Trade Name:
Regulation Number:
Product Code:
Classification Name:

Prodesse® Pro hMPV®+ Assay 21 CFR 866.3980 OEM, OOI Nucleic acid amplification assay for detection of human metapneumovirus

PREDICATE DEVICE

K123838, Pro hMPVTM+ Assay

INTENDED USE

The Prodesse® Pro hMPV + Assay is a Real-Time PCR (RT-PCR) in vitro diagnostic test for the qualitative detection of human Metapneumovirus (hMPV) nucleic acid isolated and purified from nasopharyngeal swab (NP) specimens obtained from individuals exhibiting signs and symptoms of acute respiratory infection. This Assay targets a highly conserved region of the Nucleocapsid gene of hMPV. The detection of hMPV nucleic acid from symptomatic patients aids in the diagnosis of human respiratory hMPV infection if used in conjunction with other clinical and laboratory findings. This test is not intended to differentiate the four genetic sublineages of hMPV.

Negative results do not prectude hMPV infection and should not be used as the sole basis for diagnosis, treatment or other management decisions.

PRODUCT DESCRIPTION

Confidential to Gen-Probe Prodesse, Inc.

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Total Nucleic Acid Isolation Kit (Roche) or a NucliSENS® easyMAG™ System (bioMérieux) and the Automated Magnetic Extraction Reagents (bioMérieux).

Analyte	GeneTargeted	ProbeFluorophore	AbsorbancePeak	EmissionPeak	InstrumentChannel
HumanMetapneumovirus	Nucleocapsid	FAM	495 nm	520 nm	FAM
Universal InternalControl	NA	Quasar 670	647 nm	667 nm	Cy5

DEVICE COMPARISON

The modified Pro hMPV+ Assay differs from the current kit in the following ways: Outsourcing of control stock manufacturing leading to a change in control vector; Universal Internal Control, consisting of an RNA in vitro transcript and a DNA plasmid, incorporated into the kit.

The labeling was updated accordingly to incorporate the modifications listed above.

SUBSTANTIAL EQUIVALENCE

1. The Intended Use and Warnings or Precautions of the modified device as described in the labeling have not changed.
1. The modifications detailed in the table below had not had any effect or caused any changes to the fundamental scientific technology of the device.

Modification	Potential Impact of Modification	Verification/Validation Result
Outsourcing of controlsleading to minor changes insequence	Modification of the internalcontrol may affect the ability ofthe device to detect the target	The UIC did not affect the ability ofthe Pro hMPV+ Assay to detecttarget organisms at the limit of

Confidential to Gen-Probe Prodesse, Inc.

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Modification	Potential Impact ofModification	Verification/Validation Result
Incorporation of a UniversalInternal Control, containingboth RNA and DNAinternal control sequences.	organisms. Additionally, it maychange the clinical performanceof the Pro hMPV+ Assay.	detection as evinced by the resultsof Analytical Sensitivity, ICInterference, Extractor Equivalency,and Sample Stability studies.Additionally, the results of aretrospective clinical comparisonstudy demonstrated the modifiedPro hMPV+ Assay with UICcontinues to meet the performanceclaims for the current Pro hMPV+Assay.

1. Verification and validation studies performed demonstrated that all clinical and analytical performance/functionality remains unchanged from the previous device.
1. The appropriate Design Control activities were performed;
- a. A Risk Analysis was performed and did not raise any new concerns of safety and efficacy associated with the modifications.
- b. A declaration of conformity with design controls has been submitted.

The modified Pro hMPV+ Assay is substantially equivalent to the current legally marketed device, Pro hMPV+ Assay.

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with three wavy lines extending from its body, representing the department's mission to protect the health of all Americans. The logo is surrounded by the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" in a circular arrangement.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

August 14th, 2013

Emily Ziegler Scientist I Gen-Probe Prodesse, Inc. 20925 Crossroads Circle Waukesha. WI 53186

Re: K132200

Trade/Device Name: Prodesse® Pro hMPV®+ Assay Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Virus Panel Multiplex Nucleic Acid Assay Regulatory Class: Class II Product Code: OEM, OOI Dated: July 15, 2013 Received: July 16, 2013

Dear Ms. Ziegler:

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. 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 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

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Page 2 - Emily Ziegler

forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Small Manufacturers, International and Consumer Assistance at its tollfree number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Sally 생ộjvat -S

Sally Hojvat, M.Sc., Ph.D. Director, Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indication for Use

510(k) Number (if known): K132200 Device Name: Prodesse® Pro hMPV®+ Assay

Indications for Use:

Negative results do not preclude hMPV infection and should not be used as the sole basis for diagnosis, treatment or other management decisions.

Prescription Use X (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of Center for Devices and Radiological Health (CDRH)

Tamara V퀘eldblyum -S 2013.08.14 08:33:06 -04'00'

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.