The Prodesse® ProAdeno®+ Assay is a multiplex Real Time PCR in vitro diagnostic test for the qualitative detection of human Adenovirus (HAdV) DNA isolated and purified from nasopharyngeal (NP) swab specimens obtained from individuals exhibiting signs and symptoms of acute respiratory infection. This test is intended for use to aid in the diagnosis of HAdV infections in humans in conjunction with other clinical and laboratory findings. The test detects, but does not differentiate, serotypes 1-51.

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

Device Description

The ProAdeno+ Assay enables detection of human adenovirus 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 ProAdeno+ Supermix included in the ProAdeno+ Assay Kit. The ProAdeno+ Supermix contains oligonucleotide primers, target-specific oligonucleotide probes and a Taq DNA polymerase. The primers are complementary to highly conserved regions of the HAdV hexon gene. The probes are dual-labeled with a reporter dye attached to the 5-end and a quencher dye attached to the 3'-end.

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 ProAdeno+ Assay is based on Tagman 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 SmartCycler II instrument.

AI/ML Overview

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

Acceptance Criteria and Device Performance

The provided document describes a Special 510(k) Submission, which means the device (Prodesse® ProAdeno®+ Assay) is a modification of an already cleared device (K102952, ProAdeno™+ Assay). Therefore, the primary acceptance criteria revolve around demonstrating that the modifications did not negatively impact the performance established for the predicate device and that the device continues to meet the performance claims.

The acceptance criteria are implied by the "Potential Impact of Modification" and the "Verification/Validation Result" sections. The "Verification/Validation Result" column details how the device performance was shown to meet these implicit criteria.

Acceptance Criteria (Implied)	Reported Device Performance (Verification/Validation Result)
For Outsourcing of Internal Control Stock Manufacturing (leading to minor changes in sequence):
Ability of the device to detect target organisms at the limit of detection should not be affected.	The modified UIC did not affect the ability of the ProAdeno+ 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 ProAdeno+ Assay should not be affected.	Additionally, the results of a retrospective clinical comparison study demonstrated the modified ProAdeno+ Assay with UIC continues to meet the performance claims for the current ProAdeno+ Assay.
For Modified Positive Controls (provided "at use" concentration, no dilution necessary):
The positive control's continued ability to monitor for global assay failures should not be affected at the increased testing concentration.	A Positive Control Effectiveness Study demonstrated the positive control's continued ability to monitor for global assay failures at the increased testing concentration.

Study Details

The submission focuses on proving substantial equivalence after minor modifications to an already cleared device. Therefore, the studies conducted are primarily verification and validation studies to confirm that the modifications did not alter the fundamental scientific technology or performance.

2. Sample Sizes and Data Provenance

Test Set Sample Size:
- Analytical Sensitivity, IC Interference, Extractor Equivalency, and Sample Stability studies: No specific sample sizes are provided in the document for these analytical studies.
- Retrospective Clinical Comparison Study: No specific sample size for the clinical comparison study is provided.
- Positive Control Effectiveness Study: No specific sample size is provided.
Data Provenance:
- The "retrospective clinical comparison study" indicates retrospective data.
- The document does not specify the country of origin of the data for any of the studies.

3. Number of Experts and Qualifications for Ground Truth

The document describes an in vitro diagnostic test (nucleic acid amplification assay). For such tests, "ground truth" is typically established through reference methods, gold standard assays (like sequencing or culture in some contexts), or clinical diagnosis. It does not typically involve human expert readers in the same way as imaging or pathology devices.
Therefore, the concepts of "number of experts" and "qualifications of those experts" for establishing ground truth are not applicable in this context.

4. Adjudication Method

Adjudication methods (e.g., 2+1, 3+1) are primarily relevant for studies involving human interpretation (e.g., radiology reads).
Given this is an in vitro diagnostic (IVD) assay, and the ground truth is established analytically or through reference methods, an adjudication method in the human-reader sense is not applicable.

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

No, an MRMC comparative effectiveness study was not done.
MRMC studies are typically for devices that assist human interpretation (e.g., CAD systems for radiologists). The Prodesse® ProAdeno®+ Assay is a standalone diagnostic test for detecting viral DNA, not an assistive tool for human readers.

6. Standalone Performance Study

Yes, a standalone performance was done for the device. The entire submission is about the performance of the algorithm/assay itself in detecting Human Adenovirus (HAdV) DNA.
The "Analytical Sensitivity, IC Interference, Extractor Equivalency, and Sample Stability studies" and the "retrospective clinical comparison study" all pertain to the standalone performance of the Prodesse® ProAdeno®+ Assay.

7. Type of Ground Truth Used

For the analytical studies (Analytical Sensitivity, IC Interference, etc.), the ground truth would typically be established by known concentrations of target nucleic acid or reference methods for determining presence/absence of inhibitors or specific analytes.
For the "retrospective clinical comparison study," the ground truth for HAdV infection in patient samples would likely have been established by a predicate device (ProAdeno™+ Assay) or another validated reference method for HAdV detection, but the document specifically states the comparison was to show the modified assay "continues to meet the performance claims for the current ProAdeno+ Assay," implying the predicate device's expected results served as a comparator for clinical performance. The details of the "gold standard" for the initial predicate device are not in this document.

8. Sample Size for the Training Set

The document describes an assay (Real Time PCR in vitro diagnostic test), not a machine learning or AI-based device that requires a "training set" in the conventional sense.
Therefore, the concept of a "training set sample size" is not applicable. The assay's performance is based on its chemical and biological reactions, not on data-driven learning.

9. How Ground Truth for the Training Set Was Established

As explained above, there is no "training set" for this type of device.

Summary

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K13215-9

Gen-Probe Prodesse, Inc. Prodesse® ProAdeno®+ Assay Special 510(k) Submission Page 1 of 3 7/11/2013

510(k) SUMMARY

CONTACT

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

AUG 14 2013

PREDICATE DEVICE

K102952, ProAdeno™+ Assay

NAME OF DEVICE

Trade Name: Regulation Number: Product Code: Classification Name: Prodesse® ProAdeno®+ Assay 21 CFR 866.3980 OCC, OOI Nucleic acid amplification assay for detection of human adenovirus

INTENDED USE

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

PRODUCT DESCRIPTION

Confidential to Gen-Probe Prodesse, Inc.

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ಕ

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

DEVICE COMPARISON

The modified ProAdeno+ Assay differs from the current kit in the following ways:

. Outsourcing of internal control stock manufacturing leads to changes in the internal control;
. The 1:10 dilution step of the positive control performed by customers has been removed.

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 ofModification	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 modified UIC did not affect theability of the ProAdeno+ Assay todetect target organisms at the limit

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Modification	Potential Impact ofModification	Verification/Validation Result
	organisms. Additionally, it maychange the clinical performanceof the ProAdeno+ Assay.	of detection as evinced by theresults of Analytical Sensitivity, ICInterference, Extractor Equivalency,and Sample Stability studies.Additionally, the results of aretrospective clinical comparisonstudy demonstrated the modifiedProAdeno+ Assay with UICcontinues to meet the performanceclaims for the current ProAdeno+Assay.
Modified positive controlsprovided "at use" "concentration, no dilution isnecessary.	Changes in the testingconcentration may affect theperformance of the positivecontrol in terms of stability orability to detect global assayfailures.	A Positive Control EffectivenessStudy demonstrated the positivecontrol's continued ability tomonitor for global assay failures atthe increased testing concentration.

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 ProAdeno+ Assay is substantially equivalent to the current legally marketed device, ProAdeno+ Assay.

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

August 14th, 2013

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

Re: K132159

Trade/Device Name: Prodesse® ProAdeno®+ Assay Regulation Number: 21 CFR 866.3980 Regulation Name: Respiratory Virus Panel Multiplex Nucleic Acid Assay Regulatory Class: Class II Product Code: OCC, OOI Dated: July 11, 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 mav 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 (QS) 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 A Hojivat -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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Gen-Probe Prodesse, Inc. Prodesse® ProAdeno®+ Assay Special 510(k) Submission

Indication for Use

510(k) Number (if known): K132159 Device Name: Prodesse® ProAdeno®+ Assay

Indications for Use:

Negative results do not preclude HAdV infection and should not be used as the sole basis for treatment or other patient 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 V. Feldblýum -S 2013.08.14 08:31:19 -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.