K Number

Device Name

PRODESSE PROFLU+ ASSAY

Manufacturer

GEN-PROBE PRODESSE, INC.

Date Cleared

2013-08-09

(30 days)

Product Code

OCC CLA OOI

Regulation Number

866.3980

Intended Use

The Prodesse ProFlu™+ Assay is a multiplex Real-Time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and discrimination of Influenza A Virus. Influenza B Virus, and Respiratory Syncytial Virus (RSV) nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens obtained from symptomatic patients. This test is intended for use to aid in the differential diagnosis of Influenza A. Influenza B and RSV viral infections in humans and is not intended to detect Influenza C. Negative results do not preclude influenza or RSV virus infection and should not be used as the sole basis for treatment or other management decisions. Conversely, positive results do not rule-out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. The use of additional laboratory testing and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection. Performance characteristics for Influenza A Virus were established when Influenza A/H3 and A/H1 were the predominant Influenza A viruses in circulation (2006 - 2007 respiratory season). Performance characteristics for Influenza A were confirmed when Influenza A/H1, Influenza A/H3, and Influenza A/2009 H1N1 were the predominant Influenza A viruses in circulation (2008 and 2009). When other Influenza A viruses are emerging, performance characteristics may vary. 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 department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.

Device Description

The ProFlu+ Assay enables detection and discrimination of Influenza A Virus, Influenza B Virus, RSV and universal 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 Purc 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 Influenza B/RSV Mix along with enzymes included in the ProFlu+ Assay Kit. The Influenza A/Influenza B/RSV Mix contains oligonucleotide primers and target-specific oligonucleotide probes. The primers are complementary to highly conserved regions of genetic sequences for these respiratory viruses. The probes are dual-labeled with a reporter dye attached to the 5'-end and a quencher dye attached to the 3'-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 ProFity- 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 SmartCyclerII instrument.

More Information

Contact

Type

Center

Panel

Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

Street 2

City

State

Country Code

ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

K110968

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description focuses on standard RT-PCR technology and data analysis based on fluorescent signal thresholds, with no mention of AI or ML algorithms for interpretation or analysis.

Therapeutic

No
The device is an in vitro diagnostic test designed to detect and discriminate specific viral nucleic acids (Influenza A, B, and RSV) in patient samples. It aids in diagnosis but does not provide therapy or treatment.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that the device is "an in vitro diagnostic test for the rapid and qualitative detection and discrimination of Influenza A Virus, Influenza B Virus, and Respiratory Syncytial Virus (RSV) nucleic acids" and "is intended for use to aid in the differential diagnosis of Influenza A, Influenza B and RSV viral infections in humans."

SaMD (Software as a Medical Device)

The device is a multiplex Real-Time PCR (RT-PCR) in vitro diagnostic test that involves physical components like reagents, probes, and instruments (MagNA Pure LC Instrument, NucliSENS® easyMAG™ System, Cepheid SmartCycler® II instrument) for nucleic acid isolation, purification, and amplification. It is not solely software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

The "Intended Use / Indications for Use" section explicitly states: "The Prodesse ProFlu™+ Assay is a multiplex Real-Time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and discrimination of Influenza A Virus. Influenza B Virus, and Respiratory Syncytial Virus (RSV) nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens obtained from symptomatic patients."

This statement clearly identifies the device as an in vitro diagnostic test.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The Prodesse ProFlu™+ Assay is a multiplex Real-Time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and discrimination of Influenza A Virus, Influenza B Virus, and Respiratory Syncytial Virus (RSV) nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens obtained from symptomatic patients. This test is intended for use to aid in the differential diagnosis of Influenza A, Influenza B and RSV viral infections in humans and is not intended to detect Influenza C.

Negative results do not preclude influenza or RSV virus infection and should not be used as the sole basis for treatment or other management decisions. Conversely, positive results do not rule-out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease. The use of additional laboratory testing and clinical presentation must be considered in order to obtain the final diagnosis of respiratory viral infection.

Performance characteristics for Influenza A Virus were established when Influenza A/H3 and A/H1 were the predominant Influenza A viruses in circulation (2006 - 2007 respiratory season). Performance characteristics for Influenza A were confirmed when Influenza A/H1, Influenza A/H3, and Influenza A/2009 H1N1 were the predominant Influenza A viruses in circulation (2008 and 2009). When other Influenza A viruses are emerging, performance characteristics may vary.

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 department for testing. Viral culture should not be attempted in these cases unless a BSL 3+ facility is available to receive and culture specimens.

Product codes (comma separated list FDA assigned to the subject device)

OCC, OOI

Device Description

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 Purc 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 Influenza B/RSV Mix along with enzymes included in the ProFlu+ Assay Kit. The Influenza A/Influenza B/RSV Mix contains oligonucleotide primers and target-specific oligonucleotide probes. The primers are complementary to highly conserved regions of genetic sequences for these respiratory viruses. The probes are dual-labeled with a reporter dye attached to the 5'-end and a quencher dye attached to the 3'-end (see table below).

Analyte	Gene Targeted	Probe Fluorophore	AbsorbancePeak	EmissionPeak	Instrument Channel
Influenza A Virus	Matrix	FAM	495 nm	520 nm	FAM
Respiratory Syncytial Virus A	Polymerase	CAL Fluor Orange 560	540 nm	561 nm	TET
Respiratory Syncytial Virus B	Polymerase	CAL Fluor Orange 560	540 nm	561 nm	TET
Influenza B Virus	Non-structural NS1 and NS2	CAL Fluor Red 610	595 nm	615 nm	Texas Red
Universal Internal Control	NA	Quasar 670	647 nm	667 nm	Cy5

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 ProFity- 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 SmartCyclerII instrument.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Nasopharyngeal (NP) swab specimens

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Verification/Validation Result for "Outsourcing of controls leading to minor changes in sequence Incorporation of a Universal Internal Control, containing both RNA and DNA internal control sequences.": The UIC did not affect the ability of the ProFlu+ 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. Additionally, the results of a retrospective clinical comparison study demonstrated the modified ProFlu+ Assay with UIC continues to meet the performance claims for the current ProFlu+ Assay.

Verification/Validation Result for "Outsourcing of controls leading to minor changes in sequence Two modified positive controls (Inf. A/Inf. B/RSV A Control and RSV B Control) replacing current four positive controls. Modified positive controls provided "at use" concentration, no dilution is necessary.": Stability studies demonstrated current stability claims are met. Clinical validation of the modified positive controls demonstrated their continued ability to monitor for global assay failures.

*Verification/Validation Result for "Influenza A H3N2v and H7N9 Reactivity Claims"**: Results of the Reactivity Study demonstrated the ability of the ProFlu+ Assay to detect A/Indiana/10/2011 (H3N2v) and A/Anhui/1/2013 (H7N9) nucleic acids at concentrations near the limit of detection of the assay.

Verification/Validation Result for "Increase the number of freeze-thaw cycles for the M-MLV Reverse Transcriptase and RNase Inhibitor II from five (5) to ten (10)": Stability studies demonstrated that ProFlu+ Assay performance was not affected when the MMLV Reverse Transcriptase and the RNase Inhibitor II underwent 10 freeze-thaw cycles.

Note: Although this test has been shown to detect A/Anhui/1/2013 H7N9 RNA and influenza A/ Indiana/10/2011 (H3N2v) virus cultured from positive human respiratory specimens, the performance characteristics of this device with clinical specimens that are positive for H7N9 or H3N2v influenza viruses have not been established. The Prodesse ProFlu™+ Assay can distinguish between influenza A and B viruses, but it cannot differentiate influenza A subtypes.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K110968, ProFlu™+ Assay

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

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.

Summary

K132129

Page 1 of 3 8/6/2013

Attachment D 510(k) SUMMARY

CONTACT

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

4UG 0.9 2013

NAME OF DEVICE

Trade Name: Regulation Number: Product Code: Classification Name: Prodesse ProFluTM+ Assay 21 CFR 866.3980 OCC, 001 Nucleic acid amplification assay for detection and differentiation of Influenza A, Influenza B, and RSV

PREDICATE DEVICE

K110968, ProFlu™+ Assay .

INTENDED USE

The Prodesse ProFlu™+ Assay is a multiplex Real-Time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and discrimination of Influenza B Virus, and Respiratory Syncytial Virus (RSV) nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens obtained from symptomatic patients. This test is intended for use to aid in the differential diagnosis of Influenza A, Influenza B and RSV viral infections in humans and is not intended to detect Influenza C.

PRODUCT DESCRIPTION

| Analyte | Gene Targeted | Probe
Fluorophore | AbsorbancePeak | EmissionPeak | Instrument
Channel |
|----------------------------------|-------------------------------|-------------------------|----------------|--------------|-----------------------|
| Influenza A Virus | Matrix | FAM | 495 nm | 520 nm | FAM |
| Respiratory
Syncytial Virus A | Polymerase | CAL Fluor
Orange 560 | 540 nm | 561 nm | TET |
| Respiratory
Syncytial Virus B | Polymerase | CAL Fluor
Orange 560 | 540 nm | 561 nm | TET |
| Influenza B Virus | Non-structural
NS1 and NS2 | CAL Fluor Red
610 | 595 nm | 615 nm | Texas Red |
| Universal Internal
Control | NA | Quasar 670 | 647 nm | 667 nm | Cy5 |

DEVICE COMPARISON

The modified ProFlu+ 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;
Two modified positive controls replacing the four current positive controls. In addition, the 1:10 . dilution step performed by customers has been removed;
. Additional reactivity for Influenza A/Indiana/10/2011 (H3N2v) and Influenza A/Anhui/1/2013 (H7N9).
e Increase the number of allowable freeze-thaw cycles for the M-MLV Reverse Transcriptase and RNase Inhibitor II from five (5) to ten (10).

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.
  Confidential to Gen-Probe Prodesse, Inc.

The modifications detailed in the table below had not had any effect or caused any changes to the 2. fundamental scientific technology of the device.

Modification	Potential Impact of Modification	Verification/Validation Result
Outsourcing of controls leading to
minor changes in sequence
Incorporation of a Universal
Internal Control, containing both
RNA and DNA internal control
sequences.	Modification of the internal control
may affect the ability of the device to
detect the target organisms.
Additionally, it may change the
clinical performance of the ProFlu+
Assay.	The UIC did not affect the ability of the
ProFlu+ 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. Additionally, the results of a
retrospective clinical comparison study
demonstrated the modified ProFlu+
Assay with UIC continues to meet the
performance claims for the current
ProFlu+ Assay.
Outsourcing of controls leading to
minor changes in sequence
Two modified positive controls
(Inf. A/Inf. B/RSV A Control and
RSV B Control) replacing current
four positive controls.
Modified positive controls
provided "at use" concentration,
no dilution is necessary.	Changes in the sequences, format
(pooled vs. individual), or
concentration may affect the
performance of the modified positive
controls in terms of stability or
ability to detect global assay failures.	Stability studies demonstrated current
stability claims are met. Clinical
validation of the modified positive
controls demonstrated their continued
ability to monitor for global assay
failures.
Influenza A H3N2v and H7N9*
Reactivity Claims	NA	Results of the Reactivity Study
demonstrated the ability of the ProFlu+
Assay to detect A/Indiana/10/2011
(H3N2v) and A/Anhui/1/2013 (H7N9)
nucleic acids at concentrations near the
limit of detection of the assay.
Increase the number of freeze-
thaw cycles for the M-MLV
Reverse Transcriptase and RNase
Inhibitor II from five (5) to ten
(10)	Increasing the number of freeze-thaw
cycles for the MMLV Reverse
Transcriptase and RNase Inhibitor II
may affect the assay performance.	Stability studies demonstrated that
ProFlu+ Assay performance was not
affected when the MMLV Reverse
Transcriptase and the RNase Inhibitor
II underwent 10 freeze-thaw cycles.

Although this test has been shown to detect A/Anhui/1/2013 H7N9 RNA and influenza A/ Indiana/10/2011 (H3N2v) virus cultured from positive human respiratory specimens, the performance characteristics of this device with clinical specimens that are positive for H7N9 or H3N2v influenza viruses have not been established. The Prodesse ProFlu™+ Assay can distinguish between influenza A and B viruses, but it cannot differentiate influenza A subtypes.

Verification and validation studies performed demonstrated that all clinical and analytical 3. performance/functionality remains unchanged from the previous device.
The appropriate Design Control activities were performed; 4.
- A Risk Analysis was performed and did not raise any new concerns of safety and efficacy a. associated with the modifications.
- A declaration of conformity with design controls has been submitted. b.

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

Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three tail feathers, representing the department's mission to protect the health of all Americans and provide essential human services. The eagle is positioned within a circle, and the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged around the circle's perimeter.

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

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

August 9, 2013

Re: K132129

Trade/Device Name: ProFlu™+ 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 9, 2013 Received: July 10, 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

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 vours.

Uwe Scherf - S for

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

Indication for Use

510(k) Number (if known): K132129 · Device Name: ProFluTM+ Assay

Indications for Use:

The ProFlu™+ Assay is a multiplex Real-Time PCR (RT-PCR) in vitro diagnostic test for the rapid and qualitative detection and discrimination of Influenza A Virus. Influenza B Virus, and Respiratory Syncytial Virus (RSV) nucleic acids isolated and purified from nasopharyngeal (NP) swab specimens obtained from symptomatic patients. This test is intended for use to aid in the differential diagnosis of Influenza A. Influenza B and RSV viral infections in humans and is not intended to detect Influenza C.

| 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. Feldblyum -S 2013.08.08 12:31:20 -04'00'