The SPY System is an imaging system used in capturing and viewing fluorescent images for the visual assessment of blood flow as an adjunctive method for the evaluation of tissue perfusion, and related tissuetransfer circulation in tissue and free flaps used in plastic, micro- and reconstructive surgical procedures.

Device Description

The Novadaq® Technologies SPY® Fluorescent Imaging System consists of 2 components: the SP2000 Imaging Device and the SPY Paq®. The SP2000 Imaging Device consists of an imaging head containing a charge coupled device (CCD) camera, a laser light source, motion sensor and distance sensor attached via an articulating arm to a mobile cart. The mobile cart contains a flat panel display, computer, electronics enclosure and printer. The SPY® System provides the surgeon with the capability to view record and replay fluorescent images of blood flow in vessels and bypass grafts of the heart. A laser light source is used to illuminate the area of interest. ICG is injected intravenously through the central or peripheral venous line, bypass pump, cardioplegia line and coronary graft and while it is passing through the vessels, the absorption of laser light causes excitation of the dye followed by emission of infrared energy. The result is a fluorescent image of blood flow and related tissue perfusion in the vessels. A CCD camera captures the image.

AI/ML Overview

The provided document, K072222, is a 510(k) summary for the SPY® Fluorescent Imaging System (SP2000 model), specifically concerning a proposed change to allow the use of an alternative brand of Indocyanine Green (ICG) dye (ICG Pulsation®) in addition to the already approved IC-Green™.

The document does not describe a study that explicitly sets acceptance criteria for device performance and then proves the device meets those criteria with specific statistical metrics. Instead, it focuses on demonstrating substantial equivalence to previously cleared predicate devices and proving the safety and effectiveness of using the new brand of ICG with the existing system. The "acceptance criteria" can therefore be inferred from the rigorous testing and positive clinical outcomes reported in previously cleared indications and the current submission's focus on equivalence.

Here's an analysis based on the available information:

1. Table of Acceptance Criteria and Reported Device Performance

Since explicit acceptance criteria with numerical targets are not stated, the table below infers the performance goals based on the described safety and effectiveness outcomes. The "Reported Device Performance" reflects the evidence presented to demonstrate that these inferred criteria are met.

Acceptance Criteria (Inferred)	Reported Device Performance
Safety:
1. No thermal damage to tissue: The system should not cause thermal damage to the area of interest, even after repeated imaging sequences.	1. Exposure for the SPY® System is 35 mW/cm², "far below" the maximum permissible exposure of 327 mW/cm² established by ANSI for skin exposure.
	2. Pig studies demonstrated no increase in myocardial tissue temperature.
	3. "Use of the SPY System does not cause any thermal damage to the area of interest, even after repeated imaging sequences."
2. No adverse physiological effects (cardiac, renal, hepatic): Use of the system should not induce changes in cardiac function (ECG, arterial pressure) or acute/long-term cellular, renal, or hepatic adverse effects.	1. Pig studies demonstrated "no detrimental effects on heart function, coronary flow or peripheral pressure."
	2. Over 4000 CABG procedures in humans showed "no reports of adverse acute or long-term cellular, renal or hepatic effects."
	3. "For the heart, there were no changes in electrocardiograms or arterial pressures during and/or following SPY use."
	4. "There were no acute or long-term cellular effects of using the SPY System." and "There were no acute or long-term renal or hepatic effects of using the SPY System."
3. Compatibility with ICG: The system must function safely and effectively with both IC-Green™ and ICG-PULSION® brands of ICG.	1. The document explicitly states the 510(k) "demonstrates the equivalence of IC-Green™ and ICG-PULSION ICG products when used with the SPY Intra-operative Imaging Device."
Effectiveness:
4. High-quality image acquisition: Ability to acquire high-quality, high-resolution fluorescent images of blood flow and tissue perfusion in vessels and grafts.	1. Pig studies demonstrated the ability to "acquire high quality images in a simple and reproducible manner."
	2. "The SPY System was able to acquire high quality images of the entire vascular bed on each area of interest."
	3. Clinical utility demonstrated "in producing high quality and resolution images of the entire vascular bed of the point of interest."
5. Clinical utility in identifying patency issues: Ability to non-invasively, quickly, and safely identify vascular issues (e.g., lack of patency in grafts) to aid surgeons in revision.	1. Literature reports that the SPY System "was able to non-invasively, quickly and safely identify 17 conduits in 311 patients that required revision during the surgical procedures. In all cases the lack of patency was visualized clearly by the SPY System... allowing the surgeon to revise the graft thus decreasing subsequent myocardial infarctions and the morbidity and mortality associated with poor graft patency."
6. Imaging capabilities through skin (for specific indications): Ability to image dermal and subdermal blood flow. (This is a specific indication for plastic, micro- and reconstructive surgery.)	1. "The SPY System is capable of imaging through the skin to provide a visual assessment of dermal and subdermal blood flow."
Equivalence to Predicates: The updated device (with ICG-PULSION®) must be substantially equivalent to previously cleared SPY systems and predicate devices for its intended use, without raising new questions of safety or effectiveness.	1. Animal studies, human experience, and in vitro testing from previous 510(k) clearances (K042961, K060867, K063345, K071037) demonstrated safety and effectiveness. 2. The current submission specifically "demonstrates the equivalence of IC-Green™ and ICG-PULSION ICG products when used with the SPY Intra-operative Imaging Device." 3. The FDA letter confirms the device is determined "substantially equivalent" for the stated indications, pending the drug approval for ICG-PULSION®.

2. Sample Sizes and Data Provenance

Test Set Sample Size:
- Human Data: Over 4000 CABG procedures.
- Animal Data: Six (6) pig studies.
Data Provenance:
- Human Data: Retrospective and prospective (implied by "commercially available," "over 4000 CABG procedures," and "literature reports"). Originated in Europe, Japan, and Canada.
- Animal Data: Prospective (specifically conducted for original 510(k)).

3. Number of Experts and Qualifications for Ground Truth

The document does not explicitly state the number of experts used to establish ground truth for this specific 510(k) submission's equivalence testing of the ICG brands.

However, for the original studies and clinical utility, it refers to:

"surgeons" using the system.
"literature reports" from 12 peer-reviewed journal articles, implying assessment and validation by medical professionals (surgeons, clinicians, researchers).

The qualifications of these experts are not explicitly detailed but would implicitly be surgeons and other medical specialists involved in cardiovascular, plastic, micro- and reconstructive surgeries, and researchers in those fields who authored or reviewed the peer-reviewed articles.

4. Adjudication Method

The document does not describe a formal adjudication method (like 2+1 or 3+1 consensus) for the test set as would typically be done for a diagnostic AI device. The evaluation of patency and the decision for revision were clinical decisions made by the operating surgeons based on the real-time SPY system images. The "ground truth" here is the clinical outcome or intervention guided by the system's visualization.

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

No MRMC comparative effectiveness study is mentioned comparing human readers with and without AI assistance. The SPY system is an imaging device, not an AI algorithm in the contemporary sense. It provides intra-operative visual assessment of blood flow to assist the surgeon, implying human-in-the-loop use. The document describes clinical utility and safety, not an improvement in human reader performance with AI versus without AI assistance.

6. Standalone (Algorithm Only) Performance

Not applicable. The SPY system is a medical imaging device used intra-operatively by surgeons to visualize blood flow. It is intrinsically a human-in-the-loop system and not a standalone algorithm.

7. Type of Ground Truth Used

The ground truth used is primarily clinical observation/outcomes and expert judgment (surgical decisions).

For the original CABG use, the "lack of patency was visualized clearly by the SPY System... allowing the surgeon to revise the graft." The successful revision and subsequent decrease in myocardial infarctions and morbidity/mortality serve as ultimate clinical ground truth for the system's utility.
For safety, lack of adverse events (cellular, renal, hepatic, cardiac function) observed during real-world use and animal studies serves as ground truth.
For image quality, expert assessment by surgeons and researchers (implied by peer-reviewed publications) provides the ground truth.
In pig studies, direct physiological measurements (heart function, coronary flow, peripheral pressure, myocardial tissue temperature) were used.

8. Sample Size for Training Set

The concept of a "training set" is not applicable as this is not an AI/machine learning device. The previous human experience and animal studies (from prior 510(k)s) could be considered analogous to a "development dataset" or "validation dataset" in that they established the device's fundamental capabilities.

9. How Ground Truth for Training Set Was Established

Not applicable as there is no training set in the AI sense. For the underlying science and validation of the device:

Original 510(k) (K042961) and subsequent clearances:
- Animal studies: Physiological measurements, direct observation, and imaging outcomes in six pigs.
- Human experience: Intra-operative visual assessment by surgeons, clinical outcomes, and lack of reported adverse events over 4000 CABG procedures.
- In vitro testing: Conformance to electrical, electromagnetic, and laser safety standards (IEC, UL, CFR, ANSI).
  The combination of these methods established the ground truth for the device's initial safety and effectiveness. The current submission leverages this existing ground truth to demonstrate equivalence for the new ICG brand.

Summary

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K 072222

510(k) Summary

Trade Name:	SPY® Fluorescent Imaging System	SEP - 7 2007
Model Number:	SP2000
Common Name:	Fluorescent Angiographic System
Classification:	21 CFR 892.1600
Product Code:	90 IZI
Classification:	Class II
Manufacturer:	Novadaq Technologies Inc.2585 Skymark AvenueSuite 306Mississauga, OntarioCanadaL4W 4L5905.629.3822 ext. 240
Contact Name:	Allison MannersVice President - Regulatory and Clinical Affairs

Date 510(k) Summary Prepared: July 29, 2007

Legally Marketed Predicate Devices:

The Novadaq® SPY Fluorescent Imaging System (SPY System) had received FDA 510(k) clearance for market in January 2005 (K#042961). subsequent 510(k), clearance for a labeling change in May 2006 (K#060867), clearance for use in plastic, micro- and reconstructive surgery in January 2007 (K063345), and clearance use of an alternative brand of fluorescent dye in coronary artery bypass surgery in May 2007. pending drug approval (K#071037).

The Leica FL800 had received FDA 510(k) clearance for market in September 2006 (K#061871). The Leica FL800 is intended for use to allow neurosurgeons to view blood flow.

Device Description:

The SPY Fluorescent Imaging System is currently cleared for use:

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For intra-operative visual assessment of the coronary vasculature . and bypass grafts during coronary artery bypass graft (CABG) surgerv.
As an imaging system used in capturing and viewing fluorescent . images for the visual assessment of blood flow as an adjunctive method for the evaluation of tissue perfusion, and related tissuetransfer circulation in tissue and free flaps used in plastic, microand reconstructive surgical procedures.

The Novadaq® Technologies SPY® Fluorescent Imaging System consists of 2 components:

· the SP2000 Imaging Device
= the SPY Paq®

The SPY Paqs are available in 2 configurations dependent on the manufacturer of the indocyanine green (ICG) :

. Five (5) procedure SPY Pag
Six (6) procedure SPY Pag

Each SPY Paq contains sufficient numbers of custom sterile drapes, called Novadrape® and ICG and diluent for the noted number of imaging procedures. Each configuration of SPY Paq has a unique part number assigned to it, and different Instructions for Use exist for the SPY Pags that contain the 2 brands of ICG. The different Instructions for Use also have unique part numbers for ease of assembly of the Pags and guidance for the end user.

The SP2000 Imaging Device

The SP2000 Imaging Device consists of an imaging head containing a charge coupled device (CCD) camera, a laser light source, motion sensor and distance sensor attached via an articulating arm to a mobile cart. The mobile cart contains a flat panel display, computer, electronics enclosure and printer.

The SPY® System provides the surgeon with the capability to view record and replay fluorescent images of blood flow in vessels and bypass grafts of the heart. A laser light source is used to illuminate the area of interest.

1 Novadaq provides the ICG as it is sold by the manufacturer and does not adulterate the integrity of the original packaging or labeling. IC-Green™ (Akorn, Inc.) is packaged in an IC-Green kit that contains 6 x 25 mg vials of ICG along with 6 x 10 ml ampules of Aqueous Solvent. Two IC-Green packages comprise the 6 procedure SPY Paq, since two vials or IC-Green are required for each imaging procedure. ICG-PULSION® is packaged with 5 x 25 mg vials of ICG. Two ICG PULSION packages constitute a 5 procedure SPY Paq. Sufficient quantities of Novadrapes are placed in each configuration.

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ICG is injected intravenously through the central or peripheral venous line, bypass pump, cardioplegia line and coronary graft and while it is passing through the vessels, the absorption of laser light causes excitation of the dye followed by emission of infrared energy. The result is a fluorescent image of blood flow and related tissue perfusion in the vessels. A CCD camera captures the image. These images are used to evaluate the integrity of the coronary vasculature and blood flow in the heart and bypass grafts.

There have been no significant changes or modifications made to the SP2000 Imaging device since the original 510(k) clearance in January 2005 premarket notification 510(k) K#042961, the 510(k) submitted for a label change for this device K#060867, the clearance for use in the plastic, micro- and reconstructive surgery K063345, and clearance for use of an alternative brand of fluorescent dye - ICG PULSION® - in coronary artery bypass surgery in May 2007, pending drug approval K#071037.

This 510(k) submission describes a proposed change for the use of another brand of ICG and does not alter in any way the devices fundamental scientific technology or characteristics or the Indications for Use.

Intended Use of the SPY System:

The SPY Fluorescent Imaging System is indicated for use:

As an imaging system used in capturing and viewing fluorescent images . for the visual assessment of blood flow as an adjunctive method for the evaluation of tissue perfusion, and related tissue-transfer circulation in tissue and free flaps used in plastic, micro- and reconstructive surgical procedures.

Testing:

Animal studies, human experience and in vitro testing were conducted to support the safe and effective use of the SPY System in its original premarket notification 510(k) application (K042961).

The information contained within this Special premarket notification 510(k) demonstrates the equivalence of IC-Green™ and ICG-PULSION ICG products when used with the SPY Intra-operative Imaging Device.

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In Vitro Testing:

Testing of the SPY® System was completed in conformance with the following standards. The SPY System successfully met all of the requirements for these standards.

1. Electrical per IEC 60601-1 and UL2601-1
1. Electromagnetic Compatibility per IEC 60601-1-2
1. Light Emitting Laser Products per 21 CFR 1040
1. Safe Use of Lasers in Health Care Facilities per ANSI Z136.3
1. American National Standard for Safe Use of Lasers per ANSI Z136.1

In Vivo Testing:

The SPY System is commercially available in the United States of America, Japan, Europe and Canada. To date, the SPY System has been used in over 4000 CABG procedures in humans and there have been no reports of adverse acute or long-term cellular, renal or hepatic effects, Along with the data from intra-operative imaging in CABG surgery, the use of the SPY System in plastic, micro- or reconstructive and other vascular surgery demonstrated the clinical utility of the device in producing high quality and resolution images of the entire vascular bed of the point of interest.

Results from the use of the SPY System has been the subject of 12 peer reviewed journal articles, 10 related to its use in cardiac surgery and 2 related to its use in transplantation surgeries, namely kidney and liver. Please refer to the bibliography in Section 19 - Clinical for a listing of all relevant journal articles.

The literature reports that the SPY System was able to non-invasively, quickly and safely identify 17 conduits in 311 patients that required revision during the surgical procedures. In all cases the lack of patency was visualized clearly by the SPY System using doses of ICG well below that approved for human use, allowing the surgeon to revise the graft thus decreasing subsequent myocardial infarctions and the morbidity and mortality associated with poor graft patency. Cardiac, renal and hepatic function were monitored during use of the SPY System and there were no reported adverse effects. These publications originated in Europe, Japan and Canada, where various brands of ICG are commercially available and used.

To support the original traditional 510(k) premarket notification application. the system was used in six pig studies. These studies demonstrated that:

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1. it was possible to acquire high quality images in a simple and reproducible manner using small doses of ICG well below the concentrations approved for human use:
1. it was possible to perform multiple imaging sequences with no detrimental effects on heart function, coronary flow or peripheral pressure: and
1. it was possible to acquire images with no increase in myocardial tissue temperature; and
1. it was possible to visualize all of the coronary beds with high quality images even when the heart was in a vertical position for visualizing posterior arteries.

Therefore, in totality, the in vivo evidence shows that:

The exposure for the SPY® System is 35 mW/cm² which is far 1. below the maximum permissible exposure of 327 mW/cm2 established by ANSI for exposure to the skin.
Use of the SPY System does not cause any thermal damage to 2. the area of interest, even after repeated imaging sequences.
1. For the heart, there were no changes in electrocardiograms or arterial pressures during and/or following SPY use.
1. There were no acute or long-term cellular effects of using the SPY System.
1. There were no acute or long-term renal or hepatic effects of using the SPY System.
1. The SPY System was able to acquire high quality images of the entire vascular bed on each area of interest.
1. The SPY System is capable of imaging through the skin to provide a visual assessment of dermal and subdermal blood flow.

Conclusions:

The above testing demonstrates that the SPY Intra-operative Imaging System is safe and effective in capturing and viewing fluorescent images for the visual assessment of blood flow indicative of tissue perfusion, and related tissue-transfer circulation in tissue and free flaps used in plastic. micro- and reconstructive surgical procedures, irrespective of the brand of ICG used, and is equivalent to the predicate devices.

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Basu, Sankar

From:	Allison Manners [amanners@novadaq.com]
Sent:	Monday, August 27, 2007 5:36 PM
To:	Basu, Sankar
Cc:	Lukasz Brzozowski
Subject:	Revisions for Special 510(k) K072222
Importance:	High
Attachments:	3 - Indications for Use.doc; 4 - 510(k) Summary.doc

Dear Dr. Basu,

l have just faxed to you the documents as discussed in our telephone conversation this afternoon. In addition, for ease of your review, please find attached the electronic copies of the revised Indications for Use and he 510(k) Summary.

l trust that the information is acceptable, but please do not hesitate to contact me immediately should you require additional information.

Yours truly, Allison Manners VP, Regulatory and Clinical Affairs Novadaq Technologies Inc. Tel: (905) 629-3822 Ext. 240 Cell: (416) 567-5176

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/12 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES-USA" arranged around the perimeter. Inside the circle is a stylized graphic that resembles an abstract human form or a caduceus, a symbol often associated with medicine and healthcare.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Novadaq Technologies, Inc. % Ms. Allison Manners VP, Regulatory and Clinical Affairs 2585 Skymark Avenue, Suite 306 Mississauga, Ontario, Canada L4W 4L5

SEP = 7 2007

Re: K072222

Trade/Device Name: SPY® Fluorescent Imaging System: SP2000 Imaging Device Regulation Number: 21 CFR 892.1600 Regulation Name: Angiographic x-ray system Regulatory Class: II Product Code: IZI Dated: August 8, 2007 Received: August 10, 2007

Dear Ms. Manners:

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). You may not market this device, however, until such time as the new drug application for the drug indocyanine green (ICG) manufactured by PULSION® is approved for human use by The Center for Drug Evaluation and Research, FDA. When the device is marketed, it will be subject to the general controls provisions of the Federal Food, Drug, and Cosmetic Act (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.

However, you are responsible to determine that the medical devices you use as components in the SPY® have either been determined as substantially equivalent under the premarket notification process (Section 510(k) of the Act), or were on the market prior to May 28, 1976, the enactment ්ate of the Medical Device Amendments.

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.

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Page 2 - Ms. Allison Manners

Please be advised that FDA's issuance of a substantial equivalence determination does not mean Please be advised that FDA $ Issualitat of a substainled with other requirements of the Act
that FDA has made a determination that your device complies with other may that ITDA has made a determination that your access agencies. You must of any must of the or any Federal statules and reguirements, including, but not limited to: registration and listing (21)
comply with all the Act's requirements, including, but not issos navir comply with an the Act S requirements, merces manufacturing practice requirements as set
CFR Part 807); labeling (21 CFR Part 801); good manufacturing the electronic CFR Part 807), fabeling (21 CFR Part 800); good market 820); and if applicable, the clectronic
forth in the quality systems (QS) regulation (21 CFR 1000 1050 forth in the quality systems (QD) regulations 531-542 of the Act); 21 CFR 1000-1050.
product radiation control provisions (sections 531-542 of the Act); 21 CFR 1000-1050.

This letter will allow you to begin marketing your device as described in your 510(k) premarket I his letter will and w you to begin manteling your and one of the manufactured by PULSION® fibilitation subject to approval of the indestantial equivalence of your device to a legally Medical Systems. The I DA midnig of substination of your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and If you uesne specific acvice for your assic devices), please contact the Office of Compliance at (240) 276-0120. Also, please not the regulation entitled, "Misbranding by reference to (240) 270-0720. Allso, prease note the role ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . premarket tionneation (21 Of 1000he Division of Small Manufacturers, International and responsibilities under the Ace from the British or 638-2041 or (240) 276-3150, or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Prof

Mark N. Melkerson

Dep D.A

Mark N. M elkerson Director Division of General, Restorative and Neurological Devices Office of Device Evaluation Center for Devices and Radiological Health

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Indications for Use

510(k) Number (if known): K072222_

Device Name:

SPY® Fluorescent Imaging System: SP2000 Imaging Device

Indications for Use: The SPY System is an imaging system used in capturing and viewing fluorescent images for the visual assessment of blood flow as an adjunctive method for the evaluation of tissue perfusion, and related tissuetransfer circulation in tissue and free flaps used in plastic, micro- and reconstructive surgical procedures.

(Division Sign-Off)

Division of General, Restorative, and Neurological Devices

510(k) Number_________________________________________________________________________________________________________________________________________________________________ 16012222

X_____________________________________________________________________________________________________________________________________________________________________________ Prescription Use _____________________________________________________________________________________________________________________________________________________________

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

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Page 1 of 1

Regulation Number and Section

§ 892.1600 Angiographic x-ray system.

(a)
Identification. An angiographic x-ray system is a device intended for radiologic visualization of the heart, blood vessels, or lymphatic system during or after injection of a contrast medium. This generic type of device may include signal analysis and display equipment, patient and equipment supports, component parts, and accessories.(b)
Classification. Class II.