REGISTRY OF RADIOACTIVE SEALED
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SAFETY EVALUATION OF DEVICE



|NO. WA-1220-D-102-S | DATE: 21 November 2011 | PAGE: Page 1 of 15
|------------------- | ---------------------- | ------------------



SUPERSEDES: GA-1148-D-101-S



DEVICE TYPE: Low Dose Rate Brachytherapy



MODEL: GliaSite® Radiation
Therapy System (RTS), with catheter Models 1020, 1030, & 1040.



|MANUFACTURER/DISTRIBUTOR:               | IsoRay Medical, Inc.           
|--------------------------------------- | -------------------------------
|Previously:  Cytec Surgical Products II | Suite 106                      
|3581 Haddon Hall Drive                  | 350 Hills South                
|Buford, Georgia 30519                   | Richland, Washington 99354-5411



Email: info@isoray.comPhone: 509-375-1202



RADIONUCLIDE FORM AND DESCRIPTION:



lotrexTM, a proprietary liquid solution, consisting
of a combination of iodide and sodium 3-[1-125] iodo-4- hydroxybenzenesulfonate (1-HBS).



|ISOTOPE:             | MAXIMUM ACTIVITY:                       | NOMINAL ACTIVITY:        
|-------------------- | --------------------------------------- | -------------------------
|                     |                                         |                          
|Iodine 125           | 1320 millicuries (48.84GBq)             | 1200 mCi (44.4 GBq ± 10%)
|                     |                                         |                          
|LEAK TEST FREQUENCY: | Not Applicable                          |                          
|                     |                                         |                          
|PRINCIPAL USE:       | (AA)               Manual Brachytherapy |                          
|                     |                                         |                          
|CUSTOM DEVICE        | NO                                      |                          











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|NO. WA-1220-D-102-S | DATE: 21 November 2011 | PAGE: Page 2 of 15
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|DEVICE TYPE: | Low Dose Rate Brachytherapy
|------------ | ---------------------------



DESCRIPTION:



The GliaSite® RTS System is a single-use, low-dose
rate brachytherapy system consisting of a double-wall balloon catheter filled with lotrexTM, a solution containing organically
bound 1-125. The system is intended to deliver intracavitary radiation therapy in patients with malignant brain tumors following
tumor resection surgery. Radiation therapy is delivered by inflating the balloon portion of the device with a combination of lotrexTM
solution and saline. After a patient-specific dwell time, the lotrexTM solution is removed from the catheter, and the catheter
is then removed from the patient.



The GliaSite® catheter is
constructed from common biocompatible materials and is configured similar to other currently marketed interstitial and intracavitary
brachytherapy applicators.



The GliaSite® catheter consists
of a shaft with an inflatable dual silicon balloon configuration (balloon within a balloon) at the distal (treatment) end and an
infusion port at the proximal end. The three models of the GilaSite® RTS catheter refer to different sized balloons,
and thus, different fill volumes. The balloon diameters and maximum inflation/fill volumes are contained in the table below.



|Catheter Model |  | Balloon Diameter |  | Maximum Fill Volume
|-------------- |  | ---------------- |  | -------------------
|1020           |  | 2cm              |  | 5mL                
|1030           |  | 3cm              |  | 15mL               
|1040           |  | 4cm              |  | 35mL               



The inner balloon acts as a reservoir for the IotrexTM
solution. The outer balloon serves as the backup reservoir in the event the inner balloon should rupture. The RTS catheter
shaft is constructed from radiopaque silicone and bitumen tubing, and contains a malleable titanium element to assist in positioning
the balloon. Both ends of the inner balloon have radiopaque markers along the catheter shaft. Additionally, the catheter shaft
is equipped with positioning markers at 1 cm intervals beginning at the proximal end of the balloon.



The primary catheter lumen, which is used to access the inner
balloon, is connected to the infusion port. To prevent leakage during insertion of the lotrexTM solution, the infusion port
is equipped with a self-sealing silicone septum.



Refer to Figure 1a for a picture of an inflated, 3cm diameter
GliaSite® RTS catheter. Refer to Figures 2 - 4 for a simplified step-by-step walk through of a typical GliaSite®
treatment, showing how the GliaSite® is implanted and lotrexTM is inserted.











REGISTRY OF RADIOACTIVE SEALED
SOURCES AND DEVICES
SAFETY EVALUATION OF DEVICE



|NO. WA-1220-D-102-S | DATE: 21 November 2011 | PAGE: Page 3 of 15
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|DEVICE TYPE: | Low Dose Rate Brachytherapy
|------------ | ---------------------------



Labeling:



The GliaSite® catheters
do not require standard radioactive materials labeling since (1) the catheters, when shipped, do not contain radioactive material;
(2) the only time the catheter contains radioactive material is when it is implanted in the patient; (3) radioactive material is
removed from the catheter prior to removal from the patient; and (4) the catheter is disposed as radioactive waste or decayed in
storage.



The catheter itself is marked with "ISORAY"
and the model number of the catheter.



The tray in which the catheter is provided,
as well as the box in which the catheter and its ancillary equipment is shipped, is labeled in accordance with FDA guidelines.
A sample label for the GliaSite® box is provided in Figure 5. A sample of the labels on the lotrexTM solution
vial and shipping container is provided in Figures 6 and 7. Figure 8 shows a photo of the GliaSite® catheter, uninflated
and inflated, while Figure 9 shows the GliaSite® catheter and lotrexTM vial.



DIAGRAMS:



|Figure | 1  | Inflated GliaSite® RTS catheter             
|------ | -- | --------------------------------------------
|Figure | 2  | Implanted GliaSite® catheter                
|Figure | 3  | Surgical placement of the deflated GliaSite®
|Figure | 4  | Infusion of lotrexTM solution                
|Figure | 5  | Sample GliaSite® box label                  
|Figure | 6  | Sample lotrexTM vial label                   
|Figure | 7  | Sample lotrexTM shipping container label     
|Figure | 8  | GliaSite® catheter                          
|Figure | 9  | GliaSite® catheter and lotrexTM vial         
|Figure | 10 | GliaSite®RTS Tray                           











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|NO. WA-1220-D-102-S | DATE: 21 November 2011 | PAGE: Page 4 of 15
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|DEVICE TYPE: | Low Dose Rate Brachytherapy
|------------ | ---------------------------



CONDITIONS OF NORMAL USE:



The GliaSite® catheters
are sterilized and stored in sealed containers prior to use. The catheter is inserted into the patient during surgery and the balloon
is inflated. The entire catheter will be enclosed within the patient during the treatment time. The infusion port is located beneath
the skin.



The IotrexTM solution is received at the facility within
48 hours prior to its intended use in unit dose vials of 195 millicuries (± 20mCi) each. The lotrexTM is drawn from
the vials into a syringe and injected into the GliaSite® catheter via the infusion port in the patient's private
room or other secured location. Removal of the IotrexTM solution is accomplished by reversing the insertion procedure.



Both the GliaSite®catheter and the lotrexTM
solution are single use, and are disposed as radioactive waste immediately upon removal from the patient.



Refer to the "Limitations and/or Other Considerations of
Use" section for additional information regarding use of the GliaSite® Spectrum system.



PROTOTYPE TESTING:



The GliaSite® catheter has been subjected to
a battery of tests to confirm its integrity in typical use as well as expected accident conditions. These tests included bend and
tensile testing of the catheter shaft, design pressure verification of the balloons, material interaction of the balloon (with
x-ray contrast solution, saline, and lotrexTM), and the ability to successfully image the catheter.



Since the GliaSite® catheter must be able to
withstand gamma sterilization in the mega-Rad range prior to any use, additional testing of the effects of the radiation emitted
from the lotrexTM solution is not required.



Standard leak test methods for sealed sources
cannot be used on GliaSite®. Instead, the GliaSite®catheter is evaluated based on the amount of
pressure the balloon can withstand, and the amount of liquid which will permeate the balloons over an extended period of time.
It has been confirmed during animal and clinical trials that, due to silicon's permeability to small molecules, approximately 1%
of the afterloaded activity will diffuse across the membrane into the body. This exposure has been evaluated and determined to
have no adverse effects on the patient. Uptake in the thyroid gland may be minimized by administering a thyroid-blocking agent
to the patient prior to implantation of the GliaSite®.











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|NO. WA-1220-D-102-S | DATE: 21 November 2011 | PAGE: Page 5 of 15
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|DEVICE TYPE: | Low Dose Rate Brachytherapy
|------------ | ---------------------------



PROTOTYPE TESTING (continued):



The makeup of the lotrexTM compound is such that it precludes
uptake into the body or its organs. To simulate a complete catheter failure (both balloons rupture and release the lotrexTM
solution), lotrexTM solution was injected directly into the brain and tracked through the body. Two hours following
injection, 93% had been excreted from the body, while at 4 hours, 97.2% of the initial activity had been excreted. This shows that
lotrexTM is removed from the body more rapidly than standard radioiodide, which has a biological half-life of 8 hours.



To date, clinical trials using the GliaSite®
RTS have used a maximum activity of 450 mCi of lotrexTM. Data shows the GliaSite® catheter can safely
handle up to 1200 mCi of lotrexTM.



The GliaSite® RTS catheter has a shelf life of
5 years from the date of manufacture. The GliaSite®RTS catheter has undergone accelerated aging tests to validate
that this shelf life will not adversely affect product performance or safety. The lotrexTM solution has a maximum shelf life
of 29 days based on the requirement that no more than 20% of the 1-125 can be in an unbound (iodide) form at the time of afterloading.
The amount of unbound 1-125 increases over time as the 1-HBS compound degrades.



EXTERNAL RADIATION LEVELS:



The manufacturer provided calculated exposure rates from the
head of a patient who received a 1200 millicurie GliaSite® treatment with lotrexTM. Additionally, the manufacturer
provided actual data collected during trials for patients who received GliaSite® treatments with up to 460 mCi of
lotrexTM. There is no direct correlation between administered activity and exposure rates around the patient because (1) the
location of the GliaSite® catheter with respect to the surface of the head varies from patient to patient; and (2)
the physical makeup of the patient (i.e., skull thickness and skin thickness) varies, resulting in different levels of radiation
attenuation.



The exposure rates around a patient are recorded in the table
below.





|Exposure Rate, mR/hr (uSv/hr)
|-----------------------------
|Distance from  Patient's Head
|5 cm**                       
|30 cm                        
|100 cm                       
|at room doorway              



**exposure rates were recorded at surface of head
in clinical trials











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|NO. WA-1220-D-102-S | DATE: 21 November 2011 | PAGE: Page 6 of 15
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|DEVICE TYPE: | Low Dose Rate Brachytherapy
|------------ | ---------------------------



QUALITY ASSURANCE AND CONTROL:



The manufacturer has implemented a Quality Control System which
meets the qualifications of ISO 9001:1994, EN46001, and 21 CFR Part 820 (Quality Systems Regulations), which encompasses FDA's
Current Good Manufacturing Practices.



Items that are provided by suppliers or subcontractors must
conform to the design controls and specification requirements of the manufacturer's Quality System. The design controls provide
evidence of device performance, verification and validation through all phases of use, and indicate the QC checkpoints used during
component construction.



LIMITATIONS AND/OR OTHER CONSIDERATIONS OF USE:



| | * | The GliaSite® RTS shall be distributed to persons specifically
licensed for the use of radioactive materials in the healing arts by the NRC or an Agreement State.
| | - | ------------------------------------------------------------------------------------------------------------------------------------------------------------------



| | * | Handling, storage, use, transfer, and disposal: To be determined by
the licensing authority.
| | - | --------------------------------------------------------------------------------------------



| | * | The GliaSite® RTS shall only be used under the supervision
of an authorized user, or as approved by the U.S. Food and Drug Administration (FDA).
| | - | ------------------------------------------------------------------------------------------------------------------------------------------------



| | * | Users of the GliaSite® RTS shall have completed initial
training by the manufacturer, or persons specifically licensed by the NRC or an Agreement State to provide such training, prior
to initial use.
| | - | -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------



| | * | The lotrexTM solution has not had a sealed source evaluation
performed because it is a liquid and does not meet the requirements for a sealed source. lotrexTM solution has been deemed
acceptable for use in the GliaSite® RTS.
| | - | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------



| | * | It is recommended that patients who will be administered lotrexTM
via the GliaSite® RTS also receive a pre-dose thyroid blocking agent in accordance with the precautions set out
in the Instruction Manuals.
| | - | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------



| | * | REVIEWER NOTE: Care should be taken during infusion and removal
of lotrexTM solution to minimize the potential of surface contamination of the patient.
| | - | ------------------------------------------------------------------------------------------------------------------------------------------------------











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|NO. WA-1220-D-102-S | DATE: 21 November 2011 | PAGE: Page 7 of 15
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|DEVICE TYPE: | Low Dose Rate Brachytherapy
|------------ | ---------------------------



LIMITATIONS AND/OR OTHER CONSIDERATIONS OF USE: (continued)



| | * | REVIEWER NOTE: Patients who have been administered lotrexTM
solution using the GliaSite® RTS may be monitored and handled as if they were undergoing a thyroid ablation procedure.
For example, the product insert for lotrexTM recommends, "...all clothing, bandages or linens that come into contact
with urine, sweat, or saliva should be surveyed for the presence of 125I." Following radioactive Iodine procedures
will adequately protect workers and the general public from radiation and radioactive material associated with the patient.
| | - | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------



| | * | REVIEWER NOTE: Facilities may want to consider the orientation
of the bed in the patient's room so that radiation from the head of the patient has minimal impact on radiation workers and those
in unrestricted areas.
| | - | -----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------



| | * | REVIEWER NOTE: A radioactive spill kit should be available
in the room for use by trained personnel in the event of a radioactive spill.
| | - | ----------------------------------------------------------------------------------------------------------------------------------------



| | * | This registration sheet and the information contained within the references
shall not be changed without the written consent of the Washington State Department of Health, Office of Radiation Protection.
| | - | ----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------



SAFETY ANALYSIS SUMMARY:



The GliaSite® RTS delivers radiation
therapy to the resected cavities of brain tumors. The GliaSite® catheter remains in a sterile package until implanted
in the patient following tumor resection. The system is radioactive only after the lotrexTM solution is injected into the
GliaSite® catheter, which has been previously implanted and contained wholly within the patient's body. The lotrexTM
solution, shipped within 48 hours of expected use, is contained within a double-walled balloon catheter shown to be compatible
with the body and to maintain its integrity for the duration of the therapy.



Both the GliaSite® catheter and the
IotrexTM solution are single use and are disposed as radioactive waste immediately upon completion of treatment.



Under normal use, the GliaSite® catheter
is expected to release approximately 1% of the loaded activity into the body proper due to the permeability of silicon to small
molecules. This has been evaluated by the FDA and determined to have no adverse effects on the patient.











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|NO. WA-1220-D-102-S | DATE: 21 November 2011 | PAGE: Page 8 of 15
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|DEVICE TYPE: | Low Dose Rate Brachytherapy
|------------ | ---------------------------



SAFETY ANALYSIS SUMMARY (continued):



In the unlikely event that a GliaSite®
catheter fails during treatment and releases the lotrexTM solution into the body, the lotrexTM solution will be rapidly
excreted from the body primarily through the urine. Using the maximum dose administered to date, 460 mCi, doses to vital organs
under this scenario are less than those received during a routine thyroid ablation using 150 mCi of I-131. To protect the patient
in the event of device failure, a thyroid blocking agent should be administered prior to device implantation and lotrexTM
infusion, and continued during the course of treatment as outlined in the precautions in the GliaSite® RTS Instruction
Manual.



Based on review of the GliaSite®RTS,
and the information and test data cited below, we conclude that this device is acceptable for licensing purposes. Furthermore,
we conclude that the GliaSite® RTS would be expected to maintain containment integrity under normal conditions of
use and also during accidental conditions which might occur during uses authorized in this certificate.



NOTE ABOUT THIS SSDE: This SSDE is being issued
as a "new" SSDE solely because the owners and distributors of this device are now Washington state licensees and no Agreement
state may amend an SSDE issued by another state. This "new" SSDE relies primarily on the SSDE issued by the state of
Georgia to Proxima (and later, Cytec), for this device. Only the two changes made to the device by the state of Washington licensee
were reviewed in detail. These two changes are:(1) a new vendor (Vesta) and process for producing the balloons, now using
a Liquid Injection Molding (LIM) process rather than the old dipping process, (Vesta has always produced the catheters) and (2)
reversion to the original Proxima infusion port which is now solid Titanium again as opposed to the most recent port which used
a polysulfone body and a Titanium floor. Both the prior and the current ports use silicone septa. NOTE: At the request of the current
manufacturer/distributor, IsoRay, all references and authorizations for the GliaSite® Spectrum system have been
deleted from this Sealed Source and Device evaluation.











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|NO. WA-1220-D-102-S | DATE: 21 November 2011 | PAGE: Page 9 of 15
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| | DEVICE TYPE: | Low Dose Rate Brachytherapy
| | ------------ | ---------------------------



REFERENCES:

The following supporting documents for the
GliaSite® RTS System are hereby incorporated by reference and are made a part of this registry document.



| | * | Proxima Therapeutics, Inc.'s application with enclosures dated March
6, 2001, signed by James B. Stubbs, Ph.D., Vice President, Scientific Affairs.
| | - | ---------------------------------------------------------------------------------------------------------------------------------------------------



| | * | Letter with enclosures dated August 6, 2001, signed by James B. Stubbs,
Ph.D., Vice President, Scientific Affairs.
| | - | ------------------------------------------------------------------------------------------------------------------



| | * | Letters with enclosures dated 13 November 2002, 22 January 2003, and
1 October 2003, all signed by James B. Stubbs, Ph.D., Vice President, Scientific Affairs.
| | - | --------------------------------------------------------------------------------------------------------------------------------------------------------------



| | * | State of Georgia Sealed Source & Device Evaluation, Number GA-1148-D-101-S,
last amended in entirety 7 October 2003.
| | - | --------------------------------------------------------------------------------------------------------------------



| | * | Application and attachments dated 17 August 2011 from IsoRay Medical,
Inc., signed by Dale E. Boyce, Senior Radiation Scientist, IsoRay Medical, Inc.
| | - | -----------------------------------------------------------------------------------------------------------------------------------------------------



| | * | Additional documents, graphics, labels, etc. submitted to complete
the SSD review.
| | - | ----------------------------------------------------------------------------------



| | ISSUING AGENCY: | Washington State Department of Health, Office of Radiation Protection, Radioactive Materials Section.
| | --------------- | -----------------------------------------------------------------------------------------------------



This document is not a license
to receive, possess or distribute radioactive material. Receipt, possession and distribution of radioactive material, sources and
devices containing radioactive material, are subject to the terms and conditions of applicable regulations and licenses issued
by the U.S. Nuclear Regulatory Commission or Agreement States.



|Date: | 21 November 2011 |  | Reviewer | /s/ C. DeMaris     | 
|----- | ---------------- |  | -------- | ------------------ | 
|      |                  |  |          | C. DeMaris         | 
|      |                  |  |          |                    | 
|Date: | 21 November 2011 |  | Reviewer | /s/ Anine Grumbles | 
|      |                  |  |          | Anine Grumbles     | 











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Figure 1 Inflated GliaSite catheter











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|NO. WA-1220-D-102-S | DATE: 21 November 2011 | PAGE: Page 11 of 15
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(amended in its entirety)















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|NO. WA-1220-D-102-S | DATE: 21 November 2011 | PAGE: Page 14 of 15
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FIGURE 8







FIGURE 9











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