ML100750655

NR-220-D-849-S for MDS Nordion Which Replaces NR-220-D-113-S

ML100750655
Person / Time
Issue date:	03/12/2010
From:	Bhachu U S, Jankovich J J NRC/FSME/DMSSA/LISD/LB
To:	MDS Nordion
Kime T
References
10-13
Download: ML100750655 (16)

Text

REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF DEVICE

No.: NR-0220-D-849-S DATE: March 12, 2010 PAGE 1 OF 9 (Supercedes NR-0220-D-113-S)

DEVICE TYPE:

Glass Microsphere MODEL: TheraSphere

MANUFACTURER/DISTRIBUTOR: MDS Nordion, A Division of MDS (Canada) Inc.

(Formerly Atomic Energy of Canada, Ltd.)

447 March Road

Ottawa, Ontario

Canada K2K 1X8

ISOTOPE: MAXIMUM ACTIVITY:

Yttrium-90 20 GBq (540 mCi)

LEAK TEST FREQUENCY: None

PRINCIPAL USE: (AF) Other Medical Uses

CUSTOM SOURCE:

YES x NO

REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF DEVICE

No.: NR-0220-D-849-S DATE: March 12, 2010 PAGE 2 OF 9 (Supercedes NR-0220-D-113-S)

DEVICE TYPE:

Glass Microsphere DESCRIPTION:

TheraSphere is a therapeutic device consisting of insoluble glass

microspheres in which the radionuclide yttrium-90 (Y-90) is an

integral constituent. TheraSphere is used to treat liver tumors

via a catheter inserted in the hepatic artery. The size of

microspheres causes them to be embolized in the tumor vasculature

and hence, retained within the tumor. The microspheres are not

biodegradable and, once they have entered the tumor, do not

redistribute to other organs of the body. An Administration Set (supplied with the TheraSphere device) and Administration

Accessory Kit (supplied to new user sites) facilitate the

transfer of the radioactive microspheres from their container

into the tumor.

Yttrium-90 is an integral component of the glass matrix in the

microspheres. The beta particle emitted by the yttrium-90 during

radioactive decay has an average tissue penetration of 2.5 mm

(0.1 inch) and a maximum tissue penetration of approximately 8 mm

(0.3 inch). Therefore, this device delivers highly localized

radiation doses to tumors, while minimizing the damage to

surrounding healthy liver tissue. Yttrium-90, a pure beta

emitter, decays to stable zirconium-90 with a physical half life

of 64.2 hours2.314815e-5 days <br />5.555556e-4 hours <br />3.306878e-6 weeks <br />7.61e-7 months <br /> (2.68 days).

The microspheres have a mean diameter of 25 m ( 10 m), with less than 5% below 15 m and less than 10% above 35 m. Each milligram contains between 22,000 and 73,000 microspheres. Each

product vial can contain between 22 and 216 mg of spheres, depending on the radioactivity content.

The TheraSphere dose is supplied in 0.05 mL of sterile water

suspension contained in a 0.3-mL vee-bottom vial which is secured

within a 12 mm clear lucite vial shield (Attachment 1).

TheraSphere is available in various dose sizes up to a maximum of

20 GBq (540 mCi). A pre-assembled single use Administration Set

is provided with each dose.

The Administration Set is a single use delivery system designed

to deliver the microspheres to the disease site and to minimize

radiation exposure to administering personnel.

REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF DEVICE

No.: NR-0220-D-849-S DATE: March 12, 2010 PAGE 3 OF 9 (Supercedes NR-0220-D-113-S)

DEVICE TYPE:

Glass Microsphere DESCRIPTION (cont

=d):

The pre-assembled Administration Set has inlet and outlet

needles, a needle guide set and inlet and outlet lines that

facilitate infusion of the microspheres from the dose vial.

shows the positioning needle guide and priming

needle guide. The manufacturer specified that only 20 Ga needles

with long, tapered bevels should be used. The manufacturer also

specified that an inflation syringe, capable of delivering a

liquid volume of 20 cc with a minium pressure of 10 psig, should

be used with the Administration Set. Throughout the

administration procedure, the TheraSphere dose vial remains

sealed within the clear acrylic vial shield in which it was

supplied. A removable plug at the top of the vial shield

provides access to the septum of the dose vial. The needle guide

set permits proper placement of the inlet and outlet needles

during TheraSphere priming and administration steps.

The product is shipped with a package insert detailing the

directions for administration. The Administration Set and dose

vial are stored at room temperature until use. The TheraSphere

dose and Administration Set are shipped in a F400/F390 Type A

package (Attachment 3).

The TheraSphere Administration Set is to be used with the

Administration Accessory Kit. The Accessory Kit constitutes the

equipment which provides the layout for the Administration Set.

The Accessory Kit facilitates the infusion process and provides

the medical team with beta radiation shielding. The Accessory

Kit is an assembly of re-usable components which include the

support stand, two Model RAD-60R radiation dosimeters, the

shielding acrylic box, and handling tools. Attachment 4 shows

the Accessory Kit with the Administration Set and an inflation

syringe installed. Attachment 4 lists the inflation syringe, all

components in the Administration Set, and all components in the

Accessory Kit, providing for each component its name, location, supplier/vendor, and working life.

REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF DEVICE

No.: NR-0220-D-849-S DATE: March 12, 2010 PAGE 4 OF 9 (Supercedes NR-0220-D-113-S)

DEVICE TYPE:

Glass Microsphere DESCRIPTION (cont

=d):

Before administering the first procedure with the TheraSphere

device, all institutions must undergo the TheraSphere training

program as provided by the manufacturer or equivalent. All

clinical and technical support staff, such as radiation safety

personnel, physicians, medical physicists, technicians and

nurses, are required to demonstrate proficiency both in academic

knowledge and clinical skills in their respective areas regarding

the clinical use of the system. The training program addresses

such topics as the indication for use, description of available

doses, device description, patient preparation, dose calculation, radiation monitoring, and administration. The radiation safety

aspects of the training program include licensing, radiation

safety overview, expected dose rates, and detection of

microspheres.

The shelf life of the Administration Set is three years. The

shelf life of the needle guides is six months after

sterilization.

DIAGRAMS:

See Attachments 1 - 4.

LABELING:

Because of their small size, individual microspheres cannot be

labeled, therefore, each shipping container is labeled.

The lead-pot/Lucite-shield container is labeled with a 2x3 inch

(51x76 mm) label which indicates the date of assay, activity

level (in GBq), amount of microspheres (in mg), specific activity (in GBq/mg), and displays a yellow/black radiation symbol with the words A Caution Radioactive.

@ The label designates the content as A TheraSphere Yttrium-90 Microsphere Injection.

@ On the labels the designation A Lot@ and A Lot Number

@ are used to identify the individual TheraSphere doses and administration sets

similarly to the use of serial numbers.

REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF DEVICE

No.: NR-0220-D-849-S DATE: March 12, 2010 PAGE 5 OF 9 (Supercedes NR-0220-D-113-S)

DEVICE TYPE:

Glass Microsphere CONDITIONS OF NORMAL USE:

The TheraSphere is designed for use in hospital or clinical

environments for the treatment of cancerous tumors. The

TheraSphere should be used only by physicians who are qualified

by specific training in the safe use and handling of

brachytheraphy radionuclide sources. Adequate shielding and

precautions for handling radioactive material must be maintained.

The TheraSphere dose vial is supplied with a clear acrylic vial

shield to limit production of bremsstrahlung and radiation

exposure to personnel. Because of the dose rate at the vial

shield surface, the manufacturer requires caution including the

use of tongs and a lead shielded container when possible. The

vial should always be stored in a shielded location away from

personnel.

PROTOTYPE TESTING:

Prototype testing of individual microspheres has not been

performed by MDS Nordion, due to the limitations of their

microscopic size. Traditional physical/mechanical prototype

tests cannot be performed on a microsphere. The manufacturer

provided test data on lots of bulk microspheres regarding

chemical durability and stability.

The manufacturer subjected the F400/F390 type A transport

container to a series of tests which included a water spray test, a 9 m (354 in.) drop test and two sequential penetration tests.

The container maintained its integrity in the tests. The F390

lead pot and the TheraSphere acrylic shield were drop-tested from

1 m (39.4 in.) in various configurations onto a concrete floor

and demonstrated that the containment could withstand normal

handling accidents which might occur in a hospital environment.

EXTERNAL RADIATION LEVELS:

The manufacturer reported the following external radiation levels

for a device containing an activity of 19.1 GBq (515 mCi) are as

follows:

REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF DEVICE

No.: NR-0220-D-849-S DATE: March 12, 2010 PAGE 6 OF 9 (Supercedes NR-0220-D-113-S)

DEVICE TYPE:

Glass Microsphere EXTERNAL RADIATION LEVELS (cont

=d):

Distance from Measured radiation levels

source Lucite Vial Lucite Vial in F390 Lead Pot (cm) (inch) (mrem/hr) (mSv/hr) (mrem/hr) (mSv/hr) 0 0 810 8.1 85 0.85 5 230 2.3 33 0.33 30 20 0.2 2.7 0.027

100 2.2 0.022 0.6 0.006

The level of ambient radiation in the vicinity of the

Administration Accessory kit is a function of the activity being

administered. The manufacturer reported that for a delivered

dose of 10 GBq (270 mCi) the radiation fields are typically as

listed below:

Location

Time 1" Behind Lead Pot at Dose Vial Blue Stopcock Red Stopcock

Start and After Priming* 25-30 mR/hr 1-2 mR/hr 1-2 mR/hr

During Infusion 25 mR/hr reducing to

0 mR/hr 30-50 mR/hr**

>2000 R/hr 30-50 mR/hr**

End of Successful

Infusion 0-1 mR/hr 1-4 mR/hr**

5-20 R/hr 1-4 mR/hr**

• Effective priming with only minor introduction of spheres above the dose vial.

• • Bremsstrahlung

REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF DEVICE

No.: NR-0220-D-849-S DATE: March 12, 2010 PAGE 7 OF 9 (Supercedes NR-0220-D-113-S)

DEVICE TYPE:

Glass Microsphere QUALITY ASSURANCE AND CONTROL:

MDS Nordion employs a quality assurance and quality control

program to insure that each component is manufactured to the

specifications furnished to the NRC. The quality assurance

program has been assessed and registered as meeting the

requirements of ISO 9001. The quality assurance program has been

deemed acceptable for licensing purposes by NRC. A copy of the

program is on file with NRC.

MDS Nordion provided quality assurance specifications which are

maintained for the glass frit and the microspheres made from the

acceptable frit. The specifications address physical and

chemical attributes, purity requirements, inspection

requirements, handling and storage instructions.

LIMITATIONS AND/OR OTHER CONSIDERATIONS OF USE:

$ The Model TheraSphere device shall be manufactured and distributed according to the requirements of Section 32.74, 10 CFR Part 32 and distributed only to persons specifically

licensed by the NRC or an Agreement State.

$ This registration sheet and the information contained within the references shall not be changed without the written

consent of the NRC.

$ Handling, storage, use, transfer, and disposal: To be determined by the licensing authority. The devices shall be handled only in accordance with the manufacturer

=s instructions and with appropriate equipment (e.g., due to

the activity level, forceps are recommended).

$ REVIEWER NOTE: Please ensure the safety procedures outlined in 10 CFR Part 35 are adhered to, especially as they pertain

to the handling of the devices.

REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF DEVICE

No.: NR-0220-D-849-S DATE: March 12, 2010 PAGE 8 OF 9 (Supercedes NR-0220-D-113-S)

DEVICE TYPE:

Glass Microsphere LIMITATIONS AND/OR OTHER CONSIDERATIONS OF USE (cont

=d): $ REVIEWER NOTE: The clinical staff who administers the TheraSpheres must complete a training program that is

specific to the TheraSphere administration procedure, as

described above.

$ REVIEWER NOTE: Previous experience in delivering the microspheres from the clear acrylic vial resulted in

development of the Administration Accessory Kit and needle

guide set, as well as introduction of an inflation syringe, capable of delivering a liquid volume of 20 cc with a

minimum pressure of 10 psig and 20 gauge needles with long

tapered bevels. These components are needed to enhance

delivery of the TheraSpheres and prevent misadministration.

$ REVIEWER NOTE: The TheraSpheres disposal should be handled in accordance with Information Notice 2007-10, "Yttrium 90

TheraSpheres and Sirspheres Impurities."

SAFETY ANALYSIS

SUMMARY

Based on our review of the information and test data cited below

and the past history of similar designs, we continue to conclude

that the MDS Nordion, Model TheraSphere devices are acceptable

for licensing purposes.

Furthermore, we continue to conclude that these devices would be

expected to maintain their integrity for normal and accidental

conditions of use which might occur during the uses specified in

this registration sheet.

REFERENCES

The following supporting documents for the MDS Nordion, Model

TheraSphere Yttrium-90 glass microsphere device are hereby

incorporated by reference and are made a part of this registry

document.

REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF DEVICE

No.: NR-0220-D-849-S DATE: March 12, 2010 PAGE 9 OF 9 (Supercedes NR-0220-D-113-S)

DEVICE TYPE:

Glass Microsphere REFERENCES (cont

=d): $ MDS Nordion application, dated July 2, 1999, with enclosures thereto. $ MDS Nordion letters dated August 13, 1999, December 17, 1999, January 19, 2000, and February 2, 2000, with

enclosures thereto.

$ MDS Nordion

=s letters dated September 6, 2001, March 1, 2002, March 21, 2002, and telefax dated January 9, 2002, with enclosures thereto.

$ MDS Nordion

=s facsimile dated April 15, 2002, with enclosure thereto. $ MDS Nordion

=s letters dated September 15, 2004 and December 17, 2004, with enclosures thereto.

$ MDS Nordion letter dated, July 13, 2009, with enclosures thereto.

ISSUING AGENCY

U.S. Nuclear Regulatory Commission

Date: March 12, 2010 Reviewer:

/RA/ John J. Jankovich

Date: March 12, 2010 Concurrence:

/RA/

Ujagar S. Bhachu

REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF DEVICE No.: NR-0220-D-849-S DATE: March 12, 2010 ATTACHMENT 1 (Supercedes NR-0220-D-113-S)

TheraSphere Container for Microsphere Vials

REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF DEVICE No.: NR-0220-D-849-S DATE: March 12, 2010 ATTACHMENT 2 (Supercedes NR-0220-D-113-S)

Positioning Needle and Priming Needle Guide (For Explanation of the Parts Numbers, See the Parts List in

)

REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF DEVICE No.: NR-0220-D-849-S DATE: March 12, 2010 ATTACHMENT 3 (Supercedes NR-0220-D-113-S)

Item No. Description 1 F390 Lead Pot Body 2 Shield Base (Cast Acrylic) 3 Dose Vial 3ml

4 Septum 5 Aluminum Crimp Cap 6 Shield Cap (Cast Acrylic) 7 Shield Plug (Cast Acrylic) 8 F390 Lead Pot Cap 9 Tamper Evidence Seal 10 3M Fibre Filament Tape

TheraSphere Transportation Package Schematic

REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF DEVICE No.: NR-0220-D-849-S DATE: March 12, 2010 ATTACHMENT 4 (Supercedes NR-0220-D-113-S)

(Page 1/3)

Administration Accessory Kit (Shown Assembled in the Administration Set)

(For Explanation of Parts Numbers, See Parts List in the

Following Pages)

REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF DEVICE No.: NR-0220-D-849-S DATE: March 12, 2010 ATTACHMENT 4 (Supercedes NR-0220-D-113-S)

(Page 2/3) Parts List Comp. No. Comp. Name Location Supplier or Vendor Working Life

1 Fluid Source Supplied by hospital Physician N/A 2 Piercing Pin Administration Set MDSN Single Use

3 Fluid Line Administration Set MDSN Single Use

4 Red Stopcock Administration Set MDSN Single Use

5 Inflation Syringe Accessory for Administration Set Physician or MDSN Single Use

6 Inlet Line Administration Set MDSN Single Use

7 Inlet Needle with Check Valve Administration Set MDSN Single Use

8 TheraSphere 7 Dose Vial Dose Vial MDSN Single Use

9 Lead Pot (Dose Vial) Dose Vial Packaging MDSN Single Use

10 Acrylic Vial Shield Dose Vial Packaging MDSN Single Use

11 Outlet Needle Administration Set MDSN Single Use

12 Outlet Line Administration Set MDSN Single Use

13 Blue Stopcock Administration Set MDSN Single Use

14 Vent Line Administration Set MDSN Single Use

15 Empty Vial Administration Set MDSN Single Use

16 Lead Pot (Empty Vial) Accessory Kit MDSN Permanent

17 Priming Needle Guide Administration Set MDSN Single Use 18 Needle Guide Administration Set MDSN Single Use 19 Dosimeter RAD-60R (RADOS 1) Accessory Kit MDSN Permanent REGISTRY OF RADIOACTIVE SEALED SOURCES AND DEVICES SAFETY EVALUATION OF DEVICE No.: NR-0220-D-849-S DATE: March 12, 2010 ATTACHMENT 4 (Supercedes NR-0220-D-113-S)

(Page 3/3) Parts List (Cont

=d) Comp. No. Comp. Name Location Supplier or Vendor Working Life

20 Acrylic Enclosure Cover Accessory Kit MDSN Permanent

21 Dosimeter RAD-60R (RADOS 2)

Accessory Kit MDSN Permanent

22 Stopcock Holder (Outlet Line)

Accessory Kit MDSN Permanent

23 Support Arm Accessory Kit MDSN Permanent

24 Stand Accessory Kit MDSN Permanent

25 Acrylic Enclosure Bottom Accessory Kit MDSN Permanent

26 Stopcock Extension Handle Accessory Kit MDSN Permanent

27 Tweezers Accessory Kit MDSN Permanent

28 Stopcock Holder (Inlet Line)

Accessory Kit MDSN Permanent

29 Clevis Pin Accessory Kit MDSN Permanent

30 Syringe Holder Accessory Kit MDSN Permanent

31 Hook for Fluid Source Accessory Kit MDSN Permanent