Liquid Brachytherapy Sources and Devices

Licensing Guidance - I-125 Iotrex™ Liquid Brachytherapy Source in Cytyc Surgical Products GliaSite^® Radiation Therapy System

I-125 Iotrex™ liquid brachytherapy sources are manual brachytherapy sources used for temporary brachytherapy implantation therapy in Cytyc Surgical Products' GliaSite^® Radiotherapy System (RTS).

The Cytyc Surgical Products' GliaSite^® RTS consists of Cytyc Surgical Products' GliaSite^® Radiotherapy system balloon catheter and Iotrex™ liquid brachytherapy source.

Required training and experience for authorized users is specified in 10 CFR 35.490 or, until October 25, 2005, 10 CFR 35.940 for use with materials governed by 10 CFR 35.400, as well as vendor training in use of Cytyc Surgical Products' GliaSite^® RTS.

An authorized user with experience in radiopharmaceutical therapy procedures should be on call to provide guidance in case of leakage of the implanted device.

The licensee shall follow all of the requirements in 10 CFR Part 35 for brachytherapy sources and manual brachytherapy use, except where the following license conditions provide regulatory relief:

For brachytherapy using Cytyc Surgical Products' GliaSite^® RTS, "prescribed dose" means the total dose documented in the written directive.

The written directive should include (1) before implantation: the treatment site, the radionuclide (including the chemical/physical form [Iotrex™]), and dose; and (2) after implantation but before completion of the procedure: the radionuclide (including the chemical /physical form [Iotrex™]), treatment site, and the total dose.

Procedures should specify how to confirm that the balloon does not leak before injection of the Iotrex™ or while Iotrex™ is implanted in the patient or human research subject.

"Source leakage" for the Iotrex™ implanted in the GliaSite^® RTS means leakage of I-125 that results in a dose that exceeds 0.5 Sv (50 rem) dose equivalent to any individual organ other than the treatment site (based on definition of a medical event).

The licensee shall retain a record of the leak test for three years (the period that 10 CFR 35.2067 requires for brachytherapy sources).

The licensee shall report a leaking source to the NRC within five days of the leakage test to the locations specified and provide the information identified in 10 CFR 35.3067.

The licensee shall provide instructions on how to safely handle contamination of unsealed materials, in addition to the instructions required by 10 CFR 35.410, "Safety instructions."

The following additional guidance applies when Iotrex™ is placed in vials, syringes, or radiation shields that are not labeled by the manufacturer:

Label syringes and syringe radiation shields with the radioisotope, form, and therapeutic procedure (i.e., I-125 Iotrex™ for brain brachytherapy).

Label vials and vial radiation shields with the radioisotope and form (i.e., I-125 Iotrex™).

Notes to Licensees

Change in physical conditions of use.

If the physical conditions of use exceed those reported in the SSD certificate, the limited specific medical use licensee should request an amendment for the new conditions, and broad scope licensee should perform its own engineering and radiation safety evaluation addressing those differences.

Use of other I-125 liquid brachytherapy sources or balloon treatment catheters.

The SSDR safety evaluation for Iotrex™ does not cover the use of any other I-125 source, including the preparation of NA-3-[I-125]iodo-4hydroxybenzenesulfonate by a commercial nuclear pharmacy, the medical use licensee's authorized nuclear pharmacist, or physician authorized user qualified to prepare radioactive drugs. Before authorization, the medical use of such a source will require a new SSD certificate (or safety evaluation by the broad scope medical use licensee) that addresses the conditions of use, safety of the new liquid brachytherapy source, and compatibility of the new source with the containment vessel.

The SSDR safety evaluation for the GliaSite^® RTS balloon catheter does not cover the use of any other balloon catheter to contain a liquid brachytherapy source. Before authorization, the medical use of such a balloon catheter will require a new SSD certificate (or safety evaluation by the broad scope medical use licensee) that addresses the conditions of use, safety of the new liquid brachytherapy source container, and compatibility of the new container with the liquid brachytherapy source.

Use of fluids that can reduce the effective dose delivered.

10 CFR 35.41 requires the licensee to develop, implement, and maintain written procedures to confirm that each administration is in accordance with the written directive. If any fluid used during inflation, imaging, or afterloading of the GliaSite^® RTS, (when mixed with prescribed activity of Iotrex™ in the GliaSite^® RTS) can cause an effective dose reduction of greater than 20 percent, the required procedures should describe how the licensee ensures that the fluid is not present when the Iotrex™ and saline are added to the catheter or measures the activity of the Iotrex™ upon removal of the Iotrex™ from the patient.

The licensee should try to avoid the human errors that lead to most medical events (e.g., mislabeling syringes, color code syringe/vial labeling errors, and picking up the wrong syringe because it is within reach of the intended syringes).

Note: Cytyc Surgical Products has determined that when a radiopaque dye with 330 milligrams of iodine per millimole of solution is diluted to a 25 percent strength solution, the GliaSite^® balloon can still be imaged and the diluted dye will absorb less than 20 percent of the I-125 dose from the Iotrex™. Therefore, if the licensee follows Cytyc Surgical Products' directions and dilutes the radiopaque dye every time the GliaSite^® balloon is imaged, the licensee will not have to measure the activity of the Iotrex™ upon its removal from the patient. In this case, the volumetric measurement of the removed Iotrex™ can be used to determine whether the administration was in accordance with the written directive. The licensee should contact Cytyc Surgical Products to determine the appropriate dilution factor for use with other radiopaque dyes or fluids that could cause an effective dose reduction of greater than 20 percent if mixed with Iotrex™ during treatment.

Revision of the Cytyc Surgical Products' GliaSite^® Radiotherapy System radiation safety programs to conform to changes in this licensing guidance.

The above-licensing guidance may be revised as additional experience is gained regarding the medical use of Cytyc Surgical Products' GliaSite^® RTS. A licensee already authorized to use this product that is committed by license condition to follow provisions in this guidance existing at the time of commitment must apply for and receive an amendment to its license in order to make changes to conform with the revised provisions.

An applicant initially applying for authorization for the medical use of Cytyc Surgical Products' GliaSite^® RTS, or a licensee applying for an amendment to conform with revisions in this guidance, may request authorization to allow future changes to its radiation safety program, provided the following conditions are met:

(1) the revision is in compliance with the regulations;
(2) the revision is based upon NRC's current guidance for Cytyc Surgical Products' GliaSite^® RTS 35.1000 use postes on the NRC Web site;
(3) the revision has been reviewed and approved by the licensee's radiation safety officer and licensee's management;
(4) the affected individuals are instructed on the revised program before the change is implemented;
(5) the licensee will retain a record of each change for five years; and
(6) the record will include a copy of the appropriate Web site guidance, the old procedure, the new procedure, the effective date of the change, and the signature of the licensee management that reviewed and approved the change.

If this authorization is approved, these conditions will be incorporated as license conditions in the licensee's license.