ML22018A225

Alpha Tau Alpha Dart Manual Brachtherapy Licensing Guidance

ML22018A225
Person / Time
Issue date:	03/10/2022
From:	Katherine Tapp Office of Nuclear Material Safety and Safeguards
To:
K Tapp, NMSS/MSST/MSEB
References
Download: ML22018A225 (10)

Text

Alpha Tau Alpha DaRTTM Manual Brachytherapy Licensing Guidance March 10, 2022 NRC Contact Katie Tapp (301) 415-0236 MedicalQuestions.Resource@nrc.gov

Table of Contents 1 10 CFR 35.1000 Use ............................................................................................................. 1 2 Device Description ................................................................................................................. 1 3 Licensing Guidance ............................................................................................................... 2 4 Requirements not Specific to 10 CFR 35.1000 Use .............................................................. 2 5 Specific Licensing Guidance for Alpha DaRTTM..................................................................... 2 5.1 Radionuclides, Form, Possession Limits, and Purpose of Use ...................................... 2 5.2 Training and Experience ................................................................................................. 3

6. License Conditions ................................................................................................................ 4 6.1 Procedures for Administration ........................................................................................ 4 6.2 Medical Event Reporting ................................................................................................ 4 6.4 Labeling .......................................................................................................................... 5 6.5 Surveys ........................................................................................................................... 5 6.8 Contamination Control .................................................................................................... 5 6.9 Radiation Protection Program Changes ......................................................................... 6

7. Notes to Licensees ............................................................................................................. 6 7.1 Change in Physical Conditions of Use ........................................................................... 6 7.2 Written Directives ........................................................................................................... 6 7.3 Patient Release .............................................................................................................. 6 7.4 Sealed Source and Device Registry ............................................................................... 7 7.5 Brachytherapy Source Accountability ............................................................................. 7

8. Notes to Regulators ........................................................................................................... 7 8.1 Inspection Frequency ..................................................................................................... 7 8.2 Program Code ................................................................................................................ 7

9. Paperwork Reduction Act Statement ..................................................................................... 7

10. Public Protection Notification ............................................................................................. 8

1 10 CFR 35.1000 Use Alpha DaRTTM (Diffusing Alpha-emitters Radiation Therapy) are manual brachytherapy sources, with many unique properties that merit radiation safety considerations other than those required by Title 10 of the Code of Federal Regulations (CFR) Part 35, Subpart F, Manual Brachytherapy. These unique properties include the release of radon-220 (Rn-220), an alpha emitting noble gas from the radium-224 (Ra-224) source, in tissue. As a result, Alpha DaRTTM is regulated under 10 CFR 35.1000, Other medical uses of byproduct material or radiation from byproduct material.1 2 Device Description The Alpha DaRTTM device is a source and applicator designed for manual brachytherapy. The Alpha DaRTTM source are Ra-224 seeds, which are implanted into the tumor using an Alpha DaRTTM applicator according to a pre-determined plan. Inside the tumor, the Ra-224 decays by alpha emission and the seeds release Rn-220 by recoil. Rn-220 is a noble gas and will diffuse in the extra- and intra-cellular space near the seed, occasionally entering and leaving the porous network of tumor blood vessels. Irradiation of tissue continues through beta and alpha emissions throughout the remainder of the decay chain. The seeds are made of a stainless steel with layer of Ra-224 affixed to the surface of the tube.

The applicator comprises two major components:

1. a needle or catheter, in the form of a Kapton tube, with the Alpha DaRTTM seeds placed in it. The Alpha DaRTTM seeds are stringed on a biocompatible suture and loaded inside a rigid needle or flexible catheter and sealed inside with glycerin; and

2. a stylet (plunger) inserted into the needle cannula (or catheter), reaching the back end of the Alpha DaRTTM seeds. During administration, the strung seeds are pushed through the glycerin into the tumor volume via the plunger.

In addition, there are two auxiliary components of the applicator:

1. a protective cap is attached to the needle or catheter to prevent inadvertent damage during transportation; and

2. a safety screw, which secures the needle and the stylet firmly together.

More information about the device can be found in its Sealed Source and Device Registry, MA-1426-D-101-S. The Alpha DaRTTM series device was conditionally approved by the U.S.

Food and Drug Administration in Investigational Device Exemption number G180076, dated May 10, 2018, for temporary implant therapy.

1 10 CFR 35.1000 is designated as Compatibility Category D. Agreement States are not required to adopt these regulations for purposes of compatibility but are not prohibited from adopting Compatibility Category D regulations if they so choose. If Agreement States choose to adopt this licensing guidance, references to 10 CFR should be changed to the equivalent Agreement State regulations.

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3 Licensing Guidance The license conditions listed in this document provide applicants with the acceptable means in satisfying the requirements for a license for the use of Alpha DaRTTM. This information is not intended to be the only means of satisfying the requirements. The applicant must submit the information required to meet 10 CFR 30.33, General requirements for issuance of specific licenses, and 35.12, Application for license, amendment, and renewal, as described below.

The applicant should submit additional information and commitments requested below or may, unless the information is specifically required by regulation, submit alternative information and commitments for review by the U.S. Nuclear Regulatory Commission (NRC) staff to make a licensing determination. The commitments incorporated into the license-by-license condition will be reviewed during routine inspections. If an applicant commits to the guidance provided below, the applicant must follow commitments described with the use of the word should. This guidance may be revised as additional experience is gained regarding the medical use of Alpha DaRTTM.

Applicants should also refer to NUREG-1556, Volume 9, Revision 3, Consolidated Guidance About Material Licenses: Program-Specific Guidance about Medical Use Licenses, as it provides overall licensing guidance for all medical uses of byproduct material, including applicable model procedures for audits, occupational dose monitoring program and surveys.

Guidance specific for the use of Alpha DaRTTM under 10 CFR 35.1000, Other medical uses of byproduct material or radiation from byproduct material are contained herein.

4 Requirements not Specific to 10 CFR 35.1000 Use Applicants must commit to meet the general requirements in 10 CFR Part 35, Subpart A "General Information; Subpart BGeneral Administrative Requirements; Subpart C"General Technical Requirements; Subpart LRecords; and Subpart MReports, except as specified in this guidance. Additionally, applicants must meet applicable requirements of 10 CFR Part 19, Notices, Instructions and Reports to Workers: Inspection and Investigations; Part 20, Standards for Protection Against Radiation; and Part 30, Rules of General Applicability to Domestic Licensing of byproduct material. The enclosed consolidated technical analysis table provides guidance on applicable requirements.

5 Specific Licensing Guidance for Alpha DaRTTM 5.1 Radionuclides, Form, Possession Limits, and Purpose of Use Pursuant to 10 CFR 35.12(c), the applicant must identify the radionuclide, chemical/physical form, requested maximum possession limit, and purpose of use. The information in the table below provides the suggested format for completing Item 5 (Radioactive Material) and Item 6 (Purpose of Use) on the NRC Form 313, Application for Materials License.

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Radionuclides Radium-224 permitted by (NRC Form 313 Item 5a) 10 CFR 35.1000 Chemical/Physical Form Sealed sources (NRC Form 313 Item 5b) (Manufacturer Alpha Tau Medical, Inc., Model No.

_____)

Maximum Possession Limit ___ mCi (NRC Form 313 Item 5c)

Purpose of Use Diffusing alpha emitting (NRC Form 313 Item 6) brachytherapy procedure permitted by 10 CFR 35.1000.

5.2 Training and Experience Licensees must have at least one Authorized User (AU) and Radiation Safety Officer (RSO) for Alpha DaRTTM before the source can be added to the license. NRC staff has determined the following training and experience (T&E) criteria is appropriate to authorize AUs and RSOs for Alpha DaRTTM. Applicants must submit documentation showing this criterion is met, but the applicant may submit alternative T&E commitments to be reviewed on a case-by-case basis by NRC staff. The alternative T&E commitments should include an explanation of why the applicant believes the alternative T&E commitments demonstrate that the individuals are qualified to be an AU.

5.2.1 Authorized Users (AU)

NRC has determined that individuals meeting the AU T&E criteria A and B, provided below, can be authorized for the use of Alpha DaRTTM.

A.

1. Is identified as an AU for medical use in 10 CFR 35.1000 for Alpha DaRTTM or 10 CFR 35.400, Use of sources for manual brachytherapy; or

2. Meets the T&E requirements of 10 CFR 35.490, Training for use of manual brachytherapy sources, including a written attestation when necessary.

And B.

Has successfully completed training in delivery, safety procedures, and clinical use for Alpha DaRTTM. This training may be provided by either the vendor for new users or by receiving training supervised by an AU authorized for Alpha DaRTTM. Safety procedures and clinical use training should include preparing, implanting, and removing the seeds; using administrative controls to prevent a medical event; and using procedures to minimize the risk of and monitor for contamination and to ensure proper decontamination. The individual has a written attestation that the AU has satisfactorily completed these requirements and is able to independently fulfill the radiation safety-related duties as an AU for use of Alpha DaRTTM brachytherapy.

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5.2.2 Radiation Safety Officer (RSO)

The RSO must have training as specified in 10 CFR 35.50, Training for Radiation Safety Officer and Associate Radiation Safety Officer, including training in radiation safety, regulatory issues, and emergency procedures for Alpha DaRTTM. This training requirement may be satisfied by completing training that is supervised by an RSO, an Associate RSO, or AU authorized for Alpha DaRT, as appropriate. In addition, RSOs should be aware of all license conditions and procedures specific to the individual license.

6. License Conditions The applicant shall commit to follow all applicable requirements in 10 CFR Part 35 for brachytherapy sources and manual brachytherapy use and shall commit to the following licensing commitments. The table contained in the appendix provides more details on applicable 10 CFR Part 35 requirements.

6.1 Procedures for Administration The licensee must have procedures for administration requiring a written directive as specified in 10 CFR 35.41, Procedures for administrations requiring a written directive, specifically to ensure high confidence that the patients or human research subjects identity is verified before each administration and each administration is in accordance with the written directive. In addition to requirements in 10 CFR 35.41, licensees shall commit to include verification that seeds are fully contained within the patients body during treatment to avoid significant daughter products leakage and contamination. In addition, licensees shall commit to evaluating the location of the seeds prior to removal to determine if the seeds moved during treatment to determine if a medical event occurred. Similar to 10 CFR 35.2041, Records for procedures for administrations requiring a written directive, licensees shall retain a copy of these procedures for the duration of the license. See NUREG-1556, Volume 9, Revision 3, Section 8.10.13, Procedures for Administration when a Written Directive is Required, and NUREG-1556, Volume 9, Revision 3, Appendix S for more information.

6.2 Medical Event Reporting Licensees are required to report medical events in accordance with 10 CFR 35.3045, Medical event reporting with the exceptions listed below.

• Licensees will not be required to report a medical event caused by a leaking source in accordance with 10 CFR 35.3045(a)(1)(ii)(e) or 10 CFR 35.3045 (2)(iii)(D) as Alpha DaRTTM seeds are not a sealed source.

• Licensee shall commit to report any event in which the seed is implanted directly into a location discontinuous from the treatment site, as documented in the post-implantation portion of the written directive. As stated above, total source strength only needs to include Ra-224 activity.

• Licensees shall commit to report any discovered event where the dose to the skin or an organ or tissue other than the treatment site that exceeds by 0.5 Sv (50 rem) or more the expected dose to that site from the procedure if the administration had been given in accordance with the written directive prepared or revised before administration; and 50 percent or more the expected dose to that site from the procedure if the administration had been given in accordance with the written directive prepared or revised before administration.

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6.4 Labeling Labeling requirements in 10 CFR 35.69, Labeling of vials and syringes, are not required for Alpha DaRTTM seeds. The seeds are not a radioactive drug. Licensees shall commit to keep the applicator in the labeled container (i.e., sterilized bag) provided by the manufacturer until the applicator is needed for use or conditions in 10 CFR 35.92, Decay-in-storage are met, if the applicator is not used and remains at the licensee facility.

6.5 Surveys In addition to area surveys required by 10 CFR Part 20 and 10 CFR 35.70, Surveys of ambient radiation exposure rate, a licensee shall commit to survey with a radiation detection survey instrument the area where Alpha DaRTTM seeds were prepared for use or administered after each administration. Both ambient radiation and contamination surveys should be performed. Similar to 10 CFR 35.2070, Records of surveys for ambient radiation exposure rate, licensees shall retain a record of the surveys after each administration for 3 years. The record must include the date of the survey, the results of the survey, the instrument used to make the survey, and the name of the individual who performed the survey. See NUREG-1556, Volume 9, Revision 3, Section 8.10.12, Area Surveys, Appendix K, General Radiation Monitoring Instrument Specifications and Survey Instrument Calibration Program, and Appendix R, Model Procedures for Area Surveys for more information regarding ambient radiation and contamination surveys.

6.7 Calibration As Alpha DaRTTM is a brachytherapy device, licensees do not need to determine unsealed byproduct activity in accordance with 10 CFR 35.63, Determination of dosages of unsealed byproduct material for medical use. Licensees shall commit to following 10 CFR 35.432, Calibration measurements of brachytherapy sources, and 10 CFR 35.2432, Records of calibration measurements of brachytherapy sources, for calibration and recordkeeping. In accordance with 10 CFR 35.432, licensees may use measurements provided by the source manufacturer.

6.8 Contamination Control In addition to safety precautions required in 10 CFR 35.415, the licensee shall commit to placing all unsealed seeds that are not in use and contaminated waste in a sealed container. So that a licensee can immediately place a damaged device or unused seeds in case of an emergency to reduce contamination, licensees shall commit to having a sealed container available where sources are being prepared and used. The licensees shall use a sealed container tested by the manufacturer or licensee to ensure the container prevents Rn-220 leakage. Licensees can dispose of waste in accordance with 10 CFR 35.92, Decay-in-storage, or other appropriate methods allowed in 10 CFR Part 20.

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6.9 Radiation Protection Program Changes As this guidance may be revised as additional experience is gained regarding the medical use of Alpha DaRTTM, an applicant initially applying for authorization for the medical use of Alpha DaRTTM may request to incorporate into its license a radiation protection program revisions process similar to 10 CFR 35.26. Such a change process can allow some future changes to radiation safety programs without a license amendment provided that the change process requires the following conditions to be met for revisions to the radiation safety program:

1. the revision is in compliance with the regulations; and

2. the revision is based upon NRCs current 10 CFR 35.1000 use guidance for Alpha DaRTTM posted on the NRCs Medical Uses Licensee Toolkit Web site; and

3. the revision has been reviewed and approved by the licensees RSO and licensees management; and

4. the affected individuals are instructed on the revised program before the change is implemented; and

5. the licensee will retain a record of each change for five years; and

6. the record will include a copy of the appropriate website 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.

7. Notes to Licensees 7.1 Change in Physical Conditions of Use If the physical conditions of use differ from those reported in the sealed source and device registry, a limited specific medical use licensee shall request an amendment for the new conditions and a broad scope licensee shall perform its own engineering and radiation safety evaluation addressing those differences.

7.2 Written Directives The licensee must complete a written directive in accordance with 10 CFR 35.40, Written directives. When total source strength is required to be recorded on the written directive, only Ra-224 activity needs to be included. The licensee shall retain a copy of the written directive in accordance with 10 CFR 35.2040, Records of written directives.

7.3 Patient Release The licensee should develop procedures that describe measures taken to ensure that radiation emissions from each patient or human research subject permits their release in accordance with 10 CFR 35.75, Release of individuals containing unsealed byproduct material or implants containing byproduct material. Licensees should note temporary use affixed by sutures that protrude outside of the body have a potential to become dislodged or allow for gaseous release.

Patients should not be released from the licensed facility if it is likely that the seed or seal will become dislodged under normal conditions and potentially cause public dose limits to be exceeded. If there is a potential for a seed or seal to become dislodged under unique situations, licensees must have preventative measures in place to ensure public dose limits are not exceeded. Licensees must report lost sources in accordance with 10 CFR 20.2201, Reports of theft or loss of licensed material if a seed becomes dislodged lost and is not 6

recovered or if temporary implants issued to a patient are not returned to the licensee. Additional guidance for release of patients or human research subjects following administration of radioactive materials may be found in Regulatory Guide 8.39, Release of Patients Administered Radioactive Materials.

7.4 Sealed Source and Device Registry In accordance with 10 CFR 35.400, licensees may use Alpha DaRTTM sources for manual brachytherapy uses that are not explicitly listed in the sealed source and device registry. However, the sources must be used in accordance with the radiation safety conditions and limitations described in the sealed source and device registry. As the applicators for the Alpha DaRTTM are specific for radiation safety as they are designed to minimize contamination, licensees should only use the applicators as described in the sealed source and device registry for administration.

7.5 Brachytherapy Source Accountability Licensees shall maintain accountability at all times for all brachytherapy sources in storage or use in accordance with 10 CFR 35.406, Brachytherapy sources accountability. In addition, licensees shall maintain records of brachytherapy sources accountability in accordance with 10 CFR 35.2406, Records of brachytherapy source accountability. Licensees should document the location the patient plans to reside. Licensees should also have patient contact information and provide the patient with instructions on actions to take if source is dislodged during treatment.

8. Notes to Regulators 8.1 Inspection Frequency Licenses authorizing Alpha DaRTTM should be inspected every two years. Per Enclosure 1 to Inspection Manual Chapter 2800, Materials Inspection Program licenses authorizing emerging technology under 10 CFR 35.1000 are assigned a Priority 2 inspection code.

8.2 Program Code The NRC regions should use program code 02240.

9. Paperwork Reduction Act Statement This licensing guidance provides voluntary guidance for implementing the mandatory information collections in 10 CFR Parts 30 and 35 that are subject to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et. seq.). These information collections were approved by the Office of Management and Budget (OMB), approval numbers 3150-0017 and 3150-0010. Send comments regarding this information collection to the Information Services Branch (T6-A10M),

U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, or by e-mail to Infocollects.Resource@nrc.gov, and to the OMB reviewer at: OMB Office of Information and Regulatory Affairs (3150-0017, 3150-0010), Attn: Desk Officer for the Nuclear Regulatory Commission, 725 17th Street, NW Washington, DC 20503; e-mail: oira_submission@omb.eop.gov.

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10. Public Protection Notification The NRC may not conduct or sponsor, and a person is not required to respond to, a collection of information unless the document requesting or requiring the collection displays a currently valid OMB control number.

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