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 DaRT TM..................................................................... 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 brachyt herapy sources, with many unique properties that merit radiation safety conside rations 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 tiss ue. As a result, Alpha DaRTTM is regulated under 10 CFR 35.1000, Other medical uses of byproduc t material or radiation from byproduct material.1

2 Device Description

The Alpha DaRTTM device is a source and applicator designed for manual brachyth erapy. The Alpha DaRTTM source are Ra-224 seeds, which are implanted into the tumor us ing an Alpha DaRTTM applicator according to a pre-determined plan. Inside the tumo r, the Ra-224 decays by alpha emission and the seeds release Rn-220 by recoil. Rn-220 i s 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 seed s 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 glyc erin; and

2. a stylet (plunger) inserted into the needle cannula (or cath eter), 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 applicat or:

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

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

More information about the device can be found in its Sealed So urce 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 Exemptio n 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.

1 3 Licensing Guidance

The license conditions listed in this document provide applican ts 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. T he applicant must submit the information required to meet 10 CFR 30.33, General requirement s for issuance of specific licenses, and 35.12, Application for license, amendment, and renewal, as described below.

The applicant should submit additional information and commitme nts 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 Commissio n (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 rega rding 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 Medica l Use Licenses, as it provides overall licensing guidance for all medical uses of byp roduct material, including applicable model procedures for audits, occupational dose monit oring program and surveys.

Guidance specific for the use of Alpha DaRT TM under 10 CFR 35.1000, Other medical uses of byproduct material or radiation from byproduct material are co ntained herein.

4 Requirements not Specific to 10 CFR 35.1000 Use

Applicants must commit to meet the general requirements in 10 C FR Part 35, Subpart A "General Information; Subpart BGeneral Administrative Requir ements; Subpart C"General Technical Requirements; Subpart LRecords; and Subpart MRe ports, 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 I nvestigations; Part 20, Standards for Protection Against Radiation; and Part 30, Rules of Gener al Applicability to Domestic Licensing of byproduct material. The enclosed consolidated tec hnical analysis table provides guidance on applicable requirements.

5 Specific Licensing Guidance for Alpha DaRT TM

5.1 Radionuclides, Form, Possession Limits, and Purpose of Use

Pursuant to 10 CFR 35.12(c), the applicant must identify the ra dionuclide, chemical/physical form, requested maximum possession limit, and purpose of use. T he information in the table below provides the suggested format for completing Item 5 (Radi oactive Material) and Item 6 (Purpose of Use) on the NRC Form 313, Application for Material s License.

2 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 Radia tion Safety Officer (RSO) for Alpha DaRTTM before the source can be added to the license. NRC staff has d etermined 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 i s 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 ex planation of why the applicant believes the alternative T&E commitments demonstrate that the i ndividuals 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 DaRT TM.

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 ne cessary.

And

B.

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

3 5.2.2 Radiation Safety Officer (RSO)

The RSO must have training as specified in 10 CFR 35.50, Train ing for Radiation Safety Officer and Associate Radiation Safety Officer, including training in radiation safety, regulatory issues, and emergency procedures for Alpha DaRT TM. 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 requirement s in 10 CFR Part 35 for brachytherapy sources and manual brachytherapy use and shall co mmit to the following licensing commitments. The table contained in the appendix prov ides more details on applicable 10 CFR Part 35 requirements.

6.1 Procedures for Administration

The licensee must have procedures f or administration requiring a written directive as specified in 10 CFR 35.41, Procedures for administrations requiring a wr itten directive, specifically to ensure high confidence that the patients or human research sub jects identity is verified before each administration and each administration is in accordance wi th the written directive. In addition to requirements in 10 CFR 35.41, licensees shall commi t to include verification that seeds are fully contained within the patients body during trea tment to avoid significant daughter products leakage and contamination. In addition, licensees shal l commit to evaluating the location of the seeds prior to removal to determine if the seed s moved during treatment to determine if a medical event occurred. Similar to 10 CFR 35.204 1, 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, Revi sion 3, Section 8.10.13, Procedures for Administration when a Written Directive is Requ ired, 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 w ith 10 CFR 35.3045, Medical event reporting with the exceptions listed below.

• Licensees will not be required to report a medical event cause d 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 DaRT TM 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 docum ented in the post-implantation portion of the written directive. As stated a bove, total source strength only needs to include Ra-224 activity.

• Licensees shall commit to report any discovered event where th e dose to the skin or an organ or tissue other than the treatment site that e xceeds by 0.5 Sv (50 rem) or more the expected dose to that site from the proced ure if the administration had been given in accordance with the written di rective prepared or revised before administration; and 50 percent or more the ex pected dose to that site from the procedure if the administration had been giv en in accordance with the written directive prepared or revised before administr ation.

4 6.4 Labeling

Labeling requirements in 10 CFR 35.69, Labeling of vials and s yringes, are not required for Alpha DaRTTM seeds. The seeds are not a radioactive drug. Licensees shall c ommit to keep the applicator in the labeled container (i.e., sterilized bag) prov ided by the manufacturer until the applicator is needed for use or conditions in 10 CFR 35.92, De cay-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 C FR 35.70, Surveys of ambient radiation exposure rate, a licensee shall commit to survey wit h a radiation detection survey instrument the area where Alpha DaRT TM 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 ex posure 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 u sed 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 radiat ion 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, Determinat ion 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 calibra tion and recordkeeping. In accordance with 10 CFR 35.432, licensees may use measurements p rovided by the source manufacturer.

6.8 Contamination Control

In addition to safety precautions required in 10 CFR 35.415, th e licensee shall commit to placing all unsealed seeds that are not in use and contaminated waste i n 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-22 0 leakage. Licensees can dispose of waste in accordance with 10 CFR 35.92, Decay-in-sto rage, or other appropriate methods allowed in 10 CFR Part 20.

5 6.9 Radiation Protection Program Changes

As this guidance may be revised as additional experience is gai ned regarding the medical use of Alpha DaRTTM, an applicant initially applying for authorization for the med ical use of Alpha DaRTTM may request to incorporate into its license a radiation protec tion 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 th e 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 licensee s RSO and licensees management; and

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

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

6. the record will include a copy of the appropriate website gu idance, 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 eng ineering and radiation safety evaluation addressing those differences.

7.2 Written Directives

The licensee must complete a written directive in accordance wi th 10 CFR 35.40, Written directives. When total source strength is required to be recor ded 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 t aken to ensure that radiation emissions from each patient or human research subject permits t heir release in accordance with 10 CFR 35.75, Release of individuals containing unsealed byproduct materia l or implants containing byproduct material. Licensees should note temporary use affixed by sutures that protrude outside of the body have a potential to become dislodg ed or allow for gaseous release.

Patients should not be released from the licensed facility if i t 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 bec ome 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 becom es 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 br achytherapy sources in storage or use in accordance with 10 CFR 35.406, Brachytherapy sources accoun tability. In addition, licensees shall maintain records of brachytherapy sources accountability in accordance with 10 CFR 35.2406, Records of brachytherapy source accountability. Lice nsees should document the location the patient plans to reside. Licensees should also hav e patient contact information and provide the patient with instructions on actions to take if sou rce 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 inspe ction 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 subj ect to the Paperwork Reduction Act of 1995 (44 U.S.C. 3501 et. seq.). These information collec tions were approved by the Office of Management and Budget (OMB), approval numbers 3150-00 17 and 3150-0010. Send comments regarding this information collection to the Informati on 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 f or 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 col lection displays a currently valid OMB control number.

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