ML22334A102

Advisory Committee on the Medical Uses of Isotopes (ACMUI) Fall 2022 Meeting Handout

ML22334A102
Person / Time
Issue date:	12/05/2022
From:	Advisory Committee on the Medical Uses of Isotopes, Office of Nuclear Material Safety and Safeguards
To:
Valentin-Rodriguez C
References
Download: ML22334A102 (68)

Text

ADVISORY COMMIT TEE ON THE MEDICAL USES OF ISOTOPES

FA LL 2 022 ME E TI NG D EC E MB E R 5-6, 2022

Meeting Handout MEETING AGENDA ADVISORY COMMITTEE ON THE MEDICAL USES OF ISOTOPES

December 5-6, 2022 One White Flint North Building (Commissioners Hearing Room), Rockville, Maryland Two White Flint North Building (TWFN-3D06), Rockville, Maryland

NOTE: Sessions of the meeting may be closed pursuant to 5 U.S.C. 552b to discuss organizational and personnel matters that relate solely to internal personnel rules and practices of the ACMUI; information the release of which would constitute a clearly unwarranted invasion of personal privacy; information the premature disclosure of which would be likely to significantly frustrate implementation of a proposed agency action; and disclosure of information which would risk circumvention of an agency regulation or statute.

Monday, December 5, 2022 OPEN SESSION

1. Opening Remarks C. Einberg, NRC Mr. Einberg will formally open the meeting and Mr. Williams K. Williams, NRC will provide opening comments.

2. Old Business T. Gupta Sarma, Ms. Gupta Sarma will review past ACMUI recommendations NRC 8:30 - 10:15 and provide NRC responses.

3. Open Forum ACMUI, NRC The ACMUI will identify medical topics of interest for further discussion.

4. Y-90 Medical Events Subcommittee Report M. OHara, ACMUI Dr. OHara will discuss the subcommittees recommendations on its evaluation of Y-90 medical events.

10:15 - 10:30 BREAK

5. Training and Experience for All Modalities H. Jadvar, ACMUI Subcommittee Report Dr. Jadvar will discuss the subcommittees recommendations on the impact of the American Board of Radiologys request to terminate NRC recognition of their board certification process and of the NRCs current specialty board recognition criteria.

6. Review of the Lutetium (Lu)-177-PSMA K. Brenneman, NRC Radiopharmaceutical Dr. Brenneman will provide an overview of the NRCs staff review of a new Lu-177-PSMA radiopharmaceutical 10:30 - 12:00 approved by the FDA for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy.

7. Radioactive Source Security and Accountable A. Carrera, NRC Rulemaking Mr. Carrera will provide an overview of the NRC's rulemaking to amend its regulations to require safety and security equipment and facilities to be in place for certain applicants before granting a license for possession and use of radioactive materials regulations.

12:00 - 1:15 LUNCH

8. EMT/Rb-82 Generator Rulemaking Subcommittee M. Shober, ACMUI Report 1:15 - 3:00 Ms. Shober will discuss the subcommittees recommendations regarding the NRC staffs draft regulatory basis for the rulemaking to establish requirements for Rb-82 generators and emerging medical technologies.

9. Decommissioning Financial Assurance for Sealed and G. Trussell, NRC Unsealed Radioactive Materials Mr. Trussell will provide a status update on the NRCs rulemaking that would amend its regulations for decommissioning financial assurance for sealed and unsealed radioactive materials.

3:00 - 3:15 BREAK

10. Open Forum ACMUI, NRC The ACMUI will identify medical topics of interest for further discussion.

11. Special Recognition for Dr. Ennis K. Williams, NRC 3:15 - 4:15 Mr. Williams will make a special presentation to Dr. Ennis.

12. Thoughts on Leaving the ACMUI R. Ennis, ACMUI Dr. Ennis will share his thoughts on leaving the ACMUI.

13. Administrative Closing T. Gupta Sarma, Ms. Gupta Sarma will provide a meeting summary and NRC propose dates for the spring 2023 meeting.

4:15 - 4:30 BREAK Tuesday, December 6, 2022 OPEN SESSION

14. Commission Meeting with the ACMUI ACMUI The ACMUI will brief the Commission on various topics in a public meeting.

10:00 - 12:15 15. Group Photo ACMUI The ACMUI will take a group photo with and without the Commission.

12:15 - 1:30 LUNCH Tuesday, December 6, 2022 CLOSED SESSION

16. INFOSEC Training B. Stapleton, NRC 1:30 - 3:30 17. Ethics Training J. Scro & A.

Cermeno, NRC

18. Allegations Training S. Hawkins, NRC ADJOURN

ML072670110 2019 ACMUI Recommendations and Action Items

Target ITEM DATE STATUS Completion Date for NRC Action The ACMUI endorsed the Evaluation of Extravasations Subcommittee Report, as amended, to note that under future 18 revisions to Part 35 rulemakings, extravasations be captured as a9/10/2019 Accepted Open Spring 2023 type of passive patient intervention in the definition of patient intervention.

2020 ACMUI Recommendations and Action Items

Target ITEM DATE STATUS Completion Date for NRC Action The ACMUI endorsed the Patient Intervention subcommittee report, as presented, and the recommendations provided thereinto re-4 interpret current definition of patient intervention and to report medical 3/30/2020 Accepted Open Spring 2023 events resulting from patient intervention which result in unintended permanent functional damage under 10 CFR 35.3045(b).

As part of the Non-Medical Events report, the ACMUI recommended to the NRC staff and/or NMP to evaluate the issue 11 of detection of short-lived medical isotopes in municipal waste 9/21/2020 Accepted Open Spring 2023 (waste from nuclear medicine patients that might be triggering the landfill alarms) and provide some level of guidance, best practices, or additional instructions.

2021 ACMUI Recommendations and Action Items

Target ITEM DATE STATUS Completion Date for NRC Action

6 The ACMUI endorsed the Extravasation Subcommittee report, as 9/02/2021 Accepted Open Spring 2023 amended, to support option 4 of the Subcommittee Report.

The ACMUI formed a new subcommittee on the Liberty Vision Y-7 90 Manual Brachytherapy source. The subcommittee is expected 10/04/2021 Accepted Open Fall 2022 to provide a draft report and any recommendations at the spring 2022 ACMUI meeting.

The ACMUI endorsed the Radionuclide Generator Knowledge 10 and Practice Requirements Subcommittee Report and the 10/04/2021 Accepted Open March 2026 recommendations provided therein.

The ACMUI formed a new subcommittee on Y-90 microspheres in 12 medical events. The subcommittee is expected to provide a draft 10/04/2021 Accepted Propose report and any recommendations at the spring 2022 ACMUI to close Fall 2022 meeting.

15 The ACMUI endorsed the ACMUI RG. 8.39 Subcommittee report 12/15/2021 Accepted Open Summer 2023 on CivaDerm and the recommendations therein.

Target ITEM DATE STATUS Completion Date for NRC Action

The ACMUI endorsed the ACMUI RG. 8.39 Subcommittee report 16 on the proposed revision to RG 8.39 and the recommendations 12/15/2021 Accepted Open Summer 2023 therein.

2022 ACMUI Recommendations and Action Items

Target ITEM DATE STATUS Completion Date for NRC Action

As discussed during the spring 2022 ACMUI meeting, a 1 suggestion was made for the ACMUI to review the rulemaking 4/5/2022 Accepted Open Spring 2023 plan for the ongoing NRC effort to revise Appendix B to Part 30 Quantities of Licensed Material Requiring Labeling.

Due to the increased number of medical events in 2021, a suggestion was made for the ACMUI to develop generic process 2 checklists for all user procedures. It was noted that it may be 4/5/2022 Not Accepted Propose appropriate to have the professional licensing boards take the to close N/A lead on developing, communicating, and standardizing the checklists.

The ACMUI tentatively scheduled its 2022 fall meeting for 3 September 19-20, 2022. The alternate date is December 5-6, 4/5/2022 Accepted Propose to Close Fall 2022 2022. An in-person meeting is expected for these dates.

OPEN FORUM (No Handout)

Y-90 Microsphere Medical Events Subcommittee Report

Michael OHara, PhD Advisory Committee on the Medical Uses of Isotopes December 6, 2022 December 6, 2022

1

Agenda

ACMUI Subcommittee Membership ACMUI Subcommittee Charge Key Messages

Background

Vendor Consultation Vender Consultation - Sirtex Medical Vendor Consultation - Boston Scientific Further discussion with both vendors

2 Subcommittee Members John Angle Vasken Dilsizian Josh Mailman Melissa Martin Michael OHara (Chair)

Megan Shober

NRC Staff Resource: Katie Tapp

3

ACMUI Subcommittee Charge

To evaluate the issue of Y-90 microspheres medical events in more depth and, in consultation with the vendors, propose methods to decrease the number of Y-90 microsphere medical events

4 Key Message

• The reported number of medical events involving Y-90 microspheres is low compared to the number of treatments performed

• However, it is important to evaluate causes of events to find ways to minimize the chance of similar types of events from happening again

5

Background

• Hepatic radioembolization uses Y-90 microspheres for the treatment of primary and metastatic liver malignancies

• Currently 2 vendors: Boston Scientific and Sirtex Medical

• During the past few years, both vendors have increased their hepatic radioembolization business by approximately twenty percent.

• The MEs reported during 2020 were low compared to the number of treatments performed

6 Background (cont.)

• MEs involving Y-90 microsphere administration continues to be the most common MEs

• Types of MEs for Y-90 microspheres included:

o >20% residual activity remaining in the delivery device, o delivery device setup error, o wrong dose given (treatment plan calculation error),

o wrong site treated (catheter placement error, wrong dose vial selected and wrong site listed on WD)

7

Background (cont.)

• A past ACMUI MEs Subcommittee noted that performance of a time out and the use of a checklist immediately before administration of byproduct material could have prevented some MEs

• The NRC staff issued Information Notice 19-07 to inform licensees of past ACMUI recommendations

8 Vendor Consultation

• The ACMUI subcommittee contacted both Y-90 microsphere vendors, Sirtex Medical and Boston Scientific, to discuss possible methods to reduce MEs

• Both vendors voluntarily met and greatly supported the subcommittee in this effort

9

Vendor Consultation (cont.)

• Vendors were given

• The ACMUI MEs Subcommittee Committee report presented on October 4, 2021,

• general questions to start the conversation, and

• ACMUI proposed recommendations to prevent 35.1000 Y-90 microsphere MEs

• The vendors were asked if these 3 actions are appropriate and if they had any further recommendations

10 Proposed Actions to Prevent Future MEs

The subcommittee proposed the following actions to the vendors as possible licensee actions to prevent future MEs:

• Review mechanics of Y-90 microsphere delivery device and setup procedures

• Confirm all data and calculations in the treatment plan

• Perform time out at the beginning of each procedure (name, date of birth, activity etc.)

11

Consultation - Sirtex Medical

• Sirtex evaluated the MEs reported by licensees in the 2021 ME Subcommittee report. They Identified 4 causes:

• Greater than 20% residual activity remaining in the delivery device not due to vascular stasis

• The wrong dose given (treatment plan calculation error)

• The wrong site treated (catheter placement error)

• The wrong site (written directive error)

• Sirtex agreed that greater use of the ACMUI recommendations by licensees may prevent MEs due to device set-up and procedural errors.

12 Consultation - Sirtex Medical (cont.)

Additional Actions Sirtex has taken that may reduce MEs

• Developed a Microsphere Activity Calculator

• Second check against the activity identified in WD

13

Consultation - Sirtex Medical (cont.)

Actions Sirtex has taken that may reduce MEs

• Enhance Training Evaluation Certification Program

• All necessary nuclear medical / radiation safety support is present

• Includes in-service site visits and proctor assessments

• Minimum frequency of use to continue treatments

• More vendor staff in close contact with licensees

14 Consultation - Boston Scientific (cont.)

Vendor identified issues and currently available potential solutions:

• >20% volume Y-90 spheres left in delivery device -

may need improved quality systems

• Events related to the delivery device - enhancements to the WD and /or increased familiarization with the device

• Wrong dose due to calculation errors, catheter placement errors or wrong dose vial - software tools

15

Consultation - Boston Scientific (cont.)

Resources provided to aid in the planning and facilitation of Y-90 treatments:

• Software tools to assist licensees in treatment planning and ordering Y-90 microspheres

• TheraSphere Now - online ordering tool

• TheraSphere Treatment Window Illustrator -

spreadsheet ordering tool

• TheraSphere iDoc - online dose ordering tool

16 Consultation - Boston Scientific (cont.)

Resources provided to aid in the planning and facilitation of Y-90 treatments:

• IFU supported by training at new sites for physician authorized users, RSOs and support staff

• TheraSphere Administration Checklist instructs users to confirm patient identity, instructions for administration set priming, dose vial preparation, administration set assembly final assembly before administration and disassembly and cleanup

17

ACMUI Recommendations

There should be further discussion with vendors to:

• Understand fully how these programs can reduce MEs

• How the vendor judges the effectiveness of these programs

• How the vendor tests the accuracy of spreadsheet or software tools

• What steps are being taken to minimize the chance of clogged microcatheters which causes residual activity to remain in delivery device

18 ACMUI Recommendations (cont.)

• Investigate the utility of software programs and checklists provided by the microsphere vendors with licensees.

• Issue information notice and speak at conferences to alert licensees of past MEs and share the ACMUI subcommittee recommended actions to reduce Y-90 microsphere MEs.

19

Acronyms

• ACMUI - Advisory Committee on the Medical Use of Isotopes

• MEs - Medical Events

• WD -Written Directive

• Y-90 -Yttrium 90

• IFU - Instructions for Use

20 U.S. Nuclear Regulatory Commission (NRC)

Advisory Committee on the Medical Uses of Isotopes (ACMUI)

Subcommittee on Y-90 Microsphere Medical Events

Draft Report

Submitted on: November 18, 2022

Subcommittee Members Vasken Dilsizian, MD Josh Mailman Melissa Martin Michael OHara, PhD (Chair)

Megan Shober

Consultant to the Subcommittee: John F. Angle, MD NRC Staff Resource: Katie Tapp, PhD

Charge

The ACMUI Chair, Darlene Metter, MD, established this Subcommit tee on October 4, 2021 during the ACMUI 2021 Fall Meeting to evaluate the issue of Y-90 micro sphere medical events in more depth and, in consultation with the vendors, propose methods to decrease the number of Y-90 microsphere medical events.

Subcommittee Process

The subcommittee identified three factors which contributed to avoidable medical events (MEs):

1) low frequency of administration, 2) errors in treatment plan ning, and 3) workflow time challenges during the procedure that ensure that all elements o f the treatment are in accordance with the written directive. Based on these factors, the subcommittee proposes three actions to prevent future MEs.

The vendors that currently provide yttrium (Y)-90 microspheres in the United States (Boston Scientific and Sirtex Medical) were approached for their input on the proposed recommendations. The subcommittee received written and verbal i nput from both companies.

The Subcommittee concluded that implementing the proposed recom mendations would have a positive impact on radiation safety for microsphere users.

Subcommittee Recommendations The following recommendations can be used by the NRC and the ve ndors to serve as additional learning tools for licensees. The Subcommittee recommends that the NRC have additional conversations with the vendors to understand how the vendor pro grams impact MEs and issue an information notice to alert users to events that occurred in the past that could have been prevented by these measures. Furthermore, the NRC or the ACMUI should also consider publishing a journal article or give a presentation at a nation al meeting to reach licensees.

1. On a regular basis, licensees should review the mechanics of Y-90 microsphere delivery and setup procedures as described by the manufacturer.

2. Licensees should confirm all data and calculations in the tr eatment plan, prior to administration.

3. Licensees should use a time out to assure all elements of the administration are in accordance with the written directive. Elements such as conform ation of the patients name, treatment location and dosage comparison to the written d irective.

=

Background===

Hepatic radioembolization or selective internal radiation thera py (SIRT) is the intravascular administration of labeled glass or resin microspheres into the hepatic artery to deliver a radiation dose to a tumor target within the liver. Hepatic radioembolizat ion currently uses Y-90 labeled microspheres for the treatment of primary and metastatic malign ancies of the liver. Two vendors are currently approved by the U.S. Food and Drug Administration for treatment of liver tumors with Y-90 microspheres. TheraSphere TM from Boston Scientific is approved to treat hepatocellular carcinoma and SIR-Spheres from Sirtex Medical i s approved to treat metastatic colorectal tumors of the liver. During the past few years, both vendors have increased their hepatic radioembolization business by approximately twenty percent. Similar to past years, the MEs reported during 2020 were low compared to the number of tre atments performed.

The ACMUI Medical Events Subcommittee Report from October 2021 shows that MEs involving Y-90 administration continues to be the most common ME (Agencyw ide Documents Access and Management System Accession No. ML21288A127).

Radioactive Source Total ME over 4 Years Manual Brachytherapy 31 Remote Afterloader, Teletherapy, Gamma 41 Stereotactic unit Intravascular Cardiac Brachytherapy 5 Gamma Knife Perfexion + Icon 5 Y-90 Microspheres (combined) 93

The types of MEs for Y-90 microspheres included: >20% residual activity remaining in the delivery device, delivery device setup error, wrong dose given (treatment plan calculation error),

wrong site treated (catheter placement error), wrong dose vial selected and wrong site. In 2020, 80% of the MEs for TheraSphere TM and 100% for SIR-Spheres may have been influenced by infrequent performance of the treatment procedure and inattenti on during the procedure. A past ACMUI MEs Subcommittee noted that performance of a time out and use of a checklist immediately before administration of byproduct material could h ave prevented some MEs. The ME subcommittee proposed actions to prevent Y-90 microsphere ME s that included review the mechanics of Y-90 microsphere delivery devices and setup proced ures, confirm all data and calculations in the treatment plan and perform a time out at th e beginning of each procedure to assure all elements of the treatment are in accordance with the written directive. The ME subcommittee also proposed some possible elements of a time out that include identity of the patient via two identifiers (e.g., name and date of birth), pro cedure to be performed, isotope, activity, second check of dosage calculation and that the writt en directive and dosage to be delivered are identical as well ot her elements that may be applicable. In response, the NRC staff issued information notice 19-07, Methods to Prevent Medi cal Events, to inform licensees of these ACMUI recommendations ( ML19240A450).

Vendor Consultation Introduction

Addressing MEs involving the administration of Y-90 microsphere s may be facilitated by collaboration with vendors. The ACMUI created this subcommittee to evaluate this issue in conjunction with the vendors of Y-90 microspheres. There are cu rrently two Y-90 microsphere vendors in the United States, Boston Scientific (TheraSphere TM) and Sirtex Medical (SIR-Spheres). The subcommittee contacted both vendors for assistan ce with this evaluation. Both vendors were given copies of the MEs Committee report presented at the ACMUI meeting on October 4, 2021, general questions to start the conversation, a nd the ACMUIs proposed three actions to prevent Y-90 microsphere MEs. The vendors were speci fically asked if these proposed actions to prevent Y-90 microsphere MEs are appropriat e and if there are further actions that will help to reduce the number of MEs. Teleconfere nces were held on April 20, 2022, with Sirtex Medical and on May 26, 2022, with Boston Scie ntific.

Sirtex Medical

Sirtex Medical has developed programs and taken steps that they believe will reduce MEs and increase the safe and effective use of SIR-Spheres. In respons e to the Y-90 Microspheres Subcommittees request, Sirtex Medical evaluated the MEs report ed by licensees between 2017-2020 described in the 2021 ME Subcommittee report. Their e valuation identified four causes of MEs associated with SIR-Spheres, which were:

1. Greater than 20% residual activity remaining in the delivery device not due to stasis,

2. The wrong dose given (treatment plan calculation error),

3. The wrong site treated (catheter placement error), and

4. The wrong site (written directive error).

Sirtex Medical agreed that greater use of the ACMUI recommendat ions 1-3 by licensees may prevent MEs related to licensee set up of the device and proced ural errors.

One action the vendor has taken to prevent MEs was to develop a SIR-Spheres Microspheres Activity Calculator. This may serve as second check against the activity identified in the written directive. The accuracy of these types of spreadsheet calculato rs should be confirmed by Sirtex Medical, tested by licensees and reviewed by the Medical Team at the NRC.

Another action the vendor mentioned was the SIR-Spheres Traini ng Evaluation Certification Program. This purpose of this program is to ensure that Sirtex Medicals Y-90 microspheres licensees have the infrastructure in place to use radioactive m icrospheres. This program includes guidance that all necessary nuclear medicine and radia tion safety support equipment and personnel are in place and the licensee has sufficient arte riography capabilities. It also includes In-Service site visits from Sirtex Medicals multidisciplinary team for assistance with all of microsphere implantation components and training of the trea tment physician and radiation safety officer. In addition, the vendor cited that the vendor proctors assessment is another action to prevent MEs. The proctor can recommend additional pro ctoring sessions for treating physicians and institutions before being qualified by Sirtex to use SIR-Spheres. There is also a minimum frequency of treatments with SIR-Spheres necessary for continued SIR-Spheres use according to the vendor. Sirtex Medical has also increased the case coverage in their Supplemental Training program to combat MEs by putting more of the vendors experienced staff in closer contact with the users of their Y-90 microspher es.

Further Discussion with Sirtex Medical Further discussion between Sirtex Medical and the Medical Team at the NRC is necessary to further understand how Sirtex Medicals programs outlined here affect MEs, how the vendor judges the effectiveness of these programs and how the vendor t ests the accuracy of spreadsheet tools to calculate activity. After reviewing the ME events report for 2021 (ML22112A104) from the Medical Radiation Safety Team at NRC, the vendor ide ntified clogged microcatheters as approximately 30% of the MEs. In addition, th e NRC staff should understand the steps, if any, that the vendor is taking to limit the impac t of clogged microcatheters.

Boston Scientific

Boston Scientific has developed programs and products that they believe will reduce MEs and increase safe and effective use of TheraSphere TM. The vendors post market surveillance program monitors all complaints and responds when a potential t rend emerges. This review process includes reviewing the NRC database for TheraSphere TM related MEs to determine the root cause of the medical event and take action to minimize its frequency and severity.

In response to the Y-90 Microspheres Subcommittees request, Bo ston re-analyzed the 59 MEs NRC identified from 2017 to 2020. They calculated the rate of N RC reported MEs per volume of dose vials shipped within each year and identified the rate of reported MEs is much less than one percent of volume of dose vials shipped. In addition, the r ate of MEs has decreased during this time when compared to the increase in volume of dose vials shipped.

The vendor pointed to possible actions while responding to the questions that the Subcommittee used to open the discussion. Many of these actions the licensee already has at their disposal.

For example, leaving >20% volume of TheraSphere TM in the delivery device may need improved quality systems or events related to the delivery device may ne ed enhancements to the written directive and/or increased familiarization with the device. Sof tware tools or checklists could be used to improve issues like the wrong dose given due to calcula tion errors, catheter placement errors or selection of the wrong dose vial. Greater use of the ACMUI proposed actions to prevent MEs will also possibly reduce these issues.

Boston Scientific provides resources to aid in the planning and facilitation of TheraSphere TM Y-90 treatments. The resources include the TheraSphere TM Instructions for Use which is supported by training at new sites for physician authorized use rs, radiation safety officers and support staff and software tools to assist customers in treatme nt planning and ordering TheraSphereTM. The software tools include: TheraSphere TM Now, TheraSphereTM Treatment Window Illustrator, and TheraSphere TM iDOC.

TheraSphereTM Now is an online ordering tool that notifies users of potentia l order errors at the time of the order. The vendor informed the Subcommittee that ap proximately 50% of TheraSphereTM users currently use this tool.

TheraSphereTM Treatment Window Illustrator is a spreadsheet-based tool that can assist users with ordering the appropriate dose size based upon the desired absorbed dose, timing of administration, lung shunt fraction, dose to the lungs, and ant icipated residual waste.

TheraSphereTM iDOC is an online interactive dose ordering calculator that ca n assist users in calculating and ordering the appropriate TheraSphere TM dose vial size.

The optional TheraSphereTM Administration Checklist instructs users to confirm patient id entity, instructions for administration set priming, dose vial preparat ion, administration set assembly with the dose vial, final assembly immediately before administr ation, TheraSphere administration and disassembly and cleanup. The vendor believes appropriate use all these tools could reduce MEs.

Further Discussion with Boston Scientific

Further discussion between Boston Scientific and the Medical Te am at the NRC is necessary to fully understand how the vendors programs outlined here affect MEs, how the vendor judges the effectiveness of these programs and how the vendor tests th e accuracy of spreadsheet and software tools. Specifically, are MEs lower at licensed facilit ies that use Boston Scientifics spreadsheet/ software tools? In addition, the NRC staff should understand the steps the vendor is taking, if any, to limit the impact of clogged microcatheter s.

Summary The vendors have embraced the ACMUI proposed actions to prevent Y-90 MEs. However, the vendors should include these actions in their training of new u sers, interactions with current users and in discussion of MEs with any user. The Subcommittee believes that the NRC should embrace these three proposed actions to prevent Y-90 MEs to ens ure that all Y-90 microsphere users are aware of their utility.

The use of spreadsheets, checklists, and software tools appear to be methods the vendors have employed to reduce errors in Y-90 isotope ordering, selection o f the wrong dose vial, calculation errors, and to reduce the errors during Y-90 procedures. These tools can assist the end user to order Y-90 and properly administer the therapy. The accuracy of these tools is unclear and should be investigated more fully.

Recommendations The NRC should evaluate the utility of the software programs an d checklists provided by the microsphere vendors. A regular review of these tools can improv e the licensees understanding of these software devices, assist vendors with further developm ent of these tools, and potentially catch inconsistencie s between vendors and with NRC regulations and recommendations.

In addition, the NRC should issue information notices to alert licensees of MEs and, where possible, make recommendations and suggest measures licensees c an take to prevent similar events in the future. These recommendations can be used by the NRC and the vendors to serve as additional learning tools to prevent MEs.

In summary, the three recommendations for licensees are as foll ows:

1. On a regular basis, licensees should review the mechanics of Y-90 microsphere delivery and setup procedures as described by the manufacturer.

2. Licensees should confirm all data and calculations in the tr eatment plan, prior to administration.

3. Licensees should use a time out to assure all elements of the administration are in accordance with the written directive. Elements such as conform ation of the patients name, treatment location and dosage comparison to the written d irective.

References January 24, 2022, Email to Boston Scientific

January 24, 2022, Email to Sirtex Medical

April 20, 2022, 35.1000 Y-90 Microsphere Medical Event Review b y Sirtex Medical March 23, 2022, letter to Michael OHara from Boston Scientific

April 20, 2022, Presentation entitled 35.100 Y-90 Microsphere Medical Events Review from Sirtex Medical

Respectfully submitted,

Subcommittee on Y-90 Microsphere Medical Events Advisory Committee on the Medical Uses of Isotopes U.S. Nuclear Regulatory Commission

Impacts of the American Board of Radiologys Request to Terminate NRC Recognition of the American Board of Radiologys Board Certification Processes Hossein Jadvar, MD, PhD, MPH, MBA Advisory Committee on the Medical Uses of Isotopes (ACMUI)

December 6, 2022

1

Subcommittee Members

• Hossein Jadvar, MD, PhD (Nuclear Medicine Physician; Chair)

• Ronald D. Ennis, MD (Radiation Oncologist)

• Richard Harvey, DrPH (Radiation Safety Officer)

• Darlene F. Metter, MD (Diagnostic Radiologist)

• Megan L. Shober (Agreement State Representative)

• Melissa C. Martin (Medical Physicist, Nuclear Medicine)

• Maryann Ayoade (NRC Staff Resource)

2

2 Subcommittee Charge

• To identify any potential impacts of ABRs request to terminate NRC recognition and other inactive boards identified during the NRCs evaluation of specialty boards and provide recommendations to mitigate any potential impacts

• To review and evaluate the NRCs current board recognition criteria and provide any recommendations for action

3

3

NRC Recognized Boards (certificate holder can request to NRC for granting AU status)

• American Board of Healthy Physics (ABHP)

• American Board of Science in Nuclear Medicine (ABSNM)

• American Board of Radiology (ABR)

• American Board of Medical Physics (ABMP)

• Canadian College of Physicists in Medicine (CCPM)

• Board of Pharmacy Specialties (BPS) [Formerly Board of Pharmaceutical Specialties]

• The American Board of Nuclear Medicine (ABNM)

• Certification Board of Nuclear Cardiology, Part of the Alliance for Physician Certification and Advancement' Medical Specialty Boards and Certification Programs (CBNC)

• The American Osteopathic Board of Radiology (AOBR)

• The American Osteopathic Board of Nuclear Medicine (AOBNM) --- INACTIVE since March 5, 2019recognition status under review

• Certification Board of Nuclear Endocrinology (CBNE) --- INACTIVE, no longer recognized

4

4 American Board of Radiology (ABR)

Background

• Founded in 1934 as a non-for-profit organization and a member of the American Board of Medical Specialties (ABMS), one of 24 specialty certifying boards

• Certifying board for Diagnostic Radiology (DR), Interventional Radiology (IR), Medical Phys ics (Diagnostic, Nuclear, Therapeutic), Radiation Oncology (RO), and subspecialties (Nuclear Radiology, Neuroradiology, Pediatric Radiology)

• Mission

- To certify that our diplomates demonstrate the requisite knowledge, skill, and understanding of their disciplines to the benefit of patients.

5

5

American Board of Radiology (ABR)

Background

• Prior to 2005: ABR did not provide AU-E designation on board certificates

• 2005-2023: AU-E, AMP-E, & RSO-E designations was an option for candidates

• December 31, 2023: Last date for AU-E designation on certificates (DR, IR-DR, RO, Diagnostic MP (RSO-E), Nuclear MP (RSO-E), Therapeutic MP (AMP-E)

• 2024 and beyond: No AU-E designation option; candidates provide relevant T&E documentation through their employers directly to NRC to add the employee to employers license

• REASONS (https://www.youtube.com/watch?v=hkRc9JzP2oA) March 30, 2022

- not aligned with the core ABR mission; diverts limited resources

- ABR has never issued AU status; most radiologists are not (and do not need to be) AUs

- ABR merely passed along documentation of T&E and direct pathway to becoming AU exists

- AU requirement for 700h T&E in nuclear radiology is an ACGME (residency) requirement

- IR-DR(Forms A & B), RO (2-page verification form) need not be submitted to ABR

- RISE questions will not be scored separately

- Trainees and programs should continue to keep T&E documentation

- T&E docs needed for 16-m embedded NM/DR pathway and NR fellows to sit for NR CAQ exam 6

6 7

7

8

8 Ensure a sufficient # of professionals (physicians/scientists/technologists) qualified to practice all aspects of nuclear medicine/molecular imaging now and in the future.

1. of Residents by Academic Year

NuclearMedicine NuclearRadiology Linear(NuclearMedicine) 180 161 149166 155 NRisrelativelyminoracrosstime 160 136 NMstablesince2015&expectedtorise 140 120 107 93 84 74 71 75 78 69 76 120 100 80 60 40 20 12 8 10 11 18 16 15 16 13 12 11 11 12 7 18 0

9

9

Ensure a sufficient # of professionals (physicians/scientists/technologists) qualified to practice all aspects of nuclear medicine/molecular imaging now and in the future.

1. of Commission on Accreditation of Medical Physics Education Programs (CAMPEP) Accredited Program Graduates by Academic Year

1 0

10 Ramifications & Potential Issues

• Potential confusion and challenges with burden on applicants and institutions for securing AU, AMP, or RSO status for new hires

- AU-E board certification is rapid for proof of AU eligibility; ABR may have underestimated the burden being placed on the applicants, preceptors, and program directors

- Deceased preceptors, unwilling preceptors to sign off if >7y window (per requirement in 10 CFR 35.59) or if preceptor was not involved with applicants T&E

- Potential increase in time reviewing T&E documentations (NRC & Agreement States); possible delays may impact practice of medicine (AU-E could function immediately)

• California: 4h per license amendment; ~100 AUs added per year; no time difference between ABR certification v. alternate pathway

• Wisconsin: no apparent adverse impact on regulatory agencies based on licensing databases for 2020/2021

• SECY-20-0005: Rulemaking Plan for Traini ng and Experience Requirements for Unsealed Byproduct Material (10 CFR Part 35), cost-benefit analysis, 15 hrs for NRC, 11 hrs for Agreement States, and 5 hrs for licensees 11

11

Ramifications & Potential Issues (cont.)

• ~80% of ABR certifications included AU-E; unknown what %

become AUs on RAM licenses

• Alignment of ACGME / AAPM-CAMPEP and NRC T&E requirements for AU and AMP designations

• No indications that other NRC recognized entities will follow ABRs decision

- CBNE (dissolved) and AOBNM (inactive and very small even when they were active)

• Association of University Radiol ogists (AUR) meetings may be appropriate venues for discussions and potential publication of recommendations in the AUR flagship journal, Academic Radiology 1 2

12 American Board of Radiology (ABR)

Questions

• Can ABR reveal time spent and/or expense for including AU-E designation vs.

eliminating it?

• How do ABR members (applicants, preceptors and program directors) feel about the extra burden that will be placed on them by eliminating the AU-E designation on board certificates?

• Are there other options rather than eliminating the AU-E designation on the board certification?

• Did the AU-E to clinical AU conversion play into the ABR's decision, and if so, what was this estimate and how was this estimate obtained?

• How many ABR Certified Physicists get the RSO-E designation on their certificates/year?

• If there is a significant decrease in MPs approved to be RSOs, are they any plans to increase the number of radiologists who are prepared to become RSOs?

1 3

13

Acronyms

• AAPM - American Association of Physicists in Medicine

• ABR - American Board of Radiology

• ABNM - American Board of Nuclear Medicine

• ACGME - Accreditation Council for Graduate Medical Education

• AU-E - Authorized User-eligible

• AMP-E - Authorized Medical Physicist-eligible

• CAQ - Certificate of Added Qualification

• CAMPEP - Commission on Accreditation of Medical Physics Education Programs

• IR-DR - Interventional Radiology-Diagnostic Radiology

• MP - Medical Physicist

1 4

14 Acronyms (cont.)

• NM-DR - Nuclear Medicine - Diagnostic Radiology

• NR - Nuclear Radiology

• NRC - Nuclear Regulatory Commission

• RO - Radiation Oncology

• RISE - Radioisotope Safety Exam

• RSO-E - Radiation Safety Officer-eligible

• T&E - Training and Experience

1 5

15 LicensingofLutetium177

KennethBrenneman,PhD MedicalRadiationSafetyTe a m DivisionofMaterialsSafety,Security,State,andTr i b a lPrograms OfficeofNuclearMaterialSafetyandSafeguards December5,2022

1

LicensingofLu177

• In2018,NRCissuedamemorandumcommunicatingits evaluationofthemedicaluseofLu177,followingtheFDA approvalofLU TAT H E R A,fo rthetreatmentofpancreatic (GEPNET)cancer.

• TheLicensingofLu177memorandumispostedintheNRC s MedicalToolkit(ML18136A824).

2 LicensingofLu177(cont.)

• MedicaluseofLu177 fallsunderprovisions in10CFRPa r t35, SubpartEUnsealedByproductMaterial-WrittenDirective Required.

• AUtrainingshouldcomplywith:

• 10CFR35.390, Trainingfo ruseofunsealedbyproduct material fo rwhichawrittendirectiveisrequiredor

• 10CFR35.396, Trainingfo rtheparenteraladministration of unsealedbyproduct materialrequiringawrittendirective.

• Lu177 wastedisposalshould includeassessmentfo ritsmetastable contaminant.

3

FDAApprovedNewLu177Therapyin2022

• OnMarch23,2022,theFDAapprovedLu177PLUVICTO'radioimmunotherapyfo rthetreatmentofprostatecancer.

• Prostatespecificmembraneantigenpositivemetastaticcastrationresistantprostatecancer(PSMApositive mCRPC)

• TheNRCconsideredtheradiationsafetyconsiderationsusedtoreviewLu177andLU TAT H E R A in2018fo ritsreviewof PLUVICTO'.

4 NRCRe v i e wofPLUVICTO'

• Reviewofra d i at i o nsafetyandregulator yconcerns

• Radionuclideandprogeny

• Monitoringandmeasurements

• Authorizedusertrainingandex pe rie nc e

• Pa t i e ntadministration andrelease

• Dosedelivery

• Nuclideandtherapeuticagentpharmacokinetics

• Nuclide,progeny,andcarrierbiodistribution

• Handlingandstorage

• Wa s t edisposal

5

NRCRe v i e wofPluvictoTM (cont.)

• NRCisrev isin gthe2018memorandumonthelicensingofLu177toincludePluvictoTM.

• Thememorandumiscurrentlyinconcurrence.

• ThememorandumwillbepostedtotheEmerging MedicalTechnologiespageintheNRC sMedical Toolkit

6 FurtherQuestion(s)andContact?

• KennethBrenneman,PhD

• Ken.Brenneman@NRC.gov

• EmergingMedicalTechnologiesPa ge

• https://www.nrc.gov/materials/miau/medusetoolkit/emerg licensedmedtech.html

• NRC sMedicalToolkit

• https://www.nrc.gov/materials/miau/medusetoolkit.html

7

Acronyms

• CFR CodeofFederalRegulation

• FDA FoodandDrugAdministration

• GEPNET gastroenteropancreatic neuroendocrinetumor

• PSMA prostatespecificmembraneantigen

• mCRPC metastaticcastrationresistantprostatecancer

• Lu177 Lutetium177

• NRC NuclearRegulatoryCommission

8 RADIOACTIVE SOURCE SECURITY AND ACCOUNTABILITY RULEMAKING

ADVISORY COMMITTEE ON THE MEDICAL USES OF ISOTOPES (ACMUI) 2022 FALL MEETING December 5, 2022

1

Key Messages

• Consistent with Commissions direction in SRM-SECY-17-0083, the staff is conducting a rulemaking to revise the radioactive source RULEMAKING security and accountability (RSSA) regulations in 10 CFR PROCESS

• The rulemaking would affect applicants for a

radioactive material license and licensees who transfer category 3 quantities of radioactive material.

2

2 Key Messages

• The rulemaking would address recommendations from several U.S. Government Accountability Office reports and would further deter someone with malicious intent from purchasing category 3 RULEMAKING quantities of radioactive material.

PROCESS

• The staff intends to submit a draft proposed rule

to the Commission for approval by December 21, 2022. Assuming approval by the Commission, the NRC plans to publish the proposed rule in the Federal Register in early 2023.

3

3

Proposed RSSA Revisions:

Safety and Security Equipment and Facilities

Requirements relating to validity of license applicants RULEMAKING

• 10 CFR 30.33(a), 40.32(d), and 70.23(a)

PROCESS

• Help address the concern that applicants could use a fictitious company or provide false information to obtain a valid license or radioactive materials

4

4 Proposed RSSA Revisions:

License Verification

Requirements for license verification for transfers of category 3 quantities of radioactive materials

• License Verification System (LVS) or by RULEMAKING contacting the license-issuing authority PROCESS

• 10 CFR 30.41(d), 40.51(d), and 70.42(d)

• Help address the concerns:

o altering a valid license

o use of counterfeit license

5

5

Proposed RSSA Revisions:

License Verification (cont.)

• Provide new definition

• Provide new Appendix F to 10 CFR Part 30 RULEMAKING

• Revise recordkeeping requirements PROCESS

6

6 Proposed RSSA Revisions:

Other Changes

• Remove obsolete verification method

• Administrative, clarifying and conforming RULEMAKING changes to various provisions in 10 CFR PROCESS

7

7

Proposed RSSA Revisions:

Guidance

• Website with frequently asked questions (FAQ) to provide guidance RULEMAKING

• Validity of license applicants PROCESS

• License verification requirements

• Provide accelerated guidance update to licensees

8

8 Next Steps

• Submit RSSA proposed rule to Commission (December 21, 2022)

RULEMAKING

• Publish in the Federal Register in early 2023 (assuming approval by the PROCESS Commission)

• Conduct further stakeholder engagements

9

9

Have Questions?

Please contact:

- Andrew Carrera, Ph.D.,

RULEMAKING 301-415-1078, Andrew.Carrera@nrc.gov, or PROCESS

- Anita Gray, Ph.D.,

301-415-7036, Anita.Gray@nrc.gov.

10

10 EMERGING MEDICAL TECHNOLOGIES RU L E M A K I N G

ACMUI Meeting l December 5, 2022 l Megan Shober

1

AGENDA

• Background

• Rulemaking effor ts

• Subcommittee recommendations

2

2 BACKGROUND

The last major structural revision to 10 CFR Par t 35 was in 2002.

Energy Stereotactic PolicyAct Devices

Microsources Alpha Theranostics emitters 3

3

BACKGROUND

10 CFR 35.1000 used when technologies dont fit.

• Complex devices with new components

• Tiny sealed sources that behave like a liquid

• Unsealed brachytherapy sources

• Need for device-specific training

• Physical presence requirements

• Atypical authorized users 4

4 RULEMAKING

RulemakingPlan DraftRegulatoryBasis SECY210013 (toACMUI) 2/9/2021 9/27/2022

CommissionDirection RegulatoryBasis 1/13/2022 (publiccomment)

Spring2023 5

5

RULEMAKING PL AN

• Option 1: Rubidium-82 generators only

• Option 2: Rubidium-82 generators, limited EMTs

• Option 3: Rubidium-82 generators, broadly incorporate EMTs

6

6 COMMISSION DIRECTION

Option 3:

• Rubidium-82 generators

• All current, well-established EMTs

• Create added flexibility to accommodate future EMTs

7

7

DRAFT REGUL ATORY BASIS

• Current policies and regulations

• Proposed changes to address identified issues

• Cost-benefit analysis

8

8 CURRENT POLICIES: RUBIDIUM-82 GENERATORS

10 CFR 35.60 cant calibrate for dynamic measurement 10 CFR 35.63 cant measure dose before administration

EG M13003allowedenforcementdiscretion.

9

9

CURRENT POLICIES: 10 CFR 35.1000

• Each EMT evaluated to determine risks and additional regulator y requirements.

Device-specific licensing guidance

Licensees use different versions of guidance.

Guidance not being retired.

1 0

10 REGUL ATORY ISSUES

Consistency Specificity Compatibility Adaptability Efficiency Flexibility

Rulemaking Guidance

1 1

11

PROPOSED CHANGES

Section Topic 35.200 Add rubidium and germanium generators 35.400 Add liquid and diffusing brachytherapy, IVB, and other ophthalmic sources 35.500 Add radioactive seed localization 35.600 Change from technology-specific components to radiation safety elements 35.700 Add Subpar t for microsources NEW! 1 2

12 PROPOSED CHANGES

• Definitions (e.g., physician)

• Radiation safety committee membership

• Written directives

• Device-specific training

1 3

13

SUBCOMMIT TEE EVALUATION

Well-established technology

• How widespread?

• How mature?

• How different?

1 4

14 SUBCOMMIT TEE EMT EVALUATION

Well-established Limited Not Available Ge-68 generators Alpha DaRT' ViewRay' IVB GammaPod' Epi-Rad90' RSL *RadioGenix' GliaSite Gamma Knife **Liber ty Vision Microspheres

• Staff chose to leave in 35.1000.

• • Licensing guidance not yet published. 1 5

15

SUBCOMMIT TEE RECOMMENDATIONS

New Subpar t for microsources Incorporate well-established EMTs into existing 10 CFR Par t 35 Subpar ts Changes to Radiation Safety Committee membership, written directives Device-specific training Per formance-based changes to 35.600 1

6 16 SUBCOMMIT TEE RECOMMENDATIONS

Do not add product-specific requirements in regulation unless EMT is well-established Add general requirements to address simple issues with EMTs Re-evaluate ophthalmic sources Re-evaluate authorized medical physicists Broadly consider training for atypical AUs 1

7 17

SUBCOMMIT TEE CONCLUSIONS

• Many of the current EMTs are well-established and should be moved out of 35.1000.

• Some EMTs should stay in 35.1000 due to limited operating experience.

• NRC should periodically assess whether EMTs are still in use.

• Thanks to Staff for their effor ts on this project!

1 8

18 AC RO N Y M S

AUs: Authorized Users CFR: Code of Federal Regulations EMT: Emerging medical technology EGM: Enforcement Guidance Memorandum Ge-68: Germanium-68 IVB: Intravascular brachytherapy RSL: Radioactive seed localization 1 9

19 Report of Subcommittee on Emerging Medical Technologies/Rubidiu m-82 Generator Rulemaking Draft Regulatory Basis Draft Report Submitted on: November 18, 2022 Subcommittee Members Ronald Ennis, M.D.

Richard Green Hossein Jadvar, M.D., Ph.D.

Megan Shober (Chair)

Zoubir Ouhib Harvey Wolkov, M.D.

Consultant to Committee: John Fritz Angle, M.D.

NRC Staff Resource: Maryann Ayoade Charge ACMUI Chairperson Dr. Darlene Metter established this subcommittee to review and comment on NRCs draft regulatory basis for the Emerging Medical Technologies (EMT) and Rubidium-82 Generator rulemaking.

=

Background===

Although NRC medical regulations in 10 CFR Part 35 cover a wide range of byproduct material uses, medical technologies continue to be developed that have radiation safety concerns not addressed by these requirements.

In 2002, the NRC established 10 CFR 35.1000 so that there would be codified regulatory requirements and a more clearly defined process to obtain regulatory approval for new medical uses of byproduct material.1 This section provided a mechanism for NRC to license medical technologies that had characteristics or challenges not adequately considered by the other Subparts of 10 CFR Part 35. In practice, as new medical technologies were identified which did not fit into the established Subparts of 10 CFR Part 35, NRC and Agreement States would develop licensing guidance to address the unique features of the technology. In the past 20 years, NRC has issued licensing guidance for 16 emerging medical technologies.2 After the Energy Policy Act of 2005 gave NRC regulatory authority over accelerator-produced radioactive material, the NRC identified that rubidium-82 generators were not able to meet

1 10 CFR Parts 20, 32, and 35, Medical Use of Byproduct Material; Final Rule (67 FR 20249; April 24, 2002).

2 EMT licensing guidance is posted on NRCs Medical Uses Licensee Toolkit: https://www.nrc.gov/materials/miau/med-use-toolkit.html requirements in 10 CFR 35.60 and 10 CFR 35.63 for measuring patient doses. Due to the 76 second half-life of rubidium-82, the dose calibrator within the rubidium-82 generator measures activity in a dynamic mode (i.e., as fluid flows past the detector) and the measurement results are not available prior to administering the rubidium-82 to the patient. In 2013, NRC issued an enforcement guidance memorandum (EGM-13-003)3 which authorized NRC staff not to issue violations to licensees for failure to comply with 10 CFR 35.60 and 10 CFR 35.63 if the licensee took certain additional steps to ensure the equipment was working properly, to record dosages administered to patients, and to provide device-specific training to staff.

It has long been the intent of the NRC to amend 10 CFR Part 35 to incorporate these technologies. This proposed rulemaking would accomplish that purpose.

Discussion In the proposed draft regulatory basis, the NRC outlines its pl an to incorporate rubidium-82 generators and many of the emerging medical technologies into 10 CFR Part 35, via modification to existing portions of the rule, and by creating a new Subpart to 10 CFR Part 35 for medical use of microsources.

The ACMUI Emerging Medical Technologies Subcommittee has reviewed the proposed draft regulatory basis. Responses to the specific questions posed by NRC in Appendix A of the draft regulatory basis are included in Appendix 1 of this report. The Subcommittee offers the following additional comments:

• The NRC should evaluate which emerging medical technologies are no longer being distributed in the United States. This information should be stated in Section 3.3 and reflected in the assumptions in Table 7. This information should also inform the proposed rule text.

• Some members of the Subcommittee believe the scope of the proposed rulemaking is ambitious, but reasonable. Other members of the Subcommittee be lieve the scope of the proposed rulemaking should be limited to products that are in broader use because time and clinical experience are needed to understand the technology and safety issues prior to being able to codify requirements via rulemaking.

• The Subcommittee supports the proposed changes to allow for the use of additional radionuclide generators. In addition, all Subcommittee members agree that gamma knife, microspheres, radioactive seed localization and intravascular brachytherapy (IVB) have extensive histories of clinical use and should be moved out of 10 CFR 35.1000 and into other Subparts of 10 CFR Part 35.

• The Subcommittee believes that medical technologies presenting novel radiation safety hazards should default to 10 CFR 35.1000. NRC should assess the novelty, risk, and

3 Enforcement Guidance MemorandumInterim Guidance for Dispositioning Violations Involving 10 CFR 35.60 and 10 CFR 35.63 for the Calibration of Instrumentation to Measure the Activity of Rubidium-82 and the Determination of Rubidium-82 Patient Dosages (EGM-13-003), ML13101A318.

general clinical experience (i.e., beyond clinical trials) when determining whether to move a technology out of 10 CFR 35.1000 and into other parts of 10 CFR Part 35.

• In any case, the Subcommittee cautions the NRC against putting specific requirements in 10 CFR Part 35 which are particular to devices or products that arent in widespread use (i.e., Alpha DaRT').

o The Subcommittee supports adding general requirements for contamination control for liquid or diffusing brachytherapy.

o The Subcommittee discourages adding training and experience requirements to 10 CFR Part 35 which were designed for products no longer being distributed (i.e.,

Epi-Rad90' eye applicators).

• The Subcommittee supports the proposed change to the 10 CFR 35.2 definition of physician.

• The Subcommittee supports the proposed changes to 10 CFR 35.24. Radiation safety committees should include an authorized user (AU) representative for microsource therapy and any future therapeutic emerging medical technologies.

• The Subcommittee cautions the NRC as it considers how to incorporate treatment regimen into the written directive regulations. A single written directive should not prescribe a radiopharmaceutical in cycles when the prescribed activity may vary from cycle to cycle, for example based on the patients weight, bone marrow reserve, or renal or hepatic function.

• The Subcommittee recommends a wholesale re-evaluation of the ophthalmic brachytherapy requirements. The divergent training requirements for physicians and physicists are very complicated, and the Subcommittee recommends streamlining the training requirements. Of particular note, the Subcommittee believes it is not a good practice for a devices applicable training requirements to depend on the prescribed dose.

The NRC should consider regulating ophthalmic sources that are intraocular or have shorter half-lives under standard 10 CFR 35.400 manual brachytherapy regulations, since they are significantly more complex than the traditional strontium-90 pterygium applicators. The added complexities may include dose to a specified tissue depth and stricter criteria for source calibration due to rapid decay.

• NRC should re-evaluate when authorized medical physicists (AMPs) should be required.

Why do some of the 10 CFR 35.400 uses require an AMP and some do not? What are the specific tasks or skills that must be performed by an AMP? It may be useful to pose this question during the public comment period.

• Submission of procedures for patient immobilization should be part of the licensing process for licensees using gamma stereotactic radiosurgery devices in 10 CFR Part 35, Subpart H. The Subcommittee notes that immobilization methods c an also impact emergency response.

• The Subcommittee supports the addition of 10 CFR Part 35, Subpart I (35.700) for microsource brachytherapy.

• In multiple places, Appendix A states, This section would be amended to require completion of device specific training by the medical physicist applying to be an AMP on a license authorizing use of this device. The Subcommittee notes that device-specific training is already required for AMPs in 10 CFR 35.51(c).

• In Section 10 CFR 35.415 (page A-6), it states, this section of the regulation will be amended to require licensees to lock storage of the IVB storage container and to house that storage container in a secure location. The Subcommittee notes that 10 CFR 20.1801 already requires licensees to secure radioactive material from unauthorized access. What is the basis for the additional proposed security requirement?

• In Section 10 CFR 35.3045 (page A-14), the Subcommittee recommends removing the requirement to report as a medical event a radioactive seed localization procedure that uses the wrong radionuclide. Based on the low implanted activity and the short implantation time, the dose effect of the wrong isotope is of minimal consequence.

• In Section 10 CFR 35.610 (page A-24), it states, This section will be revised to clarify that the AU and AMP, as well as any individual who will operate the unit, are required to have vendor operational and safety training. The Subcommittee recommends also allowing the operational and safety training to be given by an approved AU or AMP.

Conclusion The Subcommittee supports this rulemaking and applauds the effort it took to develop this draft regulatory basis. The Subcommittee looks forward to continued work on this rulemaking as it progresses.

Respectfully Submitted on November 18, 2022,

Subcommittee on Emerging Medical Technologies/Rubidium-82 Generator Rulemaking Draft Regulatory Basis Advisory Committee on the Medical Use of Isotopes Nuclear Regulatory Commission

Appendix 1: Responses to Selected Numbered Questions Radionuclide generators Question A.1.1:

For radionuclide generators, RSOs should have general awareness training, including functions and risks. RSOs should know what the potential emergency situations are and know how to respond to them. These responsibilities are inherent to the RSO position and documentation of device-specific training should not be required during licensing.

Question A.1.2:

The regulations should be structured so that certain devices require device-specific training for anyone using or supervising the use of the device. Device-specific training for 10 CFR 35.290 authorized users should be maintained by licensees and should not need to be approved by a regulator or tracked on a license.

Liquid Brachytherapy Question A.3.1:

Liquid brachytherapy should remain in 10 CFR 35.400. The definition of manual brachytherapy in 10 CFR 35.2 already allows for liquid sources. The liquid brachytherapy devices under consideration encapsulate the radioactive liquid in a manner conceptually no different than an encapsulated I-125 seed and therefore belong in 10 CFR 35.400. However, additional regulations are needed to address the potential for radioactive contamination.

Diffusing Sources Question A.5.1:

10 CFR Part 35, Subpart F should require routine contamination control for brachytherapy sources that are not sealed sources.

Microsources Question A.8.1:

• The Subcommittee supports the use of the term microsource. The Subcommittee does not see any reason to exclude particular radiation types or energies from the microsource definition. The Subcommittee encourages NRC to develop regulations which would allow for microsources that are sealed sources and microsources that are unsealed sources (i.e., where the radioactivity is adhered to the surface of the microsource).

• The draft regulatory basis does not address changes to 10 CFR 32.74. This section currently requires medical distributors to receive SSD authorization for 10 CFR 35.1000 technologies (including microspheres). NRC should consider whether to add 10 CFR 35.700 as a reference in 10 CFR 32.74(a).

• Sealed source microsources meet the criteria for SSD registration as described in 10 CFR 32.210, and SSD registration should be required for sealed source microsources. The NRC should seek comment on whether SSD device registration should be required for microsources that are not sealed sources.

• The Subcommittee encourages the NRC to seek comment on the dividing line between microsources and liquid brachytherapy.

Question A.8.2:

The Subcommittee believes that NRC should not define physiological equilibrium and should instead focus on safety measures to prevent non-target embolization.

Question A.8.3:

The Subcommittee cautions the NRC not to regulate licensees team approaches to medical care. The NRC should focus its efforts on training requirements for individuals who handle licensed material. This is appropriately covered by 10 CFR 35.27 Supervision. Licensees should develop, implement, and maintain procedures for microsource use, but the NRC does not need to specifically name the team approach in its regulations.

Question A.8.4:

For microsource brachytherapy, the written directive should include both the dose and the activity. Physicians intend to treat patients with a particular dose, and activity is the measurable parameter that allows licensees to determine whether the appropriate amount of radioactive material has been administered. Treatment planning worksheets from microsource manufacturers incorporate both dose and activity.

Question A.8.5:

The post-treatment portion of the written directive should specify the activity administered.

The dose delivered to the treatment site is difficult to determine without post-treatment imaging. NRC should ask a question about whether post-treatment imaging should be required and solicit input on whether there are other mechanisms to confirm that the treatment was delivered in accordance with the written directiv e.

Question A.8.6:

The Subcommittee believes that NRC does not need to specify how a licensee can meet 10 CFR 35.41.

Question A.8.7:

Most of the licensees currently using microsource material do not have authorized medical physicists. The Subcommittee has mixed perspectives on whether an authorized medical physicist should be required for microsources. The Subcommittee encourages NRC to solicit this input during the public comment period.

Question A.8.8:

NRC should not assume that all microsources will be sealed sources. SSD registration (per 10 CFR 32.210) is for sealed sources. Should the microsource section be limited to permanent implants?

Question A.8.9:

35.710 proposes a requirement that prior to the first use for patient treatment of a new delivery system, a licensee shall ensure that vendor operational and safety training is provided to all individuals involved in microsource manual brachytherapy use. The Subcommittee believes that NRC should not restrict who provides the device-specific training. For example, an authorized user who has received training from the vendor on a modified device could provide the training to other staff. There are no other areas of 10 CFR 35 that require training to be provided by the vendors. The Subcommittee also believes that NRC should limit its training requirement to individuals who handle the microsources.

Comment: Questions A.8.9 and A.8.10 appear to be the same. It is not clear what distinguishes safety procedures from safety precautions. NRC should combine these two questions.

Question A.8.11:

NRC should no longer allow conditional approval of microsource authorized users.

Conditional approval is not an option for any other type of medical authorized user.

Microsource therapy is well-established and has been an integral part of interventional radiology residencies for many years.

Question A.8.12:

The Subcommittee believes that 80 hours9.259259e-4 days <br />0.0222 hours <br />1.322751e-4 weeks <br />3.044e-5 months <br /> of classroom and laboratory training applicable to microsources is appropriate for interventional radiologists seeking to become microsource authorized users, in addition to the 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> of nuclear medicine training already required by radiology residencies.

Question A.8.13:

The NRC should seek comment on the training pathways chosen by current microsource authorized users. The Subcommittee believes that current microsphere training requirements are appropriate for 10 CFR 35.390 and 10 CFR 35.490 authorized users; however, the Subcommittee believes that most microsphere authorized users ar e interventional radiologists.

Question A.8.14:

This is a great question for public comment. The NRC should also ask whether the individuals injecting the microsources are typically authorized users or individuals working under the supervision of an authorized user.

Other 10 CFR Part 35 Changes Question A.9.5:

The Subcommittee recommends revising the 10 CFR 35.610 requirement to allow console passwords. The Subcommittee notes that, for example, the Elekta Flexitron high dose rate remote afterloader unit does not have a console key (the key instead goes in the robot).

Question A.9.6:

The Subcommittee notes that proposed changes to 10 CFR 35.615 should not conflict with other regulations, for example 10 CFR 20.1601 (access to high radiation areas) or 10 CFR Part 37 (physical security).

Decommissioning Financial Assurance Proposed Rule 10 CFR Part 30

Gregory Trussell Division of Rulemaking, Environmental, and Financial Support December 5, 2022

1

1

Purpose of Meeting

Provide a status update:

Background

Update of proposed rulemaking

Next steps/timeline

2

2

Background

ACMUI Report (August 2015)

Rulemaking process was initiated by a petition PRM-30-66 (June 2017).

Commission approved initiation of this rulemaking in SRM-SECY 0125 (Oct 2020).

The NRC published a regulatory basis in the FR (April 2022).

3

3

ACMUI

Because of the importance of Ge-68/Ga-68 generators in the diagnosis and treatment of liver and pancreatic cancers, ACMUI issued the Germanium-68 (Ge-68) Decommissioning Funding Plan (DFP) Final Report, and addendum, dated August 12, 2015.

4

4 ACMUI (cont.)

By memorandum dated July 29, 2016, (ADAMS Accession No. ML16082A415) and July 13, 2017 (ADAMS Accession No. ML17075A487), the NRC established a process for granting exemptions to the DFP requirements.

5

5

PRM-30-66

The petition was submitted by OAS.

The petition requested that that the NRC provide specific possession values for naturally-occurring and accelerator-produced radioactive materials radionuclides that are not currently listed in Appendix B to 10 CFR Part 30 so that licensees using these isotopes, especially medical licensees, would not have to apply the appendixs default values to calculate decommissioning funding requirements.

6

6 PRM-30-66 (cont.)

The OAS asserted the following:

Without possession values for the unlisted radionuclides, regulators are forced to evaluate new products against the default criteria and apply overly burdensome financial assurance obligations or evaluate case-by-case exemptions.

Rather than issuing exemptions on a case-by-case basis, the more appropriate way to address the inconsistency in Appendix B to 10 CFR Part 30 is to amend it to add appropriate radionuclides and their corresponding activities.

7

7

PRM-30-66 (cont.)

Patient health and safety are being compromised due to delays in licensing important diagnostic and therapeutic products that use radionuclides not listed in the table in Appendix B to 10 CFR Part 30.

These licensing obstacles could discourage development of new products, diminishing the possibility of new innovative and beneficial options in both medical and industrial applications.

8

8 NRC Proposed Approach

Revise the current table in Appendix B to 10 CFR Part 30 using the radionuclides and quantities from Appendix C to 10 CFR Part 20, including additional radionuclides not currently named in Appendix B to 10 CFR Part 30.

Remove all radionuclides with a half-life of 120 days or less since these radionuclides are not considered when developing DFA.

Default values would be set to equal the lowest values of the listed radionuclides.

Change the title to the table in Appendix B to 10 CFR Part 30 to reflect its proposed use for DFA as opposed to labeling.

9

9

Next Steps/Timeline

The Federal Register notice will be provided to ACMUI for a 90-day review.

10

10 Questions?

More questions?

Contact:

Gregory.Trussell@nrc.gov

11

11

Acronyms

CFR: Code of Federal Regulations

DFA: Decommissioning Financial Assurance

FR: Federal Register

Ge-68/Ga-68: Germanium-68/Gallium-68

PRM: Petition for Rulemaking

OAS: Organization of Agreement States

SRM: Staff Requirements Memorandum

12

12 OPEN FORUM (No Handout)

MARCH 2023 SPRING

Sunday Monday Tuesday Wednesday Thursday Friday Saturday

26 27 28 1 2 3 4

SIR Annual Mtg

5 6 7 8 9 10 11 Holi

SIR Annual Meeting RIC Conference

12 13 14 15 16 17 18

RIC Conference

RIC Conference

19 20 21 22 23 24 25

26 27 28 29 30 31 1

NCRP Annual Meeting

2 3 Notes:

SIR Annual Meeting (4-9)

High Country Nuclear Medicine Conference (11-14)

RIC Conference (14-16)

NCRP Annual Meeting (27 -28)

APRIL 2023 SPRING

Sunday Monday Tuesday Wednesday Thursday Friday Saturday

26 27 28 29 30 31 1

AAPM Clinical 2 3 4 5 6 7 8

Passover Begins

AAPM Spring Clinical

9 10 11 12 13 14 15

Easter Passover ends

16 17 18 19 20 21 22

Eid

International Symposium on Trends in Radiopharmaceuticals

23 24 25 26 27 28 29

30 1 Notes:

AAPM Spring Clinical (1-4)

International Symposium on Trends in Radiopharmaceuticals (17-21)

MAY 2023 SPRING

Sunday Monday Tuesday Wednesday Thursday Friday Saturday

30 1 2 3 4 5 6

7 8 9 10 11 12 13

CRCPD Annual Meeting 14 15 16 17 18 19 20

21 22 23 24 25 26 27

28 29 30 31 1 2 3

Memorial Day

1 2 Notes:

CRCPD Annual Meeting (8-11)