ML19081A145

Advisory Committee on the Medical Uses of Isotopes (ACMUI) April 3-4, 2019 Meeting Ebinder

ML19081A145
Person / Time
Issue date:	03/22/2019
From:	Office of Nuclear Material Safety and Safeguards
To:
Jamerson, Kellee
References
Download: ML19081A145 (78)

Text

MEETING AGENDA ADVISORY COMMITTEE ON THE MEDICAL USES OF ISOTOPES April 3-4, 2019 Three White Flint North Building, 11601 Landsdown Street, Room 1-C03/1-C05, North Bethesda, Maryland 20852 NOTE: Sessions of the meeting may be closed pursuant to 5 U.S.C. 552(b) 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.

Wednesday, April 3, 2019 OPEN SESSION

1. Opening Remarks C. Einberg, NRC Mr. Einberg will formally open the meeting and Ms. Kock will provide opening A. Kock, NRC remarks.

2. Old Business S. Holiday, NRC Ms. Holiday will review past ACMUI recommendations and provide NRC responses.

8:30 - 10:30 3. Open Forum ACMUI The ACMUI will identify medical topics of interest for further discussion.

4. Yttrium-90 Microspheres Brachytherapy Licensing Guidance M. OHara, ACMUI Subcommittee Report Dr. OHara will discuss the subcommittees recommendations on the NRCs draft Revision 10 to the Yttrium-90 Microspheres Brachytherapy Licensing Guidance.

5. Lucerno Dynamics LARA Infiltration Detection R. Lattanze, Mr. Lattanze will provide an overview about a product that can assist with Lucerno Dynamics detecting nuclear medicine injection infiltrations.

10:30 - 10:45 BREAK

6. Summary of Changes to 10 CFR Part 35 L. Dimmick, NRC Ms. Dimmick will discuss the changes to the final rule 10 CFR Part 35 that went into effect January 2019.

10:45 - 12:00

7. Germanium-68/Gallium-68 Subcommittee Report M. Shober, ACMUI Ms. Shober will discuss the subcommittees recommendations on the NRCs draft revision to the Germanium-68/Gallium-68 Pharmacy Grade Generator Licensing Guidance.

12:00 - 1:00 LUNCH

8. Medical Related Events DB. Howe, NRC Dr. Howe will provide an update on recent medical events.

1:00 - 2:45 9. Appropriateness of Medical Event Reporting Subcommittee Report R. Ennis, ACMUI Dr. Ennis will discuss the subcommittees recommendations on the appropriateness of the required medical event reporting in accordance with 10 CFR 35.3045.

2:45 - 3:15 BREAK (public portion ends)

WEDNESDAY, APRIL 3, 2019 CLOSED SESSION 3:15 - 5:00 10. ACMUI Working Session: Biennial Evaluations and Commission ACMUI Meeting Presentation Development THURSDAY, APRIL 4, 2019 OPEN SESSION

11. ACMUI Reporting Structure K. Jamerson, NRC Members will discuss the reporting structure of the Committee and provide feedback to the NRC staff.

8:30 - 9:30 12. Special Presentation to Ms. Weil S. Moore, NRC Mr. Moore will make a special presentation to Ms. Laura Weil

13. Thoughts on Leaving the ACMUI L. Weil, ACMUI Ms. Weil will share her thoughts on leaving the ACMUI, after serving two full terms (8 years).

9:30 - 10:00 BREAK

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 - 1:15 LUNCH

16. ACMUI Bylaws Subcommittee Report L. Weil, ACMUI Ms. Weil will discuss the subcommittees recommendations for changes to the ACMUIs Bylaws - with particular focus on the ACMUI Chairs role with respect to subcommittees.

1:15 - 2:45 17. Open Forum ACMUI The ACMUI will discuss medical topics of interest previously identified.

18. Administrative Closing K. Jamerson, NRC Ms. Jamerson will provide a meeting summary and propose dates for the fall 2019 meeting.

2:45 ADJOURN

Opening Remarks NO HANDOUT

2007 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS 33 NRC staff should modify 10 CFR 35.491(b)(2) to specify 'superficial Open ophthalmic treatments. Additionally, NRC staff should change the title of 10 10/22/07 Accepted Delayed CFR 35.491 to specify superficial ophthalmic treatments.

34 NRC staff should not revise 10 CFR 35.491 (intended for ophthalmologists)

Partially Open to include training and experience for the new intraocular device. Instead, 10/22/07 Accepted Delayed NRC staff should regulate the new intraocular device under 10 CFR 35.490.

1

2008 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS 19 NRC staff should accept the six recommendations of the Permanent Implant Brachytherapy Subcommittee report with one modification.

Recommendation six should be modified to read, When a Written Open 10/27/08 Pending Directive (WD) is required, administrations without a prior WD are to Delayed be reported as regulatory violations and may or may not constitute an ME.

26 NRC staff should revise 10 CFR 35.40 to clarify that the AU should Open sign and date both the pre-implantation and post-implantation 10/28/08 Accepted Delayed portions of the WD for all modalities with two part WDs 27 NRC staff should revise 10 CFR 35.40 to clarify that an AU, not the AU, should sign and date both the pre-implantation and post-implantation portions of the WD for all modalities with two part WDs. Open 10/28/08 Accepted

[Note this allows for one AU to sign the pre-implantation portion of Delayed the WD and another AU to sign the post-implantation portion of the WD]

1

2011 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS ACMUI created an action item to reevaluate its satisfaction with the reporting ACMUI Open 6 1/12/11 structure annually. Action indefinitely 1

2016 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS Dr. Alderson formed a subcommittee to review and evaluate the training and experience requirements for all modalities in 10 CFR Part 35. Subcommittee members include: Dr. ACMUI Open 16 2/25/2016 Langhorst, Dr. Metter, Dr. Palestro (chair), Dr. Suh and Ms. Weil. NRC staff resource: Maryann Action Indefinitely Abogunde.

The ACMUI will contact their respective professional organizations to request and encourage ACMUI Open 24 3/18/2016 interactions between the NRC and ACMUI with their organization. Action Indefinitely The Committee recommended that staff issue a generic communication (information notice) 39 regarding tubing issues (kinking, connection, hub etc.) during the administration of Y-90 10/6/16 NRC Action Open microspheres brachytherapy.

The Committee recommended that the Pathway 2 remain for the Y-90 Microsphere 42 Brachytherapy Licensing Guidance. The NRC/OAS working group should determine what the 10/7/16 NRC Action Open requirements should be for the proctoring of cases by the manufacturer(s).

The Committee recommended to support the update to the waste disposal section and the 43 review of the Y-90 radiation safety issues in autopsy and cremation in the draft revision of the Y- 10/7/16 NRC Action Open 90 Microsphere Brachytherapy Licensing Guidance.

For the NorthStar Guidance Subcommittee: The Committee recommended that NorthStar 44 10/7/16 NRC Action Open provide a video clip of how the system operates in the training module.

For the NorthStar Guidance Subcommittee: Given the unique design and operation of the 45 NorthStar system, the Committee agreed that NorthStar should have sole responsibility for the 10/7/16 NRC Action Open content of the training course and certification.

For the NorthStar Guidance Subcommittee: The Committee stated that it is important to clarify that a System Administrator can be any individual assigned by the AU without a specifically 46 10/7/16 NRC Action Open defined educational or training background. Given the unique role of the System Administrator, perhaps that individual should be named on the license.

1

2016 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS For the NorthStar Guidance Subcommittee:The Committee recommended an explicit statement regarding the System Administrator Designee, although it may not have been intended, one 47 10/7/16 NRC Action Open could infer from the description of the system administrator designee that there can be only one designee. Presumably, there can, and should, be multiple System Administrator designees.

For the NorthStar Guidance Subcommittee:The Committee recommended that the appropriate time period allotted for training on the changes and the responsibility of the 48 10/7/16 NRC Action Open vendor/manufacturer to inform and train the applicants on changes in a timely manner be specified.

For the NorthStar Guidance Subcommittee: The Committee recommended that the guidance clarify whether the generator will be non-operational until ALL individuals handling the generator 49 are trained in the changes, including the AU, RSO, system administrator, etc. or does it require 10/7/16 NRC Action Open only the AU to be trained on the changes. If the latter, once the AU is trained on the changes, is the AU then solely responsible for training all others on these changes? This should be stated.

For the NorthStar Guidance Subcommittee: The Committee recommended using the term, 50 individual tasks throughout the document for consistency and to clarify that there is only one 10/7/16 NRC Action Open protocol and software program with this system.

For the NorthStar Guidance Subcommittee: The Committee recommended that the 51 10/7/16 NRC Action Open manufacturers procedures be reviewed and incorporated into the Licensing Guidance itself.

For the NorthStar Guidance Subcommittee: The Committee recommended that the term higher 52 than expected be defined in terms of a maximum specific exposure or exposure-rate limit which 10/7/16 NRC Action Open a survey meter should be capable of measuring.

The Committee endorsed the NorthStar Mo-99/Tc-99m Generator (RadioGenix) Subcommittee ACMUI 53 10/7/16 Open Report. Action 2

2017 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS The Committee requested that the recommendations and actions pertaining to the Part 1 35 rulemaking be reviewed during the fall 2017 ACMUI meeting and that additional time 4/26/2017 NRC Action Open be provided to review each item.

The ACMUI recommended that the NRC establish a program allowing a medical use 13 licensee to evaluate MEs as described in 10 CFR 35.3045, in NRC 10 CFR 35.1000 9/11/2017 NRC Action Open licensing guidance, and in 10 CFR 35.3047 with an approved patient safety program.

The ACMUI recommended that NRC licensees with an NRC-approved patient safety program will continue to report medical events as required with the following conditions:

(1) The NRC will not include this event notification in the Event Notification Report posted on its website. If this is not possible, the ME notification posted on the website will leave the licensee information and location anonymous. (2) The NRC will not conduct a reactive inspection of the ME unless the event results or will result in death, unintended 14 permanent harm, or unintended significant temporary harm for which medical 9/11/2017 NRC Action Open intervention was or will be required to alleviate the harm or reduce radiation effects. (3)

The medical use licensee will write a report available for the next NRC inspection describing the event cause and corrective action taken. (4) NRC will develop, with ACMUI advice, new temporary inspection procedures for NRC review of licensee patient safety event reports, and will evaluate, with ACMUI advice, need to change enforcement manual procedures regarding MEs to support a test of this program.

1

2017 ACMUI RECOMMENDATIONS AND ACTION ITEMS The ACMUI recommended that NRC should test out this program with two large medical centers, two community hospitals, two rural hospitals, and two patient clinics for a year, evaluating the ME reports with the ACMUI. During this test period, the NRC, with advice from the ACMUI, should do the following: (1) Develop the minimum criteria for patient 15 9/11/2017 NRC Action Open safety program reviews; (2) Assess how this change in ME reporting impacts the NRCs ability to protect patient health and to minimize danger to the patients life; and (3)

Evaluate the different types of patient safety programs in how lessons learned from their patient safety incident reviews are shared with the medical community.

The ACMUI recommended that after completion of the test year, the NRC should consider opening the program to all NRC medical use licensees who request approval of 16 9/11/2017 NRC Action Open their patient safety program, and to Agreement States who request to implement the program with their medical licensees.

The ACMUI recommended that the NRC redefine its perspective of patient safety to be 17 9/11/2017 NRC Action Open different from occupational safety and from public safety.

The ACMUI recommended that NRC partner with the Department of Health and Human Services (HHS), specially the Agency for Healthcare and Research and Quality (AHRQ) ,

18 9/11/2017 NRC Action Open and ACMUI to develop a national database taxonomy specific for reporting patient events involving medical use of byproduct material.

The ACMUI recommended that the NRC Update its Medical Use Policy Statement and 10 CFR 35 event reporting regulations for patient safety programs to verify the active 19 9/11/2017 NRC Action Open involvement of the licensees patient safety program review of medical errors and reporting of reviews to the national patient safety database.

The ACMUI endorsed the Medical Event Reporting and Impact on Medical Licensee Patient Safety Culture Draft Report, as amended to support the concept of the pilot ACMUI 20 9/11/2017 Open program with the total number of sites and duration to be determined at a later date and Action to include the Patient Intervention Subcommittee recommendations as an addendum .

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2018 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS The ACMUI recommended that there be no breast feeding cessation for 11C, 13N, 15O, and 82Rb; a 12-hours cessation for 18 F-labeled and 68Ga-labeled; a 24-hours cessation for 99mTc-labeled; 7-days cessation for 123I-NaI and 111In-leukocytes; 14 1 2/15/2018 NRC Action Open days cessation for 201-Tl-chloride; 28 days cessation for 67Ga and 89Zr; 35 days for 177Lu, diagnostic; and total stop of breastfeeding for 131I-NaI, 177Lu, therapeutic, 223Ra and all alpha emitters.

The ACMUI endorsed the Nursing Mother Guidelines for the Medical Administration of Radioactive Materials Subcommittee Report, as amended to: (1) include recommended cessation ACMUI 2 periods for both 100 and 500 mrem limits; (2) acknowledge 2/15/2018 Open Action benefits of breastfeeding; (3) incorporate corrections as needed for gamma ray constants; (4) convert the units from conventional to SI units; and (5) correct references.

The ACMUI recommended that the AU be physically present during the initiation of all Leksell Gamma Knife Icon treatments.

However, the AU could be present in the department (defined as a two minute walk to the console area) during treatment but 3 2/15/2018 NRC Action Closed is immediately available to come to the treatment room. If there is an interruption of treatment secondary to medical or mechanical issues, the AU must return to the console prior to reinitiation.

1

2018 ACMUI RECOMMENDATIONS AND ACTION ITEMS The ACMUI recommended as a best practice that appropriately ACMUI 4 trained nursing or auxiliary staff be present at the console to 2/15/2018 Closed Action respond to any immediate medical needs.

The ACMUI unanimously endorsed the Physical Presence ACMUI 5 Requirements for the Leksell Gamma Knife Icon Subcommittee 2/15/2018 Closed Action Report.

The NRC staff will create an ACMUI Recommendations Web Open 6 page and post the full ACMUI Recommendations and Actions 3/7/2018 NRC Action Indefinitely charts on the ACMUI Web page from 2007 - present The NRC staff will send out a medical list server announcement Open 7 to inform subscribers of the availability of ACMUI and NRC ME 3/7/2018 NRC Action Indefinitely slides each time that they are posted on the Medical Toolkit.

Dr. Palestro appointed Ms. Megan Shober and Mr. Zoubir Ouhib to the Physical Presence Requirements for the Leksell ACMUI 9 Gamma Knife Icon Subcommittee. Subcommittee membership 7/16/2018 Closed Action includes: Dr. Ennis, Mr. Ouhib, Ms. Shober, Dr. Suh (Chair),

and Ms. Weil. NRC POC: Sophie Holiday The ACMUI endorsed the report of the Subcommittee on the Nursing Mother Guidelines for the Medical Administration of Radioactive Materials with added language that this document reflects the FDA approved radiopharmaceuticals on the market ACMUI 11 at this time and that licensees are obligated to carefully 9/20/2018 Open Action evaluate radiopharmaceuticals that are not encompassed in this report to keep exposures ALARA to patients, staff, and members of the public. The recommendation passed unanimously.

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2018 ACMUI RECOMMENDATIONS AND ACTION ITEMS The ACMUI endorsed the Leksell Gamma Knife PerfexionTM and Leksell Gamma Knife IconTM Licensing Guidance ACMUI 12 9/20/2018 Closed Subcommittee Report. The recommendation passed Action unanimously.

The NRC staff will provide the Committee with a copy of the Briefing on Results of the Agency Action Review Meeting presentation slides on Yttrium-90 microspheres; SECY 0048, Annual Report to the Commission on Licensee Performance in the Nuclear Materials and Waste Safety 13 9/21/2018 NRC Action Closed Program Fiscal Year 2017, which includes a discussion on medical events involving Yttrium-90 microsphere brachytherapy; and the Strategic Programmatic Overview of the Fuel Facilities and Nuclear Materials Users Business Lines Commission meeting slides related to Yttrium-90.

Dr. Palestro amended the membership of the Training and Experience for All Modalities Subcommittee. Subcommittee ACMUI 14 membership now includes Dr. Metter (chair), Dr. Ennis, Dr. 9/20/2018 Open Action Schleipman, Ms. Weil, Ms. Shober, and Mr. Sheetz. The NRC staff resource continues to be Ms. Maryann Ayoade.

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2018 ACMUI RECOMMENDATIONS AND ACTION ITEMS Dr. Palestro formed a subcommittee to review the Germanium-68/Gallium-68 Pharmacy Grade Generator Licensing Guidance.

ACMUI 15 Subcommittee membership includes Ms. Shober (chair), Dr. 9/21/2018 Open Action Metter, Mr. Sheetz, and Ms. Martin. The NRC staff resource is Dr. Said Daibes.

Dr. Palestro formed a subcommittee to review the revisions to Regulatory Guide 8.39, Release of Patients Administered Radioactive Material. Subcommittee membership includes Mr. ACMUI 16 9/21/2018 Open Sheetz (chair), Ms. Shober, Dr. Dilsizian, Dr. Schleipman, Ms. Action Martin, and Ms. Weil. The NRC staff resource is Dr. Said Daibes.

Dr. Palestro formed a subcommittee to review the Yttrium-90 Microspheres Brachytherapy Sources and Devices TheraSphere and SIR_Spheres Licensing Guidance. ACMUI 17 9/21/2018 Open Subcommittee membership includes Dr. OHara (chair), Dr. Action Dilsizian, Mr. Ouhib, Ms. Marin, Dr. Metter, and Dr. Schleipman.

The NRC staff resource is Dr. Katie Tapp.

Dr. Palestro formed a subcommittee to review and update the ACMUI Bylaws as needed, including a review of the role of the ACMUI Chair and his or her participation on subcommittees. ACMUI 18 9/21/2018 Open Subcommittee membership includes Ms. Weil (chair), Dr. Action Schleipman, Ms. Shober, and Mr. Sheetz. The NRC staff resource is Ms. Sophie Holiday.

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2018 ACMUI RECOMMENDATIONS AND ACTION ITEMS Dr. Palestro formed a subcommittee to review the appropriateness of the required elements of medical event reporting, the adherence to these requirements, and ACMUI 19 recommend actions to improve reporting. Subcommittee 9/20/2018 Open Action membership includes Dr. Ennis (chair), Ms. Weil, Ms. Martin, Mr. Ouhib, Dr. Dilsizian, and Ms. Shober. The NRC staff resource is Ms. Lisa Dimmick The Committee recommended for the NRC to draft an 20 Information Notice on the best practices that could help prevent 9/21/2018 NRC Action Open medical events.

The Committee requested a list of all the current ACMUI members, their contact information, information regarding each members term, and the subcommittee(s) they serve on. The Committee also requested that the NRC staff create a web 21 9/21/18 NRC Action Closed page that lists the active subcommittees and subcommittees that have been sunset, their members with term expiration, NRC staff resource, and the specific charge of the subcommittee.

The Committee tentatively scheduled the spring 2019 meeting ACMUI 22 for April 15-16, 2019. The alternate meeting dates are April 3-4, 9/21/18 Closed Action 2019, subject to Commission availability.

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2019 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS The ACMUI recommended adding language into the draft Training and Experience Requirements for All Modalities ACMUI 1 Subcommittee report regarding the Committee's desire to work 2/26/2019 Open Action with the NRC staff to develop a curriculum for limited-scope authorized user pathway.

The ACMUI endorsed the Training and Experience ACMUI 2 Requirements for All Modalities Subcommittee Report, and the 2/26/2019 Open Action recommendations included therein.

1

Open Forum NO HANDOUT

Sub-Committee Members

• Vasken Dilsizian, M.D.

ACMUI Sub-committee on the Draft

• Melissa Martin, M.S.

Y-90 Microspheres Brachytherapy

• Darlene Metter, M.D.

Licensing Guidance, Rev. 10

• Michael OHara, Ph.D. (Chair)

• Zoubir Ouhib, M.S.

Michael OHara, Ph.D.

• Robert Schleipman, Ph.D.

ACMUI FDA Representative April 3, 2019 NRC Resource: Katie Tapp, Ph.D.

Background Background

• Manual intra-arterial brachytherapy

• The licensing guidance was published in 2002 implants with unique properties for and revised in 2004, 2007, 2008, 2011 and 2016.

1°and 2°hepatic malignancies

• In Oct. 2016, the ACMUI provided comments on the initial draft Rev. 10 of the licensing guidance. Specific topics addressed included:

• Regulated under 10 CFR 35.1000 Other 1. Consider the elimination of Pathway 2 Medical Uses of Byproduct Material or (manufacturer AU training)

Radiation from Byproduct Material 2. Update the waste and disposal section

3. Review Y-90 radiation safety issues in autopsy and cremation 1

Background Background

• In Nov. 2017, the NRC published the draft Rev.

• The NRC/Agreement State WG updated the draft 10 of the licensing guidance in the FR for public Revision 10 licensing guidance to include the comment. The comment period ended in Jan. criteria for T&E and medical event reporting, 2018. inventory requirement specifications, and waste

• In July 2018, the final Part 35 rule, Medical Use disposal issues and aligned the guidance with of Byproduct MaterialsMedical Event the Part 35 rule.

Definitions, Training and Experience, and

• After addressing public comments, the 2016 Clarifying Amendments, was issued. The rule ACMUI comments, and the rule changes, the went into effect Jan. 14, 2019 for NRC WG provided the Subcommittee with a revised licensees. draft guidance for its review and comment.

Subcommittee Charge Comments on the Licensing Guidance

• The Subcommittee believes this is a well To review the staffs draft Revision 10 of the written and documented licensing guidance Yttrium-90 Microsphere Brachytherapy document.

Sources and Devices TheraSpheres and Sir-

• Subcommittee endorses the draft Revision 10 Spheres Licensing Guidance and provide any of the licensing guidance, subject to the comments or recommendations for following specific changes change/acceptance of the guidance.

2

Specific Comments on the Specific Comments on the Licensing Guidance Licensing Guidance

• Defining manufacturers representative

• Delineating the site to be treated more

• Keeping three hands-on cases for each type specifically (left hepatic lobe, right hepatic of microsphere delivery device. The Y-90 lobe) spheres are slightly different (glass or

• Adding activity, date of administration and polymeric) and the delivery systems of the route of administration two devices have different characteristics

• Question whether intervention should be

• RSO familiarity required with all devices used defined in the licensing guidance document at the facility

• Explicit labeling to include patient name,

• Evaluation of a possible ME for unexpected dose, date and treatment site, if feasible dose or activity to an organ or tissue other than the treatment site that is caused by catheter placement Acronyms ACMUI Advisory Committee on the Medical Uses of Isotopes AU Authorized user CFR Code of Federal Regulations FR Federal Register ME Medical Event NRC U.S. Nuclear Regulatory Commission RSO Radiation Safety Officer T&E Training and experience WG Working Group Y-90 Yttrium-90 11 3

U.S. Nuclear Regulatory Commission (NRC)

Advisory Committee on the Medical Use of Isotopes (ACMUI)

Subcommittee on Yttrium-90 Microsphere Brachytherapy Sources and Devices TheraSphere and Sir-Spheres Licensing Guidance, Revision 10 Draft Report Submitted on: March 11, 2019 Subcommittee Charge The Subcommittees charge was to review the staffs draft Revision 10 of the Yttrium-90 Microsphere Brachytherapy Sources and Devices TheraSphere and Sir-Spheres Licensing Guidance and provide any comments or recommendations for change/acceptance of the guidance.

Subcommittee Members Dr. Vasken Dilsizan Mr. Zoubir Ouhib Ms. Melissa Martin Dr. Robert Schleipman Dr. Darlene Metter Dr. Michael OHara (Chair)

NRC Staff Resource: Dr. Katie Tapp Introduction Yttrium-90, a pure beta emitter, decays to stable zirconium-90 with a physical half-life of 64.1 hours1.157407e-5 days <br />2.777778e-4 hours <br />1.653439e-6 weeks <br />3.805e-7 months <br /> (2.67 days). The average energy of the beta emissions from yttrium-90 is 0.9367 MeV with an average penetration range of 2.5 mm and a maximum range of 11 mm in tissue. Following delivery of the yttrium-90 microspheres in tumorous liver tissue, the microspheres provide an embolic effect and the beta radiation emitted provides a therapeutic effect. The microspheres are delivered into the liver tumor through a catheter placed into the hepatic artery that supplies blood to the tumor. The microspheres, being unable to pass through the vasculature of the liver due to arteriolar capillary blockade, are trapped in the tumor and exert a local radiotherapeutic effect with some concurrent damage to surrounding normal liver tissue. There are currently two Y-90 based microsphere devices that have been reviewed by the FDA. They differ slightly in composition of the spheres and in the patient population for which they are approved.

TheraSphere consists of insoluble glass microspheres where yttrium-90 is an integral constituent of the glass. A preassembled single use TheraSphere Administration Set is provided for each dose. Also provided are re-usable accessories including an acrylic box base, top shield, removable side shield, bag hook and a RADOS RAD-60R radiation dosimeter (or equivalent). TheraSphere is an approved HDE device indicated for use in radiation treatment

or as neoadjuvant to surgery or transplantation in patients with unresectable hepatocellular carcinoma (HCC) who can have placement of appropriately positioned hepatic arterial catheters.

SIR-Spheres microspheres consist of biocompatible resin microspheres containing yttrium-90 with a size between 20 and 60 microns in diameter. The administration set includes a delivery box (an acrylic box base), delivery set (including all the catheters and connectors), and a V-vial (including the shielding). Sir-sphere are an approved PMA device for the treatment of unresectable metastatic liver tumors from primary colorectal cancer with adjuvant intrahepatic artery chemotherapy (IHAC) of FUDR (Floxuridine).

Background

The Yttrium-90 Microsphere Brachytherapy Sources and Devices TheraSphere and Sir-Spheres Licensing Guidance was published in 2002 and revised in 2004, 2007, 2008, 2011 and 2016. NRC staff, stakeholders and the ACMUI identified numerous issues that needed to be addressed. NRC staff and Agreement State Representatives formed a working group to address the issues and make any necessary revisions. Revision 10 updated the criteria for training and medical event reporting, inventory requirement specifications, and waste disposal issues and aligned the guidance with the Part 35 rule entitled Medical Use of Byproduct Materials Medical Event Definitions, Training and Experience, and Clarifying Amendments which went into effect on January 14, 2019 for NRC licensees.

Overall, the Subcommittee believes this is a well written and documented licensing guidance document. The Subcommittee endorses the draft Revision 10 of the licensing guidance, subject to the specific changes outlined below.

Specific Changes to the Guidance Considered by the Subcommittee and its Recommendations Page 8, section iii, line 3: The current section readsto support training provided by a Y-90 microsphere manufacturer representative involving: We suggest defining what manufacturers representative means. This will help to ensure the manufacturers trainer has the proper experience.

Page 9, section B, paragraph 2, line 2: This section currently reads unsupervised use should include at least 3 hands-on patient cases for each type of Y-90 microsphere requested. We suggest keeping three hands on cases for each type of microsphere delivery device. The Y-90 spheres are slightly different (glass or polymeric) and the delivery systems of the two devices have different characteristics. This will ensure that the user has documented experience with both device types.

Page 11, section 4.2, line 4: The current sentence reads, An RSO already listed on a license that includes one type of microsphere device does not require additional approval for the other type of microsphere device We suggest adding to the end of the sentence, but should be familiar with all devices used at the facility.

Page 13, section 5.1, paragraph 1, last sentence: The current sentence reads, Unexpected dose or activity to an organ or tissue other than the treatment site that is caused by catheter placement during delivery of the y-90 microspheres is not considered shunting. We suggest adding and should be evaluated as a possible medical event to the end of the sentence.

Page 14, section 5.2, paragraph 3, line 2: The current sentence reads, the treatment site, the radionuclide (including the physical form (Y-90 microspheres)); the model of spheres e.g.

TheraSpheres or Sir-Spheres) or manufacturer, the prescribed dose or activity, and if appropriate for the type of microsphere used, the statement or dose or activity delivered at stasis. We suggest describing the site to be treated more specifically (left lobe, right lobe)

Page 14, section 5.2, paragraph 3, line 4: The current sentence reads, the treatment site, the radionuclide (including the physical form (Y-90 microspheres)); the model of spheres e.g.

TheraSpheres or Sir-Spheres) or manufacturer, the prescribed dose or activity, and if appropriate for the type of microsphere used, the statement or dose or activity delivered at stasis. We suggest adding activity, date of administration and route of administration Page 14, section 5.2, paragraph 4, line 6: The sentence currently reads, anatomical description of the tissue intended to receive a radiation dose We suggest changing tissue to tissue(s). Segmented doses may be delivered to various anatomic locations.

Page 15, section 5.3, paragraph 1, line 3: The current sentence reads, as a result from patient intervention, as defined in 10 CFR 35.2... We question if the term intervention should be defined in the guidance document.

Page 16, section 5.3, paragraph 1, line 1: The sentence currently reads organ or tissue other than the treatment site We suggest that treatment site should be intended treatment.

Page 16, section 5.6, paragraph 2, line 2: The current sentence reads label syringes and syringe radiation shields with the radioactive drug. We believe the label should be explicit and include patient name, dose and date, and treatment site, if feasible.

Other Recommendations There are no other recommendations from the subcommittee.

Respectfully Submitted, Subcommittee on Yttrium-90 Microsphere Brachytherapy Sources and Devices TheraSphere and Sir-Spheres Licensing Guidance, Revision 10 Advisory Committee on the Medical Use of Isotopes Nuclear Regulatory Commission

Infiltration Agenda

• Presentation - Ron Lattanze

- Overview Nuclear Medicine Injection

- Incidence Infiltrations - Patient implication/impact Ron Lattanze, Lucerno Dynamics - Solution ACMUI Meeting - Request NRC and ACMUI reconsider a 1980 April 3, 2019 decision regarding infiltrations

• Q&A - Ron Lattanze, Dr. David Townsend, and Dr. Daniel Sullivan Overview Overview - NRC and ACMUI Infiltration Position

• Bolus injection quality critical

• 1980 - Misadministration Reporting

• Infiltration definition and effects Requirements Final Rule

- infiltrations are virtually impossible to avoid

• Quality Control (QC) for injected dose, but not the dose delivered into circulation

• 2002 - Misadministration replaced by Medical Event

• 2008 - Boston VA reports an infiltration as a Medical Event 1

Nuclear Medicine Infiltration Rates Are High Infiltrations Can Matter Patient 11490 MTV Missed MetastaticSUV Lesion

• 200617 Published data: Change Routine Imaging Field of View 50+ references support

- 15.2% (3% 23%) SUV MTV Day 1 Day 5 Understated Understated how diagnostic

• 2017 Alberta QI, 9 radiopharmaceutical Lesion 1 5.27 7.43 10.49 11.34 50%

34%

centers: infiltrations can harm or Lesion 2 3.97 5.57 5.94 10.66 33%

48%

- 15.0% (0% 28%) have harmed patients Lesion 3 27.77 7.17 11.46 41.07 37%

32%

- 20.0% (8% 44%) Lesion 4 2.62 0.88 5.73 2.93 54%

70%

Lesion quantification is

• 2018 Lara QI, 7 centers: understated, but no one knows ~50% of injection sites Adversely AdverselyAffects Day 1 AffectsAssessment Treatment Day 3 when infiltration is outside the are outside image FOV ScanPlanning Conclusions

- 6.2% (2% 16%) imaging FOV 6

Infiltrations Can Exceed Reporting Limits Infiltrations Are Avoidable

• 2017 Chemotherapy rates - 0.18%

• Reporting Limit - 0.5 Sievert (Sv) effective dose equivalent to the tissue

• 2016 Contrast CT rates - 0.24%

Time Estimated Estimated effective dose

• Monitoring nuclear medicine injection quality between infiltration equivalent to the tissue can lead to significant and quick improvement injection and activity at time from injection to imaging of imaging reabsorption time Site Measure Standard Improve Standard Change Phase Rate Error Phase Rate Timeactivity Erroris indicative of an curve A 57 mins 4.55 mCi 11.5 Sv (~23x limit) ideal injection, 1.0%

before imaging. Bolus A 13.3% 2.1% 2.9% 78%

B 107 mins 0.11 mCi 2.26 Sv (~4.5x limit) B 15.7% 4.0% TACpasses 6.0%

injection is indicative of aarm largesensor and infiltration.

counts Injection sensor to2.6%

dropcountsreference remainarm 62%

highlevels during C 12.8% 1.5% 8.7% within uptake 30period.

1.3% seconds. 32%

D 2.1% 0.6% 1.9% 0.6% 10%

2

Identifying, Reporting, and Reducing Request Infiltrations

• Nuclear medicine infiltrations are avoidable Consistent with the goals of:

• Some infiltrations can negatively affect

- NRC patients

- Nuclear Medicine Societies

• Some infiltrations exceed reporting limits

- Technologists Requesting the NRC and ACMUI to reconsider

- Physicians the 1980 infiltration decision and, moving

- Patients forward, require reporting of infiltrations that meet Subpart M criteria.

Acronyms

• QI - Quality Improvement

• SUV - Standardized Uptake Value

• MTV - Metabolic Tumor Value Discussion and Q&A

• FOV - Field of View

• mCi - Millicurie

• CT - Computed Tomography

• TAC - Timeactivity Curve 3

Objective 10 CFR Parts 30, 32, and 35

• Present a summary of rule changes FINAL RULE CHANGES that became effective January 14, 2019 Lisa Dimmick, Team Leader Medical Radiation Safety Team April 3, 2019 Major Changes General Topics

• Permanent implant brachytherapy medical

• Generators

• Diagnostic event reporting & notification

• Associate RSO & Medical Uses Ophthalmic

• 10 CFR 35.300

• Name Associate Radiation Safety Officers on a medical license Physicist Radiopharma-

• Emerging ceuticals

• Training & Experience (T&E) generic Technologies

• Sealed Source &

changes for all individuals

• Notification Device Registry

• Molybdenum (Mo) breakthrough

• Manual

• Vendor Training measurement frequency and reporting of Brachytherapy

• Gamma Knife failed generators

• Training & Source Exchange Experience 1

Generators: 35.204 & 35.3204 Associate RSO (ARSO) and Ophthalmic Physicist: 35.2 & 35.24

• Breakthrough has to be measured for each elution of Mo-99/Tc-99m

• Associate Radiation Safety Officer generator Ophthalmic physicist - defined

• Revised the Preceptor definition - add

• Breakthrough in excess of regulatory ARSO limits need to be reported to NRC and the generator distributor

• Introduced provisions to appoint an ARSO

• Information that has to be reported

• Clarified requirements for licensee, RSO, and reporting timeframe is provided and ARSO Associate RSO: 35.50 Ophthalmic Physicist: 35.433

• Added ARSO

• Added ophthalmic physicist to individuals

• Permit ARSO to provide written who are required to perform certain task attestation

• Clarified the training needed to be an

• Permit new AU to be RSO on new license ophthalmic physicist

• Permit authorized individuals (AU, AMP,

• Clarified expected duties of AMP and ANP) to use authorized status be RSO on ophthalmic physicist for Strontium-90 a different license for same uses for which sources used for ophthalmic the individual is authorized 2

Emerging Technologies: 35.12 Notification: 35.13, 35.14, & 35.15

• Clarified information required for 10 CFR

• Added notification/termination provision 35.1000 medical uses application for the ophthalmic physicist

• Additional aspects needed for radiation safety not in or different from

• Added amendment requirement before requirements in the regulations an individual works as an ARSO or before

• Identification and commitment to meet the RSO can assign duties and tasks to an appropriate existing requirements. ARSO beyond the current authorization Notification: 35.13, 35.14, & 35.15 Manual Brachytherapy: 35.40

• Added notification provision for certain

• Clarified permanent implant manual brachytherapy sources brachytherapy written directive (WD)

• Removed notification attestation components:

statement - Still includes AU signature and dating

• Exempted Type A broad scope licensees before administration from needing to notify NRC when - Requiring the total source strength in permitting an ophthalmic physicist to the pre-implantation portion of the WD working as an ophthalmic physicist;

- recovery 3

Manual Brachytherapy: 35.40 cont. Manual Brachytherapy: 35.40

• Deleting the total dose from the post- The term post-treatment recovery area implantation portion of the WD added means the area or place where a total number of sources and date patient recovers immediately following

• Deleting the requirement to include the brachytherapy procedure before dose being released to a hospital intensive

• Requiring completion of the post- care unit or patient room, or in the case implantation portion of the WD before the patient leaves post treatment of an outpatient treatment, released recovery area from the licensees facility.

Manual Brachytherapy: 35.40 Manual Brachytherapy: 35.40 cont.

• Revises the definition of an ME for - The wrong individual or human permanent implant brachytherapy: research subject

- The total source strength for inside - Sealed source(s) directly delivered to and outside the treatment site the wrong treatment site compared with post-implantation - A leaking sealed source resulting in a written directive dose that exceeds 0.5 Sv (50 rem) to

- The wrong radionuclide an organ or tissue 4

Manual Brachytherapy: 35.40 Manual Brachytherapy: 35.41 What does discontiguous mean?

• All licensees must have procedures to determine if a medical event occurred

• As it relates to the ME criteria in 10 CFR 35.3045 for PIB, discontiguous

• Permanent implant brachytherapy means a location that is not licensees must have procedures to physically adjacent to or touching determine within 60 days the treatment site.

- facility Manual Brachytherapy: 35.41 cont. Training and Experience (T&E)

- The total source strength outside

• Removed written attestation from board treatment site compared to total certification pathway requirements source strength in post implant written

• Revised written attestation statement directive. - is able to independently fulfill the

- That if a patient was not available radiation safety-related duties as within the 60 days, the licensee must

• Permits residency program directors to document the reason for the provide written attestation under certain unavailability. conditions

- facility 5

T&E: 35.51 T&E: 35.57

• Grandfathered RSOs and AMPs must

• Require AMP to be board certified by meet requirements in 10 CFR 35.50(d) or board recognized under 10 CFR 35.51 35.51(c), for materials or uses not authorized earlier

• Grandfathered individuals board certified on or before October 24, 2005 by boards listed in regulation for materials and uses performed before this date Diagnostic medical uses: 35.65 Diagnostic medical uses: 35.65 cont.

• Clarified medical use does not include calibration, transmission, and reference

• Clarified when sources do not have to sources except as authorized under 10 be listed on license CFR 35.500

• Bundled or aggregated sources with activities greater than maximum single source activities in 35.65 is not permitted under 10 CFR 35.65 6

Diagnostic medical uses: 35.590 Radiopharmaceuticals:

35.300, 35.390, & 35.396

• Authorizes an AU for imaging uses for

• Clarified that 10 CFR 35.300 only applied medical use of sealed sources and to materials listed in 10 CFR 35.390 medical devices for diagnosis

• Revised listing of materials in 10 CFR 35.390 for parenteral uses by the primary emission needed for the particular medical use (i.e., is primarily used for emission)

Radiopharmaceuticals: Radiopharmaceuticals:

35.300, 35.390, & 35.396 35.300, 35.390, & 35.396 cont.

• Current Rule reads:

• New Rule reads:

- A licensee may use any unsealed - A licensee may use any unsealed byproduct material prepared for byproduct material identified in § medical use and for which a written 35.390(b)(1)(ii)(G) prepared for directive is required that is medical use and for which a WD is required that is 7

Radiopharmaceuticals: Radiopharmaceuticals:

35.300, 35.390, & 35.396 35.300, 35.390, & 35.396 cont.

10 CFR 35.390(1)(ii)(G) categories for 3 cases 3. Parenteral of any beta emitter, or a photon- emitting radionuclide with a photon energy less than 150 keV, for Current Rule reads:

which a WD is required; and/or

1. Oral 1.22 GBq (33 mCi) of NaI I-131 WD;

4. Parenteral administration of any other

2. Oral > 1.22 GBq (33 mCi) of NaI I-131 radionuclide, for which a WD is WD; required; Radiopharmaceuticals: Radiopharmaceuticals:

35.300, 35.390, & 35.396 35.300, 35.390, & 35.396 cont.

10 CFR 35.390(1)(ii)(G) categories for 3 cases 2) the same as current rule New Rule reads: 3) Parenteral administration of any

- A licensee may use any unsealed radioactive drug that contains a byproduct material identified in § radionuclide that is primarily used for its 35.390(b)(1)(ii)(G) prepared for medical electron emission, beta radiation use and for which a WD is required that characteristics, alpha radiation is characteristics, or photon energy of less than 150 keV, for which a written

1) the same as current rule.

directive is required 8

SS&D: 35.400, 35.500, & 35.600 Vendor Training: 35.610

• Clarifies that use includes uses under the

• Requires vendor training of 10 CFR 35.600 appropriate medical use that is not medical use devices when there are explicitly listed in the Sealed Source and upgrades that affect the operational and Device Registry (SSDR) safety of the unit

• Requires the use to be in accordance with radiation safety conditions and

• Vendor training must be by the vendor or limitations in SSDR someone certified by the vendor

• Differentiated between use requirements for sources and devices containing sources Gamma Knife: 35.655 Acronyms

• Clarifies in the title that the section is

• ANP - Authorized Nuclear Pharmacist addressing full-inspection servicing

• AMP - Authorized Medical Physicist

• ARSO - Associate Radiation Safety Officer

• Retains 5 year frequency for teletherapy

• AU - Authorized User units

• Ga - Gallium

• Ge - Germanium

• Changes frequency for gamma

• GBq - Gigabecquerel stereotactic units to 7 years 9

Acronyms Acronyms

• I-131 - Iodide-131

• Rb - Rubidium

• keV - kiloelectron volts

• RSO - Radiation Safety Officer

• mCi - millicurie

• Sr - Strontium

• ME - Medical Event

• SS&D - Sealed Source and Device

• Mo Molybdenum-99

• SSDR - Sealed Source and Device Registry

• T&E - Training and Experience

• NaI - Sodium Iodide

• Tc Technetium-99

• PIB - Permanent Implant Brachytherapy

• WD - written directive

• PRM - Petition for Rulemaking 10

Subcommittee Members

• Melissa Martin Subcommittee on

• Darlene Metter, M.D.

Germanium-68/Gallium-68 Generator

• Michael Sheetz Licensing Guidance

• Megan Shober (Chair)

Megan Shober Advisory Committee on the Medical Uses of Isotopes April 3, 2019 1 2 Current Ge-68/Ga-68 Generator Proposed Revision to Ge-68/Ga-68 Licensing Guidance (2017) Generator Licensing Guidance

• Expressly names Eckert and Ziegler brand of

• Brand neutral generator

• Removed reconditioning requirements for

• Includes specific breakthrough limit generators not eluted within 48 hours5.555556e-4 days <br />0.0133 hours <br />7.936508e-5 weeks <br />1.8264e-5 months <br />

• Describes steps to take if generator has not been

• Revised breakthrough reporting requirements eluted within 48 hours5.555556e-4 days <br />0.0133 hours <br />7.936508e-5 weeks <br />1.8264e-5 months <br /> (multiple failures)

• Requires notification to the NRC Operations Center if an eluate exceeds breakthrough levels

• Requires wipe tests each day of use 3 4 1

Recommendations Recommendations contd.

• Subcommittee recommends endorsing the draft 4. Due to the long time period required for guidance with changes as noted: breakthrough testing, add guidance on when breakthrough failure is effective.

1. Add alternate pathway training option for ANP user. 5. Revise survey requirements to allow increased

2. Remove brand-specific breakthrough limit. flexibility in performance.

3. Reject proposed breakthrough failure reporting requirement and recommend conformance with 10 CFR 35.3204.

5 6 Acronyms ANP - Authorized Nuclear Pharmacist CFR - Code of Federal Regulations Ga Gallium 68 Ge Germanium 68 NRC - Nuclear Regulatory Commission 7

2

Nuclear Regulatory Commission (NRC)

Advisory Committee on the Medical Use of Isotopes (ACMUI)

Subcommittee Review and Comments on Germanium-68/Gallium-68 Generator Licensing Guidance, Revision 1 Submitted on: November 30, 2018 Subcommittee Members:

Ms. Melissa Martin Dr. Darlene Metter Mr. Michael Sheetz Ms. Megan Shober (Chair)

NRC Staff Resource: Said Daibes-Figueroa, Ph.D.

Background

The subcommittee and its Chair were appointed by ACMUI Chairman, Christopher Palestro, at the ACMUI meeting on September 21, 2018. The purpose of the subcommittee was to review the NRC staffs draft proposed revision to the licensing guidance for Germanium-68 (Ge-68)/Gallium-68 (Ga-68) generators. The NRCs current licensing guidance for Ge-68/Ga-68 generators (Revision 1) was issued on July 13, 2017. At that time, the only Ge-68/Ga-68 generator approved by the U.S.

Food and Drug Administration (FDA) and available on the market was the Eckert and Ziegler GalliaPharm generator. As such, the NRC tailored its licensing guidance to this specific product.

Now that additional Ge-68/Ga-68 generators (IREs [Institute of Radio Elements] Galli Eo' generator and others) are becoming commercially available, the Ge-68/Ga-68 generator licensing guidance is being revised to eliminate reference to any specific generator manufacturer or product.

This document represents the Subcommittees report on the draft proposed revision of this licensing guidance issued by NRC staff in July 2018.

Changes to Guidance Considered by the Subcommittee and its Recommendations General Comment: Throughout the document, ensure that font sizing and bullet size and shape are uniform.

Specific Comments

Title:

The Subcommittee supports the change to the title of the proposed guidance.

Pg 1, 1st paragraph: Delete the sentence Future Ge-68/Ga-68 radionuclide generators will be addressed in revisions to the licensing guidance.

1 of 3

Pg 2, Section 4.1, 2nd paragraph: Replace the words FDA approved with if utilizing an FDA-approved kit for radiolabeling.

Pg 3, Authorized Use for commercial nuclear pharmacies: Add (Form 313 Item 5) under Radionuclides, Chemical/Physical Form, and Maximum Possession Limit.

Pg 4 Section 4.4, 1st paragraph: Replace to develop/create Ga-68 with to elute Ga-68.

Pg 4, Section 4.4: The training for authorized individuals has omitted an alternate pathway option for ANPs, similar to 10 CFR 35.55(b), and written attestation signed by a preceptor ANP.

Pg 5 Written attestation requirement: Replace 35.1000 Ge-68 generator use with 35.1000 Ge-68/Ga-68 generator use.

Pg 5, Section 4.4, last sentence: Replace Physicians or nuclear pharmacists with Other individuals.

Pg 6, 1st bullet: Delete the word to.

Pg 6, 3rd bullet: Begin the sentence with Eluting Pg 6, 7th bullet: Remove the value of 0.001 percent, as this is specific to a particular manufacturer.

Replace with a generic reference to the manufacturers recommended breakthrough limit.

Pg 6, 7th bullet: Delete the sentence Not knowingly distributing or administering to a patient or human research subject any material containing Ga-68 which is determined to exceed the manufacturers 0.001 percent breakthrough limit. This topic is covered by the revised 8th bullet, below.

Pg 6, 8th bullet: Revise to read During the course of breakthrough testing, if the eluate exceeds the manufacturers breakthrough limits, the eluate will not be distributed or administered to a patient or human research subject; Pg 6, 10th bullet: Move this bullet to be the last bullet in the series.

Pg 6, 11th bullet: The criteria for multiple and unusable are vague. Delete on multiple occasions rendering the generator unusable in human patients and research subjects. Adopt the language from the new 10 CFR 35.3204 for telephone reports to the NRC Operations Center within 7 days.

Pg 6, 12th bullet: Center should be capitalized.

Pg 7, general: Due to the extended time necessary for completing a breakthrough test, the guidance should specify when a generator failure is effective. The Subcommittee recommends specifying that a generator has failed on the date when the breakthrough calculation is 2 of 3

performed. This should be no more than 7 days from the date of the previous breakthrough calculation.

Pg 7, 1st bullet: Remove this bullet. There is no reasonable scenario where a breakthrough failure could cause a reportable medical event due to Ge-68, based on 5 rem effective dose to the whole body or 50 rem dose to an organ.

Pg 7, 2nd bullet: In the first sentence, replace manufactures with manufacturers.

Pg 7, 3rd bullet: Revise the sentence to read Conduct surveys of all areas of licensed material use, including the generator storage and kit preparation areas, for contamination each day of use; and Pg 7, 4th bullet: Remove the bullet. This bullet appears to be less stringent than the guidance in NUREG-1556, Vol. 13, Appendix R, which says that areas where licensed material is stored must be surveyed for contamination weekly. What additional survey should be performed every three months that would not be captured in the required weekly surveys?

Pg 8, Section 7.3.2: Distributor (in 2 cases) should be spelled with an o.

Pg 9, Section 7.4.1, 2nd paragraph: In the last sentence, delete the first for to read must provide financial assurance for decommissioning Pg 10, Section 8, 1st paragraph: Add Medical at the beginning of the first sentence.

Pg 10, Section 8, 2nd paragraph: Delete also.

Other recommendations The subcommittee agrees with the remainder of the licensing guidance document.

Respectfully submitted, November 30, 2018, Subcommittee on Germanium-68/Gallium-68 Generator Licensing Guidance, Advisory Committee on the Medical Use of Isotopes (ACMUI),

Nuclear Regulatory Commission (NRC) 3 of 3

Medical Events The dose threshold for diagnostic events Status of Medical Events precludes reportable events most years.

FY 2018 Each year, there are approximately 150,000 therapeutic procedures performed utilizing Donna-Beth Howe, Ph.D. radioactive materials.

Medical Radiation Safety Team April 3, 2019 1 2 Medical Events FY 2013 - 2015 Medical Events FY 2016 - 2018

• 43 Medical events reported - FY 2013

• 50 Medical events reported - FY 2016

• 46 Medical events reported - FY 2014

• 43 Medical events reported - FY 2016

• 57 Medical events reported - FY 2015

• 50 Medical events reported - FY 2018 FY13 FY14 FY15 FY16 FY17 FY18 35.200 0 1 3 35.200 4 0 0 35.300 2 3 8 35.300 4 4 2 35.400 15 5 9 (10) 35.400 6 (18) 7 13 (15) 35.600 10 10 17 35.600 6 8 (14) 10 35.1000 16 27 20 (30) 35.1000 30 24 25 (26) 3 4 1

Medical Events 2018 35.300 Medical Events 35.300 Medical events 2 Iodine-131 MIBG 1

• 50,000 to 12,000 cGy skin dose to 15 cm² Iodine-131 MIBG 1 - Patient was disconnected from infusion pump at Spiros connection to use restroom.

Radium-223 1

- At end of procedure, high activity of I-131 on patients clothing and bed linen.

- Two days later, patient reported discomfort and reddening of skin on upper right thigh erythematous lesion to desquamation the next day.

5 6*

35.300 Medical Events 35.300 Medical Events Iodine-131 MIBG (cont.) Ra-223 dichloride 1

• 50,000 to 120,000 cGy skin dose to 15 cm²

• Administered 176.1 µCi instead of 180 µCi

- Did not decontaminate patient until signs of - Signed written directive called for oral administration erythema.

- Technologist administered intravenous

- Will only disconnect patient if medical emergency.

- Will implement new written directive

- Will use adsorbent pads under administration line.

- Review current policy and procedures with staff

- Will develop patient specific decontamination procedures.

7 8 2

Medical Events 2018 35.400 Medical Events 35.400 Medical events 13 (15) Eye Plaque 1

• Prescribed 8,600 cGy - received 6,500 cGy Eye Plaque 1 Unknown procedure 1 - Used new model of eye plaque that differed from old Prostate 11 (13) model

- Isodose curves differed from brachytherapy plan.

One licensee, 3 reports 3 (5)

- Dose was deeper than expected Human error 2 Wrong site 1 Larger than pre-plan or swelling 2 9 10 35.400 Medical Events 35.400 Medical Events Prostate 9 (11)

Unknown Procedure 1 One licensee, 3 separate reports, 5 patients

• Report 1 - First patient prescribed 14,000 cGy, but

• 70% of the intended dose was delivered administered 8,990 cGy - 62% of prescribed dose

- No root cause, but attributed to human error

- Some seeds may have migrated post-implant

- Performed historical review after inspection

- Second Patient prescribed 14,500 cGy, but received 19,200 cGy - 132% of the prescribed dose

- Third Patient prescribed 14,500 cGy, but received 18,900 cGy - 130% of the prescribed dose 11 12 3

35.400 Medical Events 35.400 Medical Events One licensee, 3 separate reports, 5 patients (cont.)

• Patient prescribed 11,000 cGy, but received 5,815 cGy - 53% of dose

• Report 2 - Patient prescribed 14,500 cGy, but received - Partial seed strand implanted in the bladder 10,500 cGy - 72.4% of the prescribed dose - Removed errant seeds immediately with cystoscopy

- Attributed to human error

• Report 3 - Patient prescribed 14,500 cGy, but received - Corrective actions include:

7,000 cGy - 48% of the prescribed dose

• New written procedure

• Use of more needles, more seeds, and less aggressive sparing of the urethra

• Stop using pre-loaded stranded seeds, so improperly implanted seeds can be individually 13 14 35.400 Medical Events 35.400 Medical Events

• Patient intended 10,800 cGy, but 50% of prostate

• Patient prescribed 11,000 cGy, but received 6,215 received no dose cGy - 56.5% of dose

- Ultrasound volume of prostate was smaller on - Attributed to human error ultrasound pre-implant scan than CT post-implant - Improve imaging techniques scan

- Real-time implantation with ultrasound did not permit

• Patient prescribed 14,400 cGy, but received only potential visualization errors 73% of dose

- Attributed to human error

- Attributed to 18% increase in prostate size compared

- Corrective actions include: to pre-plan

• Additional training to personnel and improved supervision

- Planned intentional cooler coverage near rectum

• Terminate the seed implant program due to low patient volume - Additional training to personnel 15 16 4

35.400 Medical Events 35.400 Medical Events

• Patient intended 12,500 cGy, but received 1,000 cGy

• Patient intended 12,500 cGy, but received 1,000 12.5% of dose (Pd-103 seeds) cGy 12.5% of dose (Pd-103 seeds) [cont.]

- Used Foley catheter but inflated balloon in prostate - Physician and medical physicist will audibly concur urethra instead of bladder on image quality before preceding

- 32 of 54 seeds placed outside prostate and 3 seeds - Manufacturer reset new default magnification value could not be seen that will initial view of relevant prostate anatomy

- Expect risk of radiation damage to rectum and - Once first seed is implanted, fluoroscopic image will surrounding tissue be used to verify relative location of seed and Foley

- Failed to locate Foley catheter compounded by using catheter is where it is expected to be magnification factor of ultrasound device that did not give full view of relevant anatomy 17* 18 35.400 Medical Events Medical Events 2018

• Patient prescribed 12,500 cGy, but received 9,670 35.600 Medical events 10 cGy - 77% of dose (Pd-103 seeds)

- Three seeds from one needle did not remain in place HDR

- Contributing factors:

• Skin 1

• AUs preference for peripheral loading

• Potential rotation of the prostate during needle insertion

• Breast 2

• Pressure effects from using hydrogel to separate prostate

• Gynecological 7 from rectum Device malfunction 2

- Corrective actions: Wrong site 3

• No longer implant needle between urethra and rectum - will use two needles offset on axis Human mistake 2

• Use stabilized needles during surgery 19 20 5

35.600 HDR Events 35.600 HDR Events Skin 1 Skin (cont.)

- Lack of policy for custom immobilization devices for

• Patient prescribed 8 fractions of 500 cGy skin treatment each to temple area, but received 350 cGy - Therapist present at first treatment and any time there on first 2 fractions is a new physicist

- First physicist used incorrect setup - forgot to use - Photograph set up with and without patient to show accuform - second physicist used correct setup accuform

- Wrong position - gap between treatment device and - Barcode scanning to track custom set up devices patients skin 21 22*

35.600 HDR Events 35.600 HDR Events Breast 2 Breast 2

• Wrong site - 1,200 cGy to lateral breast skin

• Wrong site - 1 cc volume of skin received 850

- Patient contacted oncologist because of skin reaction cGy instead of intended 256 cGy

- Physicist used tip end instead of connector end in - Savi applicator - struts 2 and 6 mislabeled - changed treatment plan orientation of the applicator - direction of radiation

- Corrective actions: - Corrective actions:

• Additional training to personnel

• Second physicist to independently verify catheter struts in treatment plan.

• HDR review checklist - verify digitization of struts in treatment plan

• Add HDR plan review to monthly audit

• Additional training to personnel 23 24 6

35.600 HDR Events 35.600 HDR Events Gynecological 7

• Device malfunction

• Device malfunction - Device failed to fully retract at completion of treatment

- Patient to receive 1,500 cGy during 3 fractions in 13 fraction dwell points - Dose of 100 cGY to patient thigh - source was 5 cm from cylinder guide tube connector

- HDR unit malfunctioned at dwell point 9 - Source wire was bent near source

- Delay in removing source from vicinity of patient and

- Treatment adjusted after repair of the HDR unit reporting the event to RSO 25 26 35.600 HDR Events 35.600 HDR Events

• Catheter movement - connector locking nut too

• Prescribed 6 fractions of 350 cGy each - first loose, which allowed catheter to slide out fraction received 2,100 cGy

- Event discovered by skin reaction progressed to moist - Total treatment time incorrectly entered into treatment desquamation planning system

- Dose to skin of 5,154 to 8,555 cGy - Human error and poor decision making - started first

- Corrective action: treatment after hours - second physicist not available

• Retrain medical staff and AU - Corrective actions:

• AU will double check all connections and placement before and

• Second physicist has to independently verify treatment plan after each treatment

• Physicist to check that plan was exported correctly to the

• Purchased new cylinder with new design treatment console 27 28 7

35.600 HDR Events 35.600 HDR Events

• Wrong Site - 587 cGy dose to small

• Wrong site - 5.5 cm outside the treatment site intestine and bowel instead of 220 cGy received 500 cGy in 0.5 cm volume

- Patients pelvis had extensive damage from uterine - Channel 12 digitized twice with no digitization of cancel Channel 13 (Channel 13 digitization included in Channel 12 with no dwell positions for 13)

- Two dwell positions shifted to deliver dose to non-targeted small intestine/bowel in first of 3 fractions

- Treatment plan modified for next 2 fractions - Treatment plan displayed expected dose distribution to critical organs and tumor and no dwell positions for

- Licensee thought not reportable - 10 CFR 35.3045(a)(1)

Channel 13 and (3); NRC determined reportable - 10 CFR 35.3045(a)(1)(iii) and (a)(3)

- Physician approved the plan 29 30*

35.600 HDR Events 35.600 HDR Events

• Wrong site - 5.5 cm outside the treatment site

• Wrong site - 100 cGy outside treatment site received 500 cGy in 0.5 cm volume (cont.) Prescribed 1,890 cGy, but received 1,675 cGy

- Patient discomfort (full bladder) - In first of three fractions digitize the catheter as linear

- Physicist rushed to complete the plan and export to instead of as a single curved catheter treatment console - error overlooked

- Corrective action: - Physicist failed to recognize the incorrectly

• Second check by physicist that did not prepare the plan reconstructed catheter shape in planning software

• Each channel will be carefully reviewed

• Patient not brought to treatment area until plan has been

- Treatment length of 15.7 cm instead of 9 cm checked and exported to console 31 32*

8

35.600 HDR Events (cont.) Medical Events 2018

• Wrong site - 100 cGy outside treatment site 35.1000 Medical events 25 (cont.)

- Discovered on second fraction Perfexion 1 Intervascular Brachytherapy 1

- Treatment plan was not enlarged so physicist could not Radioactive seed localization 1 see the dwell points overlapping Y-90 Microspheres 22

- Corrective actions: Unidentified 2

• Enlarge each treatment plan in which the physicist signs off Therasphere 13

• Use of a formalized check list SirSphere 7 33 34 35.1000 Medical Events 35.1000 Medical Events Perfexion 1 Intravascular Brachytherapy 1

• Device malfunctioned - First extra long delivery catheter - source could not get to treatment site and retracted safely to unit

- Device recorded an error and backup power was low, - Second extra long treatment catheter - source still so the sources were returned to the shielded position could not get to treatment site but source could not be returned to IVB unit; all catheters removed

- One-third of prescribed dose delivered - Hydraulic return mechanism failed to return source.

- No dose to treatment site and 39 cGy to surrounding tissue

- Deformation of delivery catheter confirmed root cause 35 36 9

35.1000 Medical Events 35.1000 Medical Events Radioactive seed localization 1 Y-90 Microspheres 25

- Expected dose 12 cGy to tissue, but patient received 99 cGy to tissue Unknown 2

- Seed implanted and scheduled for removal 6 days later

- Insurance company rescinded approval after seed was implanted and required 3 medical opinions

- Surgery performed approximately 64 days after implant 37 38 35.1000 Unknown Y-90 Events 35.1000 Medical Events Unknown 2 Y-90 Microspheres 25

• Prescribed 13,400 cGy to a segment of the liver, but Therasphere 13 (14) received 10,300 cGy - 77% of intended dose - Overdose 1

- Catheter/Obstruction 8

• Patient received 60% of prescribed dose - Bubbles 2

- Backflow to contrast 1

- Human mistake 1 39 40 10

35.1000 Y-90 Therasphere Events 35.1000 Y-90 Therasphere Events Overdose Dose in Waste Jar

• Prescribed 13,600 cGy, but received 29,400 cGy

• Prescribed 12,000 cGy administered 1,770 cGy -

- Picked up wrong dosage, measured and compared liver volume - 14% of intended dose activity to shipping box information and not the - Licensee thought equipment did not function as written directive designed

- Shipping box was for next weeks patient

- Post administration calculations identified the - Most of the dosage was in the waste jar medical event

- Will add a dose verification step in interventional - Manufacturer could not determine root cause radiology 41 42 35.1000 Y-90 Therasphere Events 35.1000 Y-90 Therasphere Events

• Two patients received less dose than prescribed

• Prescribed activity 122 mCi - received 46 mCi - 38%

- First patient prescribed 72.6 mCi, but received 15 of intended activity mCi. Inspector thought expansion tubing resulted in - From device components sent to manufacturer no turbulent flow triggering suspension issues cause for the blockage was determined

- Second patient prescribed 72 mCi, but received 36.75 mCi - Inspector thought lack of adequate agitation - Obstruction/blockage located in microcatheter -

prior to administration or issues with quality/sizing of obstruction in the outlet tubing at the E junction microspheres

- Extension tubing no longer used - Manufacturer recommended handling microcatheters

- Manufacturer supported Inspectors findings with extra care and looking for kinks 43 44 11

35.1000 Y-90 Therasphere Events 35.1000 Y-90 Therasphere Events

• Prescribed 12,000 cGy - received 2,000 cGy (rad) One licensee - 2 reported medical events

- Malfunction in the administrative set - significantly

• Report 1 - Prescribed 64.8 mCi, but received 41 less pressure than usual to press syringe mCi - 65% of activity

- Saline accumulating in overflow vial

- Air bubbles noted in overflow tubing connected to the

- Only returned portion of administration set that infused micro-catheter dosage into patient to manufacturer

- Connected 3-way stopcock between overflow tubing

- May have been a kink or obstruction in treatment and micro-catheter aspirated bubbles to syringe with catheter but not conclusive stopcock close to patient

- Will send complete administrative set next time - Resurvey of delivery kit showed residual activity 45 46*

35.1000 Y-90 Therasphere Events 35.1000 Y-90 Therasphere Events

• Prescribed 89,200 cGy, but received 57,500 cGy -

• Report 2 - Prescribed 46 mCi but received 27 mCi - 64% of dose 59% of activity - Backflow of microspheres into contrast line and

- Used left radial artery with 5-French Sarah Radial syringe catheter with coaxial micro-catheter - Significant contamination in contrast syringe, flushing

- Nothing unusual was encountered syringe, contrast tubing, and associated y-adaptor

- No radioactive contamination of the suite - Thought contrasting syringe and tubing were made of

- Dose was in catheter, gauze, dose vial and other materials that bind microspheres more than waste administration kit - will look for same materials

- Will use clamp and one-way valve 47 48 12

35.1000 Y-90 Therasphere Events 35.1000 Y-90 Therasphere Events

• Prescribed 23 mCi, but received 7.4 mCi - 32% of the

• Prescribed 35 mCi, but received 5.4 mCi - 16% of activity activity

- Blockage occurred in the delivery apparatus - Microspheres were coagulated in the tubing

- Unexpected activity remained near the Touhy-Borst

- Imaged the administration set and saw most of the connector undelivered activity near where plunger connects to - Manufacturer thought caused by issues with the the dose vial micro-catheter

- Will flush micro-catheter immediately prior to

- Will send administration set and procedure waste to connecting it to the administration kit contractor for manufacturer 49 50 35.1000 Y-90 Therasphere Events 35.1000 Y-90 Therasphere Events

• Prescribed 13,000 cGy to left lobe of liver, but

• Prescribed 24,500 cGy, but administered 13,083 cGy received 8,490 cGy - 65% of dose - 53% of dose

- First vial administered without incident - CT scan verified dose was administered to correct

- Second vial primed and prepped, but saw a train of location bubbles in the line between the dose vial and patient

- AU stopped the procedure; did not want the bubbles - Remainder of dose hung up in catheter despite to cause the flow to reflux into gastric artery and flushing cause permanent damage to the stomach

- Could not pinpoint cause of bubbles - Catheter tubing met manufacturers specifications

- Limit number of staff trained to prime and do set-up and ensure enough are available on treatment days - No root cause identified 51 52 13

35.1000 Y-90 Therasphere Events 35.1000 Medical Events

• Prescribed 1,300 cGy to specific part of liver, but SirSphere 7 received 931 cGy - 71% of dose

- Used 3 different written directives to fractionate the - Wrong site 2 delivery - Measurement unit error 1

- Thought the small activity prescribed contributed to - Written Directive error 1 under dose because of typical losses in the valve and

- High activity clogging 1 tubing

- Low activity administration 1

- Order higher dosages for any administration below 10 mCi

- Amend license to go to different manufacturer 53 54 35.1000 Y-90 SirSphere Events 35.1000 Y-90 SirSphere Events Wrong treatment site 2 Wrong treatment site (cont.)

• Prescribed 38.4 mCi to liver but received about 13 - Difficult visualizing arterial access to the tumor mCi to abdominal wall - Micro-catheter was not advanced far enough into

- Post-treatment scan appeared normal with small correct artery uptake in bowel - Pre-existing kidney impairment precluded using more

- Pain in abdomen with erythema on abdomen - contrast thought dose was above 55 cGy but less than 1,000 - Add second monitor to refer to original arteriogram cGy without switching tasks and improve confidence of

- Thought one-third of dose migrated up a venous correct location ligament and lodged in abdominal wall - Take prophylactic measures for future patients with impaired kidney function 55* 56 14

35.1000 Y-90 SirSphere Events 35.1000 Y-90 SirSphere Events Wrong site Measurement Unit Error

• Prescribed 4,874 cGy to right lobe of liver, but

• Prescribed 0.91 GBq, but received 8.9 mCi received 11,080 cGy to left lobe

- Ordered 0.91 mCi - marked wrong box in computer

- Did not multiply measured dose value by correction

- Human error factor of 10

- Not identify until post-procedure check

- Placed catheter in left hepatic artery instead of right - Worksheet revised to be in SI units hepatic artery

- Written directive sheet to be in SI units

- Dose preparation and post-procedure forms to be in SI units 57 58 35.1000 Y-90 SirSphere Events 35.1000 Y-90 SirSphere Events Written Directive Error High activity clogging 1

• Prescribed 1,504 cGy to right lobe of liver, but

• Prescribed 4,320 cGy, but received 828 cGy - 19%

received 1,498 cGy in left lobe of the dose

- Written directive prepared incorrectly - AU wanted to - Micro-catheter clogging due to unusually large treat left lobe number of microspheres being used

- Identified after completion of the procedure - Prescribed activity was at high end of the treatment

- AU did not indicate correct treatment site on written range directive; AU did not forward pre-treatment - Patient administration delayed 1 day - 25% increase information to the RSO in number of microspheres were needed to deliver

- Clinical staff failed to identify discrepancy during the dose patient time-out just before the implantation - Will use smaller aliquots and/or slower infusion rate 59 60 15

35.1000 Y-90 SirSphere Events 35.1000 Y-90 SirSphere Events Device malfunctioned 1

• Prescribed 19.6 mCi to left lobe of liver, but

• Prescribed 32.5 mCi but received 8 mCi - 25% of received 10 mCi - 51% of activity activity - Planned to deliver activity in two split dosages

- Treatment device malfunctioned and ceased to - Written directive not properly reviewed, so split one deliver microspheres dosage in two instead of the total dosage in two

- Manufacturers representative was present, but cause - Radiation oncologist failed to check the drawn of malfunction is unknown dosages prior to injecting them

- Will return delivery device to manufacturer for - Identified after injection when the remainder of the technical analysis and root cause determination dosage was discovered 61 62*

35.1000 Y-90 SirSphere Events Acronyms

• Prescribed 19.6 mCi to left lobe of liver, but

• AU - Authorized User received 10 mCi - 51% of activity (cont.)

• cGy - centiGray

- Lack of comprehension of dose draw worksheet

• FY - Fiscal Year

• GBq - Giga Becquerel

- Miscommunication and failure to review the written

• HDR - High Dose Rate Remote Afterloader directive

• I-131 - Iodine-131

• I-124 - Iodine-124

- Failure to perform a safety pause and properly review

• IVB - Intravascular Brachytherapy the dosage to be administered against the written directive prior to the administration

• Ra-223 - Radium-223

• MBq - Mega Becquerel 63 64 16

Acronyms

• µCi - microcurie

• mCi - millicurie

• MIBG - Metaiodobenzylguanidine

• Pd-103 - Palladium-103

• RSO - radiation safety officer QUESTIONS?

• SI units - International System of Units

• Y Yttrium-90 65 66 17

Subcommittee Charge

• To review the appropriateness of the required Appropriateness of Medical Event elements of medical event reporting; the Reporting Subcommittee Report adherence to these requirements; and recommend actions to improve reporting.

Ronald D. Ennis, M.D.

April 3, 2019 Subcommittee Members Purpose of Reporting

• An ME is reported to an Agreement State or NRC per 10 CFR

• Dr. Dilsizian 35.3045 as summarized in Event Reporting Schedule for

• Dr. Ennis (Chair) Agreement States 7/29/12 and SA300, Reporting Material Events - The information collected on medical events is

• Ms. Martin invaluable in assessing trends or patterns, identifying generic

• Mr. Ouhib issues or generic concerns, and recognizing any inadequacies or unreliability of specific equipment or procedures. The

• Ms. Shober reported information is critical for initiating a timely and effective response to securityrelated events and will

• Ms. Weil significantly aid in understanding why the event occurred and identifying any actions necessary to improve the effectiveness of NRC and Agreement State regulatory programs.

1

Documents Reviewed Nuclear Material Events Database

• SA300 FSME Procedure Approval Reporting Material

• Nuclear Material Events Database (NMED)

Events

• Includes data from both Agreement States and

• SA105 Reviewing the Common Performance Indicator, NRC Technical Quality of Incident and Allegation Activities

• NMED is managed by NRCs Office of Nuclear

• Event Reporting for Agreement States of July 29, 2012 Material Safety and Safeguards

• NMED Annual Report of 2017

• The NMED contractor is responsible for coding

• OAS Letter 7/2/14 regarding proposal for a public NMED and quality control of information with general

• Root cause and corrective action pick lists oversight from the NRC NMED Project Manager

• NMED content

• Access to NMED is limited NMED Issues NMED Issues

• Frequently, narrative is inadequate for an ACMUI

• NMED lacks information from some inspections reviewer to understand an event, its cause and that has been conducted by the NRC region or contributing factors and the adequacy of the Agreement State.

corrective action.

• In 23% of MEs from FY 201718, either no cause or no corrective action was indicated in NMED

• At times, there appears to be a disconnect report.

between the narrative and the chosen cause from

• Of all 2017 MEs, 11% are incomplete and an the cause pick list. additional 11% are pending additional

• At times, there appears to be a disconnect information.

between the narrative and the chosen corrective

• Public, including AUs and RSOs, only have access action from the corrective action pick list. to an NMED annual report.

2

Recommendations of the Recommendations under Subcommittee Consideration by this Subcommittee

• Root cause and corrective action sections on NMED - In

• Modify how Event Reports are written:

addition to the pick lists, a narrative, searchable, section - Require the report use additional guidelines to be developed should be required. by this subcommittee to assure more complete and useful

• Require root cause and corrective action sections in NMED, information is provided.

both pick list and narrative sections always be completed. - Require the report be initially written by the AU and clinical

• Require information gathered from any investigation be physicists and subsequently reviewed by the inspector.

added to NMED. - Require the inspector interview all involved in the ME.

• Require that a report in NMED be completed within 12 - Require a report from the manufacturer be included if the months. event involved a device.

• Require ACMUI and NRC staff to promulgate the findings of - Corrective action should include medical as well as technical.

annual report of the ACMUI Subcommittee on Medical Events to the medical and medical physics communities. - Require the final report must be signed off by the AU, physicist and inspector.

Conclusion Acronyms

• Significant opportunities exist to enhance the

• ACMUI - Advisory Committee on the Medical Use of Isotopes utility of medical event reporting, the NMED

• AU - Authorized user database, and the promulgation of the

• FSME Office of Federal and State Materials and Environmental Management Programs information to the user community.

• FY - fiscal year

• The Subcommittee asks that it be able to

• ME - medical event continue evaluating these issues in more detail

• NMED - Nuclear Materials Event Database with a goal of creating a set of specific

• NRC - Nuclear Regulatory Commission recommendations.

• OAS - Organization of Agreement States

• RSO - Radiation Safety Officer

• SA - State Agreement 3

ACMUI Working Session

[CLOSED MEETING PORTION]

NO HANDOUT

Outline

• Current Reporting Structure Committee

• Annual Review Reporting Structure

• Meetings

• Discussion Kellee Jamerson, ACMUI Coordinator Medical Radiation Safety Team April 4, 2019 2

Current Reporting Structure Annual Review The Commission

• In September 2012, the ACMUI EDO recommended to have an annual Director, NMSS review of reporting structure.

• This is the ninth annual review.

Director, MSST ACMUI MSEB 3 4 1

Meetings Two meetings at Headquarters each year

• March/April Discussion

• September/October Approximately 2-3 teleconferences (as needed) 5 6 Points of Contact Acronyms

• Andrea Kock - MSST Director

• EDO - Executive Director for

- 301-415-2368; Andrea.Kock@nrc.gov Operations

• Christian Einberg - Designated Federal

• MSST - Division of Materials Safety, Officer (DFO), Chief, MSEB Security, States, and Tribal Programs

- 301-415-5422; Christian.Einberg@nrc.gov

• MSEB - Medical Safety and Events

• Kellee Jamerson - DFO, ACMUI Assessment Branch Coordinator

• NMSS - Office of Nuclear Material

- 301-415-7408; Kellee.Jamerson@nrc.gov Safety and Safeguards 7 8 2

Special Presentation to Ms. Laura Weil NO HANDOUT

Thoughts on Leaving the ACMUI NO HANDOUT

Commission Meeting with the ACMUI NO HANDOUT

Group Photo NO HANDOUT

Subcommittee Members ACMUI

• Robert Schleipman, M.D.

Bylaws Subcommittee

• Michael Sheetz

• Megan Shober Laura Weil

• Laura Weil (chair)

April 4, 2019 NRC Staff Resource: Sophie Holiday Subcommittee Charge Existing Language in the Bylaws Section 1.3.6 currently states:

• Review ACMUI Bylaws and recommend updates The Chair may take part in the discussion of any

• Particular focus on the role of the ACMUI subject before the ACMUI and may vote. The Chairman and his/her participation on Chair should not use the power of the Chair to bias subcommittees the discussion. Any dispute over the Chairs level of advocacy shall be resolved by a vote on the Chairs continued participation in the discussion of the subject.

1

Suggested Additional Language Existing Language - Conduct of Members The Subcommittee proposes to add the following Section 4.1 currently states:

language:

If a member believes that he or she may have a In matters where the ACMUI Chairs unique conflict of interest with regard to an agenda item to experience and knowledge would be especially be addressed by the ACMUI, this member should informative, the Chair may serve on relevant divulge it to the Chair and the DFO as soon as subcommittees. In these instances, the ACMUI possible and before the ACMUI discusses it as an Chair will not chair the subcommittee. agenda item. ACMUI members must recuse themselves from discussion of any agenda item in which they have a conflict of interest.

Suggested Language - Conduct of Members Recommendations The Subcommittee proposes to add the following:

• ACMUI Chair should be permitted to serve as a subcommittee member (not chair) when his/her Members cannot personally and substantially participate in specific expertise is necessary. A specific the review of any particular matter (including general matters such as a rulemaking) that could directly and statement to that effect should be included in the predictably affect their personal financial interest or the ACMUI Bylaws.

financial interest of:

- Their spouse or minor child

• Explicit language defining financial Conflict of

- Their general partner or organization in which they Interest (COI) should be inserted in bylaws.

serve as an officer, director, trustee, general partner, or employee

- An organization with which they are negotiating or have an arrangement for prospective employment 2

Acronyms ACMUI - Advisory Committee on the Medical Uses of Isotopes COI - Conflict of Interest DFO - Designated Federal Officer 3

U.S. Nuclear Regulatory Commission (NRC)

Advisory Committee on the Medical Use of Isotopes (ACMUI)

Subcommittee on ACMUI Bylaws Draft Report Submitted On: March 3, 2019 Subcommittee Members: Robert Schleipman, Michael Sheetz, Megan Shober, Laura Weil (Chair)

NRC Staff Resource: Sophie Holiday Subcommittee Charge:

Review ACMUI Bylaws and recommend updates, with particular focus on the question of whether the ACMUI Chair may serve as a member or chair of any ACMUI subcommittee.

Subcommittee process:

The Subcommittee and its Chair were appointed by the ACMUI Chairman, Dr. Chris Palestro, at the fall 2018 ACMUI meeting.

The Subcommittee members reviewed ACMUI Bylaws to determine whether the existing ACMUI Bylaws addressed the issue of Chair participation in subcommittee proceedings. Suggestions for possible revision regarding that question and any other concerns were made. A draft report was crafted by the Subcommittee Chair and was circulated to all Subcommittee members. The draft report was discussed, amended as necessary, and submitted to the full ACMUI for discussion at the spring 2019 meeting April 34, 2019.

Issues considered:

1. Should the ACMUI Chair be allowed to participate on subcommittees? If so, in what capacity should the ACMUI Chair participate? What language, if any, should be added to the Bylaws to clarify this question?

2. What other clarifications or additions to the ACMUI Bylaws, if any, should be considered?

Discussion:

1. ACMUI Chair participation on subcommittees It has been the practice of the NRC to prohibit the participation of the ACMUI Chair in subcommittee deliberations and recommendations. This was recently brought to the attention of the incoming ACMUI Chairman, Dr. Palestro, who was asked to relinquish his position as Chair of an ongoing subcommittee in anticipation of his role as ACMUI Chairman. Dr. Palestro felt that this issue should be investigated by a subcommittee, and an explicit recommendation be made to the ACMUI, with potential clarification in the ACMUI Bylaws. The current ACMUI Chair and Vice Chair would not vote on the recommendations put forth by this Subcommittee.

The ACMUI Bylaws do not address this point, nor does the ACMUI Charter. The documents of our sister NRC Federal Advisory Committee Act (FACA) Committee, Advisory Committee on Reactor Safeguards (ACRS) are also generally silent on this issue, although the ACRS Chair is the designated Chair of a standing subcommittee.

The ACMUI has no standing subcommittees, per its charter. There is no discussion of this issue on the FACA website, nor did consulted FACA staff suggest any required position on the issue. Several other FACA committee bylaws and charters were reviewed by the Subcommittee; none had explicit language regarding the potential for Chair membership and participation in subcommittee work. The understood rationale for the existing informal prohibition of the ACMUI Chair on subcommittees is twofold: a) the role of Chair is onerous and timeconsuming. It would be an imposition to expect the Chair to undertake additional subcommittee responsibilities, and b) the Chair might exert undue influence on subcommittee deliberations. Section 1.3.6 of the ACMUI Bylaws explicitly states, The Chair may take part in the discussion of any subject before the ACMUI and may vote. The Chair should not use the power of the Chair to bias the discussion. Any dispute over the Chairs level of advocacy shall be resolved by a vote on the Chairs continued participation in the discussion of the subject.

Each member of the ACMUI has a specific area of expertise. In some cases, there is no duplication of expertise among the ACMUI members. The Subcommittee felt that all subcommittees should be able to avail themselves of the relevant expertise of any member of the ACMUI. The potential for benefit of specific expertise on any given subcommittee outweighs the potential for undue influence by the position of Chair.

The example given was the recent subcommittee relating to gamma stereotactic radiosurgery (GSR) licensing guidance. Only one member of the ACMUI had specific and significant GSR expertise. Had that one member been the ACMUI Chair, and prohibited from subcommittee participation, the subcommittee would have been deprived of essential information and input in its deliberations. Concern was expressed that ACMUI Chair participation on a subcommittee should not overburden or compromise the ability of the Chair to perform the duties of ACMUI Chair; so it is proposed that the ACMUI Chair should not be asked to serve as any subcommittee chair.

The Subcommittee also discussed whether explicit Bylaws language is required to address this question (or whether a formal position expressed and captured at the ACMUI meeting would be adequate). The membership of the ACMUI turns over completely every eight years or sooner, and NRC staff rotate in and out of the medical team with unpredictable frequency. It is challenging to research areas of tradition and practice such as this. The minutes and transcripts of ACMUI meetings, while available, are not indexed by subject. It was felt that there are potential limits to ACMUI institutional memory, such that inclusion of specific language in the Bylaws would be the most efficient way to address this issue. New language is suggested (in bold italics) to be inserted in the existing Bylaws statement regarding ACMUI Chair discussion, participation, and voting rights. Section 1.3.6):

The Chair may take part in the discussion of any subject before the ACMUI and may vote. The Chair should not use the power of the Chair to bias the discussion. Any dispute over the Chairs level of advocacy shall be resolved by a vote on the Chairs continued participation in the discussion of the subject. In matters where the ACMUI Chairs unique experience and knowledge would be especially informative, the Chair may serve on relevant subcommittees. In these instances, the ACMUI Chair will not chair the subcommittee.

2. Additional Bylaw additions The Subcommittee felt that the existing language in the Bylaws regarding conflict of interest was vague. The bylaws currently state:

4. CONDUCT OF MEMBERS 4.1 If a member believes that he or she may have a conflict of interest with regard to an agenda item to be addressed by the ACMUI, this member should divulge it to the Chair and the DFO as soon as possible and before the ACMUI discusses it as an agenda item. ACMUI members must recuse themselves from discussion of any agenda item in which they have a conflict of interest.

It is suggested that the ACMUI Bylaws be amended to include additional language to clarify more completely what constitutes a conflict of interest for ACMUI members.

The following language is used in the ACRS Bylaws, Section 10.22, defining what constitutes a financial conflict of interest and should be considered for amending the ACMUI Bylaws:

Members cannot personally and substantially participate in the review of any particular matter (including general matters such as a rulemaking) that could directly and predictably affect their personal financial interest or the financial interest of:

Their spouse or minor child Their general partner or organization in which they serve as an officer, director, trustee, general partner, or employee An organization with which they are negotiating or have an arrangement for prospective employment However, the Subcommittee welcomes staff input on other language that will provide adequate clarification.

Summary of recommendations:

The Subcommittee recommends that the ACMUI Chair be permitted to serve as subcommittee member (not chair) when his/her specific expertise is necessary. A specific statement to that effect should be included in the ACMUI Bylaws.

The Subcommittee recommends that more explicit language be included in the ACMUI Bylaws defining conflict of interest with respect to participation of individual ACMUI members in discussion of matters that come before the Committee.

Respectfully submitted.

The ACMUI Bylaws Subcommittee

Open Forum NO HANDOUT

September 2019 Monday Tuesday Wednesday Thursday Friday 2 3 4 5 6 Labor Day X 9 10 11 12 13 16 17 18 19 20 ASTRO Annual ASTRO Annual ASTRO Annual Meeting Meeting Meeting X

23 24 25 26 27 30 Rosh Hashana

October 2019 Monday Tuesday Wednesday Thursday Friday 1 2 3 4 Rosh Hashana 7 8 9 10 11 X Yom Kippur 14 15 16 17 18 Columbus Day Sukkot Sukkot 21 22 23 24 25 Shmini Atzeret Simchat Torah 28 29 30 31