ML18053A770

Advisory Committee on the Medical Uses of Isotopes (ACMUI) March 7-8, 2018 Meeting Ebinder

ML18053A770
Person / Time
Issue date:	02/22/2018
From:	Office of Nuclear Material Safety and Safeguards
To:
Holiday, Sophie
References
Download: ML18053A770 (85)

Text

Advisory Committee on the Medical Uses of Isotopes MCI ye,vi 7-g, 20ig

MEETING AGENDA ADVISORY COMMITTEE ON THE MEDICAL USES OF ISOTOPES March 7-8, 2018 Two White Flint North Building (T2-B3), Rockville, Maryland 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, March 7, 2018 OPEN SESSION

1. Opening Remarks D. Bollock, NRC Mr. Bollock will formally open the meeting and Ms. Howell will L. Howell, NRC provide opening comments.

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

8:30 - 10:15

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

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

10:15 - 10:30 BREAK

5. Staff Response to Medical Event Reporting and its D. Bollock, NRC Impacts on Safety Culture Subcommittee Report Mr. Bollock will discuss the staffs evaluation of the ACMUIs recommendations related to how NRCs medical event reporting 10:30 - 11:30 criteria under 10 CFR 35.3045 impacts safety culture at medical institutions.

6. ACMUI Reporting Structure S. Holiday, NRC Members will discuss the reporting structure of the Committee and provide feedback to NRC staff.

11:30 - 1:00 LUNCH

7. Worldwide Supply and the Domestic Production of R. Green, Cardinal Molybdenum-99 Health Mr. Green will provide an update of the worlds supply of and 1:00 - 2:30 the domestic production of molybdenum-99 in the U.S.

8. Medical Projects on the Horizon D. Bollock, NRC Mr. Bollock will discuss the major assignments currently under review by the medical radiation safety team.

2:30 - 3:00 BREAK (public portion ends) 3:00 - 5:00 9. ACMUI Working Prepatory Session

Thursday, March 8, 2018 OPEN SESSION

10. Special Presentation to Dr. Zanzonico M. Dapas, NRC Mr. Dapas will make a special presentation to Dr. Zanzonico.

8:30 - 9:00 11. Emerging Technologies Commission Paper I. Wu, NRC Ms. Wu will provide an overview of a paper that was provided to the Commission related to the resources needed to address the development of emerging technologies.

9:30 - 10:00 BREAK

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

10:00 - 12:15

13. Group Photo ACMUI The ACMUI will take a group photo with and without the Commission.

12:15 - 1:30 LUNCH

14. Thoughts on Leaving the ACMUI P. Zanzonico, ACMUI Dr. Zanzonico will share his thoughts on leaving the ACMUI.

1:30 - 2:45 15. Open Forum ACMUI The ACMUI will discuss medical topics of interest previously identified.

2:45 16. Administrative Closing S. Holiday, NRC Ms. Holiday will provide a meeting summary and propose dates for the fall 2018 meeting.

ADJOURN ML072670110

Opening Remarks NO HANDOUT

2007 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS 2

NRC staff should remove the attestation requirement for board certified individuals and rewrite the attestation requirement for individuals seeking authorization under the alternate pathway. The rewritten attestation 6/12/07 Accepted Open should not include the word competency but should instead read has met the training and experience requirements.

3 NRC staff should revise the regulations so that board certified individuals, who were certified prior to the effective date of recognition or were 6/12/07 Accepted Open certified by previously recognized boards listed in Subpart J of the previous editions of Part 35, are grandfathered.

6 NRC staff should add the words or equivalent so it is clear that information included in a letter is the same as that which would have been 6/13/07 Accepted Open submitted in NRC Form 313A (35.12(c))

7 NRC staff should revise 10 CFR 35.50(c)(2) to include AUs, AMPs, or ANPs identified on any license or permit that authorizes similar types of use of byproduct material. Additionally, the AU, AMP, or ANP must have 6/13/07 Accepted Open experience with the radiation safety aspects of similar types of use of byproduct material for which the individual is seeking RSO authorization.

8 NRC staff should remove the attestation requirement from 10 CFR 35.50(d) for AUs, AMPs, and ANPs seeking RSO status, if the AU, AMP, 6/13/07 Accepted Open or ANP seeking RSO status will have responsibilities for similar types of uses for which the individual is authorized.

1

2007 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS 10 a) NRC staff should allow more than one RSO on a license with a designation of one RSO as the individual in charge. b) NRC should create a) Accepted a) Open a Regulatory Issue Summary (RIS) to inform the regulated community of 6/13/07 b) Accepted b) Closed NRCs interpretation. The RIS should be sent to ACMUI and the Agreement States for review and comment.

25 NRC staff should revise the current regulations to include Canadian 8/16/07 Accepted Open trained individuals who have passed the ABNM certification exam.

30 The Elekta Perfexion should be regulated under 10 CFR 35.1000 until Open 10 CFR 35.600 is modified to be performance-based, which would allow 10/22/07 Accepted Delayed the Perfexion to be regulated under 10 CFR 35.600.

31 NRC staff should require experienced RSOs and AMPs to receive additional training, if the individual is seeking authorization or 10/22/07 Accepted Open responsibility for new uses.

32 NRC staff should not require experienced RSOs to obtain written 10/22/07 Accepted Open attestation to become authorized or have responsibility for new uses.

34 NRC staff should modify 10 CFR 35.491(b)(2) to specify 'superficial Open ophthalmic treatments. Additionally, NRC staff should change the title of 10/22/07 Accepted Delayed 10 CFR 35.491 to specify superficial ophthalmic treatments.

35 NRC staff should not revise 10 CFR 35.491 (intended for ophthalmologists) to include training and experience for the new Partially Open 10/22/07 intraocular device. Instead, NRC staff should regulate the new intraocular Accepted Delayed device under 10 CFR 35.490.

2

2007 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS 36 NRC staff should not require medical licensees regulated under 10 CFR 35.400, 500, or 600, as applicable, to only use the sealed sources and 10/22/07 Accepted Open devices for the principle use as approved in the SSDR.

37 NRC staff should revise 10 CFR 35.290 to allow physicians to receive training and experience in the elution of generators and preparation of kits 10/22/07 Accepted Open under the supervision of an ANP.

3

2008 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS 2

NRC staff should pursue rulemaking to allow more than one RSO on a medical use license with the indication of one RSO as the 4/28/08 Accepted Open individual in charge.

5 NRC staff should incorporate the subcommittees recommendations Open for the 4/28/08 Accepted Delayed Gamma Knife Elekta Perfexion' in future rulemaking.

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.

22 ACMUI encouraged NRC staff to begin the rulemaking process to move the medical use of Y-90 microspheres from 10 CFR 35.1000 Partially Open to another section of the regulations, so that the training and 10/27/08 accepted Delayed experience requirements for AUs can be vetted though the public review process instead of residing in guidance space.

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 1

2008 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS 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]

28 NRC staff should revise 10 CFR 35.65 to clarify it does not apply to sources used for medical use; however, NRC should not require licensees to list the transmission sources as a line item on the license. NRC staff should also revise 10 CFR 35.590 to permit the 10/28/08 Accepted Open use of transmission sources under 10 CFR 35.500 by AUs meeting the training and experience requirements of 10 CFR 35.590 or 35.290.

29 NRC staff should revise 10 CFR 35.204(b) to require a licensee that uses Mo 99/Tc-99m generators for preparing a Tc-99m radiopharmaceutical to measure the Mo-99 concentration of each 10/28/08 Accepted Open eluate after receipt of a generator to demonstrate compliance with not administering to humans more than 0.15 microcurie Mo-99 per millicurie Tc-99m.

30 NRC staff should require licensees to report to the NRC events in which licensees measure molybdenum breakthrough that exceeds 10/28/08 Accepted Open the regulatory limits.

2

2009 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS NRC staff should revise 35.390(b)(1)(ii)(G)(3) to read "parenteral administration requiring a written directive for any radionuclide that is being used primarily because of its beta emission, or low energy photo-2 emission, or auger electron; and/or" and revise 35.390(b)(1)(ii)(G)(4) to 5/7/09 Accepted Open read "parenteral administration requiring a written directive for any radionuclide that is being used primarily because of its alpha particle emission" ACMUI recommends NRC staff delete the phrase "at a medical 10 institution" from 10 CFR 35.2, 35.490(b)(1)(ii), 35.491(b)(2) and 10/19/09 Accepted Open 35.690(b)(1)(ii).

1

2011 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS 1st/2nd Vote ACMUI endorsed the draft response to NRC comments, as reflected in the meeting handout (ML110600249). ACMUI agreed if NRC believes the release criteria should be changed from a per release criteria to an annual criteria, this change would require new 1

rulemaking, as stated in Regulatory Issue 1/5/11 Pending Open Langhorst/Gilley 9, 1, 0 Summary (RIS) 2008-07. ACMUI recommended rulemaking to clarify that the release under 10 CFR 35.75 is per release and not per year ACMUI created an action item to reevaluate ACMUI Open 6 its satisfaction with the reporting structure 1/12/11 Welsh/Zanzonico Action indefinitely annually.

(1) ACMUI feels ASTRO's approach to Permanent Implant Brachytherapy (handout) is correct approach for patient welfare (2)

ACMUI recommends that the NRC require Post-Implant dosimetry following Partially 11 4/11/11 Open Welsh/Mattmuller 11, 0, 0 brachytherapy treatment (3) ACMUI believes Accepted that prostate brachytherapy is a unique subset of brachytherapy and should therefore require a separate set of rules from non-prostate brachytherapy.

1

2011 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS 1st/2nd Vote ACMUI recommends to eliminate the written 13 attestation for board certification pathway, 4/12/11 Accepted Open Zanzonico/Guiberteau 11, 0, 0 regardless of date of certification ACMUI recommends the attestation to be revised to say has received the requisite 14 training and experience in order to fulfill the 4/12/11 Accepted Open Langhorst/Thomadsen 11, 0, 0 radiation safety duties required by the licensee ACMUI supports the statement that residency program directors can sign attestation letters, representing consensus of residency program faculties, if at least one member of the faculty 15 4/12/11 Accepted Open Thomadsen/Welsh 11, 0, 0 is an AU in the same category as that designated by the applicant seeking authorized status, and that AU did not disagree with the approval.

ACMUI continues to assert that the current regulations are based on a per release limit.

ACMUI does not recommend any change to the regulation and does not recommend the 16 4/12/11 Pending Open Langhorst/Welsh 11, 0, 0 NRC consider this topic during the current rulemaking process, as there is no clinical advantage or advantage to members of the public for using an annual limit.

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2013 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS 1st/2nd ACMUI recommended NRC staff allow use of total source strength as a substitute for total dose for determining medical 1 3/5/13 NRC Action Open events for permanent implant brachytherapy until the Part 35 rulemaking is complete.

ACMUI recommended that NRC staff solicit feedback from stakeholders, in Supplementary Information section IV.D, on whether the proposed ME definition for permanent implant 2 brachytherapy would discourage licensees from using this form 3/5/13 NRC Action Open Zanzonico/Langhorst of therapy. This recommendation was modified the caveat that NRC may utilize the language that they think is appropriate for gaining this type of information from its stakeholders ACMUI recommended the draft rule re-defining medical events 3/5/13 3 in permanent implant brachytherapy be designated as NRC Action Open 3/12/13 Compatibility Category B.

ACMUI recommended replacing the phrasing in the literature in terms of support for the 5 cubic centimeters of contiguous 4 3/5/13 NRC Action Open normal tissue provision of the ME definition, to the specific reference cited as, Nag, et al 2004 1

2013 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS 1st/2nd ACMUI recommended that licensees approved to use generator systems show specific training on the requirement now listed under 35.290 (c)(1)(ii)(G) for those individuals (Authorized Users and others) who are responsible for proper 5 operation and testing of the generator as part of their license 3/5/13 NRC Action Open conditions. ACMUI further recommended that Authorized Nuclear Pharmacists who have the adequate training and experience (T&E) are able to provide the supervised work experience for Authorized Users on the elution of generators.

ACMUI endorsed the language in the proposed rule for preceptor attestations that states a candidate is able to 6 3/5/13 NRC Action Open independently fulfill the radiation safety related duties for which authorization is being sought.

ACMUI recommended that the work experience for parenteral administrations under Sections 35.390 (b)(1)(2)(g), and 35.396 7 not be separated between parenteral administrations of a beta 3/12/13 NRC Action Open Zanzonico/Guiberteau gamma emitting radiopharmaceutical versus an alpha emitting radiopharmaceutical, as proposed in the proposed rule.

ACMUI recommended that the date of recognition of a certifying board should not impact individuals seeking to be 8 named as an Authorized User, Authorized Radiation Safety 3/12/13 NRC Action Open Zanzonico/Thomadsen Officer, Authorized Medical Physicist, or Authorized Nuclear Pharmacist through the certification pathway.

ACMUI recommended that the NRC adopt the FDA approved 9 package insert for breakthrough limits for radioisotope 3/12/13 NRC Action Open Zanzonico/Mattmuller generators 2

2013 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS 1st/2nd ACMUI recommended licensee reporting of out-of-tolerance 10 3/12/13 NRC Action Open Zanzonico/Weil generator breakthrough results to the NRC ACMUI recommended requiring testing of molybdenum 11 breakthrough on every elution of a molybdenum-technetium 3/12/13 NRC Action Open generator, rather than after only the first elution.

ACMUI recommended that the addition of Associate Radiation Safety Officers (ARSOs), and Temporary RSOs also be 12 3/12/13 NRC Action Open Zanzonico/Langhorst included in these exemptions in the same manner as AUs, ANPs, and AMPs.

In reference to the plain language requirement, the ACMUI suggested that the rule could be shortened and improved by eliminating redundancies and consolidating related sections and eliminating identical or nearly identical passages 13 3/12/13 NRC Action Open appearing multiple times throughout the draft rule. A further improvement would be the inclusion of a detailed executive summary-style section summarizing, perhaps in a bullet format, the key changes introduced in the draft rule.

3

2015 ACMUI RECOMMENDATIONS AND ACTION ITEMS Vote ITEM DATE STATUS Assigned 1st/2nd (Y/N/A)

The ACMUI recommended that events reportable under 10 ACMUI 7 CFR 35.3047 that do not result in harm to the embryo/fetus/or 03/20/2015 Open Langhorst/Costello 11, 0, 1 Action nursing child not be captured as AO's reported to Congress.

The ACMUI recommended to make the following change to the Patient Intervention Subcommittee Recommendation Issue II: Unintentional Treatment outcome due to anatomic or ACMUI 12 physiologic anomaly and/or imaging uncertainty falls into the 10/8/15 Open M. Ayoade Alderson/Palestro 10, 0, 1 Action category the Art of Medical Practice provided that the standards of medical practice are met.

The ACMUI endorsed the Patient Intervention Subcommittee ACMUI 13 Report with the modification to Issue II (listed in item 12 10/8/15 Open M. Ayoade Costello, Alderson 10, 1, 0 Action above).

The ACMUI recommended that staff issue a Generic Communication (i.e. Information Notice or Regulatory Issue 15 10/8/15 NRC Action Open M. Ayoade Summary) to licensees to inform them of the interpretation of "patient intervention."

The ACMUI endorsed the 2015 Abnormal Occurrence Criteria Subcommittee Report with the caveat that the report be amended to include an introductory paragraph that provides ACMUI 22 the rationale for the recommendations, as well as a summary 10/9/15 Open 10, 1, 0 Action paragraph to state that the Committee desires that the recommendations be incorporated into this revision of the NRC's Abnormal Occurrence Criteria Policy Statement.

1

2016 ACMUI RECOMMENDATIONS AND ACTION ITEMS Vote ITEM DATE STATUS Assigned 1st/2nd (Y/N/A)

The Committee endorsed that component of the current proposed rule re-1 defining medical events in permanent implant brachytherapy in terms of 1/6/2016 Accepted Open 10, 0, 0 activity (i.e. source strength) rather than radiation dose).

The Committee endorsed, with reservation, designating the current proposed rule re-defining medical events in permanent implant 2 1/6/2016 Accepted Open 10, 0, 0 brachytherapy as Compatibility Category C, with activity-based medical event metrics defined as an essential program element.

The Committee recommended changing the language for a wrong-location medical event in permanent implant brachytherapy from the current proposed language, Sealed source(s) implanted directly into a location where the radiation 3 1/6/2016 Accepted Open 10, 0, 0 from the source(s) will not contribute dose to the treatment site, as defined in the written directive, to Sealed source(s) implanted directly into a location discontiguous from the treatment site, as defined in the written directive.

The Committee recommended revising the passage in lines 4182-4186 on page 167 in the Draft Final Rule as follows, thereby eliminating the dose-based criteria for a leaking source medical event:

3) An administration that includes the wrong radionuclide; the 4 1/6/2016 Not Accepted Open 10, 0, 0 wrong individual or human research subject; a leaking sealed source; or a sealed source or sources implanted into a location discontiguous from the treatment site, as defined in the written directive.

The Committee endorsed the elimination of the preceptor-statement requirement for Board-certified individuals for an individual seeking 5 1/6/2016 Accepted Closed 10, 0, 0 regulatory authorization as an authorized user, authorized medical physicist, Radiation Safety Officer, or authorized nuclear pharmacist.

1

2016 ACMUI RECOMMENDATIONS AND ACTION ITEMS Vote ITEM DATE STATUS Assigned 1st/2nd (Y/N/A)

With respect to the amended requirements for preceptor attestation for an individual seeking regulatory authorization as an authorized user, authorized medical physicist, Radiation Safety Officer, or authorized nuclear pharmacist through the alternate pathway, the Committee 6 endorsed changing the language for the preceptor attestation from the 1/6/2016 Accepted Open 10, 0, 0 individual has achieved a level of competency to function independently for the authorization to the individual can independently fulfill the radiation safety-related duties associated with the authorization being requested.

The Sub-Committee recommended that the date of recognition by the NRC of a certifying board should not impact individuals seeking to be named as an authorized user, authorized medical physicist, Radiation Safety Officer, or authorized nuclear pharmacist through the certification pathway. During the discussion, this recommendation was modified in 7 the final report as follows: 1/6/2016 Accepted Open 10, 0, 0 The Sub-Committee recommends that NRC Staff consider providing guidance in the NUREG-1556, Volume 9 update to licensees on the ways individuals with board certifications prior to NRCs board recognition date may seek authorization.

The Committee recommended that the NRC adopt the parent-breakthrough limits for radioisotope generators specified in the relevant Food and Drug Administration (FDA)-approved package inserts.

ACMUI 8 During the discussion, the Committee recommended to eliminate this 1/6/2016 Open 9, 1, 0 Action recommendation and instead, revise the general comments section of the report to suggest that NRC consider, in future rulemaking, establishing conformity with the FDA breakthrough-limit regulations.

The Committee did not endorse the new requirement in the Draft Final Rule that licensees report to the NRC as well as to the 9 manufacturer/vendor generator elutions with out-of-tolerance parent- 1/6/2016 Not Accepted Open 10, 0, 0 breakthrough but, instead, recommends a single reporting requirement to the manufacturer/vendor.

The Committee endorsed allowing Associate Radiation Safety Officers 10 1/6/2016 Accepted Open 10, 0, 0 (ARSO) to be named on a medical license.

2

2016 ACMUI RECOMMENDATIONS AND ACTION ITEMS Vote ITEM DATE STATUS Assigned 1st/2nd (Y/N/A)

The Committee recommended that the designation of a board-certified authorized user, authorized medical physicist, or authorized nuclear 11 pharmacist as the Radiation Safety Officer (RSO) or as an ARSO 1/6/2016 Not Accepted Open 10, 0, 0 requires their board certification to include the designation, RSO Eligible.

The Committee did not endorse establishing a separate category of Authorized Users for parenteral administration of alpha-emitting radiopharmaceuticals but, instead, recommends deleting § Partially 12 35.390(b)(1)(ii)(G)(4) in the current Draft Final Rule and revising the 1/6/2016 Open 10, 0, 0 Accepted pertinent passage in § 35.390(b)(1)(ii)(G)(3) as follows, Parenteral administration of any radioactive drug for which a written directive is required.

The Committee endorsed the elimination of the requirement to submit copies of NRC Form 313, Application for Material License, or a letter 13 1/6/2016 Accepted Open 10, 0, 0 containing information required by NRC Form 313 when applying for a license, an amendment, or renewal.

The Sub-Committee recommended changing the medical-events language in lines 5531-5532 (page 232) of the Draft Final Rule from, A licensee shall report as a medical event, any administration requiring a written directive, except for an event that results from patient intervention, back to the language in the current Draft Final Rule, A licensee shall report any event, except for an event that results from patient intervention During the discussion, the recommendation was modified in the final report as follows:

14 The Sub-Committee recommends changing the medical-events 1/6/2016 Not Accepted Open 10, 0, 0 language in lines 5531-5532 (page 232) of the current version of the Draft Final Rule from, A licensee shall report any event, except for an event that results from patient intervention back to the language published in the Proposed Rule as presented for public comment, A licensee shall report as a medical event, any administration requiring a written directive, except for an event that results from patient intervention, 3

2016 ACMUI RECOMMENDATIONS AND ACTION ITEMS Vote ITEM DATE STATUS Assigned 1st/2nd (Y/N/A)

The Committee endorsed the 2016 Rulemaking Subcommittee Report 15 1/6/2016 NRC Action Open 10, 0, 0 with modifications as listed above.

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

The ACMUI will contact their respective professional organizations to ACMUI 24 request and encourage interactions between the NRC and ACMUI with 3/18/2016 Open Action their organization.

The Committee recommended that staff issue a generic communication 39 (information notice) regarding tubing issues (kinking, connection, hub 10/6/16 NRC Action Open Dr. Katie Tapp Ennis/Costello 9, 0, 1 etc.) during the administration of Y-90 microspheres brachytherapy.

The Committee recommended that the Pathway 2 remain for the Y-90 Microsphere Brachytherapy Licensing Guidance. The NRC/OAS working 42 10/7/16 NRC Action Open Dr. Katie Tapp Langhorst/Costello 9, 1, 1 group should determine what the 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 review of the Y-90 radiation safety issues in 43 10/7/16 NRC Action Open Dr. Katie Tapp Langhorst/Ennis 11, 0 , 0 autopsy and cremation in the draft revision of the Y-90 Microsphere Brachytherapy Licensing Guidance.

For the NorthStar Guidance Subcommittee: The Committee Dr. Donna-Beth 44 recommended that NorthStar provide a video clip of how the system 10/7/16 NRC Action Closed 10, 0, 0 Howe operates in the training module.

For the NorthStar Guidance Subcommittee: Given the unique design and operation of the NorthStar system, the Committee agreed that NorthStar 45 10/7/16 NRC Action Closed 10, 0, 0 should have sole responsibility for the 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 46 assigned by the AU without a specifically defined educational or training 10/7/16 NRC Action Closed 10, 0, 0 background. Given the unique role of the System Administrator, perhaps that individual should be named on the license.

4

2016 ACMUI RECOMMENDATIONS AND ACTION ITEMS Vote ITEM DATE STATUS Assigned 1st/2nd (Y/N/A)

For the NorthStar Guidance Subcommittee:The Committee recommended an explicit statement regarding the System Administrator Designee, although it may not have been intended, one could infer from 47 the description of the system administrator designee that there can be 10/7/16 NRC Action Closed 10, 0, 0 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 48 10/7/16 NRC Action Closed 10, 0, 0 changes and the responsibility of the 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 are trained in the changes, including the AU, RSO, system administrator, etc. or 49 10/7/16 NRC Action Closed 10, 0, 0 does it require 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, individual tasks throughout the document 50 10/7/16 NRC Action Closed 10, 0, 0 for consistency and to clarify that there is only one protocol and software program with this system.

For the NorthStar Guidance Subcommittee: The Committee 51 recommended that the manufacturers procedures be reviewed and 10/7/16 NRC Action Closed 10, 0, 0 incorporated into the Licensing Guidance itself.

For the NorthStar Guidance Subcommittee: The Committee recommended that the term higher than expected be defined in terms of 52 10/7/16 NRC Action Closed 10, 0, 0 a maximum specific exposure or exposure-rate limit which a survey meter should be capable of measuring.

5

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

The Patient Intervention Subcommittee will amend its ACMUI 8 Subcommittee Report and will report at the ACMUI fall 2017 4/27/2017 Open Action meeting or by teleconference to discuss their amended report.

The NRC staff will engage in discussions with the OAS to find a 12 9/11/2017 NRC Action Open way to centralize event reporting from the Agreement States.

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

1

2017 ACMUI RECOMMENDATIONS AND ACTION ITEMS 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 permanent harm, or unintended significant temporary harm for which medical 14 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.

2

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 safety 15 9/11/2017 NRC Action Open 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 16 medical use licensees who request approval of their patient 9/11/2017 NRC Action Open safety program, and to Agreement States who request to implement the program with their medical licensees.

The ACMUI recommended that the NRC redefine its 17 perspective of patient safety to be different from occupational 9/11/2017 NRC Action Open 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) , and 18 9/11/2017 NRC Action Open ACMUI to develop a national database taxonomy specific for reporting patient events involving medical use of byproduct material.

3

2017 ACMUI RECOMMENDATIONS AND ACTION ITEMS 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 program with the ACMUI 20 9/11/2017 Open total number of sites and duration to be determined at a later Action date and to include the Patient Intervention Subcommittee recommendations as an addendum .

The ACMUI will hold a public teleconference in the near future to discuss the amended Nursing Mothers Guidelines Subcommittee Report. Amendments will include, but are not ACMUI 21 limited to: (1) a suggested time frame for providing written and 9/11/17 Closed Action oral instructions to patients who will stop breastfeeding altogether and (2) consideration to revise the radionuclides to be non-pharmaceutical specific.

The ACMUI commented (1) that the literature review was thorough and the model calculations sound; and (2) the current ACMUI 22 dose-based approach to assessing patient releasability 9/11/17 Closed Action validated as more protective of public safety than the activity-based approach.

4

2017 ACMUI RECOMMENDATIONS AND ACTION ITEMS The ACMUI recommended that the current 5-mSv (500-mrem) and 1-mSv (100-mrem) projected dose limits for family members and the general public, respectively, should remain a 23 9/11/17 NRC Action Closed per-event limit and are appropriate for all potentially exposed cohorts, including pregnant women and children, and all radionuclide administrations.

The ACMUI recommended that the 1-mSv (100-mrem) dose 24 limit for requiring patient safety instructions should remain in 9/11/17 NRC Action Closed place.

The ACMUI commented that (1) the assumption in regulatory guidance that the internal dose contribution is negligible has been validated; (2) other assumptions and methods in regulatory guidance are excessively conservative NCRP Report ACMUI 25 9/11/17 Closed No 155; and (3) a patient staying at a hotel following Action radionuclide therapy is not a widespread practice and is unlikely to result in doses to workers and others > 1 mSv (100 mrem).

The ACMUI recommended that instructions must be provided to the patient well in advance of a planned therapy (ie not on 26 the day of administration), without compromising patient care. 9/11/17 NRC Action Open Specification of a regulatory time interval for pre-therapy instructions is not recommended --> NCRP Report No 155.

5

2017 ACMUI RECOMMENDATIONS AND ACTION ITEMS The NRC recommended that the NRC should consider updating Appendix U (NUREG 1556) to reference Regulatory 27 9/11/17 NRC Action Open Guide 8.39 rather than eliminating 8.39 or maintaining two separate guidance documents.

The ACMUI endorsed the Patient Release SECY Paper ACMUI 28 9/11/17 Closed Subcommittee Report. Action The ACMUI will hold a public teleconference in the near future to discuss the amended Physical Presence Requirements for the Leksell Gamma Knife Icon Subcommittee Report.

Amendments will include (1) the distinction between "an" or "the" AU or AMP;" (2) AU presence for re-initiation of procedure ACMUI 29 9/12/17 Closed following interruption; (3) possible incorporation of changes to Action the physical presence requirements for the Leksell Gamma Knife Perfexion; and (4) whether the physical presence requirements will be limited to the frame-based or frameless-based option for the Leksell Gamma Knife Icon.

The Committee tentatively scheduled the spring 2018 ACMUI meeting for March 1-2, 2018. The back-up dates are March 14- ACMUI 30 9/12/17 Closed 15, 2018. The final meeting date is subject to Commission Action availability.

6

2018 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE STATUS Assigned 1st/2nd Vote 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 Sophie 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 Sophie Metter/Palestro 9, 0, 0 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 Open Sophie 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.

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 Open Sophie Action respond to any immediate medical needs.

The ACMUI endorsed the Physical Presence Requirements for ACMUI 5 2/15/2018 Open Sophie Suh/Zanzonico 9, 0, 0 the Leksell Gamma Knife Icon Subcommittee Report. Action 1

Open Forum NO HANDOUT

Status of Medical Events FY 2017 Donna-Beth Howe, Ph.D.

Medical Radiation Safety Team March 7, 2018 1

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

Each year there are approximately 150,000 therapeutic procedures performed utilizing radioactive materials.

2 1

Medical Events 2012-14

• 48 Medical events reported - FY 2012

• 43 Medical events reported - FY 2013

• 46 Medical events reported - FY 2014 FY12 FY13 FY 14 35.200 2 0 1 35.300 2 2 3 35.400 15 15 5 35.600 13 10 10 35.1000 20 16 27 3

Medical Events 2015-17

• 57 Medical events reported - FY 2015

• 50 Medical events reported - FY 2016

• 42 Medical events reported - FY 2017 FY15 FY16 FY17 35.200 3 4 0 35.300 8 4 4 35.400 9(10) 6(18) 7 35.600 17 6 8(14) 35.1000 20(31) 30 23 4

2

Medical Events 2017 35.300 Medical events 4 Iodine 131 3 Radium 223 1 5

35.300 Medical Events (cont.)

Iodine-131 3

• Administered 2 mCi when none was prescribed.

- Prescribed parathyroid test but received thyroid scan.

- I-131 ordered without written directive.

- Electronic ordering and records system used without confirmation of the order prior to administration.

- Thyroid received 1,630 cGy.

- Modified procedures, confirm dosage orders, and re-trained personnel.

6 3

35.300 Medical Events (cont.)

Iodine-131 cont.

• Administered 20.2 mCi instead of 30 mCi in written directive.

- Written Directive was incorrect.

- Intended dose was given.

- Three individuals now review the Written Directive for accuracy before signing and administration.

7 35.300 Medical Events (cont.)

Iodine-131 cont.

• Administered 106 mCi instead of 150 mCi.

- Dosage delivered in two capsules.

- Patient shook the vial contents into her mouth, only swallowed one capsule, other left in vial.

- Discovered when capsule returned to the pharmacy.

8 4

35.300 Medical Events (cont.)

Ra-223 dichloride 1

• Administered 176.1 µCi instead of 108.4 µCi.

- Wrong patient.

- Two patients scheduled for Ra-223 treatment on the same day.

- Doses properly labeled with patient names on the lead pigs and syringes.

- Wrong syringe used without checking patient identity.

- Added a timeout, dosing physician verifies identity of the patient and prescribed dose in the written directive.

9 Medical Events 2017 35.400 Medical events 7 Prostate 7 One licensee 2 reports 2 Human error Anatomy Wrong site 1 Used previous activity 1 Larger then pre plan or swelling 3 10 5

35.400 Medical Events Prostate 7

• One licensee, 2 separate reports

• Case 1 - Patient received 62% of the prescribed D90 dose of 14,500cGy.

- No root cause but attributed to human error.

- Some seeds may have migrated post implant.

11 35.400 Medical Events

• Case 2 - Patient received 78% of the prescribed D90 dose of 14,500cGy.

- Caused by patient anatomy.

- Identified during post-implant CT scan and subsequent dosimetric analysis.

- Delay in reporting to State due to communication breakdown and inadequate procedures.

12 6

35.400 Medical Events cont.

• Patient received 2,760 cGy instead of 11,00cGy 74.9% less than prescribed.

- Wrong site.

- Estimated dose to the urethra at 2,602 cGy (rad), the rectum at 861 cGy, and the penile bulb at 8,689 cGy.

- human error - additional training to personnel and improved supervision.

13 35.400 Medical Events cont.

• Patient received 157.81% of the prescribed D90 dose of 12,500cGy - Pd103 seeds.

- Failed to enter correct activity per seed into physics spreadsheet that contained a value from the previous calculation.

- Did not perform independent verification of treatment data.

- New action: secondary hand calculation, require use of blank spreadsheet template, and verbal time-out to verify key parameters prior to treatment.

14 7

35.400 Medical Events cont.

• Prescribed 14,400 cGy received 73% of the dose.

- 18% increase in prostate size compared to the pre-plan and the planned intentional cooler coverage near the patient's rectum.

- Discovered during a routine audit conducted by a medical physicist.

15 35.400 Medical Events cont.

• Prescribed 14,500 cGy received 10,000 cGy - 69% of the dose.

- Administered 12/7/2016, event discovered on 12/8/2016.

- Second treatment on 12/9/2016 - eight more seeds implanted.

- Post-operative swelling and seed migration

- Perform post-implant imaging sooner to minimize the effect of swelling of the prostate gland and possible migration of the seed 16 8

35.400 Medical Events cont.

• Prescribed 14,500 cGy received 10,353 cGy - 71% of the dose.

- Order additional seeds beyond what the pre-plan requires.

- Perform post-implant x-ray and ultrasound to determine if/where additional seeds could be placed.

17 Medical Events 2017 35.600 Medical events 8(14)

HDR (9 patients)

• Gynecological(14) 7 Software Issue (9 patients) 2 Wrong site 4 Equipment failure 1 Gamma Knife 1 18 9

35.600 HDR Events (cont.)

Gynecological 7 (14)

• Generic Software issue (4 patients)

- Oncentra software versions 4.5, 4.5.1, and 4.5.2 issue with source step size with ring.

- Source step size of 5 mm instead of 2.5 mm.

- Dose to unintended site 2,800 cGy to 1,400 cGy.

- Dose to the unintended site expected too be 126 to 175 cGy per fraction.

- Elekta notified software users of problem with ring.

19 35.600 HDR Gynecological (cont.)

• Generic Software issue cont. (5 patients)

- Oncentra software versions 4.5.2 issue with source step size with ring of 5 mm instead of 2.5 mm.

- Dose to treatment site 24.46%, 21%, 31.96%,

25.58%and 20.89% less than intended.

- Did not calculate dose to the unintended site.

- Some source paths extended beyond planned endpoint and started on a return path back into the lower vagina.

- Some tissue protection by fluid-filled sleeve that provided some shielding and displacement.

20 10

35.600 HDR Gynecological (cont.)

• Wrong site 4

- 5 cm site received 500 cGy

- Wrong software orientation selected.

- Oncentra treatment planning - must choose if the treatment catheters are modeled from the tip or connecting end of the catheter.

- Catheter in the tip end mode which was incorrect.

- Provide additional training to personnel.

21 35.600 HDR Gynecological (cont.)

• Wrong Site cont.

- Capri applicator inserted into the patient's rectum instead of vagina on 2nd of 5 fractions.

- Treatment site received prescribed dose of 350 cGy (rad) during the second treatment.

- Radiologist confirmed the patient's rectum had been treated.

22 11

35.600 HDR Gynecological (cont.)

• Wrong site cont.

- 5 cm site received 500 cGy

- first two tandem and ovoid treatments were delivered as prescribed

- Incorrect tandem applicator length of 119.8 cm was entered into the treatment planning system for third fraction instead of the prescribed 131.9 cm.

23 35.600 HDR Gynecological (cont.)

• Wrong site cont.

- Received 700 cGy

- Physicist determined inserted length of the transfer guide tube was 7.5 cm shorter than intended.

- The transfer tube was deformed and added pressure needed to fully insert it into the applicator.

- Removed the transfer guide tube from service, got different design.

- Counseled staff on the event.

24 12

35.600 HDR Gynecological (cont.)

• Equipment failure.

- Received 6.4% of prescribed 500 cGy dose during the 1st of 5 fractions.

- Five separate interlocks were tripped in 1st fraction.

- fluid in the catheter may have contaminated the source and afterloader unit.

25 35.600 Gamma knife 1 Gamma Knife Model C.

• Prescribed 2000 cGy received 1540 cGy to brain lesion

- Three of five shots delivered.

- Couch retracted from the treatment position due to a clutch malfunction.

- Patient was released - repairs completed in six hours.

- Patient elected to not return.

26 13

Medical Events 2017 35.1000 Medical events 24 Intervascular Brachytherapy 1 Y-90 Microspheres 23 Therasphere 15 SirSphere 8 27 35.1000 Medical Events Intravascular Brachytherapy 1

- Prescribed dose of 1,840 cGy (rad) for in-stent restenosis in two dwell positions.

- Received 50% of dose - one position treated.

- Source train stuck - not retract to the afterloader.

- Deformation 7.3 cm distal to the strain relief - located outside the patient.

- Compression of the catheter during a challenging advancement into a commonly tortuous vessel (left internal mammary artery).

28 14

35.1000 Medical Events Y-90 Microspheres 23 Therasphere 15

- Over dose 3

- Wrong site 2

- Kinked catheter 4

- Cracked catheter 1

- Partial Obstruction 1

- Leaking connection 2

- Slow infusion 1

- Reflux to other lobe 1 29 35.1000 Therasphere Y-90 Events Overdose 3

• Prescribed 11,000 cGy administered 54,000 cGy -

right lobe

- Wrong calibration date (6/11/2017 instead of 6/4/2017) used in ordering.

- Used dose calibrator - did not question results.

- Written directive not prepared and not signed before administration.

- Shunting lung dose 2,576 cGy (rad), - intended 524 cGy (rad).

- About 6 months later no clinically significant symptomatic complications.

30 15

35.1000 Y-90 Therasphere (cont.)

Overdose cont.

• Prescribed 34,000 cGy administered 80,800 cGy -

liver volume.

- Administered before microspheres decayed to the prescribed activity - Scheduling nurse used the pre-treatment plan instead of the final treatment plan.

- The physicists pre-treatment calculations and time-out failed.

31 35.1000 Y-90 Therasphere (cont.)

Overdose cont.

• Prescribed 34,000 cGy administered 80,800 cGy -

liver volume. (cont.)

- Spreadsheet to calculate patient dose modified to check the administration vial's calibration activity and date versus the prescribed activity and procedure date.

- The time-out procedure modified to confirm the proper activity prior to administration.

32 16

35.1000 Y-90 Therasphere (cont.)

Overdose cont.

• Prescribed activity 1.05 GBq (28.37 mCi) -

administered activity was 2.05 GBq (55.35 mCi).

- Human error in converting activity from GBq to mCi.

- Corrective actions - procedure modifications, written directive revisions, and software updates to assist in unit conversions.

33 35.1000 Y-90 Therasphere (cont.)

Wrong site 3

• Prescribed 6,000 cGy - administered 4,860 cGy (rad) to the left lobe and 3,650 cGy (rad) to the right lobe.

- Challenging anatomy - a narrow window just distal to vasculature suppling right lobe - reflux to right lobe.

- Verified catheter position multiple ways before administration - no apparent complications.

- Bremsstrahlung imaging showed microspheres in both lobes.

34 17

35.1000 Y-90 Therasphere (cont.)

Wrong site 3

• Prescribed 6,000 cGy - administered 4,860 cGy (rad) to the left lobe and 3,650 cGy (rad) to the right lobe.

(cont.)

- Movement of the catheter from unnoticed patient movement (breathing) or angiographically undetected reflux caused by the difference in flow dynamics of the microspheres, contrast agent and Tc-99M macro-aggregated albumin (MAA).

35 35.1000 Y-90 Therasphere (cont.)

Wrong site cont.

• Two separate segments in the right lobe prescribed 25.6 mCi to the small segment and 64.3 mCi to the large segment.

- Later discovered only 10.27 mCi was ordered for the large segment.

- Each dose needed different calibration dates.

- Contrary to vendor guidance, the licensee used one order sheet for the two doses with one calibration date 36 18

35.1000 Y-90 Therasphere (cont.)

Wrong site cont.

• Two separate segments in the right lobe prescribed 25.6 mCi to the small segment and 64.3 mCi to the large segment. (cont.)

- Process involved several hand-offs, reviews, and verifications by different providers using different source documents - inconsistency between the written directive and the order and assay data was not identified prior to patient treatment.

37 35.1000 Y-90 Therasphere (cont.)

Wrong site cont.

• Prescribed 47.03 mCi to the left lobe - administered 46.22 mCi to right lobe (right lobe to be treated one month later).

- Interventional radiologist and radiation oncologist authorized user signed off on the planned activity for the left lobe via the left hepatic artery - the authorized user completed the written directive.

- Interventional radiologist put catheter in patient's right hepatic artery for right lobe - human error confused about later treatment of right.

38 19

35.1000 Y-90 Therasphere (cont.)

Wrong site cont.

• Prescribed 47.03 mCi to the left lobe - administered 46.22 mCi to right lobe (right lobe to be treated one month later). (cont.)

- In operating room time-out all parties confirmed the procedure, and treatment was administered.

- Modified written directive time out procedure.

39 35.1000 Y-90 Therasphere (cont.)

Kinking 4

• Prescribed 146.51 mCi -administered 11.35 mCi -

liver dose of 970 cGy (rad) and lung dose from shunting of 101 cGy (rad).

- Thought slow injection flowrate, dent in the outlet tubing from a pinch-clamp, and over-tightening of the Touhy-Borst Y-adaptor caused sedimentation of the microspheres in the delivery system.

- The manufacturer's inspection a small mass of microspheres inside the dose vial and within the outlet tubing, multiple locations with kinks, no septum fragments or other obstructions were observed, no evidence that the Tuohy fitting was over tightened.

40 20

35.1000 Y-90 Therasphere (cont.)

Kinking cont.

• Prescribed 12,000 rad - administered 6,000 rad.

- A kinked delivery catheter prohibited complete microsphere administration.

• Prescribed 51.57 - administered 39.07 mCi to the right lobe.

- Residual activity 12.5 mCi remaining in the delivery device.

- Visual kink at the hub of the catheter was identified.

41 35.1000 Y-90 Therasphere (cont.)

Kinking cont.

• Prescribed 46 mCi administered 20 mCi.

- Two separate liver segments.

- Second acrylic jar contained 56% of the microspheres intended for the patient's second liver segment.

- Protocols for dose preparation, box construction, and dose administration were followed.

- Minor resistance during the flush of the stretched out micro-catheter.

- Possible micro-catheter had a kink and be able to flush contrast and saline through it, but have microspheres clog it.

42 21

35.1000 Y-90 Therasphere (cont.)

Cracked catheter 1

• Prescribed two doses with a total activity of 54 mCi to the right and left lobes - administered 21.62 mCi

- first dose and second administrations through the radial artery of the left hand using a microcatheter (Marksman).

- Post radiation surveys both about 5 mR/hr for the microsphere vial - AU assumed first was from contaminated cloth but recognized second meant two under doses.

- Visual inspection of the microcatheter revealed a crack - the crack was determined to be the cause of the event.

43 35.1000 Y-90 Therasphere (cont.)

Partial obstruction 1

• Prescribed 47.88 mCi - administered 13.91mCi.

- Thought treatment went as planned, no issues with viewed flow before administration, no increased resistance was noted and could flush the line post administration.

- Discovered during survey of waste and performing the dose assessment.

44 22

35.1000 Y-90 Therasphere (cont.)

Partial obstruction 1

• Prescribed 47.88 mCi - administered 13.91mCi.

(cont.)

- Thought partial obstruction in catheter or line connecting the microsphere vial to the catheter, vasculature was complicated and may have resulted in movement of the micro-catheter slightly forward from initial placement.

- Greater than usual amount of saline in the overflow vial.

45 35.1000 Y-90 Therasphere (cont.)

Leaking catheter connection 2

• Prescribed 11.87 mCi - administered 8.34 mCi.

- During treatment liquid leaking from the connection between the e-line and the catheter placed in the patient was noted.

- Treatment stopped and started decontamination -

patient's thigh and groin, skin dose was calculated to be 1.1 µSv (0.11 mrem).

- Incident due to human error - poor connection between the e-line and the patient's catheter.

46 23

35.1000 Y-90 Therasphere (cont.)

Leaking catheter connection cont.

• Prescribed 25.95 mCi - administered 8.99 mCi.

- Leak occurred while connecting the infusion line from the microsphere vial to the microcatheter.

- Physician simultaneously unclamped the administration line while trying to connect it to the microcatheter.

- Physician assumed the leaking fluid only contained saline and proceeded with administration.

- Leak caused contamination of the administration area, which was immediately decontaminated.

47 35.1000 Y-90 Therasphere (cont.)

Slow injection rate 1

• prescribed 175.7 mCi - administered 43.24 mCi.

- Slow injection rate to prevent reflux into adjacent gastric artery that could not be coil embolized.

- Completed administration, three saline flushes, verified digital radiation dosimeter was reading 0.0, indicating that the microspheres had left the vial.

- Microspheres collected in the catheter outside of the patient.

48 24

35.1000 Y-90 Therasphere (cont.)

Slow injection rate 1

• prescribed 175.7 mCi - administered 43.24 mCi.

(cont.)

- External experts confirmed that a slow injection rate can result in an event like this and RSO identified catheter backup in another slow injection rate administration.

49 35.1000 Y-90 Events (cont.)

SirSphere 8

- Labeled vial shield not vial 1

- Low activity administration 3

- High activity clogging 1

- Clogging issues 3

• Needle 1

• Catheter defect 1

• Kinked 1 50 25

35.1000 Y-90 SirSphere (cont.)

Labeled vial shield not vial 1

• Prescribed 2.453 mCi to small lesion and 22.077 mCi to large lesion - administered 22.077 mCi to small lesion.

- Prepared two vials, labeled each vial shield, did not label the vials.

- Provided vial with 22.077 mCi for small lesion realized mistake when started large lesion.

- Require time-out, label both the vial and vial shield, read labels three times before administration.

51 35.1000 Y-90 SirSphere (cont.)

Low activity administration 3

• Prescribed 6.49 mCi to 2 segments - administered 4.46 mCi.

- Activity in residual waste - stasis was not reached during administration.

- Procedure modifications, form modifications, written directive adjusted to tighten up the dose drawn to match 100% of the prescribed dose, and committed to have an AMP physician present to observe low activity administrations.

52 26

35.1000 Y-90 SirSphere (cont.)

Low activity administration cont,

• Prescribed 5.49 mCi - administered 4.07 mCi.

- Cause of the event was the amount of activity delivered; the relatively low prescribed dose made the residue look comparatively large.

- Another doctor will supervise the remainder of the administrating doctors cases - part of the requirements for obtaining authorized user status.

53 35.1000 Y-90 SirSphere (cont.)

Low activity administration cont,

• Prescribed 4.05 mCi - administered 3.14 mCi.

- Radiation survey revealed residual activity of 1.06 mCi remained in the treatment device.

- The use of small doses will be carried out after greater scrutiny and review.

54 27

35.1000 Y-90 SirSphere (cont.)

High activity clogging 1

• Prescribed 84.12 mCi - administered 59.8 mCi.

- Tubing became clogged and the entire activity could not be administered.

- Due to a large dose of microspheres - increased amount of microspheres in the system clogged the micro-catheter towards the patient.

55 35.1000 Y-90 SirSphere (cont.)

Clogged needle 1

• Prescribed 32.97 mCi - administered 8.2 mCi.

- Occlusion of the vial delivery C needle due to clumping of the microspheres.

- Intended to return to manufacturer but discarded after activity decayed to background.

- Educating the administrator of the microspheres on how to clear the clogged needle, which is to reverse the valve for flushing purposes.

56 28

35.1000 Y-90 SirSphere (cont.)

Catheter defect 1

• Prescribed 12.16 mCi - administered 5.64 mCi.

- AU and interventional radiologist noticed a strong resistance as they pushed on the syringe.

- The micro-catheter was pulled from the patient - a very small defect was observed.

- Cause of the microsphere blockage was a defect in the micro-catheter.

- MedWatch FDA Adverse Event form completed.

57 35.1000 Y-90 SirSphere (cont.)

Kinked catheter 1

• Prescribed 40.4 mCi - administered 21.5 mCi.

- Think patient inhaled deeply and created a kink in the catheter.

- The first three or four aliquots were delivered before the plunger met resistance.

- Kinked catheter was confirmed by PET/CT imaging of the administration set and vial.

58 29

Acronyms

• AU - Authorized User

• cGy - centiGray

• FY - Fiscal Year

• GBq - Giga Becquerel

• HDR - High Dose Rate Remote Afterloader

• I-131 - Iodine-131

• I-124 - Iodine-124

• Ra-223 -Radium-223

• mCi - millicurie

• µCi - microcurie

• MBq - Mega Becquerel 59 QUESTIONS?

60 30

NRC Staff Response to ACMUI Safety Culture Recommendations Doug Bollock ACMUI Spring Meeting March 7, 2018 Agenda

• Review the ACMUI recommendations from ACMUI report Medical Event Reporting and Impact on Medical Licensee Patient Safety Culture

• Provide the NRC staffs responses to the ACMUI recommendations 2

1

ACMUI Recommendations

• On September 11, 2017 the ACMUI unanimously approved ACMUI report Medical Event Reporting and Impact on Medical Licensee Patient Safety Culture which included their recommendations.

3 NRC Responses

• Meeting the purpose of Medical Event Reporting

• Limitations to conducting a pilot program utilizing PSOs

• Changing criteria for an NRC reactive inspection 4

2

Acronyms

• NRC- U.S. Nuclear Regulatory Commission

• ACMUI- Advisory Committee on the Medical Uses of Isotopes

• PSO- Patient Safety Organization

• ME- Medical Event 5

3

Committee Reporting Structure Sophie Holiday, ACMUI Coordinator Medical Radiation Safety Team March 7, 2018 Outline

• Current Reporting Structure

• Annual Review

• Meetings

• Discussion 2

1

Current Reporting Structure The Commission EDO Director, NMSS Director, MSST ACMUI MSEB 3

Annual Review

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

• This is the eighth annual review.

4 2

Meetings Two meetings at Headquarters each year

• March/April

• September/October Approximately 2-3 teleconferences (as needed) 5 Discussion 6

3

Points of Contact

• Kevin Williams - Acting MSST Director

- 301-415-3340; Kevin.Williams@nrc.gov

• Douglas Bollock - Designated Federal Officer

- 301-415-6609; Douglas.Bollock@nrc.gov

• Sophie Holiday - ACMUI Coordinator

- 301-415-7865; Sophie.Holiday@nrc.gov 7

Acronyms

• EDO - Executive Director for Operations

• MSST - Division of Materials Safety, Security, States, and Tribal Programs

• MSEB - Medical Safety and Event Assessment Branch

• NMSS - Office of Nuclear Material Safety and Safeguards 8

4

Worldwide Supply and the Domestic Production of Molybdenum-99 (99Mo)

Richard L. Green, R.Ph, BCNP March 7, 2018 235U Fission Produces HSA 99Mo

• Starts with the enrichment of 235U

- Abundance in nature = 0.7%

• Enrichment level trigger point

- Low enriched uranium (LEU)

• <20%

- High enriched uranium (HEU)

• >20%

• Current HSA 99Mo production involves

- Reactor fuel (LEU or HEU)

- Targets (LEU or HEU) 2 1

Current Fission 99Mo Supply Chain neutron fission byproduct neutron neutron 235U 99Mo GE Lantheus neutron Processors Curium Fission Reactors 99Mo HSA Generators 3

Reactors Producing HSA 99Mo Global 99Mo Reactor Location Commissioning Fuel Target Processor Date Type Type HFR Petten, 1961 LEU LEU Curium /

Netherlands IRE BR2 Mol, 1961 HEU HEU Curium /

Belgium IRE SAFARI Pelindaba, 1965 LEU LEU NTP South Africa MARIA Otwock- 1974 LEU LEU IAE-Swierk, 1993 rebuilt Polatom /

Poland Curium LVR-15 Rez, Mid 1950s LEU HEU Czech Czech Nuclear Republic Research Institute / IRE OPAL Lucas Hts., 2007 LEU LEU ANSTO Australia 4

2

Current U.S.99Mo Supply Matrix Reactor Processor 99mTc Maria, Poland Generator Manufacturer HFR, Netherlands Curium, Netherlands supplying U.S.

Fission of 235U BR2, Belgium IRE, Belgium Curium, St Louis MO LVR-15, Czech Republic H GE Healthcare, Amersham, UK S SAFARI, South Africa NTP, South Africa A Lantheus, OPAL, Australia ANSTO, Australia N. Billerica, MA Neutron NorthStar, L

Capture 98Mo MURR, Missouri, USA MURR, Missouri, USA Beloit, WI S NEW A 5

American Medical Isotopes Production Act of 2009

• Provides $163 million to DOE to support Mo-99 production with LEU

• Prohibits export of HEU for medical isotopes from US after 7 years (provision to extend 3 yrs)

• Requires NRC to report disposition of previous exports of HEU

• Allows NRC to license HEU production under certain conditions

• Requires annual reports from DOE on support of US 99Mo production

• Requires a NAS study 5 years after enactment 3

Revenues 99mTc Supply Chain Challenges 4

A New U.S. 99Mo Producer !

• NorthStar Medical Radioisotopes, LLC Beloit, WI

• 8 Feb 2018 U.S. FDA approved the first domestically-produced, non-uranium based 99Mo

• A LSA, computer controlled 99Mo generator system https://www.northstarnm.com/products/northstar-solutions-radiogenix-system/ 9 NSs Current Production Method

• Short term - Missouri University Research Reactor (MURR), Columbia MO

• Neutron Capture

- 98Mo(n,)99Mo

>> using natural enrichment 98Mo

>> ~6 Ci / source vessel 10 5

NSs Future Production Method

• Neutron Capture 98Mo(n,)99Mo

>> using enriched 98Mo

>> ~18 Ci / source vessel

• Long term - linear accelerator at NorthStar facility in Beliot, WI 100Mo(p,2n)99Mo 11 LSA 99Mo Generator

• Source vessel contains ~30 mL potassium molybdate 99Mo

• Protocols

- Produce 99mTc

- Add/change reagents

- Add/exchange reagents

- Sterilize system

- Add source vessel

- Remove source vessel

- Add/exchange discarded material container 12 6

Other Potential New U.S. Producers?

• Shine Medical Technologies, Monona, WI

- Dec 12, 2016 -awarded $10 million from the U.S. DOE/NNSA as part of a $20.9 million cooperative agreement to support the establishment of domestic, commercial production of 99Mo produced without the use of HEU.

- Feb 2018 Completed construction and taken occupancy of Building One, the first building of the SHINE medical isotope production campus. Facility will be used to house the first integrated, full-size SHINE production system Neutrons from accelerator U salts 99Mo Current Processing Production & Projected Future Demand, Global, 2015 - 2020 14 7

Acronyms ACMUI - Advisory Committee on the Medical Uses of Isotopes DOE - Department of Energy EOP - end of production 99Mo - nuclide of molybdenum with 66 hour7.638889e-4 days <br />0.0183 hours <br />1.09127e-4 weeks <br />2.5113e-5 months <br /> half-life, precursor of 99mTc GTRI - Global Threat Reduction Initiative HEU - highly enriched uranium (>20%)

HSA - high specific activity LEU - low enriched uranium (<20%)

LSA - low specific activity MURR - Missouri University Research Reactor non-HEU 99Mo - molybdenum 99 manufactured without the use of highly enriched uranium NNSA - National Nuclear Security Administration NS - NorthStar 99mTc - nuclide of technetium with 6 hour6.944444e-5 days <br />0.00167 hours <br />9.920635e-6 weeks <br />2.283e-6 months <br /> half-life, used in

~85% of diagnostic nuclear medicine imaging 15 235U - radioactive form of uranium used to fuel reactors Acronyms 16 8

NRC Medical Projects on the Horizon Doug Bollock ACMUI Spring Meeting March 7, 2018 Agenda

• Discuss the major assignments currently under review by the Medical Radiation Safety Team 2

1

Major Projects

• Part 35 Rule change implementation

• Germanium/Gallium-68 Generators

• Physical Presence Requirements for Leksell Perfexion and Icon

• Yttrium-90 Microspheres

• Patient Release (Reg. Guide 8.39)

• Training and Experience paper 3

Acronyms

• NRC- U.S. Nuclear Regulatory Commission

• ACMUI- Advisory Committee on the Medical Uses of Isotopes 4

2

ACMUI Working Prepatory Session NO HANDOUT

Special Presentation to Dr. Pat Zanzonico NO HANDOUT

Emerging Medical Technologies Commission Paper Irene Wu March 7, 2018 Source: Elekta Source: NorthStar Purpose

• To provide the Commission with the NRC staffs review of the emerging medical technologies program 2

1

Content

• Process for reviewing emerging medical technologies

• Discussion of past, in process, and anticipated future reviews of medical technologies

• Resource estimates for the review of new technology and guidance development (non-public) 3 Examples of Past Reviews

• Eckert and Ziegler GalliaPharmTM Germanium-68/Gallium-68 Pharmacy Grade Generator

• Low Activity Radioactive Seeds Used for Localization of Non-Palpable Lesions and Lymph Nodes

• Radium-223 Dichloride 4

2

Examples of In Process Reviews

• Yttrium-90 Microsphere Brachytherapy Sources and Devices TheraSphere and SIR-Spheres

• Leksell Gamma Knife PerfexionTM and Leksell Gamma Knife IconTM

• Lutetium-177 dotatate 5

Examples of Anticipated Reviews

• Phosphorus-32 OncoSilTM microparticles

• MASEP InfiniTM cobalt-60 stereotactic radiosurgery

• GammaPodTM cobalt-60 stereotactic radiotherapy 6

3

Acronyms NRC - U.S. Nuclear Regulatory Commission 7

4

Commission Meeting with the ACMUI NO HANDOUT

Group Photo NO HANDOUT

Thoughts on Leaving the ACMUI NO HANDOUT