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
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Download: ML18053A770 (85)

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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 RemarksMr. Bollock will formally open the meeting and Ms. Howell w illprovide opening comments.D.Bollock, NRCL.Howell , NRC8:30 - 10:15 10:15 - 10:30 10:3 0 - 11:30 2.Old BusinessMs. Holiday will review past ACMUI recommendations andprovide NRC responses.3.Open ForumThe ACMUI will identify medical topics of interest for furtherdiscussion.4.Medical Related EventsDr. Howe will provide an update on recent medical events

.BREAK 5.Staff Response to Medical Event Reporting and itsImpacts on Safety Culture Subcommittee ReportMr. Bollock will discuss the staff's evaluation of the ACMUI' srecommendations related to how NRC's medical event reportingcriteria under 10 CFR 35.3045 impacts safety culture at medicalinstitutions.6.ACMUI Reporting StructureMembers will discuss the reporting structure of the Committeeand provide feedback to NRC staff.

S.Holiday, NRCACMUI DB. Howe, NRC D.Bollock, NRCS.Holiday , NRC 1 1: 30 - 1: 00 1: 00 - 2:30 2:30 - 3:00 3:00 - 5:00 LUNCH 7.Worldwide Supply and the Domestic Production ofMolybdenum

-99Mr. Green will provide an update of the world's supply of andthe domestic production of molybdenum

-99 in the U.S.8.Medical Projects on the HorizonMr. Bollock will discuss the major assignments currently underreview by the medical radiation safety team.

BREAK (public portion ends) 9.ACMUI Working Prepatory Session R.Green , CardinalHealth D.Bollock, NRC ML072670110 Thursday, March 8, 2018 OPEN SESSION 8:30 - 9:00 9:30 - 10:00 1 0:0 0 - 1 2: 1 5 12:15 - 1:30 10. Special Presentation to Dr. Zanzonico Mr. Dapas will make a special presentation to Dr. Zanzonico

. 11. Emerging Technologies Commission Paper 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.

BREAK 12. Commission Meeting with the ACMUI The ACMUI will brief the Commission on various topics in a public meeting. 13. Group Photo The ACMUI will take a group photo with and without the Commission.

LUNCH M. Dapas, NRC I. Wu, NRC ACMUI ACMUI 1:30 - 2:45 2:45 14. Thoughts on Leaving the ACMUI Dr. Zanzonico will share his thoughts on leaving the ACMUI.

15. Open Forum The ACMUI will discuss medical topics of interest previously identified.

16. Administrative Closing Ms. Holiday will provide a meeting summary and propose dates for the fall 2018 meeting.

ADJOURN P. Zanzonico, ACMUI ACMUI S. Holiday, NRC

Opening Remarks NO HANDOUT

2007 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATE 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

should not include the word "competency" but should instead read "has

met the training and experience requirements."6/12/07Accepted Open 3 NRC staff should revise the regulations so that board certified individuals, who were certified prior to the effective date of recognition or were

certified by previously recognized boards listed in Subpart J of the

previous editions of Part 35, are grandfathered.6/12/07AcceptedOpen 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

submitted in NRC Form 313A (35.12(c))6/13/07Accepted Open 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

experience with the radiation safety aspects of similar types of use of

byproduct material for which the individual is seeking RSO authorization.6/13/07Accepted Open 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, or ANP seeking RSO status will have responsibilities for similar types of

uses for which the individual is authorized.6/13/07Accepted Open STATUS 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 Regulatory Issue Summary (RIS) to inform the regulated community of

NRC's interpretation. The RIS should be sent to ACMUI and the

Agreement States for review and comment.

6/13/07a)Accepted b)Accepteda)Openb)Closed 25 NRC staff should revise the current regulations to include Canadian

trained individuals who have passed the ABNM certification exam.

8/16/07Accepted Open 30 The Elekta Perfexion should be regulated under 10 CFR 35.1000 until

10 CFR 35.600 is modified to be performance-based, which would allow

the Perfexion to be regulated under 10 CFR 35.600.10/22/07Accepted Open Delayed 31 NRC staff should require experienced RSOs and AMPs to receive

additional training, if the individual is seeking authorization or

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

attestation to become authorized or have responsibility for new uses.10/22/07Accepted Open 34 NRC staff should modify 10 CFR 35.491(b)(2) to specify 'superficial'

ophthalmic treatments. Additionally, NRC staff should change the title of

10 CFR 35.491 to specify 'superficial' ophthalmic treatments.10/22/07Accepted Open Delayed 35 NRC staff should not revise 10 CFR 35.491 (intended for

ophthalmologists) to include training and experience for the new

intraocular device. Instead, NRC staff should regulate the new intraocular

device under 10 CFR 35.490.

10/22/07 Partially Accepted Open Delayed 2 2007 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATE 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

devices for the principle use as approved in the SSDR.10/22/07Accepted Open 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

under the supervision of an ANP.10/22/07Accepted Open 3

2008 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATE 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

individual in charge.4/28/08AcceptedOpen 5 NRC staff should incorporate the subcommittee's recommendations for the Gamma Knife Elekta PerfexionŽ in future rulemaking.4/28/08Accepted Open Delayed 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

Directive (WD) is required, administrations without a prior WD are to

be reported as regulatory violations and may or may not constitute

an ME."10/27/08Pending Open Delayed 22 ACMUI encouraged NRC staff to begin the rulemaking process to move the medical use of Y-90 microspheres from 10 CFR 35.1000

to another section of the regulations, so that the training and

experience requirements for AUs can be vetted though the public

review process instead of residing in guidance space.

10/27/08 Partially accepted Open Delayed 26 NRC staff should revise 10 CFR 35.40 to clarify that the AU should sign and date both the pre-implantation and post-implantation

portions of the WD for all modalities with two part WDs10/28/08Accepted Open Delayed STATUS 1 2008 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATE STATUS 27NRC 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.

[Note this allows for one AU to sign the pre-implantation portion of

the WD and another AU to sign the post-implantation portion of the

WD]10/28/08Accepted Open Delayed 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

use of transmission sources under 10 CFR 35.500 by AUs meeting

the training and experience requirements of 10 CFR 35.590 or

35.290.10/28/08AcceptedOpen 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

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

the regulatory limits.10/28/08AcceptedOpen 2

2009 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATE 2 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-

emission, or auger electron; and/or" and revise 35.390(b)(1)(ii)(G)(4) to

read "parenteral administration requiring a written directive for any

radionuclide that is being used primarily because of its alpha particle

emission"5/7/09AcceptedOpen 10 ACMUI recommends NRC staff delete the phrase "at a medical institution" from 10 CFR 35.2, 35.490(b)(1)(ii), 35.491(b)(2) and

35.690(b)(1)(ii).10/19/09AcceptedOpen STATUS 1 2011 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATE1st/2ndVote 1ACMUI 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 rulemaking, as stated in Regulatory Issue Summary (RIS) 2008-07. ACMUI recommended rulemaking to clarify that the release under 10 CFR 35.75 is per release and not per year1/5/11PendingOpenLanghorst/Gilley9, 1, 0 6ACMUI created an action item to reevaluate its satisfaction with the reporting structure annually.

1/12/11ACMUI ActionOpen indefinitelyWelsh/Zanzonico 11(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 brachytherapy treatment (3) ACMUI believes that prostate brachytherapy is a unique subset of brachytherapy and should therefore require a separate set of rules from non-prostate brachytherapy.

4/11/11Partially AcceptedOpenWelsh/Mattmuller11, 0, 0 STATUS 1 2011 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATE1st/2ndVoteSTATUS 13ACMUI recommends to eliminate the written attestation for board certification pathway, regardless of date of certification4/12/11AcceptedOpenZanzonico/Guiberteau11, 0, 0 14ACMUI recommends the attestation to be revised to say - has received the requisite training and experience in order to fulfill the radiation safety duties required by the licensee4/12/11AcceptedOpenLanghorst/Thomadsen11, 0, 0 15ACMUI 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 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. 4/12/11AcceptedOpenThomadsen/Welsh11, 0, 0 16ACMUI 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 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.4/12/11PendingOpenLanghorst/Welsh11, 0, 0 2

2013 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATE1st/2nd 1ACMUI recommended NRC staff allow use of total source strength as a substitute for total dose for determining medical events for permanent implant brachytherapy until the Part 35 rulemaking is complete.3/5/13NRC ActionOpen 2ACMUI recommended that NRC staff solicit feedback from stakeholders, in Supplementary Information section IV.D, on whether the proposed ME definition for permanent implant brachytherapy would discourage licensees from using this form 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 stakeholders3/5/13NRC ActionOpenZanzonico/Langhorst 3ACMUI recommended the draft rule re-defining medical events in permanent implant brachytherapy be designated as Compatibility Category B.

3/5/13 3/12/13NRC ActionOpen 4ACMUI recommended replacing the phrasing in the literature in terms of support for the 5 cubic centimeters of contiguous normal tissue provision of the ME definition, to the specific reference cited as, Nag, et al 20043/5/13NRC ActionOpen STATUS 1 2013 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATE1st/2nd STATUS 5ACMUI 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 operation and testing of the generator as part of their license 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.3/5/13NRC ActionOpen 6ACMUI endorsed the language in the proposed rule for preceptor attestations that states a candidate is able to independently fulfill the radiation safety related duties for which authorization is being sought.3/5/13NRC ActionOpen 7ACMUI recommended that the work experience for parenteraladministrations under Sections 35.390 (b)(1)(2)(g), and 35.396

not be separated between parenteral administrations of a beta gamma emitting radiopharmaceutical versus an alpha emitting radiopharmaceutical, as proposed in the proposed rule.3/12/13NRC ActionOpenZanzonico/Guiberteau 8ACMUI recommended that the date of recognition of a certifying board should not impact individuals seeking to be named as an Authorized User, Authorized Radiation Safety Officer, Authorized Medical Physicist, or Authorized Nuclear Pharmacist through the certification pathway.3/12/13NRC ActionOpenZanzonico/Thomadsen 9ACMUI recommended that the NRC adopt the FDA approved package insert for breakthrough limits for radioisotope

generators3/12/13NRC ActionOpenZanzonico/Mattmuller 2

2013 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATE1st/2nd STATUS 10ACMUI recommended licensee reporting of out-of-tolerance generator breakthrough results to the NRC3/12/13NRC ActionOpenZanzonico/Weil 11ACMUI recommended requiring testing of molybdenum breakthrough on every elution of a molybdenum-technetium generator, rather than after only the first elution.3/12/13NRC ActionOpen 12ACMUI recommended that the addition of Associate Radiation Safety Officers (ARSOs), and Temporary RSOs also be included in these exemptions in the same manner as AUs, ANPs, and AMPs.3/12/13NRC ActionOpenZanzonico/Langhorst 13In 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 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."3/12/13NRC ActionOpen 3

2015 ACMUI RECOMMENDATIONS AND ACTION ITEMS ITEM DATE Assigned 1st/2nd Vote (Y/N/A)7 The ACMUI recommended that events reportable under 10 CFR 35.3047 that do not result in harm to the embryo/fetus/or

nursing child not be captured as AO's reported to Congress.

03/20/2015 ACMUI Action OpenLanghorst/Costello11, 0, 1 12 The ACMUI recommended to make the following change to

the Patient Intervention Subcommittee Recommendation Issue

II: Unintentional Treatment outcome due to anatomic or physiologic anomaly and/or imaging uncertainty falls into the category "the Art of Medical Practice" provided that the

standards of medical practice are met.

10/8/15 ACMUI Action OpenM.AyoadeAlderson/Palestro10, 0, 1 13 The ACMUI endorsed the Patient Intervention Subcommittee

Report with the modification to Issue II (listed in item 12

above).10/8/15 ACMUI Action OpenM.AyoadeCostello, Alderson10, 1, 0 15 The ACMUI recommended that staff issue a Generic

Communication (i.e. Information Notice or Regulatory Issue

Summary) to licensees to inform them of the interpretation of "patient intervention."10/8/15NRC Action OpenM.Ayoade 22 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

the rationale for the recommendations, as well as a summary

paragraph to state that the Committee desires that the

recommendations be incorporated into this revision of the

NRC's Abnormal Occurrence Criteria Policy Statement.

10/9/15 ACMUI Action Open 10, 1, 0 STATUS 1 2016 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATEAssigned1st/2ndVote (Y/N/A)1The Committee endorsed that component of the current proposed rule re-defining medical events in permanent implant brachytherapy in terms of activity (i.e. source strength) rather than radiation dose).1/6/2016AcceptedOpen10, 0, 0 2The Committee endorsed, with reservation, designating the current proposed rule re-defining medical events in permanent implant brachytherapy as Compatibility Category C, with activity-based medical event metrics defined as an essential program element.1/6/2016AcceptedOpen10, 0, 0 3The 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 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."1/6/2016AcceptedOpen10, 0, 0 4The 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 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."1/6/2016Not AcceptedOpen10, 0, 0 5The Committee endorsed the elimination of the preceptor-statement requirement for Board-certified individuals for an individual seeking regulatory authorization as an authorized user, authorized medical physicist, Radiation Safety Officer, or authorized nuclear pharmacist.1/6/2016AcceptedClosed10, 0, 0 STATUS 1 2016 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATEAssigned1st/2ndVote (Y/N/A)STATUS 6With 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 endorsed changing the language for the preceptor attestation from the individual "-has achieved a level of competency to function independently-" for the authorization tothe individual can "-independently fulfill the radiation safety-related duties-" associated with the authorization being requested.1/6/2016AcceptedOpen10, 0, 0 7The 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 the final report as follows: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 NRC's board recognition date may seek authorization.1/6/2016AcceptedOpen10, 0, 0 8The Committee recommended that the NRC adopt theparent-breakthrough limits for radioisotope generators specified in the relevant Food and Drug Administration (FDA)-approved package inserts.

During the discussion, the Committee recommended to eliminate this 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.1/6/2016ACMUI Action Open9, 1, 0 9The Committee did not endorse the new requirement in the Draft Final Rule that licensees report to the NRC as well as to the manufacturer/vendor generator elutions with out-of-tolerance parent-breakthrough but, instead, recommends a single reporting requirement to the manufacturer/vendor.1/6/2016Not AcceptedOpen10, 0, 0 10The Committee endorsed allowing Associate Radiation Safety Officers (ARSO) to be named on a medical license.1/6/2016AcceptedOpen10, 0, 0 2

2016 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATEAssigned1st/2ndVote (Y/N/A)STATUS 11The Committee recommended that the designation of a board-certified authorized user, authorized medical physicist, or authorized nuclear pharmacist as the Radiation Safety Officer (RSO) or as an ARSO requires their board certification to include the designation, "RSO Eligible."1/6/2016Not AcceptedOpen10, 0, 0 12The Committee did not endorse establishing a separate category of Authorized Users for parenteral administration of alpha-emitting radiopharmaceuticals but, instead, recommends deleting § 35.390(b)(1)(ii)(G)(4) in the current Draft Final Rule and revising the 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."1/6/2016Partially AcceptedOpen10, 0, 0 13The Committee endorsed the elimination of the requirement to submit copies of NRC Form 313, Application for Material License, or a letter containing information required by NRC Form 313 when applying for a license, an amendment, or renewal.1/6/2016AcceptedOpen10, 0, 0 14The 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:The Sub-Committee recommends changing the "medical-events" 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-,"1/6/2016Not AcceptedOpen10, 0, 0 3

2016 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATEAssigned1st/2ndVote (Y/N/A)STATUS 15The Committee endorsed the 2016 Rulemaking Subcommittee Report with modifications as listed above. 1/6/2016NRC Action Open10, 0, 0 16Dr. 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. Langhorst, Dr. Metter, Dr. Palestro (chair), Dr. Suh and Ms. Weil. NRC staff resource: Maryann Abogunde.2/25/2016ACMUI Action Open 24The ACMUI will contact their respective professional organizations to request and encourage interactions between the NRC and ACMUI with their organization. 3/18/2016ACMUI Action Open 39The Committee recommended that staff issue a generic communication (information notice) regarding tubing issues (kinking, connection, hub etc.) during the administration of Y-90 microspheres brachytherapy. 10/6/16NRC Action OpenDr. Katie TappEnnis/Costello9, 0, 1 42The Committee recommended that the Pathway 2 remain for the Y-90 Microsphere Brachytherapy Licensing Guidance. The NRC/OAS working group should determine what the requirements should be for the proctoring of cases by the manufacturer(s). 10/7/16NRC Action OpenDr. Katie TappLanghorst/Costello9, 1, 1 43The Committee recommended to support the update to the waste disposal section and the review of the Y-90 radiation safety issues in autopsy and cremation in the draft revision of the Y-90 Microsphere Brachytherapy Licensing Guidance. 10/7/16NRC Action OpenDr. Katie TappLanghorst/Ennis11, 0 , 0 44For the NorthStar Guidance Subcommittee: The Committee recommended that NorthStar provide a video clip of how the system operates in the training module.10/7/16NRC Action ClosedDr. Donna-Beth Howe10, 0, 0 45For the NorthStar Guidance Subcommittee: Given the unique design and operation of the NorthStar system, the Committee agreed that NorthStar should have sole responsibility for the content of the training course and certification. 10/7/16NRC Action Closed10, 0, 0 46For 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 defined educational or training background. Given the unique role of the System Administrator, perhaps that individual should be named on the license. 10/7/16NRC Action Closed10, 0, 0 4

2016 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATEAssigned1st/2ndVote (Y/N/A)STATUS 47For 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 the description of the system administrator designee that there can be only one designee. Presumably, there can, and should, be multiple System Administrator designees. 10/7/16NRC Action Closed10, 0, 0 48For the NorthStar Guidance Subcommittee:The Committee recommended that the appropriate time period allotted for training on the "changes" and the responsibility of the vendor/manufacturer to inform and train the applicants on changes in a timely manner be specified.10/7/16NRC Action Closed10, 0, 0 49For 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 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.10/7/16NRC Action Closed10, 0, 0 50For the NorthStar Guidance Subcommittee: The Committee recommended using the term, "individual tasks" throughout the document for consistency and to clarify that there is only one protocol and software program with this system. 10/7/16NRC Action Closed10, 0, 0 51For the NorthStar Guidance Subcommittee: The Committee recommended that the manufacturer's procedures be reviewed and incorporated into the Licensing Guidance itself. 10/7/16NRC Action Closed10, 0, 0 52For the NorthStar Guidance Subcommittee: The Committee recommended that the term "higher than expected" be defined in terms of a maximum specific exposure or exposure-rate limit which a survey meter should be capable of measuring.10/7/16NRC Action Closed10, 0, 0 5

2017 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATE 1The Committee requested that the recommendations and actions pertaining to the Part 35 rulemaking be reviewed during

the fall 2017 ACMUI neeting and that additional time be provided to review each item.4/26/2017NRC Action Pending 8The Patient Intervention Subcommittee will amend its Subcommittee Report and will report at the ACMUI fall 2017 meeting or by teleconference to discuss their amended report.

4/27/2017 ACMUI Action Open 12The NRC staff will engage in discussions with the OAS to find a way to centralize event reporting from the Agreement States.9/11/2017NRC ActionOpen 13 The ACMUI recommended that the NRC establish a program allowing a medical use licensee to evaluate MEs as described

in 10 CFR 35.3045, in NRC 10 CFR 35.1000 licensing guidance, and in 10 CFR 35.3047 with an approved patient safety program.9/11/2017NRC ActionOpenSTATUS 1 2017 ACMUI RECOMMENDATIONS AND ACTION ITEMS 14 Th e ACMUI recommen d e d th a t NRC licensees w ith 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 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.9/11/2017NRC ActionOpen 2

2017 ACMUI RECOMMENDATIONS AND ACTION ITEMS 15 Th e ACMUI recommen d e d th a t NRC s h ou ld t es t ou t thi s 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 program reviews; (2) Assess how this change in ME reporting impacts the NRC's ability to protect patient health and to minimize danger to the patient's life; and (3) Evaluate the different types of patient safety programs in how lessons learned from their patient safety incident reviews are shared withthemedicalcommunity.9/11/2017NRC ActionOpen 16The ACMUI recommended that after completion of the test year, the NRC should c onsider opening the program to all NRC medical use licensees who request approval of their patient safety program, and to Agreement States who request to implement the program with their medical licensees.9/11/2017NRC ActionOpen 17 The ACMUI recommended that the NRC redefine its perspective of patient safety to be different from occupational safety and from public safety. 9/11/2017NRC ActionOpen 18The 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 ACMUI to develop a national database taxonomy specific for reporting patient events involving medical use of byproduct

material.9/11/2017NRC ActionOpen 3

2017 ACMUI RECOMMENDATIONS AND ACTION ITEMS 19 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 involvement of the licensee's patient safety program review of medical errors and reporting of reviews to the national patient safety database.9/11/2017NRC ActionOpen 20The 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 total number of sites and duration to be determined at a later date and to include the Patient Intervention Subcommittee recommendations as an addendum .

9/11/2017 ACMUI Action Open 21The 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 limited to: (1) a suggested time frame for providing written and oral instructions to patients who will stop breastfeeding altogether and (2) consideration to revise the radionuclides to be non-pharmaceutical specific.

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

9/11/17 ACMUI ActionClosed 4 2017 ACMUI RECOMMENDATIONS AND ACTION ITEMS 23The 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 per-event limit and are appropriate for all potentially exposed cohorts, including pregnant women and children, and all radionuclide administrations.9/11/17NRC ActionClosed 24The ACMUI recommended that the 1-mSv (100-mrem) dose limit for requiring patient safety instructions should remain in place.9/11/17NRC ActionClosed 25The 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 No 155; and (3) a patient staying at a hotel following radionuclide therapy is not a widespread practice and is unlikely to result in doses to workers and others > 1 mSv (100

mrem).9/11/17 ACMUI ActionClosed 26The ACMUI recommended that instructions must be provided to the patient well in advance of a planned therapy (ie not on the day of administration), without compromising patient care.

Specification of a regulatory time interval for pre-therapy instructions is not recommended --> NCRP Report No 155.9/11/17NRC ActionOpen 5

2017 ACMUI RECOMMENDATIONS AND ACTION ITEMS 27 The NRC recommended that t he NRC should consider updating Appendix U (NUREG 1556) to reference Regulatory Guide 8.39 rather than eliminating 8.39 or maintaining two separate guidance documents.9/11/17NRC ActionOpen 28The ACMUI endorsed the Patient Release SECY Paper Subcommittee Report.

9/11/17 ACMUI ActionClosed 29The 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 following interruption; (3) possible incorporation of changes to 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 o ption for the Leksell Gamma Knife Icon.

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

9/12/17 ACMUI ActionClosed 6 2018 ACMUI RECOMMENDATIONS AND ACTION ITEMSITEMDATEAssigned1st/2ndVote 1The ACMUI recommended that there be no breast feeding cessation for 11C, 13N, 15O, and 82Rb; a 12-hours cessation for 18F-labeled and 68Ga-labeled; a 24-hours cessation for 99m Tc-labeled; 7-days cessation for 123I-NaI and 111In-leukocytes; 14 days cessation for 201-Tl-chloride; 28 days cessation for 67 Ga and 89Zr; 35 days for 177Lu, diagnostic; and total stop of breastfeeding for 131I-NaI, 177Lu, therapeutic, 223Ra and all alpha emitters.2/15/2018NRC ActionOpenSophie 2The ACMUI endorsed the Nursing Mother Guidelines for the Medical Administration of Radioactive Materials Subcommittee Report, as amended to: (1) include recommended cessation periods for both 100 and 500 mrem limits; (2) acknowledge benefits of breastfeeding; (3) in corporate corrections as needed for gamma ray constants; (4) convert the units from

conventional to SI units; and (5) correct references.2/15/2018ACMUI ActionOpenSophieMetter/Palestro9, 0, 0 3The 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 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.2/15/2018NRC ActionOpenSophie 4The ACMUI recommended as a best practice that appropriately trained nursing or auxiliary staff be present at the console to respond to any immediate medical needs. 2/15/2018ACMUI ActionOpenSophie 5The ACMUI endorsed the Physical Presence Requirements for the Leksell Gamma Knife Icon Subcommittee Report. 2/15/2018ACMUI ActionOpenSophieSuh/Zanzonico9, 0, 0STATUS 1 Open Forum NO HANDOUT 1 1Status of Medical Events FY 2017 Donna-Beth Howe, Ph.D.Medical Radiation Safety Team March 7, 2018 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 2 Medical Events 2012-14

• 48 Medical events reported -FY 2012

• 43 Medical events reported -FY 2013

• 46 Medical events reported -FY 2014FY12FY13FY 1435.200 2 0 135.300 2 2 335.400 15 15 535.600 13 1010 35.1000 20 1627 3 Medical Events 2015-17

• 57 Medical events reported -FY 2015

• 50 Medical events reported -FY 2016

• 42 Medical events reported -FY 2017FY15FY16FY1735.2003 4 035.300 84 4 35.400 9(10)6(18) 7 35.600 17 6 8(14) 35.1000 20(31)30 23 4 3 Medical Events 2017 35.300 Medical events 4Iodine 1313 Radium 2231 5 35.300 Medical Events (cont.)Iodine-131 3

• Administered 2mCiwhen none was prescribed.-Prescribed parathyroid test but received thyroid scan.-I-131 ordered without written directive.-Electronic ordering and records system used withoutconfirmation of the order prior to administration.-Thyroid received 1,630 cGy.-Modified procedures, confirm dosage orders, and re-trained personnel.

6 435.300 Medical Events (cont.)Iodine-131 cont.

• Administered 20.2 mCiinstead of 30 mCiin written directive.-Written Directive was incorrect.

-Intended dose was given.

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

735.300 Medical Events (cont.)Iodine-131 cont.

• Administered 106 mCiinstead 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 5 9Ra-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. 35.300 Medical Events (cont.)

Medical Events 2017 35.400 Medical events 7Prostate 7One licensee 2 reports 2 Human error

AnatomyWrong site 1Used previous activity 1Larger then pre plan or swelling 3 10 6 35.400 Medical Events Prostate 7*One licensee, 2 separate reports*Case 1 -Patient received 62% of the prescribed D90dose 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 D90dose of 14,500cGy.-Caused by patient anatomy.

-Identified during post-implant CT scan andsubsequent dosimetric analysis.-Delay in reporting to State due to communication breakdown and inadequate procedures.

12 735.400 Medical Events cont.

• Patient received 2,760 cGyinstead 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.

1335.400 Medical Events cont.

• Patient received 157.81% of the prescribed D90 dose of 12,500cGy -Pd103 seeds.-Failed to enter correct ac tivity 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 8 35.400 Medical Events cont.

• Prescribed 14,400 cGyreceived 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 rout ine audit conducted by a medical physicist.

15 35.400 Medical Events cont.

• Prescribed 14,500 cGyreceived 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 theeffect of swelling of the prostate gland and possiblemigration of the seed 16 935.400 Medical Events cont.

• Prescribed 14,500 cGyreceived 10,353 cGy-71% of the dose.-Order additional seeds bey ond 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) 2Wrong site 4Equipment failure 1 Gamma Knife1 18 10 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 issuewith source step size with ring.-Source step size of 5 mm instead of 2.5 mm.-Dose to unintended site 2,800 cGyto 1,400 cGy.-Dose to the unintended site expected too be 126 to175 cGyper fraction.-Elektanotified software us ers of problem with ring.

1935.600 HDR Gynecological (cont.)

• Generic Software issue cont. (5 patients)-Oncentra software versions 4.5.2 issue with sourcestep size with ring of 5 mm instead of 2.5 mm.-Dose to treatment si te 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 endpointand started on a return path ba ck into the lower vagina.-Some tissue protection by fluid-filled sleeve thatprovided some shielding and displacement.

20 1135.600 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.

2135.600 HDR Gynecological (cont.)

• Wrong Site cont.-Capri applicator inserted in to the patient's rectum instead of vagina on 2 nd of 5 fractions.-Treatment site received prescribed dose of 350 cGy(rad) during the second treatment.-Radiologist confirmed t he patient's rectum had been treated.22 1235.600 HDR Gynecological (cont.)

• Wrong site cont.

-5 cm site received 500 cGy-f irst two tandem and ovoid treatments were delivered as prescribed

-I ncorrect tandem applicator length of 119.8 cm was entered into the treatment planning system for third fraction instead of the prescribed 131.9 cm.2335.600 HDR Gynecological (cont.)

• Wrong site cont.-Received 700 cGy-Physicist determined inserted length of the transferguide tube was 7.5 cm shorter than intended.-The transfer tube was deformed and added pressureneeded to fully insert it into the applicator.-Removed the transfer guide tube from service, got different design.-Counseled staff on the event.

24 1335.600 HDR Gynecological(cont.)

• Equipment failure.-Received 6.4% of prescribed 500 cGydose during the 1st of 5 fractions.-Five separate interlocks were tripped in 1st fraction.

-fluid in the catheter may have contaminated the source and afterloaderunit.

2535.600 Gamma knife1Gamma Knife Model C.

• Prescribed 2000 cGyreceived 1540 cGyto 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 14 Medical Events 2017 35.1000 Medical events 24 Intervascular Brachytherapy 1 Y-90 Microspheres23 Therasphere 15 SirSphere8 27Intravascular Brachytherapy 1-Prescribed dose of 1,840 cGy(rad) for in-stentrestenosis 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 -locatedoutside the patient.-Compression of the catheter during a challengingadvancement into a commonly tortuous vessel (leftinternal mammary artery).

28 35.1000 Medical Events 15 Y-90 Microspheres 23 Therasphere 15-Over dose3

-Wrong site 2

-Kinked catheter 4

-Cracked catheter 1

-Partial Obstruction1

-Leaking connection 2

-Slow infusion 1

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

• Prescribed 11,000 cGyadministered 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 16 35.1000 Y-90 Therasphere (cont.)Overdose cont.

• Prescribed 34,000 cGyadministered 80,800 cGy-liver volume.-Administered before microspheres decayed to theprescribed activity -Scheduling nurse used the pre-treatment plan instead of the final treatment plan.-The physicist's pre-treatment calculations and time-out failed.

31 35.1000 Y-90 Therasphere (cont.)Overdose cont.

• Prescribed 34,000 cGyadministered 80,800 cGy-

liver volume.(cont.)-Spreadsheet to calculate patient dose modified tocheck 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 17 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 GBqto mCi.-Corrective actions -procedure modifications, writtendirective 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 tovasculature suppling right lobe -reflux to right lobe.-Verified catheter posit ion multiple ways beforeadministration -no appar ent complications.-Bremsstrahlung imaging s howed microspheres in both lobes.

34 18 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 angiographicallyundetected 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 mCito the small segment and 64.3 mCito the

large segment.-Later discovered only 10.27 mCiwas 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 19 35.1000 Y-90 Therasphere (cont.)Wrong site cont.

• Two separate segments in the right lobe prescribed25.6 mCito the small segment and 64.3 mCito the

large segment. (cont.)-Process involved several hand-offs, reviews, andverifications by different providers using different source documents -inconsistency between the writtendirective 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 mCito the left lobe -administered 46.22 mCito right lobe (right lobe to be treated one month later).-Interventional radiologist and radiation oncologistauthorized 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 righthepatic artery for right lobe -human error confused about later treatment of right.

38 20 35.1000 Y-90 Therasphere (cont.)Wrong site cont.

• Prescribed 47.03 mCito the left lobe -administered 46.22 mCito 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 flow rate, dent in the outlet tubing from a pinch-clamp, and over-tightening of the Touhy-BorstY-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 21 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 mCito the right lobe.-Residual activity 12.5 mCiremaining 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 mCiadministered 20 mCi.-Two separate liver segments.-Second acrylic jar contained 56% of the microspheresintended 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 toflush contrast and saline through it, but have microspheres clog it.

42 22 35.1000 Y-90 Therasphere (cont.)Cracked catheter 1

• Prescribed two doses with a total activity of 54 mCito 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/hrfor the microsphere vial -AU assumed first was from

contaminated cloth but recognized second meant two under doses. -Visual inspection of the microcatheterrevealed 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 23 35.1000 Y-90 Therasphere (cont.)Partial obstruction 1*Prescribed 47.88 mCi-ad ministered 13.91mCi.(cont.)-Thought partial obstruction in catheter or lineconnecting the microsphere vial to the catheter,vasculature was complicated and may have resulted

in movement of the micro-catheter slightly forwardfrom 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 connectionbetween 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 tobe 1.1 µSv(0.11 mrem).-Incident due to human error -poor connectionbetween the e-line and the patient's catheter.

46 24 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 fromthe microsphere vial to the microcatheter.-Physician simultaneously unclamped theadministration 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 administrationarea, which was immedi ately decontaminated.

47 35.1000 Y-90 Therasphere (cont.)Slow injection rate 1*prescribed 175.7 mCi-administered 43.24 mCi.-Slow injection rate to pr event reflux into adjacentgastric artery that c ould 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 25 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 identifiedcatheter backup in another slow injection rate administration.

49 SirSphere8-Labeled vial shield not vial1-Low activity administration3

-High activity clogging 1-Clogging issues 3*Needle 1

• Catheter defect 1

• Kinked 1 50 35.1000 Y-90 Events (cont.)

26Labeled vial shield not vial 1

• Prescribed 2.453 mCito small lesion and 22.077 mCito large lesion -administered 22.077 mCito

small lesion.-Prepared two vials, labeled each vial shield, did not label the vials. -Provided vial with 22.077 mCifor small lesion realized mistake when started large lesion. -Require time-out, label both the vial and vial shield, read labels three times bef ore administration.

5135.1000 Y-90 SirSphere(cont.)Low activity administration 3

• Prescribed 6.49 mCito 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 pr esent to observe low activity administrations.

5235.1000 Y-90 SirSphere(cont.)

27Low activity administration cont,

• Prescribed 5.49 mCi-administered 4.07 mCi.-Cause of the event was the amount of activitydelivered; the relatively low prescribed dose madethe residue look comparatively large.-Another doctor will supervise the remainder of theadministrating doctor's cases -part of therequirements for obtaining authorized user status.

5335.1000 Y-90 SirSphere(cont.)Low activity administration cont,

• Prescribed 4.05 mCi-administered 3.14 mCi.-Radiation survey revealed residual activity of 1.06mCiremained in the treatment device.-The use of small doses will be carried out after greater scrutiny and review.

5435.1000 Y-90 SirSphere(cont.)

28High activity clogging 1

• Prescribed 84.12 mCi-ad ministered 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 themicro-catheter towards the patient.

5535.1000 Y-90 SirSphere(cont.)Clogged needle

1*Prescribed 32.97 mCi-administered 8.2 mCi.-Occlusion of the vial delivery C needle due toclumping of the microspheres.-Intended to return to manufacturer but discarded after activity decayed to background.-Educating the administrator of the microspheres onhow to clear the clogged needle, which is to reversethe valve for flushing purposes.

5635.1000 Y-90 SirSphere(cont.)

29Catheter defect

1

• Prescribed 12.16 mCi-ad ministered 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. -MedWatchFDA Adverse Event form completed.

5735.1000 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.

5835.1000 Y-90 SirSphere(cont.)

30 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 1NRC Staff Response to ACMUI Safety Culture Recommendations Doug BollockACMUI Spring MeetingMarch 7, 2018 Agenda*Review the ACMUI recommendations from ACMUI report "

Medical Event Reporting and Impact on Medical Licensee Patient Safety Culture"

• Provide the NRC staff's responses to the ACMUI recommendations 2

2 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

3 Acronyms*NRC-U.S. Nuclear Regulatory Commission

• ACMUI-Advisory Committee on the Medical Uses of Isotopes

• PSO-Patient Safety Organization

• ME-Medical Event 5

1 Committee Reporting StructureSophie Holiday, ACMUI CoordinatorMedical Radiation Safety TeamMarch 7, 2018 Outline*Current Reporting Structure*Annual Review

• Meetings

• Discussion 2

2 Current Reporting Structure 3 The Commission EDO Director, NMSSDirector, MSST ACMUI MSEB Annual Review *I n September 2012, the ACMUI recommended to have an annual review of reporting structure.

• This is the eighth annual review.

4 3 Meetings Two meetings at Headquarters each year *March/April

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

4 Points of Contact*Kevin Williams -A cting MSST Director-301-415-3340; Kevin.Williams@nrc.gov*Douglas Bollock -D esignated Federal Officer-301-415-6609; Douglas.Bollock@nrc.gov*Sophie Holiday -ACMUI Coordinator-301-415-7865; Sophie.Holiday@nrc.gov 7 Acronyms*EDO -E xecutive Director for Operations

• MSST -Division of Materials Safety, Security, States, and Tribal Programs*MSEB -M edical Safety and Event Assessment Branch

• NMSS -Office of Nuclear Material Safety and Safeguards 8

1Worldwide Supply and the Domestic Production of Molybdenum-99 (99 Mo)Richard L. Green, R.Ph, BCNP March 7, 2018 2 235 U Fission Produces HSA 99 Mo*Starts with the enrichment of 235 U-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 3Current Fission 99Mo Supply ChainProcessorsReactors Fission 99 Mo HSAGenerators neutron fission byproduct 99 Mo neutron neutron neutron 235 U GE Curium Lantheus Reactors Producing HSA 99 Mo 4ReactorLocationCommissioning Date FuelTypeTarget Type Global 99 Mo Processor HFRPetten,Netherlands 1961LEULEUCurium / IRE BR2Mol, Belgium 1961HEUHEUCurium / IRESAFARIPelindaba, South Africa 1965LEULEU NTP MARIAOtwock-Swierk, Poland 19741993 rebuiltLEULEUIAE-Polatom/ CuriumLVR-15Rez, CzechRepublicMid 1950'sLEUHEUCzech Nuclear Research Institute / IREOPALLucas Hts., Australia 2007LEULEUANSTO 3Current U.S.

99Mo Supply Matrix 5Maria, PolandHFR, Netherlands BR2, BelgiumLVR-15, Czech RepublicSAFARI, South AfricaOPAL, Australia Fission of 235 U Reactor Processor 99mTc Generator Manufacturer

supplying U.S.Curium, NetherlandsIRE, BelgiumNTP, South AfricaANSTO, Australia GE Healthcare, Amersham, UKCurium, St Louis MO Lantheus, N. Billerica, MAMURR, Missouri, USA 98Mo Neutron CaptureMURR, Missouri, USANorthStar,Beloit, WINEW H S A L S AAmerican 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 99 Mo production*Requires a NAS study 5 years after enactment 4Revenues 99mTc Supply Chain Challenges 5 A New U.S.

99 Mo Producer !

9*NorthStar Medical Radioisotopes, LLC Beloit, WI*8 Feb 2018U.S. FDA approved the first domestically-produced, non-uranium based 99 Mo*A LSA, computer controlled 99 Mo generator system https://www.northstarnm.com/products/northstar-solutions-radiogenix-system/NS's Current Production Method

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

-98 Mo(n,)99 Mo >>using natural enrichment 98 Mo>>~6 Ci / source vessel 10 6 NS's Future Production Method

• Neutron Capture 98 Mo(n,)99 Mo >>using enriched 98 Mo>>~18 Ci / source vessel

• Long term -linear accelerator at NorthStar facility in Beliot, WI 100 Mo(p,2n)99 Mo 11 LSA 99 Mo Generator*Source vessel contains ~30 mL potassium molybdate 99 Mo*Protocols-Produce 99m Tc-Add/change reagents

-Add/exchange reagents

-Sterilize system

-Add source vessel

-Remove source vessel

-Add/exchange discarded material container 12 7Other 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 99 Moproduced 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 systemNeutrons from accelerator U salts 99 Mo 14Current Processing Production & Projected Future Demand, Global, 2015 -2020 8 15ACMUI -Advisory Committee on the Medical Uses of IsotopesDOE -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 99m TcGTRI -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 uraniumNNSA -National Nuclear Security AdministrationNS -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 235U -radioactive form of uranium used to fuel reactors Acronyms 16 Acronyms 1NRC Medical Projects on the Horizon Doug BollockACMUI Spring MeetingMarch 7, 2018 Agenda*Discuss the major assignments currently under review by the Medical Radiation Safety Team 2

2 Major Projects

• Part 35 Rule change implementation

• Germanium/Gallium-68 Generators

• Physical Presence Requirements for LeksellPerfexionand 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

ACMUI Working Prepatory Session NO HANDOUT Special Presentation to Dr. Pat Zanzonico NO HANDOUT 1 Emerging Medical Technologies Commission PaperIrene WuMarch 7, 2018Source:ElektaSource:NorthStar Purpose*To provide the Commission with the NRC staff's review of the emerging medical technologies program 2

2 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 GalliaPharm TM 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

3Examples of In Process Reviews 5*Yttrium-90 Microsphere Brachytherapy Sources and Devices TheraSphere and SIR-Spheres

• LeksellGamma Knife Perfexion TM and LeksellGamma Knife Icon TM*Lutetium-177 dotatateExamples of Anticipated Reviews 6*Phosphorus-32 OncoSil TM microparticles

• MASEP Infini TM cobalt-60 stereotactic radiosurgery

• GammaPod TM cobalt-60 stereotactic radiotherapy 4 AcronymsNRC -U.S. Nuclear Regulatory Commission 7

Commission Meeting with the ACMUI

NO HANDOUT

Group Photo

NO HANDOUT

Thoughts on Leaving the ACMUI

NO HANDOUT