ML19170A337
| ML19170A337 | |
| Person / Time | |
|---|---|
| Issue date: | 04/03/2019 |
| From: | Advisory Committee on the Medical Uses of Isotopes |
| To: | |
| Jamerson K | |
| References | |
| NRC-0262 | |
| Download: ML19170A337 (213) | |
Text
1 UNITED STATES OF AMERICA NUCLEAR REGULATORY COMMISSION
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ADVISORY COMMITTEE ON THE MEDICAL USES OF ISOTOPES
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SPRING 2019 MEETING
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WEDNESDAY, APRIL 3, 2019
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The meeting was convened in Room 1-C03/1-C05, Three White Flint North, 11601 Landsdown Street, Rockville, Maryland, at 8:30 a.m., Christopher J.
Palestro, ACMUI Chairman, presiding.
MEMBERS PRESENT:
CHRISTOPHER J. PALESTRO, M.D., Chairman
DARLENE F. METTER, M.D., Vice Chairman
VASKEN DILSIZIAN, M.D., Member
RONALD D. ENNIS, M.D., Member
RICHARD L. GREEN, Member
MELISSA MARTIN, Member
MICHAEL D. O'HARA, Ph.D., Member
ZOUBIR OUHIB, Member
ARTHUR SCHLEIPMAN, Ph.D., Member
MICHAEL SHEETZ, Member 2
MEGAN L. SHOBER, Member LAURA M. WEIL, Member
NON-VOTING MEMBER PRESENT:
HARVEY B. WOLKOV, M.D.
NRC STAFF PRESENT:
CHRIS EINBERG, NMSS/MSST/MSEB, Designated Federal Officer MARYANN AYOADE, NMSS/MSST/MSEB/MRST
JENNIFER DALZELL, R-III/DNMS/MCIB
SAID DIABES-FIGUEROA, NMSS/MSST/MSEB/MRST
LISA DIMMICK, NMSS/MSST/MSEB/MRST, Team Leader
SARA FORSTER, R-III/DNMS/MLB
CASSANDRA FRAZIER, R-III/DNMS/MLB
ROBERT GALLAGHAR, R-I/DNMS/MLAB
VINCE HOLAHAN, NMSS/MSST
SOPHIE HOLIDAY, NMSS/MSST/MSEB
ESTHER HOUSEMAN, OGC/GCRPS/RMR
DONNA-BETH HOWE, Ph.D., NMSS/MSST/MSEB/MRST
KELLEE JAMERSON, NMSS/MSST/MSEB/MRST, ACMUI
Coordinator
DONNA JANDA, R-I/DNMS/MLAB
JANELLE JESSIE, COMM/OCMJB
ERIN KENNEDY, R-III/DNMS/MLB 3
PENNY LANZISERA, R-I/DNMS/MLAB SARAH LOPAS, NMSS/MSST/MSEB/MRST
HENRY LYNN, OCHCO/ADHRTD/STTSB
ROBERT MACDOUGALL, NMSS/DRM/MRPB
JANICE NGUYEN, R-I/DNMS/MLAB
DENNIS O'DOWD, R-III/DNMS/MIB
PATTY PELKE, R-III/DNMS/MLB
DAVID PELTON, R-III/DNMS
SHAWN SEELEY, R-I/DNMS/MLAB
VERED SHAFFER, RES/DSA/RPB
KATIE TAPP, Ph.D., NMSS/MSST/MSEB/MRST
KEVIN WILLIAMS, NMSS/MSST, Deputy Division
Director IRENE WU, NMSS/MSST/MSEB/MRST
MEMBERS OF THE PUBLIC PRESENT:
JENNA ABBOTT, Illinois Emergency Management
Agency (IEMA)
DANNY ALLEN, NuTech, Inc.
ERIC ANDERSEN, Dana-Farber Cancer Institute
MICHAEL BAXTER, American Pharmacists Association BETTE BLANKENSHIP, American Association of Physicists in Medicine (AAPM) KENDALL BERRY, Fox Chase Cancer Center JEFF BRUNETTE, Mayo Clinic 4
JANET BUKOVCAN, British Technology Group (BTG)
MARY BURKHART, IEMA STEVEN CHILINSKI, Radiopharmacy ASHLEY COCKERHAM, SirTex Medical WHITNEY COX, IEMA WILLIE (JACK) CRAWFORD, Virginia Office of
Radiological Health
CORY DAIGNAULT, Virginia Office of Radiological
Health NICK DORRELL, University of Virginia ARIEL DOUCET, Virtua Health MARK DRISCOLL, University of Michigan BRIAN ERASMUS, BTG LYNNE A. FAIROBENT, Unaffiliated SHERRIE FLAHERTY, Minnesota Radioactive
Materials Unit
MARK FLICKINGER, Virginia Office of Radiological Health MICHAEL FULLER, Virginia Office of Radiological
Health SANDY GABRIEL, Unaffiliated REID GADZIALA, PharmaLogic
WENDY GALBRAITH, University of Oklahoma Health
Sciences Center
NOELLE GEIER, Froedtert &
the Medical College of 5
REBECCA GRABARKEWITZ, Virginia Office of
Radiological Health
MATTHEW HADDEN, Virginia Office of Radiological
Health GARY HALL, Virginia Office of Radiological
Health MATTHEW HALL, North Shore University Health
System STANLEY HAMPTON, Eli Lilly
CURTIS HICKS, Brigham and Women's Hospital, Harvard Medical School
WILLIAM HINCHCLIFFE, Yale New Haven Hospital
WILLIAM HOUSE, Virginia Office of Radiological
Health SARAH HUGHES, University of Louisville
PAUL KANABROCKI, Virginia Office of Radiological Health HEATHER KARMANSKY, SirTex Medical
CAITLIN KUBLER, Society of Nuclear Medicine and
Molecular Imaging (SNMMI)
RALPH LIETO, St. Joseph Mercy Health System
WILLIAM LORENZEN, Boston Children's Hospital, Harvard Medical School 6
RICHARD MARTIN, AAPM JEFF MASON, Virginia Office of Radiological
Health STEVE MATTMULLER, Kettering Health
ANDY McKINLEY, American Society of Nuclear
Cardiology (ASNC)
ANDREW McKUSICK, Unknown ASHLEY MISHOE, University of California, San
Francisco
CHRISTOPHER MITCHELL, Kettering Health
JOSHUA MYERS, Pennsylvania Department of
Environmental Protection
CHRISTOPHER NATION, Virginia Office of
Radiological Health
SCOTT NEMMERS, U.S. Air Force
JOSEPH OBERENDER, Virginia Office of
Radiological Health
BRAD PRICE, GE Healthcare
PRYIA RAYADURGAM, Cleveland Clinic
JOE RUBIN, United Pharma cy Partners, Inc. (UPPI)
MANAR SAKALLA, Georgetown University
EUGENIO SILVESTRINI, Northwell Health
ED SIMS, Cleveland Clinic
ANDRES SINISTERRA, UConn Health
LAKSHMI SIVASUBRAMANIAN, University of 7
Massachusetts Medical School DIANA THOMPSON, University of Illinois at
Chicago CINDY TOMLINSON, American Society of Radiation
Oncology (ASTRO)
DAVID TOWNSEND, Unaffiliated MICHAEL UJHELYI, BTG
MATTHEW WHITE, SSM Health
WILLIAM WHITE, Rush University Medical Center
NEIL WHITESIDE, Yale New Haven Hospital
MATTHEW WILLIAMS, Georgetown University
MATTHEW WILLIAMSON, Memorial Sloan Kettering
Cancer Center
ROBERT WILSON, University of Tennessee Health
Science Center
MELONIE WISSING, Virginia Office of Radiological Health MIYUKI YOSHIDA-HAY, Northwell Health
8 C-O-N-T-E-N-T-S Opening Remarks....................................9
Old Business......................................18
Open Forum........................................33
Yttrium-90 Microspheres Brachytherapy Licensing Guidance Subcommittee Report................41 Lucerno Dynamics LARA Infiltration Detection...................................68 Summary of Changes to 10 CFR Part 35.............108
Germanium-68/Gallium-68 Subcommittee Report.....................................130 Medical Related Events...........................153
Appropriateness of Medical Event Reporting Subcommittee Report........................190 Adjourn..........................................211
9 P R O C E E D I N G S 1 8:36 a.m.
2 CHAIRMAN PALESTRO: Good morning, and 3 welcome to the spring meeting -- spring 2019 meeting 4 of the ACMUI. And at this point, I will turn the 5 meeting over to Mr. Einberg for opening remarks.
6 MR. EINBERG: Okay. Thank you, Dr.
7 Palestro. As the designated federal officer for this 8 meeting, I'm pleased to welcome you to this public 9 meeting of the Advisory Committee on the Medical Uses 10 of Isotopes.
11 My name is Chris Einberg. I'm the Branch 12 Chief of the Medical Safety and Events Assessment 13 Branch, and I have been designated as the federal 14 officer for this advisory comm ittee in accordance with 15 10 CFR Part 7.11. Present today as the designated 16 federal officer is Sophie Holiday. Also as a 17 designated officer and ACMUI coordinator is Kellee 18 Jamerson.
19 This is an announced meeting of the 20 committee. It is being held in accordance with the 21 rules and regulations of the Federal Advisory 22 Committee Act and the Nuclear Regulatory Commission.
23 This meeting is being transcribed by the NRC and then 24 may also be transcribed or recorded by others. The 25 10 meeting was announced in the February 19th, 2019 1 edition of the Federal Register, Volume 84, Page 4858.
2 The function of the committee is to advise 3 the staff on issues and questions that arise on the 4 medical use of byproduct material. The committee 5 provides counsel to the staff but does not determine 6 or direct the actual decisions of the staff or the 7 Commission.
8 The NRC solicits the views of the 9 committee and values their opinions. I request that 10 whenever possible, we try to reach consensus on the 11 various issues that we will discuss today. But I also 12 recognize there may be minority or dissenting 13 opinions. If you have such opinions, please allow 14 them to be read into the record.
15 At this point, I would like to perform a 16 roll call of the ACMUI members participating today.
17 Dr. Christopher Palestro, Chairman, Nuclear Medicine 18 Physician?
19 CHAIRMAN PALESTRO: Present 20 MR. EINBERG: Dr. Darlene Metter, Vice 21 Chairman, Diagnostic Radiologist?
22 VICE CHAIRMAN METTER: Present.
23 MR. EINBERG: Dr. Vasken Dilsizian, 24 Nuclear Cardiologist?
25 11 MEMBER DILSIZIAN: Present.
1 MR. EINBERG: Dr. Ronald Ennis, Radiation 2 Oncologist?
3 MEMBER ENNIS: Here.
4 MR. EINBERG: Mr. Richard Green, Nuclear 5 Pharmacist?
6 MEMBER GREEN: Present.
7 MR. EINBERG: Ms. Melissa Martin, Nuclear 8 Medicine Physicist?
9 MEMBER MARTIN: Present.
10 MR. EINBERG: Dr. Michael O'Hara, FDA 11 Representative?
12 MEMBER O'HARA: Present.
13 MR. EINBERG: Mr. Zoubir Ouhib, Radiation 14 Therapy Physicist?
15 MEMBER OUHIB: Present.
16 MR. EINBERG: Dr. A. Robert Schleipman, 17 Healthcare Administrator?
18 MEMBER SCHLEIPMAN: Present.
19 MR. EINBERG: Mr. Michael Sheetz, 20 Radiation Safety Officer?
21 MEMBER SHEETZ: Present.
22 MR. EINBERG: Ms. Megan Shober, State 23 Government Representative?
24 MEMBER SHOBER: Present.
25 12 MR. EINBERG: Ms. Laura Weil, Patients' 1 Rights Advocate?
2 MEMBER WEIL: Present.
3 MR. EINBERG: At the table today, we also 4 have Dr. Harvey Wolkov.
Dr. Wolkov has been selected 5 as the ACMUI Radiation Oncologist. He is pending a 6 security clearance but may par ticipate in the meeting.
7 However, he does not have voting rights at this time.
8 I would also like to add that this meeting 9 is being held via GoToWebinar so other individuals may 10 be listening through webinar. The webinar ID number 11 is 144-519-715. You must register for the webinar in 12 order to obtain the bridge line and unique pin 13 assigned per individual.
14 Individuals who would like to ask 15 questions or make comments regarding a specific issue 16 the committee has discussed should requ est permission 17 to be recognized by the ACMUI chairperson, Dr.
18 Christopher Palestro. Dr. Palestro, at his option, 19 may entertain comments or questions from members of 20 the public who are participating with us today.
21 Comments and questions are usually 22 addressed by the committee near the end of the 23 presentation after the committee has fully discussed 24 the topic. We ask that one person speak at a time as 25 13 this meeting is also closed captioned. I would also 1 like to add that the handouts and agenda for this 2 meeting are available at the NRC's public website.
3 At this point, I'd like to turn the 4 meeting over to Kevin Williams who's the Deputy 5 Director of the Division of Materials Safety, 6 Security, State, and Tribal Programs for some opening 7 remarks. 8 MR. WILLIAMS: Thank you, Chris. Good 9 morning and welcome today to the spring 2019 meeting.
10 As Chris stated, my name is Kevin Williams. I am the 11 Deputy Director in the Division of Materials Safety, 12 Security, State, and Tribal Programs in the Office of 13 Nuclear -- sorry about that -- Materials Safety and 14 Safeguards, or as we commonly call it, NMSS. I 15 started this position in May of 2017.
16 I want to first begin by thanking ACMUI 17 for all of your hard work and support to the NRC. We 18 greatly appreciate that. We truly value your 19 contributions, your knowledge, and your experience. I 20 would like to highlight a few areas that may be of 21 interest to ACMUI and the meeting attendees.
22 The final rule of 10 CFR Part 35, the 23 Medical Use of Byproduct Material-Medical Event 24 Definitions, Training and Experience, and Clarifying 25 14 Amendments, was published on July 16th of 2018 and 1 became effective January 14th, 2019.
I, again, would 2 like to thank the ACMUI on your work with the staff on 3 this major initiative.
4 In October of 2018, the staff published a 5 Federal Register notice requesting specific feedback 6 on our training and experience requirements, including 7 whether requirements should be tailored, and if so, 8 how. The comment period ended on January 29th of 9 2019. The staff is considering the com ments received 10 as part of its evaluation and plans to provide for the 11 Commission's consideration a notation vote paper by 12 the fall of 2019.
13 On May 14th, 2019, the NRC staff plans to 14 hold a public meeting to inform stakeholders of the 15 staff's proposed options for a limited scope AU 16 pathway. Once the date has been confirmed, a meeting 17 notice will be published in the Federal Register, 18 announced on the medical list server, and directly 19 communicated with ACMUI.
20 Shortly after the May 2019 public meeting, 21 the NRC staff will draft its Commission paper. The 22 paper will be provided to the ACMUI for its review.
23 We anticipate receiving the ACMUI's comments on the 24 staff's draft Commission paper during a public 25 15 teleconference meeting in the summer of 2019.
1 On March 27th, 2019, the ACMUI Regulatory 2 Guide 8.39 subcommittee was provided with NRC's 3 staff's draft revision to Regulatory Guide 8.39. We 4 look forward to receiving the subcommit tee's comments 5 and recommendations as part of a separate 6 teleconference meeting this summer.
7 We recognize that the ACMUI had a public 8 teleconference on February 26, 2019 to discuss the T&E 9 for all modalities subcommittee draft report for T&E 10 requirements for 35.300 uses. As stated in the 11 report, the subcommittee recommends maintaining the 12 current board certification pathway and the 700-hour 13 T&E alternative pathway under 10 CFR 30.390 which is 14 consistent with the full commi ttee's position in 2016.
15 Thank you to the subcommittee for its efforts.
16 Now to talk about some NRC organizational 17 changes. The Office of Nuclear Material Safety and 18 Safeguards, or NMSS, Marc Dapas retired. He was the 19 Office Director. He retired in January of 2019. John 20 Lubinski is now going to be the NMSS Of fice Director, 21 and he began Monday, April 1st of 2019. John will be 22 stopping by to speak with us during the luncheon.
23 Andrea Kock was selected as the Division 24 Director of Material Safety, State, and Tribal 25 16 Programs in November of 2018.
Dan Coll ins previously 1 held that position, and he has taken a position at 2 Region I. Andrea is on travel today.
Otherwise, she 3 would be the one speaking with you. But she really 4 wanted me to let you know that she appreciates ACMUI's 5 efforts and all that you do to help the NRC think 6 outside of the box and the things that you provide the 7 staff. 8 We recently just underwent a 9 reorganization. Specifically, we consolidated from a 10 five branch model to a four branch model. This 11 resulted in an additional staff member being added to 12 the medical group.
13 Additionally, NMSS is planning an office-14 wide reorganization in which t wo divisions will merge, 15 our fuel cycle division and the division of spent 16 fuel. The Division of Rulemaking will expand to 17 include two new centers of expertise, one for 18 environmental review and one for financ ial assurance.
19 This reorganization is not expected to occur until 20 fiscal year 2020 and will have no impact on our 21 division, MSST.
22 ACMUI membership changes. This is Ms.
23 Laura Weil's last in-person me eting as her second term 24 with ACMUI ends in August. Many thanks to you for 25 17 your contributions over the past eight years. We 1 found those to be very valuable. Tomorrow morning, 2 our Deputy Office Director, Scott Moore, will be here 3 to present you with a special presentation thanking 4 you for your service.
5 Dr. Chris Palestro's second term will end 6 in September. The NRC posted a solicitation for both 7 the Patients' Rights Advocate and the Nuclear Medicine 8 Physician representative positions in the Federal 9 Register as a call for nominations on February 20th, 10 2019. The nomination period closes April 22nd, 2019.
11 So that does leave us an opportunity to celebrate 12 your contributions, Dr. Palestro, at a later time.
13 The ACMUI subcommittees have been working 14 hard, and there are a number of subcommittee reports 15 that will be discussed and brought before the ACMUI 16 today. 17 Dr. O'Hara will discuss the subcommittee's 18 recommendations on NRC's draft revision 10 to the 19 Yttrium-90 Microsphere Brachytherapy Licensing 20 Guidance.
21 Ms. Shober will discuss the subcommittee's 22 recommendations on the NRC's draft revision to the 23 Germanium Gallium Pharmacy Grade Generator Licensing 24 Guidance.
25 18 Dr. Ennis will discuss the subcommittee's 1 interim report on the appropriateness of the required 2 elements of medical event reporting.
3 This morning, Lucerno Dynamics will 4 provide a presentation on their LARA Infiltration 5 Detection device which assists with detecting nuclear 6 medicine injection infiltrations.
7 The Commission meeting with the ACMUI will 8 be held tomorrow at 10:00 a.m. at the Commissioner's 9 hearing room.
10 I will now turn the meeting back over to 11 Dr. Palestro.
12 CHAIRMAN PALESTRO: Thank you, Mr.
13 Williams. Next item on the agenda is old business.
14 Ms. Holiday will review the past ACMUI recommendations 15 and provide NRC responses. Ms. Holiday?
16 MS. HOLIDAY: Give me just one minute as I 17 pull up the PDF, and excuse my hoarse voice.
18 (Pause.) 19 MS. HOLIDAY: Okay. Good morning. So 20 like I always like to say, this is your most favorite 21 presentation that you will hear at every single 22 meeting, and this is referred to as old business.
23 This is the part of the meeting where we review all of 24 the open or pending or open delayed recommendations or 25 19 actions that have come forth from the committee.
1 Luckily at the last fall ACMUI meeting, a lot of the 2 recommendations were closed. So my voice is very 3 grateful for that.
4 On the screen, you see the 2007 chart. As 5 we always say, Items 33 and 34 are related to 35.491.
6 These are listed as open and delayed, and that means 7 that the NRC staff accepted these recommendations.
8 However, they were not included in the Part 35 9 rulemaking that we just completed and issued last 10 year. So that means it will be considered in the next 11 round of rulemaking.
12 Okay. Now what you see on the chart is 13 2008. Again, the same things for Items 19, 26, and 14 27. These all say open delayed because they were not 15 included in the current or the most recently issued 16 Part 35 rule. They will be considered in the next 17 round of rulemaking. So we leave those on the charts.
18 Okay. Item 6 in 2011 is the lone item for 19 the chart, and this is where the ACMUI created an item 20 to review its reporting structure on an annual basis.
21 It is open indefinitely as this is an item that the 22 committee has recommended that we discuss every single 23 year. You will hear that presentation from Ms. Kellee 24 Jamerson later on tomorrow -- or tomorrow morning, 25 20 sorry. 1 So this brings us to the 2016 chart. The 2 first item is the formation of the training and 3 experience requirements for all modalities in 10 CFR 4 Part 35 subcommittee. This item is open indefinitely.
5 The idea is that this group of individuals or this 6 subcommittee body will review the training and 7 experience requirements for all authorized users under 8 Part 35 on a continual basis.
9 While it does not mean that it's evaluated 10 every year, it means that this subcommittee will 11 review these requirements on a frequent basis to 12 determine if those requirements need to change. As 13 you're aware, we had a teleconference just two months 14 ago where that subcommittee provided a report.
15 The second item, Item 24, is that the 16 ACMUI, as part of its efforts to partner with NRC to 17 do a better medical community outreach, the members on 18 the committee agreed to contact and interact with 19 their respective professional organizations to 20 encourage those interactions. So we've benefitted 21 quite greatly. We've had interactions and 22 presentations at SNMMI, AAPM, ACR. Later on this 23 summer, we will have one at HPS. So thank you for 24 those efforts.
25 21 Item 39 is related to where the committee 1 requested that the NRC staff issue a generic 2 communication and information notice regarding tubing 3 issues during the administration of Yttrium-90 4 microspheres brachytherapy. That item is still 5 pending. We have not issued a generic communication.
6 So that's still on this chart.
7 Item 42 and 43 are related to 8 recommendations from the same Yttrium-90 microspheres 9 subcommittee for modifications to the Yttrium-90 10 microspheres licensing guidance. You will hear from 11 that subcommittee later on today as well.
12 Items 44 through 53 are related to the 13 NorthStar licensing guidance. While this licensing 14 guidance was issued a couple of years ago, we've left 15 these items on the chart until, as the ACMUI 16 requested, the NRC staff issue its memorandum to the 17 committee to inform you of how we dispositioned your 18 recommendations.
19 We had anticipated that this memorandum 20 would come this week. But since it has not, we will 21 leave these items on the chart until it does come 22 forth. So I suspect that we will request that there be 23 a motion at the fall meeting to close these items.
24 But until then, they will remain on these charts.
25 22 Okay. So that brings me to the 2017 1 recommendations and actions chart.
The first item is 2 that the committee requested the changes to the Part 3 35 rulemaking be reviewed and discussed at the ACMUI 4 meeting. At the time that the recommendation was 5 made, the rule had not been published yet. However, 6 it has been published and it went into effect in 7 January of this year for NRC licensees. So you will 8 hear a presentation from Ms. Lisa Dimmick today at 9 10:45 a.m. regarding the Part 35 rule.
10 Items 13 through 20 are related to the 11 medical event reporting and im pact on medical licensee 12 patient safety culture subcommittee's report. Excuse 13 me. I have left these items as open on the chart 14 because, again, a memorandum has not come forth to the 15 committee to inform you of how NRC has dispositioned 16 your recommendations. My understanding is that I 17 think Mr. Doug Bollock perhaps gave a presentation a 18 year ago. But again, no formal recommendation, so 19 these items will stay on the chart.
20 Okay. This brings us to 2018. Item 1 and 21 Item 2 are related to the nursing mothe rs' guidelines 22 subcommittee report. These two items are also tied to 23 a couple of other items later on the chart. But the 24 subcommittee finalized that report. The ACMUI 25 23 endorsed the report with a modification for some 1 language regarding FDA approved radioph armaceuticals.
2 That was passed at the September meeting.
3 However, we have left these open because 4 my understanding is that, one, a memorandum has not 5 been issued to the ACMUI, and two, the intent is that 6 the NRC staff consider this as part of its changes to 7 Regulatory Guide 8.39. So until such time, this item 8 will also stay open on the chart.
9 Items 3, 4, and 5 are related to the 10 physical presence requirements subcommittee report.
11 They were also superseded by the subcommittee's report 12 that was presented at the fall 2018 meeting related to 13 the Leksell Gamma Knife Perfexion and Leksell Gamma 14 Knife Icon licensing guidance.
15 So for Items 3 through 5, and I'll have to 16 follow up with the other item that corresponds to 17 this, I have marked these as closed. And this is my 18 asking the committee if there is a motion to close 19 Items 3 through 5 because the NRC staff issued the 20 licensing guidance on January 29th of this year. And 21 the subcommittee report that came forth from the 22 committee stated that the committee endorsed the NRC 23 agreement state working group's draft guidance.
24 So at this time, is there a motion?
25 24 MEMBER ENNIS: So moved.
1 MS. HOLIDAY: Dr. Ennis. Is there a 2 second? 3 MEMBER DILSIZIAN: Second.
4 MS. HOLIDAY: And do we have a vote to 5 close these items?
6 CHAIRMAN PALESTRO: All in favor?
7 MS. HOLIDAY: It's unanimous. Thank you.
8 Okay. Thank you.
9 Item 6 and Item 7 are both open 10 indefinitely. Items -- this is where NRC staff took 11 an action to create a recommendations web page.
12 Again, this is so that the ACMUI and future members 13 and members of the public are able to see historical 14 information as it relates to the recommendations and 15 actions that have come forth from this committee. So 16 last year, that website went live and we anticipate 17 updating it at least on an annual basis.
18 Item 7 is where we, NRC staff, agree to 19 send out a medical list server announcement to inform 20 the ACMUI -- to inform members of the public who are 21 subscribed to the list server every time that the 22 medical event slides are posted onto the medical tool 23 kit. These slides are for the PowerPoint 24 presentations that both the ACMUI gives and that the 25 25 NRC staff gives.
1 As are you aware, in the springtime, the 2 NRC staff provides that presentation.
And in the fall 3 time, the ACMUI subcommittee provides that 4 presentation. And all of the presentations have been 5 loaded, including the subcommittee's slides from the 6 most recent fall 2018 meeting.
7 Okay. Item number 9 is the other item 8 that was related to the physical presence requirements 9 for the Leksell Gamma Knife Icon subcommittee. So 10 similar to Items 3 through 5, I am asking if there is 11 a motion to close Item number 9. Dr. Ennis. Is there 12 a second?
13 VICE CHAIRMAN METTER: Second.
14 MS. HOLIDAY: Dr. Metter.
15 CHAIRMAN PALESTRO: All in favor?
16 MEMBER SCHLEIPMAN: I just had a quick 17 question.
18 MS. HOLIDAY: Yes.
19 MEMBER SCHLEIPMAN: I realize after I 20 voted. I think my security clearance is still --
21 MS. HOLIDAY: No, you have a full security 22 clearance, Dr. Schleipman.
23 MEMBER SCHLEIPMAN: Okay, thank you. They 24 were just in my office.
25 26 (Simultaneous speaking.)
1 MS. HOLIDAY: No, you are perfect. Thank 2 you. 3 MEMBER SCHLEIPMAN: Thank you.
4 MS. HOLIDAY: Okay. Item 11 is, again, 5 tied to the nursing mother guidelines subcommittee 6 report. As I stated not too long ago, this item will 7 be left open until the NRC staff dispositions it and 8 considers it as part of the revision to Regulatory 9 Guide 8.39.
10 Oh, Item 12 is also related to the Leksell 11 Gamma Knife Perfexion Icon. Is there a motion to 12 close Item 12? Dr. Ennis and Dr. Metter. Is there a 13 vote? It is unanimous.
14 Okay. Item 13 is where NRC staff 15 committed to providing the ACMUI with a copy of the 16 briefing on the Agency Action Review Meeting, also 17 known as the AARM, specifically, the presentation 18 slides related to the Yttrium-90 microspheres.
And I 19 believe Ms. Kellee Jamerson pr ovided that to the ACMUI 20 last week.
21 So at this time, I'd like to ask if there 22 is a motion to close Item 13.
Dr. Metter. Do we have 23 a second? Dr. O'Hara. And is there a vote? It is 24 unanimous. Thank you.
25 27 Item 14, Dr. Palestro amended the 1 membership of the training and experience for all 2 modalities subcommittee. I've left this item on here 3 because, for obvious reasons, this subcommittee is 4 still active.
5 Okay. Item 15, Dr. Palestro formed a 6 subcommittee to review the germanium/gallium-68 7 pharmacy grade generator licensing guid ance. We will 8 hear from that subcommittee later on today with their 9 subcommittee report.
10 Item 16, Dr. Palestro formed a 11 subcommittee to review the revisions to Regulatory 12 Guide 8.39, release of patients administered 13 radioactive material. Excuse me. The draft 14 Regulatory Guide 8.39 -- no, sir.
Thank you. Pardon 15 the interruption. The draft Regulatory Guide 8.39 was 16 provided to the respective subcommittee members last 17 week. And we anticipate that there will be a 18 teleconference this summer to receive the 19 subcommittee's recommendations and to have a 20 discussion with the committee.
21 Item 17, Dr. Palestro formed a 22 subcommittee to review Yttrium-90 microspheres 23 brachytherapy sources and devices, TheraSphere and 24 SIR-Spheres licensing guidance. We will hear from 25 28 that subcommittee later on today.
1 Item 18, Dr. Palestro formed a 2 subcommittee to review and update the ACMUI bylaws as 3 needed, including a review of the role of the ACMUI 4 chair in his or her participation on subcommittees.
5 We will hear from that subcommittee tomorrow.
6 Item 19, Dr. Palestro formed a 7 subcommittee to review the appropriateness of the 8 required elements of medical event reporting, the 9 adherence to these requirement s, and recommend actions 10 to improve reporting. We will hear from that 11 subcommittee later on today. The subcommittee's 12 report for this particular top ic is an interim report.
13 Item 20, the committee recommended that 14 the NRC draft an information notice on the best 15 practices that could help prev ent medical events. The 16 NRC staff accepted this recommendation and will draft 17 such a generic communication pending resource 18 availability.
19 Item 21, the committee requested a list of 20 all of the current ACMUI members, their contact 21 information, information regar ding each member's term, 22 and the subcommittees they serve on. The committee 23 also requested that the NRC staff create a web page 24 that lists the active subcommittees and subcommittees 25 29 that have been sunset, their members, the term 1 expiration, NRC staff resource, and the specific 2 charge of the subcommittee.
3 I perhaps have jumped the gun putting 4 closed on this. However, the latter part of the 5 action, we did create ACMUI subcommittee's web page, 6 and that went live yesterday. And this information 7 was shared with the committee last night. And I do 8 have a contact sheet which will be circulated. So 9 perhaps we will review closing this item during the 10 administrative closing part tomorrow.
11 Item 22, the committee tentatively 12 scheduled the spring 2019 meeting for April 15th and 13 16th. And alternate meetings date are April 3rd and 14 4th subject to Commission availability. We're here 15 today. It's April 3rd. Is there a motion to close 16 this item? I saw Dr. Ennis and Dr. Metter. Is there 17 a vote to close this item? It is unanimous.
18 Okay. We're on our last chart. So as I 19 stated earlier, we had a teleconference meeting in 20 February, specifically February 26th, to receive the 21 subcommittee's report as it related to the training 22 and experience requirements for authorized users under 23 35.390. 24 Item 1, the committee recommended adding 25 30 language into the report regarding the committee's 1 desire to work with the NRC staff to develop a 2 curriculum for limited scope authorized user pathway. 3 So that language was added into the final report.
4 And Item 2 is that the committee endorsed the training 5 and experience requirements for all modalities 6 subcommittee report and the recommendations included 7 therein. 8 So I guess my question to the committee 9 is, is there a motion to close either items? My 10 recommendation would be that the committee close Item 11 1 because that's an administrative item just to add 12 the language into the report.
However, the committee 13 may consider leaving Item 2 open as the NRC staff has 14 not done anything in terms of issuing any revisions or 15 putting out an official statement on whether or not 16 there will be changes to 35.390 17 VICE CHAIRMAN METTER: I move that we 18 close Item 1.
19 MS. HOLIDAY: Did you hear that, court 20 reporter? Okay. So for the record, Dr. Metter made 21 the motion. Dr. Schleipman seconded. Is there a 22 vote? It is unanimous.
23 Okay. That concludes old business. Yes 24 ma'am? 25 31 MEMBER WEIL: I had a question for you.
1 If you can just go back to 2016, Item 39. This 2 relates to the generic communication about tubing 3 issues. 4 MS. HOLIDAY: Yes.
5 MEMBER WEIL: So that's a 2016, and it's 6 2019. And it's still open. Can you explain that?
7 MS. HOLIDAY: Dr. Katie Tapp will come to 8 the microphone to address your question.
9 DR. TAPP: This is Dr. Tapp. That generic 10 communication was in regard to the Yttrium-90 11 microsphere brachytherapy and specifically it was in 12 regard to kinking, connection, hub, et cetera. When 13 the staff began evaluation of that, we realized that 14 the kinking and connection was related to the catheter 15 and the selection of the cathe ter. And we were really 16 delving into that and determined that was very much 17 practice of medicine. And we were concerned if we 18 issued guidance, we would be providing something that 19 would be interfering with the practice of medicine.
20 What the staff is considering now is 21 issuing a generic communication in a careful manner 22 that just alerts licensees that these are happening 23 and that they have to be diligent in their selection 24 with other medical events related to Y-90 and ways to 25 32 prevent them. So we are working on that one now to 1 close it. But in 2016, we evaluated it and just 2 didn't release it at that time.
3 MEMBER WEIL: So when do you expect this 4 communication to be available? I mean, it's been 5 three years. Patients are endangered. And I'm not 6 sure I agree with you that it's a practice in medicine 7 issue but defer to NRC policy on that. It just seems 8 to me that this is not a complicated thing and that I 9 think the medical community would appreciate the 10 notification.
11 DR. TAPP: We do expect that to be out 12 this year.
13 CHAIRMAN PALESTRO: Any other comments or 14 questions from the committee?
15 MEMBER OUHIB: I'm just curious. If there 16 is such what I consider as a defect perhaps, should 17 that fall under the FDA?
18 MEMBER O'HARA: If it is a product defect, 19 it does fall under the FDA. It would be our 20 jurisdiction to look at it.
21 MEMBER OUHIB: Right. So would you 22 consider this as a defect, the kinking? If a catheter 23 is kinking which should not be?
24 MEMBER O'HARA: I can't talk about FDA's -
25 33
- what we're currently doing. But we are looking at 1 that. 2 CHAIRMAN PALESTRO: Thank you. Any other 3 comments or questions? Mr. Sheetz?
4 MEMBER SHEETZ: The NRC may want to 5 consider including this recommendation on appropriate 6 catheter use for Y-90 microsph eres and including it in 7 the guidance document that was requested from the 8 subcommittee on best practices to avoid a medical 9 event. Because that was one of the issues that was 10 brought up with respect to the Y-90 microspheres. So 11 you may be able to accomplish both items with one 12 guidance document.
13 CHAIRMAN PALESTRO: Any other comments, 14 questions? Right. Move on to the next item on the 15 agenda which is the open forum.
Are there any topics, 16 medical topics of interest that anyone wishes to bring 17 up for discussion? Dr. Ennis?
18 MEMBER ENNIS: Actually, this really is 19 just kind of a continuation of the prior conversation.
20 I was going to ask the same thing as Ms. Weil, and 21 there's some things from 2017 that also are still 22 open. I'm wondering whether this committee needs to 23 look at timeliness of the responsiveness and perhaps 24 make some recommendations about improving that.
25 34 CHAIRMAN PAL ESTRO: Actually, you raise an 1 interesting point, Dr. Ennis. One of the questions 2 that I have is some of these items are open because 3 the memorandum from staff has not been issued yet.
4 And I believe, and there were a lot of items, that 5 some of them go back perhaps two years; is that 6 correct? So is there a requirement or a definition of 7 timeliness for such a memorandum?
8 MS. HOLIDAY: NRC staff doesn't have a 9 defined date for when it should issue. We do try our 10 best to be timely in our responses to both ACMUI and 11 members of the public. However, as you guys are 12 aware, the medical team has suffered great resource 13 constraints. I, myself, was gone for roughly nine 14 months, and there have been some rotations and other 15 shifts on the team as well.
16 So we've had to prioritize our work based 17 on the direction that we received both from the 18 Commission and from our senior management. However, 19 the -- for example, the NorthStar guidance memorandum, 20 the staff member that was responsible for that has 21 been directed to other projects as well. And 22 understanding that, just like the ACMUI members here, 23 everybody is a subject matter expert for their 24 respective field. And so the individuals that are 25 35 responsible for some of these items, they are one of 1 the few that can also respond to them.
2 However, we have tried our best to try to 3 go back and go through the charts and resolve any open 4 items to the best of our ability. The NorthStar 5 guidance memorandum should be coming out ideally by 6 the end of this week or next week. So for things like 7 that with the memorandums, some of it may be 8 oversight. Some of it may just be resource 9 constraints.
10 But ideally, we do our best to -- and this 11 is a Sophie fictitious time line. We try to issue a 12 memorandum reasonably within 60 days. But sometimes 13 that can't happen because of other higher priority 14 work issues.
15 MR. EINBERG: Dr. Palestro?
16 CHAIRMAN PALESTRO: Yes, Mr. Einberg?
17 MR. EINBERG: Yeah, Chris Einberg here.
18 Yeah, thank you, Sophie, for that explanation. We'll 19 take a look at the list and go through there and see 20 if we can prioritize these and make sure that they get 21 closed in a timely fashion.
22 CHAIRMAN PALESTRO: Thank you. Other 23 comments? Dr. Dilsizian?
24 MEMBER DILSIZIAN: Thank you, Dr.
25 36 Palestro. Recently, we received an important drug 1 safety information from the FDA. It's relating to 2 CardioGen Rubidium-82 generator which is used quite 3 commonly for myocardial perfusion imaging. And the 4 subject matter is that there's been a recent shortage 5 in normal saline. And you need the normal saline to 6 do the generator.
7 And the pharmacies have been sending 8 instead of normal saline Lactated Ringer's solution.
9 The problem with the Lactated Ringer's solution is 10 that it has calcium in it and that's not good because 11 calcium exchanged with stronti um results in strontium-12 82 and strontium-85 with half-lives of 30 days or a 13 month, 25 days or two months. And that goes to bone 14 marrow and results in excess radiation exposure to 15 patients.
16 The memo says patients were exposed to 17 such high levels of radiation. I guess that's how 18 they found out about it.
And the question is, is this 19 simply a medical event or shou ld the NRC be addressing 20 this? 21 CHAIRMAN PAL ESTRO: Comments, responses to 22 Dr. Dilsizian?
23 MEMBER GREEN: This is Mr. Green. Not 24 having read the directions for use for the CardioGen 25 37 or the Ruby-Fill, I'm fairly certain that the license 1 commitments when a licensee obtains one or permission 2 to have one, they commit to following the 3 manufacturer's directions for use. And apparently, if 4 they're substituting other solutions for elution 5 purposes, they're not following directions for use.
6 DR. HOWE: This is Dr. Howe. The events 7 have been happening in the state of Colorado which is 8 an agreement state. And we have been in contact with 9 Colorado, and there were medical events associated 10 with it. 11 My understanding is that a patient that 12 had a strontium rubidium proce dure was at the hospital 13 for a different reason. And a survey was done, and 14 they were determined to be radioactive when they 15 weren't expected to be. And that's how the events 16 were identified, then they went back and saw that they 17 had about eight medical events --
six to eight with a 18 strontium breakthrough. It was too high. So we do 19 have medical events. Okay?
20 But we don't have all the information yet.
21 Colorado is still collecting information.
And we're 22 anticipating putting out maybe a generic communication 23 to remind people about the issues associated not only 24 with this series of medical ev ents which was a Lugol's 25 38 solution with the calcium. But also the previous one 1 from Nevada and Florida where individuals were not 2 eluding the generators correctly or were overusing the 3 generators.
4 There was also an issue here with the 5 licensee not understanding that the generators had 6 breakthrough even though they were performing a 7 breakthrough measurement. So there are many issues 8 here. 9 CHAIRMAN PALESTRO: I think the question 10 is -- or certainly one question that arises is, can 11 the NRC do anything proactively to reduce the 12 likelihood of some of these events occurring?
13 DR. HOWE: We already have guidance and 14 requirements for licensees to perform the breakthrough 15 test. We have new requirements that went into effect 16 in January for licensees to report breakthrough when 17 they discover it to the NRC and to the distributor 18 within seven days. So we have regulatory elements 19 that would help discover these. But when you've got 20 individuals that are doing bre akthrough and they don't 21 understand the results that they're getting and they 22 don't identify that they have breakthrough in a timely 23 matter. It is an issue.
24 So that is our biggest problem right now 25 39 is people don't appreciate that they have breakthrough 1 and don't take quick action on it. It's set up so 2 that they -- if they recognize breakthrough, they 3 should not be using the material on patients. But 4 because they're not recognizing, patients are getting 5 overexposed.
6 CHAIRMAN PALESTRO: Thank you.
7 MS. KUBLER: Hi, good morning. Caitlin 8 Kubler with the Society of Nuclear Medicine. We were 9 also alerted to this and we have had a couple 10 different conference calls. And we are working with 11 ASNC. We are actually schedul ed to send out a release 12 to our members to remind them that this is standard of 13 practice.
14 We did some informal surveying amongst our 15 members, and the feedback that we got was positive, 16 that most of our members are aware that this is 17 standard of practice. The Lactated Ringers are not 18 supposed to be used. The feedback that we did get 19 where those situations occurred were incorrect or it 20 was an accident, the person that grabbed the 21 accidental Lactated Ringer and then did not notice 22 that they had done so.
23 So we are sending that alert out with ASNC 24 today just to remind our membe rs that this is standard 25 40 of practice and to be aware. And if there is a 1 situation that they have notic ed a Lactated Ringer has 2 been attached, to immediately stop the infusion. And 3 of course, we work with Bracco to make sure that the 4 language that we are sending out is accurate and what 5 is required.
6 Thank you.
7 CHAIRMAN PALESTRO: Mr. Ouhib?
8 MEMBER OUHIB: Yeah. I guess my feeling 9 is listening to this, should the manufacturer send out 10 a notice that all users should respond to with some 11 sort of a form that they will have to sign and confirm 12 that they fully understand the process? This is 13 something that probably needs to be done in my 14 opinion. 15 CHAIRMAN PALESTRO: I'm not sure that 16 that's the responsibility of the NRC to send out that 17 sort of form. Mr. Einberg?
18 MR. EINBERG: I'm not sure. I was going 19 to ask if Dr. O'Hara wanted to comment and see if 20 that's an FDA responsibility.
21 MEMBER O'HARA: The FDA is looking -- has 22 been looking into this issue. The FDA sent out the 23 dear -- I call a dear doctor letter to inform people 24 of the issue. And they are working with the sponsor 25 41 on various corrective actions.
1 CHAIRMAN PALESTRO: Thank you. Any other 2 comments or questions from the committee? Attendees 3 in the room? Bridge line? Dr. Dilsizian, does that 4 answer your question?
5 MEMBER DILSIZIAN: Yes. It seems to me 6 that FDA is addressing this is sue and that the medical 7 events will be reported, the medical events. So 8 that's, I guess, all that NRC can do at this point.
9 Thank you.
10 CHAIRMAN PALESTRO: Dr. O'Hara?
11 MEMBER O'HARA: Also the medical events 12 end up in the medical event database. It's at FDA 13 too. 14 CHAIRMAN PALESTRO: Thank you. The next 15 item on the agenda is the Yttrium-90 microspheres 16 brachytherapy licensing guidance subcommittee report. 17 It'll be presented by Dr. O'Hara.
18 MEMBER O'HARA: Next slide, please. I'd 19 like to thank the subcommittee members, Dr. Dilsizian, 20 Ms. Martin, Dr. Metter, Dr.
Ouhib, and Dr. Schleipman 21 for their efforts on this. And I would also like to 22 thank Katie Tapp for being the expert. It occurred 23 during a time when FDA was partially shut down, and I 24 was not officially allowed to work on any of this. So 25 42 I do appreciate everybody's efforts.
1 For background, this is a manual intra-2 arterial brachytherapy implant with unique properties 3 for primary and secondary hepatic malignancies. It's 4 regulated under 10 CFR 35.1000 and titled, other 5 medical uses of byproduct materials or radiation from 6 byproduct materials. Next slide, please.
7 The licensing guidance was published in 8 2002 and revised in 2004, '07, '08, '11, and '16.
9 October '16, the ACMUI provided comments on the 10 initial draft revision 10 of the licensing guidance.
11 Specific topics that were addressed included 12 consideration of the elimination of Pathway 2, a 13 manufacturer of the authorized user training, update 14 of waste and disposal section and review Y-90 15 radiation safety issues in autopsy and cremation.
16 Next slide, please.
17 November 2017, the NRC published a draft 18 on revision 10 of the licensing guidance in the 19 Federal Register for public comment. The comment 20 period ended in January 2018. In July of 2018, the 21 final Part 35 rule, Medical Use of Byproduct Material-22 Medical Events, Definitions, T raining, Experience, and 23 Clarifying Amendments, was iss ued. The rule went into 24 effect January 14th, 2019 for NRC licensees. Oh, 25 43 sorry. I was waiting for you to change it.
1 The NRC agreement state working group 2 updated the draft revision to licensing guidance to 3 include the criteria for training and experience and 4 medical events reporting, inventory requirement 5 specifications, and waste disposal issues and align 6 the guidance with Part 35 rule. After addressing 7 public comments, the 2016 ACMUI comments, and the rule 8 changes, the working group provided the subcommittee 9 with revised draft guidance for its review and 10 comment. 11 Our charge for this subcommittee was to 12 review the staff's draft revis ion 10 of the Yttrium-90 13 microspheres brachytherapy source and devices, 14 TheraSpheres and SIR-Spheres l icensing guidance and to 15 provide any comments or recommendations for change or 16 acceptance of the guidance.
17 The subcommittee believes that this is a 18 well-written and well-documented licensing guidance 19 document. The subcommittee endorsed the draft 20 revision 10 of the licensing guidance subject to the 21 following changes.
22 We believe that the manufacturer's 23 representative for training should be documented. We 24 also feel that three hands-on cases for each type of 25 44 microsphere delivery device should be kept. The Y-90 1 spheres are slightly different, being glass or 2 polymeric, and the delivery sy stems of the two devices 3 are slightly different. We also feel the RSO 4 familiarity would require all device uses at the 5 facilities. So the RSO should be familiar with both 6 manufacturers' devices.
7 Evaluation of a possible medical event for 8 unexpected dose or activity to an organ or tissue 9 other than the treatment site that is caused by 10 catheter placement should be looked at as a medical 11 event. Next slide, please.
12 Delineating the site to be treated more 13 specifically is another recommendation, i.e., left 14 hepatic lobe or right hepatic lobe. Adding activity, 15 date of administration and route of administration 16 should also be looked at. We question whether the 17 term, intervention, should be defined in the licensing 18 guidance document. And last, the explicit labeling 19 should include patient's name, dose, date, and 20 treatment site, if feasible. Next slide.
21 That's it. I'd like to make one point to 22 our earlier discussion. The FDA is also under -- I 23 was going to use the word, dif ficulty. But it's not a 24 difficulty. The FDA does not
-- we don't regulate the 25 45 practice of medicine. So if an interve ntionalist, at 1 his or her own insistence, changes the catheter, we 2 usually don't have much to say about that. And I just 3 wanted to make that clear.
4 CHAIRMAN PALESTRO: Comments or question 5 from the committee? Excuse me, from the subcommittee 6 first. Comments or questions from the committee?
7 Dr. O'Hara, I have two questions regarding 8 the slides, specific comments on the licensing 9 guidance. Your first bullet says, defining the 10 manufacturer's representative. I'm not sure I 11 understood that. Does that mean stating the 12 individual's name, or does it mean listing the 13 qualifications of the individual or both?
14 MEMBER O'HARA:
Listing the qualifications 15 of the individual.
16 CHAIRMAN PALESTRO: Okay. And then my 17 second question on that same slide, further down, it 18 says, RSO familiarity required with all devices used 19 at the facility. Is there a more precise or a more 20 structured term other than familiarity?
Because that 21 could be taken in a lot of different ways.
22 MEMBER O'HARA: What I meant was that the 23 RSO should be experienced with both delivery devices 24 and on both manufacturers' devices.
25 46 CHAIRMAN PALESTRO: Thank you. Any other 1 comments or questions from the committee? From 2 attendees in the room? Dr. Tapp?
3 DR. TAPP: Dr. O'Hara, I just had a quick 4 clarification. On this slide and the comment -- the 5 next slide, the delineation of the site to be treated 6 more specifically. You said, for example, left 7 hepatic lobe, right hepatic lobe. Are those just 8 examples for the staff to consider, or are those the 9 recommendation of the --
10 MEMBER O'HARA: Examples to consider.
11 DR. TAPP: Thank you.
12 CHAIRMAN PALESTRO: Any other comments or 13 questions from attendees here in the room? From the 14 bridge line?
15 MS. HOLIDAY: I'm not showing any.
16 CHAIRMAN PALESTRO: Ms. Holiday, at this 17 point, do we move to -- all right.
18 MS. HOLIDAY: Yes. Is there a motion to 19 approve the report and the recommendations as stated?
20 Sure. Dr. Dilsizian has a question.
21 MEMBER DILSIZIAN: I guess bullet number 22 three, how does the staff handle that? When we say, 23 question whether the term, intervention, should be 24 defined or not, how do we address that?
25 47 MS. HOLIDAY: Dr. Tapp, I think that 1 question was directed for you.
2 DR. TAPP: Sure. I think in the written 3 report, it was clear that it was a recommendation if 4 the staff believed patient intervention was defined 5 and to provide more definition into the guidance to 6 make it clearer to the user.
So the working group can 7 add the patient intervention and clearer for the user 8 to see. 9 CHAIRMAN PALESTRO: Dr. Metter?
10 VICE CHAIRMAN METTER: I have a question 11 regarding the last bullet point there about the 12 explicit labeling to include the patient name. Is 13 that part of what we need to do, or is that -- can you 14 just explain that whole bullet point there?
15 MEMBER O'HARA: There was discussion 16 amongst the subcommittee that if it was feasible, all 17 of that information should be provided from the person 18 doing the intervention. I forgot the exact 19 phraseology. But it wasn't clear that all of that 20 information could be found in a small label. That's 21 what I meant by feasible.
22 VICE CHAIRMAN METTER: Oh, the label?
23 MEMBER O'HARA: Yeah.
24 VICE CHAIRMAN METTER: You mean the 25 48 labeling of the dose?
1 MEMBER O'HARA: Yes.
2 VICE CHAIRMAN METTER: I understand.
3 Thank you.
4 CHAIRMAN PALESTRO: Mr. Ouhib?
5 MEMBER OUHIB: Yes.
This is actually just 6 a clarification because there was a medical event 7 where there were two different doses. And by 8 accident, the wrong dose was actually a dministered to 9 the wrong patient. And therefore, the vial should be 10 explicitly labeled so that way people will not make 11 those sorts of mistakes.
12 CHAIRMAN PALESTRO: Dr. Schleipman?
13 MEMBER SCHLEIPMAN: If I could just add, 14 the current sentence prior to that recommendation 15 read, label syringes and syrin ge radiation shields for 16 the radioactive drug. And we felt perhaps that wasn't 17 sufficient enough to promote p atient safety as in that 18 event. Added that, where feasible, it should also be 19 identification of the patient receiving that dose.
20 CHAIRMAN PALESTRO: Thank you. Yes?
21 MS. FAIROBENT:
Lynne Fairobent, member of 22 the public. Dr. O'Hara, if we could go back and just 23 revisit the bullet on the RSO familiarity again 24 because I got more confused listening to your 25 49 clarification.
1 I'm not sure in all cases that the RSO 2 would have experience with the devices. They would 3 have familiarity with the rad protection and rad 4 safety aspects of the devices. But I'm not sure what 5 type of experience you are referring to with it 6 because the RSO would not be the one that would be 7 involved in the use, only simp ly in the rad safety and 8 the rad protection of it.
9 MEMBER O'HARA: I think that is what the 10 subcommittee members wanted was familiarity with both 11 types of devices.
12 MS. FAIROBENT: Thank you.
13 CHAIRMAN PALESTRO: Mr. Green?
14 MEMBER GREEN: To follow up on the -- on 15 Dr. Schleipman' s comment. It's line 16 where they 16 say the patient label syringes and radiation syringe 17 release and labels with the radioactive drug.
18 I just want to point out that neither of 19 these SIRTS products are drugs. Their license is 20 medical devices. And that term should be device type 21 but not drug.
22 MEMBER O'HARA: Yes. That's correct.
23 CHAIRMAN PAL ESTRO: Thank you. Mr. Ouhib?
24 MEMBER OUHIB: Yeah. Just to comment on 25 50 the RSO. I think it's not necessarily using it per 1 se. Because there are other people involved in that. 2 But the event -- in the event that there 3 is a malfunction or something that went wrong, the RSO 4 should understand the device itself. And be able to 5 sort of evaluate and make some recommendation or 6 intervene or what not.
7 CHAIRMAN PALESTRO: Thank you. Mr.
8 Sheetz, not to put you -- I was just going to ask you 9 if you would comment because you're the RSO 10 representative here.
11 MEMBER SHEETZ: Thank you. I think it's 12 very important for the RSO to understand the delivery 13 apparatus. Understand all the plumbing, the 14 connections, the limitations, catalysts that are 15 appropriate for use with that device and so forth.
16 While they are not typically involved in 17 the administration process, it's very important for 18 them to understand that device. And all the aspects 19 of it and how it works.
20 So, I support the Subcommittee's position 21 on that. 22 CHAIRMAN PALESTRO: Thank you.
23 MS. COCKERHAM: This is Ashley Cockerham 24 with Sirtex Medical. To add onto what Mr. Sheetz just 25 51 said. 1 The -- for Sirtex, they would provide 2 manufacturer training specific to the RSO. And 3 provide certification and documentation of that 4 training specific to that device.
5 And they are very different devices with 6 different training. And it would be completely 7 different on the nuke med side and the administration 8 as a whole.
9 So, I would think for each device is very 10 specific. The training is dif ferent for both of them.
11 And that the manufacturers are able to support that 12 at least from the Sirtex side I can attest to that.
13 On the labeling, I wanted to make one 14 quick comment on the syringe shields.
And so I guess 15 this would only apply on the SIR-Sphere side because 16 there's an actual dose draw.
17 I think the way that the guidance is 18 currently written, it's actual ly impractical to label.
19 You would be covering what you're trying to see 20 through the syringe shield.
And that's not something 21 that would actually go to the patient anyway.
22 So, to back up a step, a shipping vial 23 would come in with SIR-Spheres in it. And they would 24 remove using the syringe and syringe shield, a portion 25 52 of that specific to the patient.
1 And then they would inject that into 2 another vial. All of those are clear. And you need 3 to be able to see between one and three milliliters.
4 So these are small amounts. You need good 5 visual on this. And if you're putting labels over all 6 of that, it's not going into the patient room anyway.
7 You're drawing it up in the hot lab.
8 Using it there. And then you inject it into another 9 vial that's going to go actually into the patient 10 room. 11 That vial you also need to be able to see.
12 The physician is looking at it. And watching the 13 meniscus. So, if you're putting labels, or putting 14 things over this, that's going to be a significant 15 problem just to be able to see what the admin -- what 16 you're doing with the administration.
17 So, the shipping vial that comes in 18 complies with the labeling. And I think the intent.
19 But everything after that, I t hink we're kind of going 20 into a space where maybe more discussion could be had 21 around that labeling.
22 CHAIRMAN PAL ESTRO: Thank you. Mr. Ouhib?
23 MEMBER OUHIB: I guess my question is for 24 the -- how would you avoid using the wrong dose for 25 53 the wrong patient?
1 If you have two cases that are sent back 2 to back. And you have two doses sitting there, how 3 would you -- what would the manufacturer recommend?
4 MS. COCKERHAM: I don't have a quick 5 answer for you. I was going to say, I feel like there 6 -- we need more discussion on it.
7 Because you've got a clear acrylic, you 8 know, you've got 360 view on it. And you've got to be 9 able to see it.
10 I don't know where you realistically put a 11 label. Because you're watching the spheres as you're 12 administering.
13 That visual feedback is -- is critically 14 important. On the cart?
15 MEMBER OUHIB: I fully understand that.
16 But I think whatever we introduce, we have to make 17 sure that it does not introduce additional errors per 18 se. 19 CHAIRMAN PALESTRO: Dr. Schleipman?
20 MEMBER SCHLEIPMAN: I would just agree 21 that you do need to have that visual observation.
22 But, there are transports --
23 MS. HOLIDAY: Dr.
Schleipman, can you make 24 sure your microphone is on?
25 54 MEMBER SCHLEIPMAN: I'm pushing the -- oh, 1 there we go.
2 MS. HOLIDAY: Thank you.
3 MEMBER SCHLE IPMAN: Oh, totally agree that 4 you need that visual monitoring. But, if we could 5 make a -- perhaps make this less specific to vial.
6 But, at least that there is some patient 7 identification with the transports shield or what have 8 you. 9 MEMBER OUHIB: Perhaps further discussion 10 is needed.
11 MS. HOLIDAY: Mr. Ouhib, for everyone's 12 awareness, I do have someone on the webinar who is 13 responding to this comment. His name is Matthew 14 Williams.
15 And his response is that, they label the 16 top of the vial shield. Thank you.
17 MS. COCKERHAM: Okay. You could do that 18 with a sharpie on top.
19 CHAIRMAN PAL ESTRO: Okay. Any other? Dr.
20 Ennis? 21 MEMBER ENNIS: I would imagine if we or 22 NRC made a requirement, that the company would be 23 imaginative and come up with another design for the 24 device that would allow the important visualization.
25 55 But also, for reporting patient name and 1 other things for safety purposes.
2 MS. COCKERHAM: That's a big ask to 3 redesign it and get an FDA approved new device.
4 CHAIRMAN PALESTRO: Mr. Sheetz?
5 MEMBER SHEETZ: It's not clear to me if 6 the Subcommittee endorses retaining the alternate 7 pathway with the vendor training for the AUs. While 8 they're implying the three cases should be retained, 9 I'm not sure if there's -- I don't see a specific 10 statement to that.
11 And if you could comment?
12 CHAIRMAN PALESTRO: Dr. O'Hara?
13 MEMBER O'HARA: I think, and I don't want 14 to speak for the Subcommittee here, but I think we 15 are. 16 CHAIRMAN PALESTRO: Comments from the 17 Subcommittee? Mr. Sheetz?
18 MEMBER SHEETZ: I would like to make the 19 recommendation that does the draft guidance imply or 20 suggest removing the alternate pathway for vendor 21 training of AUs. And so I would recommend that that 22 AU pathway, alternate pathway remain.
23 And make this a very important pathway for 24 the authorized users. I think they do a very thorough 25 56 job of training its equivalent or superior to being 1 supervised by another authorized user.
2 So, I strongly endorse retention of the 3 alternate pathway for Y-90 microsphere authorized 4 users. 5 CHAIRMAN PALESTRO: Yes. Ms. Shober?
6 MEMBER SHOBER: Just a clarification on 7 that, on Mr. Sheetz' comment. With the alternate 8 pathway in number two that we're talking about, the 9 previous versions of the guidance had allowed a 10 physician to be named on a license before receiving 11 the three cases.
12 And at this point, could those -- do the 13 cases from the manufacturer need to happen -- does the 14 authorized user need to get named on the license 15 before those three cases happen?
16 Or are there sufficient preceptors around 17 to -- we could allow that second pathway through the 18 manufacturer. But, they would have to get those cases 19 before being named on the license.
20 Is that -- so, it's a question about 21 timing. It's very difficult from the regulator side 22 to put someone on a license when they're not fully 23 qualified, and then track whether or not someone is 24 allowed to preceptor another position.
25 57 And so I guess my comment on that is that 1 if we're talking about the sec ond pathway, can that be 2 structured so that manufacturers' training happens 3 before the physician is named on the license? If the 4 licensee chooses to use the manufacturer as the 5 preceptoring cases.
6 CHAIRMAN PALESTRO: Dr. Tapp?
7 DR. TAPP: The draft guidance did not 8 remove the manufacturers -- the pathway right now of 9 the working group. It just added a little bit more 10 requirements to that.
11 But they could still, the current draft is 12 still allowing the license to occur. And then the 13 three cases to happen.
14 They just had to be -- the three patient 15 cases would have to be supervised by a physician.
16 That was still in the draft.
17 CHAIRMAN PALESTRO: Any other comments?
18 Questions?
19 MS. COCKERHAM: This is Ashley Cockerham 20 again with Sirtex. I get to answer your question.
21 Unequivocally yes.
22 They need the ability to be able to --
23 their AUs are not going to voluntarily on their own 24 dime, visit other people's sites to train other 25 58 physicians. That's just not the reality of how it's 1 going to happen.
2 And it's not imbedded in every fellowship 3 program where every IR coming out is going to have the 4 hands-on cases, especially with both products.
5 Because their fellowship could be one product or the 6 other. 7 And so your pool is going to be 8 significantly limited of your fellows coming out with 9 specific hands-on training.
10 So, really the only way to open a new site 11 now where you're in the community hospitals and where 12 you're out further, not in the major academic centers, 13 that pathway has to exist. And the manufacturers 14 support that by providing someone to supervise.
15 CHAIRMAN PALESTRO: Ms. Shober?
16 MEMBER SHOBER: Yes. I mean, that's what 17 we expect from every other radiopharmaceutical 18 therapy. So I'm not sure why the microsphere is a 19 special case.
20 MS. COCKERHAM: I guess the difference is, 21 if you're doing iodine, and I'm not a physician. I 22 don't know if there are any physicians that could 23 attest to the fellowship if you're coming through 24 doing iodine therapy or another therapy.
25 59 But that's built into every fellowship.
1 It's standardized across the p rograms. How would that 2 look for Y-90 if you could explain how that was 3 different?
4 I understand it's different.
5 CHAIRMAN PALESTRO: Dr. Metter?
6 VICE CHAIRMAN METTER: Well thyroid for 7 thyroid therapy, which is originally 392 and 394, 8 these are imbedded within the training experience for 9 the radiologists and nuclear radiologists in nuclear 10 medicine, the radiation oncologists.
11 So it's embedded within their training at 12 the time of graduation. And so they have completed 13 the required therapies before graduations.
14 And then they apply to be on licenses 15 where they are -- they proceed to their practice.
16 So, I think Megan's question is, when are 17 they put on the license? Is that it?
18 MEMBER SHOBER: Yes. And I -- I mean, we 19 see this all the time with some of these other drugs 20 that are parenteral administrations.
21 So the same situation where you have 22 radiologists that want to do this at a community 23 hospital, but we require those physicians to have the 24 three cases somewhere. And then get on the license.
25 60 So, I just don't see this as a different 1 situation.
2 MS. COCKERHAM: So, I guess the getting it 3 somewhere is the issue from the physician perspective.
4 You can't go to someone else's hospital.
5 You can't treat someone else's patient.
6 You can't practice medicine in a hospital where you're 7 not credentialed and where -- or in a state where you 8 aren't authorized to practice medicine.
9 And so you have to treat your patient at 10 your hospital with your radioactive materials license.
11 And if you can't get the material on y our license to 12 get the experience, you're stuck in a situation of you 13 can't go elsewhere and get it, and it can't be brought 14 to you. 15 And so this was the whole between 2007, 16 '08, '09, and then 2011, the major revision happened 17 for -- to basically bridge that gap. To not have a 18 regulatory barrier.
19 CHAIRMAN PALESTRO: Mr. Sheetz?
20 MEMBER SHEETZ: Yes. Maybe I was not 21 clear previously. But that's the point I was trying 22 to make. For a new device, you're at a brand-new 23 facility, no one is an authorized user approved.
24 The only practical pathway is for the 25 61 vendor to come in and train that authorized user or 1 that physician to become an authorized user. They 2 actually do need to be named on the license so that 3 they can perform the procedure prior to being 4 supervised of doing their actual first live patient 5 case. 6 The same thing happens with gamma knife, 7 with the new model of the gamma knife that comes out, 8 the Gamma Part 1000. The vendor does the training for 9 the AU and the AMP.
10 They will do their first case with the 11 vendor representatives there with no previous 12 authorized user or AMP approved for that model of the 13 gamma knife. So this is a very similar situation.
14 And that was my point on having the vendor 15 training daily going into a new site and training the 16 AU, have them named on the license from the Mock Three 17 trials. They've been doing the patient cases then, 18 again, supervised by the vendor, because they're not 19 going to get another authorized user from another 20 facility to come in.
21 And as I pointed out, they're not going to 22 be able to go to another facility. They will not have 23 medical privileges to do that case at another 24 institution.
25 62 CHAIRMAN PALESTRO: Thank you Mr. Sheetz.
1 Ms. Shober, does that clarify things for you?
2 MEMBER SHOBER: I mean, I hear what people 3 are saying. I just don't agree with it.
4 CHAIRMAN PAL ESTRO: Thank you. Dr. Ennis?
5 MEMBER ENNIS: Just to help. I think the 6 difference Megan, is that one is just an intravenous 7 administration, which you can watch someone do, or 8 have someone watch you do.
9 And then you can have an authorized user 10 doing that for you. As opposed to actually 11 technically doing the procedure.
12 There's just no way to get that experience 13 unless you're actually doing it. And having a 14 physician there doesn't really gain you anything, 15 because you actually have to do it.
16 So, I think there is a distinction to be 17 made between procedure type of training necessary 18 versus an intravenous administration.
19 CHAIRMAN PALESTRO: Ms. Martin?
20 MEMBER MARTIN: What type of experience 21 are you looking for to add that physician, if any, to 22 a license? Because it is sort of the cart before the 23 horse. 24 You have to add the physician with no 25 63 experience to the license with some provision (audio 1 interruption) --
2 CHAIRMAN PAL ESTRO: Could you repeat that, 3 Ms. Martin? It was cut off at the end.
4 MEMBER MARTIN: I was just wondering what 5 type of provision, or how is the process approved to 6 add a license, following up on Megan's question.
7 To add a physician with zero experience to 8 a license to perform these procedures? Because that's 9 what you're doing.
10 If they're waiting for a manufacturer to 11 train them, you're having to add them to your license 12 with no experience in sort of good faith that they're 13 going to have a manufacturer's representative come in 14 there and train them.
15 Is that --
16 CHAIRMAN PALESTRO: Dr. Tapp?
17 DR. TAPP: Yeah. This is Dr. Tapp. And 18 this alternate pathway is both in the draft and in the 19 current guidance.
20 There is training requirements before 21 these three cases. All those training requirements 22 have to be completed before they're issued on the 23 license. 24 Those are the T&E hours, similar to other 25 64 modalities. There are manufacture or other AU 1 training on the device itself.
2 And if they do not have the three patient 3 cases prior to the license, they have to have three 4 mock cases. So, after the license, is only the three 5 actual real live patient cases.
6 To actually run through the full thing 7 with a patient. So that's what's proposed after the 8 license. 9 And it's currently in guidance. And 10 that's what's in the draft.
11 CHAIRMAN PALESTRO: Ms. Martin, does that 12 answer your question?
13 MEMBER MARTIN: Yes.
14 CHAIRMAN PAL ESTRO: Thank you. Mr. Ouhib?
15 MEMBER OUHIB: I just want to switch gears 16 to another area that was of concern to me. And that 17 is the cremation component of these patients.
18 When I first thought about it, I thought 19 perhaps that took practice guidelines. But the more I 20 think about it, the more I feel like maybe not.
21 And looking at patient instructions, for 22 instance, prior to the procedure, if, you know, with -
23 - and patient instructions are the rules. You have to 24 provide patient instructions.
25 65 That's when you submit your -- and I 1 think, and I really feel like that perhaps in the 2 patient instructions, that should be in there.
3 That you cannot be cremated for such a 4 procedure. Because all, you know, the items can be 5 listed there.
6 And then therefore the patient would know 7 up front, prior to the procedure, that that is an 8 absolute no no. If their wish is to be cremated, 9 therefore they can make a decision prior to the 10 procedure, and it's not to go forward with it.
11 I really wrestled with that. But, I think 12 I came to a conclusion that perhaps that should be 13 part of the patient instructions.
14 CHAIRMAN PALESTRO: Any comments on that?
15 Ms. Martin?
16 MEMBER MARTIN: I would support Mr. -- the 17 comments made already about cremation. Because 18 serving as an RSO, it -- in an active h ospital in Los 19 Angeles, we've had a number of our encounters with the 20 various crematoriums and funeral services of disposal 21 of the bodies.
22 And it would have been so much more clear 23 if the patient had already -- if the family had made 24 that decision up front before the patient was treated.
25 66 CHAIRMAN PALESTRO: Mr. Green?
1 MEMBER GREEN: Just to echo this, the 2 comments. Very supportive of these comments regarding 3 pre-need patient counseling.
4 We've seen a published article recently 5 out of Scottsdale, Arizona Mayo Clinic regarding 6 lutetium-177 and 117m in a pat ient that was treated at 7 hospital A, but then demised at hospital B.
8 And went on and was cremated. And 9 actually had, you know, contam ination of the crematory 10 unit as well as the individual who performed the 11 cremation.
12 So, it should be advised a part -- it 13 should be part of the counseling to the patient that 14 with a certain period of time for this half-life of 15 this isotope, that other means of -- other then 16 cremation should be considered.
17 CHAIRMAN PALESTRO: Thank you. Any other 18 comments? Questions? Dr. Diabes, Figueroa?
19 DR. DIABES: Dr. Said Diabes. And Reg 20 Guide 8.39, we added a section that addresses this 21 specific issue on cremation of bodies. That -- of 22 patients have been treated and bodies that are 23 radioactive.
24 And it adds more information, 25 67 instructions, a very vast amount of data on this 1 issue, which the Subcommittee will see soon, or is 2 seeing. It's reviewing at this moment.
3 CHAIRMAN PALESTRO: Thank you. Any other 4 comments or questions? Just as an aside before we 5 move on, the issue of cremation has also come up with 6 another radiopharmaceutical, lutetium-177.
7 And it's my plan to address the issue of 8 cremation and disposal of the seeds at some point 9 later on in this meeting. I don't want to get 10 sidetracked now.
11 But I think it's an important issue. And 12 it's not just limited to yttrium-90 microspheres.
All 13 right. 14 Any other comments or questions from the 15 Committee? Attendees in the room? Bridge line?
16 (No response) 17 CHAIRMAN PALESTRO: At this point Ms.
18 Holiday, we're ready to vote on the Subcommittee's 19 report. 20 MS. HOLIDAY: We are ready for the vote.
21 CHAIRMAN PAL ESTRO: All right. May I have 22 a motion to approve the report?
23 MEMBER GREEN: I move the report be 24 approved with the change of the word drug to device.
25 68 CHAIRMAN PALESTRO: All right. Second?
1 MEMBER O'HARA: I'll second.
2 CHAIRMAN PALESTRO: All right. All in 3 favor? 4 (Voting) 5 CHAIRMAN PALESTRO: Any opposed?
6 (Voting) 7 CHAIRMAN PALESTRO: Any abstentions?
8 (Voting) 9 CHAIRMAN PALESTRO: Thank you.
10 MS. HOLIDAY: Okay. So for the record, 11 Mr. Green made the motion to approve the Subcommittee 12 report with the changing of the word drug to device.
13 The motion was seconded by Dr. O'Hara.
14 And it was unanimously approved by the 15 Committee. Thank you.
16 CHAIRMAN PAL ESTRO: Thank you Ms. Holiday.
17 Next item on the agenda is the Lucerno Dynamics LARA 18 infiltration detection.
19 And Mr. Lattanze will provide an overview 20 about a product that can assist with detecting nuclear 21 medicine injection infiltrations. Mr. Lattanze?
22 MR. LATTANZE: Good morning. And thank 23 you for the opportunity to pre sent. I'm Ron Lattanze.
24 I'm the CEO of Lucerno Dynamics.
25 69 At Lucerno, we've developed the device 1 called LARA that provides insight into nuclear 2 medicine injection infiltrations, which are sometimes 3 referred to as extravasations.
4 I'll be covering a lot of material in a 5 short amount of time. So, I've prepared comments that 6 describe infiltrations, their incidence, and patient 7 impact. 8 I'll also share evidence that 9 infiltrations can nearly be eliminated. And will 10 conclude with a request that the NRC and the ACMUI 11 reconsider a 1980 decision regarding infiltrations.
12 In anticipation of questions after my 13 comments, I'd like to introduce Dr. David Townsend, 14 who is attending this meeting by phone. David is 15 Lucerno's scientific advisor, and receives no 16 compensation.
17 He's the co-inventor of the PET CT scanner 18 and a fellow of IEEE. He's received many awards 19 including the IEEE healthcare medal, and the SNMMI 20 Paul C. Aebersold Award.
21 Also in attendance is Dr. Dan Sullivan, 22 the former NCI Associate Director, Division of Cancer 23 Treatment and Diagnosis, and the former Director of 24 the NCI Cancer Imaging Program. He's a science 25 70 advisor for the RSNA, and a founder of the 1 Quantitative Imaging Biomarkers Alliance.
2 Dan does consult with Lucerno to review 3 our scientific paper submissions. David and Dan are 4 here to answer any questions related to infiltration 5 effects on nuclear medicine imaging studies and on 6 patients in this era of precision medicine.
7 Most nuclear medicine studies are based on 8 the assumption that the radiopharmaceutical is 9 injected as a bolus, where the entire dose is 10 delivered in just a few seconds. The injection is 11 usually followed by a saline flush, and an uptake 12 period prior to imaging.
13 This process tends to ensure that by the 14 time the patient is imaged, the low background noise 15 and high counts in organs or lesions of interest 16 results in a high sensitive study.
17 An infiltration results when some or all 18 of the dose intended for a patient's vein is injected 19 into the tissue near the vein.
This not only exposes 20 this tissue to unintended radioactivity, it increases 21 noise, reduces effective counts, and reduces image 22 sensitivity. And the image quantification is 23 incorrect and understated.
24 Because the injected dose is an input to 25 71 the image quantification formula, quality control 1 measures are in place to ensure dose accuracy. Clocks 2 are synchronized in nuclear medicine departments to 3 account for radioactivity decay.
4 And technologists after injecting and 5 flushing the delivery syringe, measure the dose left 6 in the syringe, and subtract this amount for a net 7 injected dose. These QC measures increase accuracy of 8 the net dose approximately 1 to 2 percent.
9 Despite the accuracy that QC provides for 10 the net dose, there remains the assumption that the 11 net dose is actually delivered into the patient's 12 circulation.
13 Until recently there's never been a 14 routine monitoring to confirm the delivery into the 15 circulation. This is important, because an 16 infiltration can dwarf the effects of any errors 17 resulting from the residual or unsynchr onized clocks.
18 To better understand the NRC position on 19 infiltration, I've reviewed the historical records.
20 And thank you for the folks who put the ACMUI 21 information on the website. That was very helpful.
22 In 1980, the NRC published a final rule on 23 misadministration reporting requirements. From a 24 review of the supplementary information supporting 25 72 this rule, here are my interpretations of the NRC 1 conclusions regarding this administration.
2 The NRC emphasized their role in 3 protecting patients from unintended radiation 4 exposure, and from compromised diagnostic procedures 5 that could impact care.
6 They emphasized reporting is needed to 7 identify root cause. And then prevent recurrence.
8 And stated that referring physicians and patients 9 should be notified.
10 Interestingly, and in apparent to these 11 conclusions, the NRC reached their decision that an 12 infiltration should not be considered a 13 misadministration. Their decision was supported by 14 the following justification:
infiltrations frequently 15 occur in otherwise normal intravenous and intra-16 arterial injections. And are virtually impossible to 17 avoid. 18 In 2002 the term misadministration was 19 replaced with the term medical event in the 20 regulations. Additionally, re porting and notification 21 conditions and limits for these events were 22 established in Subpart M.
23 In 2008, a Boston VA patient was 24 infiltrated, aware of Subpart M, the VA reported the 25 73 medical event to the NRC, based on their estimate that 1 the infiltration may have exceeded the effective dose 2 equivalent limit to the tissue.
3 The NRC requested that the VA retract the 4 report, referencing the 1980 decision that 5 infiltration should not be considered a 6 misadministration.
7 NRC shared this decision with the ACMUI.
8 And according to the December 2008 meeting minutes, 9 the ACMUI supported the NRC decision and rationale, 10 and passed a motion that "at this time, NRC should 11 continue its policy of not requiring in filtrations of 12 diagnostic dosages to be reported as medical events." 13 Few centers have ever shared their 14 infiltration rates. But the limited av ailable global 15 data support the idea that nuclear medicine 16 infiltrations can occur frequently.
17 In the last decade, St. Louis University, 18 Ohio State University, and the University of Santiago 19 in Spain, have conducted six retrospective studies of 20 PET CT injection infiltration rates, by reviewing 21 images for infiltration evidence.
22 As states in one of these studies, rates 23 are likely under-reported, because as you can see 24 here, the injection site, like this infiltrated site 25 74 shown by the arrow, are often outside of the routine 1 PET CT imaging field of view.
2 These six st udies retrospectively reviewed 3 2,804 patient images, and found a 15.2 percent 4 infiltration rate. The studies ranged from 3 percent 5 to 23 percent.
6 In Alberta, nine centers each 7 retrospectively reviewed 25 consecutive nuclear 8 medicine bone scans for infiltrations on two separate 9 occasions.
10 In the first review of 225 patients, the 11 centers had an average infiltration rate of 15 12 percent. The centers ranged --
rates ranged from zero 13 to 28 percent.
14 The review of another 225 patient 15 injections had an average rate of 20 percent. And the 16 rates ranged from 8 to 44 percent.
17 From 2016 to 2018, Lucerno worked with 18 seven prestigious U.S. PET CT centers, including MD 19 Anderson, UCLA, Wake Forest Baptist, and UT Knoxville 20 on a project called LARA QI.
21 This quality improvement project used 22 LARA, our new monitoring device, to help clinicians 23 determine infiltration rates by prospectively 24 comparing the injection arm to the other arm for 25 75 excess radiotracer, rather than retrospectively 1 reviewing images.
2 While this ensures infiltrations are not 3 missed due to the field of view detection issues, the 4 QI project results also likely under-represent real 5 infiltration rates. That's be cause of the observer or 6 trial effect.
7 Before beginning the infiltration rate 8 measurement in LARA QI, all technologists were trained 9 on the importance of high quality injections. They 10 knew that their injections were going to be monitored 11 for infiltrated radioactivity.
12 In the LARA QI measurement phase, 2,431 13 patients were monitored. Investigators found a 6.2 14 percent infiltration rate. Ce nters' rates ranged from 15 2 to 16 percent.
Interestingly, techno logists' rates 16 ranged from zero to 24 percent.
17 These results were presented at the SNMMI 18 annual meeting last June.
During the closing session, 19 a distinguished subject matter expert summarizes in 20 what is known as the highlights lecture, selected 21 significant general nuclear medicine presentations 22 from the hundreds shared at that meeting.
23 The LARA QI findings were one of the 12 24 presentations highlighted last year.
The highlight's 25 76 lecture was published in the October issue of the 1 Journal of Nuclear Medicine.
2 Without an easy to use detection process, 3 technologists do not receive injection quality 4 feedback, are not aware of infiltrations, and thus 5 can't improve their technique.
And when infiltrations 6 are identified, there are no reporting requirements in 7 place that lead to root cause investigation, quality 8 improvement, and reduction in occurrence.
9 In summary of this slide, the data we've 10 gathered support the NRC position that nuclear 11 medicine injection infiltration rates appear to be 12 high. But, do infiltrations matter?
13 We do not believe that all diagnostic 14 infiltrations matter acutely or to the ensuing patient 15 care. But some do matter. And they can matter in 16 many ways.
17 In 1980, the NRC stated that a 18 misadministration of a diagnostic radio pharmaceutical 19 could compromise the effectiveness of the diagnostic 20 procedure. They were right.
21 A literature review since then has 22 identified over 50 references that show how 23 infiltrations can harm or have harmed patients. These 24 references are cited in a letter that I sent to the 25 77 NRC yesterday.
1 Examples of how infiltrations may 2 negatively affect patent care include missed disease 3 that impacts staging and treatment, wrong 4 quantification that adversely affects longitudinal 5 assessment scans and treatment planning, false 6 positive results that lead to unnecessary invasive 7 procedures, and repeated imaging that increases 8 patient radiation exposure.
9 I could show you many cases, patient 10 cases, but due to time limits, I'll only share two.
11 Here is a published report of a lung lesion patient 12 with an infiltrated PET CT study, the left image with 13 the infiltration circled in red.
14 That when repeated three days later with 15 study parameters kept as constant as possible, the 16 image on the right revealed a missed metastatic lesion 17 shown by the arrow. In the infiltrated image on the 18 left, only the lung lesion in the circle was 19 identified.
20 To eliminate the impact of the streaking 21 artifacts that you see emanati ng from the infiltration 22 and obscuring the torso, the patient was reimaged with 23 his arms over his head just 30 minutes after this 24 infiltrated image was produced. With a clear torso 25 78 view, the reading physician did not identify any other 1 lesions. 2 The day three non-infiltrated image on the 3 right revealed that the standardized uptake value of 4 the in -- or the SUV of the infiltrated image lesion, 5 had been understated by 44 percent. More importantly, 6 it revealed right adrenal metastatic disease.
7 With the infiltrated image guiding 8 treatment, as is commonly done in many centers today, 9 the patient would have received local regional 10 treatment rather than treatment for metastatic 11 disease. 12 Informed of the day three scan results, 13 the patient chose to spend his last five months in 14 hospice. 15 The next patient had two PET CT scans 16 performed five days apart in a controll ed test/retest 17 study. Imaging parameters were controlled. Four 18 metastatic lesions were quantified. And the results 19 from the two scans were compared.
20 This example is also important. The first 21 reason is the dramatic effect an infiltration can have 22 on quantification.
23 As you can see from the far right column, 24 the infiltration caused the SUVs of the four lesions 25 79 to be understated between 33 and 54 percent. And the 1 infiltrated image metabolic tumor volume value 2 calculations were understated between 32 and 70 3 percent. 4 Another reason this case is important is 5 because without the device, no one would have known to 6 order a repeat scan. The injection site was in the 7 left hand, outside the imaging field of view.
8 In such a scenario, an infiltrated scan 9 would provide the wrong information in assessing 10 disease progression, or in developing treatment plans.
11 This latest example is not unusual.
12 From our monitoring of over 14 thousand 13 injections to date, we know injection s ite locations, 14 and estimate that about 50 percent of i njection sites 15 are out of the routine imaging field of view.
16 A meaningful infiltration outside of the 17 field of view like the example I just shared, or an 18 infiltration that is seen, but not included in the 19 radiology report, may result in compromised care. And 20 patients and treating physicians would be unaware.
21 Not only can infiltrations negatively 22 affect care, many exceed the NRC reporting limits 23 similar to the Boston VA case.
24 One medical event reporting limit is 0.15 25 80 Sievert effective dose equivalent to the tissue.
1 We've worked with physicists, measured visible 2 infiltrations, and used Monte Carlo simulations to 3 show how diagnostic infiltrations can exceed Subpart M 4 reporting and notification limits.
5 In the letter that I sent to the NRC 6 yesterday, I've also provided engineering reports to 7 support these findings.
8 Example A is the actual case I just 9 presented, where the hand was out of the imaging field 10 of view. By knowing the injected dose and the tumor 11 quantification changes, by est imating the reabsorption 12 process, we can calculate how much infiltrated 13 radioactivity was in the hand at the time of imaging.
14 And that conservatively, the infiltration 15 resulted in an effective dose equivalent to the tissue 16 that exceeded the reporting limit by approximately 23 17 times. 18 Example B uses actual infiltration data 19 and is very interesting. It shows how the effective 20 dose equivalent of an infiltration can be easily 21 underestimated if one is just using static PET images.
22 In this example, at the time of imaging, 23 107 minutes post injection, th ere was a relatively low 24 amount of activity left at the injection site.
25 81 Approximately 100 micro curies.
1 However, by using the infiltration 2 resolution data with known infiltration volume data, 3 we can estimate that an infiltration that may appear 4 minor on imaging, can actually exceed reporting 5 limits. Again, not all diagno stic radiopharmaceutical 6 infiltrations will matter to patients, but some will.
7 Some infiltrations will exceed medical 8 event reporting limits, and should be reported. And 9 the referring physicians and the patients should be 10 notified.
11 There is good news. Infiltrations are no 12 longer virtually impossible to avoid. And 13 infiltration rates can be dramatically improved.
14 Other healthcare injection processes 15 monitor and report infiltrations. Over the last 40 16 plus years, quality improvement projects have 17 monitored more than one million chemotherapy 18 injections and infiltration rates have continued to 19 decline. 20 A 2017 QI project involved nearly 740 21 thousand patients. And found a 0.18 percent 22 infiltration rate for the peripheral IV chemotherapy 23 injection. So that's an apples to apples comparison 24 of PET CT.
25 82 Hundreds of thousands of contrast CT 1 injections have also been studied. And because of 2 monitoring and reporting, infiltration rates have 3 continued to decline.
4 Another recent QI project monitored over 5 450 thousand CT injections, and found a 0.24 percent 6 infiltration rate. The 1980 belief which was 7 reaffirmed in 2008, is no longer accurate in 2019.
8 Infiltrations are not virtually impossible 9 to avoid today. Now a device that uses sensors placed 10 on the arms, and that adds just 20 seconds to the 11 patient experience, can routinely help clinicians 12 detect infiltrations before imaging.
13 As a result, centers can provide 14 individual quality control for each injection with 15 time activity curves, or TACs like this one, 16 indicating no presence of excess radiotracers at the 17 injection site after about 30 seconds post-injection.
18 Here you can see the injection arm 19 sensor's black curve showing the bolus raise. And 20 then quickly drop to the level of activity represented 21 by the red arm, the referenced arm's red curve.
22 But not all TACs look ideal like this one.
23 Unfortunately, many look like this. Where the 24 injection arm's curve -- the injection arm's curve 25 83 never drops to the level of the reference arm, 1 indicating the presence of excess radiotracers at the 2 injection site.
3 Just as importantly, by using the device's 4 quality assurance functions, centers can identify 5 factors associated with their infiltrations. And then 6 put improvement plans in place to correct them.
7 Following a QI -- following a QI process 8 can lead to very low infiltrat ion rates, as we've seen 9 in other healthcare settings. In fact, four of the 10 seven LARA QI centers tried to improve their 11 infiltration rates.
12 As you can see by the columns highlighted 13 in red font, each center improved. Their aggregated 14 rate had a statistically signi ficant decrease from 8.9 15 percent to 4.6 percent, with the p-value of less than 16 0.0001. 17 And even better news, measuring and 18 improving results can be accomplished in approximately 19 six to eight months. In fact now, some of these 20 centers are in sight of 1 percent infiltration rates.
21 These results were also presented at the 22 annual meeting last year.
Their presentation was also 23 one of the 12 that were selected for the highlights 24 lecture. 25 84 It appears to us that addressing the 1 infiltration issue is consistent with the goals of all 2 interested parties. Minimizing infiltration seems 3 consistent with the previously stated NRC goals of 4 protecting patients from unnecessary radiation 5 exposure.
6 As well as from compromised diagnostic 7 studies of reporting determini ng causes and preventing 8 recurrence. And of ensuring referring physicians and 9 patients are notified of medical events that exceed 10 reportable limits. Limits that I will add, that 11 should be agnostic to whether the source is a 12 diagnostic or therapeutic radiopharmaceutical.
13 Identifying and reporting infiltrations 14 are also in the best interest of nuclear medicine and 15 molecular imaging societies. As the NRC knows, the 16 importance of patient safety was a consistent message 17 throughout recent public comments received by the NRC 18 with respect to the training and experience 19 requirements for authorized users.
20 The societies are also focused on 21 precision medicine. Infiltrations lead to imprecise 22 medicine.
23 Societies are also aware that in the 24 future alpha and beta therapeutic injections, with 25 85 their longer half-lives, will play an increasingly 1 important role in medicine. And they know that the 2 same personnel delivering diagnostic 3 radiopharmaceuticals today, will be delivering radio 4 therapeutics tomorrow.
5 And the SNMMI knows that infiltrations 6 have no place in their quality of practice initiative.
7 The goal of which is to ensure that members are known 8 for high quality, value driven performance, and 9 delivery of patient-centered nuclear medicine 10 practice.
11 And when we deal with individual centers, 12 the vast majority of technologists actually want 13 feedback that they are doing injections properly.
14 Physicists want reproducible imaging.
15 Safety officers want radioactive material 16 used optimally and safely.
And most in terpreting and 17 treating physicians we've spoken to, want the highest 18 quality imaging to help treat their patients.
19 Finally, and most importantly, are the 20 patients. It's their life and their care. We've met 21 with them, their families, their friends, and patient 22 advocacy groups. Their message is clear, and they all 23 want the highest quality nuclear medici ne injections.
24 On that point, let me share my last slide.
25 86 Now that there is awareness that infiltrations are 1 avoidable, that they can harm some patients, and that 2 they can exceed reporting limits, we are asking the 3 NRC and the ACMUI to review the information I sent to 4 the NRC yesterday, and reevaluate the 1980 5 infiltration policy.
6 Infiltrations that meet Subpart M 7 reporting and notification criteria should be 8 reported. This will lead to a reduction in 9 infiltrations and to an improvement in patient care.
10 Thank you for your attention. And we 11 welcome any questions you have.
12 CHAIRMAN PALESTRO: Thank you Mr.
13 Lattanze. Any questions from the ACMUI? Dr.
14 Dilsizian?
15 MEMBER DILSIZIAN: Thank you very much for 16 the nice presentation. I guess I have several 17 comments about your presentation.
18 But I'm going to start from agreeing with 19 you. That QA/QC requires that you properly inject the 20 dose. 21 And for the two examples that you gave, 22 chemotherapy, and I'm going to talk abo ut cardiology, 23 when we're injecting radiotracers with exercise, we 24 make sure that there's a blood return when you have an 25 87 IV line. Because you don't want to inject the 1 radiotracer and you'll probably get peak exercise.
2 Also for absolute blood flow measurement, 3 it's critical that when we're giving a bolus injection 4 that it's going to the patient.
5 MR. LATTANZE: Absolutely.
6 MEMBER DILSIZIAN: So, but I would like to 7 make the distinction between t he type of examples that 8 you gave. To routine imaging for bone scan that's a, 9 where you direct inject the radiotracer to the vein, 10 there's no IV line.
11 And so those are the type of things I 12 think we're mixing the two information. But 13 infiltration from radio diagnostic studies, whether 14 it's common or infrequent to really rep orting them as 15 -- from the regulatory body, I'm just questioning 16 that. 17 Now, let me address two of the things you 18 have presented. The arm down patient that you made a 19 big picture out of, --
20 MR. LATTANZE: Yes.
21 MEMBER DILSIZIAN: It would never happen 22 in most institutions. The arm should never be next to 23 it to miss that adrenal gland. It should have been up 24 anyway. 25 88 Number two, so that's not really a good 1 example. It's misleading. I mean, no one would 2 accept that. If I saw that image, I'd say repeat the 3 image with the arm up.
4 MR. LATTANZE: They did repeat the image 5 with the arm up 30 minutes later.
6 MEMBER DILSIZIAN: Yes.
7 MR. LATTANZE: They had extended uptake in 8 the SUV. And there was no evidence of that 9 metastatically.
10 MEMBER DILSIZIAN: No, what I was saying, 11 the first image, if they --
12 MR. LATTANZE: Yes.
That -- that -- no --
13 MEMBER DILSIZIAN: They misproperly 14 identified it. And the other thing you made a big 15 deal about the SUVs and all.
16 You know, I read nuclear medicine studies 17 every day. You gave a difference between seven versus 18 11, 28 versus 41, six versus 11. Clinically 19 irrelevant. They're all hot.
20 It doesn't matter if I say to you it's 21 seven versus 11, that doesn't change anything but 22 therapy. So yes, it does affect SUVs. It doesn't 23 change patient management. We
're making a bigger deal 24 than it is.
25 89 And the other thing, I'd like to caution 1 you using the word can harm or have harmed patients.
2 It's under some dramatic and exaggerated statements.
3 I agree with you that QA/QC we should do 4 our best to give the dose that's necessary to the 5 patient. I doubt it that it really has harmed or have 6 harmed patients.
7 I mean, the examples that you gave are 8 maybe rare, not common. And the percentages that you 9 give, as an SNMMI incoming President, I agree with 10 you. We should not do those.
11 But, I don't think that these are 12 significant enough events that should be reported 13 routinely, except when the whole dose for example, if 14 I'm giving a thallium dose, --
15 MR. LATTANZE: Um-hum.
16 MEMBER DILSIZIAN: And everything went to 17 the arm, I know that there's going to be skin issues.
18 Those are reportable. But not the routine ones that 19 we do every day.
20 MR. LATTANZE: So, is that done? Okay.
21 So, the question about harm, when I sent the letter 22 yesterday, I cited the 50 references that are peer 23 reviewed. That they're the ones that state how 24 patients have been harmed or can be harmed. So 25 90 that's, I'm just using what the references state.
1 The SUV use, and I hear this frequently, 2 because I talk to oncologists as well as the nuclear 3 medicine physicians. When oncologists are using the 4 SUV, and it maybe not what nuclear medicine physicians 5 want, in longitudinal assessme nt scans, they're making 6 decisions often whether they're seeing a change in 7 response.
8 And so according to the PERCIST criteria, 9 a lot of these changes would actually be more than the 10 PERCIST criteria. And they wo uld make a decision that 11 the patients have responded or not.
12 And so I think that while I understand 13 very well the variability in the SUV measurements, the 14 fact that the quality of the injection is not being 15 reported to the physician, doesn't give them the 16 opportunity to understand that they might have even 17 more variability then they would normally expect.
18 So, the oncologist, and I do talk to a lot 19 of oncologists, they are completely unaware that 20 patients are being infiltrated.
21 Your comment about the --
the arms up, and 22 getting an IV, getting blood drawn, all the centers 23 that we go into, very few -- nobody does a straight 24 stick anymore that we've seen.
25 91 They use the butterfly or the IV access.
1 And every technologist will tell you, I look for blood 2 in my return.
3 And we've been in cardiology centers as 4 well, and have seen very similar infiltration rates in 5 both stress and rest exams. That they will actually 6 draw blood back in.
7 And they will tell you, I am sure that 8 this is a good injection. And then when they look at 9 the image, they'll see that they've infiltrated.
10 So, I understand what you're saying. I 11 think it's actually my experience, we've been in some 12 other centers as well, the occurrence is far more 13 frequently than you think.
14 That's our experience.
15 CHAIRMAN PALESTRO: Any other comments or 16 questions? Mr. Ouhib?
17 MEMBER OUHIB: Yeah.
I have to apologize, 18 this is certainly not my expertise.
But listening to 19 this presentation, it sounds to me like this is a 20 practice of medicine more than anything else.
21 And society should be addressing that.
22 Not a regulatory item.
23 MR. LATTANZE: Yes. I agree that the --
24 what we found is that the main difference between 25 92 chemotherapy injections for example, which is a very 1 similar patient population to oncology PET CT 2 patients, is that it's a practice of -- that you have 3 trained clinical nurses that do chemotherapy 4 injections for a living, and technologists don't.
5 But once they get the feedback, the 6 technologists can get as good as those patients, or as 7 those nurses. However, it's not a regulatory issue 8 unless the dose that is affecting the tissue is so 9 high that you're exceeding that Subpart M reporting 10 limits. 11 So, by not reporting those doses that are 12 very high to the NRC, you don't know when patients are 13 being affected and when they're not.
14 Does that make sense? That's the 15 regulatory piece. Not the -- not the training piece 16 that can be fixed very quickly. Well, within six or 17 eight months.
18 CHAIRMAN PALESTRO: Dr. O'Hara?
19 MEMBER O'HARA: There could be a 20 regulatory piece as well, depending on how the firm 21 advertises this product.
22 MR. LATTANZE:
Absolutely. And I think we 23 met back in December, Dr. O'Hara at the FDA.
24 And we're very conscious of, you know, 25 93 what the device does is it tells a clinician, it helps 1 the clinician detect whether t hey have an infiltration 2 or not. It does not tell them they have an 3 infiltration.
4 CHAIRMAN PALESTRO: Any other comments or 5 questions Mr. Ouhib? Dr. Ennis?
6 MEMBER ENNIS: My question isn't really 7 directly related to your request, regul atory request.
8 But, more of a, I guess curiosity about your product, 9 if you'll indulge me.
10 MR. LATTANZE: Sure.
11 MEMBER ENNIS: So if you could explain why 12 CT infiltration rates and chemotherapy --
you alluded 13 to the chemotherapy one, are so low compared to what 14 you seem to be seeing with nuclear medicine 15 infiltration rates, A.
16 And B, why would a nuclear medicine 17 department need your device if CT and chemo have 18 figured out how to decrease infiltration rates without 19 a chemo detection device, or a --
20 MR. LATTANZE: That's great.
21 MEMBER ENNIS: Contra-detection device?
22 MR. LATTANZE: That's great. The 23 different -- the reason that chemotherapy and contrast 24 CT rates are so much better then nuclear medicine 25 94 rates that we've seen so far i s, for a lot of reasons.
1 One is -- the primary reason is the 2 detection issue. So, when a chemotherapy patient is 3 infiltrated, they know they've been infiltrated, 4 because it's a vesicant and does an extravasation.
5 There's immediate feedback to the nurse 6 that that patient has been inf iltrated. In a contrast 7 CT, the volumes are so large you actually see a 8 swelling in the arm. So, there's feedback.
9 Unfortunately for nuclear medicine, there 10 has been -- the technologists have never gotten the 11 feedback, because they're injecting such small doses 12 that they do not see that.
13 We have had one patient say that they felt 14 a burning sensation. And it was a large dose 15 infiltration. Larger than the one that I showed 16 earlier. 17 But that's the only case we've ever heard 18 of where a patient complained about a burning 19 sensation. So, the patients don't know. The 20 technologists don't know.
21 The injection sites are often out of the 22 imaging field of view. And the other thing we've 23 known is that infiltrations re solve during the time --
24 you know, during the 60 to 70 minutes of uptake time.
25 95 So when physicians do see them on the 1 static pad image, they actually are seeing something 2 that's much smaller than what it was during the uptake 3 period. And so the detection issue is the main 4 difference.
5 Your second question was well, once they 6 can detect it and can solve their problem, do they 7 need to continue to use the product? You know, is 8 there a need for the product?
9 And that's an issue that the market will 10 solve later. But what we've experienced in all the 11 centers that have gone on to use the device, is 12 because this is a human to human interaction, you 13 know, you have this sophisticated PET CT technology 14 that's so amazing, but it still relies on the human 15 to human interaction between a technologist and the 16 patient's arm, sometimes with very bad veins.
17 Is that if one of those humans, the 18 technologist is not having a good day, they're --
19 we've seen actually where some of the best 20 technologists at a center for over a year, will all of 21 a sudden go and infiltrate 27 percent of their 22 patients over the next nine working days. We've seen 23 that example.
24 Some things happen because they're human.
25 96 And so, the centers have chos en to continue to use it 1 as an ongoing monitoring process.
2 Also, because nuclear medicine is growing.
3 And new technologists are coming in. And there is no 4 training for this process.
5 The technologists are two year physicist 6 students. They receive their training on the job from 7 other technologists.
8 And so all the centers that have used the 9 device continue to use the device, because they 10 realize that there's a need to keep making sure that 11 as people move around, that they're doing great 12 injections.
13 CHAIRMAN PALESTRO: Any other comments or 14 questions? Dr. Metter?
15 VICE CHAIRMAN METTER: Thank you for your 16 presentation. It was very -- very informative.
17 One thing I would like to caution, is that 18 the volume of CT studies are clearly far more, and 19 performed 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> a day, usually in an institution, 20 versus nuclear medicine, which is generally performed 21 during the working hours of 8:00 to 5:00.
22 And so you're looking at perhaps like at a 23 good day for example at our institution, maybe there 24 are 30 studies in nuclear medicine, versus three 25 97 hundred or more for CT.
1 So if you looked at that, and if you look 2 at a 25 percent infiltration rate, so you have, let's 3 say, seven out of 30, versus 75 out of 300.
4 So, I caution you regarding that. Because 5 the numbers, the smaller the numbers, an error in one 6 area can raise that percentage.
7 MR. LATTANZE: Yes.
8 CHAIRMAN PALESTRO: Mr. Sheetz?
9 MEMBER SHEETZ: Thank you for an 10 interesting presentation. I have
-- was surprised by 11 the infiltration rates that you presented on slide 12 five. You don't have to go back to it.
13 But, it looks like you took a -- pulled 14 the data and took a number of studies for different 15 centers, took their infiltration rates, and then took 16 the median value as your, you know, the reported rate 17 as an average for those centers.
18 Did you look to normalize that for the end 19 number for the actual number of patients? Because 20 some centers may have had ten patients and had an 21 infiltration rate of say 44 percent.
22 Another center may have had a thousand 23 patients and an infiltration rate of two.
24 MR. LATTANZE: Yes.
25 98 MEMBER SHEETZ: And so by just taking the 1 median value of those rates per centers, it could skew 2 the percentage rates.
3 MR. LATTANZE: Yes. So, I like to often 4 report, you know, that -- the --
both values. And so 5 the -- we have seen that some centers are at the 2 to 6 3 percent rate. And they are usually the higher 7 volume centers.
8 We've also seen some high volume centers 9 have a 13 percent rate.
And so, all that information 10 will be in our -- once that LARA QI paper publishes, 11 you'll be able to see all that data.
12 And you know, also sorry, one last 13 comment. The other interesting thing is, oftentimes 14 at a center, many of the technologists can be very, 15 very low at the infiltration rate. But then you can 16 have one that is a 25 or 24 percent infiltration rate 17 technique, so.
18 CHAIRMAN PALESTRO: Ms. Martin?
19 MEMBER MARTIN: I would just comment 20 following up sort of on what Dr. Metter said. Most 21 facilities do not have anyone around that can make 22 these calculations routinely to decide whether that 23 infiltrate is at a dose of .5 Sieverts.
24 I was just wondering, who would make those 25 99 calculations routinely in a facility if it were 1 required? Because that is not something that is 2 routinely done by either nuclear medici ne physicists, 3 which are not necessarily on staff, unless you're a 4 very large facility.
5 I don't see how that could routinely be 6 happening.
7 MR. LATTANZE: So, I'm not sure how to 8 answer that question. In the centers where we've had 9 those calculations performed, the physicist involved 10 actually has done the calculation.
11 MEMBER MARTIN: Um-hum.
12 MR. LATTANZE: But, you know, I get this 13 question a lot when I go into centers that say well, 14 you know, first they say I don't think I have an 15 infiltration problem.
16 And then when they finally say, well maybe 17 I do. And we start looking at it, their real concern 18 is, well, if I'm infiltrating at 15 or 20 percent of 19 the time and I have to reschedule these patients, then 20 it's a problem.
21 And what I try to emphasize is that it's 22 only a problem for a very short period of time. Once 23 you start, like any quality improvement project, any 24 time you want to improve something, if you start to 25 100 measure it, the improvements can happen very quickly.
1 And so, I would suspect that while the 2 rates are high today, based on our experience in the 3 centers that we've been in, the rates could be 4 dramatically better very quickly if you begin to 5 actually start detecting and reporting them.
6 Any time you put that process in place, it 7 causes improvement. So then I don't think it's a big 8 problem, because very few of the
-- if you can reduce 9 the infiltrations dramatically, then even fewer will 10 be moderate or significant infiltrations what would 11 require reporting.
12 CHAIRMAN PALESTRO: Any other comments or 13 questions from the Committee? Mr. Green?
14 MEMBER GREEN: I think it was a very 15 interesting presentation. You know, it's been, you 16 pointed out and it's been --
17 MS. HOLIDAY: Rich, can you bring the 18 microphone closer?
19 MEMBER GREEN: You pointed out, and it's 20 been repeated by members of the Committee that not all 21 nuclear procedures are quantit ative. But PET with SUV 22 are. 23 And I just wanted to point out that not 24 all nuclear medicine and radiopharmaceuticals are 25 101 injected intravenously. There are now in the last 1 five years, a drug which is indicative for intradermal 2 administration, has also subcutaneous a dministration, 3 and one that's intrathecal.
4 So, if we consider things that would 5 require reporting, you know, not all drugs are 6 intravenous. You know there are five that are oral, 7 and two that are inhaled. But I'm excluding those.
8 But, via needle, not everything goes in a 9 vein. 10 CHAIRMAN PALESTRO: Mr. Ouhib?
11 MEMBER OUHIB: Yeah.
Just looking at your 12 request here. So, moving forward with required 13 reporting of infiltrations.
14 I guess I'm trying to understand, what do 15 you think that will eventually achieve? People paying 16 more attention?
17 And if so, wouldn't that be more like 18 education and training and und erstanding that? Versus 19 -- 20 MR. LATTANZE: So the current NRC policy 21 is that if a patient is injected and they're 22 infiltrated, and the dose exceeds the reporting 23 limits, is that that is not considered a 24 misadministration, even though it could, you know, it 25 102 is a misadministration.
1 It's not considered one because there was 2 the belief back in 1980 that they're virtually 3 impossible to avoid. So, my request is, to the NRC, 4 to say, well, we know now that they are not virtually 5 possible to avoid.
6 They may have been back then. And when 7 you go back and look at chemotherapy rates and 8 contrast CT rates from the 1980s, they were 9 significantly higher then than they are today, too.
10 So my request is, if you change your 11 policy and say that if you misadminister an injection, 12 and you expose a patient to above the reporting limits 13 in Subpart M, that that should be a reportable event.
14 Whether it's a therapeutic infiltration, 15 or a diagnostic infiltration, if it's receiving -- if 16 a hand -- if tissue in a hand is receiving 11 Sieverts 17 over a period of, you know, during a two-hour 18 reabsorption process that should likely be a 19 reportable event.
20 And if you do that, then people will start 21 to monitor their injections. And they will actually 22 improve their injections. Just like we've seen in 23 every center that we've been in.
24 You know, until it -- you know, we've had 25 103 a lot of physicians tell me th at, you know, we know we 1 should be doing this, but we're not going to do it 2 until we're told to do it.
Until it's required to do.
3 And I think when you begin to monitor 4 process, you'll see the results come down. And that 5 will be better for patients.
6 CHAIRMAN PALESTRO: Mr. Sheetz?
7 MEMBER SHEETZ: I'm going to go back to my 8 surprise on the infiltration rates. And I do want to 9 point out that the gamma cameras and the PET scanners 10 are very, very sensitive, so and a 15 millicurie 11 injection, if only 1 microcurie or fraction of that 12 leaks or infiltrates, you will visualize that.
13 So, I'm not sure, did you try to quantify 14 any of your infiltrations? Or if you visualize it, 15 it's an infiltration.
16 And I will say, it would probably not be 17 uncommon to be able to visualize something. But, the 18 actual amount of activity in a dose related to that 19 would be inconsequential, of no real risk or harm.
20 Certainly if you extravasated the entire 21 dose, that would be of concern. And you would want to 22 be able to monitor, detect, or know that.
23 So, I'm not sure how you would try to 24 quantify or evaluate whether t his was a slight leakage 25 104 of a microcurie or so. Or we extravasated multiple 1 millicuries.
2 MR. LATTANZE: Yeah. That's a great 3 question. So, as Dr. O'Hara pointed out, you know, 4 again we're not -- all our device can tell you is 5 whether there is excess radiotracer. And then we 6 leave it to the clinicians to determine how much is 7 there. 8 Often times to your point, they'll see 9 like a trace of a, you know, what appears to be a 10 little bit of radiotracer. Our device would pick that 11 up. But the time activity curve would be very, very 12 low above the reference arm.
13 It's the ones that are like the ones that 14 I've shown you before that were considered to be in 15 sitting down with the physicians at the site. And 16 when often times they had physicists, get involved and 17 try to image the injection site if it was available, 18 if the injection site was in the field of view. And 19 in those cases, the clinicians determined that that 20 was the infiltration.
21 But, I think the University of Santiago in 22 Spain example, they had an 18 percent infiltration 23 rate. And of those they found that they had a very 24 small percent that were moderate or significant.
25 105 And you know, my point is, if you're only 1 looking at a static image, all you're seeing is what 2 was taken at 70 minutes. You don't know whether it 3 was, you know, dramatically worse than that 4 beforehand.
5 So you'd need to have some idea of what 6 happened during the uptake period. If that makes 7 sense. 8 CHAIRMAN PAL ESTRO: All right. Thank you.
9 Any comments or questions from attendees in the room?
10 (No response) 11 CHAIRMAN PALESTRO: On the bridge line?
12 (No response) 13 CHAIRMAN PALESTRO: All right. At this 14 point we're already running behind. And I'd like to 15 end the discussion for the moment on this topic.
16 However, it's an interesting issue that's 17 been raised. And it was last addressed by the NRC in 18 1980, which is almost 40 years ago.
19 And at that time I don't -- don't know if 20 there were any intravenously administered therapeutic 21 agents. There certainly are several since then.
22 And the vast majority, if not all of the 23 intravenously administered diagnostic agents were 24 technetium based. And now we've got indium-based 25 106 agents, iodine-based agents, and so forth.
1 So, with that in mind, I'm going to form a 2 Subcommittee to reevaluate the 1980 NRC decision. And 3 you may come away with the same conclusion.
4 I have no idea. And this has nothing to 5 do with the device that Mr.
Lattanze is talking about.
6 That's not part of this.
7 And so I'd like the Subcommittee to charge 8 -- the Subcommittee is to reevaluate the NRC's 1980 9 infiltration position. And to report back to us at 10 the September meeting.
11 I'm going to ask that Ms. Martin chair 12 this Committee, Subcommittee, excuse me.
And members 13 will include Mr. Green, Ms. Shober, Mr. Sheetz, and 14 Dr. Dilsizian.
15 MR. LATTANZE: Thank you very much.
16 CHAIR PALESTRO: Thank you. And at this 17 time we will take a short break and resume -- let's 18 try to resume at five to 11:00 so we can get ourselves 19 back on schedule. Thank you.
20 MR. EINBERG: But excuse me, before we 21 break, Dr. Palestro, would you like to have a 22 patients' rights advocate on the subcommittee also?
23 Because I think this has impac ts for patients as well.
24 MS. HOLIDAY: Mr.
Einberg, Ms. Weil's term 25 107 ends in August. So she will not be here for the 1 September meeting.
2 However, I do recognize that the 3 Subcommittee would start their work prior to the 4 September meeting. Just to throw that out there for 5 consideration.
6 MR. EINBERG: To the extent that she can 7 participate while the deliberations are going on, I 8 would recommend that.
9 CHAIRMAN PALESTRO: I think that's an 10 excellent suggestion. I appreciate that. Ms. Weil?
11 MEMBER WEIL: Yes.
12 CHAIRMAN PALESTRO: You will?
13 MEMBER WEIL: I will.
14 (Laughter) 15 CHAIRMAN PALESTRO: Thank you. Okay.
16 We're adjourned for ten minutes.
17 (Whereupon, the above-entitled matter 18 went off the record at 10:44 a.m. and 19 resumed at 10:56 a.m.)
20 CHAIRMAN PALESTRO: I'm going to call the 21 session to order, please, to resume, so we can try to 22 get back on schedule.
23 MS. HOLIDAY: Dr. Palestro just requested 24 that ACMUI members return to your respective seats.
25 108 We're getting ready to restart.
1 CHAIRMAN PALESTRO: All right, and we're 2 going to resume with item number six on the agenda for 3 today, a summary of the changes to 10 CFR Part 35, and 4 it will be presented by Ms.
Lisa Dimmick from the NRC.
5 Thank you.
6 MS. DIMMICK: Thank you, and good morning, 7 everyone. So I guess I can thank the meeting planners 8 for not putting this talk after the lunch break 9 because I know, the regulation changes, how exciting 10 is that? So anyway, we'll go ahead and get started.
11 So this presentation will kind of quickly 12 step through the final rule changes, largely for 10 13 CFR Part 35, and there were some changes impacting 14 Parts 30 and 32, but largely Part 35.
15 So the objective today is to present to 16 you a summary of the rule changes that became 17 effective January 14, 2019. J ust to note that Part 35 18 was last amended in its entirety back in 2002, so this 19 rule change or set of changes really encompasses a 20 number of clarifications that needed to be made for 21 that 2002 rule.
22 So this was really a long term rule in the 23 making. There's a lot of history with this rule.
24 There's a lot of involvement with ACMUI on this rule 25 109 change, especially in the area of permanent implant 1 brachytherapy and the medical event definitions.
2 The major changes to the rule do address 3 impacts for permanent implant brachytherapy, medical 4 event reporting, and notification. The rule also now 5 names an associate radiation safety officer or 6 officers on a medical license.
7 There are generic changes to training and 8 experience requirements for all individuals, and there 9 is now a new frequency for reporting of, well, a new 10 frequency for testing the Moly breakthrough in your 11 Moly/Tech generators, as well as the reporting of 12 failed generators.
13 So those are the major changes that most 14 people are aware about. However, there are changes 15 throughout the rule, and so in that sense, the rule 16 changes were substantive because there were a lot of 17 changes.
18 So we can kind of break down our talk this 19 morning on the rule changes in 11 broad areas of the 20 Part 35 regulation, so we're going to touch on the 21 generator changes, the changes or the new associate 22 RSO, as well as the ophthalmic physicist.
23 There were some changes impacting emerging 24 technologies, changes in notifications, and some of 25 110 the rule changes or areas of interest are actually 1 found in the notification section of the regulation.
2 We have changes to manual brachytherapy, training and 3 experience.
4 There are some changes in diagnostic 5 medical uses, also in the 10 CFR 35.300, 6 radiopharmaceutical requiring a written directive, 7 sealed source and device registry, vendor training, 8 and Gamma Knife.
9 So we're going to talk just basically 10 about some of these rule changes, and in some areas, 11 I'll try to give a little bit more perspective or 12 insight as to why that rule was changed.
13 Okay, so for generators, the breakthrough 14 for the Moly/Tech generator is now to be required for 15 each generator elution. Before, the rule required 16 just the first elution of the day with that generator, 17 but now it's for each generator elution the 18 Moly/Technetium ratio needs to be checked.
19 Also, if the breakthrough limits for the 20 Moly/Tech generators, as well as the strontium 21 rubidium generators, and we also carry this into the 22 35.1000 guidance for the germanium/gallium generators, 23 if you have a breakthrough in excess of the limits, 24 there is a requirement now to report that as a failed 25 111 generator to both the NRC and the distributor.
1 So the rule change basically changes the 2 frequency for testing the Moly/Tech bre akthrough, and 3 then there is the reporting requirement for failed 4 generators.
5 So the reporting requirement for the 6 failed generators is a telephone report within seven 7 calendar days, and that telephone report needs to 8 include the manufacturer, model number, and serial 9 number or lot number of the generator, the results of 10 the measurement, the date of the measurement, and 11 whether the dosages were administered to patients or 12 human research subjects when the distributor was 13 notified and the action taken.
14 A follow up 30-day report is also required 15 to note any actions taken by the licensee, also the 16 patient dose assessment and the methodology used to 17 make that dose assessment if the eluate was 18 administered to the patient.
19 So when we were talking earlier about the 20 strontium rubidium generator and the breakthrough, so 21 now we have a new regulation that will help filter or 22 provide a path to report those situations that wasn't 23 maybe previously present in the regulations.
24 The regulations now define an Associate 25 112 Radiation Safety Officer. Here, it will be ARSO, and 1 we also identify an ophthalmic physicist. So these 2 terms are defined in the regulation. These are new 3 definitions in the regulations.
4 There are some changes to preceptors for 5 the ARSO, and also some other requirements for the 6 ARSO that I'll mention here in a moment, and it 7 provides some clarifications for the licensee, the 8 radiation safety officer, and the ARSO.
9 So the changes in the regulations are 10 found, some of the changes here are found in 35.50, 10 11 CFR 35.50. It now includes training re quirements for 12 the radiation safety officer and associate radiation 13 safety officer.
14 The changes made clarify the basic 15 training and experience requir ements are basically the 16 same for the RSO and the ARSO. The regulations also 17 permit the ARSO to provide written attestation.
18 So for example, the ARSO authorized for 19 maybe 10 CFR 35.100 uses on a license and that license 20 is authorized for 35.100 and 35.200 uses. That ARSO 21 could provide the attestation for another ARSO or a 22 radiation safety officer for the 35.100 uses because 23 that's the uses for which that ARSO is authorized. So 24 the message here is that the ARSO can provide written 25 113 attestation for another RSO or ARSO.
1 This regulation also fixed a few issues in 2 the previous regulation. It does now permit -- so if 3 an individual is seeking to be a new authorized user 4 and a radiation safety officer on a new license, that 5 can occur.
6 Previously, when a new license was issued, 7 you could not make the individual both an AU and an 8 RSO at the same time. Now with the rule, that can 9 happen for those new licenses where the AU will also 10 be the RSO.
11 The regulation, the new regulation also 12 fixes and permits authorized individuals to use 13 authorized status to be an RSO on a different license 14 for the same use for which the individual is 15 authorized.
16 Previously, the authorized individuals had 17 to be listed on the same license for which they are 18 seeking RSO status. So the rule made some 19 clarifications and provided some flexibilities that 20 weren't previously found in the rule.
21 The ophthalmic physicist, this is a new 22 role, and there are specified tasks for the ophthalmic 23 physicist, as well as certain training criteria that 24 needs to be met for the ophthalmic physicist. The 25 114 rule also clarifies the expected duties for the 1 authorized medical physicist and that of the 2 ophthalmic physicist.
3 Emerging technologies, so with regard to 4 10 CFR 35.1000, which is the other uses of byproduct 5 material, we often refer to this as emerging medical 6 technologies, there is a link to 35.1000 to 35.12. So 7 35.12 clarified information for the 35.1000 medical 8 use applications.
9 So now, in addition to the regulations in 10 35.12, an application for a license or amendment for 11 medical use of byproduct material as described in 12 35.1000 must include any additional aspects of the 13 medical use of the material that are not addressed in 14 or are different from other parts, the other subparts 15 of 10 CFR, including general information, 16 administrative requirements, technical requirements, 17 records, and reports, also the identification and 18 commitment to follow the applicable radiation safety 19 program requirements that are appropriate for that new 20 technology that are found in the other medical 21 modalities, in addition, if there is specific 22 information that should be included regarding 23 radiation safety precautions and instructions for 24 those uses under 35.1000 or the methodology for dose 25 115 measurement for doses to be administered to patients 1 or human research subjects, as well as calibration, 2 maintenance, and repair of instruments. So the 3 regulation makes the link between 35.1000 and 35.12 4 more clear.
5 So notifications is an interesting section 6 of the regulations because this is where it describes 7 what amendments or notifications are required, so in 8 this section are some of the areas that we've already 9 mentioned regarding, for example, the ophthalmic 10 physicist.
11 So for the ophthalmic physicists was added 12 to the amendment section in 35
.13. The section of the 13 regulation now allows the licensee to allow an 14 ophthalmic physicist, in addition to an AU, AMP, or 15 ANP to work without an amendment request provided the 16 individual is already listed as an ophthalmic 17 physicist on a license.
18 Also in the notification, the ARSO was 19 added to the amendment section. This section of the 20 regulation requires the licensee to submit and receive 21 approval for an amendment before it permits anyone to 22 work as an ARSO or before the RSO assigns duties and 23 tasks to that ARSO that differ from those tasks for 24 which the individual is authorized on the license.
25 116 The notifications also permit the licensee 1 to receive a sealed source from a different 2 manufacturer or to receive a different model number 3 than authorized by its license. So if the sealed 4 source is used in manual brachytherapy, it's listed in 5 the SS&D and is in a quantity for an isotope already 6 listed by the license.
7 So this rule uses the provisions of the 8 notification process to give manual brachytherapy 9 licensees the flexibility to change manufacturers or 10 models of a source for which they're au thorized, or a 11 radionuclide for which they're authorized without 12 having to wait for an approval of an amendment.
13 The notifications, there's also, in this 14 section, the regulations were revised to remove the 15 requirement for preceptor attestation for board 16 certified individuals. The regulation continues to 17 require submission of a copy of the board 18 certification and documentation of additional training 19 of clinical case work for authorized users under 10 20 CFR 35.300 or the additional t raining for an AU or ANP 21 under 35.600.
22 And then last, I wanted to note that with 23 regard to exemptions regarding Type A specific 24 licensee of broad scope, the broad scope licensee is 25 117 exempted from certain notifica tion processes such that 1 it can name its own users and an ophtha lmic physicist 2 as a new user under that broad scope licensee, that 3 the broad scope licensee can name them without 4 notification.
5 Manual brachytherapy, so the ACMUI had 6 raised concerns that the NRC's regulations that were 7 issued in 2002 did not properly address the needs of 8 the manual brachytherapy authorized users and 9 patients. Physicians were beg inning to perform manual 10 brachytherapy procedures in real time in the operating 11 room and using image guided techniques, and as such, 12 they were finding they might need to adjust the doses 13 or the dose that was going to be delivered to the 14 patient, and they were not able to calculate the 15 radiation dose to the patients.
So they believed the 16 written directive requirements and medical event 17 reporting requirements prevented them from providing 18 the best care to patients.
19 So as a result, and a long process, 35.40 20 was amended to clarify some components of the written 21 directive.
22 With the written directive, it still 23 includes an authorized user's signature and dating 24 before the administration, but instead of requiring a 25 118 dose, it now requires the total source strength in the 1 pre-implantation portion of the written directive to 2 be recorded, and what it does do is it does delete the 3 dose, so again, it's only using source strength.
4 So in the pre-implantation portion of the 5 written directive, the source strength to be 6 administered or delivered is recorded, and then upon 7 completion of the procedure, the actual source 8 strength that was delivered is what gets recorded.
9 And it does require and it introduces a 10 new term that the source strength that was delivered 11 is to be reported on the post-implantation of the 12 written directive before the patient leave the post-13 treatment recovery area.
14 And what we mean by that, and it's got a 15 specific meaning in the regulations, the term post-16 treatment recovery area in 35.40 means the area or 17 place where a patient recovers immediately following 18 the brachytherapy procedure before being released to a 19 hospital intensive care unit or patient room, or in 20 the case of an outpatient treatment, released from the 21 licensee's facility.
22 So the other change in the manual 23 brachytherapy, it revises the definition of a medical 24 event for permanent implant br achytherapy. So the new 25 119 requirements or the new criteria for reporting a 1 medical event in permanent implant brac hytherapy says 2 that licensees shall report any event as a medical 3 event except for an event that results from patient 4 intervention in which the permanent implant 5 brachytherapy, for the permanent implant 6 brachytherapy, the administration of byproduct 7 material or radiation from byproduct ma terial results 8 in a total source strength administered differing by 9 20 percent or more from the total source strength 10 documented in the post-implantation portion of the 11 written directive, or the other, going on, the total 12 source strength administered outside of the treatment 13 site exceeding 20 percent of the total source strength 14 documented in the post-implantation portion of the 15 written directive, or the administration that includes 16 any of the following, the wrong radionuclide, the 17 wrong individual or human research subject, a sealed 18 source implanted directly into a location 19 discontiguous from the treatment site as documented in 20 the post-implantation portion of the written 21 directive, or a leaking source resulting in a dose 22 that exceeds 0.5 Sv or 50 Rem to an organ or a tissue.
23 And another term was introduced in the 24 regulations being discontiguous, and what does that 25 120 mean with regard to 10 CFR 35.40? Discontiguous in 1 general terms is used to describe things that are not 2 contiguous in space, things that are not adjacent or 3 touching, and things that have a gap between, or 4 disconnected, or separate.
5 As it relates to medical event criteria in 6 35.3045 for permanent implant brachytherapy, 7 discontiguous means a location that is not physically 8 adjacent to or touching the treatment site.
9 The other component to manual 10 brachytherapy is requiring licensees to have 11 procedures to determine if medical events have 12 occurred, and the procedures must have determined 13 within 60 days.
14 So the requirement now has that the 15 procedures need to determine for permanent implant 16 brachytherapy within 60 calendar days from the date 17 that the implant was performed, the total source 18 strength administered outside of the treatment site 19 compared to the total source strength documented in 20 the post-implantation portion of the written directive 21 unless a written justification of patient 22 unavailability is documented, and that's what I just 23 referred to.
24 So concerning training and experience, 25 121 this rule did address some generic training and 1 experience changes. Primarily this rule removed the 2 written attestation and board certification pathway 3 requirements.
4 It revised the written attestation when 5 one is required to say in one portion of it that the 6 person who is being attested to is able to 7 independently fulfill the radiation safety-related 8 duties as, for instance, an authorized user, as an 9 authorized medical physicist, or authorized nuclear 10 pharmacist.
11 This regulation change also permits 12 residency program directors to provide written 13 attestation under certain conditions.
14 So one area I wanted to note was that in 15 35.51, this is for the training for the authorized 16 medical physicist. This section was amended to 17 clarify that the AMP who provides supervision for 18 meeting the requirement of this section must be 19 certified in medical physics by a specialty board 20 whose certification process has been recognized by the 21 NRC or an agreement state.
22 Under the T&E, there were some 23 grandfathering conditions that were incorporated into 24 the rule as a result of some previous petitions in 25 122 this area. The rule grandfathered
-- so grandfathered 1 RSOs and AMPs must meet the requirements in 10 CFR 2 30.50 and 30.51 for materials or uses that they were 3 not previously authorized for.
4 The grandfathered individuals who were 5 board certified on or before October 24, 2005 by 6 boards listed in the regulation for materials and uses 7 performed before this date. So there was some 8 grandfathering as a result of what we know as the 9 Ritenour petition. For those of you, that petition 10 came in several years ago.
11 There were a few clarifications made under 12 diagnostic medical uses. There was concern that the 13 sources authorized under 35.65 for calibration, 14 transmission, and reference sources were being used on 15 patients without licensees recognizing these uses 16 required by an authorized user.
17 There was also some concern that the 18 sources that have an individual maximum activity were 19 being bundled to produce a source that exceeded the 20 maximum value in the regulation, so clarifications 21 were made in that regard, and so the regulations also 22 clarify when these sources do not have to be listed in 23 the license.
24 Continuing with diagnostic medical uses 25 123 for the T&E, for use of sealed sources and medical 1 devices for diagnosis, this section was restructured 2 and expanded to clarify that both diagnostic sealed 3 sources and devices authorized under 35.500 for use of 4 sealed sources for a diagnosis are included in the T&E 5 requirements of the section.
6 A new paragraph was also added that 7 recognizes the individuals who are authorized for uses 8 listed in 35.200 or equivalent agreement state 9 regulations are also authorized for use of diagnostic 10 sealed sources or devices under 35.500.
11 So there were amendments made under 12 35.300, radiopharmaceuticals requiring a written 13 directive, and so the points I wanted to make here was 14 that under 35.300, there was a change that clarifies 15 that a licensee's authorization of the 16 radiopharmaceuticals requiring a written directive is 17 only for those types of radiop harmaceuticals for which 18 the authorized user has documented training and 19 experience.
20 This section was also amended for the 21 35.390, training for unsealed byproduct material for 22 which a written directive is required. This section 23 of the regulation was revised to identify a single 24 category of parenteral administrations of a 25 124 radionuclide.
1 Parenteral administration of any -- and 2 that changes parenteral administration of any 3 radioactive drug that contains a radionuclide that is 4 primarily used for electron emission, beta radiation 5 characteristics, alpha radiation characteristics, or 6 photon energy of less than 150 keV for which a written 7 directive is required.
8 And just to note, in 35.300 and under 9 35.396, training for parenteral administration of 10 unsealed byproduct material requiring a written 11 directive, the change concerning the parenteral 12 radiation characteristics was carried over in this 13 section to be the same as 35.390.
14 And I also wanted to note that under 15 35.396, that this is a training and experience section 16 that does still require an attestation for board 17 certified individuals.
18 I have several slides that, after looking 19 at them, are probably a little bit confusing. So 20 they're included. It's not ad vancing, so -- that talk 21 about the previous rule, the current rule through 22 35.300, but I believe they're a little bit confusing 23 and they kind of restate what I just said in regard to 24 the 35.300 and 35.390 and 396 descriptions in the 25 125 regulations that were amended, so we're going to skip 1 ahead through these for clarification purposes.
2 35.400, use of sealed sources for manual 3 brachytherapy, so this section is expanded to allow 4 for sources that are listed in the sealed source and 5 device registry for manual brachytherapy to be used 6 for other manual brachytherapy uses that may not be 7 explicitly listed in the sealed source and device 8 registry.
9 The paragraph in the regulation was 10 amended to allow sources that are listed in the sealed 11 source and device registry for manual brachytherapy 12 medical uses to be used for manual brachytherapy 13 medical uses that are not explicitly stated in the 14 sealed source and device registry provided that these 15 sources are used in accordance with the radiation 16 safety conditions and limitations described in the 17 sealed source and device registry.
18 These radiation safety conditions and 19 limitations described in the sealed source and device 20 registry may apply to storage, handling, 21 sterilization, conditions of use, or leak testing of 22 the radiation sources.
23 The NRC recognizes that the medical uses 24 specified in the sealed source and device registry may 25 126 not be all inclusive, so the final rule permits 1 physicians to use manual brachytherapy sources to 2 treat sites or diseases not listed in the sealed 3 source and device registry.
4 For example, the sealed source and device 5 registry may specify that the sources are for 6 interstitial use, but the final rule change allows 7 physicians to use sources for a topical use. It does 8 not have to be explicitly stated in the SS&D that 9 topical use is a condition of use.
10 So the NRC determined that flexibility 11 should be afforded to physicians to use at their 12 discretion in the practice of medicine brachytherapy 13 sources in this way.
14 Coming down the pipe, vendor training, so 15 there was an amendment to 35.610, safety procedures 16 for instructions for remote afterloader units, 17 teletherapy units, and gamma stereotactic radiosurgery 18 units. This section was revised and restructured to 19 add a new training requirement for the use of 20 afterloaders, teletherapy units, and gamma 21 stereotactic radiosurgery units.
22 This amendment requires all individuals 23 who operate these units to receive vend or operational 24 and safety training prior to their first use for 25 127 patient treatment of a new unit or an existing unit 1 with a manufacturer upgrade th at effects the operation 2 and safety of the unit. Again, this is a new 3 requirement in these regulations.
4 This training must be provided by the 5 device manufacturer or by an individual certified by 6 the device manufacturer to provide that training.
7 This training is also required when software upgrades 8 are made by the vendor or the manufacturer that effect 9 the operation or safety of the unit.
10 This section was also revised to clarify 11 that the training required by this paragraph on the 12 operation and safety of the unit applies to any new 13 staff who will operate the unit or the units at the 14 facility.
15 And the last regulation change I wanted to 16 mention is in the area for 35.655 for Gamma Knives 17 specifically, and this is now the full inspection 18 servicing for teletherapy and gamma stereotactic 19 radiosurgery units.
20 The section title was revised to delete 21 the five-year inspection and insert full inspection 22 servicing to more accurately reflect the requirements 23 in this section for inspection and servicing of 24 teletherapy units and gamma stereotactic radiosurgery 25 128 units. 1 The regulation was revised to extend the 2 full inspection and servicing interval between full 3 inspection servicing for gamma stereotactic 4 radiosurgery units from five to seven years to assure 5 proper functioning of the source exposure mechanism.
6 The interval between the full inspection 7 and servicing for teletherapy units remains the same, 8 so it's not to exceed five years. So it was changed 9 for GSRs to seven years and remain the same for 10 teletherapy units at five years.
11 And that, real quick, were the changes to 12 Part 35, and if you have any questions, my colleague, 13 Donna-Beth Howe -- yeah, I don't know if you want to 14 hold questions now, or if there are any questions, or 15 -- 16 CHAIRMAN PALESTRO: Thank you, Ms.
17 Dimmick, for a very concise review of a very 18 comprehensive document. We have time for one or two 19 brief questions or comments from the committee.
20 MS. DIMMICK: Let me -- I'll take 21 questions, but just, we are having -- we've had 22 several public meetings on the Part 35 changes and 23 they last anywhere from about four hours, then with a 24 lunch break, almost five hours.
25 129 So they are fairly comprehensive and take 1 a deeper dive into why the rule areas were changed.
2 We also talk about inspection changes that were made 3 to look at various areas of the regulations and 4 inspection.
5 Our next public meeting will be on April 6 24. It will be on our public meeting notice website, 7 so, and Donna-Beth Howe and Maryann Ayoade have been 8 the presenters of those webina rs and they've been very 9 well received.
10 So if anyone wants to spend a couple of 11 hours1.273148e-4 days <br />0.00306 hours <br />1.818783e-5 weeks <br />4.1855e-6 months <br /> listening more about Part 35, you are more than 12 welcome to call into that webinar.
13 CHAIRMAN PALESTRO: Thank you very much.
14 Mr. Sheetz?
15 MEMBER SHEETZ:
I actually participated in 16 the last webinar and I thought it was absolutely 17 excellent, and I think it's a must for any medical 18 RSO. 19 MS. DIMMICK: Yeah.
20 CHAIRMAN PALESTRO: Thank you. Any other 21 comments or questions? Comments or questions from 22 attendees here in the room or on the line?
23 All right, if not, then we will move onto 24 the final topic of this morning's session, the 25 130 Germanium-68/Gallium-68 Subcom mittee Report which will 1 be presented by Ms. Shober.
2 MEMBER SHOBER: Good morning. I will wait 3 for the slides to come up, I guess. Okay, yes, my 4 name is Megan Shober and I'm going to be presenting 5 the discussion from the ACMUI subcommittee on the 6 Germanium-68/Gallium-68 generator licen sing guidance.
7 Next slide.
8 The subcommittee members, as we heard 9 earlier this morning, most of them are Dr. Metter, 10 Mike Sheetz, and myself, and our NRC staff resource 11 who is very helpful is Dr. Diabes. Next slide, 12 please. 13 Okay, so just to kind of go through some 14 of the features of the existing guidance that was 15 published in 2017 -- you can click. The current 16 guidance expressly names the Eckert and Ziegler brand 17 of the generator. It also includes a specific 18 breakthrough limit that's particular to that 19 generator.
20 It has some instructions for what to do if 21 the generator hasn't been eluted within 48 hours5.555556e-4 days <br />0.0133 hours <br />7.936508e-5 weeks <br />1.8264e-5 months <br />. It 22 requires notification to the NRC operations center if 23 the eluate exceeds the breakthrough levels, and it 24 requires wipe tests on each day of use. So that's 25 131 what has been, that is functionally in place now, and 1 if you can go to the next slide?
2 So when the proposed guidance was 3 published, there were several things the NRC was 4 trying to move forward with in these future versions 5 of the guidance, and one of those is to make the 6 guidance brand neutral as there's already one 7 additional generator and several others that are 8 coming down the pipeline.
9 So the proposed revision removes the 10 reconditioning requirements for generators that are 11 not eluted within 48 hours5.555556e-4 days <br />0.0133 hours <br />7.936508e-5 weeks <br />1.8264e-5 months <br />, and there were some 12 revised breakthrough reporting requirements in the 13 proposed guidance that talked about multiple failures, 14 and so those are just some of the higher level changes 15 with the proposed licensing guidance changes. Next 16 slide. 17 Okay, so the subcommittee had a few 18 recommendations that I would like to highlight today.
19 So the guidance in its draft form had an alternative 20 pathway training option for an authorized user, but 21 not for an authorized nuclear pharmacist. So to make 22 it consistent, we suggested adding an alternate 23 pathway training option for the authorized nuclear 24 pharmacist.
25 132 As I mentioned earlier, the breakthrough 1 limit that is in the proposed guidance revision does 2 have a brand-specific breakthrough limi t, and it's my 3 understanding that some of the other generators that 4 are developed or being developed may have different 5 breakthrough limits for those products, and so our 6 recommendation was to remove the brand-specific 7 breakthrough limit from the licensing guidance.
8 And then we, as the subcommittee, wanted 9 to reject the proposed breakthrough fai lure reporting 10 requirement, and in lieu of that, we recommend 11 conformance with the recently published 10 CFR 35 that 12 we just heard about. Okay, next slide.
13 Okay, so one of the things that we had a 14 lot of discussion about in the subcommittee is at what 15 point the breakthrough is considered a generator 16 failure, and this is because unlike with other 17 generators that are commonly in use in nuclear 18 medicine, the breakthrough testing for these 19 germanium/gallium generators, it does take a couple of 20 days to actually get to the point where you can 21 determine whether the generator has breakthrough.
22 And so the question that we have that we 23 weren't really able to resolve with the current 24 licensing guidance is when does that failure happen?
25 133 Is it when you elute the generator to take the test?
1 Is it when you measure that after all of 2 the gallium has decayed? Is it later, some day later 3 when you actually calculate what that breakthrough 4 number is? And so we just were wanting some 5 clarification on that point at which that breakthrough 6 is considered failed.
7 And then with the last recommendation to 8 highlight today, we recommended revising the survey 9 requirements to allow increased flexibility in how 10 those are performed.
11 So the guidance currently specifies wipe 12 testing, but, for example, kit preparation areas, they 13 could be adequately monitoring with meter surveys.
14 And then the other comment about that is 15 that the guidance currently requires generator storage 16 areas to be surveyed quarterly, and that conflicts 17 with the existing guidance in NUREG-1556 Volume 13 for 18 radiopharmacies, which requires weekly contamination 19 surveys of storage areas.
20 So those are the recommended changes from 21 the subcommittee and that's all I had for this part of 22 the presentation.
23 CHAIRMAN PALESTRO: Okay, thank you for 24 your presentation, Ms. Shober. Any comments from 25 134 other members of the subcommittee? Mr. Green?
1 MEMBER GREEN: I think this is a very nice 2 report, a very thorough report, and it does nail down 3 some of the unique characteristics of germanium 4 generators.
5 One artifact of the germanium generator is 6 it does not have a United States Pharmacopeia 7 breakthrough percentage. The analog, the Moly/Tech 8 generator has a USP limit of 0.15 microcuries of Moly 9 per millicurie of Tech at the time of patient 10 administration.
11 There is no USP analog for that for 12 germanium/gallium because the raw trichloride is not 13 FDA approved for human use in raw form. You use that 14 as an API to label a kit that's FDA approved. So 15 there's no USP limit for the breakthrou gh percentage.
16 The manufacturer, Eckert and Ziegler, has 17 a 0.001 percent breakthrough limit that they've 18 adopted and that's the European Pharmacopoeia 19 breakthrough limit because in the European 20 Pharmacopoeia, they do have a standard for it, and so 21 generator manufacturer number one has that European 22 limit, so does generator number two. The Galli Eo has 23 the same 0.01 percent.
24 There's another manufacturer coming out 25 135 that's got a unit that's in the pipeline that has a 1 0.05 percent, so it's a value five times higher than 2 the other two manufacturers.
3 There is no U.S. limit to point to. We're 4 kind of hugging and holding the European limit for 5 those two manufacturers. Is t he NRC, is the committee 6 comfortable with saying don't exceed the 7 manufacturer's limit, but two manufacturers have a 8 value that is one-fifth of the other? Just a 9 question.
10 CHAIRMAN PALESTRO: Any other comments or 11 questions? Mr. Sheetz?
12 MEMBER SHEETZ: I actually have a question 13 or a clarification from the NRC related to the 14 licensing guidance document which was not addressed by 15 our subcommittee.
16 There was a memorandum issued on July 13, 17 2017 creating a technical basis for the exemption from 18 the decommissioning funding plan for licensing of a 19 germanium/gallium generator, but I was curious and 20 I've had questions from several licensees to me on 21 what the rationale was for still requiring the 22 financial assurance element?
23 If the requirement is for the licensee to 24 have to return the generator to the vendor or to the 25 136 manufacturer, what was the need or rationale for still 1 requiring the financial assurance?
2 Because the decommissioning funding plan 3 requires manpower to develop the plan, but the 4 financial element actually costs the licensee money, 5 and so if we could provide clarification on that, I 6 know that would because I know I have gotten questions 7 on that. Thank you.
8 MR. EINBERG: Lisa, can you address that 9 question, or Said?
10 DR. DIABES: Said Diabes. Thank you for 11 the question. So before I answer any of your 12 questions, let me clarify something. So a licensee 13 has the option of pursuing a DFP or pursuing the 14 medical exemption, so they have either one, or, you 15 know, whatever is in their best interest.
16 The whole point of providing the medical 17 exemption was to relieve a licensee from the actual 18 DFP because early on, the same rationale of being 19 expensive, too onerous, too co mplicated was brought up 20 to the committee and to staff as well, so the whole 21 point of initiating discussions of the medical 22 exemption were under that basis.
23 So going back to your question on what's 24 the point of financial assurance. When we initiated 25 137 discussions as we exempted the DFP, there had to be a 1 mechanism that provided a pock et of money or basically 2 finances to assure that in a case of bankruptcy or a 3 case of an emergency, there was funding somewhere to 4 work with decommissioning, and that was the basis.
5 I don't know if Lisa would like to provide 6 further information or our legal side. Okay, thank 7 you. 8 CHAIRMAN PALESTRO: Mr. Sheetz?
9 MEMBER SHEETZ: Thank you, and I 10 understand that rationale should the licensee go 11 bankrupt, but in the guidance, in that memorandum, it 12 left it open to agreement stat es because it's a health 13 and safety compatibility level.
14 And so the agreement states would have the 15 option of not requiring financial assurance, and 16 that's exactly what's happening across the country.
17 Some agreement states are requ iring it, other ones are 18 not, and so it makes it difficult for the licensees 19 having a double standard.
20 CHAIRMAN PALESTRO: Mr. Einberg, could I 21 ask you to respond to that?
22 MR. EINBERG: Yes, so the agreement states 23 are co-regulators, and as such, they have the latitude 24 to establish the financial assurance re quirements for 25 138 their particular state.
1 As such, again, what we find acceptable, 2 the agreement states may have more stringent 3 requirements, and as such, it seems like what you're 4 calling out is happening across the country or in 5 certain states, that they have additional requirements 6 that they want to impose, and so that's a part of the 7 compatibility that we have agreed with the agreement 8 states.
9 Our agreement state representative, Megan 10 Shober, do you have anything to add regarding that?
11 MEMBER SHOBER: So the thresholds at which 12 financial assurance is required, those are uniform 13 across the country, and I think the difference is that 14 what you're mentioning is with the amount of financial 15 assurance or whether or not there's an exemption.
16 So agreement states or the NRC can exempt 17 licensees from any rule or requirements on a case by 18 case basis, and so I don't have a lot of -- I know 19 that there was a lot of question originally when this 20 first version of the guidance came out as far as what 21 actually is being exempted.
22 And so, and we were receiving requests 23 from licensees to use these products before they 24 showed up at a lot of NRC facilities, a nd so straight 25 139 out the gates, agreement states often have -- we 1 encounter these products first.
2 We have to make these decisions early on, 3 and it took quite a while to get the memo out 4 originally about what NRC's position about financial 5 assurance was.
6 And so I think in the period of months to 7 a year, or however long it took between when these 8 products first show up versus when the NRC policy 9 statement came out, that's the time period where the 10 various states are making the best decisions they can 11 with the information that we have, and I think that's 12 where some of those gaps tend to show up, and then 13 once those exemptions have been granted, it's 14 difficult to go back and then require the financial 15 assurance from a licensee.
16 CHAIRMAN PALESTRO: Mr. Green?
17 MEMBER GREEN: I understand the confusion 18 at first when the products first came on the market, 19 and so there was the document to allow an exemption 20 for the decommissioning funding plan and that's great, 21 but it still left open for debate in different 22 agreement states the financial assurance's warranty 23 bond. 24 I can assure you that the roughly $100 25 140 cost to Federal Express a generator back to the 1 manufacturer or distributor is far outweighed by the 2 annual cost of the quarter-million dollar financial 3 assurances' warranty bond. For the generator, it's 4 just overkill.
5 For under 100 bucks, I can FedEx a package 6 and make it go away, and have a proof of delivery 7 receipt that that generator is back at the 8 manufacturer, but a quarter-million dollar financial 9 assurances' warranty bond with an annual payment of 10 one or two percent of that bond to keep that bond 11 there far exceeds $100 for FedEx.
12 CHAIRMAN PALESTRO: Other comments or 13 questions? Ms. Shober, I'd like to go back for a 14 moment. It was an issue, I think, raised by Mr.
15 Green, and then we got off on the financial assurance, 16 regarding the difference in the breakthrough levels.
17 Does the subcommittee have any concerns 18 about the fact that one company is allowing a 19 breakthrough about five times as much as two other 20 vendors? 21 MEMBER SHOBER: We, I think absent a value 22 that's in the regulations, I'm not sure that as a 23 subcommittee, I'm not sure that we want to recommend a 24 particular number, and then just looking, especially 25 141 as we look forward, I don't know what those future 1 products are going to look like. I'm not sure that 2 it's appropriate for us to specify a number.
3 CHAIRMAN PALESTRO: Thank you. That 4 answers my question. Other comments or questions?
5 Mr. Ouhib?
6 MEMBER OUHIB: Yeah, I think it only makes 7 sense to have some sort of a number that any company 8 should be below that. They don't have to meet that, 9 but they have to be somewhere below a certain number.
10 MEMBER SHOBER: So are you suggesting a 11 maximum that may not agree with any of the vendor 12 recommendations?
13 MEMBER OUHIB: Correct, but something 14 that's meaningful, you know, based on some data.
15 CHAIRMAN PALESTRO: The question to that 16 is are those data available? And absent those data, 17 it would seem at least for the moment to be the more 18 appropriate course is what the subcommittee had 19 adopted. Mr. Green?
20 MEMBER GREEN: I'm aware of one published 21 study that shows the actual effective d ose equivalent 22 from, you know, minuscule micro, submicrocurie 23 quantities of germanium in gallium, and the argument 24 could be made that even the manufacturer's level of 25 142 0.001 percent is gross overkill, but that's votes.
1 We have the European Pharmacopoeia, which 2 two manufacturers have adopted, but it really doesn't 3 bear any semblance to reality as far as level of 4 patient harm.
5 CHAIRMAN PALESTRO: Thank you. Any other 6 comments or questions from the subcommittee or the 7 committee? Comments or questions from attendees in 8 the room? Comments or questio ns from the bridge line?
9 MS. JAMERSON: Yes, we have two 10 individuals. Mr. Mattmuller, I will unmute your line.
11 MR. MATTMULLER: Yes, hi, this is Steve 12 Mattmuller. As they often say, long time listener, 13 first time caller on the radio.
14 But I certainly appreciate the comments on 15 the financial assurances because I really think while 16 they're needed, I think at the current level, they're 17 inappropriate, inappropriately high.
18 And as an example, we recently are in the 19 process of replacing our cyclotron, so we've had to 20 figure out how much it would cost to remove and have 21 our old cyclotron disposed of, and the costs and the 22 effort are in sharp contrast to what would be needed 23 for a gallium generator.
24 I mean, for a cyclotron, you have a high 25 143 energy accelerator that serves as a source of protons 1 for the radionuclide production versus a gallium 2 generator. It's a final product.
It produces -- the 3 generator itself is produced under an FDA GMP and it 4 serves as a source of gallium-68 or 5 radiopharmaceutical used in a patient.
6 The math of the two items, the cyclotron, 7 its utility cabinets, its water recirculation system, 8 its shielding all adds up to a total of 66 tons versus 9 31 pounds for the EZ generator.
10 If you consider the radionuclides, the 11 cyclotron components and concr ete floor underneath the 12 cyclotron contain activation products from its 13 operation, and the exact level and quantities are 14 really unknown at this time versus the generator where 15 you know exactly how much is in it from the 16 calibration label.
17 When it comes to disposal sites, our 18 cyclotron will go to two different sites in the U.S., 19 one in Idaho and a second one in Texas for the 20 cyclotron itself and the shields, whereas for the 21 generator, it gets returned to the manufacturer.
22 So what are the current costs for all of 23 these activities? To decommission and remove our 24 cyclotron, it will cost less than $400,000 versus 25 144 what's currently recommended by the NRC is if you have 1 less than or equal to 100 millicuries, $225,000, and 2 if you have more than 100 millicuries of germanium, 3 $1.125 million.
4 So I think as highlighted or was hinted in 5 some of the previous comments by other members, the FA 6 amounts are really inappropriate for a gallium 7 generator.
8 And I would say when the NRC staff first 9 considered the FA amounts for the licensing guidance, 10 one really couldn't fault them for erring on the 11 conservative side, but we've now had several years of 12 experience with the generator in the field with no 13 incidents.
14 And as compared to other radionuclides 15 that require financial assurances, it should be 16 emphasized that this is a final product. It is a 17 completely known entity.
Its product, gallium-68, is 18 used in patients, and its disposal is very, very 19 simple. 20 So I think it would be wonderful if the 21 same subcommittee could make a recommendation to 22 assign more reasonable levels of financ ial assurances 23 for the generators. I think $10,000 per generator 24 would be more than sufficient and appropriate. Thank 25 145 you. 1 CHAIRMAN PALESTRO: Thank you, Mr.
2 Mattmuller. Any other comments or questions from the 3 bridge line?
4 MS. JAMERSON: Yes, we have Mr. Rubin.
5 Mr. Rubin, I have unmuted your line. Mr. Rubin?
6 CHAIRMAN PALESTRO: All right, while 7 you're trying to connect with Mr. Rubin, I see that 8 Ms. Weil had a comment or a question.
9 MEMBER WEIL: I do have a comment just in 10 support of Mr. Green and Mr. Mattmuller's comments.
11 This is one of those instances where -- you can't hear 12 me -- one of those instances where an unnecessarily 13 stringent regulation may be creating a barrier for 14 patient access to a necessary piece of treatment and 15 diagnosis.
16 And I would strongly suggest that we 17 revisit this financial assurance question because 18 there are, you know, smaller institutions who don't 19 have broad scope licenses that make adding this 20 generator easy, financially easy, and it's an 21 unnecessary barrier in my opinion.
22 CHAIRMAN PALESTRO: Other comments or 23 questions? Mr. Sheetz?
24 MEMBER SHEETZ: Another point to consider 25 146 is that the Appendix B Part 30 limits are based on the 1 Appendix B Part 20 limits, and so as one looks at the 2 rationale on how those limits are established from 3 inhalation and exposure rate at 10 centimeters, the 4 limit for germanium-68 would be 10 microcuries, and 5 then it would be exempt from the financ ial assurance.
6 CHAIRMAN PALESTRO: Other comments or 7 questions? Dr. Diabes?
8 DR. DIABES: Said Diabes. I want to add 9 that we're currently working on a petition for 10 rulemaking that is addressing financial assurance all 11 across, not only for germanium/gallium, but how we 12 implement financial assurance for every single case, 13 and that is currently under review and we're working 14 on it, and it will address many of the issues that 15 we're discussing here today.
16 CHAIRMAN PALESTRO: Thank you. Any other 17 comments or questions? Sorry, Ms. Martin?
18 MEMBER MARTIN: I was just wondering if he 19 could elaborate on what they were looking at for the 20 germanium-68 because obviously these are significant 21 costs now, or to follow Mr. Sheetz's recommendation to 22 allow them to be exempt by changing the limits.
23 CHAIRMAN PALESTRO: Dr. Diabes?
24 DR. DIABES: Said Diabes. So let me see 25 147 what I can say here since we're currently working on 1 this petition, but with respect to germanium and 2 gallium, we're trying to find a way that we don't even 3 have to apply the exemption anymore.
4 So it's going to be based more on a risk 5 assessment approach per isotope and it will be applied 6 in the same manner all across, but it's still -- we're 7 working on it. I cannot expand more, but I'm going to 8 pass it to our colleague here from the legal side.
9 MS. HOUSEMAN: Hi, my name is Esther 10 Houseman. I'm an attorney in the Office of the 11 General Counsel and I just want to make a quick point 12 about the process.
13 So the staff is currently in the 14 deliberative process of reviewing the petition for 15 rulemaking. They're going to develop a paper to send 16 to the commission to make a recommendation on how to 17 disposition that petition, and the commission will of 18 course vote on it.
19 So what Dr. Diabes is explaining now is 20 that process that we're going through, but do keep in 21 mind that commission approval is necessary to move 22 forward with that proposed rulemaking.
23 CHAIRMAN PAL ESTRO: I have a question. In 24 terms of that proposal, can we get a sense, and I know 25 148 it may be difficult, of a timeline?
1 MS. HOUSEMAN: The paper to the commission 2 should go up to the commission in the next several 3 weeks to a few months. Again, that depends on upper 4 level management review, so that's the point we're at 5 in the process. How long it will take the commission 6 to vote on that paper is highly variable and we can't 7 commit to a timeline on that.
8 CHAIRMAN PALESTRO: Thank you. Any other 9 comments or questions? Mr. Green?
10 MEMBER GREEN: As we get limited 11 opportunities to meet with the commissioners directly, 12 I think it would be worth the committee's time to 13 plant the seed that they will be hearing about the 14 decommissioning funding plan, financial assurance 15 warranty bond changes.
16 And they met with us one or two years ago 17 when we first showed them a generator and they 18 developed this exemption process. They will be 19 getting a document from the staff as we just 20 described, either we have the opportunity to meet with 21 the commissioners very soon.
22 And I think it would be worth the time to 23 plant the seed that we're very supportive of the 24 forthcoming financial assurance's revisions to 25 149 facilitate generator use in the medical community.
1 CHAIRMAN PALESTRO: We are on the agenda 2 for a meeting tomorrow with the commission, but that 3 program is already set and it's not going to include 4 the Geranium-68/Gallium-68 generator, nor is there, 5 and correct me if I'm wrong, Mr. Einberg, nor is there 6 leeway to make alterations in these programs.
7 MR. EINBERG: Yes, Dr. Palestro, you're 8 correct. There is no leeway to make alterations in 9 the agenda right now.
10 So, but having said that, and in listening 11 to the dialogue here, maybe, Esther, will the ACMUI 12 have an opportunity to review the SECY paper at some 13 point or would that be appropriate for them to be able 14 to review the SECY paper that's going up to the 15 commission on decommission funding?
16 MS. HOUSEMAN: I don't believe that 17 process is built into the schedule because this 18 rulemaking, this proposed, would affect far more than 19 just medical uses.
20 If the commission were to see the paper 21 and if the paper recommends that we undertake this 22 rulemaking and they agree, and they vote to initiate 23 the rulemaking process, perhaps at the draft proposed 24 rule stage and the final, the draft final rulemaking 25 150 stage, there might be an opportunity for ACMUI review 1 at that point.
2 Again, I say might because I'd have to go 3 back to the project manager and management in the 4 rulemaking division and the lead office on such a 5 rulemaking to confirm that.
6 CHAIRMAN PALESTRO: Any other comments or 7 questions? Bridge line?
8 MS. JAMERSON: Mr. Rubin, I'm going to 9 unmute your line.
10 CHAIRMAN PALESTRO: Is he on mute?
11 MS. JAMERSON: Is your phone on mute?
12 MR. RUBIN: Hey, it's Joe Rubin. Can you 13 hear me? 14 MS. JAMERSON: Yes, we can.
15 MR. RUBIN: Oh, good, sorry about that.
16 I'm clearly having audio problems. Mr. Joe Rubin on 17 behalf of the United Pharmacy Partners. We're a group 18 of 80 nuclear pharmacies. I just wanted to echo the 19 concerns about the financial assurance --
20 MS. JAMERSON: Mr. Rubin?
21 MR. RUBIN: --
for the gallium generators.
22 We'll be submitting more formal comments, but I 23 wanted to echo the concern and thank the ACMUI and the 24 commission for taking steps to try and address this 25 151 problem, so thank you for your consideration.
1 CHAIRMAN PALESTRO: Thank you, Mr. Rubin.
2 All right, at this time, I'll entertain a motion for 3 approval of the --
4 MS. JAMERSON: One more.
5 CHAIRMAN PALESTRO: One more?
6 MS. JAMERSON: Mr. MacDougall, I'm 7 unmuting your line.
8 MR. MacDOUGALL: Yes, can you hear me?
9 MS. JAMERSON: Yes.
10 MR. MacDOUGALL: This is Rob MacDougall 11 and I'm the project manager for the petition for 12 rulemaking that Esther just spoke of, and I can at 13 least attest that if the commission does approve the 14 staff's recommendation and the rulemaking goes 15 forward, we have already built in additional time for 16 review, both during the proposed rule stage and the 17 final rule stage.
18 CHAIRMAN PAL ESTRO: Thank you. All right, 19 at this -- Mr. Einberg?
20 MS. DIMMICK: Hi, it's Lisa Dimmick, 21 medical team leader. I just wanted to add that UPPI 22 did send in a letter to the ACMUI to discuss their 23 issues and concerns with the financial assurance for 24 germanium/gallium generators, so you will have a 25 152 letter appended to the meeting for their concerns.
1 CHAIRMAN PALESTRO: Any other comments or 2 questions? All right, at this point, I'll entertain a 3 motion for approval of the subcommittee's report. Dr.
4 O'Hara is second, Mr. Sheetz.
Any discussion? All in 5 favor? Any opposed? Any abstentions? All right, 6 thank you.
7 All right, that ends this morning's 8 session and we will resume promptly at 1:00.
9 (Whereupon, the above-entitled matter went 10 off the record at 12:03 p.m.
and resumed at 1:03 p.m.)
11 CHAIRMAN PAL ESTRO: All right, we're going 12 to call the afternoon session to order.
13 But before we begin with presentation on 14 medical related events, my haste to assemble a 15 subcommittee to review the NRC's viewpoint on 16 infiltrated doses, I neglected to add a staff 17 resource.
18 And that staff resource will be Maryann 19 Ayoade. And I appreciate her willingness to 20 participate.
21 So now we're going to move on to the first 22 item on this afternoon's agenda, Medical Related 23 Events. And this will be presented by Dr.
Howe. Dr.
24 Howe. 25 153 DR. HOWE: Okay, welcome everybody back 1 from lunch. And this will be such an exciting one 2 that nobody is going to be napping. I know that.
3 So, I'm going to be talking about the 4 medical events that happened in the Fiscal Year 2018.
5 Which would have been October 1st, 2017 through the 6 end of September in 2018.
7 And medical events, we always put this 8 disclaimer. The number that's presented on this slide 9 at 150,000 therapeutic procedures is a ballpark. I 10 don't really have a reference for it but it's about a 11 right number.
12 So, the message here is that, as you see, 13 we will have very few medical events for the fiscal 14 year compared to the number of patients and treatments 15 that are being provided.
16 And previously, the ACMUI has asked for a 17 perspective on how the medical events for this year 18 compare with last year. So, I'm going to just run 19 very quickly through the, I got about the previous 20 five years and then this years.
21 So, you will see that the total medical 22 events for 2013 to 2015 range from 43 to 57. If you 23 look at the table, you'll see most of the medical 24 events are down in 35.1000.
25 154 And as in all of those years and in this 1 year, most of those medical events are going to be 2 with the TheraSpheres and the SIR-Spheres.
3 And to be more up to date, I've got 2016 4 through 2018. And I've got a couple typos on there so 5 that should be '16, '17, '18.
6 And in this slide, I've got 50 medical 7 events reported in 2018. In fact, I went back and 8 counted, and I really only have 48.
9 And as you can see, we have very few 10 diagnostic medical events. We've had zero for the 11 last few years.
12 We didn't have very many 13 radiopharmaceutical therapy events. We have a fair 14 number of manual brachytherapy. That number is 15 incorrect, it should be 11 and 13.
16 And the parenthesis is the total number of 17 patients that were affected by medical events in that 18 particular category.
19 And once again, most of the medical 20 events, over half of them are occurring in 35.1000.
21 And most of those are in the Yttrium microspheres.
22 So now I'm going to start looking at 23 medical events by modality. And as you saw before, 24 there were no medical events in the diagnostic 25 155 radiopharmaceuticals.
1 And we had t wo in the radiopharmaceuticals 2 requiring written directives. We had one for I-131 3 MIBG and we had one for Radium-223.
4 The MIBG case was an interesting one. In 5 this case, part way through the adminis tration of the 6 MIBG, the patient needed to use the restroom facility, 7 so they disconnected the patient from the pump, and 8 when they came back and they reconnected it, they 9 didn't realize that they had not connected it 10 correctly at the Spiros connector.
11 And so, at the end of the procedure, they 12 ended up with a high activity of I-131 on the 13 patient's clothing and the bed linen.
14 And even at this point, they didn't do any 15 additional testing to see if t hey had a medical event.
16 And so, it wasn't until two days later that the 17 patient reported discomfort and reddening of skin on 18 the upper right thigh and erythema lesion that went to 19 desquamation the next day. So that was a fairly hefty 20 dose that they had not expected.
21 And why did it happen? Well, for one 22 thing, the activity levels for the I-131 were quite 23 high. They did not decontaminate the patient until 24 signs of the erythema.
25 156 And it's clear that they could have done 1 some surveys to see that they had an I-131 skin 2 contamination. Even though they thought it would be 3 difficult to measure because of so much I-131 in the 4 patient. 5 And what did they do for corrective 6 measures? Well, for corrective measures they decided 7 that they will no longer disconnect the patient, 8 unless it's a medical emergency. So that they don't 9 have the issues with connecting and reconnecting.
10 That they will always use absorbent pads 11 underneath the administration line, so if there is a 12 leak on the administration line it will be absorbed 13 into the pad and not onto the patient.
14 And they will develop patient specific 15 decontamination procedures. Because with the I-131 16 MIBG, they would have had to use a different type of 17 decontamination than you would use from a water-18 soluble isotope.
19 And so, the other case was a radium 20 dichloride. And in this case, we have one of our 21 medical events where the, a medical event is when you 22 depart from the written directive.
In this case, the 23 written directive asks for something.
24 It asks for an oral administration of 25 157 radium-223, which Radium-223 is never given orally.
1 And the technologist just must have been in autopilot 2 because she administered it intravenously, which is 3 the way it should have been administered. So the 4 patient got what they were supposed to get, but the 5 treatment was not in accordance with the written 6 directive.
7 And so, as a corrective measure, the 8 licensee is going to implement new written directive 9 procedures so that it is clear what mode of 10 administration you're going to have. I think they 11 looked at the, I guess they normally did sodium iodide 12 oral administration and they just clicked the wrong 13 boxes. And they're going to do a current review of 14 their policy and procedures.
15 So that takes us to the manual 16 brachytherapy procedures in 35
.400. And this is where 17 I have some mistakes on my slide.
18 We had a total of 11 medical events 19 involving 13 patients. We had an eye plaque medical 20 event and then we have an unknown procedure.
21 And then for the prostate we had non-22 medical events with 11 patients.
23 So, what happened with the eye plaque, the 24 licensee was using a new eye plaque and they hadn't 25 158 really focused on, was there a difference between 1 their old plaque and their new eye plaque. And it 2 ended up there was a difference.
3 And so, the isodose curves differed in the 4 brachytherapy plan and the dose, because of how the 5 new eye plaque was made, put the dose deeper into the 6 tissue. So they had prescribed 8,000 centigray and 7 they only received 6,500. So that was their 8 corrective action.
9 Now, I've got an unknown procedure. And 10 you should expect that if the licensee doesn't provide 11 enough information in the NMED report, we're not going 12 to know much about this procedure. And I hope this is 13 one of the areas that will be talked about in the next 14 talk. 15 So, about all we got from this particular 16 NMED report was that it was only 70 percent of the 17 intended dose. I think I could guess that it's 18 probably going to be a prostate brachytherapy one, but 19 I don't have any information to confirm that.
20 So we'll have to go back to the regulator 21 and get additional information, okay?
22 So now we move on to the largest category 23 under manual brachytherapy, and those are the prostate 24 dose administrations.
25 159 And it was pretty interesting here because 1 we had one licensee that had three different reports 2 of medical events with prostate brachytherapy. The 3 inspectors went out and inspected the licensee and 4 found a medical event in 2018.
5 And as part of that inspection process, 6 the licensee went back and did a historical review.
7 And during that historical rev iew, they identified two 8 more medical events.
9 So the first report has three separate 10 patients within it, and then we're going to have two 11 more events that were reported later. So they did not 12 determine a root cause, but they attributed it to 13 human error.
14 They did not expand on what human error 15 was involved. It appears that some seeds may have 16 migrated post-implant.
17 So the first patient received 63 percent 18 of the prescribed dose, the second patient received 19 132 percent of the prescribed dose, the third patient 20 received 130 percent of the prescribed dose for the 21 prostate.
22 So that was the first report for that 23 particular licensee. And then subsequent to the 2018 24 medical event that was reported, they discovered two 25 160 more medical events in 2018.
1 And so, in Report Number 2 it was an 2 underdose to the patient. And in Report Number 3, it 3 was also an underdose to the patient. And not a lot 4 of additional information was provided at this point.
5 So moving on to other prostate implant 6 brachytherapy therapy. We had a patient that received 7 roughly 53 percent of the dose.
8 This was a stranded implant. And part of 9 the seeds in the strand were implanted into the 10 bladder. And so when the licensee removed those 11 seeds, immediately then the do se to the treatment site 12 was much less.
13 And they attributed it to human error.
14 And for a corrective action, t hey're now going to have 15 a new written directive procedure.
16 They're going to use more needles and more 17 independent seeds and they're going to do less 18 aggressive sparing of the urethra.
And they're going 19 to stop using pre-loaded strand seeds so that 20 improperly planted seeds can be individually placed.
21 And the next licensee, let's see, 15, 22 okay. They received 50 percent of the prostate, 23 received no dose at all.
24 They were using the ultrasound volume of 25 161 the prostate. And it was smaller on the ultrasound 1 pre-implant scan, than the CT post-implant scan. So 2 the prostate appeared to be much larger in the CT 3 post-implant.
4 And the real-time implementation didn't 5 allow them to really get a good idea of how big the 6 prostate was. And so, it didn't permit visual 7 identification of visual errors that they had during 8 the procedure.
9 They attributed the medical event to human 10 error. For additional corrective actions they're 11 going to have additional training to personnel and 12 improved supervision.
13 And they're going to terminate the seed 14 implant program due to low patient volume. So they 15 have essentially given up their manual brachytherapy 16 program. 17 And now we've got two different reports on 18 this slide. And the first one the patient received 56 19 percent of the dose they attributed to human error.
20 And they use, the corrective actions they're going to 21 improve their imaging techniques.
22 In the next one, they received 73 percent 23 of the dose. And they attributed it to the lack of 24 dose being given to the prostate as an 18 percent 25 162 increase in the prostate size when compared to the 1 pre-plan.
2 And the plan, they also planned and 3 intentionally cooler coverage near the rectum. So 4 they're going to provide additional training to their 5 personnel.
6 Okay. So now we've got a pretty 7 interesting medical event. In this case, they 8 intended to give 12,500 centigray, but they only gave 9 about 1,000 centigray.
10 They were using a Foley catheter, and they 11 should have inflated the balloon in the urethra, but 12 they inflated the balloon in the prostate. So, 32 of 13 the 54 seeds were placed outside the prostate and 14 three seeds couldn't be seen at all.
15 And they expect the risk of radiation 16 damage to the, they expect risk of the radiation 17 damage to the rectum and to the surrounding tissue 18 because of where the seeds ended up.
19 So they, part of the problem was they 20 failed to locate the Foley catheter, and that 21 compounded, was compounded by using a magnification 22 factor that didn't allow them to get a full view of 23 the treatment and relevant anatomy.
24 So, this licensee, for this particular 25 163 case, the physician and the medical physicist will now 1 audibly concur on image quality before procedure.
2 This on their corrective actions.
3 Their manufacturer was asked to re-set the 4 default magnification value so that the initial view 5 would be of the relevant prostate anatomy. And then 6 once the first seed is implant ed, they're going to use 7 the fluoroscopic image to make sure that they have the 8 relative location of the seed and the Foley catheter 9 where it's expected to be.
10 Okay. So now we've got a patient that 11 was, received about 77 percent of the prescribed dose.
12 They had three seeds in one needle but the seeds 13 didn't remain in place.
14 They considered the contributing factors 15 to be the AU's preference for peripheral loading. The 16 potential rotation of the prostate during the needle 17 insertion and pressure effects when using a hydrogel 18 to separate the prostate from the rectum.
19 So, as a result of the medical event, 20 they're no longer going to implant the needle between 21 the urethra and the rectum, they're going to use two 22 needles offset on an axis.
And they're also going to 23 use stabilizing needles during surgery so that the 24 prostate doesn't move as much.
25 164 And that brings us to the end of the 1 manual brachytherapy medical events.
2 And moving on to the 35.600, which are the 3 therapy devices. We had ten medical events. And they 4 were all with the HDR unit.
5 We had one skin, two breast and seven 6 gynecological. And as you'll see, we had a device 7 malfunction. We had a wrong site in the human error.
8 So, let's look at the first one, and that 9 was the skin. In this case, the patient was 10 prescribed to get eight fracti ons of 500 centigray for 11 each fraction to the temple area, but they only 12 received 350 centigray on the first two fractions.
13 So, the problem here was, the first 14 physicist used an incorrect setup. There is an 15 accuform that should have been in place to give the 16 proper distance from the sources to the temple area.
17 But they didn't use it.
18 And then the second physicist used the 19 correct setup. So, the first physicist did the first 20 two fractions and then the second physicist came back 21 on the third fraction, used the correct setup and then 22 they proceeded from there.
23 So, there was a gap between the treatment 24 device and the patient's skin.
25 165 So, what did they do for corrective 1 action? They lacked a policy for custom and 2 mobilization devices for skin treatment. They're 3 going to develop that now.
4 And the therapist present at the first 5 treatment, and anytime, will be present at the first 6 treatment anytime there is a new physicist.
So there 7 will be a continuation of information going from one 8 treatment to the next.
9 And another thing that contributed to it 10 is, when they had the patient setup and they were 11 running the HDR sources out, the patient orientation 12 was such that they could not really see where the 13 sources were and they couldn't see whether the 14 accuform was in place or not.
15 And so they're going to now take a 16 photograph at setup. With and without the patient to 17 show how the accuform should be used. And then 18 they're also going to check that when they do have a 19 patient. 20 And they're going to use a barcode 21 scanning system to track custom setups using their 22 devices. 23 So now we have a breast medical event.
24 And in this case, we had 1,200 centigray to the 25 166 lateral breast skin.
1 This is similar to other medical events 2 that we've seen with the HDR in the breast implants, 3 in which the physicist used the tip end instead of the 4 connector end in the treatment plan.
And so, the dose 5 was not delivered to the treatment site but out close 6 to the skin and created problems.
7 So, corrective actions are going to be 8 additional training to personnel.
9 We had a second breast medical event, 10 wrong site. In this case, the first one we didn't 11 identify whether there was a, what applicator was 12 being used, but in the second case it's a Savi 13 applicator.
14 And in this case, there are six struts and 15 two and six were mislabeled. So that changed the 16 orientation of the applicator and the direction of the 17 radiation field.
18 So, the corrective actions are that the 19 second physicist will independently verify that the 20 catheter struts are in the treatment plan and there 21 will be an HDR review checklist and they'll verify 22 digitization of the struts in the treatment plan.
23 And they're going to add an HDR review, 24 plan review, to their monthly audit so that they can 25 167 pick these things up. And they're going to provide 1 additional training to their personnel.
2 So now we move into the largest category 3 for 600 medical events, and that is the gynecological 4 treatments.
5 In the first one we have a device 6 malfunction. The patient was to receive 1,500 7 centigray during three fractions in 13 dwell positions 8 but the HDR malfunctioned at Dwell point nine and the 9 treatment stopped at that point. And then after the 10 device was repaired, then they continued with the 11 treatment.
12 We had another one that was device 13 malfunction. The device failed to fully retract at 14 completion of the treatment fraction, so that you had 15 a dose of 100 centigray to the patient thigh.
16 The source was five centimeters from the 17 cylinder guide to connector. And the source wire was 18 bent at the source.
19 And then was a delay in removing the 20 source from the vicinity of the patient and reporting 21 the event to the RSO. So they compounded the issues 22 that they had.
23 If they had been a little faster on 24 identifying the sources outside of where it was, they 25 168 might not have had a medical event.
1 Then we have catheter movement. And in 2 this case, the connector locking nut was too loose and 3 that allowed the catheter to s lide out. And the event 4 was discovered by skin reaction progressing to moist 5 desquamation.
6 The dose to the skin was between 5,000 and 7 8,500 centigray. The correcti ve action was to retrain 8 the medical staff and the AU.
9 The AU will now double check all 10 connections and placements before and after each 11 treatment to make sure they were intact during the 12 treatment. And they've purchased a new cylinder with 13 a new design that they believe won't have this 14 connection problem.
15 The next medical event there were six 16 fractions of 350 centigray each. But the first 17 fraction received 2,100 centigray.
18 So the total treatment time was 19 incorrectly entered into the treatment planning 20 system. It was human error and poor decision making.
21 They started the first treatment after 22 hours2.546296e-4 days <br />0.00611 hours <br />3.637566e-5 weeks <br />8.371e-6 months <br />. And there should have been two physicists 23 checking, but the second physicist wasn't available.
24 So the second physicist put the information in and it 25 169 wasn't correct.
1 So, their corrective actions are now to 2 have the second physicist independently verify the 3 treatment plan and the physicist to check if the plan 4 was exported correctly to the treatment console.
5 Okay. The next one is a pretty 6 interesting one. It was a wrong site.
The patient's 7 pelvis had extensive damage due to uterine cancer, not 8 cancel. 9 There were two dwell positions that 10 shifted to deliver the dose to the non-target small 11 intestine bowel in the first three fractions. So the 12 treatment plan was modified for the next two fractions 13 so they could give treatment to the treatment site.
14 And the licensee originally thought it was 15 not reportable because, in the process they gave the 16 dose to the treatment site that was asked for.
17 But NRC determined that it is reportable 18 because the licensee did not take into account that 19 the fact that the fractional dose was greater than 50 20 percent. And that the dose was delivered to the wrong 21 treatment site. They were focusing only on the 22 treatment site.
23 So, we have another wrong site. In this 24 case, the dose was delivered 5.5 centimeters outside 25 170 the treatment site. It received 500 centigray in a 1 half centimeter volume.
2 And this was a digitization issue. We had 3 digitization issues earlier. In this case, Channel 12 4 was digitized twice with no digitization of Channel 5 13. 6 And so, there were no dwell positions in 7 13. The treatment plan was displayed. There was 8 plenty of opportunity for the physicist and the AU to 9 see that there was no dwell positions in Channel 13, 10 and no one picked it up.
11 So, the physician approved the plan and 12 the physicist, neither one of them picked up that 13 there was a problem here. So, they attributed the 14 fact that they were rushing.
15 The patient was in discomfort with a full 16 bladder. They had tried to start the procedure. They 17 had the patient on the table and they tried to do the 18 procedure, while the patient was there, and the 19 patient was discomfort so they rushed to get the plan 20 and export it into the treatment console and they 21 overlooked their errors.
22 The corrective action is there will be a 23 second check by the physicist that did not prepare the 24 plan. And then each channel will be carefully 25 171 reviewed, and the patient won't be brought to the 1 treatment area until the plan has been checked and 2 exported to the console.
3 Another wrong treatment. So, in the first 4 three fractions they digitized the catheter as linear 5 instead of a single curve catheter.
6 So, the physicist failed to recognize the 7 incorrectly reconstructive catheter shape in the 8 planning software. And treatment length was 15.7 9 centimeters instead of the nine centimeters.
10 Okay. And they didn't discover the 11 problem until the second fraction. So, one of the 12 things they attributed it to was that the treatment 13 plan was not enlarged enough, so the physicist 14 couldn't see the dwell points that were overlapping in 15 that incorrectly digitized Channel 12.
16 And the corrective actions are to enlarge 17 each treatment plan in which the physicist signs off 18 and to use a formalized checkl ist. And that concludes 19 our 35.600 medical events.
20 And now we move into the emerging 21 technology or the other medical uses. We had 25 22 medical events. We had one for the Perfexion, one for 23 intravascular brachytherapy, one for radioactive seed 24 localization and then we had 22 for the Yttrium-90 25 172 microspheres.
1 For the Perfexion, the device 2 malfunctioned. The device recorded an error, the 3 backup power was low, so the sources were returned to 4 the shielded position and they had to get the device 5 repaired. So, only one-third of the prescribed dose 6 was delivered.
7 For intravascular brachytherapy, they were 8 using an extra-long delivery catheter and the source 9 would not go out to the treatment site. So they 10 retracted the source safely, they exchanged the long 11 treatment catheter for another extra-long treatment 12 catheter and the source still wouldn't go out to the 13 treatment site, but the source could not be returned 14 to the intravascular brachytherapy unit. And all the 15 catheters were removed.
16 The hydraulic return mechanism failed to 17 return the source, and no dose was given to the 18 treatment site and 39 centigray was given to the 19 surrounding tissue. And they looked at it and 20 determined there was a deformation of the delivery 21 catheter that was the root cause.
22 Okay. We had one radioactive seed 23 localization. In this case, the patient was given a 24 seed and was scheduled to come back for surgery six 25 173 days later.
1 And in the middle of this process, after 2 the seed was implanted, but before the seed could be 3 removed, the insurance company rescinded the approval.
4 And it required about, it required three medical 5 opinions before they would continue to okay the 6 surgical removal of the seed.
7 So the surgery wasn't performed until 8 approximately 64 days after the implant. So the 9 surrounding tissue from the implant was supposed to 10 get 12 centigray and the patient received 99 11 centigray.
12 And now we're going to move into the 13 Yttrium-90 microspheres. We have 25 of them. And the 14 first two, they did not identify the manufacturer.
15 So you can imagine if they didn't identify 16 the manufacturer, you're not going to see a lot of 17 information on the first two.
18 So they got, in the first one they got 77 19 percent of the intended dose. No other information.
20 The second one the patient received 60 21 percent of the prescribed dose. And no other 22 information.
23 And now we'll move on. I'll always divide 24 these up to TheraSpheres and SIR-Spheres because the 25 174 devices are not exactly the same and some of the root 1 causes are not the same.
2 So this year I'm doing the TheraSpheres 3 first. We had 13 medical events involving 14 4 patients. We had an overdose, catheter obstruction, 5 bubbles, backflow to contrast and a human mistake.
6 So, let's take a look first at the 7 overdose. They prescribed 13,670 centigray, but they 8 received 29,400 centigray.
9 They picked up the wrong dosage. They 10 measured it, they compared what they saw with what was 11 on the shipping box and not what was in the written 12 directive. So they had a shipping box that was for 13 next week's patient, and they picked that up and they 14 administered that to this week's patient.
15 So, the post-administration calculations 16 identified the medical event.
And so, as a corrective 17 action, they're going to add a dose verification step 18 in the interventional radiology department.
19 And now we're going to see a lot of cases 20 where the dose didn't end up in the patient, it ended 21 up in the waste jar. Or in the catheters or in some 22 other place, but not in the patient.
23 So they prescribed 12,000 centigray, but 24 they only administered 1,700 centigray. Fourteen 25 175 percent of the intended dose.
1 They thought the equipment didn't function 2 as designed, and most of the dosage was found in the 3 waste jar. The manufacturer w as unable to determine a 4 root cause.
5 On the next medical event we had two 6 patients. And both of them received less dose than 7 prescribed.
8 So the first patient was prescribed 72.6 9 millicuries, but they received 15 millicuries. And 10 the inspector that went out and looked at this case 11 thought the expansion tubing resulted in turbulent 12 flow triggering suspension issues.
13 The second patient was also prescribed 72 14 millicuries but received 36.7 millicuries. And the 15 inspector thought the lack of adequate agitation prior 16 to administration, or that the issues were with a 17 quality sizing of the microspheres.
18 So, as a result, the licensee is no longer 19 using extension tubing, and the manufacturer supported 20 the inspector's findings.
21 The next case, they were prescribed 122 22 millicuries but received 46 mi llicuries, 38 percent of 23 intended dose. The device com ponents were sent to the 24 manufacturer, and no cause of the blockage was 25 176 determined.
1 There was an obstruction blockage located 2 in the micro-catheter in the outlet tubing to the E 3 junction. The manufacturer recommended handling 4 micro-catheters with extra care in looking for kinks.
5 So, we have another 12,000 centigray but 6 only received 2,000 centigray. The licensee 7 attributed it to a malfunction in the administration 8 set. 9 Significantly less pressure was noted than 10 usual when pressing the syringe. Saline accumulated 11 in the overflow valve.
12 And only, they were supposed to return the 13 whole unit to the manufacturer. All the tubing and 14 everything but they only returned a portion of the 15 administration set that infused the dose into the 16 patient, to the manufacturer. So they didn't get to 17 see what the real problem was.
18 It could have been a kink or obstruction 19 in the treatment catheter, but it wasn't conclusive.
20 So their corrective actions, next time they have one 21 these, they're going to send everything back to the 22 manufacturer.
23 So we've got now one licensee with two 24 reported medical events. In Report Number 1, they 25 177 were scheduled 64 millicuries, they only got 41, 65 1 percent of the activity.
2 Air bubbles were noted in the overflow 3 tube. So they connected a three-way st opcock between 4 the overflow tube and the micro-catheter, aspirated 5 bubbles to the syringe with a stopcock close to the 6 patient. And I believe they decided to stop the 7 treatment at that point.
8 And they re-surveyed the delivery kit, 9 showed residual activity.
10 And Report Number 2, they prescribed 46 11 millicuries but only received 27. Or 59 percent of 12 the activity.
13 They used the left radial artery with a 5-14 French Sarah Radial catheter with a coaxial micro-15 catheter. They didn't see anything unusual. They 16 didn't have any radioactive contamination. But then 17 they found the dose was in the catheter, the gauze, 18 the dose vial and the other waste.
19 This one received about 64 percent of the 20 dose. There was a backflow of microspheres into the 21 contrast line and syringe. There was significant 22 contamination in the contrast syringe, the flushing 23 syringe, the contrast tubing and the associated y-24 adaptor. 25 178 Though, they thought that the contrast 1 syringe and tubing were made of materials that bind 2 the microspheres more than the administration kit.
3 And so they're going to look for things that are, have 4 the same materials as the manufacturer's recommended 5 administration kit. And they are now going to use a 6 clamp and a one-way valve.
7 This one was, received about 32 percent of 8 the activity. There was a blockage in the delivery 9 apparatus. They imaged the administrative set and saw 10 most of the undelivered activity near where the 11 plunger connects to the dose vial.
12 So they, in this case, they're going to 13 send the administration kit and procedure waste to the 14 contract. To the manufacturer.
15 And this one received 16 percent of the 16 activity. The microspheres were coagulated in the 17 tubing. There was unexpected activity remaining near 18 the Touhy-Borst connector.
19 And the manufacturer thought the cause, by 20 issues with the micro-catheter.
Their remedy will be 21 to flush the micro-catheter immediately prior to 22 connecting it to the administration kit. They think 23 that might help in getting the micro-catheters through 24 the, getting the microspheres through the micro-25 179 catheter.
1 This patient received 65 percent of the 2 dose. The first vial was administered without 3 incident.
4 They primed the second vial and they 5 prepared it, but they saw a train of bubbles in the 6 line between the dose vial and the patient. So the AU 7 stopped the procedure.
8 They didn't want the bubbles to cause the 9 flow to reflux to the gastric artery and cause 10 permanent damage to the stomach. And they couldn't 11 pinpoint a cause for the bubbl e, so they limited, they 12 now limit the number of staff trained to prime and do 13 the setup, to ensure enough are available on treatment 14 day. 15 The next patient received 53 percent of 16 the dose. They did a CT scan to verify the dose was 17 administered to the correct location, but the 18 remainder of the dose hung up in the catheter despite 19 flushing, and the catheter tube met the manufacturer's 20 specification. So no root cause was identified.
21 In this case, the patient received 71 22 percent of the dose. And this particular licensee 23 used three different written directives to fractionate 24 the delivery.
25 180 So they thought the small activity 1 prescribed in one of those fractionated doses 2 contributed to the underdose because of the typical 3 loss of microspheres in the valve and the tubing.
4 They are now going to order higher dosages 5 for any administration below ten millicuries, and 6 they're going to amend the license to go to a 7 different manufacturer. So they're switching 8 manufacturers.
9 That brings us to the end of the 10 TheraSpheres and we're now moving into the SIR-11 Spheres. We had seven medical events with SIR-12 Spheres. 13 You'll see that we have wrong site, 14 measurement unit error, written directive error, high 15 activity clogging, and low activity clogging.
16 So the first one was a wrong treatment 17 site. And the post-treatment scan appeared normal 18 with the small uptake in the bowel, but the patient 19 experienced pain in the abdomen and erythema on the 20 abdomen. 21 They thought the dose was above 55 22 centigray but less than 1,000 centigray. And they 23 thought one-third of the dose migrated up a venous 24 ligament and lodged in the abdominal wall.
25 181 I think this is one of the first ones that 1 we've seen with erythema on the abdomen. Or 2 microspheres.
3 So, they attributed their issues to 4 difficultly visualizing the arterial access to the 5 tumor. That the micro-catheter was not advanced far 6 enough into the correct artery.
7 And this particular patient had a 8 preexisting kidney impairment that precluded use of 9 more contrast, so that was attributed to why they 10 didn't get a good visualization.
11 And they're going to add a second monitor 12 to refer to the original arteriogram without switching 13 task and to improve the confidence and correct 14 location. And they're going to take prophylactic 15 measures for future patients with impaired kidney 16 function.
17 This is another wrong site. They 18 prescribed it to the left lobe of the liver, but they 19 delivered twice as much to, they prescribed it to the 20 right lobe of the liver but they received about two to 21 three times more dose to the left liver.
22 They attributed it to human error, and 23 they placed the catheter in the left hepatic artery 24 instead of the right hepatic artery.
25 182 This was an interesting one. This was a 1 measurement unit error. They prescribed .91 2 gigabecquerels but they received 8.9 millicuries.
3 They ordered it, even though it's 4 prescribed in gigabecquerels, they ordered it in 5 millicuries. They marked the wrong box in the 6 computer. And when they went to measure it, they 7 didn't multiply the measurement dose value by a 8 correcting factor of ten.
9 So they didn't identify it until the post-10 procedure check, so they are going to revise their 11 worksheets to be all in SI units. And the written 12 directives will also be in SI units, and the dose 13 preparation and post-procedure forms will be in SI 14 units. 15 So they had issues going back and forth 16 between SI units and other uni ts. So they're going to 17 make uniformity. Uniformed changes there.
18 Okay. This is a written directive error.
19 They prescribed 1,500 centigray to the right lobe of 20 the liver, but they delivered about 1,500 centigray to 21 the left lobe.
22 The written directive was prepared 23 incorrectly. The AU wanted to treat the left lobe.
24 And it was identified after completion of the 25 183 procedure.
1 It also indicates that the AU didn't 2 indicate the correct treatment site on the written 3 directive, and the AU didn't fall with the pre-4 treatment information to the RSO. So the clinical 5 staff failed to identify the discrepancy between, 6 during their patient time-out just before the 7 implementation.
8 So, we've had a number of licensees that 9 use time-out as a corrective measure, but time-out 10 doesn't always work.
11 So now we have a high activity clog where 12 19 percent of the dose was received. The micro-13 catheter clogged due to an unusually large number of 14 microspheres being used, according to the licensee.
15 The prescribed activity was at the high 16 end of the treatment range and the patient was 17 administered, the administration was delayed a day, 18 and because it was delayed a day and it decayed, then 19 they had to increase the number of microsphere volume 20 roughly by 25 percent.
21 And so, in the future they're going to use 22 smaller aliquots and do a slower infusion rate.
23 And we have a device malfunction. In many 24 of the things, licensees are now attributing most of 25 184 their problems to device malfunction.
1 So they received 25 percent of the 2 activity. They say the device malfunctioned and 3 ceased to deliver the microspheres. I think this is 4 another way of saying clogging.
5 The manufacturer's representative was 6 present, but the cause of the malfunction was unknown.
7 They'll return the delivery device to the 8 manufacturer for technical analysis and root cause 9 determination.
10 This patient received 51 percent of the 11 activity. They had planned to deliver the activity in 12 two split dosages. The written directive was not 13 properly reviewed.
14 So they split one dose into two, instead 15 of providing two separate doses. The radiation 16 oncologist failed to check the drawn dosages prior to 17 injecting them. And the identification was after the 18 injection, when the remainder of the doses was 19 delivered. Discovered.
20 So, they attributed this to lack of 21 comprehension of the dose draw worksheet, a 22 miscommunication failure to review the written 23 directive and a failure to perform a safety pause and 24 properly review the dosage to be administered against 25 185 the written directive prior to administration.
1 And that concludes my list of 48 medical 2 events for FY 2018. Are there any questions?
3 CHAIRMAN PALESTRO: Thank you, Dr. Howe.
4 Comments or questions from the ACMUI?
5 MEMBER SCHLEIPMAN: I have a question.
6 It's more just a process.
7 Who adjudicates, some of the corrective 8 actions seem quite appropriate, some seem, perhaps, 9 not enough. Who adjudicates whether th ose corrective 10 actions are sufficient and how are they followed up 11 and by whom?
12 DR. HOWE: What normally happens is, if 13 you have a medical event there's normally an 14 inspection. These medical events happen throughout 15 the agreement states in NRC.
16 And then on inspection time and reviewing 17 their reports, they give corre ctive actions. And it's 18 up to the regulator to say, yes, that appears to be 19 reasonable. And we generally will sign off on 20 retraining of people.
21 The licensee comes up with their own 22 corrective actions.
23 CHAIRMAN PALESTRO: Any other comments or 24 questions?
25 186 Comments or questions from attendees here 1 in the room?
2 On the bridge line? Mr. Ouhib?
3 MEMBER OUHIB: Yes, I just have a 4 question. I know this has been brought up in the past 5 regarding the units, which the SI units many times.
6 Any hope, any chance, any plan for that down the road?
7 DR. HOWE: Normally our SI unit problem, 8 that's been brought to our attention is, the problem 9 with the manual brachytherapy seeds being air kerma or 10 some other unit.
11 And in this case, it was a licensee that 12 appeared to have multiple different kinds of units 13 from one document to the next and didn't have 14 uniformity. So they were just kind of, it was really 15 something that was kind of asking to have an accident 16 between ordering in SI units and ordering in 17 millicuries and then making measurements.
18 So, it wasn't the normal type of unit 19 problem we have, it seemed to be kind of unique to 20 this particular licensee.
21 CHAIRMAN PALESTRO: Any other comments, 22 questions? Ms. Weil.
23 MEMBER WEIL: I have a question. Not 24 necessarily for Dr. Howe but maybe for the group.
25 187 If the NRC were to take the suggestion 1 that these high level infiltrations, where the dose to 2 an unintended tissue reached t he regulatory limit, how 3 much would that increase, do you think, the number of 4 medical events that are reported?
5 Is there any way of thinking about that?
6 DR. HOWE: I don't think we know at this 7 point. I would suspect we would get, we do have cases 8 where they report infiltrations with therapy drugs and 9 we don't call them medical events because of our 10 prior. 11 And so we have ones and twos of those.
12 But I think if there was more focus on it, we might 13 see more, I'm not sure.
14 It would also depend on whether we kept 15 the same, if we were to go to calling them medical 16 events, whether we kept the same criteria in place or 17 we developed a different criteria that might be a 18 little bit higher to take account for capturing things 19 that might have a significance for the patient. But 20 we have an able team that's going to look at that.
21 CHAIRMAN PALESTRO: Any other comments or 22 questions? Thank you very muc h, Dr. Howe. I'm sorry.
23 DR. HOWE: No, you get the --
24 PARTICIPANT: Oh, it's working now?
25 188 DR. HOWE: No.
1 MS. BLANKENSHIP: Hi. Bette Blankenship, 2 AAPM. I had a question on the SIR-Sphere medical 3 event. 4 Typically, you can only order three 5 gigabecquerel and receive three gigabecquerel from the 6 SIR-Sphere's folks. So I was curious as to why they 7 would indicate that they had received 8
.9 millicuries 8 because you can only order in gigabecquerel, receive a 9 gigabecquerel, that amount, and then draw from that 10 what your physician orders or prescribes.
11 So I was just curious on, their reporting 12 is even further confusing because they didn't receive 13 8.9 millicuries because Sirtex can't ship anything 14 other than three gigabecquerel. So they only work in 15 SI units.
16 DR. HOWE: And that's the one where they 17 confused all the SI units and --
18 MS. BLANKENSHIP: Yes. It basically says 19 prescribed .91 gigabecquerels but received 8.9. So 20 that, just that language there kind of confused me, 21 because they can only ship in one --
22 DR. HOWE: So, they were supposed to get 23 .91 gigabecquerel, they wrote it out for .91 24 millicuries.
25 189 MS. BLANKENSHIP: Okay.
1 DR. HOWE: And then when they made the 2 measurement, they didn't multiply by ten, so they 3 stopped, thought they were still down in the level 4 they were supposed to, and it wasn't until later that 5 they discovered that they were --
6 MS. BLANKENSHIP: Yes.
7 DR. HOWE: -- way off.
8 MS. BLANKENSHIP: Yes, I just, thank you.
9 DR. HOWE: Yes. I can't explain any more 10 than that.
11 CHAIRMAN PALESTRO: Mr. Sheetz.
12 MEMBER SHEETZ: In response to that, some 13 licensees will receive SIR-Spheres from a 14 radiopharmacy and they'll get a unit dose, so the 15 three gig vial will be sent to the radi opharmacy, the 16 radiopharmacy will then follow-up and then dispense 17 into the dose vial what the licensee has required. Or 18 requested.
19 MS. BLANKENSHIP: Okay.
20 CHAIRMAN PALESTRO: Any other comments or 21 questions? All right, thank you very much. Dr. Howe.
22 Next topic on the agenda is the 23 Appropriateness of Medical Event Reporting 24 Subcommittee Report, will be presented by Dr. Ennis.
25 190 MEMBER ENNIS: Good afternoon, everyone.
1 Thank you, Chairman Palestro.
2 And I couldn't have asked for a better 3 introduction. Especially the case where we didn't 4 know what site was implemented.
5 Okay. So, we formed a subcommittee 6 looking at the appropriateness of medical event 7 reporting that came out of the growth of Donna-Beth's 8 presentations over the last few years, as well as 9 mine. 10 And just take a look at the pictures on 11 the bottom, and you'll see a better rep resentation of 12 what we're doing here, than we saw this morning.
13 Next slide. Okay. So, our charge was to 14 review the appropriateness of required elements of 15 medical event reporting, the adherence to these 16 requirements and recommendations to improve reporting.
17 Next slide. So I want to thank the 18 subcommittee members, this was really an excellent 19 subcommittee. A lot of involvement of all, and 20 activity of all the members, including Dr. Dilsizian, 21 Ms. Martin, Mr. Ouhib, Ms. Shober and Ms. Weil and 22 myself. 23 Next slide. So starting, it's worth 24 reflecting on what is the purpose of reporting. And 25 191 using some of the NRC documents that describe the 1 event reporting requirements and schedules for them.
2 I will highlight for you what are relevant 3 aspects of the requirements for a higher subcommittee.
4 And that this information of medical events should be 5 used to assess trends and patterns, recognizing 6 inadequacies of unreliability of specific equipment or 7 procedures, and will significantly aid in 8 understanding why events, an event occurred and then 9 find any actions necessary to improve the 10 effectiveness of NRC and agreement state regulatory 11 programs.
12 Next slide. These are the documents that 13 we reviewed in helping us make our determination of 14 what is required. Currently in the medical event 15 reporting and what is available to the public.
16 Next slide. In the end, the events that 17 are reported are collected into a database. The 18 nuclear materials event database, otherwise known as 19 NMED. 20 It does include information for both 21 agreement states and the NRC. It's managed by an 22 office within the NRC, the Office of Nuclear Materials 23 Safety and Safeguards.
24 And there is a contractor that is 25 192 responsible for coding and quality control of the 1 information under the oversight of the NRC NMED 2 project coordinator.
3 Of note, access to NMED is limited. And 4 the general public does not have access to that.
5 Rather they have access only to an annual report that 6 is available publicly.
7 Next slide. Issues that our subcommittee 8 identified in NMED are as follows. We felt that 9 frequently the narrative was inadequate for an ACMUI 10 reviewer to understand the event, its cause and 11 contributing factors, and the adequacy of the 12 corrective action.
13 At times, there appear to be a disconnect 14 between the narrative and the chosen cause from the 15 cause pick list.
16 Just a point of clarification, there is a 17 drop-down menu within NMED for causes and for 18 corrective actions that lists many of the most common 19 causes and corrective actions with a word or phrase.
20 But that chosen corrective action or 21 cause, from the drop-down menu, often does not appear 22 to connect well to the description within the 23 corrective action or cause par ts of the NMED database.
24 Next slide. In addition, NMED lacks 25 193 information from some inspections that have been 1 conducted by NRC or agreement states, like the example 2 we talked about a minute ago.
3 We did a brief audit of a couple of issues 4 and, for example, of all the medical events in Fiscal 5 Year 2017/18, 23 percent of them, there was either no 6 cause or no corrective action identified in NMED as of 7 a month ago.
8 In addition, of all medical events 9 reported in 2017, 11 percent are still incomplete and 10 an additional 11 percent are listed as pending 11 additional information, and, again, this is as of a 12 month ago.
13 And as alluded to before the public, 14 including authorized users, RSOs, physicists, 15 authorized physicists, only have access to an annual 16 report, not to the actual data that we can see in 17 NMED. 18 Next slide. As such, our subcommittee is 19 in the process of finalizing recommendations to 20 improve and address the issues laid out in the first 21 part of this presentation.
22 Those that we are moving towards a full 23 recommendation on include the following, that the root 24 cause and corrective action sections in NMED, in 25 194 addition to the pick list, there should be a required 1 narrative and searchable section.
2 Currently there is the narrative section 3 itself of the NMED is searchab le, but there's only one 4 place for a narrative section.
It's not specifically 5 asked that there be a narrative part for the root 6 cause and corrective action aspects.
7 Currently, whoever is entering the data 8 can just do a drop down menu for those aspects, which 9 really are the crucial ones to really understanding an 10 event and helping the ultimate goals of these that we 11 discussed on the first couple of slides.
12 We also are leaning towards a 13 recommendation that the root cause and corrective 14 action sections always need to be completed. (Sound 15 system interference.)
16 PARTICIPANT: Sorry.
17 MEMBER ENNIS: We are looking at requiring 18 that information gathered from any investigations be 19 added to NMED as that is not necessarily the case at 20 this point.
21 We are looking to require that a report 22 may be fully completed within 12 months. We are 23 looking to require ACMUI and NRC staff annually 24 promulgate the findings of the ACMUI subcommittee on 25 195 medical events to the medical community and the 1 medical physics community.
2 Currently, while that report does go up on 3 the website, we might recommend that additional ways 4 of promulgating that be done on an annual basis in 5 order to educate the medical community about what can 6 be learned.
7 Next slide. Further things we are 8 considering but haven't totally come to a conclusion 9 on include requiring that the report use additional 10 guidelines that we might develop to assure more 11 complete and useful information is provided.
12 So, more specifically, what is required of 13 a root cause analysis, how can we structure the 14 requirements of causes and root cause analyses and the 15 connections between them, can we come up with ways of 16 structuring those and advising licensees that when 17 they are reporting what is required in more detail so 18 that we get better reports.
19 Another aspect we were looking at is 20 requiring that the report eventually gets submitted 21 and reported within NMED be initially written by the 22 authorized user and their phys icists and then reviewed 23 by the inspector as opposed to being written by an 24 inspector, having in mind that the authorized user and 25 196 medical physicists tend to have a deeper understanding 1 particularly of the medical aspects of what is going 2 on. 3 Require that the inspector interview all 4 involved in a medical event, to do a more in depth 5 evaluation of each medical event, require the report 6 from a manufacturer be included in the report if the 7 event reported involved the device to assure adequate 8 responsiveness from the manufacturers and input from 9 them, and then, again that gets reported within NMED 10 so that we can all learn from those individual events 11 and the manufacturer's thoughts about it.
12 We are also looking at a notion that a 13 corrective action be explicitly defined to include 14 medical aspects as well as technical aspects because 15 some of these solutions or the improvements of that 16 nature and could be helpful to other authorized users 17 to be aware of these, but would be missed if not 18 specifically required, and to require that the final 19 report, even if drafted by the physicist and the 20 authorized user, be signed off by all involved, 21 meaning the authorized user, the physicist, and the 22 inspector.
23 I think that's the end. Next slide. Ah.
24 So in conclusion we believe, our subcommittee 25 197 believes there are significant opportunities to 1 enhance the utility of the medical event reporting, 2 the NMED database specifically, and promulgation of 3 the information to user community.
4 The subcommittee asks that it be able to 5 continue evaluating these issues in more detail with 6 the goal of creating a set of specific 7 recommendations. Thank you.
8 CHAIRMAN PALESTRO: Thank you, Dr. Ennis.
9 Comments or questions from the subcommittee?
10 (No audible response) 11 CHAIRMAN PALESTRO: From the ACMUI?
12 (No audible response) 13 CHAIRMAN PALESTRO: Dr. Ennis, I have two 14 questions. One, in your recommendations you say that 15 you recommend that a report in NMED be completed 16 within 12 months. That seems like an awfully long 17 time. 18 MEMBER ENNIS: This is trying to be 19 strict. The point is as a previous slide shows that 20 about a quarter were opened two years or so. If you 21 could go back a couple slides. There we go.
22 So 2017 we reviewed all the events of 23 2017, 11 are still incomplete, 11 percent, and another 24 11 percent are still pending additional information, 25 198 so we are trying to make it a little bit stricter by 1 requiring a year.
2 I certainly wouldn't disagree that that 3 might be generous, but for a starting point at least 4 we thought that would be a good place to start.
5 CHAIRMAN PALESTRO: Are there time 6 requirements in place now?
7 (Off microphone comment) 8 CHAIRMAN PALESTRO: All right. Yes, I'm 9 sorry, Mr. Einberg.
10 (Off microphone comment) 11 PARTICIPANT: Your mic is the one that 12 died. 13 (Off microphone comment) 14 MR. EINBERG: Dr.
Palestro, yes, there are 15 no time requirements. However, the agreement states 16 and licensees report these to the agreement states and 17 the agreement states have to report into NMED and NRC 18 licensees report to us and we put it into NMED.
19 And then during the IMPEPs, which are the 20 Integrated Materials Performance Evaluation Program, 21 where we go out and evaluate agreement states, we look 22 at whether they have been entering their NMED reports 23 in a timely fashion.
24 CHAIRMAN PALESTRO: Thank you. But 25 199 without any time requirement h ow do you define timely?
1 MR. EINBERG: Well whether they have been 2 entering the reports at all.
3 CHAIRMAN PALESTRO: Okay. Thank you.
4 MS. HOLIDAY: Dr. Palestro, this is 5 Sophie. I would also like to follow up to say that 6 there have been times where medical events come in and 7 members on the medical team specifically reach out to 8 a staff member actually in our branch who is called 9 the regional coordinator and we ask that she reach out 10 to the NRC regions or to the respective RSAOs, which 11 are the Regional State Agreeme nt Officers, to ask them 12 for additional information.
13 Yet at the same time we are asking for the 14 information doesn't mean that we the medical team can 15 force them to provide us that information, but we as a 16 medical team often do reach out and ask for additional 17 information.
18 CHAIRMAN PAL ESTRO: I have another question 19 for you, Dr. Ennis. Excuse me. Where you said that 20 you require the final report must be signed off by the 21 AU, physicist, and inspector, what about the RSO?
22 MEMBER ENNIS: I wouldn't disagree with 23 that. That may have been an oversight on our 24 committee.
25 200 CHAIRMAN PALESTRO: Mr. Sheetz?
1 MEMBER SHEETZ: That was going to be one 2 of my comments, yes.
3 CHAIRMAN PALESTRO: Any other comments or 4 questions from the ACMUI?
5 (No audible response) 6 CHAIRMAN PALESTRO: From attendees in the 7 room? 8 (No audible response) 9 CHAIRMAN PALESTRO: Bridge line?
10 (No audible response) 11 CHAIRMAN PALESTRO: All right. Now this 12 is an interim report so we don't have to take any 13 action on that, am I correct, Ms. Holiday?
14 MS. HOLIDAY: Correct. That was going to 15 be my next comment. While what you guys see on the 16 slide says recommendations under consideration, as I 17 think I have alluded to previously these are not the 18 formal recommendations being put forth by the 19 subcommittee at this time.
20 These are just things that they have 21 thought about and that they are considering. When 22 they have finished their deliberations they will come 23 forth with a draft final report for vote.
24 CHAIRMAN PALESTRO: All right. Well, I'm 25 201 certainly happy to extend the term of the 1 subcommittee, Dr. Ennis, and we look forward to 2 another report from your group at the fall meeting.
3 MEMBER ENNIS: Thank you very much.
4 CHAIRMAN PALESTRO: Thank you.
5 MEMBER ENNIS: If anyone has any other 6 ideas to add we're open to hearing suggestions.
7 MR. EINBERG: And, Dr. Palestro, is there 8 a staff resource for this subcommittee?
9 MEMBER ENNIS: Yes, Lisa Dimmick.
10 MR. EINBERG: Lisa, okay. Thank you.
11 MEMBER ENNIS: I apologize for not 12 mentioning that, Lisa.
13 CHAIRMAN PAL ESTRO: Actually, you know, Mr.
14 Einberg, you made a good point.
I think we tend to be 15 negligent when we put up the members of the 16 subcommittee that we should acknowledge the staff 17 resource, because not only because they are important 18 contributors but we should know who they are as well.
19 MR. EINBERG: Yes. And that was not my 20 intent to call out Lisa, but Lisa does great work and 21 I just wanted to make sure that you were getting the 22 support that you needed.
23 CHAIRMAN PALESTRO: Thank you. I wasn't 24 suggesting it was, but I think it really should be 25 202 done. 1 MR. EINBERG: All right.
2 CHAIRMAN PALESTRO: Any other comments or 3 questions?
4 MEMBER GREEN: Dr. Palestro?
5 CHAIRMAN PALESTRO: Any other business --
6 I'm sorry. Mr. Green?
7 MEMBER GREEN: Going back to the timeframe 8 of completing the medical event report, it's a long 9 time to write regulations and do rulemaking, but could 10 we recommend that, could the subcommittee recommend 11 that that get written into the regulations and then, 12 you know, some years later it will be adopted by the 13 agreement states, but right now it's just open-ended?
14 CHAIRMAN PALESTRO: The answer is, number 15 one, this an interim report so we are not approving 16 or, not approving or rejecting any recommendations 17 today. 18 And while I am not initially thrilled with 19 the idea of a one year lag time, given the fact that 20 there is no time limit at the present time I think 21 that's a step in the right direction and then assuming 22 that eventually gets written into the records that it 23 could potentially be shortened.
Any other comments or 24 questions?
25 203 (No audible response) 1 CHAIRMAN PALESTRO: All right. I have an 2 item that I had hoped to bring up earlier this 3 morning, but we ran out of time in the open forum and 4 rather than waiting until tomorrow I would like to 5 bring it up now if I may.
6 It's an issue that came up regarding 7 cremation of a patient or patients who had received 8 lutetium-177 dotatate for treatment of neuroendocrine 9 tumors. 10 Apparently, and I actually went back and I 11 very quickly checked through the NRC website and 12 looked under cremation, deaths, tried to come up with 13 a variety of terms, and maybe I wasn't looking using 14 the right terms or looking thoroughly e nough, but the 15 only thing that I could find was a statement in NUREG-16 1556 about the explantation of plutonium-powered 17 pacemakers prior to cremation.
18 And so the issue arises is there a policy, 19 is there recommendations or are there recommendations 20 by the NRC for the handling of decedents, particularly 21 with respect to cremation when they have radioactivity 22 on board?
23 DR. DIABES: Said Diabes. We are 24 currently working on patient instructions and part of 25 204 those patient instructions is instructions for family 1 members, caregivers, on cremation and what should that 2 entail. 3 That was directed by the Commission on a 4 patient release project and we are currently working 5 on that data and that was part of the updated data on 6 Reg Guide 8.39.
7 There is a whole section on cremation and 8 instructions related to cremat ion and what information 9 shall be provided. We are currently working on other 10 initiatives, a brochure, and more information that 11 will come available later.
12 CHAIRMAN PALESTRO: So let me ask you a 13 question and, Mr. Einberg and Ms. Holiday, is this an 14 appropriate time to form a subcommittee to work with 15 you on that or for you to consult?
16 MR. EINBERG: This would be, but I think 17 Katie, Dr. Tapp, here, wants to add some additional 18 information as far as what we require at this time.
19 DR. TAPP: Yes. Just adding on to Dr.
20 Diabes, so patient release reg ulations in 10 CFR 35.75 21 do have the limits for release of patients and then 22 you have -- the release should have instructions if 23 it's likely to exceed 100 millirem.
24 So we do right now require licensees to 25 205 consider situations where the release of that patient 1 could possibly expose members of the public to over 2 100 millirem.
3 That's how we go back to Reg Guide 8.39 4 and adding in some instructions for licensees to 5 follow that will help them for cremation in the 6 future. 7 We also are adding to NUREG-1556, Volume 8 9, in the Draft Revision 3 that is going out final 9 hopefully here in the summer, a reference to NCRP-155, 10 and NCRP-155 right now has guidance for cremation.
11 But you can form a subcommittee to address 12 more of Reg Guide 8.39, I wasn't trying to stop that.
13 But I am saying right now we are going to reference 14 NCRP-155 in the near term soon to kind of have a stop 15 gap. 16 CHAIRMAN PALESTRO: Thank you. Do you 17 want to --
18 VICE CHAIRMAN METTER: Thank you. Also, 19 you know, usually when you talk about cremation you 20 also talk about autopsies and I really think that 21 should also be included in this investigation.
22 DR. TAPP: Yes. NCRP-155 discusses 23 cremation and autopsy. One other thing to mention is 24 Dr. Zanzonico, a former nuclear medicine physicist, 25 206 did have a talk with the ACMUI I believe in 2015 on 1 cremation, so there was a presentation from him where 2 he looked at gaseous plumes and had some follow-up 3 items just for consideration as you go forward.
4 CHAIRMAN PALESTRO: Mr. Green?
5 MEMBER GREEN: A question for Dr. O'Hara.
6 Would it be conceivable that the NRC, the FDA, can 7 ask the manufacturers when they revise PIs or submit 8 PIs for new NDAs that they include information on 9 graded pharmaceuticals on autopsy and cremation?
10 MEMBER O'HARA: The labeling that the FDA 11 looks at is by definition draft labeling, so we can 12 ask for that in the labeling and the ma nufacturer can 13 change that.
14 And then where it becomes, when it becomes 15 an issue is when an inspector goes to a manufacturer 16 and sees that that has been changed, but it can be a 17 long drawn out process, yes, but that is a safety 18 consideration that I think that we can at least 19 propose. 20 MEMBER GREEN: With the number of new 21 therapies, you know, we're changing nuclear medicines, 22 changing from a primarily diagnostic modality to a 23 much more robust therapeutic modality with the 24 theranostics that are coming o ur way, you'll have many 25 207 coming across the FDA desk where maybe that's an ask 1 you make for these new therapies and we'll catch up 2 the other ones later.
3 But I think it would be great to have a 4 resource to the prescriber and to other practitioners 5 that is actually in the labeling for the product on 6 autopsy and cremation.
7 MEMBER O'HARA: I will pass that on to the 8 drug side of FDA as well because the theranostics they 9 usually get the call on those.
10 CHAIRMAN PALESTRO: Any other comments or 11 questions? Ms. Holiday?
12 MS. HOLIDAY: Dr. Palestro, as Dr. Diabes 13 was mentioning, and Dr. Tapp as well, you do have an 14 existing subcommittee that is looking at the draft 15 Regulatory Guide 8.39, which they both mentioned.
16 Just to remind you guys of who the members 17 are on that subcommittee as they, those subcommittee 18 members, were provided with the draft Reg Guide last 19 week. 20 The members are Dr.
Dilsizian, Ms. Martin, 21 Dr. Schleipman, Ms. Shober, Ms. Weil, and Mr. Sheetz 22 is the Chair of that subcommittee. The NRC staff 23 resource is Dr. Diabes and in particular there is, as 24 Dr. Diabes mentioned, a section in the Reg Guide that 25 208 is related to patients who are deceased after 1 undergoing radioactive administration.
2 So I don't think that you have to amend 3 the charge of the subcommittee as their charge is to 4 review the Reg Guide in its totality and provide 5 comments to the NRC staff.
6 CHAIRMAN PAL ESTRO: Thank you. Mr. Sheetz?
7 MEMBER SHEETZ: As the Chair of that 8 subcommittee and actually I was wondering if this 9 topic was going to come up, I was going to bring it up 10 also later, because the JAMA article did get a lot of 11 media attention, I do think it's an issue that needs 12 to be evaluated further.
13 While there are NCRP-155 guidelines I am 14 not sure how practical they are. It's a very 15 difficult and sensitive situation when someone dies, 16 you know, whether they are to be cremated or not, they 17 may have pre-arrangements. It's very difficult to 18 stop that process to go with alternative plans.
19 So I think it does warrant for the study, 20 you know, is there a potential risk to workers and the 21 general public from the radiation, what's the 22 magnitude of the risk, how prevalent is the event, 23 although cremation is now over 50 percent of all 24 burials in the United States, what guidance can be 25 209 provided to reduce or mitigate that, and so these are 1 the questions we will certainly look at.
2 CHAIRMAN PALESTRO: Thank you. Is the --
3 Is Ms. Weil on that subcommittee? I'm sorry, okay.
4 Yes, I would think that would be appropriate, 5 especially appropriate for the patient rights 6 advocate.
7 MEMBER SHEETZ: Thank you.
8 CHAIRMAN PALESTRO: Mr. Ouhib?
9 MEMBER OUHIB: Yes. I just have -- I 10 think, and maybe Ms. Shober can answer this question, 11 this is not just addressing like the concern with the 12 authorized uses and all that, but this goes to the 13 cremation centers and all that that if in the event 14 there is a -- How would you determine that a patient 15 has radioactive material or not, you know, when they 16 come from cremation?
17 I guess the question is does the state get 18 involved with these cremation centers at all, is there 19 any communication?
20 MEMBER SHOBER: This is Megan Shober. So 21 I can only speak for my experience. We have been 22 involved with cremation centers in the past. Usually 23 we find out about that from the licensee where the 24 decedent had been previously treated.
25 210 And so it's not clear how that information 1 comes. You know, like there is not a process for 2 that. But as soon as our licensee found out about it 3 they followed up with us.
4 And I am not sure how else you can 5 regulate that, but it is a huge -- By the time you 6 find out about it it's happened and it's happened a 7 while ago usually.
8 CHAIRMAN PALESTRO: Thank you. Any other 9 comments, questions?
10 (No audible response) 11 CHAIRMAN PALESTRO: Mr. Sheetz, are you 12 comfortable with the subcommittee that is already 13 formed? 14 MEMBER SHEETZ: Yes. Yes, I am.
15 CHAIRMAN PAL ESTRO: All right. Thank you.
16 All right, then the afternoon session, the open 17 session is adjourned and Ms. Holiday --
18 MR. EINBERG: Wait.
19 CHAIRMAN PAL ESTRO: I'm sorry, Mr. Einberg.
20 MS. HOLIDAY: And we'll resume at 8:30 in 21 the morning tomorrow. Mr. Einberg?
22 MR. EINBERG: Yes. Actually before we 23 close this with the creation of a new subcommittee for 24 cremation does this possibly merit a separate 25 211 subcommittee because of the extensiveness of the 1 issue? 2 For 8.39 we are looking for a fairly rapid 3 turnaround on the review of that Reg Guide. We are 4 asking for a 60-day turnaround on that. Would 5 additional time and a separate subcommittee give you 6 the opportunity to explore this issue in more detail 7 or -- 8 CHAIRMAN PALESTRO: I will defer to Mr.
9 Sheetz on that.
10 MEMBER SHEETZ: Why don't you allow our 11 subcommittee to look at that and if we need further 12 time on that particular topic we could come back and 13 do that. 14 MR. EINBERG: Okay.
15 MEMBER SHEETZ: I would like to stay 16 involved in that. I have an interest. I grew up in 17 that business from my father a nd so I am interested in 18 seeing this through.
19 MR. EINBERG: Okay. Thank you.
20 CHAIRMAN PALESTRO: Any other comments, 21 questions?
22 (No audible response) 23 CHAIRMAN PALESTRO: This session is 24 adjourned. Thank you all.
25 212 MS. HOLIDAY: Thank you.
1 (Whereupon, the above-entitled matter went 2 off the record at 2:27 p.m.)
3