ML18221A170

Transcript of ACMUI Teleconference on July 16, 2018 on Comments on Draft NRC T&E Evaluation Secy Paper and Public Comments, Pages 1-51

ML18221A170
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Issue date:	07/16/2018
From:	Advisory Committee on the Medical Uses of Isotopes
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NRC-3808
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Official Transcript of Proceedings NUCLEAR REGULATORY COMMISSION

Title:

Meeting of the Advisory Committee on the Medical Uses of Isotopes Docket Number:

(n/a)

Location:

teleconference Date:

Monday, July 16, 2018 Work Order No.:

NRC-3808 Pages 1-51 NEAL R. GROSS AND CO., INC.

Court Reporters and Transcribers 1323 Rhode Island Avenue, N.W.

Washington, D.C. 20005 (202) 234-4433

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 UNITED STATES OF AMERICA NUCLEAR REGULATORY COMMISSION

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ADVISORY COMMITTEE ON THE MEDICAL USES OF ISOTOPES

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TELECONFERENCE

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MONDAY, JULY 16, 2018 The meeting was convened via teleconference at 2:00 p.m., Christopher Palestro, ACMUI Chairman, presiding.

MEMBERS PRESENT:

CHRISTOPHER J. PALESTRO, M.D., Chairman DARLENE F. METTER, M.D., Vice Chairman PHILIP ALDERSON, M.D., Member VASKEN DILSIZIAN, M.D., Member RONALD D. ENNIS, M.D., Member RICHARD L. GREEN, Member MICHAEL D. O'HARA, Ph.D., Member ZOUBIR OUHIB, Member MICHAEL SHEETZ, Member MEGAN L. SHOBER, Member JOHN H. SUH, M.D., Member LAURA M. WEIL, Member

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 NON-VOTING MEMBERS:

MELISSA MARTIN DESIGNATED FEDERAL OFFICIALS:

DOUG BOLLOCK, DFO LISA DIMMICK, Alternate DFO NRC STAFF PRESENT:

MARYANN AYOADE VINCE HOLAHAN SOPHIE HOLIDAY ESTHER HOUSEMAN KATIE TAPP IRENE WU

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 P R O C E E D I N G S 1

2:00 p.m.

2 CHAIRMAN PALESTRO: All right, thank you.

3 Good afternoon and welcome to the Advisory Committee 4

on Medical Uses of Isotopes for the comments on the 5

draft SECY paper. My name is Dr. Christopher 6

Palestro, and I am the Chair of the ACMUI.

7 Thank you all for attending the meeting.

8 And now I would like to turn it over to Mr. Doug 9

Bollock, the Designated Federal Officer.

10 MR. BOLLOCK: Thank you, Dr. Palestro.

11 Good afternoon, everyone. As the Designated Federal 12 Officer for this meeting, I'm pleased to welcome you 13 to this public meeting of the Advisory Committee on 14 the Medical Uses of Isotopes, or ACMUI.

15 My name is Doug Bollock, I'm Chief of the 16 Medical Safety and Events Assessment Branch. I have 17 been designated as the Federal Officer for this 18 Advisory committee in accordance with 10 CFR Part 19 7.11. Present today is the Alternate Designated 20 Federal Officer, Lisa Dimmick, who is also our Medical 21 Radiation Safety Team Leader.

22 This is an announced meeting of the 23 Committee being held in accordance with the rules and 24 regulations of the Federal Advisory Committee Act and 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 the Nuclear Regulatory Commission. This meeting is 1

being transcribed by the NRC, and it may also be 2

transcribed or recorded by others.

3 The meeting was announced in the June 7, 4

2018 edition of the Federal Register, volume 83, page 5

26503.

6 The function of the Committee is to 7

advise the staff on issues and questions that arise 8

on the medical use of byproduct materials. The 9

Committee provides counsel to staff, but does not 10 determine or direct the actual decisions of the staff 11 or the Commission. The NRC solicits the views of the 12 Committee and values their opinions.

13 I request that whenever possible, we try 14 to reach a consensus on the various issues that we'll 15 discuss today. And also recognize that there may be 16 minority or dissenting opinions. If you have such 17 opinions, please allow them to be read into the 18 record.

19 At this point, I'd like perform a roll 20 call of the ACMUI members participating today.

21 Dr. Christopher Palestro, Chairman.

22 CHAIRMAN PALESTRO: Here.

23 MR. BOLLOCK: Thank you. Dr. Darlene 24 Metter, Vice Chairman.

25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 VICE CHAIRMAN METTER: Here.

1 MR. BOLLOCK: Thank you. Dr. Philip 2

Alderson, Health Care Administrator.

3 MEMBER ALDERSON: Here.

4 MR. BOLLOCK: Thank you. Dr. Vasken 5

Dilsizian, Nuclear Cardiologist.

6 MEMBER DILSIZIAN: Yeah.

7 MR. BOLLOCK: Thank you. Dr. Ronald 8

Ennis, Radiation Oncology.

9 MEMBER ENNIS: Here.

10 MR. BOLLOCK: Mr. Richard Green, our 11 Nuclear Pharmacist.

12 MEMBER GREEN: Here.

13 MR. BOLLOCK: Thank you. Dr. Michael 14 O'Hara, our FDA Representative.

15 MEMBER O'HARA: Here.

16 MR. BOLLOCK: Thank you. Zouhir Ouhib, 17 our Therapy Medical Physicist.

18 MEMBER OUHIB: Here.

19 MR. BOLLOCK: Thank you. Mr. Michael 20 Sheetz, Radiation Safety Officer. Ms. Megan Shober, 21 our Agreement State Representative.

22 MEMBER SHOBER: Here.

23 MR. BOLLOCK: Thank you. Dr. John Suh, 24 Radiation Oncologist.

25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 MEMBER SUH: Here.

1 MR. BOLLOCK: Thank you. And Ms. Laura 2

Weil, our Patients Rights Advocate.

3 MEMBER WEIL: Here.

4 MR. BOLLOCK: Thank you. I confirm that 5

we have quorum of over six members. On the phone, 6

did we also have Ms. Melissa Martin?

7 MS. MARTIN: Yes, here.

8 MR. BOLLOCK: Thank you. And Mr. Robert 9

Schleipman. Okay. Ms. Martin has been selected as 10 the ACMUI Nuclear Medicine Physicist Representative.

11 And Robert Schleipman has been selected as the ACMUI 12 Health Care Administrator Representative. They are 13 both pending security clearances, but may assist in 14 the meeting. However, they do not have voting rights 15 at this time.

16 I now ask the NRC staff members who are 17 present to identify themselves. I'll start with the 18 individuals who are in the room with me.

19 MS. WU: Irene Wu.

20 MS. TAPP: Katie Tapp.

21 MS. DIMMICK: Lisa Dimmick.

22 MS. HOUSEMAN: Esther Houseman.

23 MR. HOLAHAN: Vince Holahan.

24 MR. BOLLOCK: Okay, thank you. Now I'll 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 go to NRC Headquarters employees who are on the phone.

1 MS. AYOADE: Maryann Ayoade.

2 MS. HOLIDAY: Sophie Holiday.

3 MR. BOLLOCK: Okay, thank you. Do we 4

have any NRC regional employees on the phone? Okay.

5 Members of the public who notified Ms. Ayoade that 6

they would be participating in the teleconference 7

will be captured in the transcripts.

8 Those of you who did not provide prior 9

notification, please contact Ms.

Ayoade at 10 maryann.ayoade@nrc.gov. That's M-A-R-Y-A-N-N dot A-11 Y-O-A-D-E at nrc.gov. Or (301)415-0862.

12 We have a bridge line available, and that 13 phone number is (888)677-2595. The passcode to 14 access the bridge line is 9887521, followed by the 15 pound sign. This meeting is also using the GoTo 16 webinar application to view presentation handouts 17 real time.

18 You can access this by going to 19 www.gotowebinar.com, that's www dot G-O-T-O-W-E-B-I-20 N-A-R dot C-O-M, and search in the meeting ID 419-21 602-667.

22 The purpose of this meeting is to discuss 23 the draft report of the ACMUI Subcommittee on Training 24 and Experience Required for All Modalities.

25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 This report includes the Subcommittee's 1

comments and recommendations on the NRC staff's 2

evaluation of the training and experience 3

requirements for different categories of 4

radiopharmaceuticals in Title 10 of the Code of 5

Federal Regulations, Part 35, medical use of 6

byproduct materials, Subpart E unsealed byproduct 7

material, written directive required.

8 Individuals who'd like to ask a question 9

or make a comment regarding a specific issue the 10 Committee has discussed should request permission to 11 be recognized by the ACMUI Chairperson, Dr.

12 Christopher Palestro. Dr. Palestro, at his option, 13 may entertain comments or questions from the members 14 of the public who are participating with us today.

15 Comments and questions are usually 16 addressed by the Committee at the end of the 17 presentation, after the Committee has fully discussed 18 the topic. We ask that one person speak at a time, 19 as this meeting is also close-captioned.

20 I would also like to add that handouts 21 and the agenda for this meeting are available on the 22 NRC's public website. At this time, I ask that 23 everyone on the call who is not speaking place their 24 phones on mute. If you do not have the capability 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 to mute your phone, please press star six to utilize 1

the conference line mute and unmute functions.

2 I would ask everyone to exercise extreme 3

care to make sure that the background noise is kept 4

at a minimum, as any stray background sounds can be 5

very disruptive on a conference call this large.

6 At this point, I would like to turn the 7

meeting back over to Dr. Palestro.

8 MR. BOLLOCK: All right, thank you, Mr.

9 Bollock. And at this point, I would like to turn the 10 meeting over to Dr. Darlene Metter, who is the Chair 11 of the Subcommittee on Training and Experience for 12 All Modalities, and she will present the 13 Subcommittee's evaluation of the draft SECY paper.

14 Dr. Metter.

15 VICE CHAIRMAN METTER: Thank you, Dr.

16 Palestro. And thank you for the introduction.

17 Before I start, I'd like to thank my Subcommittee 18 members, Dr. Philip Alderson, Dr. John Suh, Ms. Megan 19 Shober, and Ms. Laura Weil for their contribution to 20 this paper.

21 I'd also like to thank the opportunity to 22 review and provide recommendations for the draft SECY 23 paper entitled Staff Evaluation of Training and 24 Experience Requirements for Administering 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 Radiopharmaceuticals.

1 Now, as an introduction, I'd like to give 2

the following. In June of 2015, because of 3

stakeholder concerns that a shortage of AUs caused by 4

the 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> of training and experience required to 5

become an authorized user under Title 10, Code of 6

Federal Regulations, 35.300, specifically 35.390, 7

training for use of unsealed byproduct material, for 8

which a written directive is required, was limiting 9

patient access to therapeutic radiopharmaceuticals.

10 The ACMUI at that time formed a

11 subcommittee to look into this matter. The charge 12 of the subcommittee was to determine if the 700-hour 13 training and experience requirement placed a hardship 14 on patient access to alpha-and beta-emitting 15 therapeutic radiopharmaceuticals.

16 And if necessary, to make recommendations 17 for potential changes and establish recommendations 18 for the total number of hours of training and 19 experience for use of unsealed byproduct material for 20 which a written directive is required.

21 The Subcommittee concluded that the 22 current requirement of 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br />' training and 23 experience for authorized users did not adversely 24 affect patient access to these radiopharmaceuticals, 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 and that no change in the training and experience 1

requirements was warranted.

2 The Subcommittee also noted that the 3

current training and experience requirements had not 4

been updated in nearly 15 years and recommended that 5

in the future, periodic training and experience 6

reviews be conducted.

7 This recommendation led to the creation 8

of the Subcommittee on Training and Experience for 9

All Modalities.

This Subcommittee created a 10 standardized template for training and experience 11 reviews, which was completed for 10 CFR 35.100.

12 However, due to ongoing patient access concerns, the 13 Subcommittee was directed to expedite the review of 14 10 CFR 35.300, specifically 10 CFR 35.390.

15 During the March 1,

2018 ACMUI 16 teleconference meeting, the Training and Experience 17 Subcommittee reported that two recent developments 18 identified potential future problems with patient 19 access to 10 CFR 35.300 for radiopharmaceuticals.

20 The first was a potential increase in 21 therapeutic procedures related to the recent U.S. FDA 22 approval for broad use of the therapeutic 23 radiopharmaceutical lutetium-177 dotatate. The 24 second was a continued decrease in the number of 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 nuclear medicine physicians in training and sitting 1

for the American Board of Nuclear Medicine initial 2

certification exam.

3 Due to the potential future increase in 4

the number of procedures and the concomitant decrease 5

in

AUs, the Subcommittee recommended that an 6

alternate AU pathway should be reconsidered.

7 From this resulted a draft SECY paper, 8

which I will summarize. This draft paper addresses 9

the NRC staff initial recommendations based on 10 limited stakeholder outreach for training and 11 experience requirements for different categories of 12 radiopharmaceuticals, with a specific focus on 10 CFR 13 part 35 on the medical use of byproduct material, 14 Subpart E, unsealed byproduct material, written 15 directive required.

16 After the final re-revision of 10 CFR 17 Part 35 in August 2017, the Commission tasked the NRC 18 staff to evaluate the possibility of a limited AU 19 training and experience pathway addressing the 20 following.

One, its feasibility for certain 21 categories of radiopharmaceuticals.

22 Two, how to develop such categories.

23 Three, the appropriate training and experience 24 requirements for such categories. And four, whether 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 the training and experience requirements should be 1

based on hours or competency.

2 Under 10 CFR Part 35, Subpart E, the staff 3

considered the possibility of an alternate limited AU 4

pathway with tailored training and experience 5

requirements for certain categories of 6

radiopharmaceuticals. Options for such categories 7

were considered, along with appropriate corresponding 8

training and experience and the documentation of 9

training competency.

10 More extensive stakeholder outreach is 11 planned to address the feasibility of a limited AU 12 status for training and experience requirements and 13 competency assessment.

14 To evaluate the feasibility of a limited 15 AU pathway, the NRC staff first determined the 16 knowledge topic for a training and experience 17 curriculum. The curriculum included the current 18 training and experience categories in 10 CFR 35.390, 19 which would then be tailored to the specific category 20 of radiopharmaceuticals, with additional knowledge 21 topics as needed.

22 The staff then solicited stakeholder 23 input on three other topics. First, the fundamental 24 and specific radiopharmaceutical knowledge required 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 in 10 CFR 35.390 to safely administer the 1

radiopharmaceuticals. The stakeholder response was 2

overall support of the proposed knowledge topics.

3 The second was how to obtain this 4

knowledge. The stakeholder response on this question 5

was varied and ranged from maintaining the current 6

training and experience, saying that only American 7

Board of Radiology or American Board Nuclear Medicine 8

certifications, competency assessments, and perhaps 9

even radiopharmaceutical administration 10 requirements.

11 The third question was how to evaluate 12 the acquisition and independent application of this 13 knowledge. The stakeholder response was varied but 14 will likely require NRC and stakeholder collaboration 15 to determine this assessment.

16 Other concerns were, one, categorizing 17 radiopharmaceuticals, which had various stakeholder 18 and NRC responses. Two, how to administer the 19 training and experience requirements. And the staff 20 was considering using the Reactor Operator Licensing 21 Program as a, rather than a benchmark, but more as a 22 guide to administer these requirements.

23 Three, NRC staff estimated that the 24 required training experience would be up to 300 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 classroom hours. Four, competency assessment method 1

or methods would be an examination developed by the 2

medical community, whether it be a written exam or a 3

hybrid exam, with or without preceptor attestation, 4

and potentially also forming a new specialty board.

5 The final conclusion that the staff made 6

was it may be feasible to develop a limited AU pathway 7

for certain categories of radiopharmaceuticals with 8

a competency-based approach for tailored training and 9

experience requirements and knowledge of skills 10 assessment.

11 The ACMUI Subcommittee had several 12 comments on the SECY paper. The first was that the 13 ACMUI Training and Experience Subcommittee 14 recommended that the development of an alternate 15 pathway be reconsidered.

16 Two, the stakeholder outreach has been 17 limited and was likely related to time constraints.

18 Staff should consider a broader stakeholder outreach.

19 But this outreach could assist in defining the 20 categories for radiopharmaceutical for limited AU 21 status, tailoring the limited T&E requirements, and 22 assessing the success of the knowledge and skills 23 obtained.

24 Third, collaboration with the medical 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 community and other stakeholders to develop a 1

competency-based assessment tool, mostly likely in 2

advance, is commendable. Four, minimizing the 3

training and experience requirements and thus one's 4

knowledge and

skills, potentially jeopardizes 5

patients, personnel, and public safety.

6

Five, the initial projection of 7

authorized users was underestimated in that only 8

nuclear medicine physicians were considered. For the 9

2017-2018 academic

year, the total number of 10 residents who could potentially meet the AU training 11 and experience requirements in 10 CFR 35.390 is nearly 12 900.

13 And this is a number that's all residents 14 in training. And these are in radiation oncology, 15 nuclear

medicine, nuclear radiology, and the 16 redesigned emerging Board of Radiology pathway.

17 The data on osteopathic AUs and on AUs 18 leaving the workforce, however, is currently not 19 available. Although this revised estimate of that 20 total number of future AUs is encouraging, the 21 Subcommittee still recommends reconsideration of an 22 alternate AU pathway.

23 Number six.

The Subcommittee is 24 concerned about estimating the required training and 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 experience classroom hours for an alternate pathway.

1 Given that the curriculum for limited status AU has 2

not been established, the Subcommittee feels that 3

it's premature to address the issue of hours.

4 The Subcommittee feels strongly that 5

should a decision be made to proceed with a limited 6

AU status, the training and experience requirements 7

must be based on the knowledge and skills necessary 8

to maintain patient, personnel, and public safety, 9

and not based on a predefined number of hours.

10 Given these comments, the Subcommittee 11 has five recommendations. The first is that the 12 ACMUI Training and Experience Subcommittee recommends 13 reconsideration of the existing pathways to AU 14 status.

15 This reconsideration should have the 16 goals of first maintaining maximal safety for the 17 patient, personnel, and the public. Second, maximize 18 patient access to current and future 19 radiopharmaceuticals. And thirdly, to clearly define 20 the AU's scope of practice.

21 Second, the educational program must be 22 all-inclusive for the limited AU status. The 23 didactic component necessary to obtain limited AU 24 status under 10 35.390 must comprehensively cover the 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 knowledge topics required for all AUs involved in 10 1

CFR 35.300, thereby ensuring the safe use of 2

radiopharmaceuticals for the patient, personnel, and 3

the public.

4 Third, the assessment method or methods 5

to assess AU competency must be objective and document 6

both initial and continuing maintenance of competency 7

for the limited AU status.

8 Fourthly, there should be greater and 9

broader stakeholder input. And lastly, the NRC staff 10 should conduct ongoing monitoring for potential AU 11 shortages for 10 CFR 35.300. Data on the geographic 12 distribution and practice patterns of AUs should be 13 included in this surveillance.

14 So that's the end of our subcommittee 15 report.

Do I

have any comments from the 16 Subcommittee? Okay, hearing none, do I have any 17 comments from the ACMUI Committee itself?

18 CHAIRMAN PALESTRO: Dr. Metter, this is 19 Dr. Palestro. I have a question for you. First, the 20 Subcommittee is to be commended for doing a more 21 thorough investigation of the anticipated AUs that 22 would be, quote unquote, graduating on a yearly basis.

23 I think that's important information.

24 The Subcommittee's report says 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 approximately 900 potentially could meet the 1

requirements. How does that compare historically?

2 What numbers have been meeting those requirements and 3

obtaining AU status in the past? Is that, do you 4

have that information?

5 VICE CHAIRMAN METTER: No, I don't have 6

that information. I just looked at the current group 7

of individuals that are in training at this point.

8 We can look at that, you know, the past, though.

9 CHAIRMAN PALESTRO: Okay, that might help 10 to give a better picture of what we potentially could 11 expect in the future.

12 MEMBER SUH: Dr. Palestro, this is John 13 Suh, I just want to make a quick comment regarding 14 your question.

15 CHAIRMAN PALESTRO: Yes.

16 MEMBER SUH: So if you look at the 17 historic data which is provided from the American 18 Board of Radiology, in terms of radiation oncology 19 residents, if you look at the year 2006-2007, there 20 were 585 slots, and the vast majority of those being 21 filled. And if you look at 2016-2017, there were 808 22 slots, with the vast majority of those positions being 23 filled.

24 So in the ten-year period, there is an 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 increase of about 220 potential authorized users who 1

would be radiation oncologists.

2 CHAIRMAN PALESTRO: Okay, thank you.

3 But the numbers you give are the total enrolled in 4

the program, which is, if I'm not mistaken, four 5

years. So the number of graduates then would be, or 6

new AUs, would be approximately 25% of that on an 7

annual basis. Am I correct?

8 MEMBER SUH: Yes, it would be about 200.

9 And the number of programs for that ten-year period 10 has increased from 79 programs to 92 programs. So 11 an increase of 13 programs over that decade.

12 CHAIRMAN PALESTRO: Do you anticipate any 13 further increases in the number of programs?

14 MEMBER SUH: I do know some programs that 15 will be applying for residency. I couldn't give you 16 an exact number in terms of what that number would 17 be.

18 CHAIRMAN PALESTRO: Thank you.

19 VICE CHAIRMAN METTER: Also there's a 20 small number also in radiology with the increased 21 number of individuals in the nuclear radiology and 22 the new Board pathway for being an AU. And I have a 23 number, this past or this year, I think there were 11 24 graduates. And I think there's, that's just for this 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 year.

1 Any other comments from the Committee?

2 MEMBER GREEN: Dr. Metter, this is 3

Richard Green. I wish we had more clarity on the 4

number of authorized users, the number of licensees.

5 I mean, that's just something we don't have.

6 But I think it's a great opportunity to, 7

although the historical hours and assessments of 8

competency based on hours has been in place for 15 9

years, no one can really say, you know, it's written 10 in stone in a CFR.

11 But no one can really say what that was 12 based upon, or whether those hour levels are 13 appropriate today in today's modern modes of 14 learning, computer-based training or web training.

15 So I just think it's valuable that there's now a 16 standing committee that you chair that looks at what 17 is the current, really, the appropriate way to assess 18 competency.

19 And I just think it's great that this is 20 being refreshed now. So we can make comments 21 relative to the request from the Commissioners and 22 address the draft recommendations made by staff.

23 But to do that, we really take a look and 24 see what it would take to adequately train a physician 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 to safely administrate radiopharmaceuticals. Until 1

that's done, we are looking at history, but not really 2

knowing where it came from.

3 VICE CHAIRMAN METTER: Thank you. Are 4

there any other comments from the Committee?

5 MEMBER OUHIB: Yes, Dr. Metter, this is 6

Zoubir Ouhib. I think to answer Mr. Green's comment 7

is that my understanding is really this is based on 8

all the education that was basically required from an 9

authorized user, you know.

10 And I guess if you go back and take a 11 look at what these authorized users had to complete 12 and so on, I think that it will be a reasonable 13 estimate of that kind of a number, in my opinion.

14 VICE CHAIRMAN METTER: Okay, thank you.

15 MEMBER SHOBER: This is Megan Shober, I 16 also have a comment about the hours.

17 VICE CHAIRMAN METTER: Yes.

18 MEMBER SHOBER: So when the 10 CFR 35 had 19 its major revision the last time, the final rule was 20 in 2002, the proposed rule was issued in 1998. And 21 as part of that, and with the proposed rule, there's 22 a pretty extensive discussion on where the number, 23 the training and experience hours comes from.

24 There's about five pages of discussion 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 about where that 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> comes from. So I encourage 1

people to take a look at that original proposed rule 2

from August 13, 1998. And it informs a lot of this 3

discussion that we've been having over where the hours 4

come from.

5 VICE CHAIRMAN METTER: Okay, thank you.

6 Okay, are there any more comments from the ACMUI 7

Committee members?

8 CHAIRMAN PALESTRO: Dr. Metter, this is 9

Dr. Palestro again. In your summary of the draft 10 SECY paper, you said it addresses the NRC staff's 11 initial recommendations based on limited stakeholder 12 outreach. Could you elaborate on what constituted 13 the limited stakeholder outreach and what was the 14 basis of selection of those stakeholders?

15 VICE CHAIRMAN METTER: As far as the 16 stakeholders, I believe it was in the report.

17 Maryann, or is there an NRC staff that can help with 18 that?

19 MR. BOLLOCK: Yes, this is Doug Bollock, 20 I can address that. So we had, I think, based on 21 that paper, we had a limited time frame to get a 22 limited amount of stakeholder outreach. And we are 23 also limited by our burden requirements under OMB.

24 So we can only reach out to nine non-federal agencies 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 or non-federal entities.

1 So we made the determination of the nine.

2 We wanted to get as broad of a spectrum as we could, 3

so we asked a number of licensees, picked a couple of 4

licensees from different parts of the country trying 5

to get a large institution and maybe a smaller size 6

institution that's represented.

7 We asked one of the, a professional 8

society. We asked CORAR for, I guess manufacturing, 9

I'm trying to think what the proper term is. But we 10 asked one board, the American Board of Nuclear 11 Medicine, and we also reached out to one of our co-12 regulators, we reached out to Virginia.

13 And then we did reach out to a number of 14 federal facilities, Navy, the Army hospitals to get, 15 to kind of increase the stakeholder, from licensees 16 or from users of the radiopharmaceuticals.

17 We tried to get as broad of a, with the 18 limits of only being able to ask nine non-federal 19 entities, we tried to get as broad of a spectrum as 20 we could with that limit. So with licensees, our 21 board, professional organizations, and one state 22 regulator.

23 VICE CHAIRMAN METTER: Thank you.

24 CHAIRMAN PALESTRO: Yeah, thank you, Mr.

25

25 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 Bollock. That answers my question. I appreciate 1

that.

2 VICE CHAIRMAN METTER: Are there any 3

other questions from the ACMUI Committee or comments?

4 MEMBER OUHIB: Doctor Metter, this is 5

Zoubir Ouhib again. I do have a comment, if you 6

could go up a little bit on your document. Move to 7

page one or two. There was a statement made 8

regarding, let me just see that. I think this is 9

relating to the FDA on the new isotope.

10 My question is that the, you know, there 11 was a statement that says there's a potential increase 12 of users or something. I'm just curious, that 13 potential future increase is based on what, exactly?

14 What data is used to actually make such a statement?

15 VICE CHAIRMAN METTER: Well, the dotatate 16 has, it's going to be used for neuroendocrine tumors, 17 and can be used for several of them. Most of the 18 treatments right now with radiotherapy is limited, 19 let's say for specific use. But this can be a broader 20 use for neuroendocrine tumors.

21 Dr. Palestro, I believe you had looked 22 into that in your report.

23 CHAIRMAN PALESTRO: Yes. The answer is 24 that the previous radiopharmaceuticals that have been 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 approved were approved with a, had very narrow 1

approval. Typically, they were for patients who had 2

failed all sorts of previous therapies and very 3

specifically defined criteria.

4 Lutetium 177 dotatate, however, had a 5

much broader approval, a much more general approval, 6

and could be used conceivably at virtually any point 7

during the patient's treatment. It could be used as 8

a first line, it could be used a second line, it could 9

be used as an endline treatment. Really up to the 10 discretion of the individuals managing the patients.

11 And then in addition to that, these 12

tumors, these

gastro, entero, pancreatic, 13 neuroendocrine tumors, which were once thought to be 14 relatively uncommon, are now recognized to be the 15 second most common GI tract malignancy. So that's 16 how we came to the conclusion that the potential 17 exists for a broader use of this agent than previous 18 similar agents.

19 MEMBER OUHIB: And this is simply just 20 an estimate here, is that correct?

21 CHAIRMAN PALESTRO: Correct.

22 MEMBER GREEN: Dr. Palestro, it's also 23 an additional fact that a single patient with a 24 gastro-entero-hepatic tumor would undergo multiple 25

27 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 courses of radionuclide therapy also weighs into that 1

consideration.

2 CHAIRMAN PALESTRO: To a lesser degree 3

because patients who are being treated with radium 4

dichloride also undergo multiple courses.

5 VICE CHAIRMAN METTER: Okay. Are there 6

any additional comments from the ACMUI Committee 7

members? Okay, I'd like to open the commentary then 8

to the public.

9 OPERATOR: Thank you. Participants on 10 the phone, if you have a comment at this time, press 11 star one and record your name. One moment to see if 12 we have any comments.

13 We have a comment from Sue, your line is 14 now open.

15 MS. LANGHORST: Hi, this Sue Langhorst.

16 Hi there. I had a few questions for the ACMUI and 17 the NRC staff to consider.

18 My first question is will the NRC plan to 19 track information on the kinds of physicians who 20 utilize the specialty T&E training and experience 21 tracks, as I'm terming them, and report back to the 22 ACMUI the regulatory results and issues that come 23 from this change, that is, how effective the training 24 is for their regulatory compliance? That's my first 25

28 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 question.

1 My next question is if new licenses are 2

issued for this specialty track training and 3

experience, who will function as the RSO?

4 And my third question is will authorized 5

users with specialty track approval be able to be 6

appointed as an RSO, and if so, what additional 7

training will they be required to obtain? I thank 8

you all for considering the questions.

9 MR. BOLLOCK: Thanks, Dr. Langhorst.

10 This is Doug Bollock, I'm going to go kind of in 11 reverse order to answer your questions. It's a 12 little bit easier. So these are just the, so this 13 is nothing set in stone yet, but we just thought of 14 what are some other ways, what are possible ways to 15 allow for expanded authorized users.

16 And one way is to have a limited 17 authorized user, potentially, who would be limited to 18 whatever drug that they were going to use. But a 19 limited authorized user, we have not had any thought 20 or taken into consideration of changing the 21 requirements for an RSO.

22 Therefore, if we had an authorized, a 23 limited authorized user and is just right now, again, 24 we're just, we haven't planned on anything yet. But 25

29 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 if they're I guess lesser requirements than a full, 1

authorized user, it's unlikely that they would be, 2

that they would meet the requirements for an RSO.

3 Okay, so that likely they would not.

4 Your second question of who would 5

function as an RSO, someone who is, meets the 6

requirements for 35.50 and all the requirements in 7

the license to be an RSO at whatever facility, or 8

yeah, at a licensed facility. So those requirements 9

are not, we're not considering any changes to the 10 RSOs.

11 And then for your first question, I think 12 we did, I don't think we quite understood your first 13 question, and what. Were you asking if we, through 14 our outreach, if we're going to get more information 15 on the, on current AUs and their training or how they 16 got training? I'm not, we're not sure we understand 17 your first question, could you please repeat it?

18 MS. LANGHORST: Absolutely, absolutely.

19 MR. BOLLOCK: Thank you.

20 MS. LANGHORST: So really what, so Doug 21 what I'm talking about is if the NRC and the ACMUI 22 recommend that there be a specialty track, let's say 23 like there is for 35.392 or 35.394 for I-131 24 therapies. If there are different kinds of 25

30 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 positions, then nuclear medicine and radiation 1

oncology positions utilizing that track, will NRC be 2

considering some way of reporting back any regulatory 3

issues as far as what type of physician are having 4

these issues?

5 And if that the training that's set for 6

that level, is it adequate to meet all the regulatory 7

compliance requirements? Not that I'm asking you to 8

answer that question now, that's a question I'm 9

suggesting you consider.

10 MR. BOLLOCK: Okay, thank you for the 11 comment. We'll consider that.

12 MS. LANGHORST: Thank you all.

13 OPERATOR: Once again, if you have a 14 question or comment, please press star one and record 15 your name. Speakers, let me know whenever you're 16 ready for the next question. And it looks like we 17 have a question from Cindy Tomlinson. Your line is 18 open.

19 MS. TOMLINSON: Thank you. Chairman 20 Palestro and members of the ACMUI and NRC staff, thank 21 you for allowing me to provide this statement on 22 behalf of the American Society for Radiation 23 Oncology.

24 In response to the ACMUI's comments on 25

31 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 the draft SECY paper entitled Staff Evaluation of 1

Training and Experience Requirements for 2

Administering Radiopharmaceuticals being discussed 3

today, because the draft SECY paper is not public, 4

our comments reflect only on the ACMUI draft and 5

report and recommendations.

6 As we have commented in past statements 7

to the ACMUI, we strongly oppose any reduction in the 8

training experience requirements found in 10 CFR 9

35.390, training for use of unsealed byproduct 10 material, for which a written directive is required.

11 ASTRO believes that the requirements 12 found in this section are appropriate to protect the 13 safety of patients, public, and practitioners and 14 should not be changed. Radiopharmaceuticals are 15 highly effective in treating cancer, with possible 16 harmful effects to both the patient and the public if 17 not used correctly and under the supervision of a 18 highly trained physician.

19 The rigorous T&E requirement contributes 20 to the excellent safety record of 21 radiopharmaceuticals.

We believe that it is 22 important that the person administering the 23 radiopharmaceutical is appropriately trained in the 24 safe handling, exposure risks, and the management of 25

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(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 side effects of radiation.

1 In general, ASTRO is comfortable with the 2

broad recommendations made by ACMUI and believes that 3

a thorough and comprehensive review of current T&E 4

requirements is reasonable.

5 Additionally, we fully support the 6

ACMUI's recommendation that the NRC conduct a 7

thorough examination of geographic distribution and 8

practice patterns of current AUs under 10 CFR 35.390 9

and 300, as well as taking greater stakeholder input.

10 The American Board of Radiology estimates 11 that between 2007 and 2017, approximately 1650 12 radiation oncologists were certified by the ABR with 13 an authorized user eligibility designation and may 14 become AUs.

15 In addition, we estimate that there are 16 approximately 2200 radiation oncology facilities in 17 the US. Together with current radiation oncology 18 AUs, the 773 radiation oncology residents currently 19 in residency programs and nuclear medicine-trained 20 AUs nationwide, there are likely enough AUs to 21 administer radiopharmaceuticals.

22 We caution a change in the current 23 requirements without a comprehensive investigation 24 could result in unintended harm to

patients, 25

33 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 personnel, and the public. ASTRO looks forward to 1

continuing to work with both the ACMUI and the NRC as 2

we continue deliberations and review on this very 3

important topic. Thank you.

4 VICE CHAIRMAN METTER: Thank you.

5 OPERATOR: Once again, if you have a 6

question or comment, please press star one and record 7

your name. It looks like we have a comment from Paul 8

Wallner, your line is open.

9 MR. WALLNER: Thank you, good afternoon.

10 My name is Dr. Paul Wallner, I'm a radiation 11 oncologist who is separately Board-certified in 12 radiation oncology and diagnostic radiology in 13 nuclear medicine. I previously served as Chief of 14 the Clinical Radiation Oncology Branch of the 15 National Cancer Institute, when my research interest 16 was in targeted radiopharmaceuticals.

17 I'm speaking today on behalf of the 18 American College of Radiology, ACR. The ACR 19 represents over 35,000 diagnostic radiologists, 20 interventional radiologists, radiation oncologists, 21 nuclear medicine physicians, and medical physicists.

22 The ACR understands the tight deadline 23 and external pressures prompting the staff's draft 24 paper. However, we strongly urge more extensive 25

34 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 public engagement of the medical stakeholder 1

community before the NRC takes any significant action 2

on the issues covered by the draft paper.

3 Forward movement on this topic seems to 4

be predicated on the presumption that the 700-hour 5

training and experience requirements in 10 CFR 35.390 6

is no longer appropriate, particularly for 7

individuals without NRC-recognized Board 8

certification.

9 But the underlying concerns have yet to 10 be substantiated in a quantitative, impartial, and 11 apolitical fashion. Before there is any serious 12 movement towards modifying T&E content or hours, 13 there should be a fact-driven assessment of the 14 external criticisms regarding 35.390.

15 After all, 35.390 has a track record of 16 success in providing NRC with a reasonable assurance 17 of the adequate protection of public health and 18 safety. To help substantiate or disprove AU 19 population concerns, it's most important for NRC to 20 gather trustworthy data on the active AU population 21 providing various therapies under 35.390.

22 The collective data should enable 23 exploration of AU numbers and coverage over a multi-24 year period of time. This suggestion has been made 25

35 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 previously, and we understand that such an activity 1

would be labor-intensive and require collaboration 2

with agreement states and broad scope licensees.

3 However, without confirmation by NRC of 4

a problem, there is a questionable technical basis 5

for any rulemaking to modify 35.390 or the other 6

subparts of Part 35.

7 Moreover, any presumption of a future AU 8

shortage informed solely by ABNM trends neglects the 9

radiation oncology and new nuclear radiology 10 pathways, which we understand to be stable, or in the 11 case of nuclear radiology, expanding in size and 12 distribution.

13 While prescriptive, the 700-hour training 14 and experience prerequisite in 35.390 was 15 fundamentally intended to ensure prospective AUs, 16 without certification from the NRC-recognized board, 17 have an adequate base of knowledge and radiation 18 safety to supervise the proper use of these 19 therapeutical medical nuclear materials, including 20 medical event prevention, identification, and 21 mitigation.

22 If NRC determines, based on data, that a 23 rulemaking to overhaul 35.390 T&E requirements is 24 ultimately necessary, any future regulatory 25

36 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 modification must reasonably ensure that clinicians 1

who do not possess the expertise obtained via their 2

residency programs and fellowships can appropriately 3

fulfill AU responsibilities and protect their 4

patients, staff, and other members of the public.

5 In conclusion, the ACR supports more 6

extensive engagement of medical stakeholders on 7

issues discussed in the draft paper. We look forward 8

to seeing the final product at the end of summer and 9

hope it reflects both the needs for more public 10 engagement, as well as the need for an NRC assessment 11 of AU members to justify any further action.

12 The ACR also hopes to provide input to 13 the ACMUI on its own efforts related to these issues.

14 Thank you for your time.

15 VICE CHAIRMAN METTER: Thank you, Dr.

16 Wallner. Are there any other --

17 OPERATOR: We have a question. Yes, we 18 do have an additional question. It comes from 19 Bennett Greenspan. Your line is open.

20 MR. GREENSPAN: Hello, thank you. I'm 21 Dr. Bennett Greenspan, I'm a nuclear medicine 22 physician and radiologist and the immediate past 23 President of the Society of Nuclear Medicine and 24 Molecular Imaging. And I have a few brief comments.

25

37 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 I pretty much agree with, I shouldn't say 1

pretty much, I agree with the ACMUI's Subcommittee 2

report. I did want to point out that physicians who 3

don't know what they're doing could create severe 4

harm to patients, and even personnel in the public, 5

if they're not careful and so on.

6 And so physicians completing an alternate 7

pathway must have the knowledge and basic science and 8

clinical information to the same degree as those 9

people trained in nuclear medicine, radiology, or 10 radiation oncology.

11 And it also turns out that to do these 12 therapies properly, these physicians need to have 13 some background in understanding the imaging related 14 to these therapies for optimal patient care.

15 And one other point I'd like to mention 16 is that physicians in nuclear medicine, nuclear 17 radiology, and radiation oncology training programs 18 are now, it's supposed to be related information but 19 it immersed it during their training. They're 20 basically involved in this for several years during 21 their training.

22 And other physicians such as medical 23 oncologists do not have this training at all. And 24 so they would, they were just totally deficient in 25

38 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 anything related to radiation physics, radiation 1

safety, and so on. So you know, if they wish to do 2

these therapies, they really need to have the same 3

kind of knowledge and skills that nuclear medicine, 4

nuclear radiology, and radiation oncology physicians 5

have.

6 I did want to point out that the number 7

trainees in nuclear medicine appears to have 8

stabilized over the last couple of years.

9 And one other comment, the future of 10 these therapies I think will probably include 11 combinations of various alpha and beta emitters. And 12 so it's going to get much more complicated, and it's 13 going to take some real expertise in the physicians 14 providing these therapies. Thank you very much.

15 OPERATOR: Back to you, speakers. I'm 16 showing no other comments at this time.

17 VICE CHAIRMAN METTER: Okay. So if there 18 are no other comments, the Subcommittee, this 19 committee, or its public, I turn this over back to 20 Dr. Palestro.

21 CHAIRMAN PALESTRO: All right, thank you, 22 Dr. Metter. I do have one final comment. I do want 23 to point out that no one on the ACMUI, the 24 Subcommittee, or staff has suggested anything about 25

39 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 minimizing or fast-tracking or limiting training and 1

experience requirements. And that's certainly not 2

the intention of, and I'll take the liberty of the 3

speaking for the Subcommittee, the ACMUI and the 4

staff.

5 And in fact, I would call your attention 6

to the last page of the Subcommittee's report. At 7

the top of the page, item number four, minimizing the 8

training and experience requirements and thus one's 9

knowledge and skill potentially jeopardizes patient, 10 personnel, and public safety. And that deserves re-11 emphasis. And I will conclude my comments there.

12 Any other comments from the Subcommittee, 13 or the ACMUI?

14 OPERATOR: Excuse me, speakers, it looks 15 like we have a few additional questions queueing up.

16 Would you like to take those questions?

17 CHAIRMAN PALESTRO: Yes.

18 OPERATOR: Thank you. And it looks like 19 we have a question from Michael Guastella. Your line 20 is open.

21 MR. GUASTELLA: Thank you, and I'm sorry 22 for signaling in there a little bit late, I apologize.

23 I'm Michael Guastella, I'm the Executive Director of 24 CORAR. Mr. Bollock mentioned a little bit earlier 25

40 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 that we were one of the organizations that provided 1

feedback.

2 And I'd just like to say that first of 3

all, CORAR supports the ACMUI recommendation for the 4

reconsideration of the existing pathways for AU 5

status. And the goal, maintaining maximal safety for 6

the patient, personnel, and the public, maximizing 7

patient access to current and future 8

radiopharmaceuticals, and clearly delineating the 9

AU's scope of practice.

10 We've also supported in the past an 11 alternative pathway and an alternative to the current 12 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br />' training and experience requirements under 13 35.390. We have recommended a very specific scope 14 of training requirements for radioisotope handling 15 and radiation safety.

16 For specialists, like Hem/Oncs and 17 medical oncologists, who wish to administer IV 18 therapeutic radiopharmaceuticals, alpha-and beta-19 emitting radioisotopes, as has been mentioned, which 20 have been prepared by a licensed nuclear pharmacist 21 in a state-licensed radiopharmacy and dispensed to 22 physicians as patient-ready doses.

23 In determining the appropriate amount of 24 time and scope of content for radioisotope handling 25

41 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 and radiation safety training that physician must 1

have to safely administer these types of therapeutic 2

drugs, CORAR has offered the following for ACMUI 3

consideration.

4 And I reiterate, the limited role in 5

handling these radio-labeled therapeutic drugs that 6

are dispensed and delivered to physicians in patient-7 ready doses from licensed radio pharmacies. The 8

radiological safety profiles and radiopharmaceuticals 9

containing alpha-and beta-emitting isotopes. And 10 physician experience in training and handling toxic 11 non-radioactive therapies, such as cytotoxic 12 chemotherapy agents.

13 In closing, I'd like to say the goal of 14 the training experience requirements under an 15 alternate pathway is to provide licensed medical 16 specialists with competency and cognitive and 17 psychomotor skills necessary to effectively and 18 safely prescribe and administer specific 19 radiopharmaceuticals. Thank you.

20 OPERATOR: It looks like we have two 21 additional comments. The next one comes from Shaemus 22 Gleason. Your line is open.

23 MR. GLEASON: Hi, and thanks for taking 24 my question today. I'm Shaemus Gleason with Bayer 25

42 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 Healthcare.

1 And in support of the ACMUI findings, we 2

actually presented a petition of sorts to the degree 3

of outlining some of the research that was missing 4

around access to our drugs, particularly Xofigo.

5 And what you'll see is after five years 6

on the market, 20,000 patients treated, 1400 sites up 7

and running, we still notice significant patient 8

falloff based on availability, both regionally and 9

just generally.

10 And in addition to that, we see a number 11 that exist that shows patients unwilling to travel 12 that results in them not receiving the therapy. So 13 once again, you know, we are very supportive of the 14 ACMUI's recent attention to these issues, and look 15 forward to engaging in further conversation. Thank 16 you.

17 OPERATOR: We have a question from 18 Bennett Greenspan. Your line is open.

19 MR. GREENSPAN: Thank you. This is 20 Bennett Greenspan again. Again, I'm a nuclear 21 medicine physician and radiologist.

I'm the 22 immediate past President of the Society of Nuclear 23 Medicine and Molecular Imaging.

24 We were, we the Society of Nuclear 25

43 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 Medicine and Molecular Imaging, were expecting to 1

have a statement, and that hasn't been presented. So 2

if you don't mind, I'd like to present it on behalf 3

of the Chair of the Government Relations Committee.

4 I am a member of that committee, and we the Society, 5

appreciate the opportunity to address the ACMUI on 6

this topic.

7 SNMMI, together with representatives from 8

the American College of Nuclear Medicine, the ACNM, 9

and the American Society of Radiation Oncology, ASTRO 10 11 VICE CHAIRMAN METTER: Did we lose Dr.

12 Greenspan?

13 CHAIRMAN PALESTRO: I don't hear him on 14 the line.

15 OPERATOR: He'll need to redial back in, 16 or press star and one. It looks like we've lost him.

17 CHAIRMAN PALESTRO: All right, let's give 18 him a couple of moments, see if he can rejoin the 19 meeting.

20 MR. BOLLOCK: And this is Doug Bollock.

21 We did receive, as you know we received a letter from 22 SNMMI, ACNM, and ASTRO combined. We also received 23 one from Bayer. Yeah, those will be publically 24 available when we post the transcripts for this 25

44 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 meeting.

1 So Dr. Greenspan, if you hear us, your, 2

the combined statement from SNMMI, ASTRO, and ACNM 3

will be publically available. It has been received 4

by ACMUI and the NRC, so we do have that, we are 5

aware. And the rest of the public will be able to 6

see it when the transcripts and everything else from 7

this meeting are shared.

8 CHAIRMAN PALESTRO: All right, thank you, 9

Mr. Bollock. Are there any other comments or 10 questions from the Subcommittee, the ACMUI, or the 11 public?

12 OPERATOR: We do have an additional 13 question from the public. We have a follow-up 14 question from Michael. Your line is open, Michael.

15 MR. GUASTELLA: Thank you. This is 16 Michael Guastella again. And I guess my question is 17 more of a process question. So I realize that the 18 draft report has been presented the ACMUI. It's been 19 reviewed. Maybe Mr. Bollock can speak to what the 20 next step would be. I believe he said in March that 21 the final report, the NRC staff report, is due to the 22 Commission late summer.

23 I may have, my recollection may not be 24 accurate. I'm just kind of curious if he could 25

45 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 comment or anyone can comment on that. And will this 1

require changes to rulemaking, or are there other 2

pathways that an alternate pathway could be 3

considered? Thank you.

4 MR. BOLLOCK: Thanks for that question, 5

this is Doug Bollock again. So we owe the Commission 6

a, or we owe a product to the Commission on August 7

31, and so it'll be delivered to the Commission August 8

31 and made public within a few days of that.

9 So it will be available to the public I 10 would say probably the first week in September.

11 Yeah, subject to Commission, they get a chance to 12 look at it and then it is made public after that 13 point.

14 OPERATOR: Thank you, speakers. Once 15 again, if you'd like to ask a question or a comment, 16 please press star then one. We have a question from 17 Carol Marcus. Your line is open.

18 MS. MARCUS: Thank you very much, Dr.

19 Palestro and members of the ACMUI. I am opposed to 20 an alternate pathway. I urge the ACMUI to follow the 21 money here. The radiopharmaceutical companies want 22 to sell more drugs. The medical oncologists who 23 would not order Zevalin on their patients because 24 they couldn't make money on it now want to get 25

46 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 licenses so they can make money on it.

1 This patient access issue I think is 2

really a nonexistent issue. I think it's more a 3

money issue.

4 The NRC is jumping on this because by 5

selling more licenses, it's going to make a lot more 6

user fee money to support its medical program 7

bureaucracy. And so I think that you really have to 8

look at the money.

9 If somebody living in Podunk, USA needs 10 a triple CABG, he's not going to get it at his little 11 25-bed community hospital or county hospital where he 12 lives. He is going to have to travel. Because 13 complex medical procedures are not available all over 14 the United States anywhere you live. And people are 15 used to that fact.

16 Now, there's no limit to how low the 17 quality of medicine can get, but that doesn't mean 18 it's a good idea. I think these people who need 19 specialized nuclear medicine therapy, which is 20 combined with imaging, as I think Bennett Greenspan 21 mentioned, or somebody mentioned, more and more 22 combined. The whole reason lutetium is used for 23 therapy is that it allows imaging as well as the 24 therapy of the beta particle.

25

47 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 So you need even more qualified and 1

competent and experienced and knowledgeable 2

physicians for these therapies than you used to.

3 This is no time to degrade the training and 4

experience.

We need the highly skilled 5

practitioners.

6 Back in 1994, the ACMUI unanimously voted 7

to get rid of the 80-hour program for endocrinology, 8

on the basis that they simply do not get the education 9

and training in all the aspects of physics, radiation 10 safety, and more modern nuclear medicine requirements 11 than they did back in 1946 when that 80-hour program 12 started.

13 But the NRC ignored the ACMUI completely.

14 This was the recommendation for the 1995, 1997 I guess 15 it was, redo of all of Part 35. So when physicians 16 in non-nuclear medicine or radiology practices say 17 they want an 80-hour program as well, I think we 18 should say that doesn't work. Albert Einstein 19 couldn't learn this stuff in 80 hours9.259259e-4 days <br />0.0222 hours <br />1.322751e-4 weeks <br />3.044e-5 months <br />, let alone 20 somebody with no basic training in radiology or 21 nuclear medicine.

22 And just bear in mind follow the money 23 and let's stick with the qualifications that we've 24 got. And I would add I would like to see the NRC 25

48 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 enforce them. I have seen the NRC examine residency 1

training programs to see where the 200 and 500 hours0.00579 days <br />0.139 hours <br />8.267196e-4 weeks <br />1.9025e-4 months <br /> 2

are. And I think a lot of people's programs really 3

don't reflect that.

And I

think it needs 4

enforcement.

5 I got a letter from the head of NMSS a 6

few weeks ago commenting on a letter I had sent, who 7

insisted that the NRC does examine this. And I had 8

to write back and tell him you're really under a 9

misconception. NRC does not look at these hourly 10 trainings.

11 And the preceptor statement has nothing 12 to do with ascertaining those training hours either.

13 And in this morning's Federal Register the NRC has 14 announced among other things that the preceptor 15 requirement is gone as of, you know, mid-January.

16 So without that last-ditch preceptor 17 attestation of confidence, you really better make 18 sure that the hourly and content requirements of the 19 residency training programs are being met. And I 20 really think that in many residency training programs 21 they are not. Thank you very much.

22 VICE CHAIRMAN METTER: Thank you. Did 23 Dr. Greenspan get back on?

24 OPERATOR: Again, Michael, if you're on 25

49 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 the line, please press star one to ask a question or 1

finish your statement. One moment to see if he joins.

2 VICE CHAIRMAN METTER: Thank you.

3 MR. BOLLOCK: Dr. Palestro, this is Doug 4

Bollock, and if I may, we appreciate the comments 5

from everyone, including Dr. Marcus. I just want to 6

clarify, one clarification to Dr. Marcus's statements 7

to the Part 35 rule that went out. The preceptor 8

attestation removal was only for Board-certified AUs.

9 That's just a clarification.

10 CHAIRMAN PALESTRO: Thank you, Mr.

11 Bollock. Any additional questions or comments?

12 MS. MARTIN: This is Melissa Martin. I 13 am the incoming nuclear medicine member of the ACMUI.

14 Having served as Radiation Safety Officer 15 at multiple medical centers in Southern California, 16 I think one area that has not been considered that 17 I'm not sure how we go about it, but when you raise 18 the possibility that isotopes are going to come into 19 medical facilities being sold or delivered directly 20 to physicians, that will violate most of the 21 hospital's radioactive materials licenses. Because 22 right now, everything has to be delivered to a 23 designated point.

24 I think the other thing we have to figure 25

50 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 out is if they are now going to be delivered to a 1

nuclear medicine department or a radiation oncology 2

department, that staff's time is now going to be spent 3

taking care of a physician for which they will re-4 coop none of the cost of their time to receive the 5

isotope, prep the isotope, potentially clean up the 6

mess of the isotope.

7 I

just want those points to be 8

considered, because I think the practical end of 9

opening the range of users could be quite significant.

10 CHAIRMAN PALESTRO: Thank you for that 11 comment. Any other comments?

12 OPERATOR: No questions from the phone.

13 CHAIRMAN PALESTRO: All right. In view 14 of that, I'm going to ask if there is a motion to 15 endorse the Subcommittee's report as written.

16 MEMBER ALDERSON: So moved. This is 17 Alderson, so moved.

18 CHAIRMAN PALESTRO: Okay, thank you, Dr.

19 Alderson. Second?

20 MEMBER SHEETZ: Second from Sheetz.

21 CHAIRMAN PALESTRO: Thank you. All in 22 favor?

23 (Chorus of ayes.)

24 CHAIRMAN PALESTRO: Any opposed? All 25

51 NEAL R. GROSS COURT REPORTERS AND TRANSCRIBERS 1323 RHODE ISLAND AVE., N.W.

(202) 234-4433 WASHINGTON, D.C. 20005-3701 (202) 234-4433 right, then the motion to endorse the report as 1

written is unanimously passed. And at this point, I 2

thank all of the participants, the Subcommittee for 3

their work, the staff, the ACMUI, as well as the 4

individuals who took time out of their day to comment 5

on the bridge line.

6 And at this point, I will turn the meeting 7

over to Mr. Doug Bollock.

8 MR. BOLLOCK: Thank you, Dr. Palestro.

9 Just as a reminder to you all, the next ACMUI public 10 meeting is our fall meeting here in NRC Headquarters 11 in Rockville, MD, September 20 and 21.

12 And I'd like to thank

ACMUI, the 13 Subcommittee for reviewing our paper and providing us 14 your comments and recommendations for full Committee, 15 for your time today reviewing it and giving comments 16 and considering it.

17 And also I'd like to thank all the public 18 members who listened in today and gave comments. We 19 appreciate it greatly.

20 OPERATOR: Thanks for your participation 21 and you may disconnect at this time.

22 CHAIRMAN PALESTRO: Thanks a lot.

23 (Whereupon, the above-entitled matter 24 went off the record at 3:08 p.m.)

25

1850 Samuel Morse Drive, Reston, VA 20190-5316 P: 703.708.9000 F: 703.708.9015 www.snmmi.org

July10,2018

DouglasBollock U.S.NuclearRegulatoryCommission MailStop016G4 Washington,DC205550001

Re:Statementontrainingandexperienceforauthorizedusers:GuidancefortheNuclearRegulatory Commission(NRC)AdvisoryCommitteeontheMedicalUseofIsotopes(ACMUI)

DearMr.Bollock:

TheleadershipoftheSocietyofNuclearMedicineandMolecularImaging(SNMMI),togetherwith representativesfromtheAmericanCollegeofNuclearMedicine(ACNM)andAmericanSocietyof RadiationOncology(ASTRO)formedanadhoccommitteetooffertheircollectiverecommendationfor potentialupdatestothe10CFR35.390,Trainingforuseofunsealedbyproductmaterialforwhicha writtendirectiveisrequired.Weareofferingsuggestionsspecificallyregardingthebasicandclinical knowledgeandskillsneededforthoseseekingauthorizeduserstatusthroughthealternatepathway (10CFR35.390(b))toutilizeradioisotopestoprovidesafeandeffectiveclinicaldiagnosticand therapeuticresultstopatients.

Withregardtotrainingandexperiencerequirementsandtheinitialdeterminationofcompetency,itis ouropinionthatmasteryofthecurriculumlistedbelowwillensurehighqualitypracticeofradionuclide therapy.Thisdidacticinstructionandlaboratorytrainingisimportantforsafeandeffectivetherapies andshouldnotbeminimized.Theuseofunsealedsourcesfortherapeuticapplicationsiscomplexand hasseriousmedicalandsafetyriskassociatedwithit,notonlyforthepatientbutfortheirfamily,and thepublicatlarge.Assuch,wefeelitisimportanttomaintainthishighqualityoftrainingand experience.

Furthermore,wedonothaveevidenceofanauthorizedusershortage,andthereisnoharddatato supportapotentialshortage.BecauseofbroadlicensingbytheNRC,exactnumbersofauthorizedusers acrossvariousdisciplinesisdifficult,ifnotimpossibletoobtain.Whilethenumberofnuclearmedicine traineeshavedeclinedoverthepastfewyears,combineddiagnosticradiologyandnuclearmedicine residencieshavedevelopedandarerapidlygaininginpopularity,balancingthedeclineofnuclear medicineresidencytrainees.Furthermore,thousandsofradiationoncologistsareauthorizedusersof unsealedsourceradiotherapiesorhaveanauthorizedusereligibilityspecifiedontheirAmericanBoard ofRadiology(ABR)diploma.Inaddition,thepipelineofradiationoncologistsisstrongwith773currently inresidencyprograms.Ofnote,thisisthesameconclusionthatwasreachedintheStatementbythe AmericanSocietyforRadiationOncology(ASTRO)totheAdvisoryCommitteeontheMedicalUseof Isotopes(ACMUI)on3/1/2018.

DouglasBollock July10,2018 Page2of5

Giventhemanyauthorizeduserscurrentlyavailabletoperformthesetherapies,itisnotsurprisingthat delayinavailabilityofthesetherapiestopatientsisrare.Thiscanbeseenacrossmanytypesof radioisotopetherapiessuchasI131,Ra223,I131ibritumomab,andStrontium89.Itispossiblethat thereisapatientaccessissuetocertainradioisotopetherapies,whichcouldbeasaresultofphysician preferencesormultipleothercauses,butashortageofauthorizedusersdoesnotappeartobeoneof them.AnexampleofthisisthecurrentavailabilityofLu177Dotatate.Longwaitlistsatmost institutionsareduetotherampingupofthistherapyathospitalsaroundthecountry,primarilydueto thecomplexityofprovidingthetherapy,availabilityofinfusionspaces,andnursingsupport,butnotdue toalackofauthorizedusersavailabletoadministerthetherapy.

Assuch,theavailabilityofauthorizedtreatingphysiciansisnotavalidreasontoconsidershorteningthe trainingandexperiencerequirementsforunsealedradioisotopetherapyunder10CFR35.390(b).And, indeed,thecomplexityoftheLu177Dotatatetherapyfurtherhighlightstheneedforrigoroustraining.

Detailedintheaddendumtothisletterisadescriptionofthebasicscienceandclinicaltraining requirementsthatarenecessaryforthepropertrainingofanauthorizeduser.Italsofullydescribesthe initialcertificationofcompetencyaswellasmaintenanceofcertification.Wewouldliketostressthat thesetrainingrequirements/hoursalonearenotsufficient.Forexample,thethreemandated experiencesforagiventherapyarenotsufficientbythemselves,butrathershouldbetheculminationof manymoresuchexperiencesinresidencyandinpracticeoverseveralyears.

Basedontheabovepoints,weopposeloweringthetrainingrequirementsascurrentlystatedin10CFR 35.390(b).WethanktheACMUIfortheopportunitytoprovideinputandlookforwardtofuture discussions.

Sincerely,

BennettGreenspan,MD SNMMIImmediatePastPresident

AlanKlitzke,MD,FACNM ACNMPresident

LauraI.Thevenot CEO,ASTRO

Cc:

ChristopherPalestro,MD,Chair,ACMUI

DarleneMetter,MD,ViceChair,ACMUI

DouglasBollock July10,2018 Page3of5

AddendumtoSNMMIstatementontrainingandexperienceforauthorizedusers:Guidanceforthe NRCsACMUI.

Thefollowingarethebasicscienceandclinicaltrainingandexperiencewefeelarenecessarytohaveas partofthetotaltrainingdesignatedin10CFR35.390(b).Belowthataretheinitialcompetencyand maintenanceofcompetencymethodswefeelarevalid.

BasicScience Basicradionuclidehandlingtechniquesapplicabletothemedicaluseofunsealedbyproductmaterial andradionuclidesrequiringawrittendirective.Orderingandreceivingradiopharmaceuticals.

Radiationphysics:structureofmatter,modesofradioactivedecay,particleandphotonemissions, halflivesandenergies.Calculationsofradioactivedecay.Interactionsofradiationwithmatter, principlesofradiationdetection,radiationunits.

Mathematicspertainingtotheuseandmeasurementofradioactivity,includingdecaycalculations andcalculationsoforganandwholebodydose.Statisticsandmedicaldecisionmaking.

Biochemistry,molecularbiologyandpharmacology.

Chemistryofradioactivematerialformedicaluse,including:reactor,cyclotronandgenerator productionofradionuclides,radiochemistry,formulationofradiopharmaceuticals.

Radiationbiology:biologicaleffectsofionizingradiation.RBE.Radiationexposure.Radiation biochemistry.RadiationsyndromesClassificationofradiationdamage.Factorsaffectingradiation injury.Lateeffects.Lowdoseandlowdoserateeffects.Comparisonofrisk.

Instrumentation:Principlesofinstrumentationusedindetection,measurement,andimagingof radioactivitywithspecialemphasisongammacameras,includingsinglephotonemissioncomputed tomography(SPECT),SPECT/computedtomography(CT),positronemissiontomography(PET),and PET/CTsystems,andassociatedelectronicinstrumentationandcomputersemployedinimage productionanddisplay.Dosecalibratorsandsurveyinstruments,includingpersonnelmonitoring equipment.Dosageanddosemeasurements.Qualitycontrolofinstrumentation-QI,QA,QC, acceptancetesting.Artifacts.

Radionuclideproductionandqualitycontrol.RadiopharmaceuticalQC.Radiopharmacology.

Radiopharmacy.Surveysandmonitoringtechniques.

Radiopharmaceuticalsinvolvedinradionuclidetherapyandrelatedimaging-biodistribution, mechanismsoflocalization,potentialtoxicity.I131sodium,Ra223dichloride,Sr89chloride,Sm 153EDTMP,Y90microspheres,labeledantibodies,Lu177Dotatate,Lu177PSMA,otheralphaand betaemittingagents.

Radiationprotection,includingunits,meansofreducingradiationexposure,Occupationalandpublic radiationdoselimits,shieldingandpersonnelprotectiveequipment(e.g.,eyeprotection,syringe shields).Managementofcontamination,includingspills.Evaluationofpatientsexposedtopotentially dangerouslevelsofradiation,assistinginthemedicalmanagementofpersonsexposedtoionizing radiation,managementanddisposalofradioactivesubstances,radiationaccidentmanagement,and managementofradiationsafetyprogramsinaccordancewithfederalandstateregulations.

Demonstratecompliancewithradiationsafetyrulesandregulations,includingNuclearRegulatory Commission(NRC)oragreementstaterules,localregulations,andtheALARA(aslowasreasonably

DouglasBollock July10,2018 Page4of5

achievable)principleforradiationprotection.NRC-10CFR19,20,35,especially10CFR35.390.

Requirementsfortrainingandrecordkeeping.Nationalandinternationalagencies.Restrictedand nonrestrictedareas.Radionuclidetherapywrittendirective.Patientreleasecriteria.

Medicalevents-determinationofoccurrence,evaluationofcause(s)andconsequences.Prevention.

Internalradiationdosimetry,MIRDcalculations.Dosecalculations-calculationsofabsorbeddoses, therapeutictargets;tumordosesrequiredforeffectivetreatment.

Clinicalrequirementsforradionuclidetherapy Qualificationsofphysicians:competencein:patientevaluationtoinclude:pertinentpatient informationrelevanttotherequestedprocedureusingclinicalrequestform,patientinterview;chart andcomputerdatabasereview;Reviewofrelevantimagingstudies.Focusedphysicalexamination asindicated;andcommunicationwiththereferringphysicianifnecessary.

Patientcareandproceduralskills.Historyandphysicalexam.

CertificationinNM,NR,RO,BLS.ACLSdesirable.

Patientselection-Verificationofpatientidentity;Explanationofproceduretothepatient.Informed consent.Determinationanddocumentationofpregnancystates.Discussionofrisksandbenefitsof theprocedure,includingpatienteducationandcounselingofexpectedbenefits,possibleadverse sideeffects,radiationsafety.Determinationofclinicalindication.Evaluationoffindings-clinical (e.g.operative),pathology,labvalues(ex.FT4,TSH,thyroglobulin,WBC,platelets),relevantimaging studiesoncologicstudies,includingasappropriatestudiesofsentinelnodelocalization, fluorodeoxyglucose(FDG)imaging,MetaIodoBenzylGuanidine(MIBG),somatostatinreceptor imaging,andotheragentsastheybecomeavailable.PET,PET/CT,andotherhybridmolecular imagingstudiesforbothoncologicandnononcologicindications.

Patientpreparation:determinedesiredadministeredactivity,routeofadministration.Determine requireddosimetry.Understandrisksspecifictoeachtherapeuticradiopharmaceutical,including typesofemissions.

Patientmanagement(alongwithotherphysiciansasneeded)ofposttherapycomplications.

Supervisionofadministrationoftherapeuticradiopharmaceutical(s)topatient.Radiationprotection specifictoeachtherapeuticradiopharmaceutical.Dosimetry.

Patientrelease-timingandconditions,provisionofradiationprecautions,verbalandwritten.

Prepareacompletebutconcisenuclearmedicineprocedurereport.

Posttherapyfollowup.Followupscintigraphyasnecessary.

Assessmentoftreatmentresponse.

Recommend,plan,conduct,supervise,interpret,andreportdiagnosticandtherapeuticnuclear medicineproceduresappropriatefortheclinicalproblemorcondition.

Therapeuticadministrationofradioiodineforbothmalignantandbenignthyroiddisease.When appropriate,thyroidstudiesmustincludemeasurementofiodineuptakeanddosimetrycalculations forradioiodinetherapy.

Therapeuticadministrationofotherunsealedradiopharmaceuticalsformalignantandbenign diseases.

Evaluateradionuclideuptake,biodistribution,metabolism,retentionandclearancewith quantitativeimagingtodeterminetumordosimetryandthereforetreatmentplanning.

DouglasBollock July10,2018 Page5of5

Understandfundamentalsofimagingmoleculartargets,processesandevents,andexistingand emergingmolecularimagingtechniques,particularlyastheyrelatetocurrentclinicalpracticeof radiopharmaceuticaltherapy.

Radiopharmaceuticaland/orClinicalIndications(includingbutnotlimitedto):

o Hyperthyroidism-I131sodiumiodide o Differentiatedthyroidcancer-I131sodiumiodide o Bonepainpalliation-Sr89chloride,Sm153EDTMP o Radioembolizationforhepatocellularcancerorlivermetastases-Y90Theraspheresor SIRSpheres o Neuroendocrinetumors-I131MIBG,Lu177DotatateandotherpotentialPRRTtherapies o Radiolabeledantibodies o BonemetastasesRa223dichloride o Prostatecancer-Lu177PSMA,(Ac225PSMA-currentlyunderactiveinvestigationinEurope) o Othertherapeuticradiopharmaceuticalsastheybecomeavailableforclinicalpractice.

o Otherpotentialtherapeuticradionuclidescurrentlyunderinvestigation:

Betaemitters:Cu67,Re186,Re188,Ho166 Alphaemitters:Bi212,Bi213,At211,Tb149,Ac225 Pleasenotethatmuchofthetrainingdelineatedabovewouldbeobtainedwithinthecontextofnuclear medicinetrainingprogramsinNuclearMedicineorNuclearRadiology,ortrainingprogramsinRadiation Oncology.ForthosephysicianswhohavenothadformaltraininginNuclearMedicine/NuclearRadiology orRadiationOncologyandwishtoprovideradionuclidetherapy,theaboveinformationisconsidered essentialforcompetentpracticeofradionuclidetherapy.

Recommendationsforinitialandmaintenanceofcompetencyunder35.390(b):

1) Certificationprocessforphysiciansperformingradiopharmaceuticaltherapyasisalready recognizedunder10CFR35.390(a)-ABNMorABRNRorROcertificationissufficient.

2) ParticipationinMaintenanceofCertificationforthosewhobecameanauthorizeduserthrough thealternatepathway,similarto35.390(a).

3) AccreditationoftheNuclearMedicinelaboratory.Thisshouldincludeaproficiencytesting programthatwillassessperformanceofthetechnologistsandphysicians.

Futurepossibleevaluationofcompetencyunder35.390(b):

CertificationofphysicianswhohavecompletedaFellowshipinradiopharmaceuticaltherapyand havepassedacertificationexambyanaccreditedmedicalspecialtyboard.

Dr. Christopher Palestro, Chairman Advisory Committee on the Medical Uses of Isotopes The U.S. Nuclear Regulatory Commission RE: Written Statement to the Advisory Committee on the Medical Uses of Isotopes, the Nuclear Regulatory Commission; Training & Experience Requirements

Dear Dr. Palestro and the Advisory Committee,

In response to the topics discussed during the Advisory Committee on the Medical Uses of Isotopes (ACMUI) meeting regarding Training & Experience (T&E) hours for AUs under 10 CFR 35.300 on March 1, 2018, Bayer HealthCare Pharmaceuticals Inc. would like to share both the real world operational safety history of Xofigo and the knowledge gained after 5 years of commercial availability to help inform the Nuclear Regulatory Commission (NRC).

Bayer is requesting the NRC to consider a proposal to enable a class of physicians, notably medical oncologists and urologists, to attain Authorized User (AU) status under the limited authorization of parenteral administration of 223Ra dichloride (Xofigo) with 80 hours9.259259e-4 days <br />0.0222 hours <br />1.322751e-4 weeks <br />3.044e-5 months <br /> of classroom and laboratory training, as well as appropriate work experience (under the supervision of an AU for Xofigo or a Xofigo manufacturer) and written attestation. Xofigo is an FDA-approved and commercially available therapeutic agent in the United States.

As the NRC is aware, our distribution model limits unintended exposure and reduces the risk of misadministration since it limits the handling requirements at end user facilities to an absolute minimum.

With this demonstrably safe model of distribution along with the previously discussed reality of decreasing numbers of AUs limiting patient access to effective Xofigo treatments, Bayer is interested in identifying a path forward for other physicians to attain AU status for limited authorization to administer Xofigo to patients under their care.

Xofigo Xofigo (223RaCl2) is an alpha emitting radiopharmaceutical which is concentrated in areas of osteoblastic activity. Xofigo is currently FDA-approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases and no known visceral metastatic disease. This approval was based on showing a 2.8-month survival benefit (3.6-month survival benefit at the updated analysis) over placebo during the pivotal phase III trial, ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer).

Since the launch of Xofigo in 2013 over 90,000 doses have been delivered and administered to patients at more than 1,000 sites located across the United States (Bayer internal database).

During this time there have been very few cases of medication errors reported with the administration of Xofigo Patient Ready Doses in the US.

In our Phase III ALSYMPCA (ALpharadin in SYMptomatic Prostate CAncer) trial, there was a higher incidence of Grade 3/4 thrombocytopenia and neutropenia in the radium arm compared to placebo. Overall, there was a higher incidence of Grade 3 and 4 adverse events and more patients discontinuing treatment on the placebo arm than the active Ra-223 arm.

11 July 2018 Bayer HealthCare Pharmaceuticals Inc.

Regulatory Affairs 100 Bayer Blvd PO Box 915 Whippany, NJ 07981-0915 Phone: 862-404-4057 Fax: 862-404-3175 Email:

yuan.xue@bayer.com

Treatment-emergent AE Radium (N=509)

Placebo (N=253)

CTC Grade 3 or 4*, n (%)

339 (56) 188 (62)

Serious adverse events, n (%)

281 (47) 181 (60)

Leading to discontinuation of study treatment, n (%)

99 (16) 62 (21)

• CTC toxicity grade: 1 = mild; 2 = moderate; 3 = severe, 4 = life-threatening; and 5 = death.

Per ALSYMPCA: The number of patients who had adverse events after they received the study drug was consistently lower in the radium-223 group than in the placebo group for all adverse events (558 of 600 patients [93%] vs. 290 of 301 patients [96%]), grade 3 or 4 adverse events (339 patients [56%] vs. 188 patients [62%]), serious adverse events (281 patients [47%] vs. 181 patients [60%]), and study drug discontinuation because of adverse events (99 patients [16%] vs. 62 patients [21%]).

US Distribution/Administration Model of Xofigo During the development of our distribution model for Xofigo in the United States, an unprecedented level of detail and attention was focused on ensuring that whenever possible, potential routes of exposure and contamination to end users were removed. This resulted in an operational model that provides patient-specific unit dosages in 10 mL syringes which carry both NIST traceability and a high degree of certainty that there is no external contamination.

Before the syringe containing the appropriate unit dosage of Xofigo arrives at the customer, there is an extensive amount of training and education provided by Bayer to all end users to ensure they handle and administer the unit dosage in a safe manner. Bayer has an entire team comprised of ten health physics/nuclear medicine trained individuals, called radiotherapy specialists, to assist in clinical site setup and maintenance activities as needed.

Xofigo injection does not require long infusions, pumps, or pre-meds; no significant injection site reactions have been observed with this radiopharmaceutical in the post-approval setting.

An IV line is first established with saline to ensure patency, then the Xofigo-containing unit dosage syringe is connected via a three way stopcock (or similar) followed by a slow bolus injection over one minute. After another saline flush, all potentially contaminated materials are segregated and bagged for decay-in-storage. Due to the decay characteristics of the alpha-emitting radiopharmaceutical, external exposure is not an operational concern and internal contamination is effectively managed by using standard universal precautions. The patient is also immediately releaseable without instructions per 10 CFR 35.75(b). The dose associated with a Xofigo patient (1.6 mrem per NUREG-1556) to members of the public is less than 2%

of the NRC limit for which instructions are required; for scale this is roughly the equivalent to the radiation dose experienced on a two hour plane flight.r. This treatment process is then repeated up to 5 more times separated in time by 4 weeks (8 weeks maximum).

NRC AU Licensing of Xofigo In the fall of 2012, Bayer Healthcare along with the product inventor Algeta were asked to provide some background to the NRC on the health physics considerations of Xofigo usage, a first in class drug, to help inform the licensing decision. Subsequently in January 2013, the NRC announced that Xofigo would be licensed under 10 CFR 35.300, with T&E requirements pursuant to either 10 CFR 35.390 or 35.396, allowing nuclear medicine physicians/radiologists and radiation oncologists to be AUs for the administration of Xofigo (an alternate pathway involving the completion of 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> of T&E was available for any other physician to attain such AU status).

Issues with the current T&E requirements While this model has worked well in the past, issues have now surfaced that limit patient access, despite the fact that these patients are indicated and eligible for Xofigo treatment.

Some of the most prevalent issues are:

Diminishing numbers of AUs Geographic distribution of Authorized Users Extraordinary interest within the referring physicians community to administer Xofigo themselves allowing for simplification and optimization of patient experience.

o These physicians are also in many cases the most appropriately aligned with the clinical and safety benefits of Xofigo and the continuum of patient care.

Logistical and financial burdens for patients being forced to visit different offices at different times during the course of treatment The referring physicians, instead of the administering physicians, historically manages the treatment of adverse events related to Xofigo and other systemic therapies These considerations and hurdles do limit the access of patients to Xofigo as discussed immediately below (additional information can be provided as needed). Xofigo is a product which carries a NCCN Category I recommendation.

Below are diagrams illustrating this access limitation:

These diagrams indicate that of the 27% of patients who physicians recommend for Xofigo, only 25% are referred to a neighboring clinic for treatment. Even after a referral, 37% of patients dont end up getting Xofigo.

In addition, this patient-access limitation was also confirmed in additional market research:

Proposed path forward These issues were discussed during the March 1, 2018 ACMUI meeting. It is recognized that an environment is being created in which not all the patients prescribed Xofigo treatment during the course of their disease are actually getting it.

Of importance to the regulatory scope of the NRC are the unique radiation safety considerations that make Xofigo a safe and easy to use product based both on emission characteristics, ease of administration and minimal administered activity. A considerable investment was made to ensure the product is both received and eventually dispensed in a fashion where operational risk is mitigated by engineering controls and in those areas where this is not possible, appropriate expert training is provided by Bayer.

Therefore, Bayer respectfully requests that the NRC allows for the licensers of physicians vis a vis T&E under the current distribution model after the completion of training/experience/competency requirements provided by the manufacturer OR other appropriately-trained Authorized Users.

If there are any questions regarding this statement, please contact me at yuan.xue@bayer.com or at 862-404-4057.

Respectfully yours, Yuan Xue, PhD Global Regulatory Strategist Regulatory Affairs - Oncology Bayer HealthCare Pharmaceuticals

References:

1. Xofigo US Packaging Insert.

2. Bayer internal database.

3. Bayer Responses to NRC Questions: Radium-223 dichloride; dated 8-November-2012.

The American Board of Nuclear Medicine A Member Board of the American Board of Medical Specialties 4555 Forest Park Boulevard, Suite 119 St. Louis, Missouri 63108-2173 Telephone: (314) 367-2225 E-mail: abnm@abnm.org Website:

www.abnm.org Chair Daniel A. Pryma, M.D.

Philadelphia, Pennsylvania Vice-Chair Joanna R. Fair, M.D., Ph.D.

Albuquerque, New Mexico Secretary Treasurer Heather A. Jacene, M.D.

Boston, Massachusetts Past-Chair Erin E. Grady, M.D.

Atlanta, Georgia Directors Esma A. Akin, M.D.

Washington, District of Columbia Gholam Reza Berenji, M.D., MS Los Angeles, California Wengen Chen, M.D., Ph.D., MPH Baltimore, Maryland Ghassan El-Haddad, M.D.

Tampa, Florida Munir V. Ghesani, M.D.

New York, New York Andrei H. Iagaru, M.D.

Stanford, California Ruth Lim, M.D.

Boston, Massachusetts Jonathan E. McConathy, M.D, Ph.D.

Birmingham, Alabama Executive Director George M. Segall, M.D.

Palo Alto, California Associate Executive Director Leonie Gordon, M.D.

Charleston, South Carolina Administrator Maria J. Watts, MBA St. Louis, Missouri July 31, 2018 Christopher Palestro, M.D.

Chair, Advisory Committee on the Medical Uses of Isotopes U.S. Nuclear Regulatory Commission Washington, DC 20555-0001

Dear Dr. Palestro:

The ABNM has reviewed the February 19, 2018 draft report of the ACMUI Subcommittee on Training and Experience Requirements for All Modalities regarding the current NRC requirements for 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> of supervised training and experience for Authorized Users (AUs) of radioactive materials under 10 CFR 35.390 - Training for use of unsealed byproduct material for which a written directive is required. The Subcommittee is considering whether the 700 hour0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> training requirement decreases patient access to alpha and beta emitting therapeutic radiopharmaceuticals, and whether it should recommend changes for the total number of hours of training & experience that is required.

The Subcommittee draft interim report states there are two reasons for reasonable concern for a near-future decline in patient access to care: (1) U.S. Food and Drug Administrations approval of 177Lu dotatate for treatment of certain neuroendocrine tumors, and (2) the decrease in the number of first-time candidates sitting for the Certification Examination of the American Board of Nuclear Medicine.

The ABNM welcomes the FDA-approval mentioned above and supports efforts to bring more targeted radionuclide therapies to patients in the U.S.; however, the ABNM strongly believes that the current requirement for 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> of supervised training and experience should not be changed and that reducing the minimum requirement for 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> of supervised training and experience for unsealed radioisotope therapy raises concern for patient safety. The decrease in the number of nuclear medicine or nuclear radiology qualified AUs is likely overestimated in the Subcommittee draft interim report. The need for fact-driven evaluation before any action was also endorsed by the American College of Radiology (ACR) in comments to the NRC ACMUI sent on July 16. The ABNM fully supports the ACR statement.

The number of initial ABNM certificates issued each year has been relatively constant from 1977 - 2015. The average number of certificates issued each year was 72 during this time (range 50 - 107). The ABNM issued 43 initial certificates in 2016, and 49 certificates in 2017. No data is available for 2018 since the certification examination will not be given until October.

Page Page 2 of 3 ABNM Letter to ACMUI on Training and Experience 4555 Forest Park Boulevard, Suite 119 St. Louis, Missouri 63108-2173 Telephone: (314) 367-2225 E-mail: abnm@abnm.org Website:

www.abnm.org The ABNM has issued a total of 5,744 certificates since the board was incorporated in 1971.

There are at least 3,591 active diplomates (not deceased or retired) at the present time.

The Subcommittee draft interim report noted a decrease in the number of ACGME accredited Nuclear Medicine training programs and residents from 57 programs with 161 residents in academic year 2007 - 2008, to 41 programs with 75 residents in 2017 - 2018.

The decrease in the number of programs and trainees is partly due to an increase in the number of Nuclear Medicine physicians who are also certified in Diagnostic Radiology by the American Board of Radiology (ABR). Certification by the ABR decreases the duration of Nuclear Medicine training required for ABNM certification from 36 months to 16 months, creating the appearance of decreasing numbers of residents, when it is the duration of training that is decreasing. Contributing to this trend is the increasing availability of dual training pathways where residents training in Nuclear Medicine are counted as Diagnostic Radiology residents rather than Nuclear Medicine residents, due to the requirements of the ACGME and the ABR.

At a recent professional meeting, the ABNM learned that there are at least 35 additional radiology residents engaged in a new program through the ABR aimed at additional qualification in nuclear radiology during the usual length of their diagnostic radiology residency.

The ABNM believes that dual training will result in better-trained physicians to meet the needs of patients in the era of molecular imaging and therapy. The ABNM sees no evidence that workforce issues have decreased patient access to care, and concern for potential future issues has not considered recent positive changes in Nuclear Medicine training. The popularity of the dual training pathways in Nuclear Medicine and Diagnostic Radiology is one of the reasons for the decline in the number of ACGME accredited Nuclear Medicine programs; however total number of residents is not reflected in a similar decline in number of ABNM certificates.

The ABNM urges the subcommittee to re-evaluate the initial estimates of AUs available and those in training to provide the needed services. We also request a re-review of the number of radiation oncology physicians in training as numbers quoted in the draft interim report were erroneously low.

In addition, targeted radionuclide therapies frequently require management by experts in multiple disciplines (surgery, radiation oncology, medical oncology, radiology, nuclear medicine) at centers of excellence; no shortage of AUs has been reported at such institutions.

Finally, if the current number of AUs proves to be insufficient to make radionuclides widely available, we believe pursuing approaches to increase the number of properly trained nuclear medicine physicians, nuclear radiologists and radiation oncologists will be better for patient care than lowering the standards for administering radionuclide therapies.

Although the NRC does not oversee the insurance industry, we feel that a larger threat to patient access as compared to the number of AUs in the United States is insurance coverage.

Reducing the minimum requirement for 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> of supervised training and experience for unsealed radioisotope therapy further jeopardizes patient safety because there is no standardized

Page Page 3 of 3 ABNM Letter to ACMUI on Training and Experience 4555 Forest Park Boulevard, Suite 119 St. Louis, Missouri 63108-2173 Telephone: (314) 367-2225 E-mail: abnm@abnm.org Website:

www.abnm.org assessment of the knowledge, skill and judgment of these physicians who are not certified by the ABNM, or certified by the ABR in the subspecialty of Nuclear Radiology.

In summary, the ABNM strongly believes that the current requirement for 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> of supervised training and experience should not be changed and asks the NRC correct the errors in the number of trainees, which we would expect could reduce or end the concern on the number of AUs available to provide these services.

Sincerely, George M. Segall, M.D.

Daniel A. Pryma, MD Executive Director Chair GMS/DAP/mrf