ML25104A265
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| Issue date: | 04/14/2025 |
| From: | NRC/OCM |
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Text
1 UNITED STATES NUCLEAR REGULATORY COMMISSION
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MEETING WITH THE ADVISORY COMMITTEE ON THE MEDICAL USES OF ISOTOPES (ACMUI)
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- TUESDAY, APRIL 8, 2025
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The Commission met in the Commissioners' Hearing Room, at 10:00 a.m. EDT, David A. Wright, Chairman, presiding.
COMMISSION MEMBERS:
DAVID A. WRIGHT, Chairman ANNIE CAPUTO, Commissioner CHRISTOPHER T. HANSON, Commissioner BRADLEY R. CROWELL, Commissioner MATTHEW J. MARZANO, Commissioner ALSO PRESENT:
CARRIE M. SAFFORD, Secretary of the Commission BROOKE P. CLARK, General Counsel
2 ACMUI MEMBERS:
HOSSEIN JADVAR, Chair RICHARD GREEN MICHAEL FOLKERT RICHARD HARVEY ZOUBIR OUHIB JOHN ANGLE, Consultant
3 1
P-R-O-C-E-E-D-I-N-G-S 2
9:57 a.m.
3 CHAIRMAN WRIGHT: Let's do it. All right. Good morning 4
again everyone. I call this meeting to order.
5 In today's public meeting of the Nuclear Regulatory 6
Commission, we will have an opportunity to hear from the Advisory 7
Committee on the Medical Uses of Isotopes on the medical related topics of 8
regulatory interest.
9 We will first have members of the committee provide their 10 perspectives and views on the medical use of radioactive material, and as is 11 our custom, we'll hold questions from the Commission to the end of the 12 presentations.
13 Before we start though, let me ask my colleagues if they 14 have any comments they'd like to make before we start. Anyone?
15 (No response.)
16 CHAIRMAN WRIGHT: Okay. With that, we'll begin then.
17 This morning we are joined by Dr. Hossein Jadvar, who serves as the Chair 18 of ACMUI and nuclear medicine physician of the committee.
19 Dr. Jadvar, the floor is yours.
20 DR.
JADVAR:
Thank
- you, Chairman
- Wright, 21 Commissioners Caputo, Crowell, Hanson, and Marzano. Good morning, 22 and thank you for taking time to meet with us, the ACMUI panel.
23 Before I start my report, I just want to express my gratitude 24 in working with such a distinguished panel and also extend my sincere 25
4 thanks to the NRC staff for their expertise and support.
1 With that, I start my presentation. Can I have the next 2
slide?
3 So, I'm going to give an overview of the ACMUI activities 4
over the past year, and then Mr. Richard Green, who is the nuclear 5
pharmacist and also the ACMUI Vice Chair, will give a presentation on the 6
growth in radiopharmaceutical therapy. Next slide, please.
7 Then Dr. Michael Folkert, who is the radiation oncologist 8
on the panel, will give the ACMUI review of training and experience for 9
emerging medical technologies. And then, this is followed by a statement 10 from the ACMUI's patients' right advocate, which I will read. Next slide, 11 please.
12 These are the overview of the ACMUI. I will go over the 13 ACMUI role, the membership, the topics that we covered over 24/25, and the 14 current subcommittees and what we are going to do in the future. Next slide, 15 please.
16 ACMUI advises the U.S. NRC staff on policy and technical 17 issues that arise in the regulation of the medical use of radioactive material 18 in diagnosis and therapy.
19 We also comment on changes to NRC regulations and 20 guidance, evaluate certain non-routine uses of radioactive material, provide 21 technical assistance in licensing, inspection, and enforcement cases, and 22 we'll bring key issues to attention of the Commission for appropriate action.
23 Next slide, please.
24 We have 13 members on the ACMUI panel. The nuclear 25
5 medicine physician and Chair is myself, the nuclear pharmacist and Vice 1
Chair is Mr. Richard Green, the nuclear cardiologist is Dr. Andrew Einstein.
2 The brachytherapy radiation oncologist is Dr. Michael 3
Folkert, the Gamma stereotactic radiosurgery radiation oncologist is Dr.
4 Harvey Wolkov. The diagnostic radiologist, who recently joined us, is Dr.
5 Joanna Fair, the FDA representative is Dr. Michael O'Hara. Next slide, 6
please.
7 The nuclear medicine medical physicist is Ms. Melissa 8
Martin, the radiation therapy medical physicist is Mr. Zoubir Ouhib. The 9
patients' right advocate is Mr. Josh Mailman, the agreement state 10 representative is Ms. Megan Shober.
11 The healthcare administrator is Ms. Rebecca Allen, and 12 the radiation safety officer is Dr. Richard Harvey. Next slide, please.
13 We also continue to benefit from the expertise and advice 14 of the, our consultant interventional radiologist, Dr. John Angle. Next slide, 15 please.
16 The ACMUI provided the subcommittee's evaluation of 17 recent Y-90 microsphere medical events, after NRC staff identified a sudden 18 increase in reported events involving unexpected gastrointestinal deposition.
19 The ACMUI Subcommittee on Generic Process Checklist, 20 provided a recommendation that licensees should develop a process 21 checklist that is specific to their practice and processes, to minimize medical 22 events.
23 The subcommittee provided an example of this checklist 24 and recommended that the staff determine the best method to inform 25
6 licensees of this recommendation.
1 The ACMUI Subcommittee on Interventional Radiologist, 2
recommended that the Commission consider including an interventional 3
radiologist on the ACMUI to provide insight and recommendations regarding 4
yttrium-90 microspheres given the increased use in this area.
5 Finally, the ACMUI Subcommittee on Training and 6
Experience Requirements, provided recommendations for consideration in 7
the emerging medical technologies rulemaking. Next slide, please.
8 The ACMUI reviewed and commented on the NRC staff's 9
draft regulatory basis document for financial assurance requirements for 10 disposition of Category 1 to 3 byproduct material radioactive sealed sources 11 rulemaking.
12 The ACMUI reviewed and commented on the NRC staff's 13 draft proposal rule and associated draft implementation guidance for 14 reporting nuclear medicine injection extravasations as medical events.
15 The ACMUI reviewed and commented on the interim staff 16 guidance on implementation of training and experience. Next slide, please.
17 The ACMUI subcommittee on bylaws provided 18 recommended changes to the ACMUI bylaws to update conflict of interest 19 procedures and ensure the bylaws were updated with the new FACA 20 requirements.
21 The ACMUI also reviewed three emerging medical 22 technology licensing guidance documents that the staff developed in 2024.
23 These were the Akesis Galaxy RTi Unit, which is a gamma 24 stereotactic radiosurgery unit that includes moving sources and tables; Y-90 25
7 microspheres, which is a new Y-90 microsphere device that includes 1
properties that allow them to be seen on the fluoroscopy; and, Liberty Vision 2
Y-90 episcleral brachytherapy source.
3 For all these reviews, the ACMUI agreed with the NRC 4
staff's recommendation that they should be licensed under 10 CFR 35.1000, 5
and generally agreed with the draft guidance, but provided medical insights 6
and recommendations for each draft guidance. Next slide, please.
7 An ACMUI member provided review of seven published 8
articles describing error reduction methodologies to avoid prescription error.
9 Finally, the ACMUI reviewed historic medical events where 10 it noted that medical events are relatively low, but noted an increase in 11 medical events related to 10 CFR 35.300 and yttrium-90 microspheres 12 licensed under 10 CFR 35.1000.
13 This evaluation was an initiation point for the generic 14 process checklist report that I described earlier. Next slide, please.
15 In addition to the ACMUI presentations, NRC staff also 16 provides presentations. At every meeting, the NRC staff provides an 17 overview of updates by the medical radiation safety team, where they 18 provide ongoing rulemaking and guidance development processes and 19 schedules, overview of activities at the NRC that may impact the medical 20 industry, such as teams initiatives to look for efficiencies in licensing and 21 oversight, and updates to ACMUI policies and procedures.
22 The staff also provides a presentation giving an overview 23 of all the past years' medical events with a special presentation this year on 24 yttrium-90 microsphere medical events, following their evaluation of these 25
8 events.
1 The staff provided a status update on patient release 2
guidance. They informed the ACMUI that significant changes are being 3
made to the guidance based on feedback from the industry.
4 These changes include the addition of many more 5
examples, which will help the industry quickly release the majority of 6
patients. However, the staff is trying to maintain flexibility to provide 7
licensees guidance for unique patient situations.
8 Michael King of the NRC staff, provided an overview of the 9
ADVANCE Act in the fall of last year. The medical team also continues to 10 provide the ACMUI any updates related to the ongoing rulemaking and 11 guidance development efforts, as well as discuss medical issues of interest 12 with the ACMUI. Next slide, please.
13 The NRC provided an overview of their plans to develop 14 guidance to address patient waste concerns following release. The NRC 15 also leads a yearly discussion to discuss the ACMUI reporting structure.
16 Finally, the staff provides required training to the ACMUI.
17 This year, the staff provided an expanded ethics training to cover more 18 specific topics for apparent conflicts of interest. Next slide, please.
19 The ACMUI has formed a subcommittee to evaluate and 20 provide recommendations, if any, to ensure NRC licensing and oversight of 21 medical use of byproduct materials aligned with the NRC's mission 22 statement that was established on January 24, 2025. This subcommittee 23 plans to present findings later this year.
24 The ACMUI also has some standing subcommittees to 25
9 evaluate and provide recommendations on the staff products in their arenas, 1
in their areas.
2 This includes the NRC Mission and Medical Use Licensing 3
and Oversight, Patient Release Subcommittee, Training and Experience for 4
All Modalities Subcommittee, Medical Event Reporting and Extravasation 5
Subcommittee, Yttrium-90 GI Deposition Medical Events, Emerging Medical 6
-- next slide please, Emerging Medical Technologies and Rubidium-82 7
Generator Subcommittee, and the membership of an interventional 8
radiologist. Next slide, please.
9 The ACMUI will continue to provide advice and technical 10 assistance, comment on NRC regulations and guidance, evaluate uses of 11 radioactive material, and bring key issues to the attention of the 12 Commission.
13 And, with that next slide, these are my acronyms. And, 14 that's the conclusion of my presentation. Thank you so much.
15 CHAIRMAN WRIGHT: Thank you for your presentation, 16 Dr. Jadvar.
17 Next, we'll hear from Mr. Richard Green, who is the Vice 18 Chair and nuclear pharmacist on the committee.
19 MR. GREEN: All right. Commissioners Crowell, Caputo, 20 Hanson, and Marzano, thank you. Again, good morning.
21 Thank you for the opportunity to speak with you today. As 22 a nuclear pharmacist representative on the ACMUI, my presentation today 23 was prepared by myself, given my area of expertise, to share on the 24 projected growth of therapeutic radiopharmaceuticals as this relates to my 25
10 work reviewed by the ACMU -- as this relates to work reviewed by the 1
2 But, this presentation is not an official production or 3
presentation endorsed by the ACMUI. Next slide, please.
4 Today we'll start with a quick look backwards at the history 5
of FDA-approved therapeutic radiopharmaceuticals. Essentially, what 6
therapeutic radiopharmaceuticals are available today and when where they 7
added to the Physician's Armamentarium.
8
- Next, we'll look at the projected growth of 9
radiopharmaceutical therapies, what new radioisotopes might be utilized.
10 We'll then look at clinical trials currently underway to get a glimpse of what 11 might receive FDA approval.
12 We'll conclude with some possible new challenges that 13 may be faced by the NRC and licensees. Next slide, please.
14 For this slide, I've grouped the FDA-approved history of 15 therapeutic radiopharmaceuticals into five-year brackets.
16 In 1951, the FDA approved the first therapeutic 17 radiopharmaceutical, iodine-131 sodium iodide, for the treatment of 18 hyperthyroidism and thyroid carcinoma.
19 This was a prototype theranostic, a term we hear all about 20 today, with smaller doses administered for diagnosis and then larger doses 21 administered for therapy, or both diagnostic and therapeutic nuclides 22 attached to the same chemical entity used for diagnosis and therapy 23 respectively.
24 It was six years later in 1957, that P-32 sodium phosphate, 25
11 was FDA-approved for the treatment of polycythemia vera. And then, 17 1
years after that, that the other variant of P-32, chromic phosphate, was 2
FDA-approved for intracavitary installation for the treatment of pleural 3
effusions.
4 It was then 19 years later when strontium-89 chloride was 5
FDA-approved for bone pain palliation. Then, the pace seems to begin to 6
pick up a little quicker, with Quadramet in 1997, also for bone pain palliation.
7 In 2002, Zevalin, and then 2003, Bexxar were approved by 8
the FDA, both indicated for treating non-Hodgkin's lymphoma.
9 A decade long gap exists until 2013, when Xofigo was 10 FDA-approved for the treatment of patients with castration resistant prostate 11 cancer, who had symptomatic bone metastases and no known visceral 12 metastatic disease.
13 2018, Lutathera was approved by the FDA to treat, this is a 14 tongue twister, gastroenteropancreatic neuroendocrine tumors that are 15 positive for the hormone receptor somatostatin. That same year Azedra was 16 FDA-approved to treat patients with iobenguane-positive, unresectable, 17 locally-advanced, or metastatic pheochromocytomas or paragangliomas.
18 The newest rate pharmaceutical therapy was approved in 19 2022, is Pluvicto, indicated for the treatment of adult patients with 20 prostate-specific membrane antigen, PMSA-positive metastatic castration 21 resistant prostate cancer that had been treated with antigen receptor 22 pathway inhibition, and are considered appropriate to delay chemotherapy.
23 It was just last night that I saw my first ever in my life, 24 direct to the consumer, advertising on TV for a radiopharmaceutical, for 25
12 Pluvicto.
1 The FDA modified its indication just on March 28, to allow 2
it to be used earlier in the patient's treatment pathway, effectively opening it 3
up to use in many times more patients than it was previously.
4 In the 74 years since the first therapeutic 5
radiopharmaceutical was FDA-approved, there have been a total of 11 drugs 6
approved.
7 But, not all of these FDA-approved radiopharmaceuticals 8
therapies have remained on the market. None were withdrawn because of 9
lack of efficacy or because of patient harm.
10 Those that are gone have died an economic death.
11 They've fallen out of favor or been replaced by newer, better agents. Next 12 slide, please.
13 Okay. In 2003, the first of these therapeutic agents was 14 withdrawn from the market, Bexxar, the same year it was approved.
15 Followed by the withdrawal of both P-32 agents in 2009.
16 Zevalin was withdrawn in 2020, followed shortly thereafter 17 by Quadramet in 2021, and Azedra in 2024. So, although we have had 11 18 FDA-approved therapies approved, only five of these remain on the market 19 currently.
20 But, as we'll soon shortly discuss, this very slow rate of 21 therapeutic rate of pharmaceuticals development and approval will be 22 accelerating markedly. Next slide, please.
23 One way we could evaluate the increasing interest in 24 theranostics, is to look at the change over time of published studies via 25
13 PubMed.
1 Here you can see the dramatic increase in published 2
studies with a search term theranostic between 2014 and 2024. Quite an 3
increase in growth over the last 10 years. Next slide, please.
4 Another way to assess the projected growth of 5
theranostics, is to look at a published projection of the growth of theranostics 6
from an economic standpoint.
7 The global market for theranostics is anticipated to move 8
from 111 billion in 2024, to a projected 185 billion in 2029, just five years 9
away.
10 It is estimated that the market for U.S.
11 radiopharmaceuticals is 50 percent of the world value. This is a projected, 12 compounded annual growth rate of 10.8 percent.
13 The traditional pharmaceutical industry has discovered the 14 radiopharmaceutical market, as evidenced by all of the high-dollar 15 acquisitions in recent years.
16 It is hard to keep track of all the plant investments and 17 acquisitions that have been made public. Next slide, please.
18 The pace of approved therapeutic radiopharmaceuticals 19 will be dramatically changing soon. It is estimated there are currently 38 20 companies conducting 45 clinical trial programs.
21 You can see the companies listed on this most outer ring 22 of this chart. This graphic does a great job of graphically representing the 23 degree of commercial interest in therapeutic radiopharmaceuticals.
24 If we start in the center of the circle, there are the two most 25
14 recently approved therapeutic radiopharmaceuticals, Pluvicto and Lutathera.
1 In the dark blue band, just beyond that central circle, is the Phase III band, 2
where there are eight agents.
3 And then, moving outward, the next two light blue 4
concentric bands represent Phases II and Phase I, which have 28 agents.
5 As you can see, there are numerous agents in the outermost ring, the 6
preclinical stage.
7 All of the commercial firms are identified in the outside 8
circle. Overall, there are 275 clinical trials underway with theranostic 9
therapeutic radiopharmaceuticals.
10 This graphic goes on to identify these investigational 11 therapeutic agents as to their type, whether they're small molecule, 12 antibodies, peptides, and identifies the radionuclides involved.
13 This graphic supports the projection that there will be more 14 than a 10 percent compounded annual growth rate. There's lots of things 15 coming. Next slide, please.
16 There are several radioisotopes that will be new to nuclear 17 medicine utilized in some of these investigational new drugs, and perhaps to 18 be approved radiopharmaceuticals.
19 We'll run through these in order of their atomic number, 20 starting with scandium-47, that can be produced in reactors or cyclotrons.
21 This 3.35-day beta-emitting radioisotope, can be paired up 22 with either scandium-43 or scandium-44g, both of which are PET-emitters.
23 In addition, scandium-47 itself, has a 159-keV gamma emission that is 24 imageable via SPECT.
25
15 Copper-67 can be produced using photo nuclear reaction, 1
and is a 61.8-day, hour half-life beta-emitting radioisotope. It can be paired 2
with copper-64, a PET emitter. Copper 67 itself also has two 3
SPECT-imageable photons.
4 Terbium-161 can be produced in a reactor, and is a 6.96-5 day half-life beta-emitting radioisotope. Dosimetry analysis has revealed 6
that terbium-161 has a 1.4-fold higher energy deposition to established 7
tumors, compared to lutetium-177. There's lower energy electrons involved.
8 This ratio increases to about 4.4-fold for small cell clusters 9
and singular cells. Terbium-161 is also a SPECT-imageable emitting 10 isotope.
11 Rhenium is the last naturally occurring chemical element 12 that was discovered in 1925. Rhenium-186 is a 3.7-day half-life 13 beta-emitting isotope. Next slide, please.
14 Four more we'll cover. Lead-212 is a 10.6-hour half-life 15 radioisotope that has a decay chain that includes two beta particles and 16 culminates in a single alpha particle. Lead-203 can be used as a 17 SPECT-imaging diagnostic analog diagnostic pair.
18 Bismuth-213 can be isolated from an actinium-225 19 generator. It has a 45.6-minute half-life, and the decay chain has three beta 20 particles and one alpha particle.
21 Actinium-225, which I'm sure you've heard much about, is 22 a 10-day half-life, with a decay chain with three beta particles and five alpha 23 particles. It can be obtained either from a thorium-229 decay or from 24 accelerator production.
25
16 Cerium-134 is a PET-emitting diagnostic analog that can 1
be used as a diagnostic half of this theranostic pair.
2 The last one we'll discuss is thorium-227, an 18.7-day half-3 life, with an extensive decay chain with five beta particles and eight alpha 4
particles. Cerium-134 is also a possible PET-emitting diagnostic analog.
5 Next slide, please.
6 Here's a published graph showing the distribution of 7
therapeutic radiopharmaceutical clinical trials and the radioisotopes utilized.
8 Next slide, please.
9 From the graphic we reviewed on slide seven, it can be 10 seen that there's a great deal of interest in therapeutic radiopharmaceuticals, 11 especially theranostic agents that utilize the same molecule to localize the 12 cancer attached to either a diagnostic or a therapeutic radionuclide.
13 There are over 275 therapeutic clinical trials currently 14 underway. During 2025, this year, data will be released from 15 completed 15 clinical trials.
16 Oncology targets could include head, neck, gynecologic, 17 genital urinary, gastrointestinal, lung, and skin cancers.
18 There are all kinds of applications for therapeutic 19 radiopharmaceuticals. It could be said that we haven't even scratched the 20 surface of what radiopharmaceuticals can do.
21 Just a few weeks ago in late February, it was announced 22 that the FDA has accepted the biological license application, or BLA, of a 23 breakthrough clear cell renal carcinoma PET-imaging agent that is labeled 24 with zirconium-89.
25
17 It was granted a priority review, and provided a PDUFA 1
date in August of 2025, just a few months away, paving the way for a 2
possible U.S. commercial launch in 2025.
3 There are clinical trials currently underway for both a 4
lutetium-177 and an actinium-225 labeled therapeutic version of this kidney 5
agent.
6 So, we're going to see the diagnostic first and then one if 7
not two therapeutic versions of that agent. Next slide, please.
8 So, what challenges might licensees or the NRC encounter 9
with all this involvement in radiotheranostics and new agents coming?
10 The first, is the ability to accurately measure radionuclides 11 in our dose calibrator. This is essential for radiopharmacies and for the 12 clinic.
13 Thankfully, we have NIST. Dr. Brian Zimmerman, leader 14 of the Radioactivity Group Medical Measurement Laboratory at the National 15 Institutes of Standards and Technology, reported recently that NIST has 16 completed the development of their standard for actinium-225.
17 And, this radionuclide was added to their list of calibrations 18 available. They've already performed two calibrations for external customers 19 and provided several calibrated sources to the company that sponsored this 20 project.
21 It is imperative that the final product container vial is NIST 22 calibrated so that radiopharmacies and clinical licensees can accurately 23 measure these radioisotopes in their dose calibrators. This is true for all 24 radioisotopes that come to market.
25
18 As we mentioned, there's new ones coming. And, these 1
new ones are not clean, clear, crisp, 140-keV, like tech-99m, which is 80 2
percent of what nuclear medicine is. These have lots of betas, and alphas, 3
and small components of other emissions.
4 So, it's essential that we have support from NIST and that 5
each commercial manufacturer takes the time and effort to make sure that 6
the product vial that goes to the end user clinic or pharmacy is NIST 7
traceable and we can measure accurately.
8 The next item that, I think, might be a challenge, is that 9
older radionuclide therapies were often small volume injections, typically less 10 than 10 milliliters, and were easily accomplished in existing unit dose pigs.
11 Newer radiotherapies are higher volume infusions, 12 sometimes reaching 20 to 30 milliliters, that will require larger patient-ready 13 unit dose syringe pigs, and the corresponding DOT type-A shipping 14 containers to get them from the pharmacy to the clinic.
15 The other issue that is before the industry, is the fact that 16 the IAEA is currently revising SSR-6, which includes revisions to many of the 17 A1 and A2 values found in table two, basically, radionuclide values.
18 Most notably are the significant reductions in the A2 values 19 for medical radionuclides that emit high-energy alpha particles through 20 radioactive decay, either directly or indirectly, through their short-lived 21 progeny.
22 The significant reduction in A2 values for some 23 alpha-emitting radionuclides in the current revisions of SSR-6, will present 24 significant challenges to the development, production, and distribution of 25
19 innovative medical radionuclides and radiopharmaceuticals utilizing 1
radioisotopes such as lead-212, actinium-225, and astatine-211.
2 If these proposed changes to SSR-6 are carried out, 3
manufacturers and nuclear pharmacies will potentially need to migrate to 4
Type-B containers packaging for supply chain shipments, as well as 5
radiopharmaceutical deliveries to healthcare providers for these short-lived 6
nuclides. Next slide, please.
7 Often, there are multiple methods to produce radioisotopes 8
used in therapy. Some production methods can also produce undesirable 9
long-lived radionuclidic contaminants, such as we were encountering with 10 lutetium-177m, which is 160-day half-life impurity found in lutetium-177, 11 which is 6.6 days.
12 And, in the future, we may see actinium-227 with a 21.7-13 year half-life as a radionuclidic contaminant in actinium-225, which is 9.9 day 14 half-life.
15 The presence of these long-lived contaminants will 16 preclude decay in storage as permitted by 10 CFR 35.92, and will require the 17 services of a waste broker to assist in disposal. Let's cross our fingers that 18 we get clean isotopes. That would help.
19 Radionuclide therapy is no longer one and done. It's not a 20 single injection and you're done. It is often now a multi-course treatment 21
- regimen, sometimes involving pretreatment with renal protectants, 22 anti-emetics, et cetera, and will require multi-disciplinary coordination.
23 Yesterday, the ACMUI subcommittee on Generic 24 Checklists, recommended the creation of an information notice or other 25
20 means of communication to licensees that recommends that all licensees 1
develop tools or checklists to prevent medical events, including those 2
involving radiotherapeutics.
3 These procedures are not just analog paper checklists, but 4
should employ all the usual digital advancements that are common 5
elsewhere in the hospital, such as computerized prescription order entry, 6
electronic medical records, EMR, intravenous workflow management 7
systems, barcode medication administration.
8 We think the use of these electronic tools will help prevent 9
and reduce medical errors. And, we certainly want to do that with 10 therapeutic radiopharmaceuticals.
11 I appreciate the opportunity to speak with you this morning 12 on the exciting future of theranostic radiopharmaceuticals.
13 These next three slides, list all the acronyms used in the 14 presentation. Thank you.
15 CHAIRMAN WRIGHT: Thank you very much, Mr. Green.
16 I can't wait for the question part of this.
17 (Laughter.)
18 CHAIRMAN WRIGHT: Next, we'll hear from Dr. Michael 19 Folkert, who is the Committee's radiation oncologist. Thank you very much.
20 DR. FOLKERT: Thank you, Chairman Wright and 21 Commissioners Crowell, Caputo, Hanson, and Marzano.
22 I will be presenting on the Subcommittee on Training 23 Experience for All Modalities. Let's see. Go ahead to the next slide.
24 This is the membership of our subcommittee, myself, Dr.
25
21 Richard Harvey, Dr. Jadvar, Mr. Ouhib, Ms. Shober, and our NRC staff 1
resource for the committee has been Maryann Ayoade. So, let's move on.
2 Next slide, please.
3 So, the current charge of the subcommittee, is to review 4
and evaluate the training experience requirements for all modalities in 10 5
CFR Part 35.
6 On August 20, 2024, we received an expanded charge to 7
provide recommendations to the NRC on knowledge topics encompassing 8
the safety-related characteristics of emerging medical technologies, or 9
EMTs, required for authorized users to fulfill their radiation safety-related 10 duties and supervision roles, the methods on how these knowledge topics 11 should be acquired, the consideration for continuing education, vendor 12 training for new medical uses, and training on the NRC regulatory 13 requirements. Next slide, please.
14 Continuing innovation in the uses of radioactive byproduct 15 material, has led to new applications and indications in areas such as 16 Gamma Knife radiosurgery technology, ophthalmic treatments, diffusing 17 radioactive particle implants, and as so eloquently presented by Dr. Green, 18 an increasingly diverse array of diagnostic and therapeutic 19 radiopharmaceuticals. Next slide, please.
20 Emerging medical technologies are generally classified 21 under 35.1000, but development of new radiopharmaceuticals, 22 brachytherapy applications, and other devices utilizing radioactive byproduct 23 material normally regulated under 10 CFR 35.200, 35.300, 35.400, and 24 35.600, may incorporate novel ligand, or radioisotope combinations, or 25
22 administration methods, that may pose additional patient and radiation safety 1
risks and require additional training.
2 This is not limited just to therapeutic applications, but also 3
the many new diagnostic applications, as well as an increasing array of 4
diagnostic radioligands are integrated in the clinic. Next slide, please.
5 So, for each medical use modality, 10 CFR 35 regulations 6
prescribe the minimum hours of classroom and laboratory training, as well as 7
supervised experience.
8 Many of the core knowledge areas are included here.
9 These are represented in 35.300, 390, and 396, training areas in particular.
10 The classroom and laboratory training elements are on the 11 left and work experience on the right. We will refer back to these.
12 But, these are the core existing knowledge topics and 13 knowledge areas that are expected for authorized users. Next slide, please.
14 So, in addition to these core knowledge areas, there's 15 been an increasing complexity around aspects of patient selection, patient 16 and caregiver education, interactions of radioactive material applications with 17 other therapies and interventions, pre-and post-procedure dosimetry, patient 18 monitoring and release, and reporting of adverse reactions and medical 19 events.
20 The subcommittee also recognizes, but does not endorse, 21 that the authorized user may not be physically present in some applications.
22 For example, the administration of radiopharmaceuticals 23 by a certified nuclear medicine technologist, and may instead be monitoring 24 the dose administration virtually.
25
23 As such, it is critically important that the independent 1
educational needs of the entire healthcare team are also a consideration that 2
must be met to ensure the safe utilization of EMTs using radioactive 3
byproduct material. Next slide, please.
4 So, by way of background, for each of these medical use 5
modalities, 10 CFR regulations detail the minimum hours of classroom and 6
laboratory training, as well as supervised experience.
7 T&E requirements for EMTs are described in 10 CFR 8
35.1000 guidances. And, the current regulatory framework for AU training 9
experience was established in 2002, following a comprehensive overhaul of 10 10 CFR 35.
11 Over the past few decades, the ACMUI has revisited the 12 authorized user T&E requirements regarding board certification pathways, 13 10 CFR 35.300, radiopharmaceuticals and EMTs in various years. Next 14 slide, please.
15 And so, with the rapid increase in development of novel 16 radiopharmaceuticals that we saw in the late 2010s, stakeholders expressed 17 concerns with the perceived burden of T&E requirements for authorized 18 users.
19 The NRC staff engaged stakeholders, the ACMUI, and 20 agreement states, and explored options to reduce the regulatory burden for 21 physicians seeking to become AUs, while preserving training that was critical 22 to radiation safety.
23 And, this led the NRC staff to submit a rulemaking 24 proposal in 2020, SECY-20-0005, to modify T&E requirements in 10 CFR 25
24 35, subparts D and E, for unsealed radioactive byproduct material. Next 1
slide, please.
2 In this proposal, goals were to establish high-level radiation 3
safety training criteria in advance of the expected new EMTs and novel 4
radiopharmaceutical therapies that we are now seeing rapidly coming down 5
the pipeline, and eliminate the case by case approval of AUs in radioactive 6
byproduct materials licenses.
7 This rulemaking would have eliminated the alternate 8
pathway for unsealed byproduct material use and required AUs to be 9
certified by a recognized specialty board.
10 A medical specialty board seeking NRC recognition would 11 have needed to demonstrate that their programs met NRC training 12 requirements for T&E. In 2022, the Commission voted to maintain the status 13 quo, however.
14 But, they did recommend, as we, and this is very relevant 15 to our current charge, the evaluation of current specialty board recognition 16 areas criteria, and to evaluate knowledge topics required for AUs to fulfill 17 their radiation safety-related duties and supervision roles, the methods on 18 how knowledge topics should be acquired, and consideration for continuing 19 education, vendor training for new medical uses, and training on the NRC 20 requirement, which is the foundation of our updated charge. So, next slide, 21 please.
22 So, in 2022, the Commission approved the initiation of an 23 EMT rulemaking, SECY-21-0013, which would move many of the EMTs from 24 10 CFR 35.1000 to other sections of Part 35. This rulemaking would codify 25
25 the T&E requirements for AU physicians for these technologies.
1 In 2023, the NRC staff published a draft regulatory basis 2
for this rulemaking. And, this EMT rulemaking remains in the proposed rule 3
phase.
4 So, as a result, the NRC staff are assessing ways to make 5
the existing EMT T&E requirements more generalizable, instead of having a 6
customized set of T&E requirements for each 10 CFR 35.1000 licensing 7
guidance document.
8 And so, this subcommittee's current charge to review 9
knowledge topics for EMTs, is connected to this rulemaking in an effort to 10 identify consistent T&E elements for authorized users. So, next slide, 11 please.
12 So, moving onto the evaluation and recommendations 13 regarding this current charge. So, and, specific to knowledge, acquisition 14 and maintenance, while the subcommittee recognizes that the final review 15 and approval of AUs too, is primarily the responsibility of the NRC and 16 agreement states.
17 The subcommittee strongly feels that the acquisition of 18 general safety content and continuing educational content, should primarily 19 be the responsibility of medical boards such as the American Board of 20 Radiology, the American Board of Nuclear Medicine, the Certification Board 21 of Nuclear Cardiology, also very heavily involved; the accreditations 22 councils, such as the Accreditation Council for Graduate Medical Education 23 and the Commission on the Accreditation of Medical Physics Education 24 Programs; and professional societies that are actively engaged in the 25
26 training and certification of AUs, RSOs, associate RSOs, authorized nuclear 1
pharmacists, authorized medical physicists, and ophthalmic physicists. Next 2
slide, please.
3 So, this is not an exhaustive list, but, these professional 4
sites are actively engaged in developing this educational content that is 5
focused on safety.
6 And, this is not an exhaustive list, as I said, but, many of 7
these professional groups have been actively developing training in these 8
areas, such as the SNMMI, ASTRO, and the many other groups that are 9
listed here that are the professional societies that many of the participants on 10 the ACMUI are also involved with. Next slide, please.
11 And so, as far as engagement of these professional 12 societies, there is demonstrated interest and engagement in radiation safety 13 educational development by the professional societies.
14 For example, the SNMMI and ACNM Boards that are 15 primarily working with nuclear medicine, are circulating a joint practice 16 guideline for the use of radiopharmaceuticals.
17 ASTRO, the primary society for radiation oncologists, has 18 been developing a radiopharmaceutical safety white paper that was actually 19 released this past Friday. And, also has looked into safety training through 20 their APEx Accreditation and through the Radiation Oncology Incident 21 Learning System.
22 The American Brachytherapy Society is developing training 23 objectives for radiopharmaceutical practice.
24 And, the ACR, the American College of Radiology, has 25
27 partnered with multiple societies across all specialties to develop practice 1
parameter guidelines, for a range of diagnostic and therapeutic applications 2
involving radioisotopes.
3 And, these are regularly updated in collaboration with 4
multiple professional societies across the spectrum. Next slide, please.
5 So, while the NRC currently cannot endorse or 6
preferentially favor any specific training pathway, it is the subcommittee's 7
recommendation that the NRC evaluate whether educational materials or a 8
program meets requirements for initial certification with the technology, to 9
improve the efficiency for evaluating potential AU use.
10 This is a common thing that comes up with radiation safety 11 officers and with initial credentialing is, has the prospective AU received the 12 training that is necessary to meet all the requirements provided by the NRC.
13 And, there's no specific, basically checkoff that says 14 whether or not any of these training pathways meet those requirements.
15 And, it is likely necessary that the NRC will have to 16 develop a range of training scenarios that will depend on the time that has 17 elapsed since professional training was completed by the prospective AU, as 18 well as which training pathway the prospective AU has initially completed.
19 This is in keeping with the case scenarios request.
20 So, that was present in the recent TE report from our 21 subcommittee. And this was previously endorsed.
22 And, as per Dr. -- as per the NRC will be released this 23 week, and so, for that guidance. This also would provide an opportunity to 24 clarify scope or practice.
25
28 It is -- during the initial licensing of many authorized users, 1
there are, it has been brought to our attention that it is not clear that people 2
understand the scope that the training under 35.390 or 396 offers in terms of 3
use of radioisotopes.
4 Many people feel that it is restricted to one isotope during 5
initial training. And, this just simply does not allow us to meet the needs of 6
all of these new radioisotopes coming down the pipeline. Next slide, please.
7 The subcommittee recognizes the role for ongoing 8
continuing medical education for, in supporting quality of care and radiation 9
safety.
10 In terms of CME, the subcommittee recognizes that 11 professional societies are actively developing and providing CME for 12 practitioners administering existing and emerging technologies through 13 recorded, virtual, and in-person offerings. And, the AU will need to maintain 14 the records of their CME.
15 We recommend that professional societies develop 16 guidelines for CME minimum contact hours. And, we would also 17 recommend that the NRC explore the need to define minimum CME 18 requirements for AUs. Next slide, please.
19 Verification of ongoing training experience and continuing 20 medical education, must follow applicable state, local, and certification board 21 requirements, as well as the authority of the hospital or practice clinical 22 credentialing program.
23 Credentialing is a process where medical facilities grant 24 healthcare professionals, such as physicians, non-physician, mid-level 25
29 providers, medical physicists, medical dosimetrists, and medical 1
technologists, the ability to practice medicine and supportive services in their 2
clinical sites.
3 And, credentialing and maintenance of an associated 4
privilege is currently not regulated by the NRC. Next slide, please.
5 So, in addition to those core knowledge topics that we 6
discussed earlier that are already integrated into the existing training 7
requirements, the committee does recommend that the practical knowledge 8
base for EMTs include, this application-specific content and documentation 9
of training in these areas.
10 And, I apologize for the wall of text. Patient assessment 11 and eligibility, patient and caregiver education on the procedure and 12 radiation safety, this is particularly critical for protecting the public.
13 And so, for patients who have been administered 14 radiopharmaceuticals, how to develop site specific protocols for 15 administration and use of the medical technology, radiation safety and 16 quality control for all aspects of the procedure, including ordering, 17 preparation, administration, and disposal of contamination or waste, if 18 present, components of the written directive for therapeutic administration, 19 pre-procedure, assay and dosimetry, the role of post-procedure dosimetry, 20 patient monitoring, discharge instructions and release, including the 21 management of procedural events such as extravasations, follow-up 22 protocols for therapeutic interventions, reporting of adverse reactions and 23 medical events, and aspects of supervision of the team, of the healthcare 24 team, including the NRC regulatory requirements.
25
30 And, some aspects of these are already included in the 1
training, documentation, and safety education that's provided by SNMMI, 2
ASTRO, and other professional societies. Next slide, please.
3 In terms of supervision, the administration and use of 4
EMTs may require the direct involvement of a range of other specialties, 5
including certified nuclear medicine technologists, registered nurses, RSOs, 6
medical physicists, all under the, possibly under the remote supervision by 7
the AU.
8 Understanding of the NRC regulatory requirements for 9
these roles must be required for the AU, and the educational needs for the 10 entire team must be met to ensure the safe utilization of the EMTs.
11 So, the AUs must have a clear understanding of the roles 12 and limitations of each member of the team, and a documented plan for how 13 they would interact with those members when they are physically present or 14 managing remotely. Next slide, please.
15 So, in terms of the role of the vendors, for EMTs and for 16 new radiopharmaceutical applications, the application vendor does have a 17 significant role in recommending and providing the appropriate knowledge 18 and technical training for the safe and effective use of their technology.
19 Vendor training should cover all aspects of how to correctly 20 use the drug or the device. And, training should include contraindications to 21 use, and a reminder to trainees not to modify or substitute aspects of the 22 device or procedure without approval of the manufacturer.
23 This definitely has played into some of the medical events 24 that we've seen. Next slide, please.
25
31 Hands-on. And so, it is also the recommendation of the 1
subcommittee that training should be hands-on. And, this should be 2
expected for any new therapeutic device or drug, or any therapeutic 3
application that has a unique delivery program platform.
4 And so, this means that the prospective user would have to 5
conduct mock use, or supervised patient use, of the device drug using the 6
actual device or drug, or a model device that incorporates all practical 7
aspects of the new technology.
8 Any training must include opportunities for the prospective 9
AU to ask questions about the training material, and process and receive 10 those answers in real time.
11 And, the trainer, either a vendor and/or a current 12 authorized user, must be able to directly assess their prospective AU 13 learning in the context of the training prior to unsupervised clinical 14 implementation. Next slide, please.
15 And, it's the recommendation of the committee that the 16 trainer, either a vendor representative or an authorized user, must be 17 physically present, or in person, for the training of the prospective user and 18 their team, even in situations where the standard of care administration or 19 use of the technology may be performed with the AU supervising remotely.
20 Next slide, please.
21 And, for medical events, the NRC should encourage 22 licensees to encourage and to include information in annual refresher 23 training for appropriate individuals, authorized users, certified nuclear 24 medical technologists, et cetera, regarding the medical events involving 25
32 radiopharmaceuticals or devices used by the licensee.
1 And, we recommend that the information on known 2
medical events should also be included in initial training for a new device or 3
drug application. Next slide, please.
4 This is a summary of our recommendations. So, one, core 5
knowledge-based topics, those where they were listed from lab class and 6
work training, should be supplemented with the application specific content 7
that we discussed previously for existing and future EMTs incorporating 8
radioactive byproduct materials.
9 The NRC should enable the relevant professional societies 10 to develop curricula for initial training. And, should explore how best to 11 evaluate these curricula on an ongoing basis and how these curricula may 12 be included into an efficient licensing process.
13 The NRC should explore the need to define minimum CE 14 and CME requirements for authorized users. Training for new therapeutic 15 devices or drugs that has a unique -- for any therapeutic application that has 16 a unique delivery platform, should be both hands-on and in person, with a 17 vendor representative or an authorized user for the new technology prior to 18 unsupervised clinical implementation.
19 And, the NRC should encourage inclusion of information 20 on known medical events, and annual refresher training for drugs or devices 21 used by the licensee, and initial training of a new drug or device application.
22 Next slide, please.
23 So, these are the abbreviations used in the presentation.
24 And, thank you very much for your attention.
25
33 CHAIRMAN WRIGHT: Thank you very much, Dr. Folkert.
1 That was a lot.
2 (Laughter.)
3 CHAIRMAN WRIGHT: Now, to finish up the presentations, 4
we'll go back to Dr. Jadvar. But, this time he will be presenting on behalf of 5
the ACMUI Patients' Rights Advocate, Mr. Josh Mailman.
6 So, Dr. Jadvar, go ahead.
7 DR. JADVAR: Yes. And, thank you. So, as was 8
mentioned, I'm going to present a statement on behalf of Mr. Mailman, who 9
we value very much for his activities as a patient advocate on this panel.
10
Dear Chairman Wright,
Commissioners Caputo, Hanson, 11 Crowell, and Marzano, members of the ACMUI and the NRC staff, I had 12 looked forward to attending today's meeting in person, but due to a recent 13 major surgery, I am not permitted to travel until May.
14 I appreciate Dr. Jadvar for reading this statement into the 15 record. The topic that the Commission had wanted me to discuss included 16 patient perspectives on the new isotopes as theranostic pairs.
17 This is an area where I am especially excited about recent 18 progress and have spent a great deal of time looking at and creating tools to 19 identify new clinical trials that are using theranostic pairs. As a reminder, 20 theranostics is using same radioligand for diagnostics and therapy.
21 I have shared the tools that I have worked on with the NRC 22 staff so that they can keep track of new clinical trials that are being 23 registered with all nuclear isotopes, with the ability to track new isotope, and 24 radioligand pairs. This is about one new trial in a day.
25
34 As recent as two weeks ago, the FDA has approved 1
additional indications for prostate-specific theranostic treatment in PSMA 2
Lu-177, showing just how important this new category of radiotherapy is for 3
patients.
4 My involvement with theranostics dates back to 2007, 5
when I was diagnosed with a rare neuroendocrine tumor. In 2008, I was 6
fortunate to attend a patient conference in Toronto, Canada, where I was 7
introduced to nuclear medicine physicians from several European centers 8
already using gallium-68 dota imaging for better diagnosis and management 9
of neuroendocrine tumors under compassionate care.
10 I traveled to Germany from 2008 to 2010, for both 11 diagnostic and therapeutic care under compassionate care. I greatly 12 benefitted from the theranostic approach, which significantly improved my 13 quality and quantity of life.
14 In 2011, while attending a medical conference in Germany, 15 I met with the United States researchers who were interested in bringing this 16 theranostic approach to the United States.
17 Based on my personal experience, I then began working 18 with these researchers as a patient advisor, where I saw firsthand the 19 challenges of bringing short-lived radioisotopes to market.
20 My first interaction with the NRC was on behalf of 21 community-based radiopharmacies that could not bring gallium-68 to market, 22 as it would require a decommissioning plan.
23 At that time, germanium-68, the precursor to gallium-68, 24 was not listed correctly in the NRC guidelines for decommissioning. Thanks 25
35 to the work of the ACMUI, NRC staff, and the Commissioners, this was 1
rectified and the small radio pharmacists could use germanium-68 2
generators.
3 At the same time, the Department of Energy sent a notice 4
that they planned to exit the germanium-68 supply market, as they felt 5
commercial supplies were adequate to match the current demand.
6 I, as well as other patient advocates, launched a letter 7
writing campaign to encourage DOE to maintain its position as a backup 8
supplier for germanium-68.
9 DOE agreed to remain as a backup supplier given the 10 impending approval of gallium-68 dotatate and the potential use of this 11 isotope for other diseases, including prostate cancer.
12 June 1, 2025, marks the ninth anniversary of approval of 13 gallium-68 dotatate, now part of the standard of care for neuroendocrine 14 tumor patients. Tens of thousands of diagnostic scans are being done every 15 year using dotatate with gallium-68 or copper-64.
16 In 2017, the theranostic pair to gallium-68 dotatate, 17 lutetium-177 dotatate, was approved. Since then, lutetium-177 dotatate has 18 treated tens of thousands of neuroendocrine tumor patients.
19 The work on neuroendocrine tumors and gallium-68, led 20 the foundation for other gallium-68 and lutetium-177 therapies in prostate 21 cancer, which have treated tens of thousands of patients since their 22 approval.
23 The work in theranostics is extending and improving the 24 lives of hundreds of thousands of patients worldwide. The work of the 25
36 ACMUI and the NRC staff with the Commissioner's support, has been 1
invaluable in allowing the safe use of these medical isotopes.
2 I look forward to hearing Mr. Green's presentation on 3
growth in radiopharmaceutical therapy, and continuing my involvement with 4
the ACMUI and the NRC staff, as we work on patient release criteria, 5
decommissioning guidelines, and other areas that benefit patient care and 6
public safety.
7 And, that's the end of his statement. Thank you.
8 CHAIRMAN WRIGHT: Thank you very much, Dr. Jadvar.
9 I guess, this morning we start with questions from the Commission with 10 Commissioner Hanson.
11 COMMISSIONER HANSON: Thank you, Mr. Chairman.
12 Good morning everyone. Thanks for your presentations and particularly 13 thanks for your service to the American people, for serving on the committee 14 and so forth.
15 I really appreciated the discussion. And, I've also noticed 16 the Pluvicto commercial, Mr. Green. I actually saw it during the Olympics 17 last summer.
18 We've really, if you know what it is, it really jumps out like a 19 neon sign.
20 MR. GREEN: I saw it last night in the hotel room. I've --
21 DR. JADVAR: It's been on for like, two or three weeks 22 now.
23 MR. GREEN: I don't want much TV.
24 (Laughter.)
25
37 COMMISSIONER HANSON: Mostly during sporting 1
events. I think, they're targeting a certain demographic, if I may.
2 But, it's really something, right? Because, as you know, 3
the Pluvicto is really a, it's for, typically has been used for prostate cancers 4
that are very far progressed and are arises in a whole number of ways.
5 And so, it kind of has this niche use at the moment. And 6
yet, here's this commercial. Yeah. Anyway, I noticed it as well.
7 This is really, I've got to kind of, I want to zoom out a little 8
bit, and I've got a question for any of the members, or any of the folks here 9
who have given presentations.
10 Dr. Jadvar, you noted that Mike King from the NRC, gave a 11 presentation on the ADVANCE Act to the Committee. I think, at your 12 presentation last fall.
13 And, as you know, the ADVANCE Act really emphasizes 14 the need for the Agency to be more efficient in kind of all aspects of our 15 operations.
16 And so, in addition, I know Dr. Folkert, you mentioned one 17 area in which we could kind of improve efficiency.
18 But, I'd be interested to hear your thoughts on, either 19 additional thoughts on requirements, or licensing processes, et cetera, for 20 the medical uses of radioactive material.
21 DR. JADVAR: Thank you for that question. Yes, we did 22 have a presentation last fall. And actually yesterday also in our meeting we 23 had another reminder or brief overview of the ADVANCE Act by Dr. Katie 24 Tapp yesterday.
25
38 And for that, we actually formed a subcommittee now, a 1
ACMUI subcommittee, to explore how the ADVANCE Act can help more 2
efficient processes within the ACMUI and how we can help the NRC medical 3
team in that regard using the new mission statement that really emphasizes 4
efficiency.
5 I will let my other colleagues discuss it in particular 6
matters.
7 MR. GREEN: I think we've taken ownership of that now 8
that we have a subcommittee and saying what can we -- from our 9
perspective, what can we see that we could alert and make more efficient.
10 We are looking forward to what's coming our way to adapt to it. So we take 11 ownership of that.
12 DR. FOLKERT: And as far as much of the training is 13 concerned, so many of the elements are already there. The existing 14 structure for 35.390, 35.396, radiopharmaceuticals, does allow for broad 15 use. A lot of the bottleneck is actually happening far down the line at the 16 level of the initial licensing of authorized users at the local setting.
17 I think the education actually needs to go out to those 18 RSOs that, you know, once someone has met that training, once someone 19 has gotten established an authorized user for these various different 20 subsites that they have that scope to be able to practice using all the other 21 radiopharmaceuticals. But they need to be educated in the safety and use of 22 it. And that is where the professional societies come in, which have all been 23 developing all of this content that we need.
24 Everything that we brought up is actually something that 25
39 the professional societies have already taken the lead on and are working 1
on. So if we can capture that, if we can utilize those resources that are 2
already there, I think we can get these moving very quickly and very safely.
3 COMMISSIONER HANSON: That's great. Thank you.
4 Well, this is a great segue, actually, into my next question, which was really 5
about the mission statement, right?
6 As you all know the ADVANCE Act directed the 7
commission to revise our mission statement. And while, you know, it didn't 8
change our kind of core safety protection of the public, protection of patients, 9
protection of users of these materials, the key word that kind of did get 10 added as a point of emphasis was enabling.
11 And certainly, in my travels to medical centers in the U.S.
12 but particular internationally and in developing countries, you really get a 13 sense of how important and enabling our ensuring mission is for a regulator, 14 right?
15 If you are a country and a LINAC, for example, it is a really 16 big deal, you know, and there is only one or two for the country allowing and 17 ensuring and enabling access to that device for patient treatment is really a 18 kind of a core part of their mission.
19 And while, you know, the NRC is in a little different 20 position, we've got this big marketplace. We've got a lot of innovation in the 21 U.S. We can't pick winners and losers. There is kind of still that need to not 22 be an impediment to ensure access for patients and so forth.
23 So while you are getting and focusing on the ADVANCE 24 Act and as you say, Mr. Green, the mission statement, can you talk a little bit 25
40 about how, you know, your perspectives, at least in an initial way, on 1
maintaining the patient safety but also recognizing the language around 2
enabling that the Commission has kind of elevated or put forward?
3 DR JADVAR: I think the eventual care delivery to the 4
patient have many, many facets. You know, there will be availability, 5
accessibility and also NRC plays a role in enabling, you know, availability 6
and hopefully ready approval of these -- not approval by the FDA but also 7
the AAU education and training that they need so that we have enough 8
human resources, AUs, around in the country who can deliver these type of 9
treatments.
10 And I think Dr. Folkert in that subcommittee was talking 11 about how NRC can help work with the professional societies with the 12 vendors and others to make sure that is enabled. That pathway is open and 13 clear for all folks who are interested in these kind of treatments, an easy and 14 efficient pathway for them to become an AU with appropriate knowledge and 15 training so they can give competent care to our patient.
16 COMMISSIONER HANSON: Thank you.
17 MR. GREEN: I think the NRC has laid the foundation for 18 allowing progress to happen. I mean, there are agreement states still that 19 have line items where you have got to apply for using this and apply for 20 using that. But you've got 35.300 and you've got alphas and betas, pure 21 betas and mixed beta gammas and so all these other things that are coming 22 down the pike are going to fit nicely in there. You are not impeding anything, 23 and you are going to allow various new drugs, various nuclides, various new 24 cancers to be treated without any change to that framework.
25
41 DR FOLKERT: I think as long as the message is clear 1
from the NRC that this is the goal, that this is what you want, and this is 2
communicated with a high level of communication to RSOs at the local level 3
and state governments, you know, this is something that is going to help us 4
progress forward.
5 COMMISSIONER HANSON: Yeah, thank you. And, 6
again, you keep getting ahead of me on my questions.
7 But to your point, Dr. Folkert, I mean, I've seen this in 8
conversations with RSOs about, hey, we've got clinicians and researchers 9
who are kind of leading edge and trying to figure out, you know, and using 10 different isotopes in different ways and still want to stay within -- you know, 11 we're still trying to -- the RSOs are trying to guide those researchers and 12 practitioners to stay within -- you know, how do we kind of stay in the box?
13 But I want to ask the question more explicitly. Mr. Green, 14 you kind of previewed it a little bit. I want to make sure that the NRC's 15 regulatory framework in our specific regulations are really flexible enough. I 16 guess I will just go with flexible enough to kind of accommodate, really, the 17 tremendous growth and innovation that we have seen in some of the slides 18 that you presented.
19 MR. GREEN: I think the regulations are flexible enough. I 20 love the use groups. I think the associated documents, as I said, the A1 and 21 A2 values are going to be an issue and that we can work with the agencies 22 and other international organizations too.
23 I know that Europe has a moly-99 maximum value that can 24 be shipped in a moly generator. But in America, we have higher values, 25
42 which are essential for efficient operations. And we have an exemption or 1
something in America only. We may have to do the same thing with the A1 2
and A2 for alpha emitters.
3 COMMISSIONER HANSON: Great. Well, thank you, very 4
much. Thank you, Mr. Chairman.
5 CHAIRMAN WRIGHT: Yeah. Thank you, Commissioner 6
Hanson for getting us started this morning.
7 Commissioner Crowell, you're next.
8 COMMISSIONER CROWELL: Thank you, Mr. Chairman, 9
and thank you to all of the presenters today. This is a weighty meeting topic, 10 and there are lots of directions to go in terms of questioning.
11 I first just wanted to extend my -- reiterate my thanks to the 12 folks at Columbia/ Presbyterian Hospital in New York who were nice enough 13 to give myself and Commissioner Hanson a tour last year. That was very 14 enlightening for me on these topics and helped me see firsthand the 15 opportunities and challenges in nuclear medicine.
16 So with that, and if I address my questions to the wrong 17 person, anybody feel free to jump in, but Dr. Jadvar, maybe start with you 18 and touch on microspheres.
19 So my understanding is the subcommittee didn't find a 20 single common root cause among medical events involving unexpected 21 deposition microspheres in the GI tract, and a draft ACMUI report last month 22 stated improved technology and imaging may be why we are seeing more of 23 these events reported.
24 Could you just explain a little bit about how these events 25
43 occur and what role technology plays in detecting these events? And my 1
follow-up is how to look at being able to detect things versus -- detection 2
versus something that used to be actually addressed as a best problematic.
3 DR. JADVAR: I would like to ask my colleague, Dr.
4 Harvey, who was chair of the subcommittee to brief you on that.
5 DR. HARVEY: Testing. Is this thing on? Okay. Thank 6
you.
7 If I understand your question correctly, you are correct in 8
saying that there was no real trends or specific root cause analysis.
9 The yttrium-90 microspheres procedures are very 10 challenging, complicated procedures that work with many different services, 11 including interventional radiology.
12 Prior to treatment, there is an MAA, or macroaggregated 13 albumin mapping study with technetium-99m performed first. They will look 14 to see if there is any shunting away from the liver to the gastrointestinal tract.
15 So that MAA is not exactly the same as the microspheres, 16 but it is the best that we have. So sometimes then treatments are done, and 17 there may be shunting to the GI tract, which wasn't observed via the MAA 18 mapping or some of the angiographic procedures that are done ahead of 19 time.
20 Does that answer to your question as to how it occurs?
21 COMMISSIONER CROWELL: Yes, it does.
22 DR. HARVEY: Okay. Thank you. And you had a second 23 question, I believe.
24 COMMISSIONER CROWELL: Yeah, my second question 25
44 is to the extent you can say how -- the interplay between being able to detect 1
these things and to what extent being able to detect them is something that 2
needs to be proactively managed or if it's just -- you know, just because we 3
can detect something doesn't mean it's necessarily a problem that needs to 4
be addressed. It just may be a known quantity. Does that make sense?
5 It's kind of like when we detect pharmaceuticals in our 6
drinking water. Yes, we can detect it, but is it at a level that's problematic?
7 DR. HARVEY: Thank you very much for refreshing me on 8
that second question. So after the treatments are done, what is typically 9
performed, but not in all cases, is some post-therapeutic imaging.
10 In the past, there are some people that do the imaging, 11 some that don't. Some that would do it with planar imaging and some that 12 we might do it with SPECT or single-photon emission computed tomography.
13 So larger sites will tend to perform this post-therapeutic imaging in the best 14 way possible.
15 And we encourage, our subcommittee has encouraged, 16 that the licensees perform that post-imaging.
17 Now that the post-imaging has become a little bit more 18 prevalent, what we are seeing is potentially an uptick in the identification of 19 GI deposition. So that may be one of the reasons why we have seen a slight 20 uptick in the number of cases.
21 COMMISSIONER CROWELL: But not necessarily 22 determinative in the sense of needing to address it beyond noting its 23 detection?
24 DR. HARVEY: Well, if it is detected, right, then it should 25
45 be managed. There should be dosimetry done to understand what the 1
radiation dose to the patient is. And then that patient should be managed 2
accordingly going forward to make sure that they are safe.
3 GI deposition is certainly something not to be taken lightly, 4
something that we don't want to have happen. Some of the doses have 5
been very significant.
6 COMMISSIONER CROWELL: Okay. Understood. That's 7
very helpful.
8 DR. JADVAR: May I add --
9 DR. HARVEY: Thank you.
10 DR. JADVAR: We have an interventional radiologist here, 11 too, who actually practices this. And of course the issue is if it goes to the GI 12 tract and it is severe enough, there is a high radiation dose, you can get 13 necrosis. You can get some sort of damage or increased inflammation, 14 which may be symptomatic. Sometimes it is asymptomatic. But it is 15 something you want to avoid.
16 And at our center, we always do imaging to see if it has 17 gone to -- if it was deposited in the liver only and not elsewhere. But if it is, 18 we always monitor the patient for any symptoms that the patient may have.
19 But if you would like, we can ask Dr. John Angle also to give a clinical 20 perspective of what he has observed.
21 DR. ANGLE: John Angle from the University of Virginia.
22 So GI deposition is certainly something all practitioners are 23 very aware is a potential problem, very keen to avoiding it. We certainly are 24 concerned. In the medical events, we saw four this year where we had, you 25
46 know, zero the year before.
1 But the significance of that, as you heard, is not really clear 2
at this point. The detection is certainly better.
3 The only thing that has changed a lot is that number of 4
procedures being performed is probably a lot larger. So we are going to see 5
more events because we are simply applying the technology more often.
6 The blood supply to the liver and the gut is very closely 7
intertwined. These procedures are highly technical. I don't think this is a 8
never event or a never can be but we certainly need to watch for trends as 9
the procedure becomes more and more common.
10 COMMISSIONER CROWELL: Great. Thank you. I 11 appreciate that. Can one of you also speak to how we're -- how things are 12 evolving related to patient education and guidance following either diagnostic 13 or therapeutic treatments with new drugs and such?
14 Like I worry sometimes that there is a disconnect between 15 the application of a drug and its outcomes and what the patients are aware 16 of, how patients are -- what kind of guidance they are given after a 17 procedure is given. So, Mr. Folkert -- Dr. Folkert?
18 DR. FOLKERT: Yeah, this is an area that -- it is part of the 19 recommendations of our T&E group is to actually expand on that, on the 20 patient education and the caregiver education.
21 It is definitely going to be an increasing issue, especially 22 with drugs such as PLUVICTO. They are often given to patients who have 23 had a prostatectomy and have issues with urinary incontinence. So there is 24 a lot more issues with leakage and contamination of diapers, contamination 25
47 of other continence aids.
1 And so one of the recommendations for example in the 2
ASTRO safety white paper is to go through a social assessment of that 3
patient to see what kind of washing facilities they have at home, if they have 4
a bathroom that they can isolate into. You know, if they understand what 5
they need to do with contaminated materials, how long they need to store it, 6
where it needs to go.
7 And so there is a lengthy assessment of the patient's 8
understanding of the radiation safety needs or their specific drug application 9
and how it could affect the public. That has actually gone over every 10 administration.
11 And so it is something where it is incredibly important. It is 12 going to become even more important as these are used more and more 13 because there is going to be more radioisotope entering into the common 14 waste stream. And managing that and making sure that it is being taken 15 care of safely is a big focus.
16 COMMISSIONER CROWELL: And each patient's unique 17 social situation makes a notable difference in what kind of guidance is most 18 important to them.
19 DR. FOLKERT: Mm-hmm.
20 DR. JADVAR: I would just add that, you know, not only 21 patient but also the patient's security is very important. It turns out in my 22 practice that the wives are really in tune with what's going on with their 23 husband, and they really listen to follow all the, you know, guidelines.
24 And, of course, we see these patients every six weeks for 25
48 the next treatment and the next cycle. And we always ask them what was 1
their experiences, what went wrong and also ask about certain symptoms 2
that we may expect from that type of treatment.
3 For
- example, the prostate cancer treatment, the 4
PLUVICTO, you can get xerostomia, which is kind of a dry mouth or dry 5
eyes. So we ask about that and try to grade it and see if that's a problem, 6
it's not a problem and how to care for that.
7 So continuum of care and make sure we get feedback from 8
them and what worked, what did not work and try to educate them the best 9
we can.
10 COMMISSIONER CROWELL: And I am out of time. That 11 is the first time I have asked one question that took my entire 10 minutes, 12 which I will attest to the importance of the topic.
13 So thank you, Mr. Chairman.
14 CHAIRMAN WRIGHT: Thank you, Commissioner Crowell.
15 Next up, Commissioner Marzano.
16 COMMISSIONER MARZANO: Thank you, Mr. Chairman.
17 Good morning and thank you all for your presentations today.
18 Mr. Mailman, if you're listening or -- I want to wish you a 19 smooth and fast recovery. I hope you take good care of yourself, feel better 20 soon, and I look forward to meeting you sometime in person in the near 21 future.
22 I would like again to take a moment just to sincerely thank 23 you all for the value of work that you do as members of this advisory 24 committee but also the broader contributions you make in the field of nuclear 25
49 medicine.
1 The use of radioactive materials for diagnostic and 2
therapeutic applications continues to expand and evolve at a rapid pace as 3
is made clear today, making your expertise and insights even more critical.
4 Your continued engagement with the NRC staff is crucial to 5
ensuring that our regulatory decisions prioritize patient safety, respond to the 6
growth in the number and type of radiopharmaceutical treatments and avoid 7
limiting patient's access to care.
8 And this area is particular close to my heart. I, like millions 9
of people across the nation and the globe, have a personal connection to the 10 lifesaving potential of this suite of technologies.
11 My father was diagnosed with prostate cancer two years 12 ago and has received radiation therapy as part of his treatment. And that 13 has vastly improved his prognosis. In fact, the addition of this therapy to the 14 course of treatment for prostate cancer, as you well know, has become the 15 standard of care and has saved countless lives.
16 So this personal connection that I know I share with many 17 others further underscores the importance of the work you are doing, and I 18 thank you again for your ongoing commitment and dedication to this work.
19 So onto my questions. I think some of this will be around 20 the theme of the projected growth and how to manage that growth because 21 the increasing use of these radiopharmaceuticals and advanced treatment 22 technologies, as we have kind of discussed right here or hinted at, means 23 that the occurrence of medical events will arguably increase. We would 24 expect it to.
25
50 Obviously, the NRC has its processes for event reporting, 1
identifying the cause, corrective actions to prevent recurrence and facility 2
notifications to other licensees so they can avoid similar incidents.
3 I just wanted to kind of maybe turn the conversation to 4
some of the human performance and human error reduction techniques and 5
specifically the checklist that was mentioned here and talk a little bit more in 6
certain aspects of that.
7 As many people may expect, I am going to put on my 8
former operator hat and kind of share. Human performance is one of the 9
biggest things that we have to manage in the control room as a senior 10 reactor operator in the safe operation of a nuclear facility.
11 Now I imagine it's no different in this case. And so, you 12 know, I am aware of many different types of tools to help reduce this human 13 error.
14 So, you know, you talked about this checklist for health 15 care providers as they administer care. In particular, can you provide some 16 other examples of methods -- well, first actually, can we cover a little bit of, 17 like, how this checklist is actually used in practice and some other -- you 18 know, discuss maybe some other methods to limit human error in the 19 administration of nuclear medicine?
20 MR. GREEN: Thank you for the question. So the 21 subcommittee's position was that we would encourage the NRC to make an 22 informational notice. You can't regulate this, but we said, hey, to help 23 reduce medical events, we recommend that each licensee in each section of 24 the department -- there could be brachytherapy, there could be 25
51 radiopharmaceuticals, diagnostic, therapeutics, Gamma Knife -- each should 1
have its own checklist specific for that device or for that technology that 2
would incorporate all the things that they think are important to prevent, you 3
know, is it the right patient? Is it the right drugs? Is it the right amount? And 4
it could be paper. It could be a checklist, analog, if you want to call it that.
5 But it could also involve digital technologies, electronic prescription order 6
entry and barcode medication administration.
7 I mean, there were seven lutetium-177 overdoses that 8
were reviewed yesterday. I think all of the could have been prevented with 9
barcode medication administration. The vials of 200 millicurie, one size fits 10 all from the manufacturer. But occasionally, because of platelets or other 11 blood values, it is reduced, and the patients received the entire quantity in 12 error.
13 So I think there are technologies -- so we were suggesting 14 that licensees develop their own specific based on their SOPs. And if they 15 want to involve a timeout process, stop, look, listen. Is everything correct?
16 Check the written directive. That is up to them. But we are encouraging 17 them to develop their own failsafes.
18 And hopefully to err is human. Let's see if we can't put 19 some other technologies in there to help reduce the human error.
20 DR. FOLKERT: Yeah, I mean, we definitely when we 21 reviewed the medical events yesterday, there was a significant number of 22 them could have been avoided with the simple application of a timeout.
23 And that's something that is -- the professional side 24 definitely pushes this a lot. It is something that I incorporate in all aspects of 25
52 my practice. When I am in the operating room, we do a timeout that we 1
verify with the patient what we are doing. We verify the roles of every 2
member of the team in that room and affirm that any one of them can put a 3
hold on the procedure at any point during it. And we make sure that we are 4
doing the right procedure to the right person in the right way.
5 And I think that is something that -- especially for any 6
interventional, any therapeutic treatment, it is imperative to include it.
7 DR. JADVAR: I would just also add that although the 8
generic dose is 200 millicurie for each cycle of both Lutathera and 9
PLUVICTO, which are approved, you know, as Mr. Green mentioned, yes, 10 there are situations where you have to reduce the dose. So 200 is too much 11 because, you know, of some issue with the patient, maybe hematologic 12 toxicity or something else.
13 And it is important that these places also have 14 interdisciplinary model, disciplinary tumor boards where these unique 15 situations are discussed so all the team knows what is going on. So that, 16 you know, just don't get -- you know, grab 200 millicurie that comes, you 17 know, from the street and just inject the patient.
18 You know, if these are discussed, hopefully some of these 19 human errors are prevented.
20 COMMISSIONER MARZANO: I definitely appreciate it 21 because the analogs are becoming more clear as I think about it. I mean, 22 human performance is human performance. So, you know, I see a lot of 23 opportunity maybe to kind of look across, you know, different high 24 consequence activities and how those things are performed just broadly and 25
53 how human error is managed in those. Definitely a carryover here.
1 You know, in terms of reinforcing standards, can you talk a 2
little bit about the role of maybe professional societies, individual hospitals, 3
kind of just, you know, within disciplines of the healthcare system to, you 4
know, holding others to those standards.
5 DR. FOLKERT: Like as far as radiation oncology is 6
concerned, we do have an incident learning system. And it's a way that 7
people actually enter their experience if there is a near miss, if there is an 8
actual event, anything like that. It is a way of submitting those, and it's a way 9
of facilitating review of those potentially harmful or actually harmful events 10 and looking at ways to address it.
11 And that is something that it's actually a part of 12 accreditation for many presenting and academic radiation oncology facilities.
13 So it's already integrated in many ways. And I think there is also an instant 14 monitoring system on the nuclear medicine side as well, yeah.
15 I mean, this is something that's -- we have -- I mean, the 16 professional sides have a vested interest in keeping patients safe. And so it 17 is something that has been integrated into their practice for quite some time.
18 DR. JADVAR: I think one of our members, Mr. Ouhib, has 19 also a response. Please.
20 MR. OUHIB: Thank you. My name is Zoubir Ouhib. I am 21 the mainly specialist in brachytherapy. But I actually like your question very 22 much.
23 And we talk about checklists. We talk about timeout. But 24 the whole thing about that is really an opportunity for those, you know, 25
54 authorized users, medical physicists and dosimetrists, technologists, 1
whatever, to refocus because the culprit in a medical event or medical errors 2
is really the lack of focus.
3 It is not that these individuals don't know what they are 4
doing because after the fact, you talk to them and you say -- and they will tell 5
you, yeah, I know. I know exactly what I was supposed to do. And I 6
shouldn't have done this. And I should have done this and all that.
7 And then it was like, what exactly happened? There was 8
some distractions. There was something in the mind of that individual.
9 There was a phone call. There was an urgency to go to another unit to take 10 care of another patient and so on.
11 And so it is really the key is we try and encourage people 12 to really focus at that time. And when you are doing that, that is the only 13 thing that you need to pay attention to. Everything else will have to wait.
14 Thank you.
15 COMMISSIONER MARZANO: Thank you. That all makes 16 a lot of sense to me. It is something that I can relate to in my previous 17 experience as well.
18 Well, I am coming up on my time. And I am going to turn it 19 over here in a second. But I just want to say I have a wealth of questions I 20 would love to get a chance to discuss with you at some other point in time 21 given that this is my first introduction to the Advisory Committee.
22 So, again, thank you all for your time today and for your 23 presence here in Rockville. And with that, Mr. Chairman, thank you very 24 much.
25
55 CHAIRMAN WRIGHT:
Thank
- you, Commissioner 1
Marzano. Your passion comes through. I like that. Very good.
2 Good morning, and thank you for your presentations this 3
morning as well as the important work that you do on this committee, all of 4
you that are here.
5 Before I jump into my questions, I would also like to join 6
Commissioner Marzano and thank each of you for the important work that 7
you do outside of the work on this committee as medical professionals. So, I 8
mean, your selfless service, and it's obvious your compassionate care. You 9
are very passionate about what you do as well. It can't be overstated. It just 10 can't. And you are wonderful examples to each of us.
11 And I know it comes at the expense of time with your 12 family and your friends. But I will tell you personally, I want to thank you on 13 behalf of myself and my daughter, my oldest daughter, for your commitment 14 to the health and safety of others because like me and my oldest daughter, 15 others in this room, including Commissioner Marzano's father, we are the 16 beneficiaries of the safe and secure use of nuclear medicine, nuclear 17 technologies. And fortunately for me, the focus of my doctors as well 18 because it is very important. So I wanted to personally thank you for that.
19 And with that, I am going to dive right into my questions.
20 Dr. Jadvar, you talked about the newest subcommittee, 21 right, on NRC mission and medical use licensing and oversight in response 22 to the ADVANCE Act.
23 What are your thoughts generally? Where does this 24 committee need to start its work? Have you all focused on that? Do you 25
56 have --
1 DR. JADVAR: Well, as I said, we just had a briefing on 2
that, on the ADVANCE Act, and we formed a subcommittee to delve into it, 3
really into detail and understand it completely, and certainly try to focus and 4
see how we can align the ACMUI workflow and the process to match or align 5
with very well with the new mission statement and efficiency.
6 I think a lot of these efficiencies are already in place, but 7
maybe we can improve in many ways and also come up with topics that 8
make other activities within the ACMUI and hopefully make some 9
suggestions to the NRC for a more efficient pathway.
10 CHAIRMAN WRIGHT: So you haven't really yet identified 11 the low hanging fruit areas?
12 DR. JADVAR: It is open to my colleagues if they want to 13 have any thought on that, then please mention it.
14 CHAIRMAN WRIGHT: Is there anything that --
15 MR. GREEN: I will just mention that --
16 CHAIRMAN WRIGHT: Sure.
17 MR. GREEN; -- of the three new subcommittees that were 18 established yesterday, this one that we are discussing now is the one with 19 the highest priority and the most urgent time frame.
20 The other two were asked to report in the fall. This one is 21 planning to have meetings in the very near future. Thank you.
22 CHAIRMAN WRIGHT: Good. What can we do to help the 23 committee maybe be better prepared for that future that is coming? Do you 24 have anything now or, you know, I am going to leave that open so that you 25
57 can come back to us as well, right? Because we stand ready to help. Okay.
1 All right. And thank you.
2 Mr. Green, you have a previous background in the 3
legislature in South Carolina, and I was a utility regulator and economic 4
regulator in the state. And I remember a lot of things in that that happened 5
during that time frame that you are experiencing now with all the new drugs 6
that are coming and the new isotopes that are coming and how fast they are 7
coming.
8 We experienced the same thing in this country with 9
telecom. You could almost wake up every morning and something new in 10 telecom was happening in the early 2000s. And then when the smart grid 11 came and all these new smart technologies, they couldn't even put it up, 12 install it, and work towards cost recovery on anything because it was out of 13 date by the time they got it put up, right?
14 And you are experiencing the same thing, or you are 15 seeing that happen with -- I think you mentioned that some of these 16 medicines are kind of dying an economic death because new and better 17 drugs are out there. So it is really mind blowing about that.
18 And given that, you know, they are coming every day, they 19 will be coming this year, next year, given this potential influx of these new 20 radiopharmaceuticals, what do you -- what can we, at the NRC, what can we 21 do in cooperation maybe with the agreement states, what can we do now 22 maybe to be ready to license and provide guidance for their safe use? Is 23 there anything we can be doing right now?
24 DR. JADVAR: I am not sure if there is anything that needs 25
58 to be done immediately, whatever that definition of immediate is. But I think 1
we are already on our way, at least in this committee, trying to address a lot 2
of these flood of new radiopharmaceuticals for diagnosis and therapy that 3
are coming through.
4 But also I want -- although it is very exciting and there was 5
a nice chart that Mr. Green showed about all of these new trials, but, you 6
know, there is going to be other drugs which are not radioactive, too. So 7
there are going to be some competition. Not all of these are going to be, you 8
know, blockbusters as he showed. There were 11 approvals for 9
radiopharmaceuticals and half of them, almost half of them, you know, did 10 not continue on long term.
11 So there is a lot of excitement with understanding of 12 cancer biology and then, you know, you identify a biomarker and say, okay, I 13 am going to try this. They try it. It works. It has to fill a gap. And there will 14 be some of those. But I just want to kind of temper down a little of, you 15 know, what we see is very exciting. Definitely, I am excited. That's my line 16 of work.
17 But there are really some of this which will not be 18 successful or will not fill a specific gap per se. And there will be other 19 non-radioactive pathways that are also quite exciting that are going on, you 20 know, antibody drug conjugates and things of that source that also use 21 basically the same biomarkers and targets and all of that.
22 So I don't personally think there is anything immediate that 23 needs to be done. But I think we are already on our way. But Dr. Folkert?
24 DR. FOLKERT: I do think one thing that can be done 25
59 immediately is that high level communication to the regulators to clarify the 1
scope.
2 I mean, right now all these new drugs are coming in, but 3
they are being investigated. They are undergoing research. And it is very, 4
very difficult for the investigators to get the permissions to be able to deliver 5
these radiopharmaceuticals to see if they are even worth exploring further.
6 And so making sure that that pipeline is open so that 7
investigators can give an alpha particle based radiopharmaceutical, can 8
give, you know, 15 different types of lutetium-based radiopharmaceutical so 9
that their scope of practice is not limited in this period of time. That they are 10 investigating these drugs to see which ones are good. That, I think, can be 11 done.
12 And that is all within current guidelines, just making sure 13 that the regulators know that they should not be arbitrarily limiting the access 14 of investigators to these radiopharmaceuticals to do the research that has to 15 be done.
16 CHAIRMAN WRIGHT: Well, I mean, you play a real 17 important role. One of the things I don't want to see happen with the NRC is 18 that our regulations and our procedures are behind the times, right?
19 Because we need to keep up with the changes that are happening in the 20 medical field. And I don't want to get to the point where we are stopping 21 ourselves, right? So we are going to really need your expertise and your 22 advice and those of the professional committees and societies that are out 23 there to help us do what we need to do there so.
24 MR. GREEN: If I may, I know during our presentation 25
60 yesterday from Dr. Tapp, the health medical staff, there is a works in 1
progress to make a guidance document for licensees on medical waste, 2
talking about incontinence.
3 So that is something that I don't think has been 4
approached yet by the NRC. I think it will be a very useful document and 5
guidance for the industry.
6 CHAIRMAN WRIGHT: I am going to come right back to 7
you. You spoke about the IAEA standards and the whole regulations on 8
safe transport and all that.
9 So my question was about the potential impacts of 10 manufacturers and the nuclear pharmacies are going to face possibly with 11 the Type A packaging versus Type B. Is this is a cost or safety issue or is it 12 the availability of common carriers to transport these types of packages?
13 What can we do, you know, or do we need to do maybe in cooperation with 14 DOT to help with the issue?
15 MR. GREEN: Theres a lot of pigs. Theres a lot of pigs in 16 the circulation today. So whether it is bulk containers take raw isotope 17 manufacturer of the nuclide to the CMO that is making the 18 radiopharmaceutical, then they've got to have the containers that take those 19 out to the clinics or to the pharmacies. And then there are pigs that have to 20 take them from the pharmacies to the clinic if it's prepared unit dose patient 21 specific. And so it is just going to cascade.
22 If we can use a DOT Type A, we already have those.
23 There is no impediment to progress, to patient care. If we have to use Type 24 Bs, you know, these are short lived. You got to have much more activity in 25
61 them so you are over that threshold, over that A1 rate, too. Then you are in 1
a Type B. It may not arrive as a Type 1A or 1B quantity. It is now lower, but 2
it still has to go in that other container.
3 So if we can get some way, whether it is collaboration with 4
DOT, if we can get through that hurdle, that would be great.
5 CHAIRMAN WRIGHT: Well, maybe that's a conversation 6
that needs to be had. Okay. Thank you.
7 And before I close, real quick, I also wanted to reach out 8
to, and speak directly to Dr. Mailman's statement. One, I'm glad he is doing 9
better, and I understand he is going to be coming back to work maybe in 10 May, very soon if not. We have all been impacted by cancer at some level, 11 either personally or family or friends or anything like that.
12 But I think we are all encouraged by what is going on in the 13 whole radiopharmaceutical arena because it has the potential to just save 14 lives, which is important.
15 So I found this is a bonus. When I became a 16 commissioner, I found just how active we were on the medical side of things.
17 I was, like, wow, this is really cool. So I am very proud of what we do here in 18 this agency and what you do in trying to make sure that we are doing this 19 safely and that hopefully we can -- if we can't beat it, we can sure, you know, 20 make remission somewhat permanent and allow people to live forward.
21 So to Mr. Mailman, I look forward to seeing you again real 22 soon. Take care. And we are proud of what you do. And with that, I am 23 going to conclude my remarks and turn it over to Commissioner Caputo.
24 COMMISSIONER CAPUTO: Good morning. Thank you 25
62 for being here and thank you very much for your presentations. I am going 1
to focus on training experience requirements.
2 We spend a lot of time and a lot of effort on that in making 3
sure that there are adequate numbers of authorized users has been a point 4
of concern, I think, for the commission for many years just based on the 5
need, as several commissioners have talked about, enabling the benefits 6
here for patients while ensuring radiation safety.
7 But I have to say, I am a little curious about a couple of the 8
recommendations. So one recommendation was that the NRC should 9
explore the need to define minimum continuing education requirements.
10 So as it stands now, physicians that completed their initial 11 training experience more than seven years prior to requesting authorized 12 user status. We require proof of continuing education and training for that, 13 but the requirements here are flexible so the physicians are submitting 14 continuing education and training in accordance with the authorization that 15 they are requesting.
16 How does your approach supplement that? Because I am 17 concerned here that if we are broadening our requirements here, we are 18 adding regulatory burden. And I am looking for exactly why you think there 19 is going to be efficiency and efficiency on the part of who?
20 DR. FOLKERT: I mean, so much of the inefficiency is not 21 happening at the level of the NRC. It is happening much further 22 downstream.
23 So that continuing education requirement for example, that 24 is spelled out there. There is nothing specific about it. It just says you need 25
63 to have continuing medical education. But there is no guidance as to a 1
minimum number or what, specifically, has to be covered in that continuing --
2 into that CME.
3 So when you get down to the regulators, when you have 4
somebody who is more than seven years out and they are applying for it, a 5
lot of time the regulators, and this is feedback I have gotten from people at 6
professional sites, they are told by the regulators that we don't have any 7
clear guidance on the training that you are supposed to receive.
8 So we are going to say that you have to do 200 hours0.00231 days <br />0.0556 hours <br />3.306878e-4 weeks <br />7.61e-5 months <br />. We 9
are going to say that you actually have to go back and, you know, and you 10 can only work with one radionuclide and that's it, nothing else.
11 And so I think part of that is -- what I was looking for, and 12 at least what we were thinking, and this is by giving some more specific 13 guidelines, it lets the regulators know what is acceptable, you know, what 14 gives that clearance so that that person can move on to become an 15 authorized user because right now it's nebulous. And when it's nebulous 16 and there is no guidance, it is very easy for a regulator to just say no or to 17 draw things out for a very long period of time.
18 COMMISSIONER CAPUTO: And this is going to get a 19 little bit into my other question, the other recommendation here, because you 20 said continuing medical education. So to what extent is it feasible to define 21 our role in terms of safety versus having the commission delve into the 22 practice of medicine, which is beyond our purview?
23 DR. FOLKERT: I think what we -- so in the prior T&E 24 proposal, we had suggested providing some specific case scenarios. And 25
64 so that would represent training -- represent guidelines that would be 1
considered safe and acceptable to the NRC. I don't know if that's 2
addressing the question.
3 COMMISSIONER CAPUTO: Well, it can.
4 DR. FOLKERT: (Simultaneous speaking.)
5 COMMISSIONER CAPUTO: It can to a certain extent 6
because I think once we get into having a range of scenarios, the further you 7
go down that path, the more scenarios we are going to end up with. Well, 8
this doesn't quite fit what the NRC has. So it is not acceptable?
9 I would be concerned that we end up being prescriptive 10 and by being prescriptive, we are eliminating other scenarios that might be 11 valid simply because they weren't anticipated.
12 DR. FOLKERT: Mm-hmm.
13 COMMISSIONER CAPUTO: Not to mention the fact that 14 there is going to be a fair amount of regulatory burden because any range of 15 scenarios would then not only need to be broadened, but they are likely to 16 change over time. And they would have to constantly undergo revision.
17 DR. FOLKERT: Mm-hmm.
18 COMMISSIONER CAPUTO: So how do you thread the 19 needle between ending up in that kind of a scenario versus having a flexible 20 system that we don't have to constantly tinker with as regulators because as 21 we tinker, then all of the agreement states have to update their regulations.
22 And this becomes quite a paperwork exercise.
23 So how do you ensure that whatever approach it is going 24 to be is the juice worth the squeeze in terms of what we are accomplishing?
25
65 And is it really directly contributing to a safety benefit?
1 DR. FOLKERT: I think one thing that was brought up in 2
this more recent one is not so much setting up a pathway, but to validate the 3
training that is being offered.
4 So if the NRC were to recognize that some of the curriculum meet the requirements, then all someone has to do is go through that curriculum and then that should satisfy the regulators. So that would be an efficient way of doing it, and you would touch on all of the different safety aspects that the NRC wishes to focus on. So that would be focusing on both efficiency and safety instead of by dealing with the materials itself.
COMMISSIONER CAPUTO: So --
DR. FOLKERT: It would still take some oversight. I mean, there would have to be some time to evaluate those curricula to see that they are -- that they meet the requirements. But then those curricula would apply to a vast swath of potential practitioners.
COMMISSIONER CAPUTO: Okay. But those curricula are not necessarily going to be focused on radiation safety. It is going to be a mix of --
DR. FOLKERT: Mm-hmm. Well --
COMMISSIONER CAPUTO: -- practice of medicine and radiation safety.
DR. FOLKERT: But if they don't include that radiation safety, then the NRC doesn't have to say that they meet the requirements.
COMMISSIONER CAPUTO: Okay. But then you've got 14 professional societies listed --
66 DR. FOLKERT: Yup.
COMMISSIONER CAPUTO: -- currently.
1 DR. FOLKERT: It is some upfront work.
2 COMMISSIONER CAPUTO: Those professional societies 3
are going to be updating that curricula on a fairly regular basis.
4 DR. FOLKERT: Yup. And then --
5 COMMISSIONER CAPUTO: So we're going to have to 6
update our review --
7 DR. FOLKERT: Mm-hmm.
8 COMMISSIONER CAPUTO: -- every time they update 9
their curricula. Do you see where I am going here?
10 DR. FOLKERT: Oh, yeah. I understand.
11 COMMISSIONER CAPUTO: Are you really convinced that 12 this is going to be beneficial?
13 DR. FOLKERT: I think it would be beneficial because that 14 focus on that curricula will then have a downstream impact of thousands of 15 potential practitioners. So it is -- and so that's -- and that's thousands of 16 potential practitioners that would each have to be evaluated on an individual 17 basis for their -- for the hodgepodge of education that they went through.
18 But if they had one that had been reviewed on a yearly 19 basis, you know, I think that would speed things up.
20 COMMISSIONER CAPUTO: So has the committee looked 21 at or considered the nature of how the agency would have to staff up to do 22 what you are anticipating in terms of having people qualified to review all of 23 these curricula and create these approvals?
24 DR. FOLKERT: Yup. And we thought -- and we do 25
67 recognize that it would require a significant amount of staff time.
1 COMMISSIONER CAPUTO: Mr. Green?
2 MR. GREEN: I just wondered if it would work more 3
efficiently if we reversed the flow. On one of your slides, you've got a list of 4
all the radiation safety functions that should be done, patient education, talk 5
about incontinence, social histories, extravasations should be addressed 6
with the patients. When you go home, be aware of this.
7 There is a list that we could easily make that could be 8
provided to the medical education and the professional societies to the 9
educational programs and just say this is a list that the NRC has prepared. It 10 may have the citations of the regulations that are applicable that says make 11 sure your material covers this.
12 So rather than looking at individual programs and having a 13 staff burden, you make the document, this is radiation safety that is 14 important to us. And you provide that to the providers and ask that they 15 make sure it's in their programs.
16 COMMISSIONER CAPUTO: So with these societies, if 17 they are going to have these various curricula, how do we manage a 18 situation where one curricula might cover half of our requirements and 19 another might cover 80 percent of our requirements, and we end up with sort 20 of a hodgepodge?
21 DR. FOLKERT: I mean, that is unfortunately the situation 22 that we have right now. That is the current situation. So, I mean, it wouldn't 23 be creating more of a situation than we have as is.
24 I mean, I think the goal would be that each individual site 25
68 for the practitioners who work underneath, they would create a 1
comprehensive curricula. And you should ask that. That would be 2
something that could be spelled out.
3 DR. JADVAR: Or it could be a combination of societies 4
that work -- if they know what the requirements are, as Mr. Green just 5
mentioned, then a lot of these societies, SNMMI, ACNM, ACR, ASTRO, they 6
can certainly work together to come up with a common curriculum that can 7
be presented to the practitioners.
8 COMMISSIONER CAPUTO: Okay. But are we in a 9
chicken and an egg because our requirements exist today, but they haven't 10 tailored their curricula to make sure they meet our requirements, right, which 11 is why we end up in this situation?
12 DR. FOLKERT: Actually, I would disagree with that. And 13 so the specific requirements that are required for the NRC, the ACGME has 14 actually encoded all the standards for us for radiation oncology.
15 In order for radiation oncologists to graduate, they all have 16 to meet all of the requirements that are currently spelled out in the NRC.
17 That is an across-the-board recommendation of the residency review 18 committee for radiation oncology. So that --
19 COMMISSIONER CAPUTO: Okay. For that one, but what 20 about the other 13?
21 DR. FOLKERT: I mean, that's -- then we would want to go 22 to those. But the problem is that right now, that exists and so right now -- but 23 there are still roadblocks because of the downstream regulators. They are 24 not necessarily accepting it and that is one of the reasons why we need that 25
69 high-level communication to reaffirm that scope of practice from the NRC or 1
to jump back on that topic. Yeah.
2 COMMISSIONER CAPUTO: Okay. I am not sure that I 3
really see a clear resolution of this. But I'm out of time. Thank you.
4 CHAIRMAN WRIGHT: Thank you, Commissioner Caputo.
5 So it appears we are out of time today. And I want to thank everybody for 6
your presentations and for taking the time to be here today and for 7
everything you had to do to get prepared for today as well because it was 8
very informative. We probably could have spent another two hours on it to 9
be honest with you. You might not like it, but we would have.
10 So before I close, I just want to ask my colleagues if 11 anybody wanted to make any comments. Hearing none, I will adjourn this 12 meeting.
13 (Whereupon, the above-entitled matter went off the record 14 at 11:49 a.m.)
15