ML20030A031
| ML20030A031 | |
| Person / Time | |
|---|---|
| Issue date: | 01/28/2020 |
| From: | NRC/SECY |
| To: | |
| Shared Package | |
| ML19365A117 | List: |
| References | |
| M200128 | |
| Download: ML20030A031 (99) | |
Text
1 UNITED STATES NUCLEAR REGULATORY COMMISSION
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PUBLIC MEETING ON THE DISCUSSION OF MEDICAL USES OF RADIOACTIVE MATERIALS
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- TUESDAY, JANUARY 28, 2020
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ROCKVILLE, MARYLAND
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The Commission met in the Commissioners' Hearing Room at the Nuclear Regulatory Commission, One White Flint North, 11555 Rockville Pike, at 9:00 a.m., Kristine L.
Svinicki, Chairman, presiding.
COMMISSION MEMBERS:
KRISTINE L. SVINICKI, Chairman JEFF BARAN, Commissioner ANNIE CAPUTO, Commissioner DAVID A. WRIGHT, Commissioner
2 ALSO PRESENT:
ANNETTE VIETTI-COOK, Secretary of the Commission MARIAN ZOBLER, General Counsel NRC STAFF:
STEVEN WEST, Deputy Executive Director for Materials, Waste, Research, State, Tribal, Compliance, Administration, and Human Capital Programs KEVIN WILLIAMS, Deputy Director, Division of Materials Safety, Security, State, and Tribal Programs (MSST),
Office of Nuclear Materials Safety and Safeguards (NMSS)
LISA DIMMICK, Team Leader of the Medical Radiation Safety Team, MSST, NMSS KATHERINE TAPP, PhD, Medical Radiation Safety Team, MSST, NMSS DONNA JANDA, Chief, Medical and Licensing Assistance Branch, Division of Nuclear Materials Safety, Region I EXTERNAL STAKEHOLDER PANEL:
MURRAY SHELDON, MD, Associate Director for Technology and Innovation, Center for Devices and Radiological Health, U.S. Food and Drug Administration TERRY DERSTINE, Chair, Organization of Agreement States THOMAS EICHLER, MD, President, American Society for Radiation Oncology VASKEN DILSIZIAN, MD, President, Society of Nuclear Medicine and Molecular Imaging JOSH A. MAILMAN, President, NorCal CarciNET Community
3 P R O C E E D I N G S 1
9:01 a.m.
2 CHAIRMAN SVINICKI: Well, good morning, everyone and welcome. I call 3
the Commission's meeting to order this morning.
4 The Commission is convening in a public session to hear an update on the 5
NRC's program for medical uses of radioactive materials, a status of recent activities related to 6
the licensing and oversight of medical uses of radioactive materials, to hear the views of 7
stakeholders on recent NRC initiatives and to discuss or hear suggestions regarding 8
transformation and innovation opportunities regarding the Agency's work on this very diverse and 9
important set of topics.
10 I look forward to the discussion. In preparation I discovered there were a lot of 11 really interesting things in this area, and I do look forward to hearing from the external panel.
12 Our meeting will consist of two panels today. The first panel we will hear from 13 the NRC Staff. They're seated at the table, and I'll turn it over to them momentarily.
14 And then after a very short break we will have a panel of external perspectives 15 provided to us. Both panels will be followed by Q&A from members of the Commission.
16 But before I do turn it over to Mr. Steve West, on behalf of the Office of the 17 Executive Director for Operations, do any of my colleagues want to offer any preparatory?
18 I think we were discussing in the back how interesting the topics are today, so 19 I think we just want to dive right in with that. I will turn it over to you, Steve, to lead the Staff's 20 presentation. Thank you.
21 MR. WEST: Thank you, Kevin. Radioactive materials, next slide please.
22 Today's panel will cover the following topics. Kevin Williams, the Deputy 23 Director of the Division of Materials Safety Security State and Tribal Programs in the Office of 24
4 Nuclear Material Safety and Safeguards, will provide the status of the NRC Staff activities in the 1
medical program.
2 Lisa Dimmick, the Medical Radiation Safety team leader will discuss innovation 3
opportunities and initiatives in the medical program.
4 Dr. Katie Tapp, a medical physicist on the Medical Radiation Safety team, will 5
cover the staff efforts to prepare for the review of emerging medical technologies.
6 And Donna Janda, the Branch Chief for the Medical and Licensee Assisting 7
Branch in Region I, will provide the regional perspective on licensing and inspection of medical 8
uses of radioactive materials.
9 I'll get us started with an overview of the NRC's program of medical uses of 10 radioactive materials.
11 And next slide please. This slide shows the objectives of the NRC's medical 12 use policy statement, which guides the work of the medical team staff and others here at the NRC.
13 The NRC regulates the medical uses of radioactive materials to protect the 14 radiation safety of workers, the public and patients, all while minimizing intrusion into the practice 15 of medicine.
16 Next slide please. According to the Society of Nuclear Medicine and Molecular 17 Imaging, more than 20 million Americans, myself included, benefit each year from nuclear 18 medicine procedures used to diagnose and treat a wide variety of diseases and other ailments.
19 Broadly speaking, the medical uses regulated by the NRC fall into two 20 categories. Diagnostic and therapeutic.
21 Diagnostic uses usually involve small amounts of radioactive from imaging 22 organ systems and functions, medical fields that use radioactive materials for diagnostic 23 purposes, include nuclear medicine, nuclear cardiology, endocrinology and diagnostic radiology.
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5 Next slide please. On the other hand, therapeutic uses of byproduct material 1
usually involve larger amounts of radioactively to treat cancers and other alignments.
2 Each year there are approximately 150,000 therapeutic procedures performed 3
using radioactive materials. Some examples of therapeutic uses include radiopharmaceutical 4
therapy, teletheraphy, brachytherapy and gamma stereotactic radiosurgery.
5 Fields of medicine using therapeutic byproduct material include nuclear 6
medicine, endocrinology, radiation oncology and interventional radiology.
7 With this wide range of medical uses, the NRC strives to maintain a 21st century 8
workforce that can keep up with the evolving medical landscape.
9 We accomplish this by using the Agency's strategic workforce planning to keep 10 our staff skills current and reflective of the wide range of medical modalities and uses. And by 11 continuing to use expertise from the Regions, the Agreement States, the Advisory Committee on 12 Medical Uses of Isotopes and other medical consultants.
13 I will now turn the presentation over the Kevin. Next slide please.
14 MR. WILLIAMS: Thank you, Steve. Good morning, Chairman, 15 Commissioners. Let me start off with some recent activities in the NRC's medical program that 16 involved a great deal of coordination and communication.
17 Next slide. The NRC Staff routinely engages with stakeholders to better inform 18 our activities in order to ensure an effectively medical program at the NRC.
19 This list highlights some of the staff's recent activities that involve stakeholder 20 outreach. In addition to these activities, the medical team is developing licensing guidance for 21 several emerging technologies and working on rulemaking activities for Part 35.
22 Before I go into greater detail on each of these activities, I want to briefly discuss 23 our ongoing coordination with the Organization of Agreement States, OAS, our Advisory 24
6 Committee on the Medical Use of Isotopes, ACMUI, and the U.S. Food and Drug Administration, 1
FDA.
2 Thirty-eight Agreement States regulate approximately 91 percent of the U.S.
3 Medical Licensees. And the Staff values the close coordination with the Agreement States in 4
carrying out the radiation safety regulatory programs.
5 To achieve this coordination, the medical team works closely with OAS during 6
activities such as rulemaking and a development of licensing guidance.
7 Coordination with the ACMUI is another vital part of the NRC's medical 8
program. Through ACMUIs work on several topical subcommittees per year, the ACMUI advises 9
the NRC on medical policy and technical issues.
10 And the Staff relies on the ACMUI's medical expertise to inform our decision 11 making. The medical team also works with the FDA to coordinate our respective regulatory 12 programs for medical devices, drugs and biological products containing radioactive material.
13 Examples of this work include updating the 2002 NRC FDA memorandum of 14 understanding, conducting a workshop to share regulatory information and planning for an 15 upcoming joint public information that will solicit stakeholder input on the Agency's continued 16 coordination.
17 Next slide. One recent activity that involved a great deal of input from external 18 stakeholders was the staff evaluation of training and experience requirements for 19 radiopharmaceuticals. Over 250 comments were received from physicians, medical professional 20 societies, patient groups and industry groups.
21 The Staff's regulatory decision making was strengthened by their consideration 22 of their wide range of opinions on their training and experience requirements. The Staff's 23 evaluation also included input from several individual Agreement States, OAS, the Conference of 24
7 Radiation Control Program Directors and ACMUI.
1 Lisa Dimmick will further discus the Staff's evaluation of training and experience 2
for radiopharmaceuticals during her presentation.
3 Next slide. Another area of extensive stakeholder outreach relates to patient 4
release. The Staff published a patient brochure, patient release brochure, last May to support 5
radiation safety conversations between patients and their healthcare provider.
6 With regards to updating guidance for patient release, the Staff is taking a 7
phased approach. Phase 1 focuses on updating the patient release instructions and considers 8
an input from a wide spectrum of stakeholders, including the public, patients, patients' groups, 9
physicians, professional societies, licensees, ACMUI and OAS.
10 The revised guidance incorporating the Phase 1 changes will be issued this 11 spring. Phase 2 began last fall and will update dosimetric equations, methodologies and tables 12 used to calculate dose to members of the public.
13 Next slide. An important part of the NRC's outreach is to communicate 14 operational experience relating to preventing medical events through issuance of Generic 15 Communications.
16 This slide shows four Information Notices that were issued last year. Three 17 were associated with the use of specific radionuclides and one summarized the ACMUIs and 18 Staff's evaluation of recent medical events. And strategies to reduce or prevent all types of 19 medical events.
20 Next slide. On a related note, the medical team worked with the Office of 21 Nuclear Regulatory Research to evaluate the abnormal occurrence, AO threshold, for medical 22 events.
23 As part of this evaluation, the medical team reviewed the 55 medical event AOs 24
8 that occurred over the past five years. And found that only eight of these events had the potential 1
for causing harm. More significant than acute radiation skin complications.
2 Based on a complete evaluation, the Staff concluded that the medical event AO 3
criteria may capture events that are not significant from the standpoint of public health and safety, 4
and recommended to the Commission that the AO criteria for medical events be revised.
5 This recommendation aligns with the ACMUI and Agreement States position on 6
this topic.
7 Next slide. The last activity that I wanted to highlight is related to 8
extravasations involving radiopharmaceuticals. Generally, an extravasation is the inadvertent 9
injection of a medical fluid into tissue surrounding the vein or in artery.
10 An ACMUI subcommittee concluded that extravasation is a practice of medicine 11 issue and not an item that needs to be regulated by the NRC. And that extravasation should not 12 be considered a medical event unless there is an unattended permanent functional damage.
13 Considering ACMUI's recommendation and the interest from external 14 stakeholders, the NRC Staff has begun an independent evaluation of whether extravasation of a 15 radiopharmaceutical should be considered a medical event.
16 Additionally, the further consolidated appropriations act will require the Staff to 17 provide a separate report to congress on this matter, this spring.
18 This concludes my presentation and I will turn it over to Lisa Dimmick. Next 19 slide.
20 MS. DIMMICK: Thank you, Kevin. Good morning, Chairman and 21 Commissioners.
22 As you've heard so far, the medical team has been very busy, and we've been 23 looking for ways to improve our processes and look at them through a different lens.
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9 Next slide. The first example is the Staff's evaluation of the training and 1
experience. In response to stakeholder concerns regarding unnecessary regulatory burden of 2
the NRC's training and experience requirements for radiopharmaceuticals requiring a writing 3
directive, the Commission directed the staff to evaluate whether requirements could be tailored 4
for difference categories of radiopharmaceuticals.
5 The Staff recently provided the Commission with SECY-20-0005, Rulemaking 6
Plan for Training and Experience Requirements for Unsealed Byproduct Material. Which is 7
dated January 13th, 2020 and was made publicly available on January 17th.
8 SECY-20-0005 documents the staff's evaluation and potential options for 9
revising the training and experience, or T&E requirements. While the Staff does not recommend 10 tailoring the T&E requirements, the Staff did use the evaluation as an opportunity to determine 11 whether broader changes to the T&E regulatory framework could better prepare the Agency for 12 the expected advancements in nuclear medicine.
13 The current T&E requirements are prescriptive. They set out a specific number 14 of trainings hours, training topics and case work requirements that physicians must complete to 15 become an authorized user for broad categories of radiopharmaceuticals.
16 Licensees must submit detailed information of their physicians training and 17 experience. And the NRC and Agreement States must review and approval training and 18 experience in order to grant authorized user status to a physician.
19 In a series of internal brainstorming sessions, the Staff considered how the 20 existing regulatory framework could be changed to increase medical community involvement in 21 determining the training and experience requirements. And in credentialing authorized users.
22 Next slide. During those brainstorming sessions, the Staff debated several 23 variables related to determining T&E requirements and the overall regulatory framework for T&E.
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10 The Staff then developed several options for revising the requirements. And 1
later we published those options in a Federal Register notice for public comment.
2 The Staff's options fell under two general approaches. The first approach 3
would maintain the current regulatory framework of prescriptive T&E and NRC and Agreement 4
State review and approval for T&E of authorized users.
5 The second approach would be more performance-based. Authorized user 6
credentialing responsibility would shift the medical community while the NRC and Agreement 7
States would continue to focus regulation of medical Licensees on the safe and secured use of 8
radiopharmaceuticals with varying levels of oversight of training and experience.
9 With the exception of maintaining the status quo, all of the options were 10 transformative in that they involved relatively significant changes to the current regulatory 11 paradigm.
12 The Staff evaluated their options through the lens of whether they were aligned 13 with the Medical Policy Statement and the NRC's Principles of Good Regulation. The Staff also 14 heavily weighed input from the medical community, the ACMUI and the agreement statements.
15 Next slide. The Staff's paper provides a balanced view of these options as our 16 goal was to fully inform the Commission's policy decision.
17 The option that the Staff recommended for Commission consideration, is one 18 that shifts more responsibility for credentialing authorized users to the medical community, while 19 the NRC and Agreement States maintain oversight of T&E through recognition of medical 20 specialty boards that demonstrate their training programs meet certain high-level performance-21 based radiation safety competency requirements.
22 This would be a significant change in the current T&E paradigm because 23 recognized specialty boards would credential authorized users. The NRC and Agreement States 24
11 would no longer review and approve training and experience for authorized users. And 1
authorized users would no longer be listed on the medical user license.
2 This transformative approach for T&E could better prepared the national 3
materials program for the expected growth of nuclear medicine and the potential for increased 4
radiopharmaceutical use in different fields of medicine.
5 Next slide. Another area that we are looking to transform is our process for 6
reviewing emerging medical technologies.
7 With the growth in medical applications of radioisotopes and advancements in 8
medical technologies, it's anticipated that an increased number of emerging medical technologies 9
will be licensed by the NRC. And many of these technologies may not fit under the current 10 regulatory framework.
11 As a result, we've looked at our current review process, which takes about 14 12 months to complete, and decided to improve our internal process to gain efficiencies.
13 With our new process, instead of individual working groups reviewing each 14 medical technology, we would have the licensing guidance developed by a medical team 15 individual with support from a sealed source and devise reviewer or other technical staff as 16 necessary.
17 We would then have a standing committee, which we would review and 18 comment on the draft licensing guidance documents. The standing committee would include 19 representatives from the Regions, Agreement States, the Office of General Council.
20 The standing committee would provide oversight to this process, provide more 21 flexibility and agility by prioritizing reviews and shifting resources as necessary. And introduce 22 better consistency across all 35.1000 guidance documents.
23 This new process does not change the step where we get comments from the 24
12 Regions, Agreement States and the ACMUI, as this is an integral part of our guidance 1
development.
2 We estimate that this new process will result in a six month time savings and 3
better utilized resources across the national materials program. We have socialized this new 4
process with the Agreement States, and they view it as a good streamlined alternative to what 5
has been done in the past, while maintaining comprehensive review and input across the national 6
materials program.
7 This concludes my presentation, now I'll turn it over to Dr. Tapp.
8 DR. TAPP: Thanks, Lisa. Good morning, Chairman and Commissioners. In 9
recent years we have seen an increased use of emerging medical technologies, so I'm going to 10 discuss the efforts by the Staff to prepare for these reviews.
11 Next slide please. The NRC amended 10 CFR Part 35 in April of 2002 to add 12 Subpart K. Which is also known as 35.1000.
13 This regulation was added to allow for efficient licensing of expected new 14 medical users that are not specifically addressed in other subparts.
15 The addition of 35.1000 was forward thinking because it provides for flexible 16 regulatory framework for emerging medical technologies, which allows us to conduct licensing 17 process in an efficient and consistent manner avoiding delays in patient care.
18 Since 2002 we have used 35.1000 to license over ten emerging medical 19 technologies. Without 35.1000, each of these technologies would have required rulemaking, 20 which would have likely significantly delayed patient care.
21 Next slide please. Applications for new emerging medical technologies are 22 evaluated by the NRC on a case-by-case basis. The significant number of new medical 23 technologies fit into Subparts D through H.
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13 However, if the emerging medical technology is not addressed in these parts, 1
the Staff will develop the specific licensing conditions that are considered necessary for the 2
medical uses of these materials for 35.1000. These specific licensing conditions are listed in 3
licensing guidance documents which are posted on the NRC's medical uses licensee toolkit 4
website.
5 The first 10 CFR 35.1000 licensing guidance was issued in 2002 for Yttrium-90 6
microsphere brachytherapy. If the emerging technology is addressed in Subparts D through H, 7
there still may be a unique radiation safety aspect of the new technology that Staff may have to 8
assess and provide additional information for licensees in Regional and Agreement State 9
awareness. This information is also posted on our website.
10 Next slide please. The earlier we learn of emerging medical technologies the 11 better we can predict our workload and ensure that we have the right regulatory infrastructure and 12 workforce in place. Staff works closely with these stakeholders listed on this slide, who may 13 become aware of the technology before us.
14 The Staff also continues to work closely with these stakeholders in the 15 development of the 35.1000 licensing conditions and guidance.
16 Next slide please. Now I'd like to switch gears and discuss some of the 17 emerging medical technologies. First are the Yttrium-90 microspheres. These are manual 18 brachytherapy sources used for permanent implantation therapy.
19 However, they could not be licensed under the traditional 10 CFR Part 35 20 subpart for manual brachytherapy because of their unique properties. Such as their small size, 21 the large number of microspheres used per administration and the route of administration.
22 Therefore, Yttrium-90 microspheres brachytherapy is regulated by 35.1000.
23 While Yttrium-90 microspheres brachytherapy has been around for decades, their use has been 24
14 limited to two types, TheraSpheres and SIR-Spheres. And the licensing guidance is limited to 1
their use.
2 However, we are now aware of several new manufacturers that are in the 3
developing other microspheres and microparticle devices. So Staff is preparing to do another 4
revision of the licensing guidance to make it applicable to the other manufacturers.
5 Next slide please. Another area where we have seen an increase in new 6
technologies in Gamma Stereotactic Radiosurgery, or GSR units. The original regulations in 7
Subpart H have been developed for Leksell Gamma Knife. Which treats the brain using 8
stationary sources, helmet collimators and a head frame.
9 However, newer units are significantly different than the original gamma knife 10 units. For example, the Leksell Gamma Knife Perfexion and Icon illuminated helmets, use 11 sources in moveable sectors and has a frameless treatment option for the Icon.
12 Therefore, these GSR units are licensed under 35.1000. The initial guidance 13 for the Perfexion was published in 2007 and it was updated in 2016 to add the Icon.
14 In recent years, Staff has become aware of several new GSR units, including 15 the GammaPod. Which we issued guidance for earlier this month. And for the Infinity, which 16 we are in the process of developing 35.1000 licensing guidance for.
17 Similar to the Perfexion and Icon, both of these units have engineering changes 18 that are not covered in Subpart H, like moveable sources and collimators. The GammaPod is 19 also the first cobalt-60 GSR unit not to treat the head, but instead used for treatment of the breast.
20 We have also been made aware of several other GSR units, such as the 21 Galaxy, Orbiter and Vertex. Which we may develop 35.1000 licensing guidance for in the future.
22 Next slide please. So as you can see, there are more GSR devices coming 23 onto the market and more manufacturers entering the field in microparticles and microspheres.
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15 With the anticipated growth, development of a performance-based regulation 1
incorporating these modalities would allow for future GSR devices and microparticles to be 2
licensed without further NRC and Agreement State review.
3 To respond to the evolving medical landscape and further streamline or 4
licensing process, we are looking to update Part 35. We have begun an effort to primarily bring 5
in the modalities currently licensed under 35.1000 to be licensed under other subparts of Part 35.
6 We have chartered a joint NRC, OAS working group to develop rulemaking 7
plans and emerging medical technologies. The working group has regular meetings on this and 8
plans to submit a rulemaking plan this summer.
9 Next slide please. Another emerging medical technology of interest is the 10 Alpha DaRT. Or Diffuse Alpha Radiation Therapy. Which uses alpha particles to treat solid 11 tumors.
12 The treatment is similar to other manual brachytherapies as it has small 13 radioactive seeds that are implanted into the tumor. However, the Alpha DaRT seeds contain 14 radium-224, which release gaseous, short lived alpha emitting daughter products into the tumor 15 as it decays. It is these daughter products which travel inside the tumor to deliver the therapeutic 16 dose.
17 In 2018, the State of Massachusetts granted the sealed source and device 18 approval which enabled the manufacturers to begin clinical trials with this technology. The Staff 19 has started its evaluation and is expected to begin development of the 35.1000 licensing guidance 20 document this year.
21 We are hoping to be able to use the new emerging technology review process 22 that Lisa just mentioned.
23 Next slide please. Another new technology we are currently reviewing is the 24
16 check-cap C Scan system. This new diagnostic technology uses an ingestible capsule 1
containing byproduct material to stream for colorectal cancer using imaging.
2 The manufacturer states that this technology does not require as much 3
preparation like you do for a colonoscopy. But instead, allows the patient to continue with their 4
normally daily routine as the capsule travels through their gastrointestinal track to scan for polyps 5
in the colon.
6 The Staff has just begun its review of this technology and has not yet made a 7
determination whether it should fall under Subpart G or 35.1000. The Staff is closely evaluating 8
training and experience and waste disposal considerations to help make this determination.
9 Next slide please. In addition to medical uses, our team also reviews the use 10 of radioactive material in veterinary care. And we have begun seeing an increase in this area.
11 Historically, the most common veterinary procedures involving radioactive 12 material have been with cats, who are treated with iodine-131 for hyperthyroidism or horses, and 13 horses, who are treated Technetium-99m for imaging.
14 However, more recently, we reviewed requests for authorization for more types 15 of veterinary uses. Including treatment for osteoarthritis in dogs using tin-177m and solid tumors 16 in household pets using Yttrium-90 particles.
17 Next slide please. 10 CFR 35.75 provides the public dose limits and the 18 requirements for release of human patients, not animal patients, containing byproduct material 19 found in treatments.
20 In the case of veterinary uses, the release of animals must comply with the 21 public dose limits set in 10 CFR Part 20. Our current guidance in NUREG-1556, Volume 7, is 22 pretty specific to the treatment of cats using iodine-131.
23 And Staff, in its early stages of drafting a regulatory guidance to support the 24
17 development and review of the release of animals following other veterinary procedures using 1
byproduct material.
2 This concludes my presentation and I'll turn it over to Donna Janda.
3 MS. JANDA: Thank you, Katie. Good morning, Chairman and 4
Commissioners.
5 Regional Staff continue to serve an important role in support of the Agency's 6
mission. By performing radioactive material safety and security inspections and licensing 7
activities from medical facilities.
8 Today I'll be discussing how we implement the Part 35 rule changes and inspect 9
patient release and medical events while maintaining effective coordination with licensees, 10 Agreement States and headquarters.
11 Next slide. As you heard earlier, recent changes in Part 35 have been of 12 interest among internal and external stakeholders.
13 Amendments to the rule that the Regions have been addressing during 14 licensing and inspecting our facilities include the removal of the training and experience 15 requirements to obtain a written attestation for an individual who is certified by an NRC recognized 16 specialty board, an exemption of certain board-certified individuals from certain training and 17 experience requirements.
18 In addition, the new Part 35 introduced the concept of the allowance for 19 licensees to name Associate Radiation Safety Officers, or ARSOs on a medical license. ARSOs 20 support the licensee's radiation safety officer with specific duties and tasks assigned to each 21 ARSO as determined by the licensees needs in each ARSO's qualifications.
22 In general, licensees have not raised significant concerns to the Regions as 23 they implement the regulatory changes and appear to be pleased with the new requirements.
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18 Specifically regarding information required to be submitted for board certified individuals.
1 This decision has already saved resources for external stakeholders and for 2
Regional licensing staff. However, licensees have noted challenges in the licensing process.
3 Including the current inability to use the standard NRC 313A forms to document training and 4
experience.
5 As an update to that, we have recently received the Office of Management and 6
Budget approval on the updated forms. And these will be available on the public website shortly.
7 So that should help licensees have a quicker experience with getting that 8
training and experience documented.
9 In addition, some confusion exists among licensees regarding the specific 10 requirements involved in the naming of an Associate Radiation Safety Officer.
11 Specifically, Regional license reviewers have received several questions 12 regarding whether or not licensees may name their own ARSO, they cannot, whether or not the 13 ARSO can be named for only one site, and they are to be named by type of use and not site, and 14 whether or not they can have more than one ARSO, which they can.
15 These types of issues were addressed with issuance of supplemental guidance 16 for NUREG-1556, Volume 9, Revision 3. Which is accessible from our website, as shown on this 17 slide.
18 Note that licensees appear to be pursuing the option of naming Associate 19 Radiation Safety Officers. To date, the Regions have approximately 20 active licenses with the 20 Associate Radiation Safety Officers named in licensed condition.
21 Next slide. Regional inspectors use various methods to assess if patient 22 release is in accordance with regulations. The written directive, patient instructions and patient 23 release criteria calculations are part of what are typically reviewed during an inspection.
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19 For instructions, we want to see that the licensee has presented applicable 1
restrictions to the patient, that the patient has signed their indication of understanding these 2
restrictions and that they consent to abiding by the instructions.
3 Regarding patient release criteria, this includes whether they are released 4
based on administrative activity, dose rate surveys or patient specific release criteria. If patients 5
specific release criteria are used, we will evaluate how the licensee interviews patients to make 6
sure they can meet their criteria, and that they use the appropriate occupancy factor.
7 Regulatory Guide 8.39 is a resource we use to make sure the licensee's criteria 8
and instructions conform to guidance. Although several isotopes are not included in the 9
appendix, such as lutetium-177, licensees can develop their own independent values for patient 10 release.
11 In the case of lutetium-177, the dose rates are such that patients can generally 12 be released after half a day at the hospital. A revision to our guidance is underway to further 13 evaluate release criteria.
14 Next slide please. Medical events are defined Part 35 and include instances 15 where doses over a certain threshold are incorrectly administered or other issues occur as 16 described within the regulations. Licensees are to notify the NRC Operations Center no later 17 than the next calendar day after discovery of the medical event.
18 Since the medical event may indicate potential problems in a medical facilitys 19 use of radioactive materials, our prompt review of a reported event includes assessing the 20 licensees applicable policies and procedures and the written directive related to the medical 21 procedure that resulted in the event.
22 We also interview the staff involved in the treatment to help us construct a 23 timeline and identify what went wrong. On the right side of this slide I am shown at a facility in 24
20 Puerto Rico at which we reviewed an event involving a patient overexposure to iridium-192 during 1
a high dose-rate remote afterloader treatment.
2 In that case, we determined that the licensee had failed to develop or implement 3
an adequate written procedure to provide high confidence that each administration was in 4
accordance with the written directive.
5 We don't only react to reported medical events, but we also ask the licensees 6
during inspections if they have had any medical events. We then independently verify licensee 7
responses by reviewing treatments against written directives and ensure that licensees have a 8
policy and/or procedure in place to identify medical events.
9 Multiple events are reported throughout the national materials program this past 10 year involving administration of Y-90 microspheres.
11 In 2018, Idaho National Labs published the review of ten years of data on such 12 treatments and found that an increasing trend in Y-90 events could simply be the result of an 13 increasing number of microsphere treatments being performed. The majority of such events 14 involve patients receiving less than their prescribed dose.
15 Next slide please. Much of the coordination with our Agreement States is led 16 by our Regional State Agreement Officers as they regularly support the Agreement States with 17 technical, process and regulatory advice, including advice on the revisions to Part 35.
18 Notably, the Agreement States have until January 14th, 2022 to implement 19 changes in their own regulatory programs for compatibility with Part 35. And we stand ready to 20 support them in those efforts.
21 In terms of coordination with headquarters, Regional technical Staff actively 22 participate in working groups devoted to developing guidance for new devices, such as the 23 GammaPod and Infini gamma stereotactic radiosurgery devices and for emerging technologies.
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21 Regional expertise and directly licensing and inspecting medical and research 1
and development applications make these types of projects ideal for cross-coordination between 2
the Regions and the NMSS medical safety and events assessment branch.
3 This concludes my remarks. I will now turn it over to Steve for closing remarks.
4 MR. WEST: Thank you, Donna. And thank you to all of the Staff on the 5
medical radiation safety team and NMSS, the Regions, OGC, and others across the national 6
materials program who contributed to the work we discussed this morning. And who helped us 7
prepare our presentation.
8 And finally, thank you to the Commission for an opportunity to brief you on our 9
activities in the medical arena. And we now look forward to your comments and questions.
10 CHAIRMAN SVINICKI: Well, thank you very much, Steve, and to all the 11 presenters. And again, thank you for that acknowledgment that the work you're presenting on 12 today is supported by a lot of your colleagues here at the NRC. So we thank them all as well.
13 Some of them are probably in the room, others are probably busy at their desks working on the 14 things that you're here talking about today.
15 But, Steve, if you thought that perhaps we would get through this morning 16 without making some acknowledgment of the fact that you have indicated, and I believe I have 17 confirmed that you have announced to the broader world that you will be separating from federal 18 service, I think retirement.
19 I hesitate to use that word because I see so few of you and your peers that 20 actually end up kind of going and sitting and relaxing. You tend to have a lot of personal interest 21 in other things that you and your family want to pursue together, so I'm confident it will be a very 22 active retirement, if it is one.
23 But on behalf of the Commission, and I suspect others will weigh in before they 24
22 begin their questions, but on behalf of the Commission, and really just on behalf of, I think the 1
Federal Government, thank you for your long public service, the many contributions that you've 2
made here to the Nuclear Regulatory Commission.
3 And I won't say that we scheduled this just to make sure that Steve had to sit 4
through one more Commission briefing. You and all NRC Staff are always so respectful by 5
saying it's so great to be able to come and present to the Commission at these meetings.
6 I'm sure it's not your favoritest thing but thank you so much. And, again, you 7
occupy and will be retiring from, that really, I'll just be honest, horrible title, which I'll read for 8
everyone. Deputy Executive Director for Materials, Waste, Research, State, Tribal Compliance, 9
Administration and Human Capital Programs.
10 And I believe only Kevin is up here with a title that rivals that a little bit with his 11 division. So I think we could maybe be a little more transformational to figure out some umbrella 12 term that could house all those terms.
13 But again, thank you very much for all you've done here. And there will be 14 many other recognitions and acknowledgment as your departure approaches.
15 Another thing, which a lot of NRC Staff wish they could just kind of exit quietly, 16 but they have to be subjected to all kinds of recognitions and roasting. I guess if they've done 17 the wrong people wrong over the course of the years that have to listen to people tell stories about 18 them and stuff like that. But thank you very much.
19 And I, you know, I want to say, I hope you feel good about what we're talking 20 about today because I think as I was kind of looking at what's been happening in recent months 21 on a lot of these very important topics I notice that I think quietly this area is joining in some of our 22 innovative and transformational thinking.
23 And I hope that everyone, and the teams that they work with, are gratified 24
23 because on, you know, Lisa talked about the looking at our approach to the T&E and I, you know, 1
the paper is interesting because it has this enclosure. Which I really enjoyed but found unique.
2 And it's like, we were so innovative that we came up with so many different 3
possible approaches to the regulation here that some of them are just in an enclosure because 4
they really weren't worthy of being pursued. But to me it isn't so much about where you land in 5
an innovation or transform exercise its about how wide of a net did you cast.
6 And I was deeply impressed by really the stepping back and looking at, given 7
the state of some of the medical practitioners, the modalities, the different things going on, were 8
there other ways that we could try to look over the horizon and think about how the regulation 9
could be very robust.
10 And continuing on, Katherine a bit, in talking about Part 35.1000 and not 11 wanting to have over the course of time, and I learned this phrase from Chairman Steve Burns, 12 but I know all lawyers learn this, I don't have any formal legal training, but this notion of the 13 exception swallowing the rule, you know.
14 If everything kind of lands under the part of the rule that everything that doesn't 15 fit in Subparts D through H. At some point you want to step back and look at Part 35 broadly in 16 the review of the emerging medical technologies.
17 But I did note, also Katherine, in your presentation you said, that significant 18 number of new nuclear, new medical technologies still fit into those subparts. And then you kind 19 of, at the end of your presentation you talked again about how, I think it was the Yttrium-90 20 microspheres she said, now we've got a lot of kind of brachytherapy that could fit more traditionally 21 but then we look at engineering changes.
22 We look at maybe the way that the technology is applied to the patient and then 23 it doesn't quite fit. And it ends up back again in the exceptions.
24
24 But what I take from your presentation is this broader look at updating Part 35, 1
is going to look at that. And you don't want to have everything fall into the everything else 2
category.
3 But that being said, you also, as Lisa was emphasizing, as things are so 4
emerging in this technology and this area of medical practice, you want to be able to have it be 5
kind of robust. And I don't know if either of you would like to talk about how you have to kind of 6
balance those two things. Katherine, do you want to start?
7 DR. TAPP: Sure. It is a balance, as you mentioned. And the first thing we 8
do with all emerging technologies is we compare, rule-by-rule, every regulation in that subpart to 9
see if it fits.
10 And if something is a safety aspect that does not fit, obviously we have to move 11 it into 1000 to do the licensing conditions. So it really is a safety focus.
12 The other aspect is, if it does fit but we notice there's something that might be 13 missed by a Regional or Agreement State license reviewer because they're not doing as deep of 14 review when they first come out, that's when we'll issue a memo just to alert them as guidance.
15 There's something that's unique about this that fits, there's a regulation covering 16 that, but we want you to be aware just to make sure you know it's there and something to be 17 looking for.
18 CHAIRMAN SVINICKI: Thank you. And, Lisa, do you want to talk a little bit 19 about how you did such a broad canvassing for various options for approaches on the T&E look?
20 MS. DIMMICK: Sure. We were trying to, in the approach, not already have 21 decided what the outcome was going to be. So we stayed --
22 CHAIRMAN SVINICKI: That's refreshing.
23 (Laughter.)
24
25 MS. DIMMICK: So we stayed very open to really thinking outside the box. I 1
think we started with, if we did not have the Part 35 T&E regulations and we were crafting them 2
from the beginning, what would they look like.
3 So we went through a number of exercises trying to think in those terms as well 4
that if we were to create new regulations from scratch, how would we frame them. So I think 5
that's why we were able to stay in that mind set.
6 And along the process, we would often get, so where do you think you're 7
landing, so where do you think you're landing with regard to your recommendation. And the team 8
that was working on this was like, we're not there yet, we're really trying to be very thorough and 9
consider a spectrum of activities.
10 We looked to the international front on how do other countries regulate training 11 and experience over physicians or something similar to this.
12 We evaluated the medical event reporting. Impacts maybe that training and 13 experience may or may not have in that area.
14 And then we just really evaluated the tasking and what could we do if we were 15 to do a limited scope authorized user. How would that really look.
16 So, we identified that the medical field is expanding, it's changing. We're 17 hearing a lot of radiopharmaceuticals therapies coming down the pike. They're not routinely 18 administered yet, they're undergoing FDA clinical trials.
19 But they will be in the future. So we wanted to identify, are our regulations 20 inclusive of these new technologies that might be coming down the pike.
21 So if we have an opportunity to look at training and experience, how might we 22 prepare ourselves for the future of nuclear medicine. And that was really how we continued in 23 our process.
24
26 CHAIRMAN SVINICKI: Well, thank you. And again, hearing those 1
responses, I want to emphasize that it is important that we do have kind of a.1000 or a process 2
where we can take something genuinely and sincerely new. To modify a rule is, of course, not 3
a quick process and so that needs to exist.
4 What I was commenting more on is that you'd like to have your regulations. At 5
least have swim lanes for the general types of technologies that we're talking about.
6 And I see the updating of Part 35 is going to look at those swim lanes. And 7
then complemented by the general lane through which other things go if they don't fit into one of 8
the narrow lanes.
9 But again, I hope that as things, the Staff has an opportunity, as they did on the 10 T&E requirements, to back up and go through that exercise. I hope they found it as gratifying as 11 I found to read about it.
12 And as a decision maker, I'll just end with this, I've read the paper, I have not 13 formed any view on your recommendation or the other options that you looked at. But I am 14 always reminded in this subject matter area that I approach it with some level of humility.
15 I'm human being so I'm just, I'm trying to kind of invest my decision making with 16 the best insights that I can have. So knowing that the Staff looked broadly is something very 17 helpful as a decision maker to know that you cast a wide net because you are more expert in the 18 area.
19 But this area I approach with humility I guess for two reasons. One is its 20 complexity and it is dynamic. But the other is, of course, the fact that this area of our regulation 21 can have such a direct subject, could have such a direct impact on individual, you know, 22 Americans, their families.
23 And so, not that there is an importance in all of the applications of nuclear 24
27 materials that we regulate, but there's something about the directness on human beings of this 1
work that makes it something. That I always kind of approach it that way.
2 I'm sure we'll hear some perspectives from the next panel about, so it's awkward 3
since we haven't heard that yet, but I think the Staff has awareness of the materials provided in 4
advance, as do I. And I know that they'll be, I think probably some hunger in patients that maybe 5
we could make a bit more dramatic changes.
6 But I think it's going to be hard because it's not, we're not just covering any 7
particular one case, we've really got to have something very broad and it is interesting.
8 I've stepped back and challenged myself to say, is there a point in time in which 9
the fit of the mission of the Nuclear Regulatory Commission, with these materials, doesn't fit so 10 well and they're becoming more biologically based or there's just, medicine is changing so much 11 and it's we think that nuclear power has changed a lot. In 40 or 50 years medicine has changed 12 a lot more than power production. At least by my assessment.
13 So, the notion that Congress at some point may want to look at the division of 14 responsibilities. I respect that, but right now I think we can separate out the radiological part of 15 it and address it.
16 I hope that, I know this Commission will always be sensitive to hearing 17 perspectives that feel that maybe that's becoming an imperfect fit, but I don't think it's happening 18 today. I hope future commissions will stay sensitive to just wanting to make sure that patients 19 that need care are getting the best care, but also have access to these important new 20 technologies.
21 And I'm going to give my last few seconds to Steve because I didn't give you a 22 chance to react to my big public statement about your service here.
23 MR. WEST: That was unexpected, but I certainly appreciate it, your very 24
28 generous comment. It's been my pleasure to work at the NRC, to serve the public.
1 And to answer the one question you kind of fit into your comments, I do 2
appreciate what I heard today and what we're doing as an agency, as a public servant, an 3
employee of the NRC and as an aging American that expects to be using some of these 4
technologies.
5 And I really can't think of a better subject for my last Commission meeting to be 6
sitting at the table. Because it gave me an opportunity to hear about all the good work that's 7
being done at the national materials program led by our Staff here at the NRC.
8 And some of the things you're hearing about today where we're transforming 9
innovating things, trying to keep these technologies moving and available to the public is very 10 gratifying. Very, I'm sure you'll feel the same way.
11 But I really appreciate learning more about it. And I think I'll be using some of 12 those, so, thank you very much.
13 CHAIRMAN SVINICKI: Okay, thank you. And with that, I will turn it over to 14 Commissioner Baran.
15 COMMISSIONER BARAN: Thanks. I'd like to start with some follow-up 16 questions about the Staff's rulemaking recommendation on training and experience requirements.
17 As Staff discussed earlier, a physician can become an authorized user either 18 by being certified by a medical specialty board recognized by NRC or by completing 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> of 19 training and experience.
20 And the Staff has, was discussed earlier, is proposing essentially to drop the 21 alternate pathway of 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> while potentially expanding the number of recognized specialty 22 boards. Do we have a sense of how many additional medical specialty boards would want to 23 develop a certification process, have any expressed interest to us?
24
29 MS. DIMMICK: So, Lisa Dimmick, I'll respond to that. So, we do not have an 1
idea of how many new medical specialty boards might be interested to use, that would come in 2
under the revised specialty board criteria.
3 We know there are physician groups or types of physicians that are interested, 4
but in and of themselves they're not a board requesting to become recognized as a specialty 5
board.
6 COMMISSIONER BARAN: Well, as I'm thinking through the various options, 7
and I agree with the Chairman, I thought the Staff did a very good job laying out a bunch of 8
different options, it seems like for the recommended option this is pretty key. Because if NRC 9
didn't end up recognizing any additional medical specialty boards, maybe because they weren't 10 interested, but still dropped the alternate pathway, couldn't that make it hard to become an 11 authorized user than under the current framework?
12 Because there would be just the medical specialty board route, not the 700 13 hours1.50463e-4 days <br />0.00361 hours <br />2.149471e-5 weeks <br />4.9465e-6 months <br />. And if you don't add any additional boards to that route then it's actually narrower.
14 MS. DIMMICK: So, currently with the alternate pathway, we looked at who 15 uses the alternate pathway. And we identified in our initial assessment that physicians using the 16 alternate pathways are many, are ones that are waiting or are board-eligible so they have not yet 17 taken the board examination but they intend to take the specialty board examination. Or they 18 might be a foreign trained physician who is using the alternative pathway.
19 So we had identified through, in our assessment, that through the ANPR, the 20 Advance Notice of Proposed Rulemaking, that these were things that we would further vet. And 21 I identify how, the scope of that issue.
22 And we needed the medical community involvement for that as well.
23 COMMISSIONER BARAN: Okay. Under the Staff's proposal NRC would no 24
30 longer review and sign off on the training and experience of authorized users and authorized 1
users would no longer be listed on the license. And that would eliminate about 2,500 license 2
amendments each year.
3 It's not clear to me though that the current practice is the only possible method 4
of confirming that the training experience requirements are met for an authorized user. We don't 5
use that approach, for example, for reactor operators. They aren't listed on the license.
6 Why do we do it this way for authorized users?
7 Is there a reason that the authorized users need to be listed on the facilities 8
license, even if we stick with a 700 hour0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> alternate pathway, couldn't we have a system where a 9
licensee, a facility licensee kept a list of physicians that met the T&E requirements in that list and 10 supported documentation would be inspectable by NRC?
11 MS. DIMMICK: So, Lisa Dimmick. To answer that question, authorized 12 users, by their definition in Part 35, are a physician or a dentist or a podiatrist, depending on where 13 they fit, under which modality.
14 But they're a physician who is listed on a Commission or Agreement State 15 license. So the regulations for the definitions of an authorized user include that they are listed 16 on a Commission license.
17 COMMISSIONER BARAN: Is there some reason for that though?
18 I mean, again, if we were talking about changing the rule, is there some reason 19 not to depart from that?
20 Because if I think about the different options available, one option would actually 21 to be to keep the current structure of the specialty medical boards, the three of them, and the 700 22 hours2.546296e-4 days <br />0.00611 hours <br />3.637566e-5 weeks <br />8.371e-6 months <br />, but not verify them the same way if what we're doing now is super labor intensive and 23 different than what we do in other areas of NRC's jurisdiction. Do you see what I mean?
24
31 Is there some reason, either historically or practically, why listing folks 1
individually on the license is really critical?
2 And I ask that as a genuine question. Maybe there is and I just don't know 3
what it is.
4 MS. DIMMICK: Again, with the way the regulation is written with regard to 5
identifying that an authorized user is listed on the license, the historical part of Part 35 of how that 6
was included, they had historically been listed on the listed.
7 COMMISSIONER BARAN: I see John Lubinski standing up, and I'm interested 8
to hear him chime in --
9 MS. DIMMICK: Yes.
10 COMMISSIONER BARAN: -- but I just would kind of point out, when I read the 11 paper, and you did a great job laying out all the options and pros and cons, so many of the benefits 12 of the recommended approach flowed from moving away from the license amendment approach.
13 But that actually seems like kind of a separate issue. You can move away from 14 the license amendment approach and not drop the alternate pathway. That's why I'm kind of 15 asking about this, trying to figure out, is this really just actually another option you could have in 16 the option paper.
17 MR. LUBINSKI: Thank you, John Lubinski, Director of Nuclear Material Safety 18 and Safeguards.
19 If I could add to Lisa's comments. Distinguishing between being listed on the 20 license and doing the review, I think the more important part where Lisa was getting to is, today 21 it requires the NRC to do the specific evaluation of the individual against the alternate pathway.
22 So it's the evaluation that's being done.
23 Whether or not they end up being listed on the license or not, it's the issue of 24
32 whether or not NRC does the evaluation and is the person, for lack of a better term, the competent 1
authority to do the evaluation of that user and whether they met the 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> or not. And that 2
would be for the NRC reviewer or the Agreement State.
3 It's very efficient from the standpoint of that prescriptive nature that allows us to 4
do it in a very efficient way, even though we're doing so many authorized users a year. The 5
concept you're talking about, I think, really starts to align with either the current option that the 6
Staff is recommended or some variation of it where another group does that evaluation.
7 And I this space we would say, some medical board that was approved by the 8
NRC that we found that they had the appropriate authorization to do that.
9 In interpreting your question, I would say you're leaning more towards having 10 an authorized user or the licensee themselves continue to identify additional authorized users 11 where we could do that. That could be a next level down from the recommended option that's 12 discussed with a medical board.
13 Instead having licensees authorize their own medical, own authorized users 14 without going through an NRC review, we would review their programs. And that was an option 15 that came out during the brainstorming session, to allow licensees, authorized users, to then 16 subsequently review additional authorized users.
17 COMMISSIONER BARAN: Well, and I want to turn to another issue. I want 18 to ask about patient release too.
19 But that was also another option that was identified, having it more turned over 20 to the licensee. I could see some distinctions between what I'm talking about that, but again, 21 thanks for the additional context.
22 On patient release, NRC's current regulation requires authorized users to 23 provide post-treatment instructions to a patient before the treatment and early enough to give the 24
33 patient adequate time to make any necessary arrangements for isolation.
1 But the Staff notes in a paper that came up, I think last year, that the dominate 2
factor in determining internal and external doses to members of the public is based on the 3
behavior of the patient after release.
4 In other words, if a patient follows the doctor's instructions, their family members 5
and members of the public should be able avoid a dose higher than the regulator limit of 500 6
millirem. But if the patient doesn't follow the instructions, a family member or someone else could 7
get a dose higher than the regulatory limit.
8 That's a lot of responsibility to place on patients. And obviously the patients 9
themselves are not subject to any NRC requirements so we have no control over their behavior.
10 Again, kind of looking at it from a high level, does it make sense for NRC to rely 11 on patients following a doctor's instruction to protect members of the public from doses of 12 radiation?
13 Would it make more sense to think about requiring inpatient care in 14 circumstances where family members or members of the public could get a dose higher than the 15 regulatory limit if a doctor's instructions weren't followed?
16 MS. DIMMICK: So, Lisa Dimmick. We believe the regulation is adequate to 17 protect public health and safety.
18 The regulation to radiation exposure we believe can be safely controlled with 19 the current regulation use of calculations to assess exposures to the general public for release of 20 the patient as well as the patient instructions.
21 What we're doing, we're enhancing those instructions through issuance of the 22 brochure that we developed specifically for the patient and then also with the update to our 23 guidance document to enhance the instructions before, during, and after the patient care.
24
34 COMMISSIONER BARAN: Taking step back, I appreciate the importance of 1
the instructions and I obviously am not dismissing the importance of the physicians providing the 2
advice and the instructions to patients.
3 But I guess what I'm trying to get at is a little bit of a higher-level question of in 4
the end, we're really relying on the patient following those instructions to protect members of the 5
public, and their family members could be kids, from doses that would exceed the regulatory limit.
6 Does that make sense? The Staffs review found that family members of 7
patients treated with iodine-131 on an outpatient basis received doses between 4 millirem in 1330 8
millirem.
9 So, many of the family members are receiving doses much lower than the 10 regulatory limit of 500 millirem but some are receiving doses much higher.
11 The highest dose of 1330 millirem was to the child of a patient and the NRC 12 Staff noted in the paper that whether the patient is a child or a parent, close contact for extended 13 periods may be unavoidable. That's particularly true for families with limited means who may be 14 living in small spaces.
15 What are we doing to address those situations? If it's not practical to avoid 16 close contact with a family member at home, especially a child, the outpatient approach seems 17 problematic.
18 MS. DIMMICK: So, again, the regulation is a performance-based regulation in 19 the sense that the physician or the licensee needs to determine or assess whether or not they 20 have confidence that the patient will be able to follow the instructions.
21 So, in that sense, that should be factored in the release decision of that patient.
22 The outpatient therapy aspect is the performance-based, for the rule.
23 The current regulations don't preclude hospitalization so if a physician feels that 24
35 the patient cannot meet the criteria or they have a post-treatment living condition that they could 1
potentially exceed, a member of the public could receive more than the 500 millirem, then they 2
should not be releasing them from their control.
3 COMMISSIONER BARAN: Let me just ask one quick one. I don't know how 4
quick it is but I'll just ask one more question.
5 The 500 millirem regulatory limit for patient release is 5 times higher than the 6
general dose limit of 100 millirem to members of the public from other sources of radiation.
7 What's the basis for that differential?
8 Why is there a higher limit in this case than for all other types of sources? Have 9
ICRP or NCRP supported a 500 millirem dose limit for members of the public in the context of 10 patients treated with iodine-131?
11 MS. DIMMICK: So, ICRP and NCRP have in their documents, their standards, 12 a 100 millirem public dose limit. However, they also describe or provide for a different limit for 13 the family members or caregivers of the patient.
14 So, for NCRP that's 500 millirem and for ICRP they use some conditional 15 constraints so it could be higher than 100 millirem.
16 So, with that said, again, with our regulations in a situation where a patient could 17 exceed 100 millirem, they are to be provided written instructions on how to keep their exposures 18 as low as reasonably achievable.
19 So, that's a control that we have in our regulations to further ensure that patients 20 will keep exposures ALARA with those written instructions.
21 So, we're not completely dissimilar from ICRP or NCRP in that regard because 22 they have separate limits for the public, family caregivers, and then also women and children.
23 Whereas, our patient release limits are for all members of the public, to include the family 24
36 members.
1 COMMISSIONER BARAN: Thank you.
2 CHAIRMAN SVINICKI: Thank you, Commissioner. Commissioner Caputo?
3 COMMISSIONER CAPUTO: Good morning, I would just like to add my 4
congratulations to Steve. It's a distinguished career, there are I think two main ways to approach 5
retirement and that is, gee, what am I going to do, or, gee, what am I not going to do.
6 Considering your distinguished career, I'm sure you're in that second category 7
and I encourage you to embrace it on behalf of the rest of us, who will be here plugging on after 8
your departure.
9 MR. WEST: Thank you.
10 COMMISSIONER CAPUTO: Kevin, I think I'd like to start with you and maybe 11 Lisa.
12 There was a recent assessment done on safe use of Yttrium-90 -- maybe Dr.
13 Tapp as well -- which included a trend analysis for Yttrium-90 medical events for a ten-year period.
14 And this resulted in development of an Information Notice.
15 Can you just help me understand how do you make a decision whether to 16 conduct this kind of a trend analysis, how many events do you look for, is there a process for 17 discerning what triggers this kind of analysis.
18 And then once you have that analysis, what's the framework for making a 19 decision to issue an Information Notice?
20 MR. WILLIAMS: So, I do think that question is better answered by Dr. Tapp.
21 COMMISSIONER CAPUTO: Sure.
22 DR. TAPP: Thanks, Kevin. We do have a process to trend medical events.
23 The NRC Staff evaluates medical events on an annual basis, as well as the ACMUI does their 24
37 own separate analysis on an annual basis.
1 With that trending, we look at past events and look at the number going up.
2 For Information Notices, that's a little bit more when we notice something that we believe should 3
be spread, something occurred that we believe could be prevented and maybe not other 4
individuals aware of.
5 So, we presented four Information Notices at the MBIG event where there was 6
a patient that was contaminated. That was something new that we've never seen before and 7
was significant so we issued an Information Notice on that one to shed awareness to other 8
licensees to be aware.
9 But the Yttrium-90 Information Notice, that was found and recommended from 10 our ACMUI trending review. So, when they reviewed they noticed system events of a similar 11 nature and they recommended we issue this so other licensees were aware and could consider 12 things to prevent those type of events.
13 COMMISSIONER CAPUTO: So, with that Information Notice out there, as I 14 understand it I think it's fairly recent, how long until you'll have a sense for whether or not that 15 Information Notice actually addresses the situation and improves the safety?
16 Are you tracking that? Do we have metrics? We're sort of monitoring?
17 DR. TAPP: We do not have quantitative metrics but again, we will continue to 18 look on an annual basis and track the events as well as we attend society meetings and discuss 19 it with the manufacturers when we see events.
20 COMMISSIONER CAPUTO: Okay, so it's adequate to just continue tracking 21 it through the normal approach at this time.
22 So, this may be Lisa again, with regards to emerging medical technologies, is 23 there anything we can do to improve transparency for applicants on the status of their review?
24
38 Maybe is it feasible to give them a time estimate for their review?
1 Is it possible to maybe have some schedule and milestones like we do in other 2
parts of the Agency for licensing reviews?
3 MS. DIMMICK: So, as we're developing or implementing our new process we 4
can be aware of the milestones and metrics for developing the guidance. So, that's something 5
that we can consider or include in developing our process, or our new process, for reviewing 6
emerging medical technologies.
7 Typically, the technologies are either already just approved by the FDA or still 8
undergoing a review by the FDA as well.
9 And so there will be alignment or we try to time things so that we are ready at 10 the same time the FDA is with their approval of a new technology.
11 COMMISSIONER CAPUTO: Okay, good, that rolls right into my next question.
12 Given the new process and Dr. Tapp mentioned the evolving medical landscape 13 and increasing applications for emerging technologies, how much of an increase are we seeing 14 here? And how do you monitor that?
15 Is it enough to sort of watch the progress of new technologies through the FDA?
16 Does that give us enough time, like you said, to actually stay on track? Or are we going to face 17 some challenges if there's some sort of steep ramp?
18 DR. TAPP: I think the first question you said is how much of an increase and 19 right now we're keeping an eye on about 15 medical devices and then several 20 radiopharmaceuticals. That is a large increase from the past.
21 COMMISSIONER CAPUTO: That's a faster pace than we've seen in the past?
22 DR. TAPP: That is a faster pace. One thing, though, is we don't expect them 23 all to come out at the same time. Medical is a complex landscape and sometimes it's hard to 24
39 predict what is going to make it into the market.
1 With the FDA, there is some limitations with their ability to tell us about a device 2
that's coming to them at the beginning. So, we have changed our workings with the FDA and 3
they are alerting the manufacturer about our process and about the 35.1000 reviews.
4 But they cannot tell us themselves about a new device so they are 5
recommending them to contact us or be able to talk to us, but because of their restrictions they 6
cannot tell us about devices.
7 COMMISSIONER CAPUTO: Okay, so that sounds like it's probably in the vein 8
of business proprietary.
9 Given that we're working on an MOU with the FDA, is there room to address 10 that in our MOU to be able to have those communications directly?
11 MR. WILLIAMS: So, one of the things that we've been doing is we recognized 12 that's a challenge for us so we've been working or partnering with FDA to figure out how best to 13 share information.
14 Most recently, we were going to have a public meeting where we talk with 15 external stakeholders, make them aware of the challenges that are there.
16 But we're also looking at forming a Working Group with FDA to figure out how 17 best do we share information so that we stay ahead of these things?
18 And we can do that under the existing MOU. We don't need to revise it for that.
19 COMMISSIONER CAPUTO: Looks like you got a lifeline.
20 DR. SHELDON: Hi, I'm Dr. Murray Sheldon, I'm from the FDA Center for 21 Devices and Radiological Health and I'll be speaking on the next panel. But to address this 22 particular issue there are some things that I do want to be sure that you are aware of.
23 First of all, of course it's been understood when a manufacturer comes to us to 24
40 review any of their products, that remains confidential. And so we cannot be reporting to you 1
those issues.
2 But we've also had very similar problems with patient access to innovative new 3
medical devices because, in general, patient access also requires coverage and reimbursement 4
generally by either private payers or CMS.
5 And so in order to deal with some of those issues, we've actually created a 6
program with CMS that enables us to look at the data that's being developed in parallel 7
simultaneously.
8 It's called our Parallel Review Program, which also began with an MOU and has 9
been currently in place since 2016. I run that out of my innovation group. So, I wanted to make 10 you aware of that, that there are ways to do that, but I also wanted to make you aware of one 11 additional factor.
12 There's a new pathway, at least in the Devices Center, called the new 13 breakthrough devices program. And with that, these are for very specific life-threatening or 14 irreversibly debilitating conditions for which there's an unmet need for which we really want to 15 move a product to patients as quickly as possible.
16 We may approve that product to go onto the market with greater uncertainty 17 that we might otherwise have in the pre-market and capture the residual data in the post-market, 18 generally with registries or with other methodologies from the real world.
19 When we release these products with greater uncertainty, this makes it much 20 more difficult for payers to be able to provide coverage and reimbursement.
21 So, we've again worked with CMS and a few private payers and recently CMS 22 has instituted a program to allow new technology add-on payments for any medical device that 23 carries an FDA breakthrough designation.
24
41 COMMISSIONER CAPUTO: Thank you.
1 DR. SHELDON: So, I just wanted to be sure that you understood that there 2
are very close similarities.
3 COMMISSIONER CAPUTO: Thank you. I have one last question maybe for 4
Steven, Kevin, and Lisa, maybe the whole panel.
5 Just a very broad question, you have taken a situation where you're addressing 6
evolving technologies, new technologies perhaps, an increased pace of reviews. This isn't 7
dissimilar from what we are also seeing in the area of advanced reactors.
8 Is there anything in the nature of how you have approached this or the way that 9
you have developed processes that there might be insights to share with the advanced reactors 10 group and see if there's some cross-pollination in terms of how to approach this situation?
11 MR. WILLIAMS: So, I think right now we're in the infancy stage of it but we've 12 looked at our program, looked at our processes to see how we can streamline and what can we 13 learn from it.
14 And I think we need a little more runtime in order to be able to share what we've 15 looked at effectively or what worked for us.
16 We do recognize that some of the things that we've done in the 35.1000 area 17 has paid big dividends for us in terms of being able to pick a technology or take a modality and 18 be able to move that forward.
19 But I think right now we're analyzing and evaluating how can we streamline our 20 processes?
21 MR. WEST: I know we're running out of time but I agree with Kevin, although 22 I'll take a step further and say we should be sharing both ways.
23 Thanks for the question, it was a great question, but I think there is things we 24
42 could be learning, even at an early stage, from this program into theirs and theirs into this one.
1 So, thanks for that.
2 COMMISSIONER CAPUTO: Thank you.
3 CHAIRMAN SVINICKI: Thank you, Commissioner. Next we'll hear from 4
Commissioner Wright.
5 COMMISSIONER WRIGHT: Thank you so much and thank you for your 6
presentations. You covered a broad range of stuff. This is really a fun meeting for me, I really 7
enjoy this a lot.
8 I really appreciate also the preparation and all that you put into it. And Steve, 9
congratulations on your retirement, you're a very kind soul, you've been very helpful to me and to 10 my staff.
11 You're observant and you'll speak when you need to speak but I've noticed that 12 you're just a genuinely nice man, and I appreciate the way that you've handled yourself at the 13 Commission in the time I've been able to interact with you.
14 I wish you the best and I also hope that you don't need any of this stuff.
15 MR. WEST: Thank you very much, I really appreciate that.
16 COMMISSIONER WRIGHT: So, you know I'm a colon cancer survivor myself 17 and I'm kind of a testament to the power of innovation and to new technology in this field.
18 And everything I've heard, not just in the area of colon cancer, is just very 19 impressive. I've been in the colon cancer part and I knew about the photo pill and I wished that 20 I could have done it.
But by the way Chairman, I'm a good company man and I 21 had my colonoscopy on Martin Luther King Day so that I could be back at work the next day. But 22 I wanted to ask you about the pill real quick.
23 It's not something that's going to be used for everybody in every situation 24
43 because if you're a Crohn's or if you're some other area where you might have a blockage, that's 1
not going to be something they can use.
2 Is that right?
3 DR. TAPP: Yes, that's not something that we look at, per se, for the radiation 4
safety aspect but the manufacturer is marketing specifically to a certain section of patients.
5 When I look at their website, they market towards people who could normally 6
receive a colonoscopy but don't want to because of the prep for colonoscopy.
7 COMMISSIONER WRIGHT: I hear that. I want to get into the patient release 8
area. Commissioner Baran brought up a couple of things and I'm going to set the table just a little 9
bit, just because of concerns in other areas.
10 For example, to stay in the area of colonoscopies. So, when the Affordable 11 Care Act was passed many years back, there was a loophole that was missed. In private pay 12 insurance you would go in and have a colonoscopy.
13 It was a preventative procedure and you're co-paid and you're out. If they 14 found polyps, no big deal, you're done.
15 If you were on Medicare and you went in, up until I think they just fixed it maybe 16 at the end of the year, I think. If you went in as a Medicare patient and you went under thinking 17 you were preventative and you woke up and they found polyps, it became a diagnostic and it 18 charged you maybe $200 a polyp.
19 So, you were waking up with an $800 bill, something like that, so it was actually 20 discouraging people from going to get a colonoscopy. Doing just the opposite of what you really 21 wanted it to do.
22 So, I want to focus a little bit on the insurance part and that's where I'm coming 23 from. In patient release, are these therapies that we're talking about usually insurance-covered?
24
44 Would that be the case or no?
1 MS. DIMMICK: The iodine therapy is a traditional therapy, it would be covered 2
by insurance, the cost of the therapy.
3 COMMISSIONER WRIGHT: So, if we were to change our regulations to 4
require, say, in-hospital treatment so the patient had to stay in the hospital, would this be 5
something where an unintended consequence would be maybe the insurance company is not 6
covering something?
7 Because right now it's a doctor's choice, it would be if a doctor is working with 8
a patient and says I think you'd probably be better off, you've got somebody driving you home so 9
you're going to expose them, or you're at home and you've got too many people there.
10 I can understand that being a decision between a doctor and a patient. If we 11 change that, are we causing a problem potentially that might need some other solution before 12 something like that even was considered?
13 MS. DIMMICK: So, it's difficult to speculate if we changed our regulatory 14 requirement such that the patient could not be released, if that would then -- then what that would 15 do for an insurance company, if an insurance company would pay or not pay for that 16 hospitalization, that's information we don't have.
17 COMMISSIONER WRIGHT: Would that be something we would want to know 18 maybe? I'm just asking the question. I'm thinking just as open as I can, and transparent about 19 it.
20 And quite honestly, the next panel can address it too when it gets to my turn to 21 question.
22 MS. DIMMICK: Our current requirements do not preclude hospitalization.
23 Again, if the physician isn't confident the patient can meet the release 24
45 instructions or comply with them, then the patient should not be released outside of their control.
1 DR. TAPP: If I can add, during the evaluation that we did, we had physicians 2
comment to us that if a patient needed to stay in a hospital, they could work with insurances and 3
they get covered.
4 Insurance is a very complex world, it may not happen in every situation but 5
doctors did know to deal with insurance and in medical need they could get insurance to cover 6
hospital stays after radioiodine surgeries, radioiodine treatments.
7 COMMISSIONER WRIGHT: Hopefully. Thank you for that, I know it's 8
probably not something that you expected but I was like, the minute you make it mandatory then 9
we may cause some problems, and I just wanted to see to make sure we think through some of 10 that stuff.
11 Katie, and I guess maybe Lisa too, maybe you might want to -- maybe even 12 you. So, over the past year and a half, I've had the pleasure to go to several medical licensees 13 and talk with different interest groups and stuff in the medical community.
14 And one of the things I've heard several times, especially as it relates to the 15 GammaPods, the Gamma Knife and all that, is that doctors, some of them, a brain surgeon in 16 particular, feel like the requirement for a physical presence encroaches on their ability to practice 17 medicine.
18 Because these patients are sick and the ones that they're wanting to see are as 19 sick or sicker so they feel like they're being taken away from their ability to practice medicine with 20 their other patients while they have to be there to watch this procedure.
21 I'd like to get your thoughts about this and I was curious as to whether there are 22 any plans to re-look at the requirements for the physical presence when you update Part 35.
23 DR. TAPP: When we look at the advanced rule, we will look at physical 24
46 presence. I should note that when we do 35.1000 reviews for the new Gamma stereotactic 1
radiosurgery units, we do look at physical presence because of the new engineering safety 2
features.
3 The last three GSR units that we have licensing guidance for, the Icon 4
Perfection and GammaPod, we did modify the physical presence requirement.
5 In the regulation it requires you authorize user to be present during the duration 6
of the treatment, now it can be the authorized user to be the initiation and then another physician 7
can come and be there instead of the authorized user for the duration of treatment.
8 The reason that we have a physician present is due to the high dose rates in 9
the gamma stereotactic units using a source because it can't be turned off like an external beam.
10 And if there's a medical need to assess, you have to look at patient dose versus 11 medical need, that is a decision by the physician sometimes so that's why the physical presence 12 requirement is still there with the new systems.
13 COMMISSIONER WRIGHT: Okay, and I just have a minute or so left, and I'm 14 not going to take it to ask any more questions.
15 But I do want to make sure that I let you know and anybody who's listening that 16 where I've been going and the people that have been coming to see me and drop by some 17 periodicals and things like that, they have nothing but amazing things to say about what's 18 happening in NMSS.
19 And I shared that with John Lubinski the other day, I shared it with Margie as 20 well, and I wanted to share it with you.
21 So, congratulations on what you're doing and how you're approaching the 22 transformation and innovation and just looking at things. It's being noticed not just inside the 23 building but outside as well.
24
47 CHAIRMAN SVINICKI: I know we're hard up against the break, which is 1
always keenly desired by everybody in the room, but I feel I want to ask one question so I'll allow 2
anyone to ask a quick one question after I do this.
3 But just as a point of clarification, given the division between our regulation in 4
that we are not the regulatory agency for the practice of medicine on these techniques broadly, is 5
it a correct statement that to structure our regulations to say this radiopharmaceutical in this 6
application must always be inpatient, would that be outside the bounds of a decision?
7 No matter the radiological dose, it just has to be inpatient? My understanding 8
is that would be immediately subject to challenges outside our regulatory scope.
9 Can someone verbally answer that?
10 MS. DIMMICK: I'll answer that. Yes, I believe that would be outside the scope 11 of our swim lane.
12 CHAIRMAN SVINICKI: Okay, and I think that Dr. Tapp kind of said that in 13 terms of looking at the radiological aspects of these treatments and radiopharmaceuticals.
14 But speaking of swim lanes, which is my term of the day, we have a swim lane 15 here so there are things that are definitely outside that swim lane. Does anyone else want to --
16 yes?
17 COMMISSIONER BARAN: Well, just a follow-up on that. It would be a 18 different question if the standard were if a patient release had the potential to dose people, 19 members of the public or family members at a certain level, that would require inpatient treatment.
20 Because then we're dealing with a radiological issue.
21 CHAIRMAN SVINICKI: Yes, I agree with that. Thank you for making that 22 distinction. Okay, anyone?
23 COMMISSIONER CAPUTO: I guess I'd just like to sort of follow up to both of 24
48 those questions with just the statement that it really is a balance here because if the release 1
criteria are more extreme, might that also serve as a disincentive for some people to actually seek 2
the treatment that they may need medically because of the situation that that would provide in 3
terms of aftercare?
4 MS. DIMMICK: So, we believe that the current regulation adequately balances 5
patient safety, public safety, and patient treatment to help medical treatment for patients. In our 6
regulations our current requirements adequately balance those things.
7 COMMISSIONER CAPUTO: Thank you.
8 COMMISSIONER WRIGHT: And I want to thank the last two comments 9
because that's where I was going with the Affordable Care Act thing with not being able to come 10 in because the diagnostic would cause that issue with a patient.
11 I'm not coming in because it's going to cost me money. So, thank you for your 12 question and for your answer.
13 CHAIRMAN SVINICKI: Okay, thank you all and we will take a break now until 14 10.35 a.m. Thank you.
15 (Whereupon, the above-entitled matter went off the record at 10:28 a.m. and 16 resumed at 10:37 a.m.)
17 CHAIRMAN SVINICKI: Thank you, everyone, for taking your seats and I think 18 we will shortly be joined by one additional presenter on this panel but in the order of recognition I 19 was going to say he's not going until the second half of this panel so we will go ahead and start 20 again.
21 Now we will hear a set of perspectives on some of the topics that we just 22 discussed with the NRC Staff but potentially other topics that the presenters will raise. And we 23 will begin the presentations on this panel.
24
49 I'll just go in order that we've published them here on the notice, the Public 1
Notice, but we'll begin with Dr. Murray Sheldon, who gave us a little bit of a teaser about topics 2
generally.
3 But he is from the U.S. Food and Drug Administration, he's the Associate 4
Director for Technology and Innovation of the Center for Devices and Radiological Health.
5 So, Dr. Sheldon, please proceed.
6 DR. SHELDON: I thank you very much for inviting me here, it's been a 7
pleasure to come here. I wanted to preface my remarks by letting folks know that I am not a 8
subject-matter expert in any radioisotope pharmaceuticals nor radiation-emitting devices.
9 My background is that of a cardiac surgeon/medical device developer, but I 10 have run several innovation programs at the Center for Devices and I will tell you about what 11 we're doing and hopefully it might be helpful to you.
12 Next slide. What we do at the FDA relates to a mission which is to promote 13 and protect public health, but our vision states that patients in the United States shall have access 14 to high-quality, safe, and effective medical products of public health importance.
15 First in the world, we don't say that because it's a competition but it is an 16 aspirational goal and it's measurable.
17 However, we have found that in the past ten years or maybe a little bit longer, 18 U.S. patients don't always have timely access to life-saving and supporting medical devices.
19 And one of the big drivers for this has been the cost and time to bring these 20 devices to patients and medical manufacturers, and venture capitalists who support them have 21 often taken their products outside of the United States. And we felt this was a considerable 22 problem and we wanted to do something about it.
23 Next slide. To demonstrate some of the issues, of course, in 2008 you can see 24
50 when the peak began to drop. With the recession the startup communities diminished quite a bit 1
but unfortunately, even until 2012, 2013 it did not recover.
2 Next slide. Josh Makower from the Stanford Biodesign published his report in 3
2010 about the same issue.
4 Next slide, that when a company either took the product to the United States or 5
to outside the United States -- oh, go back one, yes, perfect -- there was a significant gap of 6
sometimes as long as ten years but often usually three to four years, and often $10 million to $12 7
million to bring a device through the U.S. regulatory systems as opposed to those outside the 8
United States. And this was a critical driver.
9 As a matter of fact, some of the newest innovations in cardiac care for 10 percutaneous heart valves, the United States was the 46th country in the world to approve those 11 valves, and that had a lot of personal consequences to people.
12 We really needed to do something about that so our Center Director -- next slide 13
-- understood about the issues and needed to do a few things about it, and I'm going to mention 14 some of the activities that we've done.
15 This is a very, very brief overview but one of the approaches, he created a 16 position that I'm currently in, the Associate Directorship for Innovation. And we ran an 17 entrepreneurs and residents program, the first one was in 2011.
18 It was time-limited, six months, we brought in outside stakeholders, often critics, 19 and matched them up with our staff in order to really have them share a lot of information, have 20 them thinking about things in a different way.
21 And the goal was really to create transformational change if we could. One of 22 the first things they did was to create a different pathway altogether called the Expedited Access 23 Pathway.
24
51 That eventually led to the breakthrough devices program. We did this actually 1
through a pilot so we would encourage a lot of pilots in these areas to understand things better.
2 Next slide. In 2011 the National Venture Capital Association put out their 3
report of what are the reasons that venture capitalists would take their money outside the United 4
States.
5 And 70 percent of them included these areas, regulatory challenges, 6
reimbursement challenges, and clinical trial cost, as I mentioned before.
7 Next slide. So, the following year we set up a second entrepreneurs residents 8
program to deal with these three issues and we really spent most of the time developing problem 9
statements.
10 We would refrain from putting out solutions too early. As a matter of fact, we 11 had a fine of a dollar for anybody who suggested a solution before the problem statement was 12 really well understood.
13 But it was incredibly important to go down to the drivers to really understand if 14 we made a change to A, would it affect the problem that we're trying to solve? And sometimes 15 it wouldn't and, of course, we needed to recognize the unintended consequences.
16 Next slide. So, for these three challenges we started the clinical trials program 17 in our Office of Device Evaluation and we instituted a new early feasibility program, adaptive trials, 18 Bayesian design and we brought in patients to get patient perspectives on what they were doing.
19 We also set up a payer communication taskforce, which is the taskforce that I 20 run. I mentioned the Parallel Review Program, we have multiple programs with payers as well 21 so we interact with folks outside of our expertise and work with them directly to address the 22 specific issue of patient access to innovative medical devices.
23 And we also try to balance the pre-market with the post-market data evaluation.
24
52 We're currently in the process of developing a national program called NEST, the National 1
Evaluation System for Health Technology, that enables us to try to capture in real time patient 2
experience with the use of medical devices in the real world.
3 Most clinical trials on which most medical devices had been approved are based 4
on randomized clinical trials with a lot of inclusion and exclusion criteria that just did not reflect 5
what we would eventually see once a product was listed for open use.
6 And so by doing this sort of approach, first of all we get a broader knowledge 7
and we're able to get some of these products onto the market a lot sooner, which is helpful to 8
patients.
9 Next slide. And we maintain our practices with continuous innovation. We 10 believe that the definition of innovation is that change is the only constant. We know things will 11 change and the only way to help create that change in the right direction is to be a part of that 12 change.
13 My group with innovation focuses on both internal and external. Our internal 14 innovation is mostly to be able to enable our staff to learn the challenges that medical device 15 developers face.
16 We have an incredibly brilliant staff as you do here. Most of our staff our 17 Ph.D.s, engineers, and other types of scientists but they often have not actually developed 18 medical devices themselves, nor have they practiced medicine.
19 So, to give them that kind of exposure we send them to accelerators and 20 incubators, and we also send them to meet with payers so they understand those challenges.
21 And we've also worked with public-private partnerships.
22 We believe this is a great opportunity to work in one particular area where 23 there's been a lack of innovation, the kidney space.
24
53 A public-private partnership between the FDA and American Society of 1
Nephrology, it's called the Kidney Health Initiative, and recently KidneyX with HHS and the 2
American Society of Nephrology, has been developed to bring innovative products for renal 3
replacement therapy.
4 Thank you very much for allowing me this opportunity to be here and to present 5
this information.
6 CHAIRMAN SVINICKI: Thank you very much, Dr. Sheldon, I'm sure Members 7
of the Commission all have questions so we'll keep all of our questions until all presentations are 8
heard.
9 The next presentation will come from Mr. Terry Derstine, who is the Chair of the 10 Organization of Agreement States. Please proceed.
11 MR. DERSTINE: Hello, my name is Terry Derstine, current Chair of the 12 Organization of Agreement States and the Radiation Protection Program, Manager for 13 Pennsylvania Department of Environmental Protection.
14 Thank you for this opportunity to share and discuss some emerging issues 15 regarding the regulation of the medical uses of radioactive material.
16 Recently, I have witnessed firsthand the development of two emerging 17 challenges concerning the licensing and inspection of radioactive material used in medicine. The 18 first is a perceptible increase in -- this is my term -- high-dose systemic liquid radiation therapy.
19 And the other item I'd like to discuss is the next generation of technitium-99m 20 generators. Perhaps most pressing due to its patient-facing nature is the increasing use of high-21 dose systemic liquid radiation therapy.
22 This cancer treatment consists of a radioactive substance delivered 23 intravenously, common over the span of several hours. The most concerning therapies are 24
54 MIBG and Iomab-B. Typically, these therapies use radioactive iodine-131.
1 Now, the radioisotope iodine-131 is used every day in nuclear medicine 2
departments worldwide primarily for the treatment of hyperthyroidism and thyroid cancer, and is 3
typically delivered in the form of a capsule.
4 Lower doses of liquid radioactive material have also been a longstanding staple 5
of nuclear medicine primarily for diagnostic studies.
6 As nuclear medicine staff are therefore familiar in handling these lower doses 7
of isotopes, it is quite common for facilities that perform some of these newer radiation therapies 8
to task the experienced technicians with delivering the high-dose treatment.
9 Without proper respect for the differences between these types of treatments, 10 complacency may develop. Understandably, there are unique safety concerns for high-dose 11 therapies compared to the typical uses of radioisotopes.
12 Most pressing among these is the risk of contamination. The duration of one 13 high-dose systemic liquid radiation therapy infusion can last several hours. Over such a length 14 of time, the risk of contamination spills because much more serious.
15 Furthermore, after the infusion, the radiation emitted from the patient in excreta 16 can provide some challenges, especially when using radioactive iodine. Again, this greatly 17 increases the risk of external contamination.
18 Another pressing concern with high-dose therapy is the detection of 19 contamination. Due to the large amounts of radioactive material in the patient's body, the 20 background radiation becomes very high, thus hindering the effectiveness of hand-held radiation 21 detectors.
22 This makes detection of any small leaks of radioactive material especially 23 difficult, compounding the possible danger of mismanagement.
24
55 And based on the number of reported events where treatment of high-dose 1
systemic liquid radiation resulted in contamination and even radiation-induced skin injuries, new 2
safety procedures should be emphasized for each treatment.
3 Facilities should strongly consider developing training and procedures to 4
specifically address this challenge, such as development of patient-specific decontamination 5
procedures, proactively looking for contamination on linens, gowns, chucks, carts, and flooring 6
and the use of beta radiation measurement devices in order to detect contamination.
7 There are also several other concepts that regulators may want to discuss with 8
licensees, development of fluid management procedure and employee familiarity with the infusion 9
system that would limit potential spills of radioactive material.
10 The establishment of a multidisciplinary committee to review and update 11 associated policies while conducting periodic drills on responding to a patient contamination 12 incident would also ensure appropriate measures are taken to preserve the safety of both patients 13 and healthcare professionals.
14 This list is by no means complete, but simply by addressing the differences in 15 developing some basic procedures specifically for high-dose systemic liquid radiation therapy all 16 staff will be reminded of the pitfalls associated with it and the potential for complacency can be 17 staved.
18 I would also like to discuss the next generation of technitium-99m generator 19 systems. The decay product of molybdenum-99, technitium-99m is used in about 80 percent of 20 all nuclear medicine procedures.
21 The United States, with over 40,000 patients imaged per day uses about 50 22 percent of the world's supply of technitium-99m. And although nuclear medicine is not growing 23 rapidly, it is still considered a pillar of modern medical diagnostics.
24
56 For decades the U.S. supply of molybdenum-99 has relied on solely on aging 1
nuclear reactors that are located outside of the United States. In part due to their age, these 2
uranium-fueled reactors have experienced an increased frequent of unplanned outages in recent 3
years.
4 Some of these outages have caused critical global molybdenum-99 supply 5
shortages, resulting in delays in patient treatment.
6 The next generation of technitium-99m generators have been designed to 7
create a redundant, reliable, commercial molybdenum-99 supply produced domestically and 8
without reliance on highly enriched uranium.
9 Even though the technitium-99m produced in these newer-generation 10 generators is interchangeable with the technitium-99m produced with current generators, these 11 next-generation generators are proving to be vastly different, relying less on human interaction 12 and incorporating automation in the production of technitium-99m.
13 The molybdenum in this system is not derived from the fission of uranium and 14 requires different processes to isolate and concentrate the technitium-99m different than existing 15 generators.
16 These newer devices are designed as closed-system to contain, move, and 17 shield all molybdenum-99 during a computer-driven process of isolating technitium-99m, a 18 significant change from the current technitium-99m generators.
19 Currently, there is only one manufacturer with FDA approval to provide the next-20 generation system, but this one system and the increased complexity associated with it has 21 created the need for licensing guidance.
22 This guidance will provide applicants with acceptable means of satisfying 23 requirements for a license as well as helping regulators understand and regulate the associated 24
57 complexities.
1 And there appear to be three more U.S.-based commercial technetium-99m 2
generating systems in development.
3 Each one may be just as unique and different from the others, requiring the 4
continued partnership of the U.S. Nuclear Regulatory Commission, the Organization of 5
Agreement States, and the Conference of Radiation Control Program Directors to ensure the safe 6
use of these next-generation of technitium-99m generators.
7 These developments prove that the role of radiation in medicine is developing 8
just as quickly as any other time during my career. It is imperative that we provide rational, 9
effective guidance to those on the forefront of radioactive medicine.
10 Thank you.
11 CHAIRMAN SVINICKI: Thank you very much. Next on the panel, we will hear 12 from Dr. Thomas Eichler, who is speaking today in the capacity of current President of the 13 American Society for Radiation Oncology.
14 Dr. Eichler, please proceed.
15 DR. EICHLER: Good morning, everybody, thank you for inviting me here 16 today.
17 As duly noted, I am Dr. Thomas Eichler, I'm a board-certified radiation 18 oncologist at the Virginia Commonwealth University Massey Cancer Center in Richmond, Virginia, 19 and also the President of the American Society for Radiation Oncology, or ASTRO.
20 ASTRO is the largest radiation oncology professional society in the world with 21 over 10,000 members, who specialized in treating patients with a variety of radiation therapy 22 techniques. And on behalf of ASTRO we thank you for your commitment to stakeholder 23 engagement and appreciate the opportunity to collaborate with the NRC.
24
58 If I can begin by commenting on the Staff's recent recommendations regarding 1
training and experience for radiopharmaceuticals, the proposal gives us cause for concern.
2 We continue to believe that there is no need to pursue additional rulemaking 3
insofar as current regulations are appropriate and protect the safety of patients, the public, and 4
practitioners.
5 If, however, the Commission ultimately decides to proceed with rulemaking, we 6
believe the board recognition criteria must ensure that existing requirements are maintained and 7
that any criteria for additional boards is equivalent to existing requirements.
8 Let's focus now on transformation and innovation opportunities from the 9
perspective of the medical community and begin by highlighting a 2017 Advisory Committee on 10 the Medical Uses of Isotopes, or ACMUI report, entitled, Medical Event Reporting and Impact on 11 Medical Licensee Patient Safety Culture.
12 In its report, the ACMUI made two important observations. First, the NRC's 13 medical event reporting criteria are set at conservative levels, including events that rarely cause 14 patient harm.
15 When compared to other criteria set by the Joint Commission, the Food and 16 Drug Administration, and the centers for Medicare and Medicaid services. This lack of 17 consistency in definitions leads to varying levels of response to a patient safety event and causes 18 confusion in the medical community.
19 Second, despite the recognition that the medical events rarely cause patient 20 harm, a licensee is required to notify the NRC no later than the next calendar day after discovery.
21 After the notification, an inspection occurs looking for violations as the cause of 22 the event.
23 In other words, the NRC's conservative medical event reporting requirements 24
59 are inconsistent with other regulatory agency requirements as well as current radiation oncology 1
processes of care, and do not encourage a culture of safety.
2 Based on these observations as well as the need to consider other ways 3
medical events could be evaluated, the ACMI made the following recommendations.
4 First, the NRC should establish a program allowing a medical use licensee to 5
evaluate medical events as described in current regulations with an approved patient safety 6
program.
7 The ACMUI describes an approved patient safety program as one or more of 8
the following: a safety program that reports medical events to a patient safety organization, or 9
PSO, which has medical expertise and medical use as defined in Part 35, a safety program 10 evaluated by a CMS-approved accrediting organization, or a safety program which is established 11 as part of accreditation by a professional organization for medical use as defined in Part 35.
12 13 Number two, NRC licensees within an NRC-approved patient safety program 14 will continue to report medical events as required but that the NRC not include these events in 15 the event notification report, or if this is not possible, posting them anonymously.
16 In addition, the NRC should not conduct a reactor inspection unless the event 17 results in or will result in death, unintended permanent harm, or unintended significant temporary 18 harm for which medical intervention is required.
19 Instead, the licensee will write a detailed report describing the event and 20 corrective action taken, which will remain available at the next NRC inspection. The NRC will 21 then develop inspection procedures to support a test of this program.
22 Third, the NRC should test this program with various medical practice sizes and 23 locations, evaluating the medical event reports with the ACMUI.
24
60 And finally, after completion of the test year, the NRC should consider opening 1
the program to all NRC medical use licensees who request approval of their patient safety 2
program and to Agreement States who request to implement the program with their medical 3
licensees.
4 ASTRO supports the recommendations offered by the ACMUI to promote a 5
culture of safety for medical licensees.
6 These progressive recommendations align with ASTRO's commitment to 7
improving quality and safety in radiation oncology and support the NRC's Safety Culture Policy 8
Statement while at the same time maintaining the NRC's regulatory authority to protect patients 9
during the medical use of byproduct materials.
10 We believe that both Astro's Accreditation Program for Excellence, or APex, 11 and the Radiation Oncology Incident Learning System, or ROILS, fulfil both the spirit and the 12 requirements set forth by the ACMUI.
13 APex was launched in 2015 with the mission to objectively assess and accredit 14 radiation oncology practices by systematically reviewing the policies, procedures, personnel, and 15 equipment to ensure the delivery of safe, high-quality patient care.
16 APex standards are centered on five fundamentals: process of care, the 17 radiation oncology team, safety, quality improvement and assurance, and patient-centered care.
18 This is a multi-step process that begins with a thorough program self-19 assessment, document upload of policies and procedures, a robust medical record review, and 20 finally, a site visit by a trained APex accreditation team.
21 Over 150 facilities have been accredited to date. The culture of safety 22 standards specifically requires the cultivation of a facility environment in which all team members 23 participate in assuring safety, capitalizing on opportunities to improve safety, and does not take 24
61 reprisals upon staff that report safety concerns.
1 Learning from these patient safety events and unsafe conditions, therefore, 2
becomes ingrained in the process of care. We believe that the most effective ways for facilities 3
to take action on a patient safety event is to take ownership of the corrective actions in a non-4 punitive environment.
5 We are pleased that the ACMUI has embraced this approach to safety, 6
especially with regards to medical event reporting.
7 The Radiation Oncology Incident Learning System, or ROILS on the other hand, 8
is a data collection tool devoted to reporting patient safety events from enrolled facilities, and then 9
suggesting process improvement by sharing learning in a non-punitive environment.
10 ROILS is part of the Agency for Healthcare Quality and Research, or AHRQ, 11 approved PSO, with over 500 facilities enrolled and more than 12,000 events reported, 12 approximately 300 of which involve radioactive materials.
13 Approximately 44 percent of the reported events sort of classified by users as, 14 quote, operational/process improvement, close quote, which is defined as a non-safety-event.
15 This suggests that practices are utilizing the system for more comprehensive 16 quality improvement.
17 An additional 12 percent of events are classified as therapeutic radiation 18 incidents where the radiation dose is not delivered as intended, with or without harm, with the 19 majority of those having a less than 5 percent dose deviation.
20 The culture of safety in medicine as a whole has shifted from one of blame to 21 one focused on learning, which has led to an increase in reporting. ROILS participants not only 22 identify patient safety events and near-misses, but also generate interventions to prevent a 23 recurrence and share relevant safety risks and solutions with others.
24
62 Analyzing safety events that were caught before reaching the patient and 1
addressing those faulty processes is a critical aspect of incident learning in medicine.
2 It is ASTRO's belief that the current NRC medical event reporting approach 3
does not focus sufficiently on learning and that the ACMUI recommendations holds greater 4
promise for process improvement.
5 In conclusion, we believe that the NRC could play a greater role in improving 6
the safety culture in radiation therapy by implemented the ACMUI's recommendations. Thanks 7
very much.
8 CHAIRMAN SVINICKI: Thank you, Dr. Eichler.
9 Next we'll hear from Dr. Dilsizian, who, while no stranger to the NRC through 10 his terms of service on the Advisory Committee on the Medical Uses of Isotopes, presents to us 11 today in the capacity as President of the Society of Nuclear Medicine and Molecular Imaging.
12 Dr. Dilsizian, please proceed.
13 DR. DILSIZIAN: Chairman Svinicki, Commissioners, I appreciate the 14 opportunity to speak on behalf of the Society of Nuclear Medicine and Molecular Imaging.
15 It's really an honor to be the president of such a large organization, established 16 since 1954. It's a multidisciplinary organization, physicists, radiochemists, technologists, and the 17 purpose of my presentation today is multifold.
18 One is the current pathways of obtaining AU status and the T&E 19 recommendations.
20 If I could have the next slide, please? The current pathways for certification is 21 one of the medical specialty boards recognized by the NRC or an Agreement State, which is the 22 ABNM, ABR, and American Board of Osteopathic Radiology.
23 The second option is completion of 200 hours0.00231 days <br />0.0556 hours <br />3.306878e-4 weeks <br />7.61e-5 months <br /> of classroom training and 500 24
63 hours7.291667e-4 days <br />0.0175 hours <br />1.041667e-4 weeks <br />2.39715e-5 months <br /> of supervised work experience. In ACGME, which is Accreditation Council of Graduate 1
Medical Education, declares the programs and those include nuclear medicine, diagnostic 2
radiology with 16-month nuclear medicine and nuclear radiology pathway, or radiation oncology.
3 And the third, a previous identification of as an authorized user or an NRC or 4
Agreement State license of permit.
5 Next slide, please. We thank the NRC for the opportunity to provide feedback 6
on the T&E requirements. Our main objective is to emphasize patient and public safety while 7
ensuring access to quality of care.
8 The NRC Advisory Board, of which I am a Member selected by you, rather 9
knowledgeable and selective-knowledge experienced group of physicists, physicians, scientists, 10 healthcare providers, patient advocates, have reviewed this topic.
11 And they've recommended that there is no authorized user shortage in their 12 revised report of July 2018 and strongly supported maintaining the current AU pathways. Thus, 13 there seems to be no clearly defined or compelling need to develop a new type of T&E pathway.
14 Next slide, please. Nonetheless, the SECY paper, the Commission paper 15 summary, suggests that the NRC Staff expects growth in the field of nuclear medicine and 16 uncertainties in the safety-related characteristics of emerging and future radiopharmaceuticals 17 such as energy level dose, half-lives, and necessary protocols.
18 And therefore, a less prescriptive and more performance-based approach in 19 regulating T&E would be beneficial because you could cover radiopharmaceuticals beyond those 20 currently known or in use.
21 I just want to spend a little bit of time about the word prescriptive. It seems like 22 we're talking about this a lot these days. I just want to emphasize that everything we do in 23 medicine, the entire medical and surgical training, is prescriptive.
24
64 We are required to have a number of CNE hours or grand rounds, we are 1
required to have a certain number of months of training in radiology and nuclear medicine, 2
different aspects of rotations.
3 We are required to do a number of years before we sit on the boards, we are 4
required to do a number of procedures of cardiac catheterization, cardiography.
5 And therefore, the idea that we have a prescribed 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> by experts to 6
assure that physicians in training are properly trained is not unusual and it's not against the current 7
medical practice.
8 So, as a matter of fact, in medical practice it's prescription plus certification.
9 So, I think that if the NRC is moving in the direction of perhaps the prescribed 10 hours1.157407e-4 days <br />0.00278 hours <br />1.653439e-5 weeks <br />3.805e-6 months <br /> are not enough, that we should assure that the physicians are competent, I think that it's 11 appropriate to request and additional certificational board examination, which is what medical 12 practice does.
13 In addition, increasing involvement by the medical community in determining 14 the appropriate safe criteria for radiopharmaceuticals and setting the associated T&E 15 requirements could -- this is very important and I underline that, if I could have that slide -- help 16 accommodate the increasing interest -- I like the word interest because I'm curious to know, 17 interest is not need, I would be interested but that doesn't mean I need -- of non-nuclear medicine 18 and non-radiation oncology physicians in using radiopharmaceuticals.
19 And the next sentence is very interesting. While the Staff considers 20 stakeholder concerns -- that's an interesting term, isn't it? No data.
21 ACMUI reviewed this, I don't understand what the term concern stands for 22 because there's no actual data to support that about patient access. The availability is to be 23 sufficiently used in not drive -- this is very important -- the Staffs evaluation of T&E.
24
65 Next slide, please. And so the additional recommendations that NRC sets is 1
to initiate a rulemaking to remove prescriptive T&E requirements, which I object to and I gave my 2
recommendation, and to eliminate the need for NRC review and approval of use.
3 The Staff recommended the option with required physician is certified by NRC-4 recognized or Agreement-State-recognized medical specialty board.
5 Now, that's important because there are legitimate medical specialty boards, 6
which is the American Board of Medical Subspecialties that currently exists.
7 And I guess I don't have clarification here whether any subspecialty can come 8
up with their own board certification independent of the ABMS. That's important.
9 Are we going to expect any societies or any organizations to have their own 10 certification or are you going to require the certification to be strictly under ABMS? I think that 11 needs clarification.
12 The second bullet, as policy recommended rulemaking, the NRC would revise 13 its board recognition criteria so that certification by specialty boards other than existing nuclear 14 radiation oncology boards would be an acceptable T&E pathway for the use of 15 radiopharmaceuticals.
16 The Staff's recommended rulemaking option would continue to protect public 17 health and safety, better align the NRC's T&E requirements with the medical policy statement, 18 and position the Agency for more effective and efficient regulatory decision-making with respect 19 to the expected increase in the number of complexity emerging radiopharmaceuticals.
20 So, the recommended option would also alleviate regulatory burden for the 21 NRC. I would think that the NRC should not be delegating their responsibility to others.
22 You are the experts, we are the experts, you should be defining what the 23 training is. That's what keeps everything safe in my opinion. Even though it may seem like the 24
66 estimated cost savings is $2.4 million per year for your organization.
1 Next slide. So, other important views then to consider, one, who will be training 2
the current oncology, urology, or other medical specialists?
3 And how do we ensure that the next generation of residents and fellows in these 4
areas receive competency-based training? Who's training them?
5 If currently there are no, or perhaps only a handful of, authorized users in these 6
medical specialties at the present time, how do we assure who's training who? And how are they 7
going to be board certified?
8 Expansion of medical specialty training requires ACGME review committed 9
discussion and approval in each of these medical specialties. NRC does not have jurisdiction to 10 require changes in the current medical and surgical residency or fellowship training.
11 Bullet Three, nuclear medicine, radiation oncology and diagnostic radiology with 12 16-month pathways are the only ACGME-approved training programs that have specific goals 13 and objectives pertaining to administration of radioactive material.
14 These have to be completed under the supervisional board certified physicians 15 who also have been trained in this area.
16 Next slide, please. Other important things to consider, independent of the 17 medical or surgical specialty board, the AU candidate must attest to the acquisition of 35.390 18 knowledge, topics, and skills by successfully completing a formal competency assessment with 19 continued formal periodic competency reassessment.
20 That's important. Just because you take a course once doesn't mean you've 21 captured it. We know that there has to be reassessments to maintain their limited-scope AU 22 status.
23 Bullet two, given that this type of training is not part of standardized program 24
67 requirements in these medical and surgical subspecialty areas, the question arises as to which 1
organization is best suited to actually ensure competency and safe administration of these from 2
individuals who have sought this additional training.
3 Which subspecialty board would be most qualified to certify these medical 4
specialty candidates as qualified and competent in radionuclear therapy?
5 American Board of Nuclear Medicine or the medical subspecialty boards 6
without adequate mentors or educators to cover the current required NRC requirements?
7 Undoubtedly, organizations that have the most experience and expertise in 8
these areas are nuclear medicine, diagnostic radiology, and radiation oncology.
9 Next slide, please. So, to switch topics to release of patients administered 10 radioactive material, again, we thank the NRC for the opportunity to provide feedback on the 11 patient release criteria.
The Society submitted comments to this patient guide in 12 June of 2017 and again in September 2019 following the current revision to provide licensees 13 with more detailed instructions for their patients before and after they have been administered 14 radioactive material.
15 The revision included a new section, death of a patient following 16 radiopharmaceutical or implants administration, dosage of radiopharmaceuticals that require 17 instructions and record when administered to patients who are breastfeeding an infant or child.
18 Next slide, please. SNMMI submitted specific comments related to radiation 19 monitoring of family members, breastfeeding interruption limits and guidance for families and 20 children.
21 SNMMI agrees that written and oral instructions must be provided to the patient 22 far enough in advance of treatment without compromising patient care to ensure that the patient 23 has sufficient time to determine whether or not he or she can actually comply with the instructions 24
68 to make whatever arrangements may be necessary for compliance.
1 I just want to emphasize that, at least in our practice in Maryland, we have 2
so-called occupancy factor. We go through all these questionnaires and based on the 3
occupancy factor, we determine whether to keep the patient there or not, independent of the dose.
4 We do take care of all the patient-related issues obviously and those would not 5
be as far as insurance is concerned. If we determined that's necessary, insurance will pay for it.
6 And the last point I think we have to be all aware that all of this is good but I've 7
been asking my patients where they get their information and often I would assume it would be 8
the endocrinologist who is referring, and the most common answer is YouTube.
9 So, we have to move where the patients are these days and I've highlighted 10 that in Bullet Three. We are keenly aware of the usage and impact of social media in education.
11 I think that those documents, long pages, is not the way we are educating our 12 communities these days. Accordingly, the Society will be planning to develop a video clip that 13 will be available on the SNMMI website.
14 We also learned that most people don't go to the website, they just Google it.
15 So once you Google it, there will be YouTube, hopefully one of those will be SNMMI-based, that 16 would educate the patients before and after the treatment.
17 Next slide. Regarding what's coming and what's exciting, the world is a huge, 18 exponentially growing area. We are moving from diagnostic to therapeutics in the field and we 19 are excited.
20 There are a number of new alpha-and beta-emitting targets that the FDA 21 approved, such as Radium-223 therapy for metastatic breast cancer and other cancers of bone.
22 Other alpha emitters targeting a variety of receptors including PSMA, or 23 prostate-specific membrane antigen, there's also already an FDA approved Lutetium-177, 24
69 somatostatin analog, which treats neuroendocrine tumors.
1 Lutetium-177 is also being labeled to PSMA for prostate cancer. Iodine-131 2
labeled antibodies for leukemia targeting, such as CD-33.
3 Other indications are currently in Phase 2 or 3 clinical trials, colorectal cancer, 4
Non-Hodgkin's Lymphoma, and leukemia.
5 So, it's an exciting area, it is important to make sure as the field grows that we 6
do administer this safely to patients.
7 And then the last slide is what are the potential barriers to patient access. I 8
think that the addition of new diagnostic and therapeutic isotopes to a radioactive material license 9
can be time-consuming.
10 And we do appreciate that the NRC is addressing that and facilitating that, 11 although, we do also understand there's a state-to-state variability in that process.
12 Rulemaking related to generators can cause delays such as decommissioning, 13 which you addressed with generators and isotope agent-specific training for targeted therapeutic 14 dosing patient administration, we the Society have taken that burden.
15 We are having road shows, chapters, different areas of the state as well as a 16 national meeting to make sure that currently practicing physicians are well educated, including 17 the new residents. Thank you very much for your attention.
18 CHAIRMAN SVINICKI: Thank you for that presentation.
19 The final presentation on this panel will come from Mr. Josh Mailman, who will 20 be addressing us in his capacity as the President of NorCal CarciNET Community.
21 Please proceed. Thank you very much.
22 MR. MAILMAN: Thank you.
23 That was fairly comprehensive. So, I can shorten what I'm doing a little bit and 24
70 that will be helpful.
1 Next slide, please.
2 I have a few disclosures. But, really, what I want to say is I have talked to a lot 3
of patients and medical providers in preparation for this, and I want to thank them for their time.
4 I want to thank the Commission for having me here as well. But the views here 5
that I talk about represent my own opinions.
6 Next slide, please.
7 So, at the end, I'm the actual end-user. I'm the one who gets all these things 8
at the end of it. I was diagnosed with a rare pancreatic neuroendocrine tumor in 2007. I was 9
able to find additional imaging therapies in Germany where I went for my first gallium-68 PET/CT 10 in 2008. I was also treated there before we had any clinical trials here or any active current 11 clinical trials on nuclear medicine therapy for neuroendocrine tumors. Subsequently, they've 12 been approved, which I'll talk to in a second.
13 I helped Society in the gallium-68 Working Group, the Society of Nuclear 14 Medicine, work on some INDs for gallium-68 that later got adopted as well. And I work with a 15 bunch of really great organizations for both patients, for research, and for nuclear medicine 16 therapists, practitioners around the world.
17 Next slide, please.
18 Just a quick background of NETS because many people don't know about them.
19 They are considered a rare disease because the prevalence is under 200,000. They fall under 20 the rare disease or orphan drug designation. There are about 20,000 new diagnoses a year.
21 But, because of the prevalence, because we are living longer, and due to better therapies, it is 22 the second-largest GI malignancy that is around, which is shown on that chart.
23 One of the things about neuroendocrine tumors is that we have these receptors, 24
71 somatostatin receptors, that make us the target child. While we've talked about diagnostic and 1
therapeutics, the term "theranostics" or "theranostic," depending on where you're from has been 2
used to describe this, the idea of using a diagnostic isotope to actually light up the tumor and, 3
then, replacing that using the same targeting agent, but replacing that isotope with something that 4
would cause a DNA break or do something to damage and kill the tumor, which is the idea behind 5
theranostic.
6 So, next slide, please. We've been very fortunate in the neuroendocrine tumor 7
space to have four approvals in the last four years, starting with NETSPOT, which was a 8
Gallium-68 Dotatate; followed on by lutetium; Azedra, which I think was mentioned here as well, 9
and also another indication for Gallium-68 Dotatoc in June, of neuroendocrine tumor patients.
10 This has led to an actual rapid adaptation of nuclear medicine in the 11 neuroendocrine tumor field. There are over 600 locations that currently can offer a Gallium-68 12 NETSPOT. There are over 150 locations performing about 8,000 treatments for Lu-177 Dotatate 13 in the United States last year.
14 Next slide, please. As was mentioned, there are many isotopes that are under 15 consideration that will be new to the medical field. Although I will bring this up in a second, I will 16 bring this up right now. You've talked about some coordination between the FDA and the NRC 17 as far as new isotopes, and I would also ask you to bring that up to Homeland Security as well 18 because many patients who are dosed end up going out of the country and come back and get 19 caught.
20 Recently, I introduced the Homeland Security to the FDA, so they could work 21 together, because they were unaware at Homeland how many patients were being dosed with 22 Lu-177. As a patient who has been caught several times coming back into this country, it is a 23 very exhausting pattern to go through because it is not recognized as an isotope in most of 24
72 Homeland Security's equipment and they are very unaware of these things. So, I would ask the 1
Commission to work with that.
2 Next slide, please. So, look, patients are overjoyed with availability. It's 3
something, you know, especially with the new diagnostics, with NETSPOT, it has allowed patient 4
care. About one-third of the patients have a change in management that will significantly change 5
their life arc.
6 But there's little understanding of the complexity of delivering nuclear medicine.
7 My guess is this is consistent not only with just neuroendocrine tumor patients, but other patients 8
as well.
9 Next slide, please. I want to echo Vasken's comments on this new options in 10 the era of information. This is how patients communicate. Most everyone has talked on 11 Facebook before they've actually talked to their doctor on what they have. This makes it hard 12 when someone goes to Homeland, gets caught, but it also makes it hard when people get different 13 release instructions, depending on where they are in the country, and then, they share them and 14 wonder why one thing has one set of release instructions versus another set of release 15 instructions.
16 And I'll get to this in a second, but one of the challenges, some places just cut 17 and paste an I-131 release instruction for a neuroendocrine tumor patient. And some of them, 18 as I list out here, have some really Draconian things for neuroendocrine tumor patients that are 19 completely appropriate for an I-131 patient as well.
20 We've talked about a little bit of the challenge of getting it paid for, and that is a 21 major concern, although it may not be of the Commission's purview.
22 Next slide, please. I believe there's three main areas, and actually, this is what 23 for the most part this hearing or this meeting has been about.
24
73 Next slide, please. Patient release criteria. We did send in comments to the 1
NRC regarding the patient release criteria. And one thing, although it was mentioned earlier that 2
Lu-177 is not on the Table 1, it did make it on to the breastfeeding and other tables.
3 I would ask the Committee to think about making sure that, even if a release 4
criteria is not needed because it falls below standards, that some mention of that be made in the 5
document. Because what happens is these reference documents get used. When someone 6
doesn't see it, they may do exactly what is done, which is copy and paste I-131 instructions for 7
NET patients, and that is problematic.
8 Obviously, I've also talked to friends in the thyroid communities who would really 9
like to also see more stringent release criteria or at least discussion of it, if it's required to be 10 hospitalized, because they do not feel that, while you were able to get insurance coverage for 11 most of your inpatient, but most of them are not able to get insurance coverage, this is sending 12 many people home 10 minutes after having an I-131 treatment.
13 Next slide, please. While I'm not an expert in training and education standards, 14 I would ask that the Committee consider making sure that -- first, we don't see in our community, 15 in the neuroendocrine tumor patients, an issue with the shortage of Authorized Users. As a 16 matter of fact, what we're finding is that they're gravitating towards centers of nuclear medicine 17 competency. And so, in fact, many centers that have the drug available to them are not getting 18 fully utilized because they're just going to where high-volume centers are to start out with.
19 We just want to make sure that, with any new rulemaking, that additional focus 20 is on the therapies that are happening as well, because I think a lot of the training was really when 21 there was much more in the imaging diagnostic and less about the therapeutics. And we are 22 entering an age where PSMA and other therapies will start dominating the scene as well, and 23 multiple isotopes, including the alpha isotopes, will change the safety profiles as well.
24
74 Next slide, please. Again, I want to thank the NRC for updating the guidance 1
in 2017 and 2019. I was on many of the phone calls trying to understand what these extra 2
burdens -- it looked like a clerical error for the issue of germanium and its breakthrough. And so, 3
I want to thank the Commission for taking care of that and listening to both the SNMMI and other 4
stakeholders, as well as the patient voice, in getting that out. And it's a testament that we have 5
really over 700, 600 facilities that are able to do a gallium-68 scan.
6 And with that, I'll conclude my remarks. So, thank you very much.
7 CHAIRMAN SVINICKI: Well, thank you again to each of you.
8 And I realize that our meeting format required you to cover a tremendous 9
amount of material in a short period of time, but I think you've set the table very well for the 10 Commission's questions.
11 Let me kind of just dive in, since I'll begin here.
12 Dr. Eichler, you talked about a topic that we really didn't spend much time on 13 with the NRC staff, and that was the medical event reporting criteria. I'm a longstanding member 14 of this Commission and I'll confess that I've struggled generally with the criteria, where they're set, 15 and as a result, the kinds of medical events that are reported. I acknowledge candidly -- and I 16 think it's explicit often in the reporting -- that there is no anticipated patient harm from the 17 preponderance of these events.
18 And therefore, as a human being, I can be certainly sensitive to the fact that, if 19 I was told as a patient, or if it was my loved one, that this requires a medical event report, you're 20 going to presume that it has some injurious effect on you or your loved one. So, the anxiety that 21 that produces, I'm not insensitive to that.
22 That being said, looking at patient harm just singularly, I would struggle with 23 that as well because, to the extent that the criteria require reporting of things where the procedural 24
75 outcome -- I'll say it this way, not the health effect, but the procedural outcome -- was not as 1
intended, it often does indicate perhaps poor training or some calibration issue with the device or 2
something else, something you would want to know about as a practitioner and correct. So that 3
the two statements are true. While there's often not patient harm, there is something 4
addressable having to do with the event.
5 So, again, I look continually at that, on the frequency that the Agency 6
reevaluates those medical event criteria. I think it is always worthwhile for us to spend some 7
time thinking about the conundrum that I've put forward there.
8 You've talked about other kinds of corrective action programs into which events, 9
if they are procedural matters that need to be addressed, are corrected or training inadequacies.
10 I know that the medical community itself has a lot of monitoring and looks at the lessons learned 11 there.
12 But can you talk a little bit or do you have any advice for me in terms of striking 13 the right balance, if it is, indeed, your view that we haven't struck the right balance right now in 14 the criteria?
15 DR. EICHLER: Well, I think what we were talking about there with the patient 16 safety organizations, there are a lot of those out there. I talked about one that we use, the ROILS 17 system, with 12,000 events in there and 500 organizations already in there. And ROILS I think 18 does a very good job of making the information available anonymously and publishing reports 19 with regularity about how to fix these different issues that are coming into the registry.
20 So, I think maybe erring on the side of allowing a little more flexibility with 21 involvement in PSOs, and without going off on a huge tangent here, a lot of the hospital systems, 22 the bigger ones, have their own in-house PSOs. So, HCA, for instance, where I was for 15 years, 23 they use a system called Radiation Right. And it's the same thing. There's a lot, you know, a 24
76 fair amount of paperwork involved and a fair amount of reporting, but, nevertheless, the whole 1
thing is designed for patient safety.
2 So, I can't give you a direct answer in terms of what you should do, other than 3
to maybe be a little more flexible in terms of using patient safety organizations as a tool.
4 CHAIRMAN SVINICKI: Dr. Dilsizian, did you want to weigh-in?
5 DR. DILSIZIAN: Yes. Thank you very much.
6 So, one of the things at ACMUI did, as you know, is in the spirit of safety culture.
7 We're reported to you several times. And one of the, I think, kind of immediate solutions is that 8
we always equate medical event equals to medical error. Now, as you know, there are medical 9
events that are minor; there are medical events that are major; high impact versus low impact.
10 One of the recommendations we made was to consider, why is that important?
11 It's because of the urgency of the reporting, the urgency to do it in 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br />. So, that urgency of 12 reporting will make everyone very nervous or may not report. That's the concern.
13 So, if we somehow divide it up into high impact versus low impact reporting, 14 where the low impact one would be two weeks, just kind of give time to analyze the data, why it 15 happened, I think it may go far. And I think also that can fit into the PSO --
16 DR. EICHLER: Yes, that's an interesting proposal. Okay.
17 DR. DILSIZIAN: Yes, yes.
18 DR. EICHLER: Yes.
19 CHAIRMAN SVINICKI: Thank you for that.
20 Dr. Sheldon, again, thank you so much for being here today. And although you 21 wouldn't have a basis to know how relevant your remarks are to other aspects of what we regulate 22 here on the advanced technologies or advanced reactor systems for power production, as an 23 Agency, we do confront the same assertion that some investors are going outside the United 24
77 States for approval of new power production systems.
1 As just a personal perspective, I feel that those decisions about which country's 2
regulatory system to enter I think has a lot to do with factors that are outside of our regulatory 3
system. Sometimes it's where they would project their customer base might be to sell their 4
reactor power systems.
5 But, that being said, it was noteworthy to me your slide 6 had a survey of what 6
was causing venture capitalists and others to want to take their investment outside the United 7
States. Regulatory challenges came in at, I think, 38 percent, which dominated the responses 8
there. We've not, to my knowledge, done any kind of a similar survey among advanced reactor 9
developers in the U.S., but we do certainly confront a view that our regulatory system is in some 10 ways a very complicated kind of edifice to approach and enter and if you're not familiar with the 11 system.
12 I would think that medical technology developers would already probably be 13 pretty familiar with the FDA system. Maybe venture capitalists are not. Do you have any 14 insights into, of that 38 percent that regulatory challenges causes people to take their systems 15 outside the U.S. for investment or development, do you think there's a perception element to that 16 or is that community pretty familiar with FDA regulatory processes, that it was really the process 17 itself that was causing them to take their systems elsewhere for approval?
18 DR. SHELDON: Thank you for the question.
19 I don't think it was as much perception as it was actual reality. When we looked 20 at it ourselves for innovative medical devices that required what we call a PMA, Premarket 21 Approval, the time to approve a medical device was approximately 422 days in the U.S. in about 22 2010.
23 I mentioned in my initial remarks that, although I practiced cardiac surgery for 24
78 20 years, I also developed medical devices for about 10 years. And I actually 1
produced/developed medical devices during those same 10 years that we described. I can tell 2
you personally that I had one minimal interaction with FDA and all the rest of my work was in 3
Europe for those 10 years, and these were for real reasons. And we knew that and we just went 4
elsewhere because FDA was definitely a large barrier. FDA did not want to know that before 5
with some of the other Center Directors, but the current Center Director, Jeff Shuren, recognized 6
that and saw that it was correct and put in corrective action to change things.
7 Actually, one of the interesting parts about it is that 422 days is now down to a 8
median time of 30 days. That's a long discussion to tell you how we got there. But, nonetheless, 9
the perception hasn't changed as much that FDA remains a barrier. That has been changing, 10 but changing very, very slowly. So, it's kind of like, if you lose a customer, it takes 10 times longer 11 to get that customer back than to keep that customer. So, it was a real issue.
12 CHAIRMAN SVINICKI: Well, I thank you for that. And since it is part of a 13 longer conversation, I'll be inquiring with the NRC staff after this meeting whether perhaps some 14 of the FDA experts that were a part of that longer journey to get to those results could get in touch 15 with some of our innovation leads here. I think we're entering well into year two of looking at lot 16 of our Agency processes, and it sounds at least preliminarily like there may be some experiences 17 that the NRC staff would welcome an opportunity to in a different setting talk to folks in the Center 18 you lead and talk to them about that.
19 DR. SHELDON: I would be more than happy to introduce them.
20 CHAIRMAN SVINICKI: Thank you.
21 And just turning quickly to -- and I'm confident my colleagues will pursue this 22 more thoroughly -- but there was discussion with the Staff panel about the recommendation that 23 is currently laid before the Commission. I, like other members of the Commission, are still just 24
79 kind of trying to differentiate between the options that the Staff looked at and the recommendation 1
they've made. But, as Commissioner Baran pointed out, of course, the elimination of the 2
alternate pathway is a significant discriminator amongst these various options and things that the 3
Staff looked at.
4 Would anyone who's kind of deep as a practitioner in the field, if that were 5
eliminated, the Staff indicated that their assessment of practitioners using the alternate pathway 6
were kind of two things: people who hadn't yet entered a Board certification process and perhaps 7
medical practitioners who have been educated outside the United States.
8 I guess my first question is, is that generally an accurate description of people 9
pursuing the alternate pathway? And then, what do you think would be the effect of eliminating 10 the alternate pathway? In immediate terms, what would we observe in the two or three years 11 after it were eliminated?
12 DR. DILSIZIAN: Is the question to me? I'm going to be fair. Even though I'm 13 the President of the Society for Nuclear Medicine, I'm also a cardiologist. And so, if you were to 14 say cardiologists cannot practice nuclear cardiology and I wouldn't have the alternative pathway, 15 that I would only have to be a radiologist or a nuclear medicine physician, that would not be fair, 16 I would think.
17 So that the alternate pathway that exists is because, currently, as you know, 18 endocrinologists who are practicing therapy can, beyond their Board certification, fulfill that criteria 19 and treat patients. It is true that the AU pathway of training is good and that some physicians 20 don't pass their Boards or don't take their Boards, and there's a limit of, say, six years you will 21 have to take it. And then, afterwards, you just have to take it again. So, during that period of 22 six years, if that's their subspecialty, it will be nice that AU allows them to treat and not limit their 23 practice by board certification. I think that it is a fair thing to have it there and to maintain 24
80 because, necessarily, board certification should not allow someone to practice -- as long as you're 1
board-eligible, you should be able to continue practicing until you document that you can't pass 2
the boards.
3 So, I support keeping it and, then, you know, I'd like to go beyond that. But it's 4
not just the hours that you're spending, it's competency afterwards as well.
5 CHAIRMAN SVINICKI: Well, thank you for that, and that tees up a lot of 6
interesting topics, which I will allow Commissioner Baran and others to pursue. Thank you.
7 COMMISSIONER BARAN: Your confidence is warranted. I will ask about 8
this.
9 So, just following up Dr. Dilsizian on that -- and others can chime-in if you have 10 thoughts about this -- you noted that there are currently three medical specialty boards recognized 11 by NRC for the purpose of certifying Authorized Users. Do you have a sense of -- and this is a 12 little bit of a variation of the question I asked the staff -- a sense of how likely it is that additional 13 medical special boards would want to develop a certification process? And how challenging or 14 straightforward would it be for them to do so?
15 DR. EICHLER: I was just going to say I think it's an extraordinary expense 16 process to start that up.
17 COMMISSIONER BARAN: Okay.
18 DR. EICHLER: And it's hard for me to imagine that someone is going to want 19 to take that on, to be perfectly honest. I can tell you right now that, if we were to take over 20 certification of, say, all of radiation oncology, it wouldn't happen. The ABR already does it well.
21 Why reinvent the wheel?
22 COMMISSIONER BARAN: Right. So, if the Staff or we were banking on the 23 fact that there's going to be additional specialty boards that want to run in and fill this gap if the 24
81 alternate pathway goes away, we should really question whether that's a solid assumption?
1 DR. DILSIZIAN: I have no doubt that certain subspecialties are interested in 2
training their physicians. As I pointed out in my presentation, they don't have the background to 3
train, to educate, and it's going to take a long time.
4 I think that the quickest way for me is to maintain what's already worked as an 5
Authorized User pathway and have the competency test being provided by experts who already 6
know and provide the tests. That's a very simple thing. Why reinvent the wheel? You can do 7
this, 20 different subspecialties -- urology, oncology, cardiology, et cetera -- or you have one that's 8
an ABNM subspecialty and just say certification for all subspecialties, as long as they fulfill their 9
AU criteria. So, that would be simple. You can monitor that much better and you can supervise 10 that much better than having 20 different ones.
11 And again, the other question is, what are you going to consider a board? If 12 I'm an organization and I'm going to create my own board, that's not under ABMS. Are you going 13 to recognize that? So, it's a little bit complicated.
14 COMMISSIONER BARAN: Uh-hum. There's also this issue where the staff's 15 approach addresses future physicians who could become Authorized Users through board 16 certification, but there's the question of existing physicians who have been certified by a board 17 already that doesn't currently have a radiation safety program. And the Staff says, well, they 18 could do guidance on that.
19 Do you have a sense of or thoughts about how easy or hard it would be to 20 address that situation where you've got someone who is board-certified, but before that board 21 went ahead and had a radiation safety component? Maybe that's being too in the weeds, but it 22 does seem like another -- it's easy to say, well, we do guidance for that, but I just don't know how 23 tricky that's going to be to deal with.
24
82 DR. DILSIZIAN: Well, again, I think that if you have a training and experience 1
guideline to say that, even if you're in practice now, retrospectively, we realize that there are new 2
radioisotopes or radiopharmaceuticals that are being introduced. Now you want to be trained at 3
this. There has to be an educational pathway where you would be certified on those isotopes 4
only, no matter what subspecialty you are.
5 So, again, my recommendation would be to fulfill the 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> and, then, to 6
take a certification exam, and that can apply to whether you're trained now or 20 years ago. It's 7
a very clear pathway and it's a very simple pathway. There's no confusion in multiple directions 8
on how you're going to approve different boards.
9 COMMISSIONER BARAN: Go ahead.
10 DR. EICHLER: Twenty-five years ago or 30 years ago when I trained, the only 11 radioactive isotopes that people were using were iodine-131, phosphorus-32 in ovarian cancer, 12 that sort of thing. And then, all of a sudden, this stuff called Metastron appeared, strontium-90, 13 and then, it was Quadramet. And then, a few years later, it was something else. And now, you 14 saw the list up there. It's an amazing list of isotopes that are coming out now. So, we didn't 15 have any training in that. We had to go to courses and whatnot to learn how to use them. There 16 was no 700 hours0.0081 days <br />0.194 hours <br />0.00116 weeks <br />2.6635e-4 months <br /> in terms of that back then. But, anyway, for historical purposes.
17 COMMISSIONER BARAN: Terry, I read the comments of OAS and CRCPD 18 on this training and experience issue. And CRCPD argued strongly for sticking with the current 19 approach while OAS seemed more supportive of making a change.
20 Given that there's a lot of overlap in the individuals involved in the two groups, 21 can you talk a little bit about what accounts for kind of the divergent recommendations?
22 MR. DERSTINE: Probably the difference is the people that review the 23 proposed changes and how vocal they are --
24
83 COMMISSIONER BARAN: I see.
1 MR. DERSTINE: -- and the states and which organization that they --
2 COMMISSIONER BARAN: So, OAS is just, for maybe obvious reasons, more 3
focused on the effort that went into the actual review on their end of people leading the team?
4 MR. DERSTINE: That would probably be a safe assumption to say.
5 COMMISSIONER BARAN: I see.
6 MR. DERSTINE: But I can't speak for CRCPD and, then, how well they did it.
7 COMMISSIONER BARAN: I talked about it a little bit on the first panel. I 8
could see another option. It seems like options are proliferating. But I could see another option 9
of keeping the current structure of the three recognized medical specialty boards and a 700-hour 10 alternative pathway, but thinking about moving away from listing Authorized Users on the license, 11 the facilities licenses, and that could, then, maybe eliminate the processing of the 2500 license 12 amendments each year, I think 90 percent of which are the Agreement States doing that.
13 Do any of you have thoughts about an approach like that, whether something 14 like that would make sense?
15 DR. EICHLER: I think hospitals and insurance companies might be a little bit 16 leery of that.
17 COMMISSIONER BARAN: Okay.
18 DR. EICHLER: I think they would want to know who's doing what and are they 19 competent to do it, and that there's some sort of codification that they're listed somewhere. But 20 I think insurance companies would be very nervous.
21 COMMISSIONER BARAN: Nervous about the NRC not actually signing off on 22 the team you meant?
23 DR. EICHLER: I think they like having you guys sign off on that stuff.
24
84 COMMISSIONER BARAN: Okay. Do you have the same sense?
1 DR. DILSIZIAN: I really think that I want to emphasize that everything is safe, 2
everything is done right I think needs your guidance and supervision. I don't think NRC should 3
delegate this with other institutions.
4 COMMISSIONER BARAN: I wanted to just ask a brief question or two on 5
patient release, because I agree with my colleagues this is a complex issue. It's not a black-and-6 white kind of issue. And there are a lot of factors you're trying to balance here. Commissioner 7
Wright wisely asked about insurance as being one of those factors.
8 I visited Washington Hospital Center last January, and I think they do more 9
iodine-131 treatments than any other facility, and they do most of those treatments on an inpatient 10 basis. I had heard going in that insurance typically wouldn't cover that or it would be a challenge, 11 but they said there that insurance hadn't been a problem for them. I think you maybe made a 12 similar point.
13 What's your sense of whether insurance coverage is a barrier to treating 14 patients with iodine-131 or another radiopharmaceutical on an inpatient basis?
15 DR. DILSIZIAN: Again, I think that, like everything else we do in medicine, 16 preclearance, et cetera, advice, a lot of insurance companies will -- they're responsible and will 17 listen to the recommendations of the physicians.
18 So, when I started in Maryland, I was given, when I first started with I-131, I was 19 given the six forms to fill out. And as I was filling those out, I was telling the patients, "Just bear 20 with me. This is required by NRC. I have to fill out all of these forms." I was letting them know 21 that it's all detailed and everything was completed, and it takes about 30 minutes.
22 And then, later on, I learned, after I joined the NRC, that this was just the 23 Maryland criteria. NRC doesn't require any forms, forms to fill out.
24
85 But it was very good in that, because if you don't treat a lot, it makes you go 1
through every step, teaching, lecturing. So, I was recommending -- and again, I don't want the 2
NRC to micromanage medicine, but you have to guide us. I mean, you have to go give us some 3
forms. Why do we have that? Because if I miss something, my RSO will find it, and then, the 4
Human Use Committee will discuss it and will let me know. So, again, it's a safety culture thing.
5 It's the right thing. It's not punitive. It's just letting me know what needs to be done.
6 I think that if NRC does these kind of recommendations and some forms to say 7
what needs to be done, occupancy factor, what questions you should ask, which patients should 8
be admitted or not -- I don't want you to, again, tell us what to do, but just recommending what 9
dose is recommended and levels. I think it would go far.
10 DR. EICHLER: So, I don't think you have to worry about the NRC 11 micromanaging anything. The insurance companies already do that. Okay? And they will 12 micromanage this.
13 I think the release issue is very interesting because it's isotope-dependent, it's 14 patient-dependent, and it's clinician-dependent. You could have all the uniform instructions you 15 want, everybody gets the same thing if they get -- throw in the isotope -- the same set of 16 instructions. But you're going to understand those instructions better than the farmer who has 17 an eighth grade education. But, believe it or not, the farmer is going to listen to you better and 18 will have the fear of God struck in him by the clinician; whereas, you might say, "I don't feel bad.
19 I don't need to do any of this stuff." So, it's very different for everybody.
20 MR. MAILMAN: But I don't think it's universal. I mean, we spent some time 21 with ThyCa discussing this, and I think they do have challenges with thyroid patients who need to 22 be admitted or aren't considered for admission because of insurance challenges as well. And I 23 know, certainly with Lutathera, when a patient is determined to need hospitalization due to 24
86 something, it becomes a challenge as far as both insurance coverage for the hospitalization, but, 1
even more so, it becomes an inpatient treatment versus an outpatient treatment, and the entire 2
way that gets paid becomes complex and challenging. So, it has more complexity than I think 3
we're giving it credit for.
4 DR. EICHLER: Yes, we could go down the rabbit hole on preauthorization 5
here, which I'm not going to do because we're going to blow up the whole meeting. But it's a 6
mess in radiation oncology; I'll tell you that right now. Most practices now have hired people 7
specifically to do nothing but preauthorization, which is ridiculous.
8 COMMISSIONER BARAN: Thank you.
9 CHAIRMAN SVINICKI: On that sobering note, Commissioner Caputo.
10 (Laughter.)
11 COMMISSIONER CAPUTO: I guess I'm going to put my oar in the water on 12 training and experience. I think, obviously, we've heard from three very qualified people today 13 that everything should stay the way it is; that there is no limit to access, there are no problems 14 with access.
15 But, obviously, OAS has got to have a basis for its position, support of what the 16 Staff has recommended. Can you just give us a little more detail on what's behind where OAS 17 came out, whether or not you're seeing some problems in terms of patient access, and whatnot, 18 that you feel argues in favor of a revision?
19 MR. DERSTINE: Yes, well, that was some of the comments that we got, was 20 that it might be limiting to patient access and stuff like that with the current position. So, they're 21 the basis of the comments that were received.
22 COMMISSIONER CAPUTO: So, I know there were comments made earlier 23 about stakeholder concerns and fairly dismissive of that, for a lack of a data. Is OAS gathering 24
87 data on sort of this access question, or do you believe the NRC Staff should gather data on this?
1 MR. DERSTINE: Well, all the people that are out there dealing with each 2
licensee, each facility, are the perfect people to start gathering that data. So, yes, it probably 3
would be a good OAS-NMP program to start maybe looking a little bit deeper into that.
4 COMMISSIONER CAPUTO: Okay. Thank you.
5 And because you've had a fairly easy ride yet today, I'll hit you with another 6
question.
7 MR. DERSTINE: Oh-oh.
8 COMMISSIONER CAPUTO: On abnormal occurrence criteria, as has been 9
stated several times today, there may be cause to revise those criteria because they may be 10 capturing events that are not significant from the standpoint of public health and safety. Could 11 you just elaborate a little more on OAS's position on that issue?
12 MR. DERSTINE: Well, I know for reporting reportable events, and everything, 13 I know every Agreement State makes it a big deal to get out there and investigate. And it has to 14 be reported, and it's up to the licensee to determine a reportable event and they have a timeframe, 15 after they determine that it is a reportable event, to get it to us. Then, we have a timeframe to 16 pump it on up through to the NRC. And then, we also have to get out there and investigate.
17 We learn a lot from reportable events. So, they are important for us, for a 18 licensee to report it to us, and it gets the information out there to share with all the licensees 19 throughout the country. And that's very important as well.
20 Yes, I would hate to take away some of the requirements for a reportable event.
21 It's a great learning experience for everybody, even though I do see the other side. The facility 22 does struggle. They don't want their name being out there. Everyone perceives it that a mistake 23 happened, and that's not always the case.
24
88 COMMISSIONER CAPUTO: So, maybe what we are doing is room to draw a 1
bit of a distinction. Abnormal occurrence for us means that it actually triggers reporting to 2
Congress on each of these events. Is there room for sort of refining a breakdown between what 3
actually warrants that level of reporting versus a more normal level of reporting and tracking? Is 4
there a breakdown that sounds reasonable there?
5 MR. DERSTINE: Yes, that sounds like a decent proposal, yes.
6 COMMISSIONER CAPUTO: Okay. Mr. Mailman, you've also gotten off easy 7
so far. And so, I have a fairly basic question for you. So, we have developed a brochure for 8
patients: "What you should know about treatment with radioactive drugs". Are you familiar with 9
it?
10 MR. MAILMAN: I have not reviewed it yet.
11 COMMISSIONER CAPUTO: Okay.
12 MR. MAILMAN: I just reviewed the actual guidelines themselves.
13 COMMISSIONER CAPUTO: Okay. All right. Well, I guess I'd be curious, 14 once you have reviewed it, whether or not you think it hits the mark in terms of the level of 15 education, the level of information that patients need in order to feel comfortable with the 16 procedure and the ramifications.
17 MR. MAILMAN: I do think one of the challenges for any generic piece is that 18 these isotopes are pretty specific in the energy and what kind of considerations you're going to 19 have to do as well. And so, it is a challenging -- they also need to be developed at the isotope 20 or therapy level as well.
21 COMMISSIONER BARAN: Okay.
22 DR. EICHLER: Commissioner, ASTRO would also love to see that brochure.
23 We have a very extensive education arm that started off very broad with prostate cancer and 24
89 breast cancer. Now it's narrowed down to stereotactic radiosurgery and things like this. So, we 1
would be very interested in seeing that.
2 COMMISSIONER CAPUTO: I'll just start with this.
3 (Laughter.)
4 DR. EICHLER: Okay.
5 COMMISSIONER CAPUTO: The color came out a little funky on the printer, 6
but there you go.
7 DR. EICHLER: Thanks so much.
8 COMMISSIONER CAPUTO: And I'm sure you can find that on our website.
9 DR. EICHLER: Thank you very much.
10 COMMISSIONER CAPUTO: Because I'm sure I can get another one later.
11 So, Dr. Sheldon, I have a couple of questions for you. We've talked a little bit 12 today about how our two agencies work together. So, just one kind of open question about, are 13 there ways that you think we can maybe work smarter together? And considering that we are 14 working on an MOU, are they all captured in that MOU? Are we making enough progress on 15 bringing that MOU to completion, to really help each other as sister agencies to move forward?
16 DR. SHELDON: Well, of course, I'm not familiar with your MOUs and where 17 you're working on that with FDA.
18 COMMISSIONER CAPUTO: Okay.
19 DR. SHELDON: That's not been an area that I've been. But what I would 20 definitely recommend is, as the Chairman mentioned, have some follow-up afterwards. I know 21 the people that do that type of work, and I think it would be really helpful for both of us to learn 22 from each other lessons learned, et cetera. I've been involved with multiple activities outside of 23 the FDA, with the NIH, with CMS, as I've mentioned, and others. And I'm never surprised by 24
90 what we learn from each other.
1 COMMISSIONER CAPUTO: Okay.
2 DR. SHELDON: So, I think it's a good idea.
3 COMMISSIONER CAPUTO: Well, thank you. I think there are probably two 4
areas. One, just in terms of the nature of how we both operate in closely-related space with 5
regard to medical isotopes, but, also, the broader issue in terms of your introspective analysis of 6
how to respond to the need to make more timely decisions and the response to criticisms that this 7
drives business decisions. We do receive a fair amount of that ourselves. So, I think, obviously, 8
I wholeheartedly support what the Chairman discussed earlier because I think there's a lot of room 9
there for us to sort of do our own introspective look and come up with, hopefully, some frank 10 observations and room for improvement.
11 But one that you mentioned, in particular, that caught my eye was your 12 entrepreneur-in-residence. Now, for us here, my immediate reaction to that is we would be 13 quickly criticized for being cozy with industry in terms of either bringing an industry person to 14 educate our staff or placing our staff in a company to learn.
15 So, given the fact that FDA would have the same need for ensuring 16 independence and objectivity and ethical standards, how did you handle that sort of fox-in-the-17 henhouse criticism in terms of bringing your entrepreneur into residence?
18 DR. SHELDON: So, that's always a very big challenge. And it's very 19 interesting, I'm relatively new to the FDA, about six or seven years, but I've already seen two or 20 three, or maybe four, new Commissioners in that period of time. And every new Commissioner 21 always gets grilled about the relationship between industry and the regulators.
22 And it's always seemed that the regulators and those who develop the products 23 are, I guess, adversarial. What we've done, at least in the Center for Devices, is to recognize 24
91 that we're really on the same team, and the team that we're on is the team for the patients, the 1
people that need the services. Once you put the patient in the middle, some of those things go 2
away.
3 We sometimes like to even say that at least the Device Center is not 4
fundamentally a regulatory organization. We're a public health organization and regulation is the 5
process by which we improve public health.
6 So, if we focus on the patient, the user, why we're trying to do this, we must 7
work with industry very, very closely. We must learn from them and work together. It's a 8
challenge, but we also recognize that innovation flourishes at the borderline between different 9
expertise. And innovation also means that change is the only constant.
10 We know that there are others who will criticize that, but, in the end, if the work 11 that comes out benefits the user, which in our case the customer is the patient, and we improve 12 public health, it tends to go away.
13 COMMISSIONER CAPUTO: Got you. Thank you.
14 CHAIRMAN SVINICKI: Thank you very much.
15 Commissioner Wright, please proceed, and thank you for your patience.
16 COMMISSIONER WRIGHT: I've just enjoyed listening to the questions and 17 the dialog.
18 And to pick up real quick on the insurance and the preauthorization stuff, I agree 19 with Mr. Mailman; I believe this is a lot more difficult in areas. And I hear you, Doctor, and I'm 20 sure in some hospitals and some practices it's easier. But I have known personally of some other 21 outcomes and I know that I'm sure that Mr. Mailman knows the same thing. So, I do think it's 22 something that really needs to be looked at and considered as a whole, as part of the whole thing.
23 But I really did enjoy that discussion. Thank you so much.
24
92 Dr. Sheldon, I really have enjoyed listening to you today because we're trying 1
to transform here at the NRC, as you probably know. And it's helpful to hear that other agencies 2
are going through the same thing possibly and probably. It's interesting for me to learn how the 3
regulators are maybe approaching, in other agencies how you are approaching it.
4 It sounds like FDA's reforms to its licensing process would or might require the 5
staff to change how they look at licensing and maybe to accept a little bit more risk, to include 6
risk. Would that be fair?
7 DR. SHELDON: Yes, it would. Most of what we faced was an internal culture 8
change process, because there are a lot of staff that have been at FDA for many, many years.
9 And I would often hear, as I also hear from physicians routinely, "I've been doing it this way for 35 10 years and I'm not about to change now." And that is really counterproductive because, as Darwin 11 has shown us, everything changes, and if you don't change, you become extinct.
12 COMMISSIONER WRIGHT: I'd be interested in hearing a little bit about how 13 maybe they addressed making some of those changes or if some of the risks were perceived as 14 being too high. How did you go about addressing it?
15 DR. SHELDON: We went about it in two or three ways. One, of course, was 16 the entrepreneurs-in-residence program, where we actually allowed our staff to be interacting with 17 those experts outside, often who were identified as the biggest critics.
18 That was always a funny challenge. My mentor in medical device development 19 is Tom Fogarty. I don't know if anybody knows who Tom Fogarty is. He's probably the most 20 impressive medical device developer in the world for cardiovascular devices; received a medal 21 from President Obama just for that.
22 Tom is about 86-87 years old; in 2011, became an entrepreneur-in-residence.
23 But he tells the story that, when he got the telephone call from Jeff Shuren, "Would you like to 24
93 come and help us?", it took him quite a while to pick up the phone after laughing so hard. He 1
said, "Do you know who you're calling?" He said, you know, "You don't want me." And Jeff 2
said, "Yes, we actually do. We think it's time to listen."
3 And really, it was all important because of the patients. When I hear Mr.
4 Mailman's story of having to go to Germany and patients coming back from elsewhere, and we 5
learn that we're the 46th country in the world to approve percutaneous heart valves, when the 6
companies who built the percutaneous heart valves are all U.S. companies, we say, that's a 7
problem and it must be addressed.
8 And so, we really needed to reach out. Of course, our staff resisted. And one 9
of the things, as I mentioned, we went from 422 days as a median to 30. The staff resisted 10 immediately. "So, you just want us to give up our standards and just rubberstamp everything 11 that comes to us?" He said, "Absolutely not, but there are a lot of things that you can do."
12 One of the biggest things -- and I'll never forget this -- when Rob Califf became 13 one of the new Commissioners, I interacted with him previously because he's a cardiologist. And 14 he came by the office and he said, "Now that I'm here, tell me, what is it that you guys really do 15 the best?" And without blinking an eye, I told him, "Rob, one of the things I've learned is we build 16 great silos."
17 (Laughter.)
18 All silos, thick silos, no windows, no walls. And that's one of the things that we 19 do the best. I don't think that's really so good.
20 And so, the first thing that we started to do was to break down the silos. We 21 got out sledgehammers. We put in doors. We put in windows. And we told our review staff, 22 "If you've got a problem with something that you're seeing, pick up the phone; call the sponsor, 23 call the manufacture, and discuss it with them and try to figure out how you can work this out 24
94 today" not by buying a catapult and putting in all of your materials and shoving it over the wall, 1
and it lands with a big thud with dust all over the place. And then, you look at it and we put it in 2
the FDA catapult and send it back.
3 And the communication is very, very poor. Nobody understands what they're 4
talking about. So, direct communication we found has been incredibly useful, and our staff kind 5
of loves it. And they're all very excited to help to bring new, innovative products to patients.
6 Now they're really engaged.
7 DR. EICHLER: Murray is absolutely right. Doctors as a rule don't like change.
8 Just take an extreme example. If it takes me six weeks to treat something, and somebody comes 9
along and says, "I have a way to do this in one day," the first thing you say is not "Wow, that's 10 fantastic. That's great for the patient." It's, "What's that going to do to the coding? What's it 11 going to do to reimbursement?" Because, I mean, there's a whole string of questions that pop 12 up that shouldn't pop up at all.
13 DR. SHELDON: The only people who like change is our babies with wet 14 diapers.
15 (Laughter.)
16 Change is very difficult to deal with, but it's mandatory. It will happen.
17 DR. EICHLER: Well, you either have to do it or it will be done to you.
18 DR. SHELDON: That's right.
19 COMMISSIONER WRIGHT: Exactly. So, I really appreciate the comments.
20 Again, earlier the Chairman was suggesting that we ought to have more dialog 21 with FDA, and I think this is another area where we share a lot of the same kind of silos --
22 DR. SHELDON: Yes.
23 COMMISSIONER WRIGHT: -- that we're trying to break down. So, thank you 24
95 for your comments. I learned more about how you're doing it.
1 DR. SHELDON: More than happy to interact.
2 COMMISSIONER WRIGHT: Quickly, Mr. Derstine, I join Commissioner 3
Caputo; it would really be good to get a little bit more data, if you all can pull that together, as to 4
how you reached the position that OAS did. I was at the meeting when Mike Fuller from Virginia 5
made the presentation, and it was like an "Oh, wow" moment there, and it has sparked a lot of 6
discussion. So, if you have any comment, I would be glad to hear.
7 MR. DERSTINE: Thank you. I'll take that back to the OAS and even, yes, 8
maybe on our next monthly call with the NRC-OAS-CRCPD, throw that out there.
9 COMMISSIONER WRIGHT: Fine.
10 MR. DERSTINE: And maybe we can brainstorm the best way to get that data.
11 COMMISSIONER WRIGHT: Okay. Thank you.
12 And for you two, you discussed earlier about social media a little bit and about 13 providing useful information, and how to stop misinformation from getting around. And I think 14 you're spot-on with that.
15 So, talk to me a little bit more about how you help patients and others navigate 16 this to ensure that they're going to get accurate information. I mean, is there more that we need 17 to do? And if you can be a little bit more specific, that would be great.
18 DR. EICHLER: Yes, that has become, obviously, a huge problem in the 19 information age. Especially, social media has changed everything. There's a ton of stuff out 20 there now that's completely inaccurate.
21 But how I would approach it with patients is I would direct them to specific 22 websites. And we give everybody a piece of literature specific to their cancer and it lists the 23 websites that we have already vetted. And then, we have an in-house one called 24
96 RTAnswers.org, which is spectacular. It's got two-minute videos, five-minute videos. It's got all 1
kinds of information in there. So, I make sure they're directed to that.
2 But, again, it comes down to the patient. Not everybody has, believe it or not, 3
not everybody has internet savvy, and you've got to sit and talk with those folks and make sure 4
they understand in very plain terms what you're going to do to them and what the expectations 5
are, what the chances of success are.
6 So, it's still a very individualized process. Social media and the internet are 7
both a blessing and a curse. There are people that walk in the office sometimes with shopping 8
bags full of books and want to discuss every little piece of information that's out there. So, you 9
really kind of have to guide them to the right place, and over a period of time you get used to 10 doing that. I think there's, from my own perspective, a fair amount of success in doing that.
11 DR. DILSIZIAN: So, I agree. I think, obviously, it's generational, right. The 12 older patients are still going to be listening to you and not go to Facebook or YouTube. But the 13 majority of the patients are in the new era of media through Facebook, through YouTube. And I 14 agree that there's a lot of noise out there.
15 But I think at least that my experience is, I used to think -- I was pretty 16 naive -- that that brochure that you handed them, I mean, that's what we used to do. We printed 17 those up, give to the patient. You know, "Here's radiation safety instructions. Here's what 18 you're going to read." And, you know, I thought that would fulfill it. Of course, it's not because 19 some people don't read at all; they misplace it.
20 And I'm looking at my kids; I mean, their education of high-level physics and 21 quantum physics is on media. I mean, they're just getting a lot of good information.
22 So, I agree with you, how do we guide them? Again, first, to make the tape, 23 the video clip, and the next thing is to guide them. So, I think that we're going to be targeting not 24
97 just the SNMMI website, but the endocrinologists, patient advocacy. So, the same clip has to be 1
everywhere that the patient may have access. Otherwise, it would be naive for us to think that 2
they're going to come to our site only. So, it's just a matter of being clever and saying, where do 3
patients get their information, and target those sites.
4 MR. MAILMAN: And also, make them patient-relative, relatable information.
5 Because, I mean, I was looking at the back page. The back page is actually the one that I was 6
making large comments on. That's really generic, sleep alone. Okay. I look at that. That's 7
why people, then, go get their own apartment for a week to stay away from their family, which 8
might be interesting for I-131, really not interesting for Lu-177. But just like that you can really 9
lose people.
10 So, this has to be relatable to the experience they're going through. You have 11 to be multi-modality, in different channels, whether it's YouTube, whether it's Twitter. There have 12 to be ways to have information that's accessible to patients in a language they understand, 13 because, otherwise, they just make stuff up.
14 It's one of the things I do when I'm on the road shows with the SNMMI as well.
15 Even docs make stuff up when they don't know things, and we've got to stop making stuff up and 16 really have good, credible, easy-to-understand information that can be accessed in a multitude of 17 ways.
18 DR. EICHLER: So, as a major cancer therapeutical "doubty," we commission 19 surveys every couple of years to find out what are patients hearing; what do they want to know; 20 what are we not doing well, and try to change to accommodate the patient population.
21 Even with these brochures that I mentioned that went out, the videos that went 22 out, they had been edited again and again and again to get it to the right level of education for the 23 patients. So, it's an ongoing effort.
24
98 MR. MAILMAN: And another thing that I do is patient communication 1
education because, for the most part, when we leave your office, we're going to forget 85 percent 2
of what you told us, and that 15 percent that we actually retain, we're going to get half of it wrong.
3 So, it's a repetition. There are studies that are done about this. And it really 4
is having the material ready when someone needs it, when they can absorb it, and then, retesting 5
it because, in fact, even if you think they have it, they don't.
6 DR. EICHLER: So, I encourage people to bring someone with them and tell 7
them at the outset, "You're only going to remember 50 percent of what I say. Your job is to 8
remember the other 50 percent."
9 COMMISSIONER WRIGHT: Yes, yes. And with that, on the brochure, any 10 feedback -- I appreciate Commissioner Caputo giving it to you -- and any feedback you can give 11 us would be very helpful. So, thank you.
12 Thank you.
13 CHAIRMAN SVINICKI: All right. Well, thank you again to our panelists.
14 Again, it's interesting because we do have on a routine frequency a meeting of 15 our Commission with the Advisory Committee on the Medical Uses of Isotopes. And I'll just 16 candidly admit that, when this meeting was proposed, not by me, but by my colleagues, I wasn't 17 sure that there wasn't a redundancy there, but I observe that we had a very different dialog today 18 on different topics. And maybe some of it, we got to see the cross-connections and we got to 19 just kind of view it all from standing back a little further. I found it very valuable. I thank my 20 colleagues for proposing the meeting.
21 And I want to thank all of you for being here today, and for the NRC staff for 22 their hard work and their presentation.
23 With that, we are adjourned. Thank you.
24
99 (Whereupon, the above-entitled matter went off the record at 12:17 p.m.)
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