ML22326A362

Draft Regulatory Basis Document for the Rulemaking to Establish Requirements for Rubidium-82 Generators and Emerging Medical Technologies for ACMUI Review

ML22326A362
Person / Time
Issue date:	11/22/2022
From:	Advisory Committee on the Medical Uses of Isotopes
To:
References
RIN 3150-AK90, NRC-2016-0297
Download: ML22326A362 (118)

Text

RULEMAKING TO ESTABLISH REQUIREMENTS FOR RUBIDIUM-82 GENERATORS AND EMERGING MEDICAL TECHNOLOGIES RIN: 3150-AK90 Docket ID: NRC-2018-0297 Regulatory Basis Document March 2023

Table of Contents Executive Summary .................................................................................................................vi

1. Introduction ....................................................................................................................... 1

2. Background and Existing Regulatory Framework .......................................................... 1 2.1 Rubidium-82 Generators .............................................................................................. 1 2.2 Emerging Medical Technologies .................................................................................. 2 2.3 Agreement State Regulatory Program ......................................................................... 3

3. Regulatory Issues ............................................................................................................. 4 3.1 Rubidium-82 Generators .............................................................................................. 4 3.2 Continued Licensing of Well-Established Emerging Medical Technologies Under 10 CFR Part 35, Subpart K ............................................................................................. 5 3.3 Current Emerging Medical Technologies ..................................................................... 6 3.3.1 Germanium-68/Gallium-68 Pharmaceutical Grade Generators ..............................6 3.3.2 Intravascular Brachytherapy Systems ....................................................................7 3.3.3 Liquid Brachytherapy Sources and Devices ...........................................................7 3.3.4 Radioactive Seed Localization ...............................................................................8 3.3.5 Manual Brachytherapy Using Diffusing Sources ....................................................8 3.3.6 Ophthalmic Applicator Sources and Devices .........................................................9 3.3.7 Gamma Stereotactic Radiosurgery and Photon Emitting Teletherapy Units .........10 3.3.8 Microsource Manual Brachytherapy .....................................................................11 3.4 Other 10 CFR Part 35 Changes ..................................................................................12

4. Evaluation of Alternatives ...............................................................................................14 4.1 Alternative 1Status Quo...........................................................................................14 4.2 Alternative 2Rulemaking Only for Rubidium-82 Generators .....................................15 4.3 Alternative 3Limited-Scope Rulemaking to Establish Requirements for Rubidium-82 Generators and Certain Emerging Medical Technologies ..............................................15 4.4 Alternative 4Performance-Based Rulemaking to Increase Regulatory Flexibility (NRC Recommendation) .........................................................................................................16 4.5 Recommendation ........................................................................................................17

5. Basis for Proposed Changes ..........................................................................................17

6. Backfitting and Issue Finality Analysis ..........................................................................18

7. Stakeholder Involvement .................................................................................................18

8. Cost/Impact Considerations............................................................................................18 8.1 Affected Entities ..........................................................................................................18 8.2 Analysis Assumptions .................................................................................................19 8.3 NRC ............................................................................................................................20 8.4 Agreement States .......................................................................................................20 ii

8.5 Licensees ...................................................................................................................20 8.6 Summary of Alternatives and Cost ..............................................................................21 8.7 Additional Unquantified Benefits of Proposed Changes ..............................................23

9. Uncertainty Analysis........................................................................................................24

10. Rulemaking Cost Justification ........................................................................................24

11. Cumulative Effects of Regulation ...................................................................................25

12. Regulatory Flexibility Act ................................................................................................26

13. Environmental Analysis ..................................................................................................26

14. NRC Strategic Plan ..........................................................................................................26

15. Decision Rationale ...........................................................................................................26

16. References .......................................................................................................................27 Appendix AProposed Changes to 10 CFR Part 35 ............................................................. 1 A.1 Strontium-82/Rubidium-82 Generators and Germanium-68/Gallium-68 Pharmaceutical Grade Generators .......................................................................................................... 1 A.2 Intravascular Brachytherapy Systems .......................................................................... 4 A.3 Liquid Brachytherapy Sources and Devices ................................................................. 8 A.4 Radioactive Seed Localization ....................................................................................11 A.5 Manual Brachytherapy Using Diffusing Sources .........................................................15 A.6 Ophthalmic (Eye) Applicator Sources and Devices .....................................................18 A.7 Gamma Stereotactic Radiosurgery and Photon Emitting Teletherapy Units ................21 A.8 Microsource Manual Brachytherapy ............................................................................27 A.9 Other 10 CFR Part 35 Changes ..................................................................................36 Appendix B - Data Tables ....................................................................................................... 1 Appendix C - Summary and Tables of Costs for Each Alternative by NRC, Agreement States, and Licensees.............................................................................................................. 1 Appendix D - Uncertainty Analysis ........................................................................................ 1 D.1 Uncertainty Analysis Assumptions ............................................................................ D-1 D.2. Uncertainty Analysis Inputs ....................................................................................... D-1 D.3 Uncertainty Analysis Results ..................................................................................... D-1 D.4 Sensitivity Analysis ................................................................................................... D-2 List of Tables Table ES-1: Summary Table of Alternatives and Net Benefits (Costs) ...................................... vii Table 2: Advantages and Disadvantages of Alternative 2 .........................................................15 Table 3: Advantages and Disadvantages of Alternative 3 .........................................................16 Table 4: Advantages and Disadvantages of Alternative 4 .........................................................17 Table 5: Alternatives and Net Benefits (Costs) ..........................................................................21 Table 6: Alternative 4 Net Benefits for NRC, Agreement States, and Licensees .......................22 iii

Table 7: Emerging Medical Technology Licensing Assumptions ............................................. B-2 Table 8: Alternatives 1-4 Data Tables ..................................................................................... B-5 Table 9: Alternative 1 - NRC Reviewing Exemptions (Costs).................................................. C-1 Table 10: Alternative 1 - NRC Rb-82 Generator Inspections (Averted Costs) ......................... C-1 Table 11: Alternative 1 - Agreement States Reviewing Exemptions (Costs) ........................... C-2 Table 12: Alternative 1 - Agreement States Rb-82 Generator Inspections (Averted Costs) .... C-3 Table 13: Alternative 1 - Licensees Submitting Exemptions (Costs) ....................................... C-4 Table 14: Alternative 1 - Licensees Rb-82 Generator Inspections (Averted Costs)................. C-4 Table 15: Alternative 2 - NRC Regulatory Review (Costs) ...................................................... C-5 Table 16: Alternative 2 - Agreement States Rulemaking Participation (Costs) ........................ C-6 Table 17: Alternative 2 - Agreement States Rulemaking (Costs) ............................................ C-6 Table 18: Alternative 2 - Licensees Rulemaking Participation (Costs) .................................... C-7 Table 19: Alternative 2 - NRC Rb-82 Generator Inspections (Averted Costs) ......................... C-7 Table 20: Alternative 2 - Agreement States Rb-82 Generator Inspections (Averted Costs) .... C-8 Table 21: Alternative 2 - Licensees Rb-82 Generator Inspections (Averted Costs)................. C-9 Table 22: Alternative 3 - NRC Rulemaking Implementation (Costs)...................................... C-10 Table 23: Alternative 3 - NRC Regulatory Review (Costs) .................................................... C-10 Table 24: Alternative 3 - Agreement States Rulemaking Participation (Costs) ...................... C-11 Table 25: Alternative 3 - Agreement States Rulemaking and Implementation (Costs) .......... C-11 Table 26: Alternative 3 - Licensees Rulemaking Participation (Costs) .................................. C-12 Table 27: Alternative 3 - Licensees Rulemaking Implementation (Costs) ............................. C-12 Table 28: Alternative 3 - NRC Emerging Medical Technology Licensing Averted Costs) ...... C-13 Table 29: Alternative 3 - Development of Emerging Medical Technology Licensing Guidance (Averted Costs) ..................................................................................................................... C-14 Table 30: Alternative 3 - Agreement States Emerging Medical Technology Licensing (Averted Costs) ..................................................................................................................... C-15 Table 31: Alternative 3 - Licensees Emerging Medical Technology Licensing (Averted Costs) ..................................................................................................................... C-17 Table 32: Alternative 4 - NRC Rulemaking Implementation (Costs)...................................... C-18 Table 33: Alternative 4 - NRC Regulatory Review (Costs) .................................................... C-18 Table 34: Alternative 4 - Agreement States Rulemaking Participation (Costs) ...................... C-19 Table 35: Alternative 4 - Agreement States Rulemaking and Implementation (Costs) .......... C-19 Table 36: Alternative 4 - Licensees Rulemaking Participation (Costs) .................................. C-20 Table 37: Alternative 4 - Licensees Rulemaking Implementation (Costs) ............................. C-21 Table 38: Alternative 4 - NRC Emerging Medical Technology Licensing (Averted Costs) ..... C-21 Table 39: Alternative 4 - NRC Development of Emerging Medical Technology Licensing Guidance (Averted Costs) ..................................................................................................... C-23 Table 40: Alternative 4 - Agreement States Emerging Medical Technology Licensing (Averted Costs) ..................................................................................................................... C-25 Table 41: Alternative 4 - Licensees Emerging Medical Technology Licensing (Averted Costs) ..................................................................................................................... C-26 List of Figures Figure 1: Incremental Net Costs for Alternative 4 (7-Percent Discount Rate) .......................... D-2 Figure 2: Alternative 4 Cost Drivers (7-Percent Discount Rate) ............................................... D-3 iv

Abbreviations and Acronyms ACMUI Advisory Committee on the Medical Uses of Isotopes AMP authorized medical physicist AU authorized user CFR Code of Federal Regulations EGM enforcement guidance memorandum EMT emerging medical technology FR Federal Register Ga gallium Ge germanium GSR gamma stereotactic radiosurgery HDR high dose-rate Mo molybdenum NPV net present value NRC U.S. Nuclear Regulatory Commission OAS Organization of Agreement States Rb rubidium RSO radiation safety officer SECY Office of the Secretary of the Commission SRM staff requirements memorandum Sr strontium T&E training and experience Tc technetium TEDE total effective dose equivalent Y yttrium v

Executive Summary The U.S. Nuclear Regulatory Commission (NRC) is considering revising Title 10 of the Code of Federal Regulations (10 CFR) Part 35, Medical Use of Byproduct Material, to add requirements that address calibration and dosage measurement for strontium-82/rubidium-82 generators (hereafter referred to as rubidium-82 (Rb-82) generators) and to establish performance-based requirements for existing and future emerging medical technologies (EMTs).

The Commission approved initiation of this rulemaking in the Staff Requirements Memorandum (SRM) Staff RequirementsSECY-21-00013Rulemaking Plan to Establish Requirements for Rubidium-82 Generators and Emerging Medical Technologies, dated January 13, 2022 (Agencywide Documents Access and Management System Accession No. ML22013A266). As outlined in the rulemaking plan, the next step in the NRCs rulemaking process is the development of a regulatory basis that serves as a precursor to the proposed rule. This regulatory basis document summarizes the current regulatory framework, describes the regulatory issues and proposed changes to 10 CFR Part 35, and evaluates alternatives for establishing requirements in 10 CFR Part 35 for Rb-82 generators and EMTs. This regulatory basis also includes preliminary cost estimates for the NRC, Agreement States, and licensees for each alternative. Table ES-1 shows the estimated net costs (negative values shown in parentheses) or averted costs (positive values) associated with the alternatives considered.

The NRC is conducting rulemaking as described in Alternative 4 of this regulatory basis. Under Alternative 4, the NRC would update 10 CFR Part 35 to: (1) establish calibration and dosage measurement requirements for Rb-82 generators, (2) establish risk-informed, performance-based requirements for existing EMTs based on operating experience, and (3) revise other outdated, prescriptive requirements with risk-informed, performance-based requirements such as revisions to quality assurance program requirements for devices regulated under 10 CFR Part 35, Subpart H, Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units. Alternative 4 would align the NRCs medical regulations with advancements in technology and operating experience gained since the 2002 rulemaking that revised the NRCs regulatory framework for medical use and would improve the overall flexibility of 10 CFR Part 35 to better accommodate future EMTs.

The rulemaking would result in net averted costs totaling $1,169,000 over 15 years using a 7-percent discount rate.1 There are additional unquantified benefits of the rulemaking as described in Section 8.7 of the regulatory basis. The NRC will further refine these preliminary cost and benefit estimates in the regulatory analysis for the proposed rule, as informed by comments on this regulatory basis.

1 Benefit-cost values in this regulatory basis document are net present value, calculated using a real discount rate of 7 percent in accordance with Office of Management and Budget Circular A-94, Guidelines and Discount Rates for Benefit-Cost Analysis of Federal Programs, available at http://www.whitehouse.gov/wp-content/uploads/legacy_drupal_files/omb/circulars/A94/a094.pdf.

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Table ES-1: Summary Table of Alternatives and Net Benefits (Costs)

DESCRIPTION Net Benefits in 2022 Dollars Undiscounted 7% NPV 3% NPV Alternative 1 - Status Quo ($117,000) ($324,000) ($236,000)

Alternative 2 - Generators Only Rulemaking ($963,000) ($1,042,000) ($1,042,000)

Alternative 3 - Limited Scope Rulemaking $7,627,000 $959,000 $3,774,000 Alternative 4 - Expanded Scope Rulemaking $9,387,000 $1,169,000 $4,573,000

• NPV = net present value

• Values in parentheses, e.g., (), are negative and denote a cost. Averted costs are positive and are shown without parentheses.

• Values rounded to the nearest thousand. There may be differences among the tables due to rounding.

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1. Introduction In SECY-21-0013, Rulemaking Plan to Establish Requirements for Rubidium-82 Generators and Emerging Medical Technologies, dated February 9, 2021 (Agencywide Documents Access and Management System Accession No. ML20261H562), the staff sought Commission approval to initiate rulemaking for Title 10 of the Code of Federal Regulations (10 CFR) Part 35, Medical Use of Byproduct Material, that would add requirements for calibration and dosage measurement for strontium-82/rubidium-82 generators (hereafter referred to as rubidium-82 (Rb-82) generators) and establish performance-based requirements for existing and future EMTs (the NRC uses the term EMT to describe any medical technology licensed under 10 CFR 35.1000, Other medical uses of byproduct material or radiation from byproduct material). The Commission approved initiation of this rulemaking in the staff requirements memorandum (SRM) to SECY-21-0013, dated January 13, 2022 (ML22013A266).

Additionally, in the SRM to SECY-20-0005, Staff Requirements MemorandumRulemaking Plan for Training and Experience Requirements for Unsealed Byproduct Material, dated January 27, 2022 (ML22027A519), the Commission directed the staff, as part of the rulemaking for SECY-21-0013, to reconsider the full complement of training and experience requirements within the current paradigm and obtain stakeholder comments on the knowledge topics encompassing the safety related characteristics of EMTs required for Authorized Users to fulfill their radiation safety-related duties and supervision roles; the methods on how knowledge topics should be acquired; and consideration for continuing education, vendor training for new medical uses, and training on the NRC regulatory requirements.

Accordingly, the NRC has prepared this regulatory basis, which does the following:

• Provides background information on the current policies and regulations relative to the issues.

• Explains proposed changes to the regulations and how they could resolve the issues.

• Provides the technical and policy information used to support the regulatory basis.

• Identifies different approaches that could address the regulatory issues and evaluates the cost and benefits of rulemaking and the alternatives.

• Explains limitations on the scope and quality of the regulatory basis, such as known uncertainties in the data or methods of analysis and the mitigation measures that address these limitations.

2. Background and Existing Regulatory Framework This section briefly discusses background information, including the existing regulatory framework, for Rb-82 generators, EMTs, and other areas where changes are being considered to make 10 CFR Part 35 more flexible and performance-based to accommodate future EMTs.

2.1 Rubidium-82 Generators Rubidium-82 generators produce Rb-82 chloride, a positron-emitting radiopharmaceutical used for cardiac imaging. These generators are licensed under 10 CFR 35.200, Use of unsealed byproduct 1

material for imaging and localization studies for which a written directive is not required. However, the short half-life of Rb-82 and the generators automated elution and patient infusion makes Rb-82 generators different from other generators licensed under 10 CFR 35.200. Licensees cannot meet the requirements in: (1) 10 CFR 35.60, Possession, use, and calibration of instruments used to measure the activity of unsealed byproduct material, for the calibration of radiation detectors associated with medical use, and (2) 10 CFR 35.63, Determination of dosages of unsealed byproduct material for medical use, to determine the activity of each dosage administered before medical use.

Because licensees cannot meet the requirements of 10 CFR 35.60 and 10 CFR 35.63, the NRC may exercise enforcement discretion in certain circumstances per Enforcement Guidance Memorandum (EGM) 13-003, Enforcement Guidance MemorandumInterim Guidance for Dispositioning Violations Involving 10 CFR 35.60 and 10 CFR 35.63 for the Calibration of Instrumentation to Measure the Activity of Rubidium-82 and the Determination of Rubidium-82 Patient Dosages, dated April 18, 2013 (ML13101A318). Enforcement discretion may be used if the following criteria are met:

1) Licensees have written test procedures to ensure that the infusion pump flow rate is consistent and accurate, and that the radiation detector meets the manufacturers specifications. Licensees perform the tests at least every twelve months (and repeated after repair or replacement) and maintain records documenting the performance and results of these tests.

2) Authorized users (AUs) for the generator and the radiation safety officer (RSO) successfully complete training specific to the manufacturer and model of generator and infusion cart being used.

3) The licensee records the activity of each dosage administered, as provided by the infusion cart.

As discussed in Section 3, Regulatory Issues, enforcement discretion is not intended to be a long-term solution to regulatory compliance issues. The alternatives evaluated in this regulatory basis involve exemptions or rulemaking to resolve the calibration and dosage measurement compliance issues for Rb-82 generators.

2.2 Emerging Medical Technologies In 2002, the NRC amended 10 CFR Part 35, in part, to add generic requirements for new medical uses of byproduct material or radiation from byproduct material. 2 Subpart K of 10 CFR Part 35, Other Medical Uses of Byproduct Material or Radiation from Byproduct Material, (also referred to as 10 CFR 35.1000), defines the process to obtain a license or license amendment for EMTs. A given EMT may need unique provisions for training and experience (T&E) of AUs, facilities and equipment, or other safety-related considerations that the NRC does not capture in the existing 10 CFR Part 35 subparts. Therefore, the NRC or Agreement States evaluate each radioactive materials license application for an EMT on a case-by-case basis to determine the specific risks associated with the EMT and any additional regulatory requirements needed for its medical use.

The NRC or Agreement States may develop licensing guidance that is specific to the EMT, with input from the Advisory Committee on the Medical Uses of Isotopes (ACMUI) and EMT vendors as appropriate. EMT licensing guidance consists of general licensing considerations, specific radiation 2 10 CFR Parts 20, 32, and 35, Medical Use of Byproduct Material; Final Rule (67 FR 20249; April 24, 2002).

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safety aspects of the EMT, and T&E expectations for those authorized to use the technology. EMT licensing guidance documents may be revised based on feedback from the EMT vendor, licensees using the EMT, and regulators with experience in licensing and inspecting the EMT. The NRC has revised the original guidance documents for some EMTs several times to adopt changes in the devices, administrations, and T&E requirements.

The regulatory requirements and licensing process for EMTs are in 10 CFR 35.1000, while 10 CFR 35.12, Application for license, amendment, or renewal, includes the specific information licensees and applicants must provide to the NRC in support of an application for use under 10 CFR 35.1000. Model- and vendor-specific EMT licensing guidance assists licensees and applicants in their submission of licensing information required by 10 CFR 35.12 and guides the NRC and Agreement State staff in their reviews of EMT licensing information. NUREG-1556, Volume 9, Revision 3, Consolidated Guidance About Materials Licenses: Program-Specific Guidance About Medical Use Licenses, Final Report (September 2019; ML19256C219), also assists licensees and applicants in submitting the information to support an application or amendment for an EMT.

Licensing guidance for EMTs provides applicants with an acceptable means to satisfy the requirements for a license for the EMT, but the NRC does not intend that guidance be the only means for satisfying the requirements, and the guidance is not binding on licensees. Therefore, during licensing to approve use of an EMT, the NRC issues license conditions for applicants who commit to following the EMT licensing guidance, making the guidance a requirement for licensees.

If an applicant submits information describing alternative methods that are deemed by the NRC to be acceptable, those commitments would be placed in license conditions, making them a requirement for the licensee.

Since its issuance in 2002, the Subpart K regulatory framework has enabled the NRC and Agreement States to license 16 EMTs. 3 Some EMTs, such as yttrium-90 (Y-90) microspheres and newer generations of gamma stereotactic radiosurgery (GSR) units, are frequently licensed and widely used in the medical community, whereas other EMTs are less commonly used. The NRC is currently developing EMT licensing guidance for three EMTs, and the staff expects to develop EMT licensing guidance for several additional EMTs in the near term.

2.3 Agreement State Regulatory Program Section 274 of the Atomic Energy Act of 1954, as amended, authorizes the NRC to enter into agreements with individual States, known as Agreement States, providing them the authority and responsibility for administering a regulatory program for the safe use of radioactive materials within their borders. Agreement States have the authority to regulate the materials covered by the agreement for the protection of public health and safety. Agreement States are required to adopt regulations in accordance with the compatibility category designation (A, B, C, D, NRC, and H&S) assigned to each NRC regulation, as described in NRC Management Directive 5.9, Adequacy and Compatibility of Program Elements for Agreement State Programs, dated April 26, 2018 (ML18081A070).

3 The NRC has issued EMT licensing guidance more than two dozen times since 2002, including revisions to existing guidance to address small changes in the devices, administrations, and T&E requirements. The Medical Uses Licensee Toolkit on the NRC website (https://www.nrc.gov/materials/miau/med-use-toolkit.html) lists EMTs the agency has previously evaluated and their associated licensing guidance.

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This rule would revise multiple sections of 10 CFR Part 35 (see Appendix A for the proposed changes). The staff expects that compatibility categories for revisions to existing regulations would be maintained, and any new regulations would be assigned the same compatibility category as similar existing regulations. 4 The NRC will coordinate with the Standing Committee on Compatibility to determine compatibility categories for revised and new regulations.

3. Regulatory Issues This section describes the regulatory issues that will be addressed by this rulemaking. The NRC defined the existing medical uses in 10 CFR Part 35, Subparts D through H, in 2002. Existing regulated medical uses of byproduct material have evolved because of changing medical practices, associated technological advancements, and increased operational experience, making aspects of the current 10 CFR Part 35 regulatory framework outdated or even obsolete. In this section, the staff has identified the challenges associated with licensing Rb-82 generators and existing and future EMTs under the existing medical uses in 10 CFR Part 35, Subparts D through H. The proposed changes to 10 CFR Part 35 to regulate calibration and dose measurement for Rb-82 generators and license current and future EMTs outside 10 CFR Part 35, Subpart K, are listed in Appendix A.

3.1 Rubidium-82 Generators CardioGen-82 and RUBY-FILL are two brands of Rb-82 generator systems that produce Rb-82 chloride injection for intravenous use. Given the short half-life of Rb-82, the Rb-82 generator eluate is injected directly into the patient through an infusion cart, and the patient is imaged immediately following infusion. The infusion cart contains a radiation detector and flow rate meter to measure and calculate the activity of the Rb-82. The radiation detector works in a dynamic mode with fluid continuously flowing past the detector during operation. 5 Section 35.60 of 10 CFR Part 35 requires licensees to calibrate the instrumentation that measures the activity of unsealed byproduct administered to each patient or human research subject. This calibration may either be performed in accordance with nationally recognized standards or calibration instructions provided by the manufacturer. However, there are currently neither nationally recognized standards nor specific calibration procedures that meet the requirements of 10 CFR 36.60 for calibrating radiation detectors in a dynamic mode. Until such standards or procedures are developed, Rb-82 generator licensees cannot comply with 10 CFR 35.60. Furthermore, 10 CFR 35.63 requires licensees to determine the activity of each dosage administered before medical use. Due to the direct infusion into the patient, Rb-82 generator licensees are unable to measure patient dosages of Rb-82 prior to administration using an instrument that is calibrated in accordance with 10 CFR 35.60.

As discussed in Section 2.1, EGM 13-003 discusses how the NRC may disposition violations of 10 CFR 35.60 and 10 CFR 35.63 based on the inherent issues associated with Rb-82 generators if certain criteria are met by licensees. However, longstanding reliance on temporary enforcement guidance to exercise enforcement discretion is inconsistent with the NRCs Enforcement Policy, dated January 15, 2020 (ML19352E921), and is not a substitute for resolving the underlying technical issues associated with calibration and dosage measurement for Rb-82 generators. The guidance states that the EGM will remain effective until the underlying technical issue is dispositioned through rulemaking or other regulatory action.

4 Compatibility categories for 10 CFR Part 35 are available on the NRCs Regulation Toolbox website at https://scp.nrc.gov/regsumsheets_newregs.html.

5 Typically, radiation detectors that determine dose activity operate in a static mode with the stationary fluid and are not dependent on flow rate meter measurements.

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3.2 Continued Licensing of Well-Established Emerging Medical Technologies Under 10 CFR Part 35, Subpart K While 10 CFR Part 35, Subpart K, has proven to be a flexible way to review and license new EMTs, the continued licensing of well-established EMTs under Subpart K provides minimal regulatory benefit and is contrary to the NRCs principles of good regulation. 6 As discussed in Section 2.2, the basis for licensing EMTs is established through license conditions rather than regulations. This was identified as a problem and addressed for other well-established EMTs in the final regulatory analysis for the 2002 rulemaking for 10 CFR Part 35, which states, NRC has identified the following six problems require revisions to 10 CFR Part 35[R]evisions are needed to place the basis for regulation of certain well-established technologies into 10 CFR Part 35.

Specifically, the regulations in 10 CFR Part 35 currently do not address high dose-rate remote brachytherapy, low dose-rate remote brachytherapy, pulsed dose-rate remote brachytherapy, and gamma stereotactic radiosurgery. The regulatory basis for these technologies is currently established by license conditions rather than regulations. 7 With sufficient operating experience, EMTs that are no longer considered emerging can be moved out of 10 CFR Part 35, Subpart K, and their regulations can be established in existing or new medical use subparts in 10 CFR Part 35. Continued licensing of commonly used and now well-established EMTs under 10 CFR Part 35, Subpart K, could create the following regulatory issues:

• Implementation of EMT licensing guidance is subject to individual interpretation by regulators, and the EMT licensing guidance is not legally binding until it is incorporated into a license through a license condition. Furthermore, EMT licensing guidance is a Compatibility Category C program element, which could create inconsistency in applying some requirementssuch as T&E for AUs and medical event reporting, which are Compatibility Category B requirements for technologies licensed under the other subparts of 10 CFR Part 35. 8 For example, T&E requirements in EMT licensing guidance could be adopted differently among the States, which would pose cross-jurisdictional issues in the licensing of AUs for EMTs (i.e., each States licensing program would not be able to use another States license authorization for AUs for EMTs since their regulations would not be identical). This compatibility issue has been raised by Agreement States, and the NRC responded to a request from the Organization of Agreement States (OAS) for clarification on two regulatory topics addressed in EMT licensing guidance: (1) T&E for Y-90 microspheres, and (2) use of safety evaluation reports as license conditions for the NorthStar RadioGenix Mo-99/Tc-99m Generator System. 9 While less regulatory certainty may be needed in the early stages of licensing new EMTs under 10 CFR Part 35, Subpart K, establishing regulations for commonly-used EMTs will promote consistency, 6 The NRCs principles of good regulation are independence, openness, efficiency, clarity, and reliability (accessed at https://www.nrc.gov/about-nrc/values.html on August 6, 2022).

7 See Attachment 12, Final Regulatory Analysis, 10 CFR Parts 20, 32, and 35, in SECY-00-0118, Final Rules -

10 CFR Part 35, Medical Use of Byproduct Material and 10 CFR Part 20, Standards for Protection Against Radiation, May 31, 2000. (Accessed at https://www.nrc.gov/reading-rm/doc-collections/commission/secys/2000/secy2000-0118/2000-0118scy.pdf, on August 6, 2022.)

8 Compatibility Category C means that Agreement States should adopt the essential objectives of the provisions in the EMT licensing guidance, but they do not have to adopt them essentially as written. Compatibility Category B means that Agreement States must adopt these requirements in an essentially identical manner.

9 State and Tribal Communication (STC)20-049, Responses to the Organization of Agreement States (OAS)

Requests Regarding Clarification of Compatibility Categories for Medical Licensing Guidance Documents; and Use of Safety Evaluation Reports (SERs) as a Legally Binding Requirement, dated June 30, 2020 (ML20178A610).

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compatibility, and efficiency across the National Materials Program (i.e., licensing and inspection by the NRC and Agreement States), and will improve clarity.

• Developing and frequently updating EMT licensing guidance can be time- and resource-intensive for the NRC and Agreement States. EMT licensing guidance is model- and vendor-specific, so each new model or vendor of even a similar type of technology requires a new guidance document or a revision to a current guidance document. Furthermore, EMT licensing guidance is updated more frequently than other medical use guidance documents (e.g., the generic regulatory guidance in NUREG-1556, Volume 9). The NRC has revised the original guidance documents for some EMTs several times to adopt small changes in the devices, administrations, and T&E requirements. Performance-based regulations that focus on the essential safety-related elements of EMT licensing guidance will minimize the need to develop or revise EMT licensing guidance for new models or vendors of existing EMTs and the need to update outdated EMT licensing guidance.

3.3 Current Emerging Medical Technologies Sections 3.3.1 through 3.3.9 address the EMTs that will be considered in this rulemaking. 10 These sections provide brief background information on the EMTs and why the NRC determined they should be licensed under 10 CFR 35.1000 when the technology emerged. Appendix A discusses proposed changes to 10 CFR Part 35 that the NRC is considering that would establish regulations for these EMTs, thereby allowing them to be licensed without the need to meet the requirements in 10 CFR 35.1000.

3.3.1 Germanium-68/Gallium-68 Pharmaceutical Grade Generators Gallium-68 (Ga-68) is a positron emitter that is used to label radiopharmaceuticals for positron emission tomography imaging. Gallium-68 can be produced in a cyclotron or by the elution of a germanium-68/gallium-68 (Ge-68/Ga-68) radionuclide generator.

Germanium-68/gallium-68 generators are similar to conventional molybdenum-99/technetium-99m (Mo-99/Tc-99m) and Rb-82 generators, both of which are regulated under 10 CFR Part 35, Subpart D, because breakthrough of the parent radionuclide is possible when eluting the generator. In the case of Ge-68/Ga-68 generators, this could lead to Ge-68 contaminating the Ga-68 radiopharmaceutical causing an unnecessarily high radiation exposure to patients.

Section 35.204 of 10 CFR Part 35, Permissible molybdenum-99, strontium-82, and strontium-85 concentrations, provides permissible concentration limits for parent radionuclides for Mo-99/Tc-99m and Rb-82 generators to limit such exposure, but no such limit is specified for Ge-68/Ga-68 generators. Therefore, the use of a Ge-68/Ga-68 generator to prepare Ga-68 10 This rulemaking will not establish regulations for the NorthStar RadioGenix Mo-99/Tc-99m Generator System.

The unique methods to isolate and concentrate Tc-99m in the NorthStar RadioGenix Mo-99/Tc-99m Generator System make it a more complex and higher radiation safety risk generator than traditional Mo-99/Tc-99m, Rb-82, and Ge-68/Ga-68 generators. Risk characteristics of the NorthStar RadioGenix Mo-99/Tc-99m Generator System include higher activity and radiation exposure rates and automated systems with multiple user interfaces. To accommodate the radiation safety risks associated with the NorthStar RadioGenix Mo-99/Tc-99m Generator System, significant revisions to 10 CFR Part 35, Subpart D would be required.

Furthermore, there are no NRC medical licensees authorized to use the NorthStar RadioGenix Mo-99/Tc-99m Generator Systemcurrently only nuclear pharmacies (which are licensed under 10 CFR Part 32, Specific Domestic Licenses to Manufacture of Transfer Certain Items Containing Byproduct Material) are using the NorthStar RadioGenix Mo-99/Tc-99m Generator System. The staff anticipates nuclear pharmacies will continue to be the primary users of the NorthStar RadioGenix Mo-99/Tc-99m Generator System. Therefore, the staff determined that maintaining licensing of the NorthStar RadioGenix Mo-99/Tc-99m Generator System under 10 CFR Part 35, Subpart K, would be the most practical and cost-effective regulatory approach.

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radiopharmaceuticals for imaging and localization studies authorized under 10 CFR Part 35, Subpart D, is regulated under 10 CFR Part 35, Subpart K. Since the potential for Ge-68 breakthrough exists, the NRC requires appropriate commitments for breakthrough testing and allowable concentrations of Ge-68 from applicants that use these generators prior to granting authorization to possess and use Ge-68/Ga-68 generators under 10 CFR Part 35, Subpart K. The most recent licensing guidance for Ge-68/Ga-68 generators was issued in July 2019 (ML19106A367).

3.3.2 Intravascular Brachytherapy Systems Intravascular brachytherapy (IVB) is a type of brachytherapy where the sources are placed within blood vessels for treatment. The current 10 CFR 35.1000 licensing guidance is for the Best Vascular (formally Novoste') Beta-Cath' IVB System, which is manually controlled and utilizes a strontium-90 (Sr-90) source to deliver high dose rates of beta radiation.

Intravascular brachytherapy has use characteristics that allow it to be considered for licensing as manual brachytherapy under 10 CFR Part 35, Subpart F, Manual Brachytherapy, or as a high dose-rate (HDR) afterloader under Subpart H, Photon Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units. These uses are defined in 10 CFR 35.2, Definitions. In manual brachytherapy, small sources (e.g., seeds or ribbons) are manually placed topically on or inserted either into the body cavities that are in close proximity to a treatment site or directly into the tissue volume. An HDR afterloader remotely delivers a dose rate in excess of 12 gray (Gy) (1,200 rads) per hour at the point or surface where the dose is prescribed. Since IVB devices can deliver a dose rate in excess of 12 Gy (1,200 rads) per hour, they are similar to HDR afterloader treatments. However, they are not delivered remotely like HDR afterloader treatments, and in that sense IVB is more like manual brachytherapy. Therefore, IVB devices do not directly fall into either 10 CFR 35, Subparts F or H.

Intravascular brachytherapy also has specific safety concerns that are addressed in licensing guidance. Examples include requiring the use of an introducer sheath and a dual syringe system to reduce the risk of a medical event; and requiring written procedures for treatment of an area longer than the effective treatment length of the source (which is known as source-stepping).

As a result of these differences from the technologies currently regulated in 10 CFR Part 35, Subparts F and H, and the additional safety concerns that are not currently addressed in the regulations, the NRC determined that the use of the Best Vascular (formally Novoste')

Beta-Cath' device should be regulated under 10 CFR Part 35, Subpart K. The licensing guidance for Best Vascular Beta-Cath' IVB System was issued in August 2006 and is available at the NRCs website at https://www.nrc.gov/materials/miau/med-use-toolkit/intravascular.html.

3.3.3 Liquid Brachytherapy Sources and Devices Liquid brachytherapy is a type of manual brachytherapy that treats cancer with devices that are implanted temporarily. The current 10 CFR 35.1000 licensing guidance is for the I-125 Iotrex' Liquid Brachytherapy Source in Cytyc Surgical Products GliaSite Radiation Therapy System (GliaSite). GliaSite is a single-use low dose-rate brachytherapy system consisting of a double-wall balloon catheter filled with lotrex', a liquid brachytherapy solution consisting of iodine-125 (I-125) and saline. The system is intended to deliver intracavity radiation therapy to patients with malignant brain tumors following tumor resection surgery.

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Liquid brachytherapy has use characteristics similar to the existing medical uses in 10 CFR Part 35, Subpart F. However, the current regulations in 10 CFR Part 35, Subpart F, do not cover all the safety concerns associated with use of GliaSite. Safety concerns for GliaSite include removal of all liquid from the device, leak testing of the device before use, and the need for an AU with experience in radiopharmaceutical procedures to be on-call to provide guidance in case of leakage. Additionally, the current written directive requirements 11 do not include requirements specific to liquid brachytherapy to ensure that the prescribed dose is administered.

As a result of these differences from the technologies currently regulated in 10 CFR Part 35, Subpart F, and the additional safety concerns that are not currently addressed in the regulations, the NRC determined that the use of GliaSite should be regulated under 10 CFR Part 35, Subpart K. The licensing guidance for GliaSite was issued in August 2006 and is available at the NRCs website at https://www.nrc.gov/materials/miau/med-use-toolkit/liquid-brach.html.

Although the Sealed Source and Device (SS&D) registry 12 for the GliaSite Radiation Therapy System is inactivewhich means this device can no longer be made or soldthe NRC supports establishing regulations for liquid brachytherapy to capture operational experience for future liquid brachytherapy technologies.

3.3.4 Radioactive Seed Localization Radioactive seed localization (RSL) procedures implant low-activity I-125 or palladium-103 seeds to help physicians locate non-palpable lesions and lymph nodes. These procedures use decayed radioactive seeds previously approved for the treatment of tumors under 10 CFR Part 35, Subpart F, or low-activity radioactive seeds approved by the U.S. Food and Drug Administration (FDA) specifically for RSL.

The procedures using RSL are not therapeutic; therefore, RSL does not meet the definition of brachytherapy in 10 CFR 35.2 and subsequently does not meet the requirements of 10 CFR Part 35, Subpart F. The sealed nature of the RSL sources means that the unsealed byproduct material requirements in 10 CFR Part 35, Subpart D, do not apply. The application of RSL for location only, and the sources original use in therapeutics, also means that the diagnostic purposes in 10 CFR Part 35, Subpart G, Sealed Sources for Diagnosis, do not apply. As a result of these differences from the technologies currently regulated in 10 CFR Part 35, Subparts D, F, and G, the NRC determined RSL should be regulated under 10 CFR Part 35, Subpart K.

Revision 1 of the licensing guidance for RSL was issued in October 2016 (ML16197A568).

3.3.5 Manual Brachytherapy Using Diffusing Sources The Alpha DaRT' (Diffusing Alpha-emitters Radiation Therapy) uses interstitial radioactive sources that continuously release radon-220 alpha particles through diffusion to treat tumors.

These sources are made of stainless-steel tubes with a layer of radium-224 embedded into the surface of the tube. The sources are temporarily inserted into the tumor volume and removed when the treatment is complete.

The Alpha DaRT' source and applicator are similar to other manual brachytherapy uses that fall under 10 CFR Part 35, Subpart F. However, the diffusing release of radon-220 (which is an alpha-11 10 CFR 35.40, Written directives, and 35.41, Procedures for administrations requiring a written directive.

12 The SS&D registry is a national registry that contains all the registration certificates, generated by both the NRC and the Agreement States, that summarize the radiation safety information for sealed sources and devices and describe the licensing and use conditions approved for the products.

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emitting noble gas from the radium-224 source) in tissue is a unique property that merits additional radiation safety considerations not addressed by the current regulations. Examples of other areas not addressed in current regulations for this use include: (1) the use of a sealed container for all waste and unsealed sources to control contamination, and (2) the need to ensure the integrity of the applicator seal before administration to verify calibration measurements and assess for a possible leak. As a result of these differences from the technologies currently regulated in 10 CFR Part 35, Subpart F, the NRC determined that use of this device should be regulated under Subpart K. The licensing guidance for Alpha DaRT' was issued in March 2022 (ML22018A225),

along with a regulatory guidance chart that provides a list of 10 CFR Part 35 regulations and conditions that are applicable to the use of Alpha DaRT' (ML22018A223).

3.3.6 Ophthalmic Applicator Sources and Devices The use of Sr-90 ophthalmic (eye) applicator sources is regulated under 10 CFR Part 35, Subpart F. One type of eye applicator source and device system, the NeoVista, Inc. Epi-Rad90' Ophthalmic System, is currently regulated under 10 CFR 35.1000, and the NRC is currently developing licensing guidance for another eye applicator sourcethe LV Liberty Vision Yttrium-90 Disc Source.

3.3.6.1 NeoVista, Inc. Epi-Rad90TM Epiretinal (Strontium-90) Ophthalmic System The NeoVista, Inc. Epi-Rad90' Epiretinal Ophthalmic System (Epi-Rad90') is an Sr-90 eye applicator device used for treatment of age-related macular degeneration. The design and operation are significantly different from that of traditional Sr-90 superficial eye applicators because the device is used intraocularly and the dose is delivered internally. The Epi-Rad90' system needs a retinal surgeon to remove the vitreous clear gel from the middle portion of the eye and place the Sr-90 source to treat the affected area. Training and experience for AUs follows 10 CFR 35.490, Training for use of manual brachytherapy sources, or 35.491, Training for ophthalmic use of strontium-90, however, additional training is required. All AUs, non-AU retinal surgeons, authorized medical physicists (AMPs), and RSOs must receive additional training in the operation, safety procedures, and clinical use of the Epi-Rad90' system. There are also specific requirements related to written directives and radiation safety precautions and instructions. As a result of these differences from the eye applicator sources and devices currently regulated in 10 CFR Part 35, Subpart F, the NRC determined that use of the Epi-Rad90'system should be regulated under 10 CFR 35, Subpart K. The Epi-Rad90' system licensing guidance was issued in April 2009 (ML091140370).

3.3.6.2 LV Liberty Vision Yttrium-90 Disc Source The LV Liberty Vision Yttrium-90 Disc Source (hereafter the LV Y-90 Disc Source) is a temporary eye applicator source used to treat superficial eye conditions, as well as some ocular tumors and benign growths, as part of a hand-held manual brachytherapy applicator system. The applicator system is like traditional Sr-90 eye applicators licensed under 10 CFR 35, Subpart F, because the source is affixed to the applicator and the applicators handles allow for movement of the source.

However, the Y-90 source makes the LV Y-90 Disc Source different from traditional eye applicators. Until the LV Y-90 Disc Source, Sr-90 has been the standard radionuclide for ophthalmic radiotherapy.

Section 35.400 of 10 CFR Part 35 allows use of a Y-90 source for ophthalmic radiotherapy.

However, the regulations limit the AU to a physician with T&E under 10 CFR 35.490, i.e., a radiation oncologist. Other types of physicians with additional training under 10 CFR 35.491, such 9

as ophthalmologists, could perform ophthalmic radiotherapy under 10 CFR 35.400, but the regulations restrict these physicians to the ophthalmic use of Sr-90 sources. Additional regulations are also limited to Sr-90 sources, including 10 CFR 35.433, Strontium-90 sources for ophthalmic treatments, which requires an AMP or ophthalmic physicist to perform specific tasks related to source decay and treatment time and written procedures, and 10 CFR 35.2433, Records of decay of strontium-90 sources for ophthalmic treatments.

Because it uses a different radionuclide from eye applicator sources currently regulated in 10 CFR Part 35, Subpart F, the NRC determined that the use of the LV Y-90 Disc Source should be regulated under 10 CFR Part 35, Subpart K. The licensing guidance for the LV Y-90 Disc Source is expected to be issued in summer of 2023, and will be available at the NRCs website for emerging medical technologies at https://www.nrc.gov/materials/miau/med-use-toolkit/emerg-licensed-med-tech.html.

3.3.7 Gamma Stereotactic Radiosurgery and Photon Emitting Teletherapy Units Multiple radiation beams in GSR units precisely target tumors and other treatment sites to deliver radiation, while sparing the surrounding areas. In 2002, the NRC developed requirements in 10 CFR Part 35, Subpart H, that allowed for the use of GSR units. Previous GSR units utilized stationary sources, helmet collimators, and a head frame for treatments of the brain. Since that time, newer GSR units have design and engineering elements that make their operation significantly different than those currently regulated in 10 CFR Part 35, Subpart H. To account for the radiation safety concerns of these engineering changes, the NRC developed licensing guidance specific to the model and vendor of three GSR units: Leksell Gamma Knife Perfexion',

Leksell Gamma Knife Icon', and Xcision GammaPod'. The NRC is also developing guidance for the Akesis Galaxy unit and is aware of additional GSR models in various developmental stages. The ViewRayTM System for Radiation Therapy (hereafter the ViewRayTM System), a teletherapy unit, is also regulated under 10 CFR Part 35, Subpart K, due to similar technological advancements.

3.3.7.1 Leksell Gamma Knife Perfexion' and Leksell Gamma Knife Icon' The Leksell Gamma Knife PerfexionTM and Leksell Gamma Knife Icon TM (hereafter the PerfexionTM and IconTM, respectively) include several engineering changes that make their components and operation significantly different from the GSR units currently regulated in 10 CFR Part 35, Subpart H. These engineering changes include: (1) the elimination of helmets, relative helmet factors, helmet microswitches, hydraulic backups, trunnions, and a trunnion centricity point; (2) the location of the sources in moveable sectors; (3) the location of the source exposure indicator on the treatment room wall and not on the unit itself; and (4) a moveable patient couch. The PerfexionTM unit uses a stereotactic head frame and frame adapter. The Icon' unit is an upgrade from the PerfexionTM unit that uses cone beam computed tomography imaging to obtain stereotactic reference information and position references. The Icon' unit uses a stereotactic head frame and frame adapter or a frameless thermoplastic mask and mask adapter system to immobilize the patients head. The Icon' also uses a high-definition motion management system to monitor movements of the patient during setup and treatment while the patient is immobilized by the mask. As a result of these differences from the GSR units currently regulated in 10 CFR Part 35, Subpart H, the NRC determined that the PerfexionTM and IconTM units should be regulated under Subpart K. Revision 1 of the licensing guidance for Leksell PerfexionTM and IconTM was issued in January 2019 (ML18333A365).

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3.3.7.2 Xcision Gammapod' The Xcision Gammapod' is a type of GSR unit that delivers a therapeutic dose to a partial volume of the breast for treatment of tumors. This device includes several design and engineering elements that make its components and operation significantly different from the gamma stereotactic radiosurgery units currently regulated in 10 CFR Part 35, Subpart H. These engineering differences include the lack of helmets, relative helmet factors, helmet microswitches, hydraulic backups, trunnions, and a trunnion centricity point. Additionally, GammaPod' has several engineering features that are not included in Subpart H, including its vacuum-assisted breast cup immobilization and stereotactic localization system, rotating source and collimator carriers, and table motion during treatment. As a result, the NRC determined that the GammaPod' should be regulated under 10 CFR Part 35, Subpart K. The licensing guidance for the Xcision Gammapod' was issued in January 2020 (ML19304B370).

3.3.7.3 ViewRay System' The ViewRay' System is a radiation therapy device containing three cobalt-60 sources on a rotating gantry assembly, integrated with a magnetic resonance imaging system capable of imaging during treatment. This device can be used for both teletherapy and GSR. Significantly different components and operation of the ViewRay' System include real time image guidance, multi-leaf collimation, and beam gating to block radiation should the patient move outside of a pre-set threshold. As a result, the NRC determined that the ViewRay' System should be regulated under 10 CFR Part 35, Subpart K. The licensing guidance for the ViewRay' System was issued in July 2013 (ML13179A287).

3.3.8 Microsource Manual Brachytherapy Yttrium-90 microspheres are manual brachytherapy sources used as permanent implants for treatment of liver and hepatic tumors. TheraSphere glass microspheres and SIR-Sphere resin microspheres are delivered by flushing of the delivery vial using a manual or automatic delivery system through tubing into a prepositioned catheter placed in the patients hepatic artery. The microspheres become lodged within the tumor vasculature and deliver radiation dose over several days until the microsources decay.

Yttrium-90 microspheres are described as manual brachytherapy devices that have use characteristics similar to the manual brachytherapy uses licensed under 10 CFR Part 35, Subpart F. However, Y-90 microspheres have many unique properties that merit radiation safety considerations other than those required by 10 CFR Part 35, Subpart F. These properties include their small size; the large number of microspheres used in a treatment; the route of administration (injection through tubing); and their use by radiation oncologists, nuclear medicine physicians, and interventional radiologists. Therefore, Y-90 microsphere manual brachytherapy sources do not fit under 10 CFR Part 35, Subpart F, and the NRC determined that Y-90 microspheres should be regulated under Subpart K. The guidance to initially license Y-90 microspheres was issued in October 2002 (ML082340866) and has been revised 12 times to address updates to devices, stakeholder input, and medical event reporting. The most recent licensing guidance was issued in April 2021 (ML21089A364).

Two types of Y-90 microspheres are currently described in the NRCs guidance, TheraSphere and SIR-Spheres. The NRC anticipates that additional technologies using permanent implantation therapy of microspheres or microparticles will require evaluation in the coming years. OncoSilTM uses phosphorus-32 embedded in silicon microparticles for the treatment of pancreatic cancer and 11

has been issued an Investigational Device Exemption by the FDA for use in clinical trials.

Additionally, QuiremSpheres uses holmium-166 microspheres for the treatment of liver and hepatic tumors through a similar mechanism to Y-90 microspheres but with improved imaging capabilities. QuiremSpheres are currently used in Europe.

3.4 Other 10 CFR Part 35 Changes In addition to conforming changes throughout 10 CFR Part 35 to establish regulations for the EMTs discussed above, the staff is considering changes to additional sections of 10 CFR Part 35 to revise or clarify outdated requirements. This section describes these additional regulatory issues being considered by the NRC, and Section A.9 of Appendix A describes the proposed changes.

Physician Definition (10 CFR 35.2)

The definition of a Physician in 10 CFR 35.2 is limited to an individual with a medical degree (medical doctor or doctor of osteopathy) that is licensed by a State or Territory in the United States, the District of Columbia, or the Commonwealth of Puerto Rico. This requirement limits a physician to a Doctor of Medicine or Doctor of Osteopathy degree, which means that to become an AU, licensed physicians with a foreign equivalent degree to practice medicine in the U.S. must request an exemption from the medical doctor or doctor of osteopathy requirement.

(This NRC definition of a physician is different than those for podiatrist, dentist, and pharmacist, which allow for an individual licensed to practice that specialty by a State or Territory in the United States, the District of Columbia, or the Commonwealth of Puerto Rico.)

Radiation Safety Committee (10 CFR 35.24)

Under 10 CFR 35.24, Authority and responsibilities for the radiation safety program, licensees must establish a Radiation Safety Committee if they are authorized for two or more different types of uses of byproduct material under Subparts E, F, and H, or two or more types of units under Subpart H. The Radiation Safety Committee oversees all uses of byproduct material permitted by the license. The requirement states that the Radiation Safety Committee must include an AU of each type of use permitted by the license, the RSO, a representative of the nursing service, and a representative of management who is neither an AU nor an RSO. Based on the current language in 10 CFR 35.24, EMTs under 10 CFR Part 35, Subpart K, are not considered in the requirement to establish a Radiation Safety Committee, nor are AUs for EMTs required to be part of the Radiation Safety Committee. Furthermore, the requirement to include a representative of the nursing service as a Radiation Safety Committee member is unclear, because large medical institutions may have various nursing services, many with no responsibilities related to the use of licensed byproduct material.

Supervision (10 CFR 35.27)

The supervision regulation allows supervised individuals to receive, possess, prepare, use, and transfer byproduct material under the supervision of an AU or an authorized nuclear pharmacist.

The licensee must instruct supervised individuals in, and require supervised individuals to follow, the licensees written radiation protection procedures, written directive procedures, applicable medical regulations, license conditions, and procedures for preparing byproduct material for medical use. This requirement clearly defines the instruction requirements for the supervised individual, but it does not require that the supervising AU or authorized nuclear pharmacist has also been instructed in these same procedures, regulations, and license conditions. (The T&E regulations in 10 CFR Part 35 do not require instructions in these specific topics.) Furthermore, the 12

regulation only requires that the licensee be responsible for the acts and omissions of the supervised individual, but not the acts and omissions of the supervising individual.

Procedures for Administrations Requiring a Written Directive (10 CFR 35.41)

Licensees are required to develop, implement, and maintain written procedures for any administration that requires a written directive, to assure that the patients or human research subjects identity is verified before each administration and that each administration is in accordance with the written directive. However, licensees are not required to verify that the written directive is correct, nor are licensees required to take any initial or refresher training on the requirements for written directives. Given an increase in medical events involving incorrect written directives, the increase in number of medical procedures that require written directives, and the increase in complexity of these procedures, the NRC is considering amending this regulation to require that licensees have procedures in place to verify that the written directive is correct, to require training on written directive procedures for AUs, and to require an annual review of the procedures.

Patient Release (10 CFR 35.75)

In accordance with 10 CFR 35.75, Release of individuals containing unsealed byproduct material or implants containing byproduct material, licensees may authorize the release from their control any individual who has been administered unsealed byproduct material or implants containing byproduct material if the total effective dose equivalent (TEDE) to any other individual from exposure to the released individual is not likely to exceed 5 millisieverts (0.5 rem). As clarified in the Statements of Consideration for the 1997 final rule for patient release criteria (62 FR 4120; January 29, 1997), this 5 millisieverts (0.5 rem) TEDE limit to an individual from the released patient applies to each patient treatment.

As part of the staffs evaluation of the NRCs patient release program, documented in SECY-18-0015, Staff Evaluation of the U.S. Nuclear Regulatory Commissions Program Regulating Patient Release After Radioisotope Therapy, dated January 29, 2018 (ML17279B139),

the staff considered whether the patient release limit should be changed from a per-release limit to a per-year limit. The staff noted that rulemaking to require the limit to be a per-year limit would be consistent with the occupational and public dose limits in 10 CFR Part 20, Standards for Protection Against Radiation, as well as with national and international standards. However, at the time of the evaluation, the staff concluded that rulemaking was not necessary to change the limit because it was rare for a patient to receive more than one radioactive treatment per year.

However, since 2018, the FDA has approved several new therapeutic radiopharmaceuticals, including Lutathera and Pluvicto, which have multiple administrations of lutetium-177 over the course of a single treatment regimen, and there are additional radiopharmaceuticals in clinical trials or research phases that also include multiple administrations in a single treatment regimen.

Therefore, the assumption that it would be rare for a patient to receive more than one radioactive treatment per year no longer applies and changes would be made to account for multiple releases for a single patient during a treatment regimen. Conforming changes would be made to define the term regimen in 10 CFR 35.2, update the written directive requirements in 10 CFR 35.40 to include regimen, and update medical event reporting in 10 CFR 35.3045 to allow the AU to change a regimen during the treatment protocol if medically necessary.

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Training and Experience Each subpart in 10 CFR Part 35 contains the T&E requirements necessary for a physician to become an AU for the use described in that subpart. As directed by the Commission in the SRM for SECY-20-0005, the NRC is seeking stakeholder feedback, via questions in Appendix A, on the knowledge topics encompassing the safety-related characteristics of EMTs required for AUs to fulfill their radiation safety-related duties and supervision roles; the methods on how knowledge topics should be acquired; and consideration for continuing education, vendor training for new medical uses, and training on NRC regulatory requirements. Stakeholder input will inform the establishment of T&E regulations for the EMTs addressed in this regulatory basis document.

Recentness of Training (10 CFR 35.59)

The requirements for continuing education and work experience do not currently include T&E for EMTs regulated under 10 CFR 35, Subpart K. Conforming changes would be made to this regulation to account for EMT T&E that would be established in 10 CFR Part 35.

4. Evaluation of Alternatives This section summarizes the four alternatives that the NRC considered. Alternative 1 is the status quo, which involves the use of exemptions. Alternatives 2, 3, and 4 are rulemaking alternatives.

Alternatives 2, 3, and 4 build on each other, with Alternative 2 being the most limited-scope rulemaking and Alternative 4 being the expanded-scope rulemaking. Under every alternative, EGM 13-003 would be retired, because it was intended for use only temporarily while the NRC determined an appropriate regulatory path. The regulatory framework of 10 CFR 35, Subpart K, would remain unchanged and available for future EMTs that may not fit into the revised medical use subparts of 10 CFR Part 35.

Costs are negative values and are denoted in parentheses, i.e., (); averted costs are positive values and are denoted without parentheses. All costs and averted costs are presented assuming a 7-percent net present value and are rounded to the nearest thousand. Costs and averted costs of each alternative are discussed in more detail in Section 8, Cost/Impact Considerations.

4.1 Alternative 1Status Quo The staff evaluated maintaining the status quo, where the NRC would use a non-rulemaking option to address the licensing of Rb-82 generators. Without rulemaking, approximately 220 NRC and Agreement State licensees would need to apply for exemptions from 10 CFR 35.60 and 10 CFR 35.63 to continue use of these generators. Submitting and processing exemptions would cost the NRC, Agreement States, and licensees approximately ($682,000) over 4 years using a 7 percent discount rate. Future Rb-82 generator licensees would also need to submit exemption requests. After exemptions are in place, the NRC, Agreement States, and licensees may realize some averted costs for Rb-82 generator inspection totaling $359,000 over 15 years13 associated with no longer having to document the conditions required for enforcement discretion. The estimated total net cost for Alternative 1 is ($324,000) using a 7 percent discount rate. 14 13 The staff chose 15 years after the rule goes into effect for the NRC and the Agreement States as the period to evaluate operational savings resulting from implementation of the rule, because this is the duration of a materials license.

14 Alternatives 2, 3, and 4 would also retire EGM 13-003through rulemaking instead of exemptionstherefore the net costs of these alternatives include the averted costs associated with avoiding the need for exemptions plus inspection efficiencies.

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The staff does not recommend Alternative 1 because continuous and widespread use of exemptions would not be an effective means of regulating Rb-82 generators. Rather, establishing appropriate regulatory requirements for Rb-82 generators would eliminate the compliance issues that exist today, and would provide a more efficient, clear, and reliable regulatory framework for these generators.

4.2 Alternative 2Rulemaking Only for Rubidium-82 Generators This rulemaking would solely address calibration and dosage measurement requirements for Rb-82 generators. It would not result in any changes related to EMTs. The estimated total net cost of Alternative 2 is ($1,042,000) using a 7 percent discount rate over 15 years.

Table 2: Advantages and Disadvantages of Alternative 2 Advantages

• Would remove the need for licensees to submit exemption requests for 10 CFR 35.60 and 10 CFR 35.63 (exemptions would be required absent EGM 13-003 or a rulemaking).

• Would provide opportunity for public comment on calibration and dosage measurement requirements for Rb-82 generators.

• Would improve regulatory openness, efficiency, clarity, and reliability for Rb-82 generators, and result in averted costs of $940,000 for the NRC, Agreement States, and licensees associated with inspection efficiencies and avoiding the need for exemptions.

• Rulemaking and implementation costs would be comparatively less than those for Alternatives 3 and 4: ($680,000) for the NRC and ($1,179,000) for the Agreement States using a 7 percent discount rate.

Disadvantages

• The NRC would continue to license EMTs with extensive operating experience using guidance, and without the benefit of public feedback on these established technologies.

• Compatibility issues and inconsistency in guidance implementation for EMTs would continue across the National Materials Program.

• Regulators and licensees would need continued resources to develop, maintain, and use 10 CFR 35.1000 licensing guidance, which is updated more frequently than other medical use guidance.

• Because this rulemaking would only address Rb-82 generators, there would be no averted costs related to increased EMT licensing efficiencies, and the total net cost of Alternative 2 would be ($1,042,000) over 15 years using a 7 percent discount rate.

4.3 Alternative 3Limited-Scope Rulemaking to Establish Requirements for Rubidium-82 Generators and Certain Emerging Medical Technologies In addition to Rb-82 generators, this limited-scope rulemaking would address GSR units and microspheres. These EMTs are well-established and commonly used. Alternative 3 would amend 10 CFR Part 35 such that current and future GSR units could be licensed under 10 CFR Part 35, Subpart H, and the NRC would develop a new subpart for current and future microsphere and microparticle technologies. Rule language would be performance-based, focusing on intended functions and outcomes rather than prescriptive requirements. For example, outdated requirements to test helmet microswitches and trunnions that no longer exist in newer generation GSR units would be replaced with testing requirements for functional items (e.g., dose delivery accuracy and positional accuracy). Risk-informed and performance-based requirements would be informed by operating experience, recommendations from the ACMUI, nationally recognized standards, recommendations from appropriate medical professional societies, and the medical 15

community. The Alternative 3 rule would accommodate device updates and T&E changes for GSR units and would create a new subpart for microspheres and microparticles, with the goal of creating flexibilities to accommodate the safe use of potential new models and vendors of these technologies. The estimated total net averted costs for Alternative 3 is $959,000 over 15 years.

Table 3: Advantages and Disadvantages of Alternative 3 Advantages

• Would maintain safety while increasing regulatory openness, consistency, clarity, and reliability for commonly used EMTs and Rb-82 generators.

• Would improve regulatory consistency and resolve compatibility issues across the National Materials Program for commonly used EMTs; and resolve Rb-82 generator issues as discussed under Alternative 2.

• Would provide an opportunity for public comment on proposed regulations and associated licensing guidance for these commonly used EMTs.

• The NRC would no longer develop or update EMT licensing guidance for these technologies.

• Would require less resources than Alternative 4 by focusing NRC and Agreement State rulemaking resources on widely used, well-established EMTs with expected continued use.

• The NRC, Agreement States, and licensees would realize increased licensing efficiencies for GSR units and microspheres, resulting in an estimated $1,031,000 in averted costs over 15 years for the NRC, an estimated $3,981,000 in averted costs over 15 years for Agreement States, and an estimated $672,000 in averted costs over 15 years for licensees.

Disadvantages

• The NRC would still require licensing under 10 CFR 35.1000 for other EMTs, precluding the regulatory benefits and efficiencies associated with establishing regulations for these technologies.

• Rulemaking, rulemaking participation, and implementation for Alternative 3 would require more time and resources than Alternative 2, resulting in costs of ($895,000) for the NRC,

($3,113,000) for Agreement States, and ($1,657,000) for affected licensees.

4.4 Alternative 4Performance-Based Rulemaking to Increase Regulatory Flexibility (NRC Recommendation)

Alternative 4 is an expanded version of the Alternative 3 rulemaking. In addition to developing performance-based requirements for Rb-82 generators, GSR units, and microspheres/microparticles, the NRC would evaluate how to make additional sections of 10 CFR Part 35 more flexible. Alternative 4 would revise specificities in the 10 CFR Part 35 subparts for General Information, Technical Requirements, Administrative Requirements, Records, and Reports. Like Alternative 3 but on a larger scale, Alternative 4 would replace outdated, prescriptive quality assurance regulations with risk informed, performance-based requirements.

Risk-informed and performance-based requirements would be informed by operating experience, recommendations from the ACMUI, nationally recognized standards, recommendations by appropriate medical professional societies, and the medical community. The Alternative 4 rule would enable licensing of all approved EMTs, future updates to currently licensed EMTs, and potentially new EMTs, with reduced reliance on 10 CFR 35.1000. The estimated total averted costs for Alternative 4 are $1,169,000 over 15 years using a 7 percent discount rate.

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Table 4: Advantages and Disadvantages of Alternative 4 Advantages

• Alternative 4 has similar advantages as Alternative 3 but on a larger scale: it would maintain safety while increasing regulatory openness, consistency, clarity, reliability, public participation, and efficiency.

• Would reduce reliance on 10 CFR 35.1000 by developing performance-based requirements for all well-established EMTs that would accommodate updated or new EMT models, new vendors, and similar new technologies.

• The NRC and Agreement States would realize increased licensing efficiencies for EMTs included in the Alternative 4 rulemaking, resulting in estimated averted costs of $1,153,000 over 15 years for the NRC and $4,298,000 in averted costs over 15 years for Agreement States.

Disadvantages

• The medical community has a good understanding of the current licensing framework for EMTs; therefore, not all stakeholders may fully support changing this framework significantly under the Alternative 4 rulemaking.

• Alternative 4 would be the most resource-intensive rulemaking and would require the most time to complete of the three alternatives. Rulemaking, rulemaking participation, and implementations costs would be ($1,658,000) for the NRC and ($2,939,000) for the Agreement States. Rulemaking participation and implementation costs for affected licensees would be similar to Alternative 3 at ($1,546,000).

4.5 Recommendation The NRC recommends Alternative 4, Performance-Based Rulemaking to Increase Regulatory Flexibility. The Alternative 4 rulemaking would provide an opportunity for greater performance-based regulation of existing and potentially new EMTs. Rather than regulating each EMT and use on a case-by-case basis through license conditions that make prescriptive EMT licensing guidance legally binding, the revised regulations and accompanying licensing guidance would focus on the essential performance-based requirements necessary for radiation safety to protect workers, the general public, and patients. Alternative 4 would also allow the NRC to address the flexibility of other regulations in 10 CFR Part 35, which would improve the NRCs regulation of future medical use. The NRC staff previously provided a similar evaluation of the four alternatives and rulemaking recommendation in SECY-21-0013, and the Commission approved the Alternative 4 rulemaking in the SRM to SECY-21-0013.

5. Basis for Proposed Changes Appendix A explains the proposed changes to 10 CFR Part 35 that the NRC is considering, discusses the technical bases and assumptions used to support those changes, and describes how the considered changes could resolve the issues identified in Section 3 of this document.

Most of the changes described in Appendix A would establish regulations to codify the essential safety-related elements of existing EMT licensing guidance. Licensees authorized to use these EMTs are likely already in compliance with the changes described in Appendix A. However, stakeholder feedback on this regulatory basis will inform the proposed rule, and so the NRC has asked a series of questions throughout Appendix A to obtain stakeholder input on certain regulatory issues or proposed regulatory approaches to an issue. The NRC is particularly interested in feedback (with bases and rationale) on the following topics: (1) whether there is enough operating experience to inform regulations for diffusion brachytherapy, (2) whether the effort to establish regulations for less widely used EMTs is warranted, (3) the proposed regulatory 17

framework for the new microsource manual brachytherapy subpart, and (4) whether changes to T&E requirements for EMTs are warranted.

6. Backfitting and Issue Finality Analysis There are no backfitting or issue finality provisions in 10 CFR Part 35. The Commissions backfitting provisions and issue finality provisions do not apply to the applicants or licensees that would be affected by this rulemaking.

7. Stakeholder Involvement Members of the public will be provided an opportunity to comment on this regulatory basis document, and those comments will inform the draft proposed rule.

In accordance with Management Directive 5.3, Agreement State Participation in Working Groups, dated June 22, 2016 (ML18073A142), the staff provided early opportunities for Agreement State engagement on this rulemaking. A representative from OAS served on the working group that developed the rulemaking plan (SECY-21-0013), and Agreement States were provided an opportunity to comment on the draft rulemaking plan. A representative from OAS served on the working group that developed this regulatory basis, and one or more OAS representatives will participate in the rulemaking working group that will develop the proposed and final rules.

The Agreement States had an opportunity to review a draft of this regulatory basis and provide comments. The OAS Board, as well as (# OF STATES), provided specific comments. The NRC considered these comments in developing this regulatory basis, as described below:

• State comment and how NRC considered.

• State comment and how NRC considered.

• Consider an appendix for summarizing and addressing Agreement State comments.

8. Cost/Impact Considerations This section discusses cost and other impacts related to the Alternative 4 rulemaking for Rb-82 generators and EMTs. This section discusses potential impacts on three groups: (1) the NRC, (2) the Agreement States, and (3) licensees. The analyses presented in this section are based on the NRCs preliminary assessment and estimates. The staff will carry out a more detailed cost/impact evaluation as part of the regulatory analysis that will be developed in accordance with NUREG/BR-0058, Revision 5, Regulatory Analysis Guidelines of the U.S. Nuclear Commission, Draft Final Report (ML19261A277), during the proposed rule phase of the rulemaking.

8.1 Affected Entities The proposed changes to 10 CFR Part 35 would impact NRC and Agreement State materials licensees that currently use, or will apply to use in the future, Rb-82 generators, existing EMTs, and future EMTs that can be licensed under the revised 10 CFR Part 35 subparts. These licensees are mostly 10 CFR Part 35 licensees, but for some generator systems, can also include licensees regulated under 10 CFR Part 32, Specific Domestic Licenses to Manufacture or Transfer Certain 18

Items Containing Byproduct Material. The affected entities of the Alternative 4 rulemaking are these materials licensees, the NRC, and the Agreement States.

Sections 8.3 through 8.5 present Alternative 4 rulemaking costs, implementation costs, and averted costs associated with licensing and inspection for the NRC, Agreement States, and licensees. Costs are negative values and are denoted in parentheses, i.e., (); averted costs are positive values and are denoted without parentheses. All costs and averted costs are presented assuming a 7-percent net present value and are rounded to the nearest thousand.

8.2 Analysis Assumptions Cost estimates for the four alternatives include several actions related to rulemaking, implementation of the new rule, and licensing actions under the new rule, which would be done by the NRC, Agreement States, and affected licensees. The assumptions used in developing the cost estimates are based on: (1) a search of the NRCs Web-Based Licensing system for an approximate number of NRC-licensed EMTs and Rb-82 generators, (2) labor and licensing action estimates provided by NRC regional licensing and inspection staff, and (3) information from STC-22-034, Annual Count of Active Radioactive Materials Licenses in the National Materials Program (ML22139A026).

For calculating future costs, the cost estimate assumes 40 Agreement States. This estimate assumes recent Agreement State applicants Connecticut and Indiana would be Agreement States by the effective date of the rulemaking, and excludes Wyoming, which does not have regulatory jurisdiction over materials that would be impacted by this rulemaking. According to the licensee count data from STC-22-034, the total number of medical use licenses issued by the NRC and Agreement States is 7,933. Using that data, by the effective date of this rule, the NRC would regulate about 7 percent of the total number of medical use licenses in the National Materials Program (555 NRC medical licensees) and Agreement States would regulate about 93 percent (7,378 Agreement State medical licensees).

NRC regional licensing and inspection staff developed hourly labor estimates for: (1) review of EMT license applications, renewals, and various amendments under the existing 10 CFR 35.1000 EMT licensing guidance process and under a revised 10 CFR Part 35; (2) inspection of Rb-82 generators after EGM 13-003 is retired; (3) review of requests for exemption from 10 CFR 35.60 and 10 CFR 35.63 for Rb-82 generators; and (4) implementation of the new rule by licensees, the NRC, and Agreement States. The NRC relied on experience of NRC regional licensing and inspection staff to develop the hourly labor estimates associated with licensing actions and inspections, and the NRC estimated the number of future licensing actions based on historical workload and the probable future use of the EMT or a similar technology. The staff combined the hourly labor estimates with information from the NRCs Web-Based Licensing system on numbers of affected licensees, along with the estimated numbers of future EMT applications, to develop estimated costs and averted costs for each of the alternatives. These NRC-based estimates were also applied to the Agreement States, although the NRC acknowledges that there is variability among the NRC and Agreement States in the hourly labor resources required for licensing actions and inspections.

The NRC estimated that the NRC and Agreement States would realize increased efficiencies in licensing actions for existing and future EMTs after implementation of the Alternative 3 or Alternative 4 rules. This is because EMT licensing actions would no longer require review and documentation of additional specific license conditions based on the EMT licensing guidance or other approved methods for compliance with the safety objectives of the licensing guidance.

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Table 7 in Appendix B, Emerging Medical Technology Licensing Assumptions, details the future EMT licensing resource assumptions that the NRC used to calculate the averted costs for EMT licensing under the Alternative 4 rule. Table 8 in Appendix B, Alternatives 1-4 Data Tables shows the NRCs assumptions and data for each alternative, including the assumptions explained in Table 7.

8.3 NRC The NRC estimates that the projected costs of Alternative 4 for the NRC consist of: (1) rulemaking costs of ($1,381,000); (2) rulemaking implementation costs of processing license amendments for affected NRC licensees plus compatibility reviews of new Agreement State regulations of

($277,000); (3) averted costs of $102,000 associated with avoiding the need to review Rb-82 generator exemptions; and (4) after the Alternative 4 rule goes into effect, averted costs of

$1,202,000 over a 15-year period through increased licensing efficiency for EMTs, increased inspection efficiencies for Rb-82 generators, and minimizing the need to develop and update EMT licensing guidance documents. The net averted cost for the NRC over 15 years would be $353,000 using a 7-percent discount rate.

8.4 Agreement States The Agreement States will participate in the NRCs rulemaking process through the rulemaking working group, government-to-government and public meetings, and reviewing and providing written comments on rulemaking documents. The NRC estimates that for the Alternative 4 rulemaking, the Agreement States will incur a total cost of ($170,000) for participation in the NRC rulemaking process. After the Alternative 4 rule is effective, the Agreement States have 3 years to adopt compatible regulations. Following this, the Agreement States will need to implement their new regulations, which the staff assumed would be similar to NRC implementation (i.e., processing license amendments for affected licensees). The NRC estimates that the Agreement States will have total rulemaking and implementation costs of approximately ($2,769,000). Agreement State rulemaking costs may be lower if the Agreement States choose to incorporate the regulatory changes by reference. The Agreement States would realize averted costs associated with avoiding the need to review Rb-82 generator exemptions of $442,000. After the Agreement States adopt compatible regulations for the Alternative 4 rulemaking, the NRC estimates averted costs for the Agreement States of $4,417,000 over a 15-year period. Averted costs would result from increased efficiencies in licensing existing and future EMTs and increased inspection efficiencies for Rb-82 generators. The net averted costs for the Agreement States over 15 years would be $1,920,000 using a 7-percent discount rate.

8.5 Licensees The NRC estimates that licensees would incur a cost of ($63,000) to voluntarily participate in the rulemaking process (this could include participating in public meetings and reviewing and submitting comments on rulemaking documents). The NRC estimates that affected licensees would incur total implementation costs of ($1,484,000). Implementation costs would impact medical licensees with uses that are currently licensed under 10 CFR Part 35, Subpart H (i.e.,

licensees using GSR, teletherapy, or HDR afterloader devices). The NRC believes that licensees with GSR, teletherapy, or HDR afterloader devices may need to revise their procedures related to calibration and spot checks of these devices, train their staff on revised procedures, and potentially submit revised procedures to the NRC or Agreement States as either a notification or license 20

amendment application. The NRC estimated affected licensees may need an average of 20 hours2.314815e-4 days <br />0.00556 hours <br />3.306878e-5 weeks <br />7.61e-6 months <br /> each to complete these implementation tasks.

The NRC does not anticipate that other changes to 10 CFR Part 35 would result in additional implementation costs for licensees. This is because the proposed revisions to 10 CFR Part 35 would primarily establish regulations from existing EMT licensing guidance documents that many EMT licensees already comply with through license conditions, and additional changes being considered to 10 CFR Part 35 would clarify existing regulations. However, the NRC will further examine implementation costs for each proposed regulation change as part of the regulatory analysis for the proposed rule.

Licensees with Rb-82 generators would save $138,000 associating with avoiding the costs of submitting exemptions from 10 CFR 35.60 and 10 CFR 35.63, and they may see increased Rb-82 generator inspection efficiencies estimated to result in averted costs of $89,000 over 15 years.

Like the licensing efficiencies that would be realized by the NRC and Agreement States, some medical licensees may realize increased efficiencies in licensing existing and future EMTs because licensing EMTs would no longer require license conditions to impose EMT licensing guidance commitments. Furthermore, licensees would benefit from the increased reliability and clarity of regulations versus guidance. The NRC estimated averted costs for licensees through increased EMT licensing efficiencies could range from 0 to 25 percent of the estimated averted costs for the NRC and Agreement States. For this initial benefit-cost analysis, the NRC assumed EMT licensing averted costs for licensees would be 12.5 percent of the estimated averted costs for the NRC and Agreement States. This assumption results in averted EMT licensing costs of $922,000 over 15 years for licensees. Net costs for licensees over 15 years would be ($673,000) using a 7-percent discount rate.

The NRC is interested in receiving feedback from licensees on whether they would realize averted costs related to more streamlined licensing of existing and future EMTs and why. Based on this feedback, the NRC will further refine EMT licensing averted costs in the draft regulatory analysis for the proposed rule.

8.6 Summary of Alternatives and Cost Appendix B to this regulatory basis tabulates the assumptions and inputs by alternative for each affected entity. Appendix C summarizes Alternatives 1-4 and shows the costs and averted costs for each alternative for the NRC, the Agreement States, and licensees.

Table 5: Alternatives and Net Benefits (Costs)

Net Benefits (Costs) in 2022 Dollars DESCRIPTION Undiscounted 7% NPV 3% NPV Alternative 1 - STATUS QUO NRC Rulemaking $0 $0 $0 Alternative 1 NRC ($3,861) ($44,367) ($26,290)

Alternative 1 Agreement States ($185,966) ($275,576) ($240,396)

Alternative 1 Licensees $73,230 ($3,901) $31,101 Alternative 1 Total Net Benefits (Costs) ($116,597) ($323,844) ($235,586) 21

Net Benefits (Costs) in 2022 Dollars DESCRIPTION Undiscounted 7% NPV 3% NPV Alternative 2 - RULEMAKING ONLY FOR RB-82 GENERATORS Alternative 2 NRC Rulemaking ($537,000) ($505,624) ($522,858)

Alternative 2 NRC ($112,020) ($125,658) ($124,261)

Alternative 2 Agreement States ($1,344,015) ($1,178,991) ($1,288,805)

Alternative 2 Licensees $231,895 $85,417 $148,743 Averted Rb-82 Generator Exemptions $798,276 $682,461 $744,927 Alternative 2 Total Net Benefits ($962,865) ($1,042,394) ($1,042,254)

Alternative 3 - LIMITED SCOPE RULEMAKING FOR RB-82 GENERATORS AND CERTAIN EMERGING MEDICAL TECHNOLOGIES Alternative 3 NRC Rulemaking ($760,867) ($716,410) ($740,829)

Alternative 3 NRC $1,846,893 $852,613 $1,307,612 Alternative 3 Agreement States $5,796,213 $867,845 $2,953,340 Alternative 3 Licensees ($743,329) ($984,871) ($934,423)

Averted Rb-82 Gen Exemptions $798,276 $682,461 $744,927 Rb-82 Generator Inspection Efficiencies $689,327 $257,331 $443,241 Alternative 3 Total Net Benefits $7,626,514 $958,969 $3,773,869 Alternative 4 - PERFORMANCE-BASED RULEMAKING TO INCREASE REGULATORY FLEXIBILITY

[STAFF RECOMMENDATION]

Alternative 4 NRC Rulemaking ($1,545,939) ($1,380,706) ($1,470,782)

Alternative 4 NRC $2,110,680 $875,696 $1,429,820 Alternative 4 Agreement States $7,300,572 $1,358,865 $3,829,513 Alternative 4 Licensees $33,659 ($624,569) ($403,405)

Averted Rb-82 Gen Exemptions $798,276 $682,461 $744,927 Rb-82 Generator Inspection Efficiencies $689,327 $257,331 $443,241 Alternative 4 Total Net Benefits $9,386,576 $1,169,078 $4,573,314

• NPV = Net Present Value

• Values in parentheses, e.g., (), are negative and denote a cost.

Table 6: Alternative 4 Net Benefits for NRC, Agreement States, and Licensees Net Benefits (Costs) in 2022 Dollars DESCRIPTION Undiscounted 7% NPV 3% NPV NRC Rulemaking ($1,545,939) ($1,380,706) ($1,470,782)

NRC Regulatory Review of Agreement State

($234,520) ($167,465) ($202,358)

Regulations NRC Rule Implementation ($144,144) ($109,967) ($128,070)

NRC Averted Rb-82 Generator Exemption Request

$113,256 $102,384 $108,356 Review NRC Averted Rb-82 Generator Inspection Costs $116,780 $49,159 $79,084 NRC Averted EMT Licensing Costs $1,552,694 $719,248 $1,097,931 NRC Averted EMT Licensing Guidance Costs $936,650 $433,880 $662,318 NRC Alternative 4 Net Benefits $794,777 ($353,465) $146,478 22

Net Benefits (Costs) in 2022 Dollars DESCRIPTION Undiscounted 7% NPV 3% NPV Agreement State Rulemaking Participation ($187,871) ($170,226) ($179,821)

Agreement State Development of Regulations and Rule

($3,877,172) ($2,768,590) ($3,345,457)

Implementation Agreement State Averted Rb-82 Generator Exemption

$522,287 $442,274 $485,348 Request Costs Agreement State Averted Rb-82 Generator Inspection

$336,585 $118,947 $211,463 Costs Agreement State Averted EMT Licensing Costs $11,365,615 $4,297,681 $7,354,791 Agreement States Alternative 4 Net Benefits $8,159,443 $1,920,085 $4,526,323 Licensees Rulemaking Participation ($73,970) ($62,638) ($68,738)

Licensee Rule Implementation ($2,330,044) ($1,483,689) ($1,912,107)

Licensees Averted Rb-82 Generator Exemption Request

$162,733 $137,803 $151,224 Costs Licensees Averted Rb-82 Generator Inspection Costs $235,963 $89,225 $152,694 Licensees Averted EMT Licensing Costs $2,437,673 $921,758 $1,577,440 Licensees Alternative 4 Net Benefits $432,356 ($397,541) ($99,487)

Alternative 4 Total Net Benefits $9,386,576 $1,169,078 $4,573,314

• NPV = Net Present Value

• Values in parentheses, e.g., (), are negative and denote a cost.

The NRC is recommending Alternative 4, Performance-Based Rulemaking to Increase Regulatory Flexibility. The Alternative 4 rulemaking would have a total net benefit of approximately $1,169,000 in averted costs over a 15-year period using a 7 percent discount rate after NRC and Agreement State implementation of the rule. Most costs for the Alternative 4 rulemaking are borne by affected licensees for updating certain safety procedures for GSR, teletherapy, or HDR afterloader devices (see Section 8.5; this cost is the same for licensees for Alternative 3); the NRC for the rulemaking process; and the Agreement States for the development of compatible regulations. However, the Alternative 4 rulemaking would result in averted costs for the NRC, Agreement States, and potentially also licensees, through increased licensing efficiency for existing and future EMTs.

Additionally, the NRC would save resources by minimizing the need to develop new or update existing 10 CFR 35.1000 licensing guidance documents.

8.7 Additional Unquantified Benefits of Proposed Changes

• Establishing regulations for commonly used EMTs would promote consistency, compatibility, clarity, reliability, and efficiency across the National Materials Program for licensing and inspection of these medical uses.

• Adding requirements for calibration and dosage measurement for Rb-82 generators would address the regulatory issues associated with the long-standing EGM 13-003 and would increase inspection efficiency for Rb-82 generators.

• Revising the requirements in the existing medical use subparts of 10 CFR Part 35 to be less prescriptive and more performance-based could allow the NRC to license new EMTs with less reliance on 10 CFR Part 35, Subpart K, and would improve the overall 23

applicability of 10 CFR Part 35 for expected future medical uses of byproduct material. This could increase the availability of EMTs for patient use, because currently, if licensing guidance has not yet been developed for an EMT, the use of that EMT is typically limited to broad scope licensee facilities.

• Similarly, establishing regulations that focus on the essential safety-related elements of EMT licensing guidance would minimize the need to develop new EMT licensing guidance for new models or vendors of existing EMTs and the need to update outdated licensing guidance. Licensees could use new and or updated models of EMTs without waiting for revised licensing guidance, and patients could receive treatment with these EMTs without undue delay.

• Revising requirements related to the definition of a physician, patient release limits per treatment regimen, and radiation safety committees would improve the clarity of these requirements and improve efficiency of patient release planning.

• Adding requirements to confirm the accuracy of a written directive, require training on written directive procedures, and require that supervising individuals be instructed in basic safety procedures and pertinent regulations will improve radiation safety for patients and workers.

• Rulemaking will include opportunities for public comment on proposed requirements for Rb-82 generators and EMTs, and this feedback could result in improvements in knowledge for these technologies.

9. Uncertainty Analysis Appendix D documents the NRCs uncertainty analysis for this regulatory basis. To inform the uncertainty analysis, the NRC completed a Monte Carlo sensitivity analysis using the specialty software @Risk. The Alternative 4 mean net benefit is $1,169,000 in 2022 dollars, with a 90-percent confidence interval that net averted costs are between $574,000 and $1,755,000 using a 7-percent discount rate. In addition to estimating the probability distributions for the net benefits (costs) of the rule, the staff used Monte Carlo simulation to conduct a sensitivity analysis to determine the variables that have the greatest impact on the resulting net costs. The NRC is specifically looking for feedback from licensees on whether and how they would realize increased EMT licensing efficiencies and averted costs after the Alternative 4 rule is implemented.

10. Rulemaking Cost Justification The NRC estimates that, considering overall costs and averted costs for the NRC, Agreement States, and licensees, the Alternative 4 rulemaking would be cost-justified, resulting in a net benefit of $1,169,000 in averted costs at a 7-percent discount rate over the 15-year analysis period. This estimate may increase or decrease based on input from licensees on whether and how they would realize averted costs associated with licensing EMTs after the Alternative 4 rule is implemented.

The NRCs assumption that licensees would save at a rate of 12.5 percent of the NRC and Agreement State averted costs will be examined in more detail in the draft regulatory analysis of the proposed rule. Furthermore, using a 3-percent discount rate, the Alternative 4 rulemaking would have a total net benefit of $4,573,000 in averted costs over 15 years. The net benefits are broken down by NRC, Agreement States, and licensees, below (and in Table 6, above).

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• The NRC estimates a cost of ($1,658,000) for rulemaking, implementation of the rule, and review of Agreement State regulations (see Table 6 in Section 8, and Tables 32 and 33 in Appendix C). The NRC estimates it will save 19,017 labor hours for EMT licensing and Rb-82 generator licensing and inspection actions over the 15-year analysis period after implementation of the rule (including avoiding the need to review Rb-82 generator exemptions and reducing the need to develop new or update existing EMT licensing guidance documents). These labor hour savings result in averted costs of approximately

$1,305,000 at a 7-percent discount rate over the 15-year analysis period (see Tables 9, 19, 38, and 39 in Appendix C). Net costs for the NRC over 15 years would be ($354,000) using a 7-percent discount rate.

• The NRC estimates a cost of ($2,959,000) for rulemaking and implementation of compatible regulations for Agreement States (see Tables 34 and 35 in Appendix C). The NRC estimates Agreement States will save 166,836 labor hours for EMT licensing and Rb-82 generator licensing and inspection actions over the 15-year analysis period after implementation of the rule by the Agreement States (including avoiding the need to review Rb-82 generator exemptions). These labor hour savings result in averted costs of

$4,859,000 at a 7-percent discount rate over the 15-year analysis period (see Tables 11, 20, and 40 in Appendix C). Net averted costs for Agreement States over 15 years would be

$1,920,000 using a 7-percent discount rate.

• The NRC estimates a total cost of ($1,546,000) for licensees to participate in the Alternative 4 rulemaking and implement the rule (see Tables 36 and 37 in Appendix C).

Licensees will save 17,576 labor hours for EMT licensing and Rb-82 generator licensing and inspections (including avoiding the need to submit exemption requests for Rb-82 generators) over the 15-year analysis period after implementation of the rule across the National Materials Program. These labor hour savings result in averted costs of $1,149,000 at a 7-percent discount rate over the 15-year analysis period (Tables 13, 21, and 41 in Appendix C). The NRC will use public comments on this regulatory basis to refine estimated licensee averted costs during the regulatory analysis for the Alternative 4 rule.

Net costs for licensees over 15 years would be ($398,000) using a 7-percent discount rate.

11. Cumulative Effects of Regulation The NRC has implemented a program to address the possible cumulative effects of regulation in the development of regulatory bases for rulemakings. The cumulative effects of regulation are an organizational effectiveness challenge that results from a licensee or other affected entity implementing several complex positions, programs, or requirements within a prescribed implementation period and with limited available resources. The proposed rulemaking activity to establish requirements for Rb-82 generators and EMTs would reduce the future licensing effort for licensees and regulators by providing a streamlined regulatory structure for regulating Rb-82 generators and licensing existing and future EMTs. Licensees authorized for Rb-82 generators will no longer need to rely on enforcement discretion or request exemptions from current regulatory requirements that cannot be met given the generator design, and licensees and regulators will no longer need to rely on 10 CFR 35.1000 licensing guidance to license existing and some future EMTs. There will be implementation costs for licensees authorized under Subpart H of 10 CFR Part 35. The NRC is requesting feedback from the public at the regulatory basis stage on the cumulative effects that may result from the NRC rulemaking to amend 10 CFR Part 35 as described in the regulatory basis.

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12. Regulatory Flexibility Act The Regulatory Flexibility Act, as amended by the Small Business Regulatory Enforcement Fairness Act, requires the NRC to consider the impact of its rulemakings on small entities and evaluate alternatives that would accomplish regulatory objectives without unduly burdening small entities or erecting barriers to competition. In developing the proposed rule, the staff will evaluate the number of small entities potentially affected by this rulemaking and what steps the NRC can take to mitigate the economic impacts on small entities. The staff will use public comments received on this document to inform this analysis.

13. Environmental Analysis This rulemaking would revise 10 CFR Part 35 to add requirements for the calibration and dosage measurement for Rb-82 generators and establish performance-based requirements for existing and future EMTs. Pursuant to 10 CFR 51.21, Criteria for and identification of licensing and regulatory actions requiring environmental assessments, the NRC will develop an environmental assessment along with this rulemaking to determine whether issuing this rule will result in any significant impacts.

14. NRC Strategic Plan The planned rulemaking supports the NRCs Strategic Plan, NUREG-1614, Vol. 8, Strategic Plan, Fiscal Years 2022-2026 (ML22067A170), to ensure the safe and secure use of radioactive material and inspire stakeholder confidence in NRC actions. The rulemaking will contribute to the safety and security objective, Ensure that Regulatory Requirements Adequately Support the Safe and Secure Use of Radioactive Materials, by improving the effectiveness and efficiency of the regulatory framework for EMTs and Rb-82 generators. The requirements for the safe use of these EMTs are better understood than when they were initially licensed, and 10 CFR Part 35 can be amended to make changes needed for more risk-informed and performance-based regulations for these technologies. Furthermore, since Rb-82 generators have a design such that licensees cannot meet the calibration and dose measurement requirements in 10 CFR 35.60 and 10 CFR 35.63, revising 10 CFR Part 35 to add requirements for alternative methods that account for the calibration and dose measurement issues will improve regulatory effectiveness and efficiency for licensing and inspection. The NRC currently exercises enforcement discretion, but this is not intended to be a long-term solution.

Stakeholders will have opportunities to comment on this rulemaking as well as participate in public meetings. The NRC will consider all comments on the regulatory basis in preparing the proposed rule. Public comments on the proposed rule will be considered in preparing the final rule.

15. Decision Rationale The NRC supports revising 10 CFR Part 35 to: (1) establish calibration and dosage measurement requirements for Rb-82 generators, (2) establish risk-informed, performance-based requirements for existing EMTs based on operating experience, and (3) revise other outdated, prescriptive requirements with risk-informed, performance-based requirements. The Alternative 4 rule would align the NRCs medical regulations with advancements in technology and operating experience gained since the last major medical rulemaking in 2002, would promote consistency, compatibility, clarity, reliability, and efficiency across the National Materials Program for licensing and inspection of these medical uses, improve the overall flexibility of 10 CFR Part 35 to better accommodate future EMTs, and as discussed in Section 10, avert some costs to the NRC and Agreement States.

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16. References Atomic Energy Act of 1954, Pub. L.83-703, 42 U.S.C. 2011 et seq.

Administrative Procedure Act of 1946, Pub. L. 404-79, 5 U.S.C. 500 et seq.

Energy Policy Act of 2005, Pub. L. 109-58, 42 U.S.C. 15801 et seq.

Regulatory Flexibility Act of 1980, Pub. L.96-354, 5 U.S.C. 601 et seq.

Small Business Regulatory Enforcement Fairness Act of 1996, Pub. L 104-121, 5 U.S.C. 601 et seq.

U.S. Nuclear Regulatory Commission, Alpha Tau Alpha DaRT' Manual Brachytherapy Licensing Guidance, March 10, 2022 (ML22018A225).

U.S. Nuclear Regulatory Commission, Enforcement Guidance Memorandum 13-003, Enforcement Guidance MemorandumInterim Guidance for Dispositioning Violations Involving 10 CFR 35.60 and 10 CFR 35.63 for the Calibration of Instrumentation to Measure the Activity of Rubidium-82 and the Determination of Rubidium-82 Patient Dosages, April 18, 2013 (ML13101A318).

U.S. Nuclear Regulatory Commission, Germanium-68/Gallium-68 Pharmaceutical Grade Generators Licensing Guidance, July 2019 (ML19106A367).

U.S. Nuclear Regulatory Commission, Leksell Gamma Knife Perfexion' and Leksell Gamma Knife Icon' Licensing Guidance, Revision 1, January 10, 2019 (ML18333A365).

U.S. Nuclear Regulatory Commission, Licensing Guidance for the Intraocular Use of NeoVista, Inc.s Epi-Rad90' (Strontium-90) Ophthalmic System, April 2009 (ML091140370).

U.S. Nuclear Regulatory Commission, Licensing Guidance - TheraSphere and SlRSphere Yttrium-90 Microspheres, October 31, 2002 (ML082340866).

U.S. Nuclear Regulatory Commission, Low Activity Radioactive Seeds Used for Localization of Non-Palpable Lesions and Lymph Nodes Licensing Guidance, Revision 1, October 7, 2016 (ML16197A568).

U.S. Nuclear Regulatory Commission, Management Directive 5.3, Agreement State Participation in Working Groups, June 22, 2016 (ML18073A142).

U.S. Nuclear Regulatory Commission, Management Directive 5.9, Adequacy and Compatibility of Program Elements for Agreement State Programs, April 26, 2018 (ML18081A070).

U.S. Nuclear Regulatory Commission, NRC Enforcement Policy, January 14, 2022 (ML21323A042).

U.S. Nuclear Regulatory Commission, NUREG/BR-0058, Revision 5, Regulatory Analysis Guidelines of the U.S. Nuclear Regulatory Commission, Draft Final Report, January 28, 2020 (ML19261A277).

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U.S. Nuclear Regulatory Commission, NUREG-1556, Volume 9, Revision 3, Consolidated Guidance About Materials Licenses: Program-Specific Guidance About Medical Use Licenses, Final Report September 2019 (ML19256C219).

U.S. Nuclear Regulatory Commission, NUREG-1614, Volume 8, Strategic Plan Fiscal Years 2022-2026, April 2022 (ML22067A170).

U.S. Nuclear Regulatory Commission, Revision of Technical Basis for Granting Specific Exemption from Decommissioning Funding Plan Requirements for Germanium-68/Gallium-68 Generators, July 13, 2017 (ML17075A487).

U.S. Nuclear Regulatory Commission, SECY-18-0015, Staff Evaluation of the U.S. Nuclear Regulatory Commissions Program Regulating Patient Release After Radioisotope Therapy January 29, 2018 (ML17279B139).

U.S. Nuclear Regulatory Commission, SECY-21-0013, Rulemaking Plan to Establish Requirements for Rubidium-82 Generators and Emerging Medical Technologies, February 9, 2021 (ML20261H562).

U.S. Nuclear Regulatory Commission, Staff RequirementsSECY-20-0005Rulemaking Plan for Training and Experience Requirements for Unsealed Byproduct Material (10 CFR Part 35),

January 27, 2022 (ML22027A519).

U.S. Nuclear Regulatory Commission, Staff RequirementsSECY-21-0013Rulemaking Plan to Establish Requirements for Rubidium-82 Generators and Emerging Medical Technologies, January 13, 2022 (ML22013A266).

U.S. Nuclear Regulatory Commission, State and Tribal Communication 20-049, Responses to the Organization of Agreement States (OAS) Requests Regarding Clarification of Compatibility Categories for Medical Licensing Guidance Documents; and Use of Safety Evaluation Reports (SERs) as a Legally Binding Requirement, June 30, 2020 (ML20178A610).

U.S. Nuclear Regulatory Commission, State and Tribal Communication 22-034, Annual Count of Active Radioactive Materials Licenses in the National Materials Program, May 19, 2022 (ML22139A026).

U.S. Nuclear Regulatory Commission, ViewRay' System for Radiation Therapy Licensing Guidance, July 24, 2013 (ML13179A287).

U.S. Nuclear Regulatory Commission, Xcision GammaPod' Licensing Guidance, January 22, 2020 (ML19304B370).

U.S. Nuclear Regulatory Commission, Yttrium-90 Microsphere Brachytherapy Sources and Devices TheraSphere and SIR-Spheres Licensing Guidance, April 20, 2021 (ML21089A364).

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Appendix AProposed Changes to 10 CFR Part 35 This appendix is organized by technology in Sections A.1 through A.9. For each technology, there is a brief discussion of the overall rationale for the proposed changes, followed by the proposed changes organized by 10 CFR Part 35 subpart and section. Section A.10 addresses revisions to 10 CFR Part 35 that are not associated with any one technology. In several sections, questions are provided in bold italic font. The NRC is specifically seeking public comment in these areas to inform the development of the proposed rule.

A.1 Strontium-82/Rubidium-82 Generators and Germanium-68/Gallium-68 Pharmaceutical Grade Generators The proposed changes include amendments to 10 CFR Part 35, Subpart B, General Administrative Requirements, Subpart C, General Technical Requirements, and Subpart D, Unsealed Byproduct MaterialWritten Directive Not Required, to allow for the use of Ge-68/Ga-68 generators under Subpart D and resolve outstanding technical items for Rb-82 generators that are currently dispositioned through use of enforcement discretion.15 To move the regulation of Ge-68/Ga-68 generators from 10 CFR 35, Subpart K, Other Medical Uses of Byproduct Material or Radiation from Byproduct Material, to Subpart D, an allowable concentration of Ga-68 must be established in Subpart D and associated reporting requirements must be established in Subpart M, Reports. 16 To continue regulating Rb-82 generators under 10 CFR Part 35, Subpart D without the need for enforcement discretion, changes would need to be made to Subpart C to allow for the currently accepted methods for calibration of radiation detectors in a dynamic mode.

Subpart BGeneral Administrative Requirements

• 10 CFR 35.27, Supervision This section would be amended to require individuals using radionuclide generators under the supervision of an authorized user (AU) to have training on the specific type and model of radionuclide generator that is in use.

• 10 CFR 35.50, Training for radiation safety officer and associate radiation safety officer The types of generator systems authorized by 10 CFR Part 35, Subpart D, have become increasingly complex and different among models of devices. Therefore, the requirements 15 Enforcement Guidance Memorandum 13-003, Enforcement Guidance MemorandumInterim Guidance for Dispositioning Violations Involving 10 CFR 35.60 and 10 CFR 35.63 for the Calibration of Instrumentation to Measure the Activity of Rubidium-82 and the Determination of Rubidium-82 Patient Dosages, dated April 18, 2013 (ML13101A318).

16 The rulemaking described in this regulatory basis document would not address the current concerns with decommissioning funding plans associated with Ge-68/Ga-68 generators. It is expected that licensees would continue to use the exemption process outlined in the memorandum dated July 13, 2017, Revision of Technical Basis for Granting Specific Exemption from Decommissioning Funding Plan Requirements for Germanium-68/Gallium-68 Generators (ML17075A487). The NRC is conducting a rulemaking that would address decommissioning funding requirements in part for germanium-68/gallium-68 generators. Information about that rulemaking can be found at https://www.regulations.gov/ under Docket ID NRC-201-0031.

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for training for radiation safety officers (RSOs) 17 in this section would be amended to require device-specific training for all 10 CFR Part 35, Subpart D, generator systems.

Question A.1.1 Do RSOs need device-specific training for all 10 CFR Part 35, Subpart D generator systems, or is general awareness on radionuclide generators, including their functions and risks, sufficient? Please provide a basis for your response.

Subpart CGeneral Technical Requirements

• 10 CFR 35.60, Possession, use, and calibration of instruments used to measure the activity of unsealed byproduct material This section would be amended to allow for alternate methods of calibrations of dynamic detectors used in Rb-82 generators. Specifically, this section would be revised to allow licensees to develop and maintain written test procedures to ensure that the infusion pump flow rate is consistent and accurate, and that the radiation detector meets the manufacturers specifications. The tests would need to be performed at least every twelve months and repeated after repair or replacement. The licensee would need to maintain records documenting the performance of and results of these tests. The test results would need to be compared to the radiation detector specifications for the detectors electronics and response to the radiation to ensure results are aligned with the manufacturer's specifications. The licensee would be able to use documentation of the infusion cart maintenance performed by the manufacturer to document the completion and results of the infusion rate and radiation detector test. If a nationally recognized standard becomes available for radiation detectors in a dynamic mode, then licensees would be permitted to use a nationally recognized standard in accordance with 10 CFR 35.60(b).

Subpart DUnsealed Byproduct MaterialWritten Directive Not Required

• 10 CFR 35.204, Permissible molybdenum-99, strontium-82, and strontium-85 concentrations Currently, this section provides permissible concentration limits for parent radionuclides for Mo-99/Tc-99m and Rb-82 generators, but no such limit is specified for Ge-68/Ga-68 generators. This section would be amended to include a limit for the allowable concentration of Ge-68 in each eluate of the generator. Currently, the U.S. Food and Drug Administration (FDA) works with manufacturers to establish safe values for permissible concentration limits for parent radionuclides. Typically, these limits are specific to each radionuclide generator.

The NRC would determine appropriate permissible concentration limits for Ge-68 with input from the FDA and available literature, including manufacturer information.

• 10 CFR 35.290, Training for imaging and localization studies To date, training and experience (T&E) requirements for AUs of Rb-82 chloride have been required as a condition for enforcement discretion in EGM 13-003. The guidance in EGM 13-003 will be incorporated into 10 CFR 35.290 to require that AUs who are using 17 Regulations that apply to RSOs also apply to associate RSOs.

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Rb-82 chloride have successfully completed training specific to the manufacturer and model of generator and infusion cart being used. Training would be required to include (1) elution and quality control procedures needed to determine Rb-82 activity and the Sr-82 and Sr-85 breakthrough levels; (2) dose calibrator calibration procedures; and (3) safety procedures for the clinical use of Rb-82 chloride.

Question A.1.2 The NRC has found that 10 CFR 35.290 AUs have sufficient understanding of radionuclide generators, and the NRC is proposing to revise 10 CFR 35.27 to require device-specific training requirements for supervised individuals. Should 10 CFR 35.290 AUs also be required to have device-specific training for all radionuclide generators for which they supervise the use? Please provide a basis for your response.

Subpart LRecords

• 10 CFR 35.2060, Records of calibrations of instruments used to measure the activity of unsealed byproduct material This section would be amended to require elements of the calibration of dynamic detectors on Rb-82 generators.

• 10 CFR 35.2204, Records of molybdenum-99, strontium-82, and strontium-85 concentrations This section would be amended to require records for Ge-68.

Subpart MReports

• 10 CFR 35.3204, Report and notification for an eluate exceeding permissible molybdenum-99, strontium-82, and strontium-85 concentrations This section would be amended to require report and notification for an eluate exceeding permissible Ge-68 concentrations.

Other 10 CFR Part 35 Subparts The following subparts require no changes to address radionuclide generators:

• Subpart EUnsealed Byproduct MaterialWritten Directive Required

• Subpart FManual Brachytherapy

• Subpart GSealed Sources for Diagnosis

• Subpart HPhoton Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units

• Subpart I [Reserved] (Staff is proposing this as a new subpart, Microsource Manual Brachytherapy)

• Subpart J [Reserved]

• Subpart KOther Medical Uses of Byproduct Material or Radiation From Byproduct Material A-3

• Subpart NEnforcement A.2 Intravascular Brachytherapy Systems The NRC is considering revisions to 10 CFR Part 35, Subpart F, Manual Brachytherapy, to incorporate intravascular brachytherapy (IVB) into this subpart. The current guidance for this use 18 references several requirements of 10 CFR 35, Subpart F.

Regulatory changes that need to be addressed to include IVB in 10 CFR Part 35, Subpart F include T&E requirements. In the current licensing guidance, T&E requirements for AUs of IVB are the same as those in 10 CFR 35.690, Training for use of remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units. Additionally, all members of the care team, including the AU and authorized medical physicist (AMP), must have additional device-specific training related to hands-on device operation, safety procedures, and clinical use commensurate with the individuals duties, which is beyond the T&E required in 10 CFR Part 35, Subpart H.

Other regulatory changes that need to be addressed for IVBs inclusion in 10 CFR Part 35, Subpart F, include requirements for physical presence, operating procedures, and emergency procedures, like the requirements currently in 10 CFR 35.615, Safety precautions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units, and servicing by qualified individuals in 10 CFR 35.605, Installation, maintenance, adjustment, and repair.

Finally, the requirements for written directives specific to IVB would need to be included in 10 CFR 35.40, Written Directives.

Additionally, the requirements in 10 CFR 35.604, Surveys of patients and human research subjects treated with a remote afterloader unit, 10 CFR 35.605, 35.610, Safety procedures and instructions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units, 10 CFR 35.615, and 10 CFR 35.652, Radiation surveys, are applicable to IVB and therefore need to be reflected in 10 CFR Part 35, Subpart F.

Subpart AGeneral Information

• 10 CFR 35.8, Information collection requirements: OMB approval The information collection requirements under this section would be amended to reflect new procedures requiring submission under 10 CFR 35, Subpart F.

• 10 CFR 35.12, Application for license, amendment, or renewal Requirements for application for licenses, amendments, or renewals under this section would be amended to reflect changes to 10 CFR 35, Subpart F, regarding the submission of procedures that cover the practice of source-stepping with this device.

• 10 CFR 35.13, License amendments This section would be amended to reflect the citation of the applicable requirement added to 10 CFR 35, Subpart F, which requires a procedure for source-stepping. As required by 18 The licensing guidance for Best Vascular Beta Cath' IVB System was issued in August 2006 and is available at the NRCs website at https://www.nrc.gov/materials/miau/med-use-toolkit/intravascular.html.

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10 CFR 35.13(h), 19 any revisions to the procedure that could reduce radiation safety would need to be approved via a license amendment before use.

Subpart BGeneral Administrative Requirements

• 10 CFR 35.27, Supervision This section would be amended to include supervision requirements pertaining to IVB.

Specifically, procedures should be conducted under the supervision of an AU, who should consult with the interventional cardiologist/physician before initiating treatment. Additionally, this section would be amended to include a requirement that individuals under the supervision of an AU receive device-specific training before using the device.

• 10 CFR 35.40, Written directives This section would be amended to include written directive requirements for IVB. It would require that the written directive include the specific treatment site, the radionuclide, and the dose before the start of treatment with IVB.

• 10 CFR 35.51, Training for an authorized medical physicist This section would be amended to require completion of device specific training by the medical physicist applying to be an AMP on a license authorizing use of this device. This training should be given by either the vendor or an AMP who is authorized for use of the same IVB system. The device-specific training requirement would include hands-on device operation, safety procedures, clinical use, and operation of the treatment planning system.

• 10 CFR 35.57, Training for experienced Radiation Safety Officer, teletherapy or medical physicist, authorized medical physicist, authorized user, nuclear pharmacist, and authorized nuclear pharmacist This section would be amended to add the effective date of the final rule and specify that authorized individuals and RSOs added to a license on or before the effective date need not comply with revised training requirements. This would allow these authorized individuals and RSOs to maintain their authorization (i.e., legacy individuals, formerly referred to as grandfathered individuals).

Subpart FManual Brachytherapy

• 10 CFR 35.400, Use of sources for manual brachytherapy This section would be amended to exclude the use of manual brachytherapy technologies that require additional device-specific training for AUs (such as the EMTs being incorporated into 10 CFR Part 35, Subpart F, through this rulemaking).

• 10 CFR 35.401 (proposed new section) 19 Paragraph (h) of 10 CFR 35.13 requires that a licensee apply for and receive a license amendment before it revises procedures required by sections 35.610, 35.642, 35.643, and 35.645, as applicable, where such revision reduces radiation safety.

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This new section would be added to 10 CFR Part 35, Subpart F, to include manual brachytherapy technologies that require AUs to complete device-specific training in addition to the T&E required in 10 CFR 35.490, Training for use of manual brachytherapy sources.

This would include the EMTs addressed in this rulemaking: IVB, liquid brachytherapy, diffusing sources, and the two EMT eye applicator sources.

• 10 CFR 35.404, Surveys after source implant removal This section would be amended to ensure that immediately following source retraction from patient or a human research subject, a licensee shall survey the patient or the human research subject and the IVB unit with a portable radiation detection survey instrument to confirm that the source(s) have been removed from the patient or human research subject and returned to the safe shielded position. The licensee would be required to retain a record of these surveys in accordance with 10 CFR 35.2404, Records of surveys after source implant and removal.

• 10 CFR 35.405 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart F, to include the requirement that IVB devices be inspected and serviced at intervals recommended by the manufacturer and that maintenance and repair of the device only be performed by the manufacturer or persons specifically licensed by the NRC or an Agreement State to perform such services.

The licensee would need to retain a record of the maintenance, adjustment, and repair of IVB devices in accordance with 10 CFR 35.2605, Records of dosimetry equipment used with remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units.

• 10 CFR 35.410, Safety instruction This section would be amended to include a requirement for licensees to develop, implement, and maintain written emergency procedures for both stuck and detached sources including the provision of appropriate emergency response equipment and any appropriate surgical procedures. These written emergency procedures would be similar to those required for HDR remote afterloader treatments as detailed in 10 CFR 35.610. The licensee would need to retain a copy of the procedure, as required in 10 CFR 35.2610, Records of safety procedures. Additionally, this section of the regulation will be amended to require annual emergency drills and operational training similar to those required by 10 CFR 35.610 for HDR remote afterloader treatments.

• 10 CFR 35.415, Safety precautions This section would be amended to include a physical presence requirement during IVB treatment because of the high dose rates delivered to the treatment site. Specifically, this requirement for IVB procedures should be similar to that described in 10 CFR 35.615(f)(2) that states an AU and an AMP should be physically present during the initiation of all patient treatments involving the unit; and an AMP and either an AU or a physician, under the supervision of an AU, who has been trained in the operation and emergency response for the unit, should be physically present during continuation of all patient treatments involving the unit. Additionally, this section of the regulation will be amended to require licensees to lock storage of the IVB storage container and to house that storage container in a secure location.

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• 10 CFR 35.432, Calibration measurements of brachytherapy sources This section would be amended to include calibration measurement requirements pertaining to IVB. Specifically, for IVB, the licensee should perform independent measurement of source output, before the first patient treatment, using a dosimetry system that meets the requirements of 10 CFR 35.630(a).

• 10 CFR 35.492 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart F, to address the T&E requirements specific to be an AU for IVB and other uses under 10 CFR 35.401 (i.e., liquid brachytherapy, diffusion brachytherapy, and eye applicators). The T&E requirements would be similar to those in 10 CFR 35.690 and would include the completion of device-specific training by the physician applying to be an AU, provided by either the vendor, or an AU or AMP who is authorized for the use of the same IVB system. The training would include items such as hands-on device operation, safety procedures, and clinical use.

Question A.2.1 Are the T&E requirements for AUs outlined in the current EMT licensing guidance documents for IVB, liquid brachytherapy, diffusing sources brachytherapy, and eye applicators sufficient? Please provide a basis for your response.

Specifically, the NRC is seeking feedback on the knowledge topics encompassing the safety-related characteristics of these EMTs required for AUs to fulfill their radiation safety-related duties and supervision roles; the methods on how knowledge topics should be acquired; and consideration for continuing education, vendor training for new medical uses, and training on NRC regulatory requirements.

Subpart LRecords

• 10 CFR 35.2605, Records of installation, maintenance, adjustment, and repair of remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units This section would be amended to add IVB devices to the title and to reflect the recordkeeping requirements for maintenance and repair detailed in 10 CFR 35.405.

Other 10 CFR Part 35 Subparts The following subparts require no changes to address IVB:

• Subpart CGeneral Technical Requirements

• Subpart DUnsealed Byproduct MaterialWritten Directive Not Required

• Subpart EUnsealed Byproduct MaterialWritten Directive Required

• Subpart GSealed Sources for Diagnosis

• Subpart HPhoton Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units A-7

• Subpart I [Reserved] (Staff is proposing this as a new subpart, Microsource Manual Brachytherapy)

• Subpart J [Reserved]

• Subpart KOther Medical Uses of Byproduct Material or Radiation from Byproduct Material

• Subpart MReports

• Subpart NEnforcement A.3 Liquid Brachytherapy Sources and Devices Liquid Brachytherapy is a form of manual brachytherapy that uses sources that are temporarily implanted for radiation therapy. Changes to 10 CFR 35, Subpart F, are warranted along with revisions to other pertinent sections including 10 CFR 35.40, 35.41, and 35.67.

Subpart AGeneral Information

• 10 CFR 35.2, Definitions This section would be amended to: (1) revise the definition of manual brachytherapy to include liquid sources; (2) clarify that for liquid brachytherapy, "prescribed dose" means the total dose documented in the written directive; and (3) define the term source leakage as it relates to liquid brachytherapyin this instance, it means leakage that results in a dose that exceeds 0.5 Sieverts (50 rem) dose equivalent to any individual organ other than the treatment site, based on the definition of a medical event.

Question A.3.1 Should the definition of manual brachytherapy be revised to include liquid brachytherapy and exclude microsources? Or, because hazards of microsources are similar to liquid brachytherapy, should liquid brachytherapy be included in the newly proposed 10 CFR Part 35, Subpart I, Microsource Manual Brachytherapy? Please provide a basis for your responses.

• 10 CFR 35.8, Information Collection Requirements: OMB approval The information collection requirements under this section would be amended to reflect new procedures requiring submission under 10 CFR 35, Subpart F.

• 10 CFR 35.13, Application for license, amendment, or renewal This section would be amended to reflect the citation of the applicable regulation added to 10 CFR 35, Subpart F, which requires a procedure for the verification that the device is not leaking before treatment. Any revisions to that procedure that could reduce radiation safety would need to be approved via a license amendment before use.

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Subpart BGeneral Administrative Requirements

• 10 CFR 35.40, Written directives This section would be amended to include written directive requirements for liquid brachytherapy. It would require the written directive to include the following information:

(1) before implantationthe treatment site, the radionuclide (including the chemical/physical form), and dose; and (2) after implantation but before completion of the procedurethe radionuclide (including the chemical /physical form), the treatment site, and the total dose.

• 10 CFR 35.41, Procedures for administrations requiring a written directive This section would be amended to include language in 10 CFR 35.41(b) to require that the written procedure required by 10 CFR 35.41(a) address situations that can cause an effective dose reduction of greater than 20 percent. To ensure that each administration is in accordance with the written directive, the written procedure should describe how licensees will ensure that the use of fluid that can cause effective dose reduction is not present when the radionuclide mixture is added to the catheter or when the licensee measures the activity of the radionuclide mixture upon removal from the patient.

• 10 CFR 35.57, Training for experienced Radiation Safety Officer, teletherapy or medical physicist, authorized medical physicist, authorized user, nuclear pharmacist, and authorized nuclear pharmacist This section would be amended to add the effective date of the final rule and specify that authorized individuals and RSOs added to a license on or before the effective date need not comply with revised training requirements. This would allow these authorized individuals and RSOs to maintain their authorization (i.e., legacy individuals, formerly referred to as grandfathered individuals).

Subpart CGeneral Technical Requirements

• 10 CFR 35.67, Requirements for possession of sealed sources and brachytherapy sources This section would be amended to require leak testing of the device that will contain the liquid brachytherapy source prior to the procedure. Devices found to be leaking would be reported in accordance with the requirements stated in 10 CFR 35.3067, Report of a leaking source.

• 10 CFR 35.69, Labeling of vials and syringes This section would be amended to incorporate requirements for labeling vials and syringes pertaining to liquid brachytherapy. Specifically, the licensee should label syringes and syringe radiation shields not labeled by the manufacturer with the radioisotope, form, and therapeutic procedure, and label vials and vial radiation shields with the radioisotope and form.

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Subpart FManual Brachytherapy

• 10 CFR 35.400, Use of sources for manual brachytherapy This section would be amended to exclude the use of manual brachytherapy technologies that require additional device-specific training for AUs (such as the EMTs being incorporated into 10 CFR Part 35, Subpart F, through this rulemaking).

• 10 CFR 35.401 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart F, to include manual brachytherapy technologies that require AUs to complete device-specific training in addition to the T&E required in 10 CFR 35.490, Training for use of manual brachytherapy sources.

This would include the EMTs addressed in this rulemaking: IVB, liquid brachytherapy, diffusing sources, and the two EMT eye applicator sources.

• 10 CFR 35.410, Safety instruction This section would be amended to add language to include instructions on how to safely handle contamination of unsealed material for brachytherapy. This instruction would be in addition to other instructions already included in this section of the regulation. Further, this section of the regulation would need to be amended to require licensees to develop and maintain procedures that specify how a licensee will confirm that the balloon does not leak before injection of the liquid brachytherapy source or while the source and device are implanted in the patient or human research subject.

• 10 CFR 35.415, Safety precautions This section would be amended to require that an AU with experience in radiotherapy procedures be on call to provide guidance in the case of leakage of the implanted liquid brachytherapy device.

• 10 CFR 35.492 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart F, to address the T&E requirements specific to be an AU for liquid brachytherapy and other uses permitted under 10 CFR 35.401 (i.e., IVB, diffusion brachytherapy, and eye applicators). The T&E requirements specific to liquid brachytherapy would include those required in 10 CFR 35.490 in addition to training in delivery, safety procedures, and clinical use of the liquid brachytherapy system provided by either a vendor or qualified AU.

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Question A.3.2 Are the T&E requirements for AUs outlined in the current EMT licensing guidance documents for IVB, liquid brachytherapy, diffusing sources brachytherapy, and eye applicators sufficient? Specifically, the NRC is seeking feedback on the knowledge topics encompassing the safety-related characteristics of these EMTs required for AUs to fulfill their radiation safety-related duties and supervision roles; the methods on how knowledge topics should be acquired; and consideration for continuing education, vendor training for new medical uses, and training on NRC regulatory requirements. Please provide a basis for your responses.

Subpart MReports

• 10 CFR 35.3067, Report of a leaking source This section would be amended to add a requirement to report leaking liquid brachytherapy devices within 5 days of the leakage test, similar to the requirements currently in this section for a leaking sealed source.

Other 10 CFR Part 35 Subparts The following subparts require no changes to address liquid brachytherapy sources and devices:

• Subpart DUnsealed Byproduct MaterialWritten Directive Not Required

• Subpart EUnsealed Byproduct MaterialWritten Directive Required

• Subpart GSealed Sources for Diagnosis

• Subpart HPhoton Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units

• Subpart I [Reserved] (Staff is proposing this as a new subpart, Microsource Manual Brachytherapy)

• Subpart J [Reserved]

• Subpart KOther Medical Uses of Byproduct Material or Radiation From Byproduct Material

• Subpart LRecords

• Subpart NEnforcement A.4 Radioactive Seed Localization Radioactive seed localization (RSL) may use decayed radioactive seeds previously approved for the treatment of tumors under 10 CFR Part 35, Subpart F, or low activity radioactive seeds approved by the FDA specifically for RSL use. While this technology has similar characteristics as the technologies in 10 CFR Part 35, Subparts D and F, RSL is most similar to the types of uses regulated under Subpart G, Sealed sources for diagnosis. In addition to revisions to 10 CFR Part 35, Subpart G, additional revisions would be made to other subparts as applicable.

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Subpart AGeneral Information

• 10 CFR 35.2, Definitions This section would be amended to add a new definition for RSL, specifying that RSL does not require a written directive and is a procedure for diagnostic purposes rather than therapeutic purposes.

• 10 CFR 35.8, Information collection requirements: OMB approval This section would be amended to include any changes to information collection requirements if there are changes in 10 CFR Part 35, Subpart G that require information collection.

Subpart BGeneral Administrative Requirements

• 10 CFR 35.27, Supervision This section would be amended to add training requirements for individuals under the supervision of an AU. Specifically, training requirements for radiologists, surgeons, and pathology personnel involved in RSL would need to be added. This training would need to be completed before these individuals work under the supervision of the AU, as currently stated in the guidance. 20

• 10 CFR 35.49, Suppliers for sealed sources or devices for medical use This section would be amended to allow use of decayed sealed sources that were originally intended to deliver a therapeutic dose and were not specifically approved in the sealed source & device (SS&D) registry for RSL use.

• 10 CFR 35.57, Training for experienced Radiation Safety Officer, teletherapy or medical physicist, authorized medical physicist, authorized user, nuclear pharmacist, and authorized nuclear pharmacist This section would be amended to add the effective date of the final rule and specify that authorized individuals and RSOs added to a license on or before the effective date need not comply with revised training requirements. This would allow these authorized individuals and RSOs to maintain their authorization (i.e., legacy individuals, formerly referred to as grandfathered individuals).

Subpart GSealed Sources for Diagnosis

• 10 CFR 35.500, Use of sealed sources and medical devices for diagnosis.

This section would be amended to exclude RSL. The use of sealed sources under 10 CFR 35.500 is limited to sealed sources that are approved for diagnostic medical use in the SS&D registry. RSL allows for the use of seeds approved in the SS&D registry for therapeutic use (that have decayed to an acceptable activity) or other medical uses.

20 Low Activity Radioactive Seeds Used for Localization of Non-Palpable Lesions and Lymph Nodes, Revision 1, dated October 7, 2016 (ML161978568).

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• 10 CFR 35.501 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart G, to specifically allow for the use of sources for RSL, including sources specifically approved in an SS&D registry for RSL and those sources that were previously approved for therapeutic use that have decayed to less than or equal to 300 microcuries.

• 10 CFR 35.504 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart G, to include a requirement for surveys to be completed after RSL source implant and removal, similar to that in 10 CFR 35.404.

• 10 CFR 35.506 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart G, to include a requirement for licensees to develop, implement, and maintain a procedure for source accountability, similar to that 10 CFR 35.406. This procedure would not need to be submitted during license application but would be reviewed during inspection.

• 10 CFR 35.510 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart G, to include a requirement similar to the requirements in 10 CFR 35.610. The licensee would be required to submit written procedures for: (1) the assessment of the radiation dose to tissue for seeds remaining in place for an extended period of time and to provide for a no later than date for explantation to ensure a dose greater than 0.5 Sieverts (50 rem) is not delivered; (2) the radiation safety program for all departments involved in RSL including surgical and pathology; (3) routine monitoring before, during, and after all uses of the seeds to ensure rapid identification of seed localization; (2) remediation of contamination resulting from a broken or leaking source; and (5) emergency procedures for responding to an abnormal situation. Emergency procedures for responding to an abnormal situation should include instructions for responding to a source rupture and instructions to pathology personnel for responding to a leaking/cut source, the process for restricting access and posting in the event of a leaking/cut source, instructions for patient follow-up should they not return for explantation, and the names and telephone numbers of AUs and RSOs to be contacted.

• 10 CFR 35.515 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart G, to include a requirement that the licensee maintain emergency response equipment near each surgery suite and pathology laboratory during specimen handling.

• 10 CFR 35.532 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart G, to include a requirement for the activity of sources to be verified prior to each patient implant using a dosimetry system that meets the requirements of 10 CFR 35.630(a) or by using the sealed source activity measurements, after correcting for decay, provided by the manufacturer for pre-A-13

loaded/pre-packaged needles approved by the FDA for RSL use. This would be written in a similar manner to 10 CFR 35.432.

• 10 CFR 35.591 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart G, to incorporate the multiple T&E pathways a physician can use to become an AU for RSL. This new section would codify the requirements for becoming an AU for RSL that are already stated in the current guidance document.

Subpart LRecords

• 10 CFR 35.2024, Records of authority and responsibilities for radiation protection programs This section would be amended based on changes made to 10 CFR 35.24.

• 10 CFR 35.2026, Records of radiation protection program changes This section would be amended based on changes made to 10 CFR 35.26.

• 10 CFR 35.2406, Records of brachytherapy source accountability This section would be amended to require recordkeeping of source accountability records for sealed sources and brachytherapy sources. Specifically, the title of the regulation would be changed along with the existing regulatory text to include sealed sources used for RSL.

• 10 CFR 35.2432, Records of calibration measurements of brachytherapy sources This section would be amended to require recordkeeping of calibration measurement of sealed sources used in RSL similar to the requirements for brachytherapy sources.

Subpart MReports

• 10 CFR 35.3045, Report and notification of a medical event This section would be amended to include medical event reporting criteria specific to RSL.

These criteria include: The administration of byproduct material results in a dose that exceeds 0.05 Sv (5 rem) effective dose equivalent or 0.5 Sv (50 rem) to an organ or tissue from any of the following: a) an administration of the RSL procedure using the wrong radionuclide; b) an administration of the RSL procedure to the wrong patient or human research subject; c) an administration of the RSL procedure using the wrong number of radioactive seeds; or d) if the licensee fails to perform the explantation surgery.

Other 10 CFR Part 35 Subparts The following subparts require no changes to address RSL:

• Subpart CGeneral Technical Requirements

• Subpart DUnsealed Byproduct MaterialWritten Directive Not Required A-14

• Subpart EUnsealed Byproduct MaterialWritten Directive Required

• Subpart FManual Brachytherapy

• Subpart HPhoton Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units

• Subpart I [Reserved] (Staff is proposing this as a new subpart, Microsource Manual Brachytherapy)

• Subpart J [Reserved]

• Subpart KOther Medical Uses of Byproduct Material or Radiation From Byproduct Material

• Subpart NEnforcement A.5 Manual Brachytherapy Using Diffusing Sources Subpart F of 10 CFR Part 35 would be amended to address the unique properties and radiations safety considerations of diffusing manual brachytherapy sources. Existing requirements in other sections of 10 CFR Part 35 would be amended as appropriate to capture the regulatory requirements specific to this use.

Question A.5.1 What radiation safety issues should be considered if manual brachytherapy using alpha-emitting diffusing sources were added to 10 CFR Part 35, Subpart F?

Question A.5.2 Are calibration requirements in 10 CFR 35.432, Calibration measurements of brachytherapy sources, sufficient for diffusing sources? Please provide a basis for your response.

Subpart AGeneral Information

• 10 CFR 35.8, Information collection requirements: OMB approval This section would be amended to reflect information collection if there are changes in 10 CFR Part 35, Subpart F, that require information collection.

Subpart BGeneral Administrative Requirements

• 10 CFR 35.27, Supervision This section would be amended to require that individuals receive specific training in the uses they are being supervised for before acting under the supervision of an AU.

• 10 CFR 35.40, Written directives This section would be amended to state that for manual brachytherapy using a diffusing source, when total source strength is required to be recorded, the written directive may be limited to the activity of the parent radionuclide only.

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• 10 CFR 35.57, Training for experienced Radiation Safety Officer, teletherapy or medical physicist, authorized medical physicist, authorized user, nuclear pharmacist, and authorized nuclear pharmacist.

This section would be amended to add the effective date of the final rule and specify that authorized individuals and RSOs added to a license on or before the effective date need not comply with revised training requirements. This would allow these authorized individuals and RSOs to maintain their authorization (i.e., legacy individuals, formerly referred to as grandfathered individuals).

Subpart CGeneral Technical Requirements

• 10 CFR 35.69, Labeling of vials and syringes This section would be amended to add requirements pertaining to diffusing sources used for manual brachytherapy. Specifically, labeling of vials and syringes does not apply to these types of seeds, however, licensees are required to keep the applicator in a labeled container provided by the manufacturer until the applicator is needed for use or conditions in 10 CFR 35.92, Decay-in-storage, are met.

• 10 CFR 35.70, Surveys of ambient radiation exposure rate This section would be amended to require, after each administration, completion of surveys with a radiation detection survey instrument of the area where diffusing sources were prepared for use or administered. Both ambient radiation and contamination surveys should be performed as contamination is more likely with a diffusing source. (Licensees would need to meet the requirements in 10 CFR 35.2070, Records of surveys for ambient radiation exposure rate, including recordkeeping of survey records for three years.)

Subpart F - Manual Brachytherapy

• 10 CFR 35.400, Use of sources for manual brachytherapy This section would be amended to exclude the use of manual brachytherapy technologies that require additional device-specific training for AUs (such as the EMTs being incorporated into 10 CFR Part 35, Subpart F, through this rulemaking).

• 10 CFR 35.401 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart F, to include manual brachytherapy technologies that require AUs to complete device-specific training in addition to the T&E required in 10 CFR 35.490, Training for use of manual brachytherapy sources.

This would include the EMTs addressed in this rulemaking: IVB, liquid brachytherapy, diffusing sources, and the two EMT eye applicator sources.

• 10 CFR 35.410 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart F, to include the requirement for vendor operational and safety training prior to the first treatment of a new applicator A-16

model or an existing applicator model, similar to the vendor training requirement in 10 CFR 35.610.

• 10 CFR 35.415, Safety precautions This section would be amended to require the licensee to place all diffusing sources that are not in use and contaminated waste in a sealed container because of the gaseous diffusion.

Additionally, to be able to immediately place a damaged or unused source in a container, the regulation will be amended to require a sealable container be available where diffusive manual brachytherapy sources are prepared and used (this requirement is needed to help reduce contamination). Additionally, this section will be amended to require that licensees use a sealed container that has been tested by the manufacturer or licensee to ensure the container prevents radon leakage.

• 10 CFR 35.492 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart F, to address the T&E requirements specific to AUs for diffusion brachytherapy and other uses under 10 CFR 35.401 (i.e., IVB, liquid brachytherapy, and eye applicators). The T&E requirements for diffusion brachytherapy would be similar to those in 10 CFR 35.490 but would require the completion of device-specific training in the delivery, safety procedures, and clinical use of the diffusion brachytherapy source by the physician applying to be an AU. This training could be provided by either the vendor or another qualified AU.

Question A.5.3 Are the T&E requirements for AUs outlined in the current EMT licensing guidance documents for IVB, liquid brachytherapy, diffusing sources brachytherapy, and eye applicators sufficient? Please provide a basis for your response.

Specifically, the NRC is seeking feedback on the knowledge topics encompassing the safety-related characteristics of these EMTs required for AUs to fulfill their radiation safety-related duties and supervision roles; the methods on how knowledge topics should be acquired; and consideration for continuing education, vendor training for new medical uses, and training on NRC regulatory requirements.

Subpart MReports

• 10 CFR 35.3045, Report and notification of a medical event This section would be amended to exempt manual brachytherapy using diffusing sources from some requirements in 10 CFR 35.3045 and to add requirements specific to manual brachytherapy using diffusing sources. Specifically, licensees will not be required to report a medical event caused by a leaking source in accordance with 10 CFR 35.3045(a)(1)(ii)(E) or 10 CFR 35.3045(2)(iii)(D) as diffusing sources are not considered a sealed source. This section would be amended to require licensees to report any event in which a diffusing source is implanted directly into a location discontinuous from the treatment site, as documented in the post-implantation portion of the written directive. As stated above, total source strength as documented on a written directive for diffusion manual brachytherapy A-17

only needs to include the parent radionuclide activity. Licensees would be required to report any discovered event where the dose to the skin or an organ or tissue other than the treatment site exceeds by 0.5 Sv (50 rem) or more the expected dose to that site if the administration had been given in accordance with the written directive prepared or revised before administration; and exceeds by 50 percent or more the expected dose to that site if the administration had been given in accordance with the written directive prepared or revised before administration.

Other 10 CFR Part 35 Subparts The following subparts require no changes to address manual brachytherapy using alpha emitters:

• Subpart DUnsealed Byproduct MaterialWritten Directive Not Required

• Subpart EUnsealed Byproduct MaterialWritten Directive Required

• Subpart FManual Brachytherapy

• Subpart GSealed Sources for Diagnosis

• Subpart HPhoton Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units

• Subpart I [Reserved] (Staff is proposing this as a new subpart, Microsource Manual Brachytherapy)

• Subpart J [Reserved]

• Subpart KOther Medical Uses of Byproduct Material or Radiation From Byproduct Material

• Subpart NEnforcement A.6 Ophthalmic (Eye) Applicator Sources and Devices The NeoVista, Inc. Epi-Rad90TM Ophthalmic System and the LV Liberty Vision 90Yttrium Disc Source are different than traditional ophthalmic sources and applicator systems in their use, design, and operation. The licensing guidance for the NeoVista, Inc. Epi-Rad90TM Ophthalmic System calls for two pathways for physicians to become AUs. Authorized users using the FDA-approved Investigational Device Exemption procedure of 24 gray for treatment must meet the T&E requirements described in 10 CFR 35.491, while AUs for all other applications of the device must meet the T&E requirements in 10 CFR 35.490, 35.690, or 35.57. Additionally, all members of the care team, including the non-AU retinal surgeon, must have additional device-specific training related to hands-on device operation, safety procedures, and clinical use commensurate with the individuals duties, which is beyond the T&E required in 10 CFR Part 35, Subpart F or Subpart H. The LV Liberty Vision 90Yttrium Disc Source uses Y-90, which is different from what is currently allowed for use by physicians authorized under 10 CFR 35.491.

Current regulations for use of ophthalmic eye applicator sources by non-radiation oncology AUs are specific for use of Sr-90. As such, changes to 10 CFR Part 35, Subpart B, are needed to require device-specific training for ophthalmic sources and applicator systems. Changes to 10 CFR Part 35, Subpart F, are needed to allow for use of Y-90 in ophthalmic treatments.

Additionally, changes are needed to 10 CFR Part 35, Subparts F and L to require various safety precautions such as emergency procedures, physical presence, T&E requirements for AUs and AMPs, and recordkeeping requirements for use of Y-90 for ophthalmic treatments.

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Subpart AGeneral Information

• 10 CFR 35.8, Information collection requirements: OMB approval The information collection requirement would be amended to include new requirements for documentation that the licensee would be required to submit or maintain including new procedures and new records as applicable for use of ophthalmic applicator sources and devices.

Subpart BGeneral Administrative Requirements

• 10 CFR 35.40, Written directives The requirement for written directives for all other brachytherapy under paragraph b(7)(i) of this section would be amended to also require the source activity before implantation.

• 10 CFR 35.50, Training for Radiation Safety Officer and Associate Radiation Safety Officer The requirements for RSO training in this section would be amended to require device-specific training that would account for all ophthalmic sources and applicator systems under 10 CFR Part 35, Subpart F.

• 10 CFR 35.51, Training for an authorized medical physicist The requirements for training AMPs in this section would be amended to require device-specific training for all ophthalmic sources and applicator systems under 10 CFR Part 35, Subpart F.

• 10 CFR 35.57, Training for experienced Radiation Safety Officer, teletherapy or medical physicist, authorized medical physicist, authorized user, nuclear pharmacist, and authorized nuclear pharmacist This section would be amended to add the effective date of the final rule and specify that authorized individuals and RSOs added to a license on or before the effective date need not comply with revised training requirements. This would allow these authorized individuals and RSOs to maintain their authorization (i.e., legacy individuals, formerly referred to as grandfathered individuals).

Subpart FManual Brachytherapy

• 10 CFR 35.400, Use of sources for manual brachytherapy This section would be amended to exclude the use of manual brachytherapy technologies that require additional device-specific training for AUs (such as the EMTs being incorporated into 10 CFR Part 35, Subpart F, through this rulemaking).

• 10 CFR 35.401 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart F, to include manual brachytherapy technologies that require AUs to complete device-specific training in addition A-19

to the T&E required in 10 CFR 35.490, Training for use of manual brachytherapy sources.

This would include the EMTs addressed in this rulemaking: IVB, liquid brachytherapy, diffusing sources, and the two EMT eye applicator sources.

• 10 CFR 35.415, Safety precautions This section would be amended to require: (1) that written emergency procedures address source recovery for cases where the source does not get to the treatment site or cases when the source does not return to the shielded storage position; the procedures would be required to include a description of the required emergency response equipment and any appropriate surgical interventions; (2) that service and maintenance of ophthalmic sources and applicator systems be conducted at intervals specified in the SS&D registry by persons specifically licensed by the NRC or an Agreement State to perform such services; (3) that licensees develop, implement, and maintain procedures for performing quality control testing on ophthalmic sources and applicator systems in accordance with the manufacturers instructions, performing pre-treatment and post-treatment visuals inspections and surveys of ophthalmic sources and applicator systems, and safe handling procedures for ophthalmic sources and applicator systems.

This section would also be amended to physical presence requirements for use of ophthalmic sources and applicator systems that are regulated under 10 CFR 35, Subpart K.

Specifically, for certain types of non-invasive standard protocol21 ophthalmic procedures, the physical presence of an AMP or AU or RSO with device-specific or device- and non-standard protocol-specific authorizations would be sufficient to meet the physical presence requirements. For non-standard protocol ophthalmic procedures, the AU would be required to consult with the eye physician specialist (retinal surgeon or ophthalmologist) and an AMP authorized for use of the same device before the treatment. Additionally, the procedure would need to be performed in the physical presence of either an AU authorized for non-standard protocols, or an AMP authorized for use of the same ophthalmic source and applicator system.

• 10 CFR 35.433, Strontium-90 sources for ophthalmic treatments This section would be amended to allow Y-90 sources for ophthalmic treatments. The title of this section would be amended to include Y-90 sources and this section would be amended to allow for AMPs and certain ophthalmic physicists to be able to perform decay calculations for treatment times. Additionally, these individuals would be allowed to assist the licensee in developing, implementing, and maintaining written procedures to provide high confidence that the administration is in accordance with the written directive.

• 10 CFR 35.492 (proposed new section)

This new section would be added to 10 CFR Part 35, Subpart F, to address the T&E requirements specific to AUs for ophthalmic applicator systems used intraocularly and ophthalmic applicator systems that use radionuclides other than Sr-90, in addition to other uses under 10 CFR 35.401 (i.e., IVB, liquid brachytherapy, and diffusion brachytherapy).

The T&E requirements for these ophthalmic applicators would outline the various pathways for qualification of AUs, including the T&E in 10 CFR 35.490, 35.491, and 35.690, as 21 Standard protocol means the FDA-approved Investigational Device Exemption procedure of 24 gray for the treatment of age-related macular degeneration.

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applicable to the protocol requested. Additionally, device-specific training on the operation, safety procedures, and clinical use of the ophthalmic sources and applicator systems would be required to be provided by a vendor or a qualified AU.

Question A.6.1 Are the T&E requirements for AUs outlined in the current EMT licensing guidance documents for IVB, liquid brachytherapy, diffusing sources brachytherapy, and eye applicators sufficient? Please provide a basis for your response.

Specifically, the NRC is seeking feedback on the knowledge topics encompassing the safety-related characteristics of these EMTs required for AUs to fulfill their radiation safety-related duties and supervision roles; the methods on how knowledge topics should be acquired; and consideration for continuing education, vendor training for new medical uses, and training on NRC regulatory requirements.

Subpart LRecords

• 10 CFR 35.2433, Records of decay of strontium-90 sources for ophthalmic treatments Based on changes to 10 CFR Part 35, Subpart F, the title of this section would be amended to include Y-90 sources for ophthalmic treatments and the regulation would be expanded to apply to Y-90 source for ophthalmic treatments.

Other 10 CFR Part 35 Subparts The following subparts require no changes to address ophthalmic applicator sources and devices:

• Subpart CGeneral Technical Requirements

• Subpart DUnsealed Byproduct MaterialWritten Directive Not Required

• Subpart EUnsealed Byproduct MaterialWritten Directive Required

• Subpart GSealed Sources for Diagnosis

• Subpart HPhoton Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units

• Subpart I [Reserved] (Staff is proposing this as a new subpart, Microsource Manual Brachytherapy)

• Subpart J [Reserved]

• Subpart KOther Medical Uses of Byproduct Material or Radiation From Byproduct Material

• Subpart MReports

• Subpart NEnforcement A.7 Gamma Stereotactic Radiosurgery and Photon Emitting Teletherapy Units The 2002 revisions to the regulations in 10 CFR Part 35, Subpart H, were based on technology that was current in the early 2000s. There have since been significant technological advancements which have allowed for major design and engineering changes in GSR and photon emitting teletherapy units. Because of these changes, many new GSR and photon A-21

emitting teletherapy units have been regulated under 10 CFR Part 35, Subpart K. Changes are needed throughout 10 CFR Part 35, Subpart H, to allow for the regulation of GSR and photon emitting teletherapy units currently licensed under 10 CFR Part 35, Subpart K. The proposed changes include a shift from a focus on specific device components to a focus on the functional elements such as source output, source collimation, source position, source attenuation, patient safety, and facility safety. This approach would allow for one set of spot check requirements and one set of calibration requirements for all uses under 10 CFR Part 35, Subpart H, including remote afterloader units. The proposed changes include creation of definitions, amendments to general administration requirements, and a restructure of 10 CFR Part 35, Subpart H, to align with a focus on functional elements instead of individual components.

Subpart AGeneral Information

• 10 CFR 35.2, Definitions This section would be amended to (1) include new definitions for gamma stereotactic radiosurgery unit and teletherapy unit to delineate between the two devices and types of use, and (2) revise the existing definition for stereotactic radiosurgery to clarify stereotactic guidance and align with the medical communitys definition of stereotactic radiosurgery.

• 10 CFR 35.8, Information collection requirements: OMB approval The information collection requirements under this section would be amended to reflect the proposed restructure of Subpart H. Specifically, reference to regulations that are removed from Subpart H would be removed.

• 10 CFR 35.12, Application for license, amendment, or renewal Requirements for application for licenses, amendments, or renewals under this section would be amended to reflect the proposed restructure of 10 CFR Part 35, Subpart H.

• 10 CFR 35.13, License amendments Requirements for license amendments under this section would be amended to reflect the proposed restructure of 10 CFR Part 35, Subpart H. Additionally, this regulation would be amended to require the submittal of the procedures for activities required by 10 CFR 35.632, Full calibration measurements on teletherapy units. Based on the significant increase in the number of deficiencies during NRC inspections associated with this regulatory requirement and lack of published protocols by nationally recognized bodies specific to the newer devices, the NRC believes it is pertinent to review licensees procedures associated with 10 CFR 35.632 prior to authorization. Additionally, the proposed revision of 10 CFR 35.632 will allow additional flexibility for licensees when they are developing and implementing calibration measurement requirements, and because of this flexibility the procedures must be reviewed prior to authorization.

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Subpart BGeneral Administrative Requirements

• 10 CFR 35.40, Written directives The requirement for written directives under 10 CFR 35.40(b)(3) and 10 CFR 35.40(b)(4) would be amended to require the date, total dose for each treatment site, treatment site(s) including volume and anatomically unique treatment site identifiers, dose per fraction and the number of fractions for treatment plans requiring multiple fractions, and geometry settings (or treatment plan including geometry settings). This would accommodate new GSR and photon emitting teletherapy units and reduce emphasis on specific components.

• 10 CFR 35.41, Procedures for administrations requiring a written directive The ability to safely stop and start therapeutic deliveries of radiation from GSR and teletherapy units has improved, however, this still presents a risk for a medical event. This section would be amended to require determination of whether there was a pause of treatment for significant patient movement or other factors which could affect localization and if so, require verification of patient positioning systems, including immobilization devices, as appropriate, prior to re-initiation or new shot, as applicable. In addition, this section would be amended to require verification of patient positioning systems, including immobilization devices, prior to initiation.

• 10 CFR 35.50, Training for Radiation Safety Officer and Associate Radiation Safety Officer The types of devices authorized by 10 CFR Part 35, Subpart H, have become increasingly complex and different among models of devices. Therefore, the requirements for training for RSOs in this section would be amended to require model-specific training for all 10 CFR Part 35, Subpart H devices.

Question A.7.1 Should model-specific training for RSOs only be required for certain 10 CFR Part 35, Subpart H devices? Please provide a basis for your response. If so, how should it be determined which devices would require model-specific training?

• 10 CFR 35.51, Training for an authorized medical physicist The types of devices authorized by 10 CFR Part 35, Subpart H, have become increasingly complex and different among models of devices. Therefore, the requirements for training for AMPs in this section would be amended to require model specific training for all Subpart H devices, exclusive of HDR remote afterloader units.

• 10 CFR 35.57, Training for experienced Radiation Safety Officer, teletherapy or medical physicist, authorized medical physicist, authorized user, nuclear pharmacist, and authorized nuclear pharmacist This section would be amended to add the effective date of the final rule and specify that authorized individuals and RSOs added to a license on or before the effective date need not comply with revised training requirements. This would allow these authorized individuals and A-23

RSOs to maintain their authorization (i.e., legacy individuals, formerly referred to as grandfathered individuals).

Subpart HPhoton Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units Subpart H of 10 CFR Part 35 will be amended to allow for a fundamental shift in the regulatory requirements for these technologies, from a focus on specific components to a focus on the element such as source output, source collimation, source position, source attenuation, patient safety, and facility safety. Various conforming text changes may be made through 10 CFR Part 35, Subpart H, to align with the restructure of and shift in approach.

Question A.7.2 The proposed changes to 10 CFR Part 35, Subpart H, focus on elements rather than specific components. Current NRC requirements in 10 CFR Part 35, Subpart H are focused on components that are critical to patient and facility safety for the use of these devices. The proposed changes shift to a focus on elements and objectives rather than specific components. What other elements should be considered, if any? Please provide a basis for your response.

• 10 CFR 35.610, Safety procedures and instructions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units This section will be revised to clarify that the AU and AMP, as well as any individual who will operate the unit, are required to have vendor operational and safety training.

• 10 CFR 35.615, Safety precautions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units Based on operating experience with 10 CFR Part 35, Subpart H, technologies, it is evident that equipment performance is reliable if patient set up is done correctly and calibrations are properly performed. The physical presence requirements in this section would be amended to require that an AMP and AU be present at initiation of the treatment and require that an AMP and a physician under the supervision of an AU be present throughout the treatment.

Additionally, the AU would need to be physically present at the facility and able to return to the treatment if necessary.

• 10 CFR 35.632, Full calibration measurements on teletherapy units The requirements for full calibration measurements on photon emitting teletherapy units, remote afterloader units, and GSR units would be combined into one regulation. The title of this section would be amended to Full calibration measurements on remote afterloader units, photon emitting teletherapy units, and gamma stereotactic radiosurgery units. The other calibration sections10 CFR 35.633, Full calibration measurements on remote afterloader units, and 10 CFR 35.635, Full calibration measurements on gamma stereotactic radiosurgery unitswould be eliminated.

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The full calibration measurements requirements would be revised to remove the reference to specific components and require certain objective tests to be completed. For example, the regulation could require:

o measurements for output and geometric accuracy for a range of field sizes and distances o condition, function, and accuracy of all distance measuring, localizing, attenuation, and collimation devices to include source transfer tubes and applicators o timer accuracy o timer linearity o on-off error o emergency retraction devices o backup power devices Question A.7.3 What types of objective tests should the NRC require to be completed for full calibration measures for 10 CFR Part 35, Subpart H devices? Additionally, what functional elements should be considered critical to safety? Please provide a basis for your response.

• 10 CFR 35.633, Full calibration measurements on remote afterloader units This section would be incorporated into 10 CFR 35.632 and eliminated.

• 10 CFR 35.635, Full calibration measurements on gamma stereotactic radiosurgery units This section would be incorporated into 10 CFR 35.632 and eliminated.

• 10 CFR 35.642, Periodic spot-checks for teletherapy units The requirements for periodic spot-checks for photon emitting teletherapy units, remote afterloader units, and GSR units would be combined into one regulation. The title of this section would be amended to Periodic spot-checks on photon emitting remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units. The other spot-check sections10 CFR 35.643, Periodic spot-checks for remote afterloader units, and 10 CFR 35.645, Periodic spot-checks for gamma stereotactic radiosurgery unitswould be eliminated.

The requirements would be revised to remove references to specific components and require certain objective tests to be completed. For example, the regulation could require:

o assurance of source output o difference between the measured output and the anticipated output o difference between the output or dose rate and the computer-generated output or dose rate o operation of all distance measuring, localizing, attenuation, and collimation devices to include source transfer tubes and applicators A-25

o operation of electrical or mechanical stops installed for the purpose of limiting use of the primary beam of radiation o operation of treatment room doors with electrical power turned off o geometric accuracy o timer accuracy o on-off error o emergency retraction devices o operation of electrical interlocks on the treatment room entrance o operation of source exposure lights on the console and in the facility inside and outside treatment room o operation of viewing and intercom systems o operation of radiation monitors used to indicate source position o availability of emergency response equipment o confirmation of treatment console and unit computer date and time o confirmation of the decayed source activity in the treatment console and unit computer, and o operation backup power devices.

Question A.7.4 What types of objective tests should the NRC require to be completed for periodic spot-checks for 10 CFR Part 35, Subpart H devices? Additionally, what functional elements should be considered critical to safety? Please provide a basis for your response.

• 10 CFR 35.643, Periodic spot-checks for remote afterloader units This section would be incorporated into 10 CFR 35.642 and eliminated.

• 10 CFR 35.645, Periodic spot-checks for gamma stereotactic radiosurgery units This section would be incorporated into 10 CFR 35.642 and eliminated.

• 10 CFR 35.690, Training for use of remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units This section would be amended to require that AU training be specific for the type of use and for the specific model of the unit being used to accommodate the radiation safety differences between types of units of each use under 10 CFR Part 35, Subpart H.

Subpart LRecords Conforming changes to 10 CFR Part 35, Subpart L, would be made based on revisions to Subpart H. Revisions to the requirements would be made based on the proposed rule.

• 10 CFR 35.2642, Records of periodic spot-checks for teletherapy units This section would be amended to include records for period spot-checks of photon emitting teletherapy units, remote after loader units, and GSR units. The other sections for records of A-26

spot-checks10 CFR 35.2643, Records of periodic spot-checks for remote afterloader units, and 10 CFR 35.2645, Records of periodic spot-checks for gamma stereotactic radiosurgery unitswould be eliminated.

• 10 CFR 35.2643, Records of periodic spot-checks for remote afterloader units This section would be incorporated into 10 CFR 35.2642 and eliminated.

• 10 CFR 35.2645, Records of periodic spot-checks for gamma stereotactic radiosurgery units This section would be incorporated into 10 CFR 35.2642 and eliminated.

Other 10 CFR Part 35 Subparts No changes are needed to the following subparts to address gamma stereotactic radiosurgery and photon emitting teletherapy units:

• Subpart CGeneral Technical Requirements

• Subpart DUnsealed Byproduct MaterialWritten Directive Not Required

• Subpart EUnsealed Byproduct MaterialWritten Directive Required

• Subpart GSealed Sources for Diagnosis

• Subpart I [Reserved] (Staff is proposing this as a new subpart, Microsource Manual Brachytherapy)

• Subpart J [Reserved]

• Subpart KOther Medical Uses of Byproduct Material or Radiation From Byproduct Material

• Subpart MReports

• Subpart NEnforcement A.8 Microsource Manual Brachytherapy The use of microspheres for permanent implant manual brachytherapy has significantly grown over the past 20 years and has provided valuable operating experience into their use.

Microsphere use is expected to continue to increase, and the NRC anticipates that additional new technologies, including microparticles and new microsphere systems, may be authorized in the years to come. To incorporate the use of new and existing microspheres and microparticles for manual brachytherapy, the NRC proposes creating a new subpart within 10 CFR Part 35 to address their unique characteristics. This subpart would be created in the currently reserved Subpart I of 10 CFR Part 35. The proposed changes include creating a new definition for these types of sources to be defined as microsources under a new type of use to be called microsource manual brachytherapy. To create a new subpart, amendments are needed throughout 10 CFR Part 35 to distinguish between current manual brachytherapy technologies and microsource manual brachytherapy. The new 10 CFR Part 35, Subpart I, would mirror the structure of Subparts F and H, but the requirements would be specific to the use of microsource manual brachytherapy.

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Subpart AGeneral Information

• 10 CFR 35.2, Definitions This section would be amended to include new definitions for: (1) Microsource to be defined as a microparticle or microsphere; (2) Physiological equilibrium to include stasis or other states of equilibrium based on medical determination; and (3) Microsource manual brachytherapy to include use of microsources to allow for a new type of use of byproduct material.

This section would be amended to clarify the definition for Type of use to include 10 CFR 35.700 for medical use of microsources. Additionally, conforming changes to the definition of Prescribed dose or Prescribed dosage will be made based on revisions to 10 CFR 35.40 described below.

Question A.8.1 The proposed changes to bring 10 CFR Part 35, Subpart K, microspheres into the regulatory framework include defining a microsource in 10 CFR 35.2 as microparticles and microspheres. What types of radiation (such as alpha, beta, gamma) should be covered by the definition of microsource? Should microspheres be limited to specific types of radiation or certain energies? Should microsources be limited to sealed sources with an SS&D registry? Are there any additional changes needed to the current regulations for microsource brachytherapy that would create added flexibility for future microsource brachytherapy? Please provide a basis for your responses.

Question A.8.2 The proposed changes to bring microsphere EMTs into the regulatory framework include defining physiological equilibrium to include stasis or other states of equilibrium in 10 CFR 35.2. What should be included in physiological equilibrium or other considerations for physiological stop points? Please provide a basis for your response.

• 10 CFR 35.8, Information collection requirements: OMB approval This section would be amended to add information collection requirements in the new 10 CFR Part 35, Subpart I.

• 10 CFR 35.12, Application for license, amendment, or renewal This section would be amended to include the use of byproduct material as described in 10 CFR 35.700 for medical use of microsources. This would include changes for the collection of certain procedures during licensing and the inclusion of the new 10 CFR Part 35, Subpart I.

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• 10 CFR 35.13, License amendments This section would be amended to include notifications for AUs receiving device-specific training under 10 CFR 35.790 for the AU under 10 CFR 35.700. This regulation will be revised to include requesting amendments for revisions to procedures required by 10 CFR Part 35, Subpart I for 10 CFR 35.700 usesrevisions that could reduce radiation safety would need to be approved via a license amendment before use.

• 10 CFR 35.14, Notifications This section would be amended to include notifications for AUs receiving device-specific training under 10 CFR 35.790.

Subpart BGeneral Administrative Requirements

• 10 CFR 35.24, Authority and responsibilities for the radiation protection program Because a new subpart I in 10 CFR Part 35 would be created, paragraph (f) of this section would be amended to require licensees that are authorized for two or more different types of uses of byproduct material under Subparts E, F, H, the new Subpart I of 10 CFR Part 35; or two or more types of units under Subpart H; or two or more types of uses under the new Subpart I of 10 CFR Part 35, to establish a Radiation Safety Committee to oversee all uses of byproduct material permitted by the license.

• 10 CFR 35.27, Supervision The use of microsource manual brachytherapy is complex and the safe use of microsources typically involves support from multiple clinicians in a team approach. As such, this section would be amended to include requirements for licensees to ensure appropriate training of individuals involved in the administration, handling, and use of microsource manual brachytherapy. This change would require that licensees develop, implement, and maintain procedures for the team approach to ensure safe use of microsources. These procedures would include a training program for individuals of the team to ensure training is commensurate with the duties of each individual on the team.

Question A.8.3 As the complexity of the medical use of byproduct material increases, use of teams in medical care is becoming more common. What are the fundamental elements of a successful team-approach program? Please provide a basis for your response.

• 10 CFR 35.40, Written directives This section would be amended to clarify that requirements for manual brachytherapy uses under 10 CFR Part 35, Subpart F, are found in 10 CFR 35.40(b)(6). The requirements for written directives for microsource manual brachytherapy uses under 10 CFR Part 35, Subpart I, will be listed under a new item in 10 CFR 35.40(b). The new item will include:

(i) Before implantation: The treatment site, the radionuclide, the radioactive drug or device A-29

name and manufacturer, and the prescribed activity or dose; and (ii) after implantation but before the patient leaves the licensee's control: The treatment site, total activity or dose, determination of physiological equilibrium, and the date.

Question A.8.4 For microsource manual brachytherapy, should the written directive require the dose or activity? Please provide a basis for your response.

Question A.8.5 For microsource manual brachytherapy, should the written directive specify the activity administered or should it specify the activity or dose delivered to the treatment site? Please provide a basis for your response.

• 10 CFR 35.41, Procedures for administrations requiring a written directive This section would be amended to include the uses under 10 CFR Part 35, Subpart I. To provide reasonable assurance of the safe use of microsource manual brachytherapy, this regulation would be amended to require procedures for calculating and documenting the dose or activity to the treatment site, preparing the dose, estimating migration to non-treatment site prior to administration, and determining physiological equilibrium.

Question A.8.6 Section 35.41 of 10 CFR Part 35 requires procedures to determine if a medical event, as defined in 10 CFR 35.3045, has occurred. Should the NRC require calculating and documenting the activity administered, or activity or dose specifically delivered to the treatment site? If so, by what timeframe (e.g., 48 hours5.555556e-4 days <br />0.0133 hours <br />7.936508e-5 weeks <br />1.8264e-5 months <br />, 7 days, etc.) should this determination be made? Please provide a basis for your response.

• 10 CFR 35.50, Training for Radiation Safety Office and Associate Radiation Safety Officer The types of devices authorized by 10 CFR Part 35, Subpart I, would be diverse in models, delivery, and involved individuals. Therefore, the requirements for training for RSOs in 10 CFR 35.50 would be amended to require model-specific training for all 10 CFR Part 35, Subpart I devices, similar to the recommended changes described in Section A.7.

• 10 CFR 35.51, Training for an authorized medical physicist Question A.8.7 Is there any task that would require an AMP for the use of microsphere manual brachytherapy? If so, would there be any need to change the T&E requirements for AMPs? Please provide a basis for your response.

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• 10 CFR 35.57, Training for experienced Radiation Safety Officer, teletherapy or medical physicist, authorized medical physicist, authorized user, nuclear pharmacist, and authorized nuclear pharmacist This section would be amended to add the effective date of the final rule and specify that authorized individuals and RSOs added to a license on or before the effective date need not comply with revised training requirements. This would allow these authorized individuals and RSOs to maintain their authorization (i.e., legacy individuals, formerly referred to as grandfathered individuals).

• 10 CFR 35.59, Recentness of training This section would be amended to include 10 CFR Part 35, Subpart I.

Subpart CGeneral Technical Requirements

• 10 CFR 35.60, Possession, use, and calibration of instruments used to measure the activity of unsealed byproduct material Currently this section only applies to unsealed byproduct material. The title of this section and requirements would be amended to include microsources. Specifically, this section would be amended to include the measurement of microsources activity. Instruments used to measure the activity of microsources for determination of the dose to the patient must be calibrated in accordance with the microsources manufacturer recommendations and a nationally recognized standard or instrument manufacturer recommendation when a standard is not available.

• 10 CFR 35.63, Determination of dosages of unsealed byproduct material for medical use Currently this section only applies to unsealed byproduct material. The title of this section and the requirements for determination of dosages would be amended to include microsources for medical use.

• 10 CFR 35.67, Requirements for possession of sealed sources and brachytherapy sources Since microsources are not individual discrete sources, this section would be amended to clarify that microsources are not required to be leak tested or inventoried like other brachytherapy sources.

• 10 CFR 35.69, Labeling of vials and syringes Since some microsources are not considered radioactive drugs, this section would be amended to include labeling of vial radiation shields and syringe radiation shields for microsources.

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Subpart I 10 CFR Part 35, Subpart I, would be used to establish the requirements for microsource manual brachytherapy. At a minimum, this subpart would address requirements to for the safe use of microsource manual brachytherapy.

Question A.8.8 What types of use should be permitted under a new subpart for microsource manual brachytherapy? Should the use of microsources be limited to the use(s) approved in the SS&D registry? Please provide a basis for your response.

• 10 CFR 35.700 (proposed new section)

This new section would establish the use of microsources only for the use(s) approved in the SS&D registry or other materials prepared for microsource manual brachytherapy that are obtained from approved sources. This regulation would, at a minimum, require that the microsources be used in accordance with the radiation safety conditions and limitations described in the SS&D registry. Additionally, the microsources may be used in research to deliver therapeutic doses for medical use in accordance with an active Investigational Device Exemption application accepted by the FDA, provided the requirements of 10 CFR 35.49(a) are met.

• 10 CFR 35.704 (proposed new section)

This new section would establish survey requirements for patients or human research subjects after source implant and removal for temporary implants, if applicable. In addition, this new section would establish survey requirements for all areas where microsources are handled. The frequency for these surveys would be immediately after use for unrestricted areas and end of day for restricted areas.

• 10 CFR 35.706 (proposed new section)

This new section would establish microsource accountability for temporary microsource manual brachytherapy sources that are in storage or in use.

• 10 CFR 35.710 (proposed new section)

This new section would establish safety procedures and instructions to include: (1) radiation safety instruction requirements for personnel caring for patients or human research subjects who are receiving microsource manual brachytherapy and cannot be released under 10 CFR 35.75; (2) a requirement to develop, implement, and maintain written procedures for responding to an abnormal situation such as spills, leaks, or emergent patient conditions; and (3) a requirement that prior to the first use for patient treatment of a new delivery system, a licensee shall ensure that vendor operational and safety training is provided to all individuals involved in microsource manual brachytherapy use. This training must be provided to all individuals preparing, measuring, performing dosimetry calculations, or administering microsources pursuant to 10 CFR 35.27.

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Question A.8.9 The proposed changes to bring microspheres into the regulatory framework include establishing safety procedures and instructions. These changes are based on current licensing guidance for Y-90 microspheres and expected new uses of microsources. Are there other items that should be included in a new requirement for safety procedures in instructions for microsource manual brachytherapy? Please provide a basis for your response.

• 10 CFR 35.715 (proposed new section)

This new section would establish safety precautions to include: (1) requirements for patients or human research subjects receiving microsource manual brachytherapy that cannot be released under 10 CFR 35.75; (2) a requirement to have applicable emergency equipment available near each treatment room to respond to spills, leaks, contamination, or losses of pressure in a system; (3) notifications to the RSO, or his or her designee, and an AU as soon as possible if the patient or human research subject has a medical emergency or dies.

Question A.8.10 The proposed changes to bring microspheres into the regulatory framework include establishing safety precautions. These changes are based on current licensing guidance for Y-90 microspheres and expected new uses of microsources. Are there other items that should be included in a new requirement for safety precautions for microsource manual brachytherapy? Please provide a basis for your response.

• 10 CFR 35.790 (proposed new section)

This new section would establish training for AUs for use of microsource manual brachytherapy.

Question A.8.11 The current licensing guidance for Y-90 microspheres requires that an AU successfully complete training in the operation of the delivery system, safety procedures, and clinical use for the specific type of Y-90 microsphere for which authorization is sought. The guidance specifies that clinical use training to support unsupervised use should include at least three hands-on patient cases for each type of Y-90 microsphere requested, conducted in the physical presence of an AU who is authorized for the type of Y-90 microsphere for which the individual is seeking authorization.

The guidance allows conditional approval of an AU prior to completing these three hands-on patient cases if a proposed AU cannot complete patient cases prior to authorization. The A-33

reason this conditional approval was originally added to the guidance was there were limited Y-90 microsphere licensees and AUs to provide training to future AUs. As there has been a significant increase in the use of Y-90 microspheres, is there still a need for conditional approval for Y-90 microspheres? Should the NRC continue to allow this pathway for all microspheres and microsources AUs? Please provide a basis for your responses.

Question A.8.12 The current licensing guidance for Y-90 microspheres has a pathway for interventional radiologists to become AUs for Y-90 microspheres use. This pathway requires the interventional radiologist to demonstrate that they have 80 hours9.259259e-4 days <br />0.0222 hours <br />1.322751e-4 weeks <br />3.044e-5 months <br /> of classroom and laboratory training in specific topics and specific work experience important to radiation safety in addition to demonstrating they have sufficient clinical interventional radiology and diagnostic radiology experience.

Are there any additional topics or specific T&E areas that are not currently listed in the licensing guidance that should be considered? Are there any topics or specific T&E areas that should be removed? Is 80 hours9.259259e-4 days <br />0.0222 hours <br />1.322751e-4 weeks <br />3.044e-5 months <br /> an appropriate amount of time to ensure these topics are adequately covered? Who should supervise the work experience to ensure the future AUs have adequate radiation safety knowledge? Please provide a basis for your responses.

Question A.8.13 The current licensing guidance for Y-90 microspheres provides a pathway for interventional radiologists and physicians that meet the T&E requirements in 10 CFR 35.390 and 10 CFR 35.490 to become AUs for Y-90 microspheres use. This pathway does not require any additional classroom and laboratory training or specific work experience for these physicians besides demonstration of successfully completed training in the operation of the delivery system, safety procedures, and clinical use (including hands-on patient cases) for the type of Y-90 microsphere for which the physician seeks authorization. Should additional classroom and laboratory training topics or specific work experience be required for these physicians to become AUs for all microspheres or other types of microsources in 10 CFR Part 35, Subpart I? If so, what additional training and work experience should be considered? Please provide a basis for your responses.

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Question A.8.14 The current licensing guidance for Y-90 microspheres provides pathways for interventional radiologists and physicians that meet the T&E requirements in 10 CFR 35.390 and 35.490 to become AUs for Y-90 microspheres use. Is there a need for additional pathways for other types of physicians to become AUs for use of microspheres or other types of microsources? Please provide a basis for your response.

Subpart LRecords

• 10 CFR 35.2060, Records of calibrations of instruments used to measure the activity of unsealed byproduct material This section would be amended to make conforming changes based on the creation of 10 CFR Part 35, Subpart I, and revisions to Subpart C. The title of this section would be amended to refer to measurements of microsources.

• 10 CFR 35.2063 This section would be amended to make conforming changes based on the creation of 10 CFR Part 35, Subpart I, and revisions to Subpart C. The title of this section would be amended to refer to measurements of microsources.

• 10 CFR 35.2310 This section would be amended to make conforming changes based on the creation of 10 CFR Part 35, Subpart I, and revisions to Subpart C. This section would be amended to refer to 10 CFR 35.710.

• 10 CFR 35.2404 This section would be amended to make conforming changes based on the creation of 10 CFR Part 35, Subpart I, and revisions to Subpart C. This section would be amended to refer to 10 CFR 35.704

• 10 CFR 35.2406 This section would be amended to refer to 10 CFR 35.706 which would require that 10 CFR 35.2406(b) and 10 CFR 35.2406(c) be changed to specifically reference individual discrete source implants. Section 35.2406(d) will be added to provide record requirements for microsources. Alternatively, 10 CFR 35.2406(c) could be amended to reference aggregate microsources. In either case, the title of the section would be amended to reference microsources.

• 10 CFR 35.2710 (proposed new section)

This section would be created for maintenance of records regarding safety procedures.

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Subpart MReports

• 10 CFR 35.3045, Report and notification of a medical event This section would be amended to adjust reporting requirements for microsource manual brachytherapy. For example, a new set of requirements for microsource manual brachytherapy would be created based on current licensing guidance for microsphere manual brachytherapy and operating experience from these types of uses. Additionally, an exclusion would be included for medical events due to reaching physiological equilibrium during microsource manual brachytherapy. Conforming changes would be needed to differentiate current brachytherapy use medical event criteria from microsource manual brachytherapy medical event reporting criteria.

Other 10 CFR Part 35 Subparts No changes are needed to the following subparts to address microsource manual brachytherapy:

• Subpart DUnsealed Byproduct MaterialWritten Directive Not Required

• Subpart EUnsealed Byproduct MaterialWritten Directive Required

• Subpart FManual Brachytherapy

• Subpart GSealed Sources for Diagnosis

• Subpart HPhoton Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units

• Subpart J [Reserved]

• Subpart KOther Medical Uses of Byproduct Material or Radiation From Byproduct Material

• Subpart NEnforcement A.9 Other 10 CFR Part 35 Changes The NRC would consider the following additional issues in this rulemaking to increase flexibilities in 10 CFR Part 35 to accommodate emerging radiopharmaceutical uses and future EMTs.

Subpart AGeneral Information

• 10 CFR 35.2, Definitions This section would be amended to expand the definition of a physician to include individuals with a foreign-equivalent degree to a medical doctor or doctor of osteopathy. The physician would still need to be licensed by a State or Territory of the United States, the District of Columbia, or the Commonwealth of Puerto Rico to prescribe drugs in the practice of medicine.

To accommodate changes to 10 CFR 35.75, this section would also be amended to include the definition of treatment regimen."

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Subpart BGeneral Administrative Requirements

• 10 CFR 35.24, Authority and responsibilities for the radiation protection program This section would be amended to expand the requirement in 10 CFR 35.24(f) for licensees to establish a Radiation Safety Committee if they are authorized for two or more different types of uses of byproduct material under 10 CFR Part 35, Subparts E, F, G, H, I and K, or two or more types of units under Subpart H, two or more types of uses under Subpart I, or two or more types of uses under Subpart K. This requirement would be amended to account for any EMTs under 10 CFR Part 35, Subpart K; current EMTs that would be incorporated into other subparts; Subpart G that now includes RSL procedures; and the new Subpart I for microsource manual brachytherapy. These subparts are not currently accounted for in 10 CFR 35.24.

Additionally, 10 CFR 35.24(f) would be amended to clarify that the nursing service representative is required to serve on a Radiation Safety Committee must be experienced in oversight or performance of licensed activities.

• 10 CFR 35.27, Supervision This section would be amended to include that the licensee must provide instruction to the supervising individual in addition to the supervised individual in the licensees written radiation protection procedures, written directive procedures, regulations of 10 CFR Part 35, and license conditions with respect to use of byproduct material. Further, 10 CFR 35.27(c) will be amended to clarify that licensees that permit supervised activities are responsible for both the acts and omissions of both the supervising individual and the supervised individual.

Additionally, a new requirement would be added to this section requiring the licensee to provide instruction to both the supervising individual and supervised individual on the definition of a medical event and associated reporting requirements for medical events.

• 10 CFR 35.40, Written directives To support revisions to the patient release regulations to account for radiopharmaceutical therapy regimens with multiple administrations (see discussion of proposed changes to 10 CFR 35.75 below), this section would be amended to require written directives to include dosage per administration and number of administrations (if a regimen is planned) and total dosage.

• 10 CFR 35.41, Procedures for administrations requiring a written directive This section would be amended to include a requirement that licensees have procedures in place to verify that the written directive is correct, to require training on these procedures for AUs, and to require an annual review of the procedures.

• 10 CFR 35.59, Recentness of training This section would be amended to include 10 CFR Part 35, Subpart K.

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Question A.9.1 Due to the increased number and complexity of EMTs, should the NRC require continuing education for AUs? If so, what should the continuing education entail, what should be the frequency at which it should be acquired, and how should knowledge topics be acquired? Please provide a basis for your responses.

Subpart CGeneral Technical Requirements

• 10 CFR 35.75, Release of individuals containing unsealed byproduct material or implants containing byproduct material This section would be amended to address the significant increase in fractionated radiopharmaceutical treatments. Specifically, 10 CFR 35.75 would be amended so that the current limits are per treatment regimen and not per release.

Subpart DUnsealed Byproduct MaterialWritten Directive Not Required

• 10 CFR 35.190, Training for uptake, dilution, and excretion studies This section would be amended to address T&E requirements for uses authorized under 10 CFR 35.100, Use of unsealed byproduct material for uptake, dilution, and excretion studies for which a written directive is not required. Specifically, 10 CFR 35.190 would be amended to clarify in the preamble that individuals who qualify as AUs under 10 CFR 35.290, Training for imaging and localization studies, and 10 CFR 35.390, Training for use of unsealed byproduct material for which a written directive is required, may be authorized to use 10 CFR 35.100 materials.

• 10 CFR 35.290, Training for imaging and localization studies This section would be amended to address T&E requirements for uses authorized under 10 CFR 35.200, Use of unsealed byproduct material for imaging and localization studies for which a written directive is not required. Specifically, 10 CFR 35.290 would be amended to clarify in the preamble that individuals who qualify as AUs under 10 CFR 35.390 who have generator elution experience as described in 10 CFR 35.290(c)(1)(ii)(G) may be authorized for use of 10 CFR 35.200 materials.

The NRC is considering further amendments to this section to address T&E requirements for eluting, measuring, testing, and processing of eluate from radionuclide generator systems.

Radionuclide generator systems, facilities, and individual users have changed significantly since the regulations relating to generator systems were last updated in 1994. 22 In evaluating these industry changes, the Advisory Committee for the Medical Use of Isotopes (ACMUI) deliberated the intent of the existing language in 10 CFR 35.290(c)(1)(ii)(G) regarding T&E requirements for AUs. The ACMUI affirmed their belief that AUs must be familiar with how radionuclide generators work, how breakthrough is tested, and how reagent kits are used to label radioactive drugs, but the direct hands-on work experience 22 Preparation, Transfer for Commercial Distribution, and Use of Byproduct Material for Medical Use, (59 FR 29525; December 2, 1994).

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currently required by 10 CFR 35.290(c)(1)(ii)(G) is not necessary. 23 In accordance with this recommendation, 10 CFR 35.290(c)(1)(ii)(G) would be amended to increase the flexibility of generator-specific training required for AUs.

Question A.9.2 Do AUs for 10 CFR 35.200 need device-specific training on radionuclide generators? If so, what should the scope of the training include? Should the training be specific to the radionuclide generator for which they are supervising the use? Please provide a basis for your response.

Subpart EUnsealed Byproduct MaterialWritten Directive Required

• 10 CFR 35.392, Training for the oral administration of sodium iodide I-131 requiring a written directive in quantities less than or equal to 1.22 gigabecquerels (33 millicuries),

10 CFR 35.394, Training for the oral administration of sodium iodide I-131 requiring a written directive in quantities greater than 1.22 gigabecquerels (33 millicuries), and 10 CFR 35.396, Training for the parenteral administration of unsealed byproduct material requiring a written directive These sections would be amended to clarify the T&E requirements for uses of unsealed byproduct material requiring a written directive. Specifically, 10 CFR 35.392 would be amended to clarify that physicians trained under 10 CFR 35.390 or 10 CFR 35.394 are eligible to administer sodium iodide I-131 in quantities less than or equal to 33 millicuries.

Additionally, 10 CFR 35.394 would be amended to clarify that physicians trained under 10 CFR 35.390 are eligible to administer sodium iodide I-131 in quantities greater than 33 millicuries. Similarly, 10 CFR 35.396 would be amended to clarify that a physician authorized under 10 CFR 35.390 would be eligible to perform parenteral administration of unsealed byproduct material requiring a written directive.

Question A.9.3 Do physicians authorized for full use under 10 CFR 35.300 need additional new T&E to fulfill their radiation safety-related duties and supervision roles due to expected emerging therapeutic radiopharmaceuticals? Do these 10 CFR 35.300 AUs need additional training on regulatory requirements for emerging therapeutic radiopharmaceuticals? If so, what should the scope of the T&E include? Should these AUs be required to have any specific training (such as vendor training on clinical use and safety procedures), prior to use for the first time, or have continuing education? Please provide a basis for your response.

Subpart G - Sealed Sources for Diagnosis

• 10 CFR 35.590, Training for use of sealed sources and medical devices for diagnosis 23 See ACMUI Subcommittee on Radionuclide Generator Knowledge and Practice Requirements, Final Report, October 14, 2021 (ML21288A126).

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Question A.9.4 Is the current AU T&E requirement for use of sealed sources and medical devices for diagnosis in 10 CFR 35.590 (i.e., 8 hours9.259259e-5 days <br />0.00222 hours <br />1.322751e-5 weeks <br />3.044e-6 months <br /> of classroom and laboratory training in basic radionuclide handling techniques specifically applicable to the use of the device authorized under 10 CFR 35.500, as well as device-specific training in the use of the device) appropriate for future emerging sealed sources and medical devices containing sealed sources? If AUs for 10 CFR 35.500 need additional new training and work experience topics due to future emerging sealed sources and medical devices containing sealed sources for diagnosis, what should the scope of the training include? Please provide a basis for your response.

Subpart HPhoton Emitting Remote Afterloader Units, Teletherapy Units, and Gamma Stereotactic Radiosurgery Units

• 10 CFR 35.610, Safety procedures and instructions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units To align requirements with the technology of newer model GSR units and other devices regulated under 10 CFR Part 35, Subpart H, the NRC is considering amending this section to include requirements for console passwords.

Question A.9.5 Are there specific changes that are needed to secure consoles, keys, and passwords for remote afterloader units, teletherapy units, and GSR units that should be considered based on the changes in technology? If so, what changes are suggested? Please provide a basis for your response.

• 10 CFR 35.615, Safety precautions for remote afterloader units, teletherapy units, and gamma stereotactic radiosurgery units The NRC is considering amending this section to clarify what types of doors are acceptable at the treatment room entrance for the licensee to control access to the treatment room.

Question A.9.6 What types of doors or entry controls are acceptable to maintain security of licensed material while not interfering with patient care? (Should a physical door be required or are other entry controls such as lasers acceptable?) Please provide a basis for your response.

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• 10 CFR 35.2075, Records of the release of individuals containing unsealed byproduct material or implants containing byproduct material Conforming changes to this section would be made based on changes to 10 CFR 35.75 to incorporate release of patients undergoing a multiple treatment regimen.

• 10 CFR 35.3045, Report and notification of a medical event To support changes to 10 CFR 35.75, the reporting requirements for medical events will be amended to allow the AU to change a regimen during a treatment protocol if medically necessary.

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Appendix B - Data Tables Table 7, Emerging Medical Technology Licensing Assumptions, contains the NRCs assumptions about future emerging medical technology (EMT) licensing over a period of 15 years from 2030 through 2044, after implementation of the Alternative 4 rule by the National Materials Program. The assumptions inform the time (hours) the NRC, Agreement States, and licensees would save on EMT licensing actions after implementation of the Alternative 4 rule. The predicted numbers of future licensing actions for each EMT include licensing actions for updated models of the EMT and new technologies that could be licensed under the revised medical use subpart. For example, the predicted number of future licensing actions for microspheres includes the possibility of new technologies (e.g., microparticles) that could be licensed under the new Subpart I, Microsource Manual Brachytherapy.

The NRC first estimated NRC licensing action labor hour savings, and then extrapolated Agreement State licensing action labor hour savings assuming the Agreement States will regulate 93 percent of medical licensees by 2030. The NRC used data from STC-22-034, Annual Count of Active Radioactive Materials Licenses in the National Materials Program, to calculate the ratio of licensees regulated by the Agreement States and the NRC. The NRC estimated that licensee licensing action labor hour savings could range from zero to 25 percent of the NRC and Agreement State savings. For the purpose of the cost-benefit analysis, the NRC calculated licensee licensing action labor hour savings assuming that licensee savings would be 12.5 percent of the total NRC and Agreement State estimates. As previously noted, the NRC is interested in obtaining feedback from licensees on whether and how licensees would realize averted licensing costs as a result of the Alternative 4 rulemaking.

The licensing action labor hour savings in Table 7 (i.e., Licensing Hours Saved Over 15 Years) inform the Submission and Review of EMT License Applications and Amendments data in Table 8 and the operation benefits tables for Alternatives 3 and 4 in Appendix C.

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Table 7: Emerging Medical Technology Licensing Assumptions Licensing Hours NRC Emerging Medical Technology Licensing Resource Saved Over 15 Years Assumptions Technology Agreement Submission and Review of Initial License Applications Licensees NRC States and Amendment Requests Germanium-68/Gallium-68 153 80 1,143

• 25% savings for initial license; no amendments needed.

Pharmaceutical Grade Generators

• 40 hours4.62963e-4 days <br />0.0111 hours <br />6.613757e-5 weeks <br />1.522e-5 months <br /> for initial license review.

• Less than 10 licensed by NRC to date; NRC will license 8 in the next 15 years.

NeoVista, Inc.'s Epi-Rad90 (Sr-90) 344 180 2,571

• 50% savings for initial license and amendments.

Opthalmic System

• 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> for initial license review; 4 hours4.62963e-5 days <br />0.00111 hours <br />6.613757e-6 weeks <br />1.522e-6 months <br /> for amendment review.

• 7 licensed by NRC to date; NRC will license 5 in the next 15 years.

• Each licensee (including existing licensees) will submit 5 amendment requests each in the next 15 years.

Best Vascular, Inc. Beta-Cath 401 210 3,000

• 50% savings for initial license and amendments.

Intravascular Brachytherapy System

• 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> for initial license review; 4 hours4.62963e-5 days <br />0.00111 hours <br />6.613757e-6 weeks <br />1.522e-6 months <br /> for amendment review.

• 10 licensed by NRC to date; NRC will license 5 in the next 15 years.

• Each licensee (including existing licensees) will submit 5 amendment requests each in the next 15 years.

I-125 Iotrex Liquid Brachytherapy 306 160 2,286

• 50% savings for initial license and amendments.

Source in Cytyc GliaSite Radiation

• 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> for initial license review; 4 hours4.62963e-5 days <br />0.00111 hours <br />6.613757e-6 weeks <br />1.522e-6 months <br /> for amendment Therapy System review.

• 5 licensed by NRC to date; NRC will license 5 in the next 15 years.

• Each licensee (including existing licensees) will submit 5 amendment requests each in the next 15 years.

ViewRay System for Radiation 172 90 1,286

• 25% savings for initial license and amendments.

Therapy

• 40 hours4.62963e-4 days <br />0.0111 hours <br />6.613757e-5 weeks <br />1.522e-5 months <br /> for initial license review; 4 hours4.62963e-5 days <br />0.00111 hours <br />6.613757e-6 weeks <br />1.522e-6 months <br /> for amendment review.

• 3 licensed by NRC to date; NRC will license 3 in the next 15 years.

B-2

Licensing Hours NRC Emerging Medical Technology Licensing Resource Saved Over 15 Years Assumptions Technology Agreement Submission and Review of Initial License Applications Licensees NRC States and Amendment Requests

• Each licensee (including existing licensees) will submit 5 amendment requests each in the next 15 years.

Low Activity Radioactive Seeds Use 1,582 828 11,829

• 50% savings for initial license and amendments.

for Localization of Non-Palpable

• 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> for initial license review; 4 hours4.62963e-5 days <br />0.00111 hours <br />6.613757e-6 weeks <br />1.522e-6 months <br /> for amendment Lesions and Lymph Nodes review.

• 30 licensed by NRC to date; NRC will license 24 in the next 15 years.

• Each licensee (including existing licensees) will submit 5 amendment requests each in the next 15 years.

Gamma Knife - Perfexion 268 140 2,000

• 25% savings for initial license; 50% savings for amendments.

• 40 hours4.62963e-4 days <br />0.0111 hours <br />6.613757e-5 weeks <br />1.522e-5 months <br /> for initial license review; 4 hours4.62963e-5 days <br />0.00111 hours <br />6.613757e-6 weeks <br />1.522e-6 months <br /> for amendment review.

• 4 licensed by NRC to date; NRC will license 5 in the next 15 years.

• Each licensee (including existing licensees) will submit 5 amendment requests each in the next 15 years.

Gamma Knife - Icon 325 170 2,429

• 25% savings for initial license; 50% savings for amendments.

• 40 hours4.62963e-4 days <br />0.0111 hours <br />6.613757e-5 weeks <br />1.522e-5 months <br /> for initial license review; 4 hours4.62963e-5 days <br />0.00111 hours <br />6.613757e-6 weeks <br />1.522e-6 months <br /> for amendment review.

• 7 licensed by NRC to date; NRC will license 5 in the next 15 years.

• Each licensee (including existing licensees) will submit 5 amendment requests each in the next 15 years.

GammaPod 153 80 1,143

• 25% savings for initial license; 50% savings for amendments.

• 40 hours4.62963e-4 days <br />0.0111 hours <br />6.613757e-5 weeks <br />1.522e-5 months <br /> for initial license review; 4 hours4.62963e-5 days <br />0.00111 hours <br />6.613757e-6 weeks <br />1.522e-6 months <br /> for amendment review.

• None have been licensed by NRC to date; NRC will license 4 in the next 15 years.

• Each licensee (including existing licensees) will submit 5 amendment requests each in the next 15 years.

Masep Infini 344 180 2,571

• 25% savings for initial license; 50% savings for amendments.

• 40 hours4.62963e-4 days <br />0.0111 hours <br />6.613757e-5 weeks <br />1.522e-5 months <br /> for initial license review; 4 hours4.62963e-5 days <br />0.00111 hours <br />6.613757e-6 weeks <br />1.522e-6 months <br /> for amendment review.

B-3

Licensing Hours NRC Emerging Medical Technology Licensing Resource Saved Over 15 Years Assumptions Technology Agreement Submission and Review of Initial License Applications Licensees NRC States and Amendment Requests

• None have been licensed by NRC to date; NRC will license 8 in the next 15 years.

• Each licensee (including existing licensees) will submit 5 amendment requests each in the next 15 years.

Sirtex Microspheres 11,159 5,840 83,429

• 50% savings for initial license and amendments.

• 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> for initial license review; 4 hours4.62963e-5 days <br />0.00111 hours <br />6.613757e-6 weeks <br />1.522e-6 months <br /> for amendment review.

• 100 licensed by NRC to date; NRC will license 120 in the next 15 years.

• Each licensee (including existing licensees) will submit 10 amendment requests each in the next 15 years.

• 50% savings for initial license and amendments.

• 24 hours2.777778e-4 days <br />0.00667 hours <br />3.968254e-5 weeks <br />9.132e-6 months <br /> for initial license review; 4 hours4.62963e-5 days <br />0.00111 hours <br />6.613757e-6 weeks <br />1.522e-6 months <br /> for amendment review.

• 50 licensed by NRC to date; NRC will license 75 in the next 15 years.

• Each licensee (including existing licensees) will submit Nordion Microspheres 5,541 2,900 41,429 10 amendment requests each in the next 15 years.

B-4

Table 8: Alternatives 1-4 Data Tables Mean Low High Description Distribution Mid Estimate Estimate Estimate Estimate ALTERNATIVE 1 - STATUS QUO PROCESSING EXEMPTIONS - COSTS Timing: 4 years (2023-2026) inclusive Licensees Submitting Exemption Requests Number of exemptions per year 55 Hours for licensees to prepare and submit exemption requests 8 Pert 7 8 9 Agreement States Reviewing Exemption Requests Number of exemptions per year 49.5 Pert Hours for Agreement States to review exemption requests (36) Pert (39.6) (36.0) (32.4)

NRC Reviewing Exemption Requests Number of exemptions per year 11 Pert Hours for NRC to review exemption requests (36) Pert (40) (36) (32)

INSPECTION OF RB-82 GENERATORS AFTER EXEMPTIONS - AVERTED COSTS Timing: 15 years (2024-2038) inclusive Licensees Inspections Number of Rb-82 generator inspections per year 85 Hours saved per inspection 2 Pert 1.8 2 2.2 Agreement States Inspections Number of Agreement State inspections of Rb-82 generators per 76.5 year Hours saved per Agreement State inspection 4.0 Pert 3.6 4.0 4.4 NRC Inspections Number of NRC inspections of Rb-82 generators per year 8.5 Hours saved per NRC inspection 6 Pert 5 6 7 ALTERNATIVE 2 - RULEMAKING ONLY FOR RB-82 GENERATORS RULEMAKING AND UPDATING GUIDANCE - COSTS Timing: 2.25 years (2022-2024) inclusive Licensees Rulemaking Participation Number of Rb-82 generator licensees participating in rulemaking 11 Pert 10 11 12 Hours for each Rb-82 licensee to participate in rulemaking (4) Pert (4) (4) (4)

Agreement States Rulemaking Participation Number of Agreement States 40 40 Hours for each Agreement State to participate in rulemaking (28) Pert (30) (28) (25)

NRC Rulemaking Number of NRC FTE 3 Pert 2.7 3 3.3 B-5

Mean Low High Description Distribution Mid Estimate Estimate Estimate Estimate FTE Hours (1,524) Pert Rulemaking Comment Management $0 $0 IMPLEMENTATION OF NEW RULE - COSTS Timing: 3 years (2025-2027) inclusive Licensees Implementation of New Rule (No rulemaking implementation costs for licensees) 0 0 Hours 0 0 Agreement States Rulemaking Number of Agreement States 40 40 Cost per Agreement State to develop compatible regulations (40,000) Pert ($44,000) ($40,000) ($36,000)

NRC Regulatory Review of New Agreement State Regulations Hours for NRC regulatory review for each Agreement State (40) Pert (44) (40) (36)

INSPECTION OF RB-82 GENERATORS - AVERTED COSTS Timing: 15 years (2028-2042) Inclusive Licensees Inspections Number of Rb-82 generator inspections each year 85 Hours saved per inspection 2 1.8 2 2.2 Agreement States Inspections Number of Agreement State inspections of Rb-82 generators each 76.6 year Hours saved per Agreement State inspection 4 Pert 3 4 5 NRC Inspections Number of NRC inspections of Rb-82 generators each year 8.5 Hours saved per NRC inspection 6 Pert 4 6 8 ALTERNATIVE 3 - LIMITED SCOPE RULEMAKING FOR RB-82 GENERATORS AND CERTAIN EMERGING MEDICAL TECHNOLOGIES RULEMAKING AND UPDATING GUIDANCE - COSTS Timing: 2.75 years (2022-2024) inclusive Licensees Rulemaking Participation Number of medical licensees that would participate in rulemaking 100 Pert 90 100 110 Hours for each licensee to participate in rulemaking (8) Pert (9) (8) (7)

Agreement States Rulemaking Participation Number of Agreement States 40 40 Hours for each Agreement State to participate in rulemaking (47) Pert (52) (47) (43)

NRC Rulemaking Number of NRC FTE 4.3 Pert 4.0 4.25 4.9 B-6

Mean Low High Description Distribution Mid Estimate Estimate Estimate Estimate FTE Hours (1,524) (1,524)

Rulemaking Comment Management ($152,500) Pert ($172,500) ($150,000) ($142,500)

IMPLEMENTATION OF NEW RULE - COSTS Timing: 4 years (2025-2028) Inclusive Licensees Implementation of New Rule Number of Affected NRC Licensees 126 Number of Affected Agreement State Licensees 1,134 Number of Affected Licensees 1,260 Pert 1,134 1,260 1,386 Hours per Licensee Implementation (20) Pert (22) (20) (18)

Agreement States Rulemaking and Implementation Number of Agreement States 40 40 Cost per Agreement State to develop compatible regulations and ($97,604) Pert ($107,365) ($97,604) ($87,844) implementation NRC Rule Implementation Hours for NRC regulatory review for each Agreement State (41) Pert (46) (40) (38)

Hours for NRC rule Implementation (8)

SUBMISSION AND REVIEW OF EMT LICENSE APPLICATIONS AND AMENDMENTS - AVERTED COSTS Timing: 15 years (2029 to 2043) inclusive By 2026, NRC will regulate 7% of Medical Licensees 7%

By 2026, Agreement States will regulate 93% of Medical Licensees 93%

Licensees ViewRay System for Radiation Therapy Hours 172 Uniform 0 344 Agreement States ViewRay System for Radiation Therapy Hours 1,286 Pert 1,157 1,286 1,414 NRC ViewRay System for Radiation Therapy Hours 90 Pert 81 90 99 Licensees Gamma Knife - Perfexion Hours 268 Uniform 0 535 Agreement States Gamma Knife - Perfexion Hours 2,000 Pert 1,800 2,000 2,200 NRC Gamma Knife - Perfexion Hours 140 Pert 126 140 154 Licensees Gamma Knife - Icon Hours 325 Uniform 0 650 Agreement States Gamma Knife - Icon Hours 2,429 Pert 2,186 2,429 2,671 NRC Gamma Knife - Icon B-7

Mean Low High Description Distribution Mid Estimate Estimate Estimate Estimate Hours 170 Pert 153 170 187 Licensees GammaPod Hours 153 Uniform 0 306 Agreement States GammaPod Hours 1,143 Pert 1,029 1,143 1,257 NRC GammaPod Hours 80 Pert 72 80 88 Licensees Masep Infini Hours 344 Uniform 0 688 Agreement States Masep Infini Time Hours 2,571 Pert 2,314 2,571 2,829 NRC Masep Infini Hours 180 Pert 162 180 198 Licensees Sirtex Microspheres Hours 11,159 Uniform 0 22,317 Agreement States Sirtex Microspheres Hours 83,429 Pert 75,086 83,429 91,771 NRC Sirtex Microspheres Hours 5,840 Pert 5,256 5,840 6,424 Licensees Nordion Microspheres Hours 5,541 Uniform 0 11,082 Agreement States Nordion Microspheres Hours 41,429 Pert 37,286 41,429 45,571 NRC Nordion Microspheres Hours 2,900 Pert 2,610 2,900 3,190 NRC Averted EMT Licensing Guidance Costs Hours Per Year 343 Pert 309 343 378 Licensees Agreement States NRC Sum Hours 17,961 134,286 9,400 ALTERNATIVE 4 - PERFORMANCE-BASED RULEMAKING TO INCREASE REGULATORY FLEXIBILITY [STAFF RECOMMENDATION]

RULEMAKING AND UPDATING GUIDANCE - COSTS Timing: One time over 4 YEARS (2022-2025) inclusive Licensees Rulemaking Participation Number of medical licensees that would participate in rulemaking 100 Pert 90 100 110 Hours for each licensee to participate in rulemaking (8) Pert (9) (8) (7)

Agreement States Rulemaking Participation Number of Agreement States 40 40 B-8

Mean Low High Description Distribution Mid Estimate Estimate Estimate Estimate Hours for each Agreement State to participate in rulemaking (64) Pert (71) (64) (58)

NRC Rulemaking Number of NRC FTE 8 Pert 7.1 7.5 8.6 FTE Hours (1,524)

Comment Management ($203,333) Pert ($230,000) ($200,000) ($190,000)

IMPLEMENTATION OF NEW RULE - COSTS Timing: One time over four years (2026-2029) Inclusive Licensees Implementation of New Rule Number of Affected NRC Licensees 126 Number of Affected Agreement State Licensees 1,134 Number of Affected Licensees 1,260 Pert 1,134 1,260 1,386 Hours per Licensee Implementation (20) Pert (22) (20) (18)

Agreement States Rulemaking and Implementation Number of Agreement States 40 40 Cost per Agreement State to develop compatible regulations and (96,929) Pert ($106,622) ($96,929) ($87,236) implementation NRC Rule Implementation Hours for NRC regulatory review for each Agreement State (41) Pert (48) (40) (38)

Hours for NRC rule implementation (8)

SUBMISSION AND REVIEW OF EMT LICENSE APPLICATIONS AND AMENDMENTS - AVERTED COSTS Timing: 15 years (2030 to 2044) inclusive Licensees Germanium-68/Gallium-68 Pharmaceutical Grade Generators Hours 153 Uniform 0 306 Agreement States Germanium-68/Gallium-68 Pharmaceutical Grade Generators Hours 1,143 Pert 1,029 1,143 1,257 NRC Germanium-68/Gallium-68 Pharmaceutical Grade Generators Hours 80 Pert 72 80 88 Licensees NeoVista, Inc.'s Epi-Rad90 (Sr-90) Opthalmic System Hours 344 Uniform 0 688 Agreement States NeoVista, Inc.'s Epi-Rad90 (Sr-90) Opthalmic System Time (Hours) 2,571 Pert 2,314 2,571 2,829 NRC NeoVista, Inc.'s Epi-Rad90 (Sr-90) Opthalmic System Hours 180 Pert 162 180 198 Licensees Best Vascular, Inc. Beta-Cath Intravascular Brachytherapy System Time (Hours) 401 Uniform 0 803 Agreement States Best Vascular, Inc. Beta-Cath Intravascular Brachytherapy System Hours 3,000 Pert 2,700 3,000 3,300 B-9

Mean Low High Description Distribution Mid Estimate Estimate Estimate Estimate NRC Best Vascular, Inc. Beta-Cath Intravascular Brachytherapy System Hours 210 Pert 189 210 231 Licensees I-125 Iotrex Liquid Brachytherapy Source in Cytyc GliaSite Radiation Therapy System Hours 306 Uniform 0 611 Agreement States I-125 Iotrex Liquid Brachytherapy Source in Cytyc GliaSite Radiation Therapy System Hours 2,286 Pert 2,057 2,286 2,514 NRC I-125 Iotrex Liquid Brachytherapy Source in Cytyc GliaSite Radiation Therapy System Hours 160 Pert 144 160 176 Licensees ViewRay System for Radiation Therapy Hours 172 Uniform 0 344 Agreement States ViewRay System for Radiation Therapy Hours 1,286 Pert 1,157 1,286 1,414 NRC ViewRay System for Radiation Therapy Hours 90 Pert 81 90 99 Licensees Low Activity Radioactive Seeds Use for Localization of Non-Palpable Lesions and Lymph Nodes Hours 1,582 Uniform 0 3,164 Agreement States Low Activity Radioactive Seeds Use for Localization of Non-Palpable Lesions and Lymph Nodes Hours 11,829 Pert 10,646 11,829 13,011 NRC Low Activity Radioactive Seeds Use for Localization of Non-Palpable Lesions and Lymph Nodes Hours 828 Pert 745.2 828 910.8 Licensees Gamma Knife - Perfexion Hours 268 Uniform 0 535 Agreement States Low Activity Gamma Knife - Perfexion Hours 2,000 Pert 1,800 2,000 2,200 NRC Gamma Knife - Perfexion Hours 140 Pert 126 140 154 Licensees Gamma Knife - Icon Hours 325 Uniform 0 650 Agreement States Low Activity Gamma Knife - Icon Hours 2,429 Pert 2,186 2,429 2,671 NRC Gamma Knife - Icon Hours 170 Pert 153 170 187 Licensees GammaPod Hours 153 Uniform 0 306 Agreement States Low Activity GammaPod Hours 1,143 Pert 1,029 1,143 1,257 NRC GammaPod B-10

Mean Low High Description Distribution Mid Estimate Estimate Estimate Estimate Hours 80 Pert 72.0 80 88 Licensees Masep Infini Hours 344 Uniform 0 688 Agreement States Masep Infini Hours 2,571 Pert 2,314 2,571 2,829 NRC Masep Infini Hours 180 Pert 162. 180 198.0 Licensees Sirtex Microspheres Hours 11,159 Uniform 0 22,317 Agreement States Sirtex Microspheres Hours 83,429 Pert 75,086 83,429 91,771 NRC Sirtex Microspheres Hours 5,840 Pert 5,256 5,840 6,424 Licensees Nordion Microspheres Hours 11,159 Uniform 0 22,317 Agreement States Nordion Microspheres Hours 41,429 Pert 37,286 41,429 45,571 NRC Nordion Microspheres Hours 2,900 Pert 2,610 2,900 3,190 NRC Averted EMT Licensing Guidance Costs Hours Per Year 437 Pert 393 437 480 Licensees Agreement States NRC Sum Hours 26,364 155,114 10,858 B-11

Appendix C - Summary and Tables of Costs for Each Alternative by NRC, Agreement States, and Licensees The Appendix C tables show the calculations for the net costs and averted costs associated with each alternative by the NRC, Agreement States, and licensees. (Refer to Table 5 for rulemaking costs for the NRC for each rulemaking alternative.)

ALTERNATIVE 1 - STATUS QUO Table 9: Alternative 1 - NRC Reviewing Exemptions (Costs)

1. Net Benefits - Costs Year Activity Hours NRC hourly rate Exems Undiscounted 7% NPV 3% NPV 2023 NRC Reviewing Exemptions (36) 11 $143 ($56,628) ($52,923) ($54,979) 2024 NRC Reviewing Exemptions (36) 11 $143 ($56,628) ($49,461) ($53,377)

Total Net Benefits - Costs (72) ($113,256) ($102,384) ($108,356) 15-year Average ($7,550) ($6,826) ($7,224)

Annualized with 7% discounting ($11,241)

Annualized with 3% discounting ($9,077)

Table 10: Alternative 1 - NRC Rb-82 Generator Inspections (Averted Costs)

Net Benefits - Averted Costs Year Activity Hours # Insp NRC hourly rate Undiscounted 7% NPV 3% NPV 2025 NRC Inspections 6 8.5 $143 $7,293 $5,953 $6,674 2026 NRC Inspections 6 8.5 $143 $7,293 $5,564 $6,480 2027 NRC Inspections 6 8.5 $143 $7,293 $5,200 $6,291 2028 NRC Inspections 6 8.5 $143 $7,293 $4,860 $6,108 2029 NRC Inspections 6 8.5 $143 $7,293 $4,542 $5,930 2030 NRC Inspections 6 8.5 $143 $7,293 $4,245 $5,757 2031 NRC Inspections 6 8.5 $143 $7,293 $3,967 $5,589 2032 NRC Inspections 6 8.5 $143 $7,293 $3,707 $5,427 2033 NRC Inspections 6 8.5 $143 $7,293 $3,465 $5,269 C-1

Net Benefits - Averted Costs Year Activity Hours # Insp NRC hourly rate Undiscounted 7% NPV 3% NPV 2034 NRC Inspections 6 8.5 $143 $7,293 $3,238 $5,115 2035 NRC Inspections 6 8.5 $143 $7,293 $3,026 $4,966 2036 NRC Inspections 6 8.5 $143 $7,293 $2,828 $4,822 2037 NRC Inspections 6 8.5 $143 $7,293 $2,643 $4,681 2038 NRC Inspections 6 8.5 $143 $7,293 $2,470 $4,545 2039 NRC Inspections 6 8.5 $143 $7,293 $2,309 $4,412 Total Net Benefits - Averted Costs 90 $109,395 $58,017 $82,066 15-year Average $7,293 $3,868 $5,471 Annualized with 7% discounting $6,370 Annualized with 3% discounting $6,874 Table 11: Alternative 1 - Agreement States Reviewing Exemptions (Costs)

Net Benefits - Costs Year Activity Hours Agreement State hourly rate Exems Undiscounted 7% NPV 3% NPV Agreement States Reviewing 2023 (36) 49.5 $73 ($130,572) ($122,030) ($126,769)

Exemptions Agreement States Reviewing 2024 (36) 49.5 $73 ($130,572) ($114,046) ($123,076)

Exemptions Agreement States Reviewing 2025 (36) 49.5 $73 ($130,572) ($106,585) ($119,492)

Exemptions Agreement States Reviewing 2026 (36) 49.5 $73 ($130,572) ($99,612) ($116,011)

Exemptions Total Net Benefits - Costs (144) ($522,287) ($442,274) ($485,348) 15-year Average ($34,819) ($29,485) ($32,357)

Annualized with 7% discounting ($48,559)

Annualized with 3% discounting ($40,656)

C-2

Table 12: Alternative 1 - Agreement States Rb-82 Generator Inspections (Averted Costs)

Net Benefits - Averted Costs Year Activity Hours Agreement State hourly rate Insp Undiscounted 7% NPV 3% NPV 2026 Agreement States Inspections 4 76.5 $73 $22,421 $17,105 $19,921 2027 Agreement States Inspections 4 76.5 $73 $22,421 $15,986 $19,341 2028 Agreement States Inspections 4 76.5 $73 $22,421 $14,940 $18,778 2029 Agreement States Inspections 4 76.5 $73 $22,421 $13,963 $18,231 2030 Agreement States Inspections 4 76.5 $73 $22,421 $13,049 $17,700 2031 Agreement States Inspections 4 76.5 $73 $22,421 $12,196 $17,184 2032 Agreement States Inspections 4 76.5 $73 $22,421 $11,398 $16,684 2033 Agreement States Inspections 4 76.5 $73 $22,421 $10,652 $16,198 2034 Agreement States Inspections 4 76.5 $73 $22,421 $9,955 $15,726 2035 Agreement States Inspections 4 76.5 $73 $22,421 $9,304 $15,268 2036 Agreement States Inspections 4 76.5 $73 $22,421 $8,695 $14,823 2037 Agreement States Inspections 4 76.5 $73 $22,421 $8,127 $14,391 2038 Agreement States Inspections 4 76.5 $73 $22,421 $7,595 $13,972 2039 Agreement States Inspections 4 76.5 $73 $22,421 $7,098 $13,565 2040 Agreement States Inspections 4 76.5 $73 $22,421 $6,634 $13,170 Total Net Benefits - Averted Costs $336,321 $166,698 $244,952 15-year Average $22,421 $11,113 $16,330 Annualized with 7% discounting $18,303 Annualized with 3% discounting $20,519 C-3

Table 13: Alternative 1 - Licensees Submitting Exemptions (Costs)

Net Benefits - Costs Year Activity Hours Licensee hourly rate Exems Undiscounted 7% NPV 3% NPV 2023 Licensees Submitting Exemptions (8) 55 $92 ($40,683) ($38,022) ($39,498) 2024 Licensees Submitting Exemptions (8) 55 $92 ($40,683) ($35,534) ($38,348) 2025 Licensees Submitting Exemptions (8) 55 $92 ($40,683) ($33,210) ($37,231) 2026 Licensees Submitting Exemptions (8) 55 $92 ($40,683) ($31,037) ($36,147)

Total Net Benefits - Costs (32) ($162,733) ($137,803) ($151,224) 15-year Average ($10,849) ($9,187) ($10,082)

Annualized with 7% discounting ($15,130)

Annualized with 3% discounting ($12,668)

Table 14: Alternative 1 - Licensees Rb-82 Generator Inspections (Averted Costs)

Net Benefits - Averted Costs Year Activity Hours # Insp Licensee hourly rate Undiscounted 7% NPV 3% NPV 2024 Licensees Inspections 2 85 $92 $15,731 $13,740 $14,828 2025 Licensees Inspections 2 85 $92 $15,731 $12,841 $14,396 2026 Licensees Inspections 2 85 $92 $15,731 $12,001 $13,977 2027 Licensees Inspections 2 85 $92 $15,731 $11,216 $13,570 2028 Licensees Inspections 2 85 $92 $15,731 $10,482 $13,174 2029 Licensees Inspections 2 85 $92 $15,731 $9,796 $12,791 2030 Licensees Inspections 2 85 $92 $15,731 $9,156 $12,418 2031 Licensees Inspections 2 85 $92 $15,731 $8,557 $12,056 2032 Licensees Inspections 2 85 $92 $15,731 $7,997 $11,705 2033 Licensees Inspections 2 85 $92 $15,731 $7,474 $11,364 2034 Licensees Inspections 2 85 $92 $15,731 $6,985 $11,033 2035 Licensees Inspections 2 85 $92 $15,731 $6,528 $10,712 2036 Licensees Inspections 2 85 $92 $15,731 $6,101 $10,400 C-4

Net Benefits - Averted Costs Year Activity Hours # Insp Licensee hourly rate Undiscounted 7% NPV 3% NPV 2037 Licensees Inspections 2 85 $92 $15,731 $5,702 $10,097 2038 Licensees Inspections 2 85 $92 $15,731 $5,329 $9,803 Total Net Benefits - Averted 16 $235,963 $133,902 $182,324 Costs 15 15-year Average $15,731 $8,927 $12,155 Annualized with 7% discounting $14,702 Annualized with 3% discounting $15,273 ALTERNATIVE 2 - RULEMAKING ONLY FOR RB-82 GENERATORS Table 15: Alternative 2 - NRC Regulatory Review (Costs)

1. Total Net Benefits - Costs Year Activity Hours NRC hourly rate A.S.

Undiscounted 7% NPV 3% NPV NRC Regulatory Review of New 2025 (13) 40 $143 ($76,267) ($62,256) ($69,795)

Agreement State Regulations NRC Regulatory Review of New 2026 (13) 40 $143 ($76,267) ($58,183) ($67,762)

Agreement State Regulations NRC Regulatory Review of New 2027 (13) 40 $143 ($76,267) ($54,377) ($65,788)

Agreement State Regulations Total Net Benefits - Costs (40) ($228,800) ($174,817) ($203,345) 15-year Average ($15,253) ($11,654) ($13,556)

Annualized with 7% discounting ($19,194)

Annualized with 3% discounting ($22,326)

C-5

Table 16: Alternative 2 - Agreement States Rulemaking Participation (Costs)

Total Net Benefits - Costs Year Activity Hours # A.S. Agreement State hourly rate Undiscounted 7% NPV 3% NPV Agreement States 2022 (9) 40 $73 ($26,867) ($26,867) ($26,867)

Rulemaking Participation Agreement States 2023 (9) 40 $73 ($26,867) ($25,109) ($26,084)

Rulemaking Participation Agreement States 2024 (9) 40 $73 ($26,867) ($23,466) ($25,324)

Rulemaking Participation Total Net Benefits - Costs (28) ($80,600) ($75,442) ($78,275) 15-year Average ($5,373) ($5,029) ($5,218)

Annualized with 7% discounting ($8,283)

Annualized with 3% discounting ($8,594)

Table 17: Alternative 2 - Agreement States Rulemaking (Costs)

1. Agreement State Cost to Total Net Benefits - Costs Year Activity A.S. Develop Regulations Undiscounted 7% NPV 3% NPV 2025 Agreement States Rulemaking 13 ($40,000) ($533,333) ($435,359) ($488,076) 2026 Agreement States Rulemaking 13 ($40,000) ($533,333) ($406,877) ($473,860) 2027 Agreement States Rulemaking 13 ($40,000) ($533,333) ($380,259) ($460,058)

Total Net Benefits - Costs 40 ($1,600,000) ($1,222,496) ($1,421,993) 15-year Average ($106,667) ($81,500) ($94,800)

Annualized with 7% discounting ($134,223)

Annualized with 3% discounting ($156,127)

C-6

Table 18: Alternative 2 - Licensees Rulemaking Participation (Costs)

Total Net Benefits (Costs)

Year Activity Hours Licensee hourly rate Lic Undiscounted 7% NPV 3% NPV 2022 Licensees Rulemaking Participation (1.3) 11 $92 ($1,356) ($1,356) ($1,356) 2023 Licensees Rulemaking Participation (1.3) 11 $92 ($1,356) ($1,267) ($1,317) 2024 Licensees Rulemaking Participation (1.3) 11 $92 ($1,356) ($1,184) ($1,278)

Total Net Benefits - Costs (4) ($4,068) ($3,808) ($3,951) 15-year Average ($271) ($254) ($263)

Annualized with 7% discounting ($418)

Annualized with 3% discounting ($434)

Table 19: Alternative 2 - NRC Rb-82 Generator Inspections (Averted Costs)

Total Net Benefits - Averted Costs Year Activity # Insp Hours NRC hourly rate Undiscounted 7% NPV 3% NPV 2026 NRC Inspections 8.5 6 $143 $7,299 $4,863 $6,113 2027 NRC Inspections 8.5 6 $143 $7,299 $4,545 $5,935 2028 NRC Inspections 8.5 6 $143 $7,299 $4,248 $5,762 2029 NRC Inspections 8.5 6 $143 $7,299 $3,970 $5,594 2030 NRC Inspections 8.5 6 $143 $7,299 $3,710 $5,431 2031 NRC Inspections 8.5 6 $143 $7,299 $3,468 $5,273 2032 NRC Inspections 8.5 6 $143 $7,299 $3,241 $5,119 2033 NRC Inspections 8.5 6 $143 $7,299 $3,029 $4,970 2034 NRC Inspections 8.5 6 $143 $7,299 $2,831 $4,825 2035 NRC Inspections 8.5 6 $143 $7,299 $2,645 $4,685 2036 NRC Inspections 8.5 6 $143 $7,299 $2,472 $4,548 2037 NRC Inspections 8.5 6 $143 $7,299 $2,311 $4,416 2038 NRC Inspections 8.5 6 $143 $7,299 $2,159 $4,287 C-7

Total Net Benefits - Averted Costs Year Activity # Insp Hours NRC hourly rate Undiscounted 7% NPV 3% NPV 2039 NRC Inspections 8.5 6 $143 $7,299 $2,018 $4,162 2040 NRC Inspections 8.5 6 $143 $7,299 $1,886 $4,041 2041 NRC Inspections 8.5 6 $143 $7,299 $1,763 $3,923 Total Net Benefits -

136.1 96 $116,780 $49,159 $79,084 Averted Costs 15-year Average $7,785 $3,277 $5,272 Annualized with 7% discounting $5,397 Annualized with 3% discounting $6,625 Table 20: Alternative 2 - Agreement States Rb-82 Generator Inspections (Averted Costs)

Total Net Benefits - Averted Costs Year Activity Hours Agreement State hourly rate Insp Undiscounted 7% NPV 3% NPV 2029 Agreement States Inspections 76.6 4 $73 $22,439 $12,205 $17,198 2030 Agreement States Inspections 76.6 4 $73 $22,439 $11,407 $16,697 2031 Agreement States Inspections 76.6 4 $73 $22,439 $10,661 $16,210 2032 Agreement States Inspections 76.6 4 $73 $22,439 $9,963 $15,738 2033 Agreement States Inspections 76.6 4 $73 $22,439 $9,311 $15,280 2034 Agreement States Inspections 76.6 4 $73 $22,439 $8,702 $14,835 2035 Agreement States Inspections 76.6 4 $73 $22,439 $8,133 $14,403 2036 Agreement States Inspections 76.6 4 $73 $22,439 $7,601 $13,983 2037 Agreement States Inspections 76.6 4 $73 $22,439 $7,104 $13,576 2038 Agreement States Inspections 76.6 4 $73 $22,439 $6,639 $13,181 2039 Agreement States Inspections 76.6 4 $73 $22,439 $6,205 $12,797 2040 Agreement States Inspections 76.6 4 $73 $22,439 $5,799 $12,424 2041 Agreement States Inspections 76.6 4 $73 $22,439 $5,419 $12,062 2042 Agreement States Inspections 76.6 4 $73 $22,439 $5,065 $11,711 2043 Agreement States Inspections 76.6 4 $73 $22,439 $4,733 $11,370 Total Net Benefits - Averted Costs 60 $336,585 $118,947 $211,463 C-8

Total Net Benefits - Averted Costs Year Activity Hours Agreement State hourly rate Insp Undiscounted 7% NPV 3% NPV 15-year Average $22,439 $7,930 $14,098 Annualized with 7% discounting $13,060 Annualized with 3% discounting $17,714 Table 21: Alternative 2 - Licensees Rb-82 Generator Inspections (Averted Costs)

Total Net Benefits - Averted Costs Year Activity # Insp Hours Licensee hourly rate Undiscounted 7% NPV 3% NPV 2028 Licensees Inspections 85 2 $92 $15,731 $9,156 $12,418 2029 Licensees Inspections 85 2 $92 $15,731 $8,557 $12,056 2030 Licensees Inspections 85 2 $92 $15,731 $7,997 $11,705 2031 Licensees Inspections 85 2 $92 $15,731 $7,474 $11,364 2032 Licensees Inspections 85 2 $92 $15,731 $6,985 $11,033 2033 Licensees Inspections 85 2 $92 $15,731 $6,528 $10,712 2034 Licensees Inspections 85 2 $92 $15,731 $6,101 $10,400 2035 Licensees Inspections 85 2 $92 $15,731 $5,702 $10,097 2036 Licensees Inspections 85 2 $92 $15,731 $5,329 $9,803 2037 Licensees Inspections 85 2 $92 $15,731 $4,980 $9,517 2038 Licensees Inspections 85 2 $92 $15,731 $4,654 $9,240 2039 Licensees Inspections 85 2 $92 $15,731 $4,350 $8,971 2040 Licensees Inspections 85 2 $92 $15,731 $4,065 $8,710 2041 Licensees Inspections 85 2 $92 $15,731 $3,799 $8,456 2042 Licensees Inspections 85 2 $92 $15,731 $3,551 $8,210 Total Net Benefits - Averted Costs 30 $235,963 $89,225 $152,694 15-year Average $15,731 $5,948 $10,180 Annualized with 7% discounting $9,796 Annualized with 3% discounting $12,791 C-9

ALTERNATIVE 3 - LIMITED SCOPE RULEMAKING FOR RB-82 GENERATORS AND CERTAIN EMERGING MEDICAL TECHNOLOGIES Table 22: Alternative 3 - NRC Rulemaking Implementation (Costs)

Total Net Benefits - Costs Year Activity Hours # Lic. NRC hourly rate Undiscounted 7% NPV 3% NPV 2025 NRC Rule Implementation (8) 126.00 $143 ($1,144) ($934) ($1,047)

Total Net Benefits - Costs (8) ($1,144) ($934) ($1,047) 15-year Average ($76) ($62) ($70)

Annualized with 7% discounting ($103)

Annualized with 3% discounting ($115)

Table 23: Alternative 3 - NRC Regulatory Review (Costs)

Total Net Benefits - Costs Year Activity Hours # A.S. NRC hourly rate Undiscounted 7% NPV 3% NPV 2025 NRC Regulatory Review (14) 40.00 $143 ($77,538) ($63,294) ($70,958) 2026 NRC Regulatory Review (14) 40.00 $143 ($77,538) ($59,153) ($68,891) 2027 NRC Regulatory Review (14) 40.00 $143 ($77,538) ($55,283) ($66,885)

Total Net Benefits -

(41) ($232,613) ($177,730) ($206,734)

Costs 15-year Average ($15,508) ($11,849) ($13,782)

Annualized with 7% discounting ($19,514)

Annualized with 3% discounting ($22,698)

C-10

Table 24: Alternative 3 - Agreement States Rulemaking Participation (Costs)

Total Net Benefits - Costs Year Activity Hours # A.S. Agreement State hourly rate Undiscounted 7% NPV 3% NPV Agreement States 2022 (15.8) 40 $73 ($46,357) ($46,357) ($46,357)

Rulemaking Participation Agreement States 2023 (15.8) 40 $73 ($46,357) ($43,324) ($45,007)

Rulemaking Participation Agreement States 2024 (15.8) 40 $73 ($46,357) ($40,490) ($43,696)

Rulemaking Participation Total Net Benefits - Costs (47) ($139,071) ($130,172) ($135,060) 15-year Average ($9,271) ($8,678) ($9,004)

Annualized with 7% discounting ($14,292)

Annualized with 3% discounting ($14,829)

Table 25: Alternative 3 - Agreement States Rulemaking and Implementation (Costs)

Agreement States Cost to Total Net Benefits - Costs Year Activity # A.S. Develop Regulations and Implement New Rule Undiscounted 7% NPV 3% NPV Agreement States Rulemaking 2025 13 ($97,604) ($1,301,389) ($1,062,321) ($1,190,956) and Implementation Agreement States Rulemaking 2026 13 ($97,604) ($1,301,389) ($992,824) ($1,156,268) and Implementation Agreement States Rulemaking 2027 13 ($97,604) ($1,301,389) ($927,873) ($1,122,590) and Implementation Total Net Benefits - Costs 40 ($3,904,168) ($2,983,018) ($3,469,813) 15-year Average ($260,278) ($198,868) ($231,321)

Annualized with 7% discounting ($327,519)

Annualized with 3% discounting ($380,967)

C-11

Table 26: Alternative 3 - Licensees Rulemaking Participation (Costs)

Total Net Benefits - Costs Year Activity Hours Licensee hourly rate Lic Undiscounted 7% NPV 3% NPV 2022 Licensees Rulemaking Participation (2.7) 100 $92 ($24,657) ($24,657) ($24,657) 2023 Licensees Rulemaking Participation (2.7) 100 $92 ($24,657) ($23,044) ($23,938) 2024 Licensees Rulemaking Participation (2.7) 100 $92 ($24,657) ($21,536) ($23,241)

Total Net Benefits - Costs (8) ($73,970) ($69,236) ($71,836) 15-year Average ($4,931) ($4,616) ($4,789)

Annualized with 7% discounting ($7,602)

Annualized with 3% discounting ($7,887)

Table 27: Alternative 3 - Licensees Rulemaking Implementation (Costs)

Total Net Benefits - Costs Year Activity Hours # Lic Licensee hourly rate Undiscounted 7% NPV 3% NPV Licensees 2025 Implementation of New (20.0) 126 $92 ($233,004) ($190,201) ($213,232)

Rule Licensees 2028 Implementation of New (20.0) 1,134 $92 ($2,097,040) ($1,397,346) ($1,756,238)

Rule Total Net Benefits -

(40) ($2,330,044) ($1,587,547) ($1,969,470)

Costs 15-year Average ($155,336) ($105,836) ($131,298)

Annualized with 7% discounting ($174,304)

Annualized with 3% discounting ($216,237)

C-12

Table 28: Alternative 3 - NRC Emerging Medical Technology Licensing Averted Costs)

Total Net Benefits - Averted Costs Year Activity Hours NRC hourly rate Undiscounted 7% NPV 3% NPV NRC Review of EMT License 2026 Applications and Amendment 627 $143 $89,613 $68,366 $79,620 Requests NRC Review of EMT License 2027 Applications and Amendment 627 $143 $89,613 $63,893 $77,301 Requests NRC Review of EMT License 2028 Applications and Amendment 627 $143 $89,613 $59,713 $75,050 Requests NRC Review of EMT License 2029 Applications and Amendment 627 $143 $89,613 $55,807 $72,864 Requests NRC Review of EMT License 2030 Applications and Amendment 627 $143 $89,613 $52,156 $70,742 Requests NRC Review of EMT License 2031 Applications and Amendment 627 $143 $89,613 $48,744 $68,681 Requests NRC Review of EMT License 2032 Applications and Amendment 627 $143 $89,613 $45,555 $66,681 Requests NRC Review of EMT License 2033 Applications and Amendment 627 $143 $89,613 $42,575 $64,739 Requests NRC Review of EMT License 2034 Applications and Amendment 627 $143 $89,613 $39,789 $62,853 Requests NRC Review of EMT License 2035 Applications and Amendment 627 $143 $89,613 $37,186 $61,022 Requests NRC Review of EMT License 2036 Applications and Amendment 627 $143 $89,613 $34,754 $59,245 Requests C-13

Total Net Benefits - Averted Costs Year Activity Hours NRC hourly rate Undiscounted 7% NPV 3% NPV NRC Review of EMT License 2037 Applications and Amendment 627 $143 $89,613 $32,480 $57,519 Requests NRC Review of EMT License 2038 Applications and Amendment 627 $143 $89,613 $30,355 $55,844 Requests NRC Review of EMT License 2039 Applications and Amendment 627 $143 $89,613 $28,369 $54,218 Requests NRC Review of EMT License 2040 Applications and Amendment 627 $143 $89,613 $26,513 $52,638 Requests Total Net Benefits - Costs 9,400 $1,344,200 $666,255 $979,017 15-year Average $89,613 $44,417 $65,268 Annualized with 7% discounting $73,151 Annualized with 3% discounting $82,009 Table 29: Alternative 3 - Development of Emerging Medical Technology Licensing Guidance (Averted Costs)

Total Net Benefits - Averted Costs Year Activity Hours NRC hourly rate Undiscounted 7% NPV 3% NPV NRC Development of EMT Licensing 2026 343 $143 $49,097 $37,456 $43,622 Guidance NRC Development of EMT Licensing 2027 343 $143 $49,097 $35,005 $42,351 Guidance NRC Development of EMT Licensing 2028 343 $143 $49,097 $32,715 $41,118 Guidance NRC Development of EMT Licensing 2029 343 $143 $49,097 $30,575 $39,920 Guidance NRC Development of EMT Licensing 2030 343 $143 $49,097 $28,575 $38,757 Guidance NRC Development of EMT Licensing 2031 343 $143 $49,097 $26,705 $37,629 Guidance C-14

Total Net Benefits - Averted Costs Year Activity Hours NRC hourly rate Undiscounted 7% NPV 3% NPV NRC Development of EMT Licensing 2032 343 $143 $49,097 $24,958 $36,533 Guidance NRC Development of EMT Licensing 2033 343 $143 $49,097 $23,325 $35,468 Guidance NRC Development of EMT Licensing 2034 343 $143 $49,097 $21,800 $34,435 Guidance NRC Development of EMT Licensing 2035 343 $143 $49,097 $20,373 $33,432 Guidance NRC Development of EMT Licensing 2036 343 $143 $49,097 $19,041 $32,459 Guidance NRC Development of EMT Licensing 2037 343 $143 $49,097 $17,795 $31,513 Guidance NRC Development of EMT Licensing 2038 343 $143 $49,097 $16,631 $30,595 Guidance NRC Development of EMT Licensing 2039 343 $143 $49,097 $15,543 $29,704 Guidance NRC Development of EMT Licensing 2040 343 $143 $49,097 $14,526 $28,839 Guidance Total Net Benefits - Costs 5,150 $736,450 $365,022 $536,376 15-year Average $49,097 $24,335 $35,758 Annualized with 7% discounting $40,078 Annualized with 3% discounting $44,930 Table 30: Alternative 3 - Agreement States Emerging Medical Technology Licensing (Averted Costs)

Total Net Benefits - Averted Costs Year Activity Hours Agreement State hourly rate Undiscounted 7% NPV 3% NPV Agreement States Review of EMT License 2029 8,952 $73 $655,964 $408,501 $533,358 Applications and Amendment Requests Agreement States Review of EMT License 2030 8,952 $73 $655,964 $381,777 $517,824 Applications and Amendment Requests Agreement States Review of EMT License 2031 8,952 $73 $655,964 $356,801 $502,741 Applications and Amendment Requests Agreement States Review of EMT License 2032 8,952 $73 $655,964 $333,459 $488,098 Applications and Amendment Requests C-15

Total Net Benefits - Averted Costs Year Activity Hours Agreement State hourly rate Undiscounted 7% NPV 3% NPV Agreement States Review of EMT License 2033 8,952 $73 $655,964 $311,644 $473,882 Applications and Amendment Requests Agreement States Review of EMT License 2034 8,952 $73 $655,964 $291,256 $460,080 Applications and Amendment Requests Agreement States Review of EMT License 2035 8,952 $73 $655,964 $272,202 $446,679 Applications and Amendment Requests Agreement States Review of EMT License 2036 8,952 $73 $655,964 $254,394 $433,669 Applications and Amendment Requests Agreement States Review of EMT License 2037 8,952 $73 $655,964 $237,751 $421,038 Applications and Amendment Requests Agreement States Review of EMT License 2038 8,952 $73 $655,964 $222,198 $408,775 Applications and Amendment Requests Agreement States Review of EMT License 2039 8,952 $73 $655,964 $207,661 $396,869 Applications and Amendment Requests Agreement States Review of EMT License 2040 8,952 $73 $655,964 $194,076 $385,309 Applications and Amendment Requests Agreement States Review of EMT License 2041 8,952 $73 $655,964 $181,379 $374,087 Applications and Amendment Requests Agreement States Review of EMT License 2042 8,952 $73 $655,964 $169,513 $363,191 Applications and Amendment Requests Agreement States Review of EMT License 2043 8,952 $73 $655,964 $158,424 $352,613 Applications and Amendment Requests Total Net Benefits - Averted Costs 134,286 $9,839,453 $3,981,035 $6,558,214 15-year Average $655,964 $265,402 $437,214 Annualized with 7% discounting $437,096 Annualized with 3% discounting $549,359 C-16

Table 31: Alternative 3 - Licensees Emerging Medical Technology Licensing (Averted Costs)

Total Net Benefits - Averted Costs Year Activity Hours Licensee hourly rate Undiscounted 7% NPV 3% NPV Licensees Submission of EMT License 2029 1,197 $92 $110,712 $68,946 $90,019 Applications and Amendment Requests Licensees Submission of EMT License 2030 Applications and Amendment Requests 1,197 $92 $110,712 $64,436 $87,397 Licensees Submission of EMT License 2031 Applications and Amendment Requests 1,197 $92 $110,712 $60,220 $84,852 Licensees Submission of EMT License 2032 Applications and Amendment Requests 1,197 $92 $110,712 $56,281 $82,380 Licensees Submission of EMT License 2033 Applications and Amendment Requests 1,197 $92 $110,712 $52,599 $79,981 Licensees Submission of EMT License 2034 Applications and Amendment Requests 1,197 $92 $110,712 $49,158 $77,651 Licensees Submission of EMT License 2035 Applications and Amendment Requests 1,197 $92 $110,712 $45,942 $75,390 Licensees Submission of EMT License 2036 Applications and Amendment Requests 1,197 $92 $110,712 $42,936 $73,194 Licensees Submission of EMT License 2037 Applications and Amendment Requests 1,197 $92 $110,712 $40,127 $71,062 Licensees Submission of EMT License 2038 Applications and Amendment Requests 1,197 $92 $110,712 $37,502 $68,992 Licensees Submission of EMT License 2039 Applications and Amendment Requests 1,197 $92 $110,712 $35,049 $66,983 Licensees Submission of EMT License 2040 Applications and Amendment Requests 1,197 $92 $110,712 $32,756 $65,032 Licensees Submission of EMT License 2041 Applications and Amendment Requests 1,197 $92 $110,712 $30,613 $63,138 Licensees Submission of EMT License 2042 Applications and Amendment Requests 1,197 $92 $110,712 $28,610 $61,299 Licensees Submission of EMT License 2043 Applications and Amendment Requests 1,197 $92 $110,712 $26,738 $59,513 C-17

Total Net Benefits - Averted Costs Year Activity Hours Licensee hourly rate Undiscounted 7% NPV 3% NPV Total Net Benefits - Averted Costs 17,961 $1,660,685 $671,912 $1,106,883 15-year Average $110,712 $44,794 $73,792 Annualized with 7% discounting $73,772 Annualized with 3% discounting $92,720 ALTERNATIVE 4 - PERFORMANCE-BASED RULEMAKING TO INCREASE REGULATORY FLEXIBILITY Table 32: Alternative 4 - NRC Rulemaking Implementation (Costs)

Total Net Benefits - Costs Year Activity Hours # Lic NRC hourly rate Undiscounted 7% NPV 3% NPV NRC Rulemaking 2026 (8) 126 $143 ($144,144) ($109,967) ($128,070)

Implementation Total Net Benefits -

(8) ($144,144) ($109,967) ($128,070)

Costs 15-year Average ($9,610) ($7,331) ($8,538)

Annualized with 7% discounting ($12,074)

Annualized with 3% discounting ($14,061)

Table 33: Alternative 4 - NRC Regulatory Review (Costs)

Total Net Benefits - Costs Year Activity Hours # A.S. NRC hourly rate Undiscounted 7% NPV 3% NPV 2026 NRC Regulatory Review (14) 40 $143 ($78,173) ($59,638) ($69,456) 2027 NRC Regulatory Review (14) 40 $143 ($78,173) ($55,737) ($67,433) 2028 NRC Regulatory Review (14) 40 $143 ($78,173) ($52,090) ($65,469)

Total Net Benefits - ($234,520) ($167,465) ($202,358)

(41)

Costs C-18

Total Net Benefits - Costs Year Activity Hours # A.S. NRC hourly rate Undiscounted 7% NPV 3% NPV 15-year Average ($15,635) ($11,164) ($13,491)

Annualized with 7% discounting ($18,387)

Annualized with 3% discounting ($22,218)

Table 34: Alternative 4 - Agreement States Rulemaking Participation (Costs)

Total Net Benefits - Costs Year Activity Hours # A.S. Agreement State hourly rate Undiscounted 7% NPV 3% NPV Agreement States ($46,968) ($46,968) ($46,968) 2022 (16) 40 $73 Rulemaking Participation Agreement States (16) ($46,968) ($43,895) ($45,600) 2023 40 $73 Rulemaking Participation Agreement States (16) ($46,968) ($41,023) ($44,272) 2024 40 $73 Rulemaking Participation Agreement States (16) ($46,968) ($38,340) ($42,982) 2025 40 $73 Rulemaking Participation Total Net Benefits - Costs (64) ($187,871) ($170,226) ($179,821) 15-year Average ($12,525) ($11,348) ($11,988)

Annualized with 7% discounting ($18,690)

Annualized with 3% discounting ($19,743)

Table 35: Alternative 4 - Agreement States Rulemaking and Implementation (Costs)

Agreement States Cost to Total Net Benefits - Costs Year Activity # A.S. Develop Regulations and Implement New Rule Undiscounted 7% NPV 3% NPV Agreement States 2026 Rulemaking and 13 ($96,929) ($1,292,391) ($985,959) ($1,148,273)

Implementation C-19

Agreement States Cost to Total Net Benefits - Costs Year Activity # A.S. Develop Regulations and Implement New Rule Undiscounted 7% NPV 3% NPV Agreement States 2027 Rulemaking and 13 ($96,929) ($1,292,391) ($921,457) ($1,114,828)

Implementation Agreement States 2028 Rulemaking and 13 ($96,929) ($1,292,391) ($861,175) ($1,082,357)

Implementation Total Net Benefits - Costs 40 ($3,877,172) ($2,768,590) ($3,345,457) 15-year Average ($258,478) ($184,573) ($223,030)

Annualized with 7% discounting ($303,976)

Annualized with 3% discounting ($367,313)

Table 36: Alternative 4 - Licensees Rulemaking Participation (Costs)

Total Net Benefits - Costs Year Activity Hours Licensee hourly rate Lic Undiscounted 7% NPV 3% NPV

($18,492) ($17,283) ($17,954) 2023 Licensees Rulemaking Participation (2) 100 $92 (2) ($18,492) ($16,152) ($17,431) 2024 Licensees Rulemaking Participation 100 $92 (2) ($18,492) ($15,095) ($16,923) 2025 Licensees Rulemaking Participation 100 $92 (2) ($18,492) ($14,108) ($16,430) 2026 Licensees Rulemaking Participation 100 $92 Total Net Benefits - Costs (8) ($73,970) ($62,638) ($68,738) 15-year Average ($4,931) ($4,176) ($4,583)

Annualized with 7% discounting ($6,877)

Annualized with 3% discounting ($7,547)

C-20

Table 37: Alternative 4 - Licensees Rulemaking Implementation (Costs)

Total Net Benefits - Costs Year Activity Hours # Lic Licensee hourly rate Undiscounted 7% NPV 3% NPV Licensees 2026 Implementation of New (20) 126 $92 ($233,004) ($177,758) ($207,021)

Rule Licensees 2029 Implementation of New (20) 1,134 $92 ($2,097,040) ($1,305,931) ($1,705,085)

Rule Total Net Benefits - Costs (40) ($2,330,044) ($1,483,689) ($1,912,107) 15-year Average ($155,336) ($98,913) ($127,474)

Annualized with 7% discounting ($162,901)

Annualized with 3% discounting ($209,939)

Table 38: Alternative 4 - NRC Emerging Medical Technology Licensing (Averted Costs)

Total Net Benefits - Averted Costs Year Activity Hours NRC hourly rate Undiscounted 7% NPV 3% NPV NRC Review of EMT License Applications 2027 and Amendment Requests 724 $143 $103,513 $73,803 $89,291 NRC Review of EMT License Applications 2028 and Amendment Requests 724 $143 $103,513 $68,975 $86,690 NRC Review of EMT License Applications 2029 and Amendment Requests 724 $143 $103,513 $64,463 $84,165 NRC Review of EMT License Applications 2030 and Amendment Requests 724 $143 $103,513 $60,245 $81,714 C-21

Total Net Benefits - Averted Costs Year Activity Hours NRC hourly rate Undiscounted 7% NPV 3% NPV NRC Review of EMT License Applications 2031 and Amendment Requests 724 $143 $103,513 $56,304 $79,334 NRC Review of EMT License Applications 2032 and Amendment Requests 724 $143 $103,513 $52,621 $77,023 NRC Review of EMT License Applications 2033 and Amendment Requests 724 $143 $103,513 $49,178 $74,780 NRC Review of EMT License Applications 2034 and Amendment Requests 724 $143 $103,513 $45,961 $72,602 NRC Review of EMT License Applications 2035 and Amendment Requests 724 $143 $103,513 $42,954 $70,487 NRC Review of EMT License Applications 2036 and Amendment Requests 724 $143 $103,513 $40,144 $68,434 NRC Review of EMT License Applications 2037 and Amendment Requests 724 $143 $103,513 $37,518 $66,441 NRC Review of EMT License Applications 2038 and Amendment Requests 724 $143 $103,513 $35,063 $64,506 NRC Review of EMT License Applications 2039 and Amendment Requests 724 $143 $103,513 $32,770 $62,627 NRC Review of EMT License Applications 2040 and Amendment Requests 724 $143 $103,513 $30,626 $60,803 C-22

Total Net Benefits - Averted Costs Year Activity Hours NRC hourly rate Undiscounted 7% NPV 3% NPV NRC Review of EMT License Applications 2041 and Amendment Requests 724 $143 $103,513 $28,622 $59,032 Total Net Benefits - Averted Costs 10,858 $1,552,694 $719,248 $1,097,931 15-year Average $103,513 $47,950 $73,195 Annualized with 7% discounting $78,970 Annualized with 3% discounting $91,970 Table 39: Alternative 4 - NRC Development of Emerging Medical Technology Licensing Guidance (Averted Costs)

Total Net Benefits - Averted Costs Year Activity Hours NRC hourly rate Undiscounted 7% NPV 3% NPV NRC Development of EMT 2027 437 $143 $62,443 $44,521 $53,864 Licensing Guidance NRC Development of EMT 2028 437 $143 $62,443 $41,609 $52,295 Licensing Guidance NRC Development of EMT 2029 437 $143 $62,443 $38,887 $50,772 Licensing Guidance NRC Development of EMT 2030 437 $143 $62,443 $36,343 $49,293 Licensing Guidance NRC Development of EMT 2031 437 $143 $62,443 $33,965 $47,858 Licensing Guidance NRC Development of EMT 2032 437 $143 $62,443 $31,743 $46,464 Licensing Guidance NRC Development of EMT 2033 437 $143 $62,443 $29,666 $45,110 Licensing Guidance NRC Development of EMT 2034 437 $143 $62,443 $27,726 $43,796 Licensing Guidance NRC Development of EMT 2035 437 $143 $62,443 $25,912 $42,521 Licensing Guidance NRC Development of EMT 2036 437 $143 $62,443 $24,217 $41,282 Licensing Guidance C-23

Total Net Benefits - Averted Costs Year Activity Hours NRC hourly rate Undiscounted 7% NPV 3% NPV NRC Development of EMT 2037 437 $143 $62,443 $22,632 $40,080 Licensing Guidance NRC Development of EMT 2038 437 $143 $62,443 $21,152 $38,913 Licensing Guidance NRC Development of EMT 2039 437 $143 $62,443 $19,768 $37,779 Licensing Guidance NRC Development of EMT 2040 437 $143 $62,443 $18,475 $36,679 Licensing Guidance NRC Development of EMT 2041 437 $143 $62,443 $17,266 $35,611 Licensing Guidance Total Net Benefits - Averted Costs 6,550 $936,650 $433,880 $662,318 15-year Average $62,443 $28,925 $44,155 Annualized with 7% discounting $47,638 Annualized with 3% discounting $55,480 C-24

Table 40: Alternative 4 - Agreement States Emerging Medical Technology Licensing (Averted Costs)

Total Net Benefits - Averted Costs Year Activity Hours Agreement State hourly rate Undiscounted 7% NPV 3% NPV Agreement States Review of EMT 2030 License Applications and Amendments 10,341 $73 $757,708 $440,993 $598,141 Requests Agreement States Review of EMT 2031 License Applications and Amendments 10,341 $73 $757,708 $412,143 $580,720 Requests Agreement States Review of EMT 2032 License Applications and Amendments 10,341 $73 $757,708 $385,180 $563,806 Requests Agreement States Review of EMT 2033 License Applications and Amendments 10,341 $73 $757,708 $359,981 $547,384 Requests Agreement States Review of EMT 2034 License Applications and Amendments 10,341 $73 $757,708 $336,431 $531,441 Requests Agreement States Review of EMT 2035 License Applications and Amendments 10,341 $73 $757,708 $314,422 $515,962 Requests Agreement States Review of EMT 2036 License Applications and Amendments 10,341 $73 $757,708 $293,852 $500,934 Requests Agreement States Review of EMT 2037 License Applications and Amendments 10,341 $73 $757,708 $274,628 $486,344 Requests Agreement States Review of EMT 2038 License Applications and Amendments 10,341 $73 $757,708 $256,662 $472,178 Requests Agreement States Review of EMT 2039 License Applications and Amendments 10,341 $73 $757,708 $239,871 $458,426 Requests Agreement States Review of EMT 2040 License Applications and Amendments 10,341 $73 $757,708 $224,178 $445,073 Requests C-25

Total Net Benefits - Averted Costs Year Activity Hours Agreement State hourly rate Undiscounted 7% NPV 3% NPV (Agreement States) Submission and 2041 Review of EMT License Applications and 10,341 $73 $757,708 $209,512 $432,110 Amendments (Agreement States) Submission and 2042 Review of EMT License Applications and 10,341 $73 $757,708 $195,806 $419,524 Amendments (Agreement States) Submission and 2043 Review of EMT License Applications and 10,341 $73 $757,708 $182,996 $407,305 Amendments (Agreement States) Submission and 2044 Review of EMT License Applications and 10,341 $73 $757,708 $171,025 $395,442 Amendments Total Net Benefits - Averted Costs 155,114 $11,365,615 $4,297,681 $7,354,791 15-year Average $757,708 $286,512 $490,319 Annualized with 7% discounting $471,862 Annualized with 3% discounting $616,086 Table 41: Alternative 4 - Licensees Emerging Medical Technology Licensing (Averted Costs)

Total Net Benefits - Averted Costs Year Activity Hours Licensee hourly rate Undiscounted 7% NPV 3% NPV Licensees Submission of EMT License 2030 Applications and Amendment Requests 1,758 $92 $162,512 $94,583 $128,288 Licensees Submission of EMT License 2031 Applications and Amendment Requests 1,758 $92 $162,512 $88,396 $124,552 Licensees Submission of EMT License 2032 Applications and Amendment Requests 1,758 $92 $162,512 $82,613 $120,924 C-26

Total Net Benefits - Averted Costs Year Activity Hours Licensee hourly rate Undiscounted 7% NPV 3% NPV Licensees Submission of EMT License 2033 Applications and Amendment Requests 1,758 $92 $162,512 $77,208 $117,402 Licensees Submission of EMT License 2034 Applications and Amendment Requests 1,758 $92 $162,512 $72,157 $113,982 Licensees Submission of EMT License 2035 Applications and Amendment Requests 1,758 $92 $162,512 $67,437 $110,662 Licensees Submission of EMT License 2036 Applications and Amendment Requests 1,758 $92 $162,512 $63,025 $107,439 Licensees Submission of EMT License 2037 Applications and Amendment Requests 1,758 $92 $162,512 $58,902 $104,310 Licensees Submission of EMT License 2038 Applications and Amendment Requests 1,758 $92 $162,512 $55,048 $101,272 Licensees Submission of EMT License 2039 Applications and Amendment Requests 1,758 $92 $162,512 $51,447 $98,322 Licensees Submission of EMT License 2040 Applications and Amendment Requests 1,758 $92 $162,512 $48,081 $95,458 Licensees Submission of EMT License 2041 Applications and Amendment Requests 1,758 $92 $162,512 $44,936 $92,678 Licensees Submission of EMT License 2042 Applications and Amendment Requests 1,758 $92 $162,512 $41,996 $89,979 C-27

Total Net Benefits - Averted Costs Year Activity Hours Licensee hourly rate Undiscounted 7% NPV 3% NPV Licensees Submission of EMT License 2043 Applications and Amendment Requests 1,758 $92 $162,512 $39,249 $87,358 Licensees Submission of EMT License 2044 Applications and Amendment Requests 1,758 $92 $162,512 $36,681 $84,814 Total Net Benefits - Averted Costs 17,576 $2,437,673 $921,758 $1,577,440 15-year Average $162,512 $61,451 $105,163 Annualized with 7% discounting $101,204 Annualized with 3% discounting $132,137 C-28

Appendix D - Uncertainty Analysis The NRC completed a Monte Carlo sensitivity analysis for this regulatory analysis using the specialty software @Risk. The Monte Carlo approach answers the question, What distribution of net benefits results from multiple draws of the probability distribution assigned to key variables?

D.1 Uncertainty Analysis Assumptions As this regulatory analysis uses estimates of labor and predicted future licensing actions, the staff analyzed the variables that have the greatest amount of uncertainty. To perform this analysis, the staff used a Monte Carlo simulation analysis using the @Risk software program.

This was done to determine the robustness of the costs and net benefits of the rulemaking. The NRC examined how anticipated costs and averted costs change due to uncertainties associated with the NRCs analytical assumptions and input data shown in Appendix B to this document.

D.2. Uncertainty Analysis Inputs The probability distributions chosen to represent the different variables in the analysis were bounded by the range-referenced input and the NRC staffs professional judgment. When defining the probability distributions for use in a Monte Carlo simulation, summary statistics are used to characterize the distributions. These summary statistics include the minimum, most likely, and maximum values of a program evaluation and review technique (PERT) distribution.

The staff used the PERT distribution to reflect the relative spread and skewness of the distribution defined by the three estimatesthe minimum, most likely, and maximum.

Figure C-1 provides the probability distribution function and the descriptive statistics of the inputs used in the uncertainty analysis. Appendix B to this document shows the inputs.

D.3 Uncertainty Analysis Results Figure 1 depicts the results of the uncertainty analysis of Alternative 4 net costs using a 7-percent discount rate. This figure displays the curve of the incremental net averted cost for the rulemaking. The uncertainty analysis graph shows that the Alternative 4 mean net averted cost is $1,169,000 in 2022 dollars with a 90-percent confidence interval that the averted costs are between $574,000 and $1,755,000 using a 7-percent discount rate. Note that there may be differences in totals if the random number generator uses a different seed to initiate the random number sequence.

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Figure 1: Incremental Net Costs for Alternative 4 (7-Percent Discount Rate)

D.4 Sensitivity Analysis In addition to estimating the probability distributions for the net benefits of the rule, the staff used Monte Carlo simulation to conduct a sensitivity analysis to determine the variables that have the greatest impact on the resulting net costs. Variables shown to have a large effect on the resulting net benefits may deserve more attention and scrutiny than variables shown to have a small or minimal effect.

Figure 2 shows a tornado diagram that identifies the key variables whose uncertainty drives the largest impact on net benefits for this recommended alternative. Figure 2 ranks the variables based on their contribution to cost uncertainty.

The estimate that has the greatest variation in the Alternative 4 overall results is the licensee time in hours for submission and review of EMT License Applications and Amendments for Sirtex Microspheres. The uncertainty in this variable would result in a change to D-2

the mean of $714,000, a difference in averted costs that ranges between $802,000 to $1,516,000 with a 90-percent confidence interval.

The estimate that has the second greatest variation in the Alternative 4 overall results is the licensee time in hours for submission and review of EMT license applications and amendments for Nordion Microspheres. The uncertainty in this variable would result in a change to the mean of $703,000, a difference in averted costs that ranges between $819,000 to $1,522,000 with a 90-percent confidence interval.

The estimate that has the third greatest variation in the Alternative 4 overall results is the cost per Agreement State to develop compatible regulations and implementation. The uncertainty variable would result in a change to the mean of $334,000, a difference in averted costs that ranges from $1,002,000 to $1,336,000 with a 90-percent confidence interval.

The estimate that has the fourth greatest variation in the Alternative 4 overall results is the cost per Agreement State time in hours for submission and review of EMT license applications and amendments for Sirtex Microspheres. The uncertainty variable would result in a change to the mean of $305,000, a difference in averted costs that ranges from $1,019,000 to $1,324,000 with a 90-percent confidence interval. The remainder of the variables result in small or minimal effect on the costs.

Figure 2: Alternative 4 Cost Drivers (7-Percent Discount Rate)

Alternative 4 - PERFORMANCE-BASED RULEMAKING TO INCREASE REGULATORY FLEXIBILITY [STAFF RECOMMENDATION]

Inputs Ranked by Effect on Output Mean Time (Hours) (Licensees) Sirtex Microspheres $801,699 $1,516,114 Time (Hours) (Licensees) Nordion Microspheres $819,415 $1,521,625 Input High Input Low patible regulations and implementation $1,002,013 $1,335,520 Time (Hours) (Agreement States) Sirtex Microspheres $1,019,412 $1,323,657 Baseline = $1,169,081 0.80 0.90 1.00 1.10 1.20 1.30 1.40 1.50 1.60 Values in Millions ($)

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