ML21326A168

Draft Revision 2 of Regulatory Guide 8.39, Release of Patients Administered Radioactive Material, for ACMUI Review

ML21326A168
Person / Time
Issue date:	11/22/2021
From:	Advisory Committee on the Medical Uses of Isotopes
To:
Valentin-Rodriguez, Celimar NMSS/MSST
References
RG-8.039, Rev. 2
Download: ML21326A168 (55)

Text

U.S. NUCLEAR REGULATORY COMMISSION DRAFT REGULATORY GUIDE DG-8061

Proposed Revision 2 to Regulatory Guide 8.39 Issue Date: Month 2021 Technical Lead: Vered Shaffer

RELEASE OF PATIENTS ADMINISTERED RADIOACTIVE MATERIAL

A. INTRODUCTION

Purpose

This regulatory guide (RG) provides methods that are acceptable to the U.S. Nuclear Regulatory Commission (NRC) staff for release of patients after a medical procedure involving the administration of unsealed byproduct material, such as radiopharmaceuticals, or i mplants that contain radioactive material.

The RG provides tables of an activity threshold and dose rate t hat may be used by licensees for the release of the patients and meeting NRC regulatory requirements.

This RG also provides licensees with a methodology to modify th e threshold and dose rate values on a patient-specific basis. In addition, the RG provide s licensees with instructions for patients before and after they are administered radioactive material, as well as requirements for recordkeeping.

Applicability

This RG applies to all NRC medical use licensees subject to Tit le 10 of the Code of Federal Regulations (10 CFR) Part 35, Medical Use of Byproduct Material, Section 35.75, Release of Individuals Containing Unsealed Byproduct Material or Implants Containing Byproduct Material (Ref.

1).

Applicable Regulations

• 10 CFR Part 35 provides requirements and provisions for the rad iation safety of workers, the general public, patients, and human research subjects.

o 10 CFR 35.75(a) permits the licensee to authorize the release o f any individual from its control who has been administered unsealed byproduct material or implan ts 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 (mSv) (0.5 rem).

o 10 CFR 35.75(b) requires the li censee to provide the released individual or the individuals parent or guardian with instruc tions, including written instruc tions, on actions recommended to maintain doses to other indivi duals as low as is reasonably achievable (ALARA) if the TEDE to any other individual is likely to exceed 1 mSv (0.1 rem). If the dose to a breastfeeding infant or child could exceed 1 mSv (0.1 rem) with out the patients interruption of breastfeeding, the instructions shall also include (1) guida nce on the interruption or discontinuation of breastfeeding and (2) information on the pot ential consequences of failure to follow the guidance.

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o 10 CFR 35.75(c) and 35.2075(a) require the licensee to maintain a record of the basis for authorizing the release of an individual for 3 years after the date of release if the TEDE to any other individual from exposure to the released individual is ca lculated by using the retained activity rather than the activity administered, using an occupancy factor less than 0.25 at 1 meter, using the biological or effective half-life, or consider ing the shielding by tissue.

o 10 CFR 35.75(d) and 35.2075(b) require the licensee to maintain a record of instructions provided to a breastfeeding female for 3 years after the date of release if the TEDE to a nursing infant or child is likely to exceed 5 mSv (0.5 rem) without breastfeeding interruption.

Related Guidance

• Current version of NUREG-1556, Consolidated Guidance about Mat erials Licenses: Program-Specific Guidance about Medical Use Licenses, Volume 9 (Ref. 2).

Purpose of Regulatory Guides

The NRC issues RGs to describe to the public methods that the s taff considers acceptable for use in implementing specific parts of the agencys regulations, to explain techniques that the staff uses in evaluating specific problems or postulated events, and to provi de guidance to licensees. Regulatory guides are not substitutes for regulations, and compliance with them i s not required. Methods and solutions that differ from those set forth in RGs will be deemed acceptable if they provide a basis for the findings required for the issuance or continuance of a permit or license by the Commission.

Paperwork Reduction Act

This RG provides voluntary guidance for implementing the mandat ory information collections in 10 CFR Part 35 that is subject to the Paperwork Reduction Act o f 1995 (44 U.S.C. 3501 et. seq.). These information collections were approved by the Office of Manageme nt and Budget (OMB), approval number 3150-0010. Send comments regarding this information collection to the FOIA, Library, and Information Collections Branch (T6-A10M), U.S. Nuclear Regulatory Commission, Washington, DC 20555-0001, or by e-mail to Infocollects.Resource@nrc.gov, and to the OMB reviewer at: OMB Office of Information and Regulatory Affairs (3150-0010), Attn: Desk Officer for the Nucl ear Regulatory Commission, 725 17th Street, NW Washington, DC 20503; e-mail: oira_submission@omb.eop.gov.

Public Protection Notification

The NRC may not conduct or sponsor, and a person is not require d to respond to, a collection of information unless the document re questing or requiring the col lection displays a currently valid OMB control number.

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TABLE OF CONTENTS

A. INTRODUCTION.................................................................................................................................. 1 B. DISCUSSION........................................................................................................................................ 4 C. STAFF REGULATORY GUIDANCE.................................................................................................. 7

1. Release Criteria....................................................................................................................... 7 1.1 Release of Patients Based on the Administered Activity................................................. 8 1.2 Release of Patients Based on the Measured Dose Rate................................................. 11 1.3 Release of Patients After a Hold Time........................................................................... 12

2. Breastfeeding Patients............................................................................................................ 13

3. Patient-Specific Dose Calculations........................................................................................ 1 6 3.1 Release of Patients Based on the Administered Activity............................................... 17 3.2 Release of Patients Based on the Measured Dose Rate................................................. 17 3.3 Release of Patients After a Hold Time........................................................................... 17

4. Instructions............................................................................................................................. 18 4.1 Activities and Dose Rates That Require Instructions................................................... 18 4.2 Content of Instructions................................................................................................. 1 9 4.2.1 Pretreatment Discussions on the Administration of Radiop harmaceuticals..... 20 4.2.2 Patient Instructions............................................................................................ 21 4.2.3 Patient Acknowledgement of Instructions........................................................ 23 4.2.4 Patient Precautions............................................................................................ 23 4.3 Death of a Patient Following Radiopharmaceutical Administr ation or Implants......... 23

5. Records................................................................................................................................... 25 5.1 Records of Release....................................................................................................... 26 5.2 Records of Instructions for Breastfeeding Patients...................................................... 26

6. Material Separated from the Patient...................................................................................... 27 D. IMPLEMENTATION.......................................................................................................................... 27 REFERENCES................................................................................................................................................ 28 APPENDIX A (Radionuclide Data Tables).................................................................................................. A-1 APPENDIX B (Patient-Specific Modifying Factors and Methods).............................................................. B-1 APPENDIX C (Example Calculations)........................................................................................................ C-1

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B. DISCUSSION

Reason for Revision

This revision of RG 8.39 (Revis ion 2) provides updated guidance to calculate basic release thresholds for patient release after they have been administered radioactive material. In this revision, threshold calculations assume unity for the occupancy factor in threshold calculations when patient specific information is not know n to avoid underestimating expo sure when patients have close contact with individuals, referred to as bystanders. Updated thresholds for administered activity and measured dose-rates are tabulated for individual radionuclides. Updated activity thresholds for radiopharmaceuticals are also presented for patients who may continue breastfeeding an infant or child after administration, and breastfeeding interruption times are recommended for example administered activities.

This revision also provides an acceptable methodology for patient release when patient-specific information is considered. This methodology includes factors fo r biokinetics, occupancy, geometry, and attenuation based on patient-specific information. Additionally, the calculational methodology in this RG provides flexibility to accommodate new radiopharmaceuticals th at could be used for diagnostic or therapeutic purposes. Therefore, revision 2 incorporates curre nt scientific knowledge that would lead to more accurate estimates of public doses from released patients, resulting in better licensee decisions regarding the timing, circumstances, and risks associated with patient release following byproduct material administration.

=

Background===

Title 10 of the Code of Federal Regulations (10 CFR) 35.75, Release of individuals containing unsealed byproduct material or im plants containing byproduct ma terial, was revised in the 1979 rule often referred to as the Patient Release Rule. It was revised because the 1991 revision of 10 CFR Part 20 revised the dose limits for membe rs of the general public in 10 CFR 20.1301, but did not clarify how the new public dose limit was related to the release of patients. NRC determined that while doses should be maintained ALARA, the new public dose limit did not apply to ra diation exposure from a patient and that a dose limit of 5 mSv (0.5 rem) provides adequate protection. T he new Patient Release Rule allows a licensee to authorize the release of a patient from its control if the total effective dose equivalent (TEDE) to any other individual, from exposure to the released patient, is not likely to exceed 5 mSv (0.5 rem). In addition, 10 CFR 35.75 requires that a licensee provide the rel eased individual, or the patients family or other caregivers, with appropria te instructions, including writ ten instructions, on recommended actions to maintain doses to other individuals ALARA if the TEDE to any other individual is likely to exceed 1 mSv (0.1 rem).

The Commission directed the NRC staff in Staff Requirements Memorandum-COMAMM 0001/COMWDM-14-0001, Background a nd Proposed Direction to NRC Staff to Verify Assumptions Made Concerning Patient Release Guidance, to Revise Regulator y Guide 8.39, and subsequently NUREG-1556, Volume 9, to specify guidelines for patient informa tion and instructional guidance. NRC staff responded to Staff Requirements Memorandum-COMAMM-14-0001 /COMWDM-14-0001in SECY-18-0015, Staff Evaluation of the U.S. Nuclear Regulatory Commi ssions Program Regulating Patient Release after Radioisotope Therapy. In SECY-18-0015, the NRC staff concluded that the current patient release regulations are protective for public health and safety, and that rulemaking to change the release criteria is not warranted. However, the staff determined that a comprehensive update to the NRCs patient release guidance, including incorporation of guidance currently provided in generic communications, as well as updates to the equations and methodologies described in the NRC guidance for calculating dose to members of the public from released patients, is warranted. NRC staff updated NUREG-1556, Volume 9, Rev. 3, to refer to this RG to remove duplicative patient relea se guidance and avoid inconsistencies.

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Following up on the determination for a comprehensive update to the NRCs patient release guidance, the staff has developed Revision 2 to RG 8.39 to prov ide a methodology for licensees to determine when it is appropriate to release a patient from thei r control and when instructions or records are required. Per 10 CFR 35.75, licensees can authorize release of an individual, referred to as the patient in this RG, from its control if the TEDE to any other individual f rom exposure to the released individual is not likely to exceed 5 mSv. To ensure compliance with this reg ulation, licensees must ensure dose to all other individuals other than the patient is likely to be below this limit based on the amount of activity retained in the patient at the time of release and expected patient interactions with ot hers. Individuals being exposed to the patient are referred to as bystanders in this gu idance. Bystanders are all members of the public, including family members and caregivers. This guidance provides administered activity and measured dose rate thresholds to demonstrate compliance for com monly used and emerging radiopharmaceuticals. Seldom used radionuclides listed in the o riginal RG are retained in this revision to address the potential for their return to usage in future radio pharmaceuticals. This guidance offers calculational methodologies to accommodate threshold modificati ons for patient-specific exposure situations. This is accomplished with patient-specific modifyin g factors for biokinetics, occupancy, geometry, and attenuation based on patient-specific information. In addition, this guidance provides activity thresholds for radiopharmaceuticals for patients who may continue breastfeeding an infant or child after administration, and breastfeeding interruption times reco mmended for example medical dosages.

Implementing fundamentals outlin ed in the National Council on R adiation Protection and Measurements (NCRP) Report No. 155, Management of Radionuclide Therapy Patients (Ref. 3), and NCRP Report No. 37, Precautions in the Management of Patients Who Have Received Therapeutic Amounts of Radionuclides (Ref. 4), this RG is structured so th at licensees can satisfy requirements for patient release, issuing instructions, or maintaining records. For a majority of clinical procedures, a simple comparison of the administered activity to conservative basic t hresholds is sufficient to reach patient release conclusions without invoki ng the patient-specific modifying factors. Licensees are guided to consider the patient-specific modifying factors when the admini stration activity is above the basic threshold values. Determining these factors yields modified, p atient-specific thresholds that are more realistic for a particular patient. If calculations show radiation dose could exceed the limits, an administrative hold of the patient in the medical facility may be appropriate, and this guidance provides a methodology to calculate the hold time. NUREG-1556 Vol. 9 provi des guidance on controls needed for patients who cannot be released in accordance with 10 CFR 35.75. Instructions for the patient, unexpected death of the patient, maintaining records, and radioactive mate rial separated from the patient are also addressed.

Consideration of International Standards

The International Atomic Energy Agency (IAEA) works with member states and other partners to promote the safe, secure, and peaceful use of nuclear technologies. The IAEA develops Safety Requirements and Safety Guides for protecting people and the en vironment from harmful effects of ionizing radiation. This system of safety fundamentals, safety requirements, safety guides, and other relevant reports, reflects an international perspective on what constitutes a high level of safety. The NRC considered IAEA Safety Requirements and Safety Guides pursuant to the Commissions International Policy Statement, published in the Federal Register on July 10, 2014 (Ref. 5), and Management Directive 6.6, Regulatory Guides dated May 2, 2016 (Ref. 6).

The IAEA (Ref. 7) provides guidance for releasing patients afte r radioactive material administration that is related to the basic safety principles considered in developing this RG. The instructions to patients included in the IAEA report are al so similar to the instructions listed in this RG. The IAEA guidance is based on retained activity in the patient such that doses to a bystander would not exceed a few mSv (rem).

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IAEA recommends special considerations for patients who are or may become pregnant, patients who are breastfeeding children, as well as patients who unexpectedly die soon after treatment. The NRC notes that the U.S. dose limits in 10 CFR Part 35 differ from many interna tional regulatory requirements.

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C. STAFF REGULATORY GUIDANCE

This section describes in detail the methods, approaches, and d ata that the NRC staff considers acceptable for meeting the requirements of the applicable regul ations cited in the introduction.

1. Release Criteria

Fundamental Dose Equation for Patient Release

Radioactive material activities administered to patients qualifying for patient release were calculated with updated parameters that implement fundamentals outlined in the National Council on Radiation Protection and Measurements (NCRP) Report No. 155, Management of Radionuclide Therapy Patients (Ref. 3) and NCRP Report No. 37, Precautions in the Management of Patients Who Have Received Therapeutic Amounts of Radionuclides (Ref. 4). Radiol ogical exposure of a bystander to radioactive material in the released patient is estimated in a two-tiered approach.

In the first tier, a basic dose assessment is performed using g eneric, conservative assumptions.

= 1.44 0 (Equation 1) where

= External dose equivalent, mSv 1.44 = Constant for reciprocal of the natural logarithm of 2

= Radiological (physical) half-life, h

= Dose-rate constant for a point source at 1 m,

= Activity of the radionuclide administered to the patient, G Bq

Equation 1 is used to calculate the administered activity below which patients may be released without patient-specific information. These basic activity thre sholds include several general assumptions:

• external dose equivalent to a point in tissue is calculated from the photon emissions (including electron bremsstrahlung) of a point source surrounded by an inf initely thin sphere of tissue;

• dose rate is calculated at a distance of 1 m;

• radionuclide loss from the patient only includes physical decay ;

• external dose begins immediately after administration and lasts through infinity, i.e., total decay;

• an occupancy of 100% at 1 meter is assumed; and

• implants are encapsulated in 50 m of titanium.

As Equation 1 does not account for patient-specific information, these assumptions are meant to be overly conservatism to avoid underestimation of dose in likely situations. Conservative assumptions include assuming full occupancy and not including biological loss. Through the use of these conservative generic assumptions, this basic equation can demonstrate compli ance with 10 CFR Part 35 for many lower activity and external dose-rate procedures without detailed patient-specific information. The second tier can be used when increased realism with patient-specific information is necessary to provide a basis for

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release and demonstrate compliance with 10 CFR 35.75 (refer to Section 3).

The external dose pathway is considered to be dominant, and int ernal dose pathways are not included. Dose implications fro m potential intakes by househol d members and members of the public have been shown to be small (less than a few percent) relative to external doses (Refs. 7, 8, 9 and 10).

When internal dose pathways are negligible, TEDE equals the accumulated external dose equivalent,

and the basic activity threshold is calculated by replacing with :

=. (Equation 2)

where

= Basic activity threshold, GBq

= TEDE limit, mSv

Licensees are authorized to release the patient when TEDE to t he maximally exposed bystander is not likely to exceed 5 mSv. Instructions to minimize dose to th e bystander are required when TEDE is likely to exceed 1 mSv (0.1 rem). Basic activity thresholds for dose limits of 5 mSv for patient release and 1 mSv for issuing dose-minimizing instructions are denoted as and, respectively. At the standard measurement distance of 1 m, the basic measurement threshold is closely related to the basic activity threshold

= (Equation 3) where

= Basic measurement threshold at 1 m,

Denoted by and, basic measurement thresholds are computed from Equation 3 for dose limits of 5 mSv (0.5 rem) for patient release and 1 mSv (0.1 re m) for issuing instructions, respectively. To avoid redundancy, equations in th is section avoid the subscript notation. Compliance can be demonstrated by either (i) comparing the administered activity 1 to the basic activity threshold or (ii) comparing the measured dose rate at 1 m at the time of administration1 to the basic measurement threshold. These thresholds are provided in Tabl es 1 and 2 in Sections 1.1 and 1.2, respectively. Licensees may use one of the following options discussed in Sections 1.1 - 1.4 to release a patient who has been administered radiopharmaceuticals or implants that contain radioactive mater ial.

Equations 1 3 consider externa l exposure to the patient and d o not include internal dose contributions.

However, internal doses are important, and licensees must calcu late internal dose for infants or children who continue to breastfeed to de termine if instructions are needed in accordance with 10 CFR 35.75(b).

Breastfeeding is considered in Section 2 of this guide. In addition, licensees may need to consider both internal and external exposure to a bystander from byproduct ma terial which could have become separated or excreted from a patient for patient-specific situations described in Section 6 of this guide.

1.1 Release of Patients Based on the Administered Activity

Licensees can demonstrate compliance with the dose limit in 10 CFR 35.75(a) for releasing

1 Activity retained in the patient at the time of release, as determined by the licensee, can replace the administered activ ity in comparisons to the basic activity threshold. The measured dose rate at the time of release can also be compared to the basic measurement threshold. These replacements are permitted because basic thresholds neglect biological clearance (i.e., =1).

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patients from licensee control if the administered activity is not greater than the basic activity threshold listed in Column 1 of Table 1. Basic activity thresholds in Col umn 1 of Table 1 were calculated using Equation 2 and are based on a TEDE to an individual of 5 mSv (0.5 rem) for the previously listed conservative assumptions. The basic activity thresholds do not include the dose from internal intake by household members and members of the public because internal do se from potential bystander intake is expected to be small for most radiopharmaceuticals (less than a few percent) relative to external dose.

When the activity administered, (GBq), is not greater than (GBq) in Column 1 of Table 1

( ), release of the patient is authorized and no record is require d of the basis for authorizing release of the patient, unless the patient is breastfeeding an infant or child as discussed in Section 2.

Table 1. Basic Activity Thresholds for Radionuclides

COLUMN 1 COLUMN 2 RADIONUCLIDE Patient Release Threshold Instruction Threshold (GBq) (mCi) (GBq) (mCi)

Ag-111 4.4 120 0.88 24 At-211 17 460 3.3 89 Au-198 0.88 24 0.18 4.9 Bi-213 210 5,700 41 1,100 C-11 68 1,800 14 380 C-14b 0.0014 0.038 0.00028 0.0076 Cr-51 1.1 30 0.23 6.2 Cs-131 1.1 30 0.21 5.7 Cs-131 implanta 1.1 30 0.23 6.2 Cu-64 9.7 260 1.9 51 Cu-67 3.7 100 0.75 20 Dy-165 320 8,600 65 1,800 Er-169b 130 3,500 26 700 F-18 13 350 2.5 68 Ga-67 2.1 57 0.42 11 Ga-68 22 590 4.4 120 Ho-166b 26 700 5.2 140 I-123 6.7 180 1.3 35 I-124 0.20 5.4 0.041 1.1 I-125 0.074 2.0 0.015 0.41 I-125 implanta 0.084 2.3 0.017 0.46 I-131 0.32 8.6 0.063 1.7 In-111 0.64 17 0.13 3.5 Ir-192 0.015 0.41 0.0030 0.081 Ir-192 implanta 0.016 0.43 0.0033 0.089 Lu-177 4.1 110 0.82 22 N-13 140 3800 28 760 O-15 680 18,000 140 3,800 P-32b 9.2 250 1.8 49 P-33b 64 1,700 13 350 Pd-103 0.27 7.3 0.055 1.5 Pd-103 implanta 0.39 11 0.077 2.1 Ra-223 0.27 7.3 0.054 1.5

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Rb-82 960 26,000 190 5,100 Re-186 6.2 170 1.2 32 Re-188b 16 430 3.1 84 Ru-106b 180 4,900 37 1,000 Ru-106b implanta 200 5,400 550 15,000 Sc-47 3.1 84 0.62 17 Se-75 0.0080 0.22 0.0016 0.043 Sm-153 6.8 180 1.4 38 Sn-117m 0.29 7.8 0.058 1.6 Sr-89b 3.3 89 0.66 18 Sr-90b 0.055 1.5 0.011 0.30 Tc-99m 30 810 6.1 160 Tl-201 1.2 32 0.23 6.2 Xe-127 0.073 2.0 0.015 0.41 Xe-133 2.1 57 0.42 11 Y-90b 34 920 6.8 180 Yb-169 0.094 2.5 0.019 0.51 Zr-89 0.21 5.7 0.042 1.1

a. Implants including eye plaques are assumed to be encapsulated in 50 m of titanium.

b. Greater than 5% of due to bremsstrahlung production.

NOTE: Agreement State licensees should check their State regul ations before using these values.

If the activity administered exceeds the activity in Column 1 of Table 1 0 >, the licensee may select one of the following options:

a. Consider releasing the patient according to measured dose rates as described in Section 1.2.

b. Release the patient when the activity retained in the patient h as decreased to (GBq) in Column 1 of Table 1. In this case, 10 CFR 35.75(c) and 35.2075( a)(1) require the licensee to maintain a record of the basis for authorizing the release beca use it is based on the retained activity instead of on the administered activity.

c. Consider patient-specific modifi cation of the activity threshol d as described in Section 3. In this case, 10 CFR 35.75(c) and 35.2075( a) require the licensee to maintain a record of the basis for authorizing the release when it incorporates an occupancy factor less than 0.25 at 1 meter, use of the biological or effective half-life, or includes shielding by tissue.

d. Calculate a hold time as described in Section 1.3. In this case, 10 CFR 35.75(c) and 35.2075(a)(1) require the licensee to maintain a record of the basis for authorizing the release because it is based on the retained activity instead of on the administered activity.

Radionuclide data used in the calculation of the basic threshol ds are tabulated in Appendix A. If the licensee administers a radionuclide that is not listed in T able 1, it may demonstrate compliance with the regulation in 10 CFR 35.75 by maintaining a record of the calcu lation (for NRC inspection) of the release activity that corresponds to the dose limit of 5 mSv (0.5 rem).

Release activities in Column 1 of Table 1 do not consider the d ose to a breastfeeding infant or child from the ingestion of rad iopharmaceuticals contained in a patients breast milk. When the patient is breastfeeding an infant or child, the activities in Column 1 of Table 1 do not apply to the infant or child.

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More information regarding breastfeeding guidance can be found in Section 2.

1.2 Release of Patients Based on the Measured Dose Rate

Licensees may release patients administered radionuclides in amounts greater than the activities listed in Column 1 of Table 1 ( > ) if the measured dose rate at 1 meter from the patient is no greater than the value in Column 1 of Table 2 for that radionuclide.

Table 2. Basic Measurement Thresholds for Radionuclides d

COLUMN 1 COLUMN 2 RADIONUCLIDE Patient Release Thresholdc Instruction Thresholdc (mSv/h) (mrem/h) (mSv/h) (mrem/h)

Ag-111 0.019 1.9 0.0039 0.39 At-211 0.49 49 0.096 9.6 Au-198 0.054 5.4 0.011 1.1 Bi-213 4.6 460 0.90 90 C-11 10 1000 2.1 210 C-14 0.000000070 0.0000070 0.000000014 0.0000014 Cr-51 0.0051 0.51 0.0011 0.11 Cs-131 0.015 1.5 0.0029 0.29 Cs-131 implanta 0.014 1.4 0.0030 0.30 Cu-64 0.27 27 0.053 5.3 Cu-67 0.056 5.6 0.011 1.1 Dy-165 1.5 150 0.30 30 Er-169b 0.016 1.6 0.0031 0.31 F-18 2.0 200 0.38 38 Ga-67 0.044 4.4 0.0088 0.88 Ga-68 3.1 310 0.62 62 Ho-166 0.13 13 0.026 2.6 I-123 0.26 26 0.051 5.1 I-124 0.034 3.4 0.0070 0.70 I-125 0.0024 0.24 0.00050 0.050 I-125 implanta 0.0024 0.24 0.00049 0.049 I-131 0.018 1.8 0.0036 0.36 In-111 0.051 5.1 0.010 1.0 Ir-192 0.0020 0.20 0.00039 0.039 Ir-192 implanta 0.0019 0.19 0.00040 0.040 Lu-177 0.022 2.2 0.0043 0.43 N-13 21 2,100 4.2 420 O-15 100 10,000 21 2,100 P-32b 0.010 1.0 0.0020 0.20 P-33b 0.0057 0.57 0.0012 0.12 Pd-103 0.0084 0.84 0.0017 0.17 Pd-103 implanta 0.0086 0.86 0.0017 0.17 Ra-223 0.013 1.3 0.0025 0.25 Rb-82 160 16,000 32 3,200 Re-186 0.039 3.9 0.0076 0.76 Re-188 0.21 21 0.040 4.0 RG 8.39, Rev. 2, Page 11

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Ru-106 0.00038 0.038 0.000078 0.0078 Ru-106 implanta 0.00038 0.038 0.000077 0.0077 Sc-47 0.043 4.3 0.0087 0.87 Se-75 0.0012 0.12 0.00024 0.024 Sm-153 0.075 7.5 0.015 1.5 Sn-117m 0.010 1.0 0.0021 0.21 Sr-89b 0.0029 0.29 0.00057 0.057 Sr-90b 0.000014 0.0014 0.0000028 0.00028 Tc-99m 0.57 57 0.12 12 Tl-201 0.049 4.9 0.0094 0.94 Xe-127 0.0039 0.39 0.00081 0.081 Xe-133 0.027 2.7 0.0055 0.55 Y-90b 0.054 5.4 0.011 1.1 Yb-169 0.0045 0.45 0.00091 0.091 Zr-89 0.044 4.4 0.0088 0.88

a. Implants including eye plaques assumed to be encapsulated in 50 m of titanium

b. Greater than 5% of due to bremsstrahlung production

c. If the release is based on the dose rate at 1 meter in Column 2, the licensee must maintain a record as required by 10 CFR 35.75(c) and 35.2075(a)(4) because the measurement includes shielding by tissue. See Staff Regulatory Guidance 3.1, Records of Release, for information on records.

d. Values listed in the table are c alculated and shown for completeness. Values do not consider detection capabilities.

NOTE: Agreement State licensees should check their State regul ations before using these values.

If the measured dose rate at 1 meter is greater than the value, licensees may choose to perform patient-specific release calculations as described in Section 3 or hold the patient for release as described in Section 1.3. Unlik e activity thresholds, measured dose rates intrinsically include geometric radionuclide distribution within t he patients body and patient tissue attenuation effects. Measured dose rates at times after administration may also include some amount of biological clearance. Therefore, the regulation 10 CFR 35.75(c) and 35.2075(a) requires licensees to maintain a record of the basis for authorizing release as described in Section 5.

If a licensee administers a radionuclide not listed in Table 1 and chooses to release a patient based on the measured dose rate, the licensee must calculate a dose rate that corresponds to the 5 mSv (0.5 rem) dose limit to determine when a patient can be released per 10 C FR 35.75. Dose-rate constants are preferred over exposure rate constants because dose-rate constants are calculated for dose to tissue rather than exposure to air. For radionuclides not listed, an approach to d etermine dose-rate constants for new radionuclides is described, with s upporting details (Ref. 9) th at include a comparison of dose-rate constants to exposure-rate constants publis hed by other researchers (e.g., Refs. 11 and 12).

1.3 Release of a Patient After a Hold Time

When the administered activity or measured dose rate at 1 m exceeds the basic activity or dose rate threshold for release, a licensee may choose to hold a pat ient until the threshold for release has been satisfied. A conservative administrative hold time can be calculated based on radioactive decay

=1.44 ln (Equation 4)

where hold times apply only when >. More information regarding guidance and specific

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regulations for in-patients can be found in NUREG-1556, Volume 9, Revision 3. A licensee may also choose to do a patient specific calculation as described in Section 3 to determine if the threshold for release is satisfied after justifying more realistic values of the modi fying factors for the patient.

2. Breastfeeding Patients

10 CFR 35.75(b) states that a licensee will provide instruction regarding breastfeeding, including guidance on interruption or discontinuation of breastfeeding, i f the TEDE to a nursing infant or child is likely to exceed 1 mSv (0.1 rem) assuming there were no interru ption of breastfeeding following the release. To ensure compliance, licensees must determine a patients breastfeeding status, as appropriate, prior to release if the dose to t he infant or child could exceed 1 mSv (0.1 rem).

Breastfeeding activity thresholds were calculated for common ra diopharmaceuticals that could lead to 5 mSv (0.5 rem) or 1 mSv (0.1 rem) to a nursing infant or child if there is no interruption in breastfeeding (Ref. 9). The thresholds for 1 mSv are listed in Column 2 of Table 3. If the patient could be breastfeeding an infant or child after release and if the patie nt were administered a radiopharmaceutical with an activity above the value s tated in Column 2 of Table 3, additional breastfeeding instructions must be provided in accordance with 10 CFR 35.75(b). The instruction s must include appropriate recommendations on whether and how long to interrupt breastfeed ing. The instructions must inform the patient of the consequences of failure to follow the recommendation to interrupt or discontinue breastfeeding. The licensee should explain the consequence in a manner that will help the patient understand that, in some cases, breastfeeding after an administration of certain radionuclides should be avoided. For example, a conseque nce of procedures involving iod ine (I)-131 is that continued breastfeeding could harm the infants or childs thyroid.

The requirement in 10 CFR 35.20 75(b) states that a licensee shall retain a record of instructions provided to the patient if the radiation dose to the infant or child from continued breastfeeding would likely result in a TEDE exceeding 5 mSv (0.5 rem). The breastfeeding activity thresholds that could result in 5 mSv (0.5 rem) to a nursing infant or child are listed in C olumn 1 of Table 3 and are further described in supporting documentation (Ref. 9). If the administered activ ity is above this threshold, a record of the instructions provided to the pa tient shall be maintained for 3 years after patient release.

Table 4 provides the recommended duration of interrupting (or d iscontinuation) of breastfeeding to minimize the dose to below 5 mSv (0.5 rem) and 1 mSv (0.1 rem) for typical administrations of certain radiopharmaceuticals (Ref. 9). When the biological half-time, (h), of a radiopharmaceutical is known, effective half-life, (h), can be calculated as

= (Equation 5)

When breastmilk is pumped and di scarded during interruption, the interruption time, (h), equals

= 1.44 ln l (Equation 6) where

l = Breastfeeding activity threshold for instructions shown in T able 3.

For administrations of radiopharmaceuticals not listed in Table s 3 or 4 to a patient who could be breastfeeding, the licensee shall evaluate whether instructions or records (or both) are required. A method for calculating dose to the infant or child is documented separ ately (Ref. 9). Records of the calculation RG 8.39, Rev. 2, Page 13

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shall be maintained and instructions on interrupting breastfeeding are expected if the dose to the nursing child or infant is likely to ex ceed 5 mSv (0.5 rem) without breastfeeding interruption.

Table 3. Breastfeeding Activity Thresholds Assuming No Breastfeeding Interruption

COLUMN 1 COLUMN 2 RADIO-PHARMA-5-mSv Breastfeeding Activity 1-mSv Breastfeeding Activity NUCLIDE CEUTICAL Requiring a Record l Threshold for Instructions l (GBq) (mCi) (GBq) (mCi)

C-11 choline 2 60 0.5 10 Cr-51 EDTA 30 800 6 200 F-18 FDG 1 30 0.2 6 Ga-67 citrate 0.08 2 0.02 0.4 Ga-68 octreotate 9 200 2 50 MIBG 1 40 0.3 8 I-123 OIH 2 40 0.3 8 NaIa 0.002 0.05 0.0004 0.01 I-124 NaIa 0.00003 0.0008 0.000006 0.0002 I-125 OIH 0.1 3 0.02 0.6 NaIa 0.00007 0.002 0.00001 0.0004

I-131 OIH 0.08 2 0.02 0.4 NaIa 0.000004 0.0001 0.0000009 0.00002

In-111 octreotate 0.9 30 0.2 5 WBC 0.08 2 0.02 0.4 Lu-177 octreotate 0.4 10 0.08 2 N-13 Any 10 400 3 70 O-15 water 10 300 2 60 Ra-223 dichloride 0.000002 0.00005 0.0000004 0.00001 Rb-82 chloride 10 300 2 60 DISIDA 0.2 6 0.05 1 DTPA 50 1000 10 300 DTPA aerosol 100 4000 30 700 glucoheptonate 20 600 5 100 HAM 0.2 7 0.05 1 MAA 2 60 0.4 10 MAG3 40 1000 8 200 Tc-99m MDP 40 1000 9 200 MIBI 30 800 6 200 pertechnetate 0.5 10 0.1 3 PYP 0.7 20 0.1 4 RBC in vitro 50 1000 10 300 RBC in vivo 40 1000 8 200 sulfur colloid 0.5 10 0.1 3 WBC 0.8 20 0.2 4 Tl-201 chloride 2 50 0.4 10 Zr-89 panitumumab 0.01 0.3 0.002 0.07

a. l and l based on thyroid dose equivalent to nursing child or infant after patient release.

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NOTE: Agreement State licensees should check their State regul ations before using these values.

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Table 4. Recommended Breastfeeding Interruption Times for Radiopharmaceutical Administrations

RADIO-PHARMA-Example Administered Activity Interruption Time [h]

NUCLIDE CEUTICAL (GBq) (mCi) for 5 mSv for 1 mSv C-11 any 0.925 25 - -

Cr-51 EDTA 0.00185 0.05 - -

F-18 FDG 0.74 20 - 3 Ga-67 citrate 0.333 9 120 250 Ga-68 octreotate 0.185 5 - -

MIBG 0.37 10 - 4 I-123 OIH 0.074 2 - -

NaI*(HYP) 0.185 0.01 78 110 I-124 NaI*(HYP) 0.074 2 620 750 I-125 OIH 0.00037 0.01 - - NaI*(CA) 0.0185 0.05 1,100 1,400

I-131 OIH 0.011 0.3 - - NaI*(CA) 5.55 150 1,700 1,900

In-111 octreotate 0.185 5 - - WBC 0.037 1 - 50 Lu-177 octreotate 7.8 210 350 540 N-13 any 0.925 25 - -

O-15 water 1.85 50 - -

Ra-223 dichloride 0.00385 0.1 1,400 1,700 Rb-82 chloride 1.85 50 - -

DISIDA 0.296 8 1 10 DTPA 1.11 30 - -

DTPA aerosol 0.04 1 - -

glucoheptonate 0.74 20 - -

HAM 0.296 8 - 8 MAA 0.151 4 - -

Tc-99m+ MAG3 0.37 10 - -

MDP 1.11 30 - -

MIBI 1.48 40 - -

pertechnetate 0.37 10 - 6 PYP 0.555 15 - 7 RBC in vitro 1.11 30 - -

RBC in vivo 1.11 30 - -

sulfur colloid 0.222 6 - 5 WBC 0.37 10 - 5 Tl-201 chloride 0.148 4 - -

Zr-89 panitumumab 0.075 2 140 270

• Interruption time based on most restrictive infant thyroid do se equivalent for mothers with hyperthyroidism (HYP) or thyroid cancer (CA).

10% of the activity administered as I-123 (to consider nuclide contamination).

+ 24-hour interruption is generally applied to Tc-99m pharmaceuti cals.

A dash (-) indicates that no interruption of breastfeeding is required.

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3. Patient Specific Dose Calculations

The threshold activity and dose rate values provided in Section 1 were calculated using highly conservative assumptions to demonstrate dose limits in 10 CFR 3 5.75 following release of a generic patient without knowledge of patie nt-specific information. Licensees may release patients with larger activities or dose rates than that shown in Tables 1 and 2 by a pplying patient-specific information to demonstrate that the maximally exposed bystander is not likely to exceed 5 mSv (0.5 rem). Licensees must maintain a record of the basis authorizing patient release in accordance with the criteria in 10 CFR 35.2075(a). In the basis, licensee s must document any patient-s pecific modifying factors used in the calculation and a general description of how that information was acquired (e.g., patient interview, patient image, etc.). Patient instructions must match or be more limiti ng than patient-specific factors used to release patients to assure that dose limits will not likely be exceeded after release in accordance with 10 CFR 35.75.

Based on the same fundamentals in Equation 1, second-tier assessments include four additional terms with patient specific information. These terms are referred to as modifying factors. When patient-specific details are considered, the basic dose assessment shown in Equation 1 includes four unitless modifying factors

= 1.44 (Equation 7) where

= External dose equivalent, mSv 1.44 = Constant for reciprocal of the natural logarithm of 2

= Radiological (physical) half-life, h

= Dose-rate constant for a point source at 1 m,

= Activity of the radionuclide administered to the patient, G Bq

= Biokinetic modifying factor, unitless

= Occupancy modifying factor, unitless

= Geometry modifying factor, unitless

= Attenuation modifying factor, unitless

The external dose pathway is considered to be dominant, and int ernal dose pathways are not included. Therefore, the external dose equivalent,, in Equation 7 is also the TEDE.

When basic thresholds are calculated according to Equation 2, t he four modifying factors were not shown because they were each assigned a value of unity (1) acco rding to conservative assumptions. Refer to Appendix B (and Ref. 9) for modifying factor definitions and methods to determine patient-specific values. The patient-specific activity threshold is determined by modifying the basic activity threshold as follows

= (Equation 8)

where

= Basic activity threshold, GBq

= Patient-specific activity threshold at administration, GBq

Patient-specific activity thresholds for dose limits of 5 mSv ( 0.5 rem) for patient release and 1 mSv (0.1 rem) for issuing dose-minimizing instructions are deno ted as and, respectively.

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Patient-specific information is needed when a licensee utilizes modifying factors to demonstrate that release will not result in a dose in excess of limits contained in 10 CFR 35.75. Patient-specific information should be obtained by the licensee through discussi ons with the patient.

3.1 Release of Patients Based on the Administered Activity

To demonstrate compliance, licensees may calculate patient-specific thresholds on a case-by-case basis. Licensees can justify the release of patients with activities greater than the basic threshold listed in Column 1 of Table 1 by accounting for patient biokinetics, byst ander occupancy, exposure geometry, and patient attenuation factors. When licensees calculate a patient-specific activity threshold, (GBq),

according to Equation 8, the patient can be released when the administered activity, (GBq), does not exceed.

When the administered activity exceeds the patient-specific activity threshold ( > ),

licensees can consider releasing patients based on the measured dose rate according to Section 3.2 or based on a calculated hold time in Section 3.3.

3.2 Release of Patients Based on the Measured Dose Rate

Licensees may decide to release patients based on measuring the external dose rate at 1 m from the patient. As biokinetics, attenuation, and geometry already infl uence survey measurements, these factors must not be used to modify the measurement threshold because do ing so would underestimate dose.

Measured dose rates are independent of occupancy; therefore, modification of the measurement threshold is only permitted by considering the occupancy factor for the maximally exposed bystander.

When the measured dose rate at 1 m from a patient exceeds the b asic measurement threshold for patient release shown in Column 1 of Table 2, the licensee can either:

a. Calculate a patient-specific measurement threshold as by considering occupancy. Refer to Appendix B for calculating occupancy factor values.

b. Wait for the measured dose rate to decrease below the basic measurement threshold without considering occupancy.

c. Calculate a hold time described in Section 3.3.

3.3 Release of a Patient After a Hold Time

When the administered activity exceeds the patient-specific activity threshold for release, an administrative hold time,, shall be calculated based on administered activity as well as radioactive decay and biological removal via patient retention as follows

= ( ) ln (Equation9)

where

= Time after administration corresponding to the patients rad ionuclide retention, h

= Retention fraction of radionuclide in the patient at time, unitless Hold times are only needed when >. When radiopharmaceutical retention data are

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available for the patient (e.g., retention curve over time), th e hold time can be assigned to the time when the patients retention fraction equals. Refer to Appendix B, Section B.3 to determine and,

including how is calculated from these parameters. To confirm retention dat a, a dose rate from the patient should be measured prior to release from hold. The rat io of measured dose rate to the basic measurement threshold should b e generally consistent with (Section 3.2).

4. Instructions

4.1 Activities and Dose Rates That Require Instructions

In accordance with 10 CFR 35.75(b ), licensees must give instruc tions to released patients, including written instructions, on how to maintain doses to oth er individuals ALARA if the TEDE to any other individual is likely to e xceed 1 mSv (0.1 rem). Licensee s may always choose to provide instructions to keep radiation dose ALARA even if the dose limit is not like ly to be exceeded. Licensees may use Column 2 of Table 1 to determine the administered activity or C olumn 2 of Table 2 for the corresponding dose rates at 1 m above which i nstructions must be given.

To determine if dose-minimizing instructions are required based on activity thresholds:

a. Compare the administered radionuclide activity, (GBq), to the basic activity threshold for issuing instructions shown in Column 2 of Table 1, (GBq).

b. If the administered radionuclid e activity does not exceed the b asic activity threshold for instructions ( ), the patient can be released w ithout dose-minimizing instruct ions.

c. When patient-specific calculati ons are performed as described i n Section 3, the administered radionuclide activity can be compar ed to the patient-specific a ctivity threshold for issuing instructions, (GBq). Appendix B provides details on determining the modifyin g factors.

d. If the administered radionuclid e activity does not exceed the p atient-specific activity threshold for issuing instructions ( ), the patient can be released without dose-minimizing instruct ions.

e. Dose-minimizing instructions are required for cases when neithe r criterion b nor d are met. In addition, instructions must be i ssued if the basis for the occu pancy modifying factor relies on restrictions to patient behavior regarding time spent near byst anders.

The decision process for providing instructions based on activi ty thresholds is summarized in Figure 1.

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Figure 1. Patient instruction decision based on activity thresh olds.

Alternatively, the dose rate mea sured at 1 m can be compared to the instruction threshold. Note, measured dose rates are influen ced by patient biokinetics, radi oactive decay, geometric distribution, and attenuation so those factors shoul d not be used if patient spec ific dose rates are used for this determination.

For these reasons, the measured dose rate after administration can be compared to the basic measurement threshold divided by the occupancy modifying factor, (unitless). Refer to Appendix B for details on determining the occupancy modifying factor.

To determine if dose-minimizing instructions are required based on measurement thresholds:

a. Compare the measured dose rate at 1 m at administration, (mSv/h), to the basic measurement threshold for issuing instructi ons shown in Column 2 of Table 2, (mSv/h).

b. If the dose rate at administra tion does not exceed the basic me asurement threshold for instructions

( ), the patient can be released without dose-minimizing instruct ions.

c. If the dose rate at 1 m at the time of release, (mSv/h), does not exceed the basic measurement threshold divided by the occupancy modifying factor, the patient can be released without dose-minimizing instructions.

d. Dose-minimizing instructions are required for cases when neithe r criterion b nor d are met. In addition, instructions must be i ssued if the basis for the occu pancy modifying factor relies on restrictions to patient behavior regarding time spent near byst anders to ensure dose is unlikely to exceed dose limits in accord ance with 10 CFR 35.75.

Figure 2 summarizes the decision process for providing instruct ions based on measurement thresholds.

Figure 2. Patient instruction decision based on measured dose r ates at 1 meter.

If the patient is breastfeeding an infant or child, additional instructions may be required (refer to Sections 2 and 5.2).

4.2 Content of Instructions

This section describes differen t aspects that the licensee shou ld consider when developing patient release instructions before and after a patients treatment bas ed on discussions with the patient or caregiver. Generally, when a licensee releases a patient, it is to the patients home where family or other caregivers may be present. To pr ovide adequate release instruct ions under 10 CFR 35.75(b), the licensee should confirm the patient or caregiver ability to understand a nd follow the release instructions. The RG 8.39, Rev. 2, Page 20

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licensee must thoroughly ascertain the patients posttreatment destination(s) including means of travel to provide instructions and recommende d restrictions to maintain doses ALARA and ensure that the dose limit will not likely be exceeded. Note that the proposed pretr eatment plans made days before treatment may change and the instructions that were developed based on those plans may need to be changed to reflect the actual arrangements made the day of administration.

I-131 is currently the medical radioisotope of highest concern, as it is the most commonly used radionuclide in radiopharmaceutical therapy and has the potenti al for a higher external exposure to members of the public because of its high-energy gamma emission and potential volatility (Ref. 10).

However, the regulations in 10 CFR 35.75 apply to other medical radioisotope therapies such as yttrium (Y)-90, I-125, lutetium (Lu)-177, and radium (Ra)-223. Instructions should be specific to the type of treatment given and should include additional information for t he patients posttreatment situations. Note that instructions that are needed to meet the requirements for release should also not interfere with or contradict the best medical judgm ent of the treating physician. Instructions should include a telephone number for the patient to contact with any questions.

4.2.1 Pretreatment Discussions on the Administration of Radiopharmaceuticals

Engaging the patient, and caregi ver or family member, early in the treatment process (i.e., during treatment planning) may help the licensee better familiarize the patient and caregiver or family member with the treatment procedures, posttreatment radiation safety p recautions, and protective measures to minimize radiation exposure to b ystanders. In addition, prerelease discussions are necessary if licensees intend to use patient-specific modifying factors such as occupancy as part of their release basis. The prerelease discussion also lets the licensee make appropriate a rrangements if the patient cannot be immediately released (i.e., arrange a temporary hold or hospita lization if necessary). Early engagement helps to identify any patient-specific aspects that may prohibit release after treatment due to the potential of exceeding the 10 CFR 35.75 do se limit, determine whether the patient will be able to follow necessary release instructions, and allow time for the patient or caregivers to ask questions on following instructions to keep doses ALARA. If the licensee determines that the patients posttreatment plansincluding planned mode of transportation, posttreatment destination(s), o r any instructions that it believes the patient cannot followare likely to cause a dose to bystanders that wil l exceed 5 mSv (0.5 rem), the licensee cannot release the patient until the dose to bystanders is not likely to exceed 5 mSv (0.5 rem). This discussion should include medical issues such as complications, side effects, and dietary and medication changes, as appropriate.

As soon as radiopharmaceutical or implant therapy is considered as a treatment option, the licensee should interview the patient or caregiver, or both, to fully as sess the patients specific circumstances, especially if the licensee intends to use patient-specific occupancy factors. The licensee and patient or caregiver should discuss and consider the following topics duri ng the pretreatment discussion:

a. What type of posttreatment lodging (e.g., single family home, g roup home, apartment, nursing home, hotel, detention facility) will the patient use?

b. What are the patients plans for travel to his or her posttreatment recovery location?

(1) Will the patient use a private vehicle, taxi service, ride-book ing service, or public transportation (i.e., bus, train, or airplane)? The use of pub lic transportation should be discouraged.

(2) If the patient is traveling with other individuals, what is the duration of the trip? Based on the duration of the trip, can the patient keep an adequate distance from others? Emphasis RG 8.39, Rev. 2, Page 21

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should be made to minimize the number of traveling companions.

(3) Will the patient be traveling internationally post treatment? Patients who travel via motor vehicles through international border checkpoints or on airplan es are subject to screening for radiation. Patients should be advised of this fact and provided appropriate documentation (procedure, isotope, date/time of release, treati ng facility and physician, contact information, etc.) to present to officials when alarms are triggered.

c. Which household members, if any, will be present at the patients posttreatment recovery location?

For example, consider their age and gender and whether there is a nursing infant or pregnant woman in the household.

d. Can the patient be appropriately isolated from others in the ho usehold after treatment?

e. Can the patient take care of himself or herself, and is he o r she capable of complying with the release instructions?

f. Can the patient sleep alone in a separate bedroom or area?

g. Is the patient incontinent?

h. Are there any necessary household or dietary changes, or fluid intake restrictions (e.g., preexisting medical conditions)?

i. Are there any factors that might prevent treatment (e.g., br eastfeeding, pregnancy)?

j. Can the patient delay their return to work? What kind of wo rk does the person do (e.g., daycare provider)?

k. What are the potential restrictions on burial or cremation s hould the patient pass away within a certain period of time following treatment?

By gathering this information be fore the treatment (i.e., during the treatment planning stage) when the activity to be administered is expected to exceed the basic activity threshold for release, the licensee can begin to estimate patient-specific modifying factors for use in the release calculations. This information can be used to (1) provide a patient-specific estimate of the l ikely cumulative dose to other members of the public, (2) direct appropriate pro tective measures, (3) allow the licensee to make arrangements if the patient cannot be immediately released (i.e. arrangements to temporarily hold the patient or hospitalize the patient), (4) allow the patient time to plan for his or her pot ential isolation after release, and (5) allow the licensee to assess the patients capacity to understand the procedure and precautions to ensure dose limits in 10 CFR 35.75 will not likely be exceeded. Note that immediately prior to treatment, licensees should verify that the patients plans d id not change in a way that wo uld alter the patient-specific factors used in release calculations which might require a different plan (i.e., need for instructions or inability to release at planned time) or content of the final release instructions.

4.2.2 Patient Instructions

To comply with 10 CFR 35.75, the licensee must ensure that the radiation dose to bystanders is not likely to exceed 5 mSv (0.5 rem) from a released patient who ha s been administered radiopharmaceuticals or permanent implants that contain radioactive material before releasing the patient. It is understood that once a patient is released, the licensee has no control of the patient. However, licensees can rely on RG 8.39, Rev. 2, Page 22

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discussions with the patients where the patient or caregivers d emonstrate they are able and willing take the necessary precautions described in instructions to ensure dose to the maximum bystander is not likely to exceed 5 mSv (0.5 rem) from the released patient. In addition, patient instructions must be given to keep exposures ALARA in accordance with 10 CFR 35.75(b).

The instructions should be appropriate and easy to follow to en able the patient to understand how to minimize radiation exposure t o bystanders (Ref. 7). Consideration should be given to providing instructions in the patients n ative or primary language. For most therapies, experience shows that radiation exposure from patients can be safely controlled throu gh appropriate treatment specific release instructions provided by licensees and followed by patients. However, if the patient or caregiver is mentally, physically unable, or will not agree to comply with t he release instructions, the licensee may have to consider holding the pa tient as an in-patient following treatment until the patient can be released without having to follow any specific instructions. The license e must hold the patient as an in-patient following treatment in these ca ses until the dose to bystanders is not likely to exceed 5 mSv (0.5 rem) without the instructions the pa tient cannot or will not follow.

The list below provides some basic posttreatment instructions t hat the patient may need to follow for managing radiation exposure to bystanders. The instructions should always be tailored to the specific patient situation and type and amount of radioactive material administered or implanted. To ensure dose limits are not likely to be exceeded, licensees must ensure patients can follow instructions if they are used to justify patient-specific modifying factors to demonstrate ex posures will be less than 5 mSv (0.5 rem).

Pre-treatment discussions with patients, or caregivers, such as those described in the section above, can help a licensee determine if a p atient is able to follow the in structions and identify patients who cannot. If a patient is unable or unwilling to follow necessary instructions for release, they may need to be held longer than others with similar administrations. Instruction should also be realistic and provide how long the precautions should be followed. As a guideline, the licensee may consider using several (three to five) effective half-lives of the administered radionuclide for the i nstruction duration.

a. Wash hands frequently and bathe daily.

b. Wash laundry separately from others.

c. Use dedicated or disposable kitchen utensils, and do not share them with others.

d. Use a dedicated sole-use bathroom, if possible. Always sit on t he toilet. Flush the toilet twice after each use.

e. Use disposable gloves and wipes when cleaning.

f. Discard trash separately and hold it to allow for radioactive d ecay.

g. Sleep alone in a separate bedroom.

h. Abstain from any intimate contact.

i. Avoid preparing or sharing food with others.

j. Avoid using public transportation.

k. Maintain good hydration, as directed by a physician.

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l. Minimize the amount of time in close proximity to other people, especially children and pregnant women.

The licensee should instruct family members and caregivers to n otify the treating medical facility of a medical emergency or if a patient dies. Further informatio n on death of a patient following radiopharmaceutical administration or implants can be found in Section 4.3. The licensee should also inform the patient on how to clean up an area contaminated with body fluids (e.g., urine, vomit) and how to dispose of the cleaning materials.

4.2.3 Patient Acknowledgment of Instructions

The patient should acknowledge receipt of instructions before he or she is released, and the licensee may acknowledge that the patient received the instruct ions as communicated using a form signed by both parties. Through the fo rm, the patient acknowledges the receipt of the following:

a. He or she has received a clear explanation of the treatment pro cess prior to treatment.

b. He or she has been informed of the need to limit exposure to ot hers, especially to young children and pregnant women, and has been informed on how long he or she must exercise special care.

c. He or she has discussed with the healthcare provider final plan s for the following:

(1) transportation from the clinic to home or to the posttreatment destination;

(2) arrangements for protecting others once he or she has arrived a t the posttreatment destination;

(3) minimization of the exposure of people both inside and outside the home;

(4) management of biological wastes and trash;

(5) emergency care; and

(6) contact information (i.e., the n ame and telephone number of a knowledgeable person) if questions arise about the radiation safety instructions during the recovery period.

4.2.4 Patient Precautions

The licensee should consider the following precautions or measures for most patients to minimize exposures to others and to keep radiation exposures to others a t or below the 5-mSv (0.5-rem) limit. The patient precautions can be considered by the licensee but are not requirements of the NRC. The licensee should use judgement with the ins tructions needed for the patient on a case-by-case basis based on the treatment. The licensee should discuss the following precautions and measures with the patient as appropriate. Note that this list is not inclusive and should be modified for each treatment or radioactive material administered.

a. The greatest radiation dose potential to bystanders from the released patient is from external exposure. Therefore, the most important precautions to take are measures to reduce or avoid the radiation exposure emanating fro m the patient, especially in the early time period after the administration.

(1) Emphasize the importance of keeping an adequate distance from o thers, especially RG 8.39, Rev. 2, Page 24

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children and pregnant women. Can a rrangements be made for famil y members (including children and any pregnant house hold members) to lodge elsewhere temporarily? Or can another individual come and take care of the children and any pregnant household member in their home?

(2) If the patient is traveling with other individuals to a post tr eatment lodging location, emphasis should be made to mini mize the number of traveling com panions and to maximize the distance from the patient.

(3) Emphasize abstention from all forms of intimate contact.

b. The release instructions may include measures that are necessary to limit the transfer of radioactive contamination to oth ers. The licensee should provide specific information on how to limit direct contact with others and on measures necessary to l imit the contamination of objects, surfaces, and the spread of radioactive contamination. Patient education and awareness of how to minimize, isolate, and clean radioactive contamination is impor tant in minimizing exposure to others.

(1) Encourage the patient not t o prepare or share food with others.

(2) Encourage the use of a bathroom reserved exclusively for the patient, if possible.

(3) Encourage the use of kitchen utensils that are dedicated solely to the patient (i.e., not shared with other household members) and that are washed separately from other dishes.

Alternately, encourage patients to us e disposable eating utensils.

(4) Encourage the use of disposable gloves and wipes and frequent hand washing.

(5) Encourage the laundering of a patients clothing separately from another household members clothing.

(6) Advise the patient on the recommended length of time he o r she should wait before becoming pregnant to minimize radiation exposures to a de veloping fetus.

(7) Discuss how to clean up an area contaminated with body fluids ( e.g., urine, vomit) and how to dispose of cleaning materials.

(8) Evaluate the need to dispose of patient-related trash in a separate strong plastic bag that is not mixed with other household member s trash, holding the patients trash to allow for radioactive decay and implementing ways to reduce radiation exposure from this trash.

Holding trash to allow for radioactiv e decay will be important as most landfills can detect the radiation and send the trash back to the patient.

(9) Discuss how the patient may contact the licensee if needed. Pro vide information to a family member or caregiver to contact the treatment medical facility if the patient has a medical emergency or passes away.

(10) In the case of a medical emergency, the patient, or a caregiver or family member, should inform the ambulance or the emergency care location of the rece ntness of the radioactive therapy treatment.

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(11) Provide posttreatment release instructions to the patient verba lly and in writing, including how long he or she should follow the release instructions.

The licensee may encourage patients to have available plastic bags, disposable gloves and wipes before treatment. The licensee should provide specific informat ion on how to limit direct contact with others and on measures necessary to limit the contamination of objects, surfaces, and the spread of radioactive contamination. Patient education and awareness of h ow to minimize, isolate, and clean radioactive contamination is im portant in minimizing exposure t o others.

With regard to female patients of child-bearing age, the NRC recognizes that pregnancy tests have limited ability to detect early pregnancies. The NRC encourages licensees to advise their patients to contact the licensee immediately if a female patient discovers that she was pregnant at the time the medical treatment was administered. Licensees must report any dose to an embryo or fetus that is greater than the 50-mSv (5-rem) dose equivalent resulting from the treatment to a pregnant individual unless the authorized user specifically approved the dose to the embryo or fetus in a dvance in accordance with 10 CFR 35.3047, Report and Notification of a Dose to an Embryo/Fetus or a Nurs ing Child.

Patients receiving radiopharmaceutical treatment need to be awa re that they might trigger the alarms of radiation detectors at national borders, at airports, at cruise ports, within cities, or at their place of employment for several weeks or months following treatment. Consequently, the licensee should consider issuing the patient a l etter or card that contains app ropriate information about the treatment in case any officials need to verify that information.

4.3 Death of a Patient Following Radiopharmaceutical Administration or Implants

The licensee should instruct the patients family to notify the treating authorized user and the radiation safety office (RSO) immediately if a patient has died after recent administration of a therapeutic quantity of radioactive material. If the death occurs in an NR C licensed hospital, the hospital should have internal procedures to handle th e death of a radioactive patient. If the hospital does not have a radioactive material license, the licensee that administered the radioactive material or a nearby licensee should provide radiation safety support inform ation to the non-licensed hospit al to control access to the room occupied by the deceased.

For the vast majority of administered radiopharmaceuticals, act ivity levels in released patients will not result in radioactive cadave r exposure exceeding the dose limits of 10 CFR Part 20. However, the analysis of administration of 131I (in five different pharmaceuticals), 166Ho, 177Lu, and 188Re indicates that dose rates exceeding 0.02 mSv/h (2 mrem/hr) or total doses in e xcess of 1 mSv (0.1 rem) are possible if unexpected death were to occur w ithin days of release and knowl edge of the radioactive administration is not communicated (Ref. 9). Depende nt on administered activity of a given pharmaceutical and timing of unexpected patient death, the potential exists for exceeding a regulatory limit for several identified procedures. Radionuclides with a hypothetical total dose to a b ystander above 1 mSv (0.1 rem) exceeded the limit by no more than a factor of two with conservative exp osure assumptions. Dose rates, however, are more restrictive because potential dose rates were found to exceed 0.02 mSv/h (2 mrem/hr) by more than an order of magnitude at s hort times after patient release. From a patient death perspective, limiting dose rate to an acceptable level for all radionuclides will be protective in terms of total dose. No radioactive implant was identified as potentially important fro m the perspective of external exposure following patient death. For patient death outside the medical facility, there is a low likelihood that regulatory limits on external dose would be exceeded if the radioactive implant were to remain in place.

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The RSO should be consulted to d etermine the amount of activity remaining in the deceased patient and a determination shoul d be made if there are any sta te or municipal restrictions on burial or cremation.

a. If the activity remaining in the body results in an external do se that is greater than regulatory public dose limits of 10 CFR Part 20, the RSO should determine the radiation precautions that should be followed.

b. Precautions should be based on dose limits, a generic safety as sessment of the need for monitoring personnel who carry out these procedures, the need for monitori ng the premises, the need for minimizing external radiation exposure, and the potential for c ontamination (Ref. 3).

The administering licensee should provide precautions to the fa mily members and the public to follow during visitation prior to burial or internment.

5. Records

5.1 Records of Release

The NRC has no requirement for recordkeeping on the release of patients who were released in accordance with the information in Column 1 of Table 1. However, if the release of the patient is based on a dose calculation that considered retained activity, an occupa ncy factor of less than 0.25 at 1 meter, the effective half-life, or shielding by tissue, 10 CFR 35.2075(a) requires the licensee to maintain a record of the basis for authorizing the patients release. Therefore, calculating and releasing patients based on patient-specific thresholds will often require a record unless the occupancy factor is greater than 0.25 and geometry, biokinetic, and attenuati on factors are equal to or greater than 1.

This record should include the pa tients identifier in a way that ensures that confidential patient information is not traceable or attributable to a specific pati ent, the radioactive material administered, the administered dosage, and the date of the administration. In add ition, depending on the basis for authorizing the release of patients, records should include the following i nformation:

a. For Immediate Release of a Patient Based on a Patient-Specific Calculation. The record shall include the basis for authorizing release in accordance with 10 CFR 35.75, including the equation used and bases for the patient-sp ecific modifying factors (see Appendix B to this guide). As exposure is highly dependent on patient-specific behavior follo wing release, use of generic instructions without patient acknowledgment that they can follo w them is not an appropriate basis to modify occupancy factors to demonstrate compliance with 10 C FR 35.75. Examples of appropriate bases for occupancy factors include patient questionnaires or notes from discussions with patients to discuss their intended behavior following trea tment and acknowledge they can follow instructions as given. In some situations, a calculation may be case specific for a class of patients who all have the same pa tient-specific factors. In this case, the record for a particular patients release may reference the calculation for the class of patients, but a basis may be necessary to demonstrate how this patient meets the class of patients. See Appendix C for additional examples of appropriate bases for other modifying fa ctors.

b. For Immediate Release of a Patient Based on a Measured Dose Rate. The record should include the results of the measurement, the specific survey instrument used, and the name of the individual performing the survey.

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c. For Delayed Release of a Patient Based on a Radioactive Decay Calculation. The record should include the time of the administration, the date and tim e of release, and the results of the decay calculation. If release is based on patient-specific calculations in addition to radioactive decay, then the record should include items listed in a.

d. For Delayed Release of a Patient Based on a Measured Dose Rate. The record should include the results of the survey meter measurement, the specific survey instrument used, and the name of the individual who performed the survey. If release is based on patient-specific calculations in addition to measured dose rate, then the record should include items listed in a.

Records should be kept in a ma nner that ensures the patients p rivacy and confidentiality (i.e., the records should not contain the p atients name but instead a pat ient identification number, date, and treatment type). These recordkeeping requirements may be used to verify that licensees have proper procedures in place for assessing bystander exposure associated with and arising from exposure to patients administered radioactive material.

5.2 Records of Instructions for Breastfeeding Patients

If a patients failure to interrupt or discontinue breastfeedin g could result in a dose to the infant or child in excess of 5 mSv (0.5 rem), 10 CFR 35.2075(b) requires a record that the licensee gave the patient instructions. For the radiopharmaceuticals commonly used in medical diagnosis and treatment, Column 1 of Table 3 lists the activities that require such records when administered to patients who are breastfeeding. The record should include the patients identifi er, the radiopharmaceutical administered, the administered dosage, the date of the administration, and whethe r instructions were provided to the patient who could be breastfeeding an inf ant or child. The patients id entifier should be prepared in a way that ensures the confidentiality of the information.

6. Material Separated from the Patient

While public dose limits in 10 CFR Part 20 do not apply to expo sure from individuals administered radioactive material and released under 10 CFR 35. 75 as described in 10 CFR 20.1003, dose limits in 10 CFR Part 20 do apply to exposure from radioactive material separated from a released patient, such as contaminated bodily fluids, dislodged implants or sourc es. Public dose limits in 10 CFR Part 20 apply to all members of the pub lic, other than the patient, whe n exposure is from the radioactive material separated, excreted, removed, or dislodged from a patients body. If a licensee discovers a member of the public exceeds the public dose li mits in 10 CFR 20.1301 from ra dioactive material no longer affixed to a released patient, licensees must report the event in accordance with 10 CFR 20.2203.

Licensees should ensure all tempor ary and permanent implants are affixed to the patient so that they are highly unlikely to become dislodged. Patients must not be released from the licensed facility if it is possible under normal conditions for a source to become dislodged and separated from the patient. If there is a potential for a source to become dislodged under uni que situations, licensees must have preventative measures in place to ensure public dose limits are not exceeded. Licensees must report lost sources in accordance with 10 CFR 20.2201 if an implant becomes dislodged and is not recovered or if temporary implants issued to a patient are not returned to the licensee. In addition, licensees must have written procedures to determine if a medical event as defined i n 10 CFR 35.3045 has occurred in accordance with 10 CFR 35.41. If a patient is released in accordance with 10 CFR 35.75 while treatment is ongoing, these procedures need to include how a licensee will d etermine if the source moved or became dislodged to determine if a medical event occurred.

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which could result in increased exposure from radioactive mater ial in body fluids, excreted in urine or feces to ensure dose limits are not exceeded. For example, if a patient proposed to receive radiopharmaceutical therapy is incontinent or requires dialysis an evaluation is necessary to determine if a bystander could be exposed in excess of public limits listed in 10 CFR 20.1301 by material separated from the patient. If it appears the bystander could be exposed in ex cess of the public limits, the licensee must consider actions to ensure the public dose limits are not exceeded, such as ensuring the patient can manage their own waste, provide shielde d containers for waste, or hold the patient at the licensees facility until it is possible to release the patient. Dialysis is another patient -specific situation for which additional patient-specific evaluation may be necessary. For additional awareness, licensees may need to have supplementary controls to minimize dose to the patients organs or tissues ot her than the treatment site, such as the skin, due to unique patient-specific conditions such as incontinence. Licensees must report a medical event as defined in 10 CFR 35.3045 even if the exposure occurs after the patient is released under 10 CFR 35.75.

D. IMPLEMENTATION

The NRC staff may use this regulatory guide as a reference in its regulatory processes, such as licensing, inspection, or enforc ement. Backfitting, forward fit ting, and issue finality considerations do not apply to 10 CFR Part 35, Medical Use of Byproduct Material licensees and applicants because 10 CFR Part 35 does not include backfitting or issue finality provisio ns and the forward fitting policy in Management Directive 8.4, Mana gement of Backfitting, Forward F itting, Issue Finality, and Information Requests, (Ref. 13) does not apply to these licensees.

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REFERENCES

1. U.S. Code of Federal Regulations, Medical Use of Byproduct Material, Part 35, Chapter 1, Title 10, Energy.

2. U.S. Nuclear Regulatory Commission (NRC), NUREG-1556, Consolid ated Guidance about Materials Licenses: Program-Specific Guidance about Medical Use Licenses, Volume 9, Washington, DC.2

3. National Council on Radiation Prot ection and Measurements (NCRP) Report No. 155, Management of Radionuclide Therapy Patients, Bethesda, MD: De cember 2006.3

4. NCRP Report No. 37, Precautions in the Management of Patients Who Have Received Therapeutic Amounts of Radionuclides, Bethesda, MD, October 1, 1970.

5. NRC, Nuclear Regulatory Commiss ion International Policy Statement, Federal Register, Vol.

79, No. 132, July 10, 2014, pp. 39415-39418.

6. NRC, Regulatory Guides, Management Directive 6.6, ADAMS Accession No. ML18073A170.

7. IAEA, Safety Reports Series No. 63, Release of Patients after Radionuclide Therapy, Vienna, Austria, 2009.

8. NRC, Advisory Committee on Medical Uses of Isotopes, Subcommit tee Review and Comments on Draft Final Proposed Regulatory Guide 8.39, Release of Patients Administered Radioactive Materials, Revision 1 (Phase 1), Washington, DC, Final Report, March 25, 2020. (ADAMS Accession No. ML20085H267).

9. RCD Radiation Protection Associates. Activity Thresholds, Pati ent-Specific Modifying Factors, Breastfeeding Interruption Times, and Other Supporting Data, Research Information Letter Report for Phase 2 Revisions to Regulatory Guide 8.39: Release of Patients Administered Radioactive Material. RCD-21-181-0. Corvallis, OR. June 30, 202 1. (ML21214A223)

10. NRC, SECY-18-0015, Staff Evalua tion of the U.S. Nuclear Regula tory Commissions Program Regulating Patient Release after Radioisotope Therapy, Washing ton, DC, January 29, 2018.

[ADAMS Accession No. ML17279B139 (package)].

11. Peplow, D.E. Specific gamma-ray dose constants with current emission data. Health Physics.

118(4): 402-416; 2020.

12. Smith, D.S.; Stabin M.G. Exposure rate constants and lead shielding values for over 1,100 radionuclides. Health Physics. 102(3): 271-291; 2012.

2 Publicly available NRC published documents are available electronically through the NRC Library on the NRCs public Web site at http://www.nrc.gov/reading-rm/doc-collections/ and through the NRCs Agencywide Documents Access and Management System (ADAMS) at http://www.nrc.gov/reading-rm/adams.html. The documents can also be viewed online or printed for a fee in the NRCs Public Document Room (PDR) at 11555 Rockville Pike, Rockville, MD. For problems with ADAMS, contact the PDR staff at (301) 415-4737 or (800) 397-4209; fax (301) 415-3548; or e-mail pdr.resource@nrc.gov.

3 Copies of reports from The National Council on Radiation Protection and Measurements (NCRP) may be obtained through its Web site: http://www.ncrponline.org/Publications/Publications.html] or by writing to the NCRP at 7910 Woodmont Avenue, Suite 400, Bethesda, Maryland 20814-3095, Phone: 301-657-2652, fax: 301-907-8768.

RG 8.39, Rev. 2, Page 30

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13. NRC Management Directive 8.4, Management of Facility-Specific Backfitting and Information Collection, Washington, DC.

RG 8.39, Rev. 2, Page 31

Draft for ACMUI Review APPENDIX A RADIONUCLIDE DATA TABLES

Table A-1. Radiological Half-Lives and Dose-Rate Constants for Radionuclides

RADIOLOGICALc DOSE-RATE CONSTANTd RADIONUCLIDE HALF-LIFE, (days) AT 1 METER, Ag-111 7.45 0.00442 At-211 0.3006 0.0288 Au-198 2.696 0.0615 Bi-213 0.0317 0.0218 C-11 0.0142 0.154 C-14b 2,080,000 0.00000502 Cr-51 27.703 0.00465 Cs-131 9.689 0.0144 Cs-131 implanta 9.689 0.0130 Cu-64 0.5292 0.0277 Cu-67 2.576 0.0150 Dy-165 0.09725 0.00464 Er-169b 9.4 0.000121 F-18 0.0762 0.148 Ga-67 3.261 0.0207 Ga-68 0.04702 0.143 Ho-166b 1.117 0.00507 I-123 0.553 0.0390 I-124 4.176 0.167 I-125 59.4 0.0332 I-125 implanta 59.4 0.0291 I-131 8.0207 0.0576 In-111 2.8047 0.0798 Ir-192 73.827 0.125 Ir-192 implanta 73.827 0.121 Kr-81m 0.000152 0.0385 Lu-177 6.647 0.00527 N-13 0.00692 0.154 O-15 0.00141 0.154 P-32b 14.263 0.00105 P-33b 25.4 0.0000887 Pd-103 16.991 0.0306 Pd-103 implanta 16.991 0.0220 Ra-223 11.43 0.0475 Rb-82 0.000884 0.172 Re-186 3.7183 0.00631 Re-188b 0.7085 0.0127 Ru-106b 373.59 0.00000212 Ru-106b implanta 373.59 0.00000188 Sc-47 3.3492 0.0140 Se-75 119.78 0.153 Sm-153 1.938 0.0115

RG-8.39, Rev. 1, Appendix A, Page A-1 Sn-117m 13.76 0.0364 Sr-89b 50.53 0.000875 Sr-90b 10,508 0.000255 Tc-99m 0.2506 0.0194 Tl-201 3.038 0.0405 Xe-127 36.41 0.0535 Xe-133 5.243 0.0128 Y-90b 2.67 0.00157 Yb-169 32.026 0.0477 Zr-89 3.267 0.207

a. Implants and eye plaques assumed to be encapsulated in 50 m of titanium

b. Greater than 5% of due to bremsstrahlung production

c. Nuclear decay data based on International Commission on Radiological Protection (ICRP) Publication 107 (Ref. A-1)

d. External dose equivalent rate to tissue from photon and electron emissions with bremsstrahlung for a point source surrounded by an infinitely thin sphere of tissue (Ref. A-2)

RG 8.39, Rev. 2, Appendix A, Page A-2 REFERENCES FOR APPENDIX A4

A-1. International Commission on Radiological Protection. Nucle ar Decay Data for Dosimetric Calculations. Annals of the ICRP. Publication 107. Vol. 38(3); 2008.

A-2. RCD Radiation Protection Associates. Activity Thresholds, Patient-Specific Modifying Factors, Breastfeeding Interruption Times, and Other Supporting Data, Research Information Letter Report for Phase 2 Revisions to Regulatory Guide 8.39: Release of Patients Administered Radioactive Material. RCD-21-181-0. Corvallis, OR. June 30, 202 1. (ML21214A223) 1

16. Publicly available NRC published documents are available electronically through the NRC Library on the NRCs public Web site at http://www.nrc.gov/reading-rm/doc-collections/ and through the NRCs Agencywide Documents Access and Management System (ADAMS) at http://www.nrc.gov/reading-rm/adams.html. The documents can also be viewed online or printed for a fee in the NRCs Public Document Room (PDR) at 11555 Rockville Pike, Rockville, MD. For problems with ADAMS, contact the PDR staff at (301) 415-4737 or (800) 397-4209; fax (301) 415-3548; or e-mail pdr.resource@nrc.gov.

RG 8.39, Rev. 2, Appendix A, Page A-3 APPENDIX B

PATIENT-SPECIFIC MODIFYING FACTORS AND METHODS

Licensees may authorize the release of 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 i s not likely to exceed 5 mSv (0.5 rem) in accordance with 10 CFR 35.75(a). Basic activity thresholds provided in Table 1 were calculated using conservative assumptions so that they can be used without patie nt-specific information to demonstrate that the release of an individual is unlikely to exceed 5 mSv (0.5 rem) (see Section 1 of the Regulatory Guidance). However, licensees can release patients above these thresholds if patient-specific information is known and demonstrates that the maximally exposed bystander is not likely to exceed 5 mSv (0.5 rem) from exposure to the released individual in accordance with 10 CFR 35.75(a). Consistent with Section 3, patient-specific modification includes four factors:

= 1.44 0 (Equation B-1) where

= External dose equivalent, mSv 1.44 = Constant for reciprocal of the natural logarithm of 2

= Radiological (physical) half-life, h

= Dose-rate constant for a point source at 1 m,

= Activity of the radionuclide administered to the patient, G Bq

= Biokinetic modifying factor, unitless

= Occupancy modifying factor, unitless

= Geometry modifying factor, unitless

= Attenuation modifying factor, unitless

Several acceptable approaches for determining the modifying factors are presented in this appendix. The likely dose to the maximally exposed bystander (i.e., person for whom the product of modifying factors is greatest) must be determined for demonstra ting compliance with 10 CFR 35.75. To demonstrate TEDE is below 5 mSv (0.5 rem), modifying factors for biokinetics, occupancy, geometry, and attenuation are incorporated int o a patient-specific activity threshold as follows

= (Equation B-2)

where

= Basic activity threshold, GBq

= Patient-specific activity release threshold at administration, GBq

Patient-specific activity thresholds should be calculated prior to administration. This assures the licensee and the patient are prepared in case it is determined the patient needs to be held following treatment. In addition, this allows the licensee to determine appropriate and realistic modifying factor values and determine if the pa tient will have to follow any instructions to assure dose limits are not exceeded. Licensees should confirm any instructions needed to ensure dose limits are ones that the patient can and is willing to follow prior to administration as a patient might not be able to be released in accordance with 10 CFR 35.75 if a licensee learns a patient is not able to follow them after administration. If a licensee decides to perform a patient-specific calculation for a breastfeeding infant or child, further information is available (Ref. B-1).

RG-8.39, Rev. 1, Appendix B, Page B-1 Modifying factors for geometry and attenuation can take values greater than 1 as described below. The assumption of unity for occupancy and biokinetics provides significant conservatism such that this possibility is unlikely to lead to exposures greater than 5 mSv (0.5 rem). However, if a licensee chooses to use more realistic, patient-specific information to modify occupancy or biokinetic factors such that a record is required per 10 CFR 35.2075, a basis for geome try and attenuation factors must also be provided as values could realistically be greater than 1. Atte nuation plots are available for 40 radionuclides (Ref. B-1). When adde d realism is incorporated by applying patient-specific information to other modifying factors, licensees should also estimate an atte nuation factor for the patient. Note that in some cases attenuation factors may be greater than 1 due to bui ldup of scattered radiation. The combination of geometry and attenuation factors should be defen sible or conservative for the patient.

A patient questionnaire, such as that shown in Figure B-1, whil e not required, is one acceptable method to gather patient-specific information. Modification of the survey is encouraged for the types of procedures performed at the medical facility. Licensees may ne ed additional discussions based on the patients responses to the questions to determine patient specific modifying factors.

RG 8.39, Rev. 2, Appendix B, Page B-2 Figure B-1. Example Patient Questionnaire for Determining Patie nt-Specific Modifying Factors.

To Be Completed by the Licensee Patient Identification Number Patient is able and willing to fo llow discharge instructions including behavior restrictions based on discussions prior to administration? yes no Estimate the patients overlying tissue for attenuation and bui ldup: ______ cm Is a patient-to-bystander distance less than 1 m expected with a geometric modifying factor greater than 1? yes no To Be Completed with Patient Input How long is the return trip home?

Will someone accompany you on the return trip home? yes How will you be no train plane othereturning home? my vehicle bus taxi r When will you Do you spend more than 10 hours1.157407e-4 days <br />0.00278 hours <br />1.653439e-5 weeks <br />3.805e-6 months <br /> per week closer than 10 yes return to work? feet from the same person at work? no Who do you see in person on a routine basis?

Do you anticipate spending more than yes If yes, at what an hour a day closer than arms length distance and (1 meter) from another individual? no for how long?

getting on and off Do you/have you ever chairs walking using the restroom bathing needed help with the getting in and out cooking/ reading/understanding following tasks? of vehicles eating instructions none of the above

Do you live in an apartment or facility with other people in ad jacent rooms/on adjacent floors? yes no Are you currently nursing yes Could you be pregnant? yes Do you share a bed with anyone? yes (breastfeeding) a child? no no no Are you able to sleep in your own bed without another person fo r some length of time after the yes procedure? no

Are you able and willing to change your behavior as directed by the specific preliminary posttreatment yes instructions discussed with and explained to you to minimize ex posure to bystanders? no Are you able and willing to change your behavior as directed by the specific final posttreatment yes instructions discussed with and explained to you to minimize ex posure to bystanders? no To Be Completed the Day of Administration by Licensee

Confirm appropriate changes were made to the form and calculati ons if patient plans changed. yes no

RG 8.39, Rev. 2, Appendix B, Page B-3 B.1 Modifying Factor for Occupancy,

The occupancy factor represents the total number of radionuclid e disintegrations during the bystanders close contacts with the patient relative to total disintegrations in the patient. Behaviors during early times after release have a greater relative importance when the effective half-life of the administered radiopharmaceutical is short. To accommodate a large range of potential patient-specific factors, bystander behaviors, and occupancy values, is calculated by applying the effective half-life of the radiopharmaceutical in two parts: (1) bystander exposure during the patients travel from the medical facility; and (2) bystander exposure to the patient after trave l. Note if biological half-life is not known, physical half-life can be used in place of effective half-life.

Occupancy is calculated for short-term exposure during travel a s and long-term exposure after travel as. If the same bystander is exposed during travel and after trav el, add them such that equals

+. Compliance must be demonstrat ed for the maximally exposed bystander. Licensees should note that the maximally exposed bystander is not always the bystande r with the highest occupancy but is likely the bystander who has the highest product of both the geometry and occupancy factors. When the licensee instructs a patient to follow specific behavior restrictions, t he occupancy factor can be based on anticipated bystander exposure, including appropriate and reali stic restricted behavior when the patient states they are able and willing to follow the instructions. Th e instructions issued to the patient must communicate those same restrictions if they are used as basis to demonstrate dose limits will not be exceeded. If a patient or caregiver states they are unable or unwilling to follow the appropriate instructions, occupancy factor will need to be modified accordi ngly. Note and can be 0 if a bystander does not have contact with the patient during the tra vel or post-travel time periods, respectively.

Occupancy during travel is calculated as

=. ( ). ( ) (Equation B-3) where

= Occupancy factor for the maximally exposed bystander during travel, unitless

= Fraction of time bystander spends in close contact with the patient during travel, unitless

= Time between medical administration and patient release in effective half-lives, unitless

= Travel duration in effective half-lives, unitless

In many travel situations (e.g., plane, bus, car) when the pati ent travels with a companion, the bystander exposure fraction for close contact with the patient can be con servatively assumed to be 100% ( 1).

When it is advantageous, Equation B-3 can also accommodate single exposure events for which the start and end times may be different from travel.

Occupancy during potential long-term exposure after travel is c alculated as

=. ( ). ( ) +. ( ) (Equation B-4) where

= Occupancy factor for the maximally exposed bystander after travel, unitless

= Fraction of time bystander spends in close contact during t he instruction period, unitless

= Fraction of time bystander spends in close contact after th e instruction period, unitless

= Instruction period duration in effective half-lives, unitle ss

Figure B-2 depicts the time periods used in the calculation. Ti mes (typically in hours) are intentionally converted into th e number of effective half-lives (unitless) so that a single set of tabulated values will apply to a broad range of radiopharmaceuticals. Lic ensees with details on the timing of anticipated exposure may calculate for specific bystanders.

RG 8.39, Rev. 2, Appendix B, Page B-4 Figure B-2. Time Periods and Pa rameters Utilized to Calculate O ccupancy.

If the licensee determines that a patient is willing and able to follow instructions to minimize bystander exposure, then can be modified based on the in struction. In addition to direc t discussions with the patient, questionnaire responses can be useful to dete rmine if a patient can follow instructions and if anticipated behavior after release is realistic for the patient. It is inappropr iate and unrealistic to assume a patient will isolate or physically separate from bysta nders if the patient has difficulty in understanding or following dose-minimizing instructions, such a s someone needing assistance to perform daily tasks. Instead, a more appropriate, realistically conserv ative value for occupancy should be selected.

For example, based on discussions with a patient, a daily fract ion for close contact greater than 0.1 should be used when a patient does not believe they can fol low the instructions to restrict close contact to less than 2 hours2.314815e-5 days <br />5.555556e-4 hours <br />3.306878e-6 weeks <br />7.61e-7 months <br /> per day. No adjustment is needed when the licensee confirms the appropriateness of the issued ins tructions for the patient and is confident that those instructions will be followed. If instructions direct the patient to avoid close co ntact with others for a specified instruction duration and a licensee determin es the patient is willing and a ble to follow the instructions, then can be assigned a small value, including 0 while the patient is in iso lation. If the patient is expected to have close contact with a bystander for mor e than a negligible time (i.e., more than a couple minutes per day of close contact) during the instruction period, assign to a value greater than 0.

Per 10 CFR 35.2075(a)(2), a reco rd of the basis for authorizin g release is required when an occupancy factor less than 0.25 at 1 m is used. A patient quest ionnaire, similar in format to Figure B-1, and its arising conclusions may be used as a basis of patient-s pecific information. Licensees should exercise caution on low occupancy factors based solely on a pat ients typical behavior. For example, if an occupancy factor is determined to be less than 0.1 due to minim al close contact with bystanders on a typical basis, licensees may need to enquire about the patient s specific plans following treatment and ensure the instructions match thi s expected behavior prior to u sing an occupancy factor less than 0.1 to justify bystander exposure will likely not exceed 5 mSv (0.5 re m).

Occupancy considers exposure c omponents during travel and after travel. Patient-specific instructions on dose minimization tend to be more effective whe n they address the larger of the two components. The patients abilit y to adhere to instructions is most important in situations when patient release relies on behavior to meet the stated restrictions in t he instructions. This condition can be confirmed when an alternate unrestricted occupancy factor, as suming no restrictions on patient behavior, yields a bystander dose exceeding 5 mSv (0.5 rem). Th ere is no requirement for determining unrestricted occupancy factors; however, if the patient-specifi c unrestricted occupancy factor results in bystander dose exceeding 5 mSv (0.5 rem) then the licensee must have confidence the patient and their caregivers understands, are willing, and are able to comply wit h the instructions before using them as a basis for release. Record of the method for verifying patient a bility and intent to fo llow these instructions must be in accordance with 10 CFR 35.2075 for these types of re lease.

RG 8.39, Rev. 2, Appendix B, Page B-5 B.2 Modifying Factor for Geometry,

For the basic threshold calculation, the conservative geometry between a patient and the bystander is assumed to be point to point at a 1 m distance. One meter is used because it is assumed to be the average typical close contact distance over time. Licen sees can modify the geometry to provide realism using the geometry modifying factor. The geometry modif ying factor,, is a unitless factor to represent dose rate to a bystander at a distance from the patients body relative to the tissue dose rate at a point 1 m away from a point-source of the radionuclide. Equat ion 1 already utilizes a dose-rate constant for a point at 1 m away from a point source. The geometry facto r modifies this equation for patient-specific exposure geometries. As shown in Table B-1, this facto r is highly dependent on the patient-to-bystander separation distance (Ref. B-1). Values of can exceed unity (1) for instances with separation distances of less than 1 m. Time spent closer than 1 m, such as time spent holding another person, traveling immediately after release, and sleeping in the same bed with another person, should be included in the patient-specifi c assessment, especially if they occur within two effective half-lives following administration. In addition, the geometry factor can be modified to remove the conservatism from an assumption that both the source and bystander are point s (Ref. B-1).

should be selected for the bystanders total exposure without overestimating separation distance. Point-Line refers to a point-like source across from the end of a 0.7-m receptor line for distributed bystander organs; these geometry values are supplie d in Table B-1 for point-like sources, implants, or radionuclides concentrating in a particular organ (e.g., hyperthyroid retention of radioiodine in the thyroid or prostate implants). Line-Line refers to a 1.7 -m source length with a 0.7-m receptor length. Line-Line values are provided for more widely distribut ed radionuclides within the patients body (e.g., radioiodine treatment for thyroid cancer). Alternatively, licensees may make patient-specific geometric adjustments or perform more detailed three-dimensiona l modeling to calculate (Ref. B-1).

Table B-1. Geometric modifying factors,, at various bystander separation distances, (m).

Patient-to-Bystander Separation Distance, (m) Point-Line Line-Line (unitless) (unitless) 0.2 (typical for holding a child) 7.6 9.2 0.3 (typical for mobility assistance) 5.6 4.6 0.5 2.7 2.3 0.7 (typical for travel seating) 1.6 1.4 1.0 (typical for close contact) 0.87 0.79 1.5 0.42 0.39 2.0 0.25 0.25 Distances greater than 2 m 1 1

Exposure to bystanders during tr avel must be considered when the patient does not travel alone if it is possible that dose limits could be exceeded; this include s public transportation and ride sharing.

Travel includes the return trip home (or to work) and would inc lude time spent in lodging during the trip.

When the patient travels alone u sing private transportation, ex posure to members of the public during travel would be small and can be neglected when the maximally e xposed bystander is associated with exposure after travel. Judgment should be applied on when and t o whom external doses are expected to be the largest. For the combination of very short-lived radionucli des with patient travel times that represent several half-lives, retained activity in the patient after travel can be a small fraction of that at the beginning of travel. In this situ ation, the travel period would be important to consider. Exposure considerations must include both occupancy (time spent) and geo metry (separation distance) when exposure is expected to be significant at distances closer than 1 m. Patients who require mobility

RG 8.39, Rev. 2, Appendix B, Page B-6 assistance or aid another person can be assumed to hold that person for two hours per day unless patient-specific details indicate differently. Although exposures to by standers more than 3 m away and not within the direct line of sight of the patient are seldom limiting, pa tients who live alone in an apartment or other facility with nearby occupants may expose those bystanders for prolonged periods of time.

B.3 Modifying Factor for Time-Integrated Biokinetics,

is the ratio of the total disintegrations occurring in the patient to the total disintegrations of the administered activity. Licensees with radiopharmaceutical retention data for the patie nt can quickly obtain a conservative estimation of the biokinetic modifying factor us ing a single data point as shown

=. ( ) (Equation B-5)

where

= Radiological half-life for the radionuclide, h

= Time after administration when latest retention fraction is determined, h

= Retention fraction in the patient at time after administration, unitless

Values for and represent a data point in the patients retention curve. Note: >48h is recommended for radionuclides with >24h. For example, given a patient who exhibits 19% retention 96 hours0.00111 days <br />0.0267 hours <br />1.587302e-4 weeks <br />3.6528e-5 months <br /> after administration of a radionuclide with a radiolog ical half-life of 160 h, Equation B-5 yields

= 0.693 96 160 ln(0.19)=0.24. (Equation B-6)

Alternatively, licensees with patient retention data for the ra diopharmaceutical can utilize the generalized template shown in F igure B-3. After plotting patien t retention data on the template, the retention curve can be drawn fro m the initial point at 100% through each data point. The value of equals the smallest template value intercepted by the data. To accommodate all radionuclides, time after administration was converted into the number of radiological ha lf-lives. For the same example above, 96 h represents 0.6 radiological half-lives. Plotting 19% at 0.6 r adiological half-lives generates a data point below the dashed line for 0.3. Thus, =0.3 from the template in Figure B-3, which is slightly more conservative than Equation B-1. Radionuclide retention over tim e can be inferred from several dose rate measurements at the same distance from the patient. For therapeutic procedures with a pretreatment planning administration, the pa tients pretreatment data could estimate retention after the therapeutic dosage of the radiopharmaceutical is administered especially wh en the same radiopharmaceutical is used.

When patient retention data are not available, licensees can assume the patient exhibits slow biological clearance according to the manufacturer excretion information u nless the patients medical condition or voiding habits affects biological clearance and excretion rates. Medical conditions such as reduced kidney or liver function may affect clearance rates. For permanent cap sulated implants or seeds, or when biological clearance rates are unknown, use =1.

RG 8.39, Rev. 2, Appendix B, Page B-7 Figure B-3. Generalized graphical template to determine from patient retention data.

Mathematical integration of mor e detailed retention functions (e.g., double exponential relationships for fast and slow clearance) provides the greates t flexibility when specific exposure times are either known or approximated from patient-specific data. Eq uations in this subsection were derived from mathematical integration w ith radiopharmaceutical retentio n modeled by a single exponential.

Modifications for double exponential retention can be pursued o n a case-by-case basis. Supporting details are available (Ref. B-1). Example calculations are presented in Appendix C.

B.4 Modifying Factor for Attenuation,

The modifying factor for attenuation,, accounts for photon scatter, buildup, and absorption at patient tissue thicknesses different than standard zero thickne ss of tissue. is unitless. Provided in Appendix A, dose-rate constants from a point source at 1 m assu me no shielding from tissue and were used in calculating the activity and measurement thresholds in Tables 1 and 2. These thresholds can be modified using to account for photon scatter, buildup, and absorption in tiss ue. As an example, the influence of tissue thickness on the standard dose-rate constan t is provided in Figure B-4 for 99mTc. As shown, values of can exceed unity (1) when photons only travel through a short distance of tissue before leaving the body. Patie nt attenuation and buildup can be significant. should be justified in the calculation of patient-specific thresholds when other patient s pecific modifying factors are used to remove conservatism. To consider patie nt attenuation with buildup, lic ensees may select the tissue thickness appropriate for the patient by es timating torso radius for wide ly distributed radionuclides or the thickness of tissue overlying the thyroid for radioiodine treatments. Att enuation factors have been precalculated for 40 radionuclides (Ref. B-1).

RG 8.39, Rev. 2, Appendix B, Page B-8 Figure B-4. Attenuation modifying factor for Tc-99m as a functi on of attenuating tissue thickness.

REFERENCE FOR APPENDIX B 5

B-1. RCD Radiation Protection Associates. Activity Thresholds, Patient-Specific Modifying Factors, Breastfeeding Interruption Times, and Other Supporting Data, R esearch Information Letter Report for Phase 2 Revisions to R egulatory Guide 8.39: Release of Patients Administered Radioactive Material. RCD 181-0. Corvallis, OR. June 30, 202 1, (ML21214A223) 1

16. Publicly available NRC published documents are available electronically through the NRC Library on the NRCs public Web site at http://www.nrc.gov/reading-rm/doc-collections/ and through the NRCs Agencywide Documents Access and Management System (ADAMS) at http://www.nrc.gov/reading-rm/adams.html. The documents can also be viewed online or printed for a fee in the NRCs P ublic Document Room (PDR) at 11555 Rockville Pike, Rockville, MD. For problems with ADAMS, contact the PDR staff at (301) 415-4737 or (800) 397-420 9; fax (301) 415-3548; or e-mail pdr.resource@nrc.gov.

RG 8.39, Rev. 2, Appendix B, Page B-9 APPENDIX C

EXAMPLE CALCULATIONS

Several examples illustrate the methodologies discussed in this guide.

EXAMPLE A - USE OF QUESTIONNAIRE TO DETERMINE MODIFYING FACTORS

Information collected by the questionnaire can support modifyin g factor selection. The two brief examples of completed questionnaires for different patients bel ow, however, emphasize the occupancy factor. Refer to other examples in this appendix for determinat ions of the remaining modifying factors.

Example 1: On Friday afternoon, a patient travels home by private automobile without a companion after a medical administration of a r adiopharmaceutical with an effec tive half-life of 60 hours6.944444e-4 days <br />0.0167 hours <br />9.920635e-5 weeks <br />2.283e-5 months <br />. The patient lives alone and returns to work on Monday morning. Figure C-1 shows a completed questionnaire.

The maximally exposed bystanders will likely be coworkers as this patient lives and travels home alone in a private vehicle. Because the patient does not expect to return to work until Monday morning, the total time elapsed between administration and the start of coworkers prolonged exposure is about 66 hours7.638889e-4 days <br />0.0183 hours <br />1.09127e-4 weeks <br />2.5113e-5 months <br /> or =1.1 effective half-lives. Through discussion with the patient, the licensee understands the patients typical workday is eight hours. For an eight-hour wor kday, the fraction of time for bystander close contact,, is or approximately 0.33. For this patient. Equation B-3 is not n ecessary for calculating the occupancy factor because there is no bystander exposure during travel. Additionally, there is no close bystander contact during the instruction period whi le the patient is home alone before returning to work. For these conditions, Equation B-4 simplifie s to

=. ( ) (Equation C-1) where

= Occupancy factor for the maximally exposed bystander after travel, unitless

= Fraction of time for bystander close contact after the inst ruction period, unitless

+ + = Total elapsed time between medical administration and byst ander exposure in effective half-lives, unitless.

For the parameter values described above, the following calcula tion is performed

=0.33. (. ) =0.15 (Equation C-2)

The occupancy factor,, is 0.15 for this patient.

RG-8.39, Rev. 1, Appendix C, Page C-1 Figure C-1. Completed Questionnaire for Example Patient Who Liv es and Travels Home Alone.

To Be Completed by the Licensee Patient Identification Number 1342966322 Patient is able and willing to f ollow discharge instructions including behavior restrictions based on discussions prior to administration? yes no Estimate the patient s overlying tissue for attenuation and buildup: ______ cm 5 Is a patient-to-bystander distance less than 1 m expected with a geometric modifying factor greater than 1? yes no To Be Completed with Patient Input How long is the return trip home? 1 hour1.157407e-5 days <br />2.777778e-4 hours <br />1.653439e-6 weeks <br />3.805e-7 months <br /> Will someone accompany yes How will you my vehicle bus taxi you on the return trip no train plane other be returning home? home?

When will you Do you spend more than 10 hours1.157407e-4 days <br />0.00278 hours <br />1.653439e-5 weeks <br />3.805e-6 months <br /> per week closer Next week yes return to work? than 10 feet from the same person at work? no Who do you see in person on a routine Coworkers on workdays basis?

Do you anticipate spending more than yes If yes, at what an hour a day closer than arms length distance and n/a (1 meter) from another individual? no for how long?

getting on and Do you/have you ever off chairs walking using the restroom bathing needed help with the getting in and cooking reading/understandin following tasks? out of vehicles /eating g instructions none of the above

Do you live in an apartment or facility with other people in adjacent rooms/on adjacent floors? yes no Are you currently yes Could you be yes Do you share a bed with yes nursing (breastfeeding) no no no pregnant? anyone?

a child?

Are you able to sleep in your own bed without another person for some length of time after the yes procedure? no Are you able and willing to change your behavior as directed by the specific preliminary yes posttreatment instructions discussed with and explained to you to minimize exposure to no bystanders?

Are you able and willing to change your behavior as directed by the specific final yes posttreatment instructions discussed with and explained to you to minimize exposure to bystanders? no To Be Completed the Day of Administration by Licensee

Confirm appropriate changes were made to the form and calculations if patient plans changed. yes no

RG 8.39, Rev. 2, Appendix C, Page C-2 Example 2: A different patient travels a long distance with a companion to arrive at the medical facility for the same radiopharmaceutical administration and effective h alf-life of 60 h. The companion is the patients spouse, and they share a bed. The patient is released 6 hours6.944444e-5 days <br />0.00167 hours <br />9.920635e-6 weeks <br />2.283e-6 months <br /> after the administration. This delay time equates to =0.1 effective half-lives. The spouse and patient travel together o n Friday and during the weekend and return home on Sunday. The full duration of tra vel is estimated to be 42 hours4.861111e-4 days <br />0.0117 hours <br />6.944444e-5 weeks <br />1.5981e-5 months <br /> after release or =0.7 effective half-lives. Through a discussion with the patient, t he patient indicated that during the day at home, close contact with the spouse is not ex pected. At night however, the patient will typically spend 8 hours9.259259e-5 days <br />0.00222 hours <br />1.322751e-5 weeks <br />3.044e-6 months <br /> (equal to 0.33 fraction of a day) in th e same bed, and the patient is unable to change this pattern. Based on discussions with the patient, the licensee determines that the maximally exposed bystander is the patients spouse. A completed patient questionnaire is displayed in Figure C-2.

Exposure to the patients spouse should be considered during tr avel and at home after travel. The licensee conservatively assumes the patient is in close contact with the spouse during the entire trip. The occupancy factor is calculated from Equations B-3 and B-4. Occ upancy during travel is calculated as

=. ( ). ( ) (Equation C-3) where

= Occupancy factor for the maximally exposed bystander during travel, unitless

= Fraction of time bystander spends in close contact with the patient during travel, unitless

= Time between medical administration and patient release in effective half-lives, unitless

= Travel duration in effective half-lives, unitless

For the parameter values described above, the following occupan cy calculation is performed during travel

=1. (. ). (.. ) = 0.36 (Equation C-4)

After travel, there is no difference in behavior expected for t his patient. As shown in Figure C-2, the patient is not willing to fo llow behavior changes in posttr eatment instructions to minimize exposure to bystanders. For this reason, an instruction period, during whic h behavior restrictions would be followed, is unnecessary for determining bystander occupancy after travel. According to Equation B-4, both parameters associated with the instruction period take values o f zero. For this patient, Equation B-4 reduces to

=. ( ) (Equation C-5)

For the parameter values described above, bystander occupancy during potential long-term exposure after travel is calculated as

=0.33. (.. ) = 0.19 (Equation C-6)

Because bystander occupancy during and after travel relate to the same person (patients spouse),

these results are summed to yield an occupancy factor of 0.55 for the maximally exposed bystander.

Figure C-2 also shows that the licensee elected to not estimate overlying tissue thickness when acquiring patient-specific information to reduce conservatism a nd modify thresholds. When patient-specific modification is pursued and no information is available to justify a modifying factor, a conservative value must be applied to that modifying factor. In this case, the largest value of the attenuation factor should be selected for the administered radi onuclide. As shown in precalculated plots (Ref. C-1), the largest value could exceed unity (1).

RG 8.39, Rev. 2, Appendix C, Page C-3 Figure C-2. Completed Questionnaire for Example Patient With a Travel and Living Companion.

To Be Completed by the Licensee Patient Identification Number 70784431 Patient is able and willing to fo llow discharge instructions in cluding behavior no restrictions based on discussions prior to administration? yes Estimate the patients overlying tissue for attenuation and buildup: ______ cm Not estimated Is a patient-to-bystander distance less than 1 m expected with a geometric modifying factor greater than 1? yes no To Be Completed with Patient Input How long is the return trip home? 3 days with overnight stays Will someone accompany yes How will you my vehicle bus taxi you on the return trip no train plane other be returning home? home?

When will you Do you spend more than 10 hours1.157407e-4 days <br />0.00278 hours <br />1.653439e-5 weeks <br />3.805e-6 months <br /> per week closer Retired yes return to work? than 10 feet from the same person at work? no Who do you see in person on a routine Spouse and friends basis?

Do you anticipate spending more than yes If yes, at what an hour a day closer than arms length distance and Sleeping with spouse (1 meter) from another individual? no for how long?

getting on and Do you/have you ever off chairs walking using the restroom bathing needed help with the getting in and cooking reading/understandin following tasks? out of vehicles /eating g instructions none of the above

Do you live in an apartment or facility with other people in adjacent rooms/on adjacent floors? yes no Are you currently yes Could you be yes Do you share a bed with yes nursing (breastfeeding) no no no pregnant? anyone?

a child?

Are you able to sleep in your own bed without another person for some length of time after the yes procedure? no Are you able and willing to change your behavior as directed by the specific preliminary yes posttreatment instructions discussed with and explained to you to minimize exposure to no bystanders?

Are you able and willing to change your behavior as directed by the specific final yes posttreatment instructions discussed with and explained to you to minimize exposure to no bystanders?

To Be Completed the Day of Administration by Licensee

Confirm appropriate cha nges were made to the form and calculations if patient plans changed. yes no

RG 8.39, Rev. 2, Appendix C, Page C-4 EXAMPLE B - RELEASE OF PATIENT BASED ON ADMINISTERED ACTIVITY

A 56-year-old male receives an administration of 1.29 GBq 90Y microspheres for the treatment of hepatocellular carcinoma. As shown in Columns 1 and 2 of Table 1, the basic activity thresholds are 34 GBq for authorizing patient release and 6.8 GBq for requiring d ose-minimizing instructions, respectively.

Because the administered activity of 1.29 GBq is below these basic thresholds, the licensee is authorized to release the patient without dose-minimizing instructions. Al though some licensees may independently decide to issue dose-minimizing instructions to the patient, th ere is no regulatory requirement to do so. In this case, a patient-specific determination of modifying factor s for biokinetics, occupancy, geometry, and attenuation is unnecessary. No records are required for regulat ory purposes.

EXAMPLE C - RELEASE OF PATIENT WHO IS BREASTFEEDING

A 35-year-old female, who is breastfeeding a child, receives 0.74 GBq 18F fluorodeoxyglucose for positron emission tomographic imaging. From Columns 1 and 2 of Table 1, the basic activity release threshold for 18F is 13 GBq, and the threshold for instruction is 2.5 GBq, resp ectively. The assessment progresses through multiple stages as numerated in Figures C-3 and C-4 and described in the text.

0.74 GBq 2.5 GBq 13 GBq Instruction Threshold Release Threshold (Table 1, Column 2) (Table 1, Column 1)

Dose to 1

Bystander No release Release authorized Release with instructions

Figure C-3. Administered activity comparison to instruction and patient release thresholds.

The administered activity is less than both basic thresholds ( release and instruction).

Dose-minimizing instructions are not required to satisfy regula tory requirements for 10 CFR 35.75(a).

Although some licensees may independently decide to issue dose-minimizing instructions in the patients discharge instructions, there is no regulatory requirement to i ssue instructions. In this case, a patient-specific determination of modifying factors for biokine tics, occupancy, geometry, and attenuation is unnecessary.

Because the patient is breastfeeding, dose to the child from nu rsing is initially assessed assuming no breastfeeding interruption. From Column 2 of Table 3, the ad ministered activity of 0.74 GBq is shown to exceed the 1-mSv activity threshold l of 0.20 GBq. Therefore, a breastfeeding interruption time must be established and incorporated into the required breastfe eding instructions for discharge.

0.2 GBq 1.0 GBq0.74 GBq Instruction Threshold Record Threshold (Table 3, Column 2) (Table 3, Column 1)

Dose to 2 Breastfeeding Infant or Child Breastfeeding Breastfeeding Breastfeeding instructions instructions not required instructions required required with interruption

Figure C-4. Administered activity comparison to breastfeeding thresholds.

RG 8.39, Rev. 2, Appendix C, Page C-5 The licensee suggests a breastfeeding interruption time corresponding to a child dose of less than 1 mSv (0.1 rem). From Column 2 of Table 3, the retained activit y in the patient of 0.20 GBq for l equates to a child dose of 1 mSv (0.1 rem) for breastfeeding. F or 18F ( =1.83h) fluorodeoxyglucose, the licensee estimates the biological half-life specific to thi s patient as = 100 h. The effective half-life is calculated as 1.80 h from Equation 5. According to Equation 6 for a retained activity equaling the tabulated l value of 0.20 GBq, the breastfeeding interruption time is calculated to be 3.4 h from 1.44 1.80 ln... This interruption time is cons istent with the recommendation in Table 4.

Because the administered activity exceeds l, the licensee is required to issue breastfeeding instructions if the patient could be breastfeeding after releas e. The patient can be released with instruction to interrupt breastfeeding and discard breastmilk for the specified time. As an alternative to discarding pumped breastmilk, breastmilk storage for radioactive decay can be permitted under direction by the licensee if desired. Because the administered activity did not exceed the record threshold l of 1 GBq shown in Column 1 of Table 3, a r ecord of instructions provided to the patient is not required.

EXAMPLE D - RELEASE OF PATIENT WITH INSTRUCTIONS BUT WITHOUT BEHAVIOR MODIFICATION

A 46-year-old female receives 2.0 GBq 131I as sodium iodide for hyperthyroidism (i.e., thyroid ablation). From Columns 1 and 2 of Table 1, the basic activity threshold of 131I for patient release is 0.32 GBq and the threshold over which instructions must be provided is 0.063 GBq. The administered activity is greater than both basic thresholds. The licensee decides to calculate patient-specific thresholds to determine if immediate release is allowable and if instructions are required.

The licensee applies a double exponential model for 131I retention with uptake fractions of 0.2 and 0.8 for the extrathyroidal and thyroid components with respecti ve effective half-lives of 7.7 h and 125 h.

The biokinetic modifying factor f or double exponential retentio n is calculated as a weighted sum of effective half-lives relative to the radiological half-life (Ref. C-1):

= (. )(. h) (. )( h) h=0.53. (Equation C-7)

During initial treatment plan discussions with the patient, th e patient stated that she will be sleeping with her spouse 8 hours9.259259e-5 days <br />0.00222 hours <br />1.322751e-5 weeks <br />3.044e-6 months <br /> a day. The licensee determined that the spouse was the maximally exposed individual and the patient -specific occupancy factor was estimated to be 0.33. The geometry factor was estimated at 0.87 for a separation distance of 1 m f or close contact with a point-like source for 131I concentrated in the thyroid. To account for attenuation and b uildup for this patient, the licensee assigns 2 cm as the tissue thickness overlying the thyroid and obtains = 1.0 from Figure C-5, as reproduced from precalculated plots (Ref. C-1).

RG 8.39, Rev. 2, Appendix C, Page C-6 Figure C-5. Attenuation modifying factor for I-131 as a functio n of attenuating tissue thickness.

Using this initial information and Equation 8, the licensee cal culates the following patient-specific thresholds for release and instruction

=.....=2.1 (Equation C-8)

and

=.....= 0.41. (Equation C-9)

However, on the day of procedure, the patient stated to the li censee that her plans had changed and she was going on a family vaca tion the very next day and th e patient was not willing to modify any of her behaviors post treatment. The licensee amends the patient questionnaire, as shown in Figure C-6, in order to re-calculate the occupancy factor. The family trip i s expected to take approximately 4 days (96 hours0.00111 days <br />0.0267 hours <br />1.587302e-4 weeks <br />3.6528e-5 months <br />). During this trip, the licensee assumes 12 h per day of close contact (50 percent) for the maximally exposed bystander at a distance of 1 m. After this trip, 6 h p er day of close contact (25 percent) is expected during routine family behavior. To account for these p lans, the licensee calculates occupancy according to Equations B-3 and B-4 with a single effective half -life of 102 h (i.e., product of radiological half-life and the result from Equation C-7). In other words, a nd the effective half-life can be approximated as

= x = 0.53 x 192 h = 102 h. (Equation C-10)

By neglecting a delay in bystander exposure on the day of admin istration and not including a time period for behavior modification, the licensee assigns the following d elay, travel, and instruction times equate to

= h h=0; = h h=0.94; and = h h=0 (Equation C-11)

effective half-lives, respectivel y. For parameter values descri bed above, occupancy during the family trip (travel) is calculated as

=0.5. ( ). (. ) = 0.24 (Equation C-12)

Occupancy for the long-time period after the family trip is cal culated without an instruction period of behavior modification as

= 0.25. (. ) = 0.12 (Equation C-13)

RG 8.39, Rev. 2, Appendix C, Page C-7 Because bystander occupancy during and after travel relate to the same person in the patients family, these results are summed to yield an occupancy factor of 0.36 for the maximally exposed bystander.

Based on this updated information according to the patients p lans, the licensee recalculates patient-specific thresholds for release and instruction

=.....= 1.93 (Equation C-14)

and

=.....= 0.38. (Equation C-15)

The administered activity of 2.0 GBq exceeds the patient-specific activity threshold for release. By substituting terms in Equations 9 and B-5, a hold time can be c alculated from the following relationship

=. ln (Equation C-16)

For the parameter values in this example,

=. ln.. =5.2h. (Equation C-17)

After this hold time, the patient is authorized for release wit h dose-minimizing instructions. In this case, behavioral restrictions are not required over a specified time period, because the patient does not intend to adhere to those restrictions and the licensee has established a sufficient basis for release without behavior restrictions. A record of the basis for release is required bec ause the calculation involved one or more of the following considerations: retained activity, occupancy factor less 0.25 at 1 meter, biological or effective half-life, or tissue shielding. The record must be retained for 3 years after the date of release.

Calculating and releasing patients based on patient-specific thresholds will often require a record.

Exceptions include an occupancy factor of at least 0.25 with a geometry factor consistent with 1 meter or closer and biokinetic and attenua tion factors both equaling uni ty (1).

RG 8.39, Rev. 2, Appendix C, Page C-8 Figure C-6. Completed Questionnaire for Patient in Example D.

To Be Completed by the Licensee Patient Identification Number 802764113 Patient is able and willing to follow discharge instructions in cluding behavior no restrictions based on discussions prior to administration? yes Estimate the patients overlying tissue for attenuation and buildup: ______ cm 2 Is a patient-to-bystander distance less than 1 m expected with a geometric modifying factor greater than 1? yes no To Be Completed with Patient Input How long is the return trip home? 0.5 hours5.787037e-5 days <br />0.00139 hours <br />8.267196e-6 weeks <br />1.9025e-6 months <br /> Will someone accompany yes How will you my vehicle bus taxi you on the return trip no train plane other be returning home? home?

When will you Do you spend more than 10 hours1.157407e-4 days <br />0.00278 hours <br />1.653439e-5 weeks <br />3.805e-6 months <br /> per week closer In 3 weeks yes return to work? than 10 feet from the same person at work? no Who do you see in person on a routine Husband and children basis?

Do you anticipate spending more than yes If yes, at what Family vacation an hour a day closer than arms length distance and (1 meter) from another individual? no for how long? starting tomorrow getting on and Do you/have you ever off chairs walking using the restroom bathing needed help with the getting in and cooking reading/understandin following tasks? out of vehicles /eating g instructions none of the above

Do you live in an apartment or facility with other people in adjacent rooms/on adjacent floors? yes no Are you currently yes Could you be yes Do you share a bed with yes nursing (breastfeeding) no no no pregnant? anyone?

a child?

Are you able to sleep in your own bed without another person for some length of time after the yes procedure? no Are you able and willing to change your behavior as directed by the specific preliminary yes posttreatment instructions discussed with and explained to you to minimize exposure to no bystanders?

Are you able and willing to change your behavior as directed by the specific final yes posttreatment instructions discussed with and explained to you to minimize exposure to no bystanders?

To Be Completed the Day of Administration by Licensee

Confirm appropriate changes were made to the form and calculations if patient plans changed. yes no

RG 8.39, Rev. 2, Appendix C, Page C-9 EXAMPLE E - RELEASE OF PATIENT AFTER AN ADMINISTRATIVE HOLD

A 63-year-old male receives the first administration of 18.5 G Bq 131I iobenguane (AZEDRA) for cancer treatment. From Columns 1 and 2 of Table 1, the basic activity threshold of 131I for patient release is 0.32 GBq and the threshold over which instructions must be p rovided is 0.063 GBq. The administered activity is greater than both basic thresholds. The licensee de cides to calculate patient-specific thresholds to determine if immediate release is allowable and if instructions are required. Evaluation of patient release initially considers release at 56 hours6.481481e-4 days <br />0.0156 hours <br />9.259259e-5 weeks <br />2.1308e-5 months <br /> after administration and the patients spouse accompanying the patient on the 1-h trip hom e by private automobile. Per lic ensee direction and instruction, the patient agrees to sleep in a separate bed and minimize close contact wi th others for 7 days after returning home but requires physical assistance while at home. Dose-minimizing instructions are prepared consistent with these restrictions, and the daily close contact for physical assistance is assumed to be 2.4 h (10 percent) during the instruction period. After the instruction period of 7 days, the licensee anticipates that the patient and spouse will resume sharing a bed during the nig ht and increases the fraction of daily close contact to 12 h (50 percent) after the instruction period.

The licensee obtains biokinetic information from pretreatment dosimetric data and finds the patient retained 38% of radioactivity at 96 h after administrat ion. Therefore, according to Equation B-5,

= (. ) ( h)( h) (. )=0.36, (Equation C-18)

and the effective half-life can be approximated as

= x = 0.36 x 192 h =69 h. (Equation C-19)

As described in Figure B-2, the delay, travel, and instruction times equate to

= h h= 0.812; = h h= 0.014; and = h h=2.43 (Equation C-20)

effective half-lives, respectively.

Exposure to the patients spouse is considered during travel and at home after travel. The licensee assumes the patient is in close contact with the spouse during the 1-h trip home. The occupancy factor is calculated from Equations B-3 and B-4.

For the parameter values described above, occupancy during trav el is calculated from Equation B-3 as

=1. (. ). (. ) = 0.006 (Equation C-21)

For this patient, the bystander occupancy during travel is smal l because the 1-h trip duration is a small fraction of the 69-h effective half-life, and the trip commence s after a delay time of nearly one effective half-life.

According to Equation B-4, occupancy after travel includes exp osure during and after the instruction period as follows

=0.1. (. ). (. ) + 0.5. (. ) = 0.098 (Equation C-22)

Because bystander occupancy during and after travel relate to the same person (patients spouse),

these results are summed to yield an occupancy factor of 0.104 for the maximally exposed bystander.

A record of the basis for author izing patient release is required when the licensee uses an occupancy factor less than 0.25.

RG 8.39, Rev. 2, Appendix C, Page C-10 According to Table B-1, a geomet ry factor of 1.4 is assigned t o a separation distance of 0.7 m for travel and daily physical assistance when instructions are foll owed to limit prolonged close contact.

Because exposure during travel is negligible, the geometry fact or of 1.4 is applied to close contact while the patient is receiving physical assistance.

To account for attenuation and bui ldup in the patient, the lic ensee obtains a girth measurement to estimate the torso radius (a mea sure of average tissue thicknes s) of 14 cm for this patient. From Figure C-7 as reproduced from supporting documentation (Ref. C-1), the licensee determines that = 0.92.

Figure C-7. Attenuation modifying factor for I-131 as a functio n of attenuating tissue thickness.

From Equation 8, patient-specific thresholds for release and in struction become

=.....=6.6 (Equation C-23) and

=.....=1.3 (Equation C-24)

The administered activity of 18.5 GBq is greater than both pati ent-specific thresholds, so a hold time is calculated according to Equation 9 as

= (. ) ln.. = 102 h (Equation C-25)

For this high external dose-rate therapeutic procedure, this p atient will be held in the medical facility for a total of 102 h after administration prior to bei ng released to assure the 5-mSv dose limit will not likely be exceeded. After thi s hold time, the patients ret ained activity is calculated to be less than the patient-specific release threshold ( ) but greater than the patient-specific instruction threshold

( ). A record of the basis for rel ease is required because the cal culation involved one or more of the following considerations: retained activity, occupancy factor l ess 0.25 at 1 meter, biological or effective half-life, or tissue shielding. T he record must be retained for 3 years after the date of release. The record could include specifics of the a dministration, instructions pro vided to the patient, and justification for the selection of each modifying factor used in the calculation incl uding the patient questionnaire or notes from a pretreatment discussion re garding patient behavior. Refe r to Section 5 for guidance on records.

RG 8.39, Rev. 2, Appendix C, Page C-11 REFERENCE FOR APPENDIX C 6

C-1. RCD Radiation Protection Associates. Activity Thresholds, Patient-Specific Modifying Factors, Breastfeeding Interruption Times, and Other Supporting Data, Research Information Letter Report for Phase 2 Revisions to Regulatory Guide 8.39: Release of Patients Administered Radioactive Material. RCD-21-181-0. Corvallis, OR. June 30, 202 1. (ML21214A223) 1

16. Publicly available NRC published documents are available electronically through the NRC Library on the NRCs public Web site at http://www.nrc.gov/reading-rm/doc-collections/ and through the NRCs Agencywide Documents Access and Management System (ADAMS) at http://www.nrc.gov/reading-rm/adams.html. The documents can also be viewed online or printed for a fee in the NRCs Public Document Room (PDR) at 11555 Rockville Pike, Rockville, MD. For problems with ADAMS, contact the PDR staff at (301) 415-4737 or (800) 397-4209; fax (301) 415-3548; or e-mail pdr.resource@nrc.gov.

RG 8.39, Rev. 2, Appendix C, Page C-12